Systemic mastocytosis (SM), a rare myeloid neoplasm, is defined as a clonal and neoplastic proliferation of mast cells in at least one extracutaneous organ(s). The pathologic diagnosis and treatment of SM are challenging.We presented a 44-year-old male patient who had endured abdomen discomfort for 4 years and diarrhea for 5 months. Colonoscopy and PET/CT found a protuberant lesion in the cecum with adjacent lymphadenopathy. Histopathology of the cecum biopsy showed diffuse infiltration of medium-sized round/oval cells in lamina propria with immunohistochemical expressions of CD45, CD117, CD25, CD68, CD123, CD56, CD4, and CD35, mimicking blastic plasmacytoid dendritic cell neoplasm. Sanger sequencing revealed missense mutation (D816V) in the exon 17 of KIT gene. Serum tryptase level was 38.56 ng/ml. No abnormality was found in skin examination and bone marrow biopsy. No primitive cells were observed in bone marrow smear and peripheral blood smear. The diagnosis of aggressive SM with intestinal tract involvement was established. The patient received avapritinib treatment at an initial dosage of 200 mg once daily and exhibited dramatic clinical improvement but memory impairment within 1 month. No recurrence was observed in 1-year follow-up at the adjusted avapritinib dose (75 mg once daily).SM is very rare and should be considered in patients with long-term diarrhea symptoms and hematopoietic/lymphoid-appearing tumors. KIT D816V mutation contributes to the differentiation of CD123, CD4, and CD56 immunoreactive SM from blastic plasmacytoid dendritic cell neoplasm. The rare side-effect of memory impairment in this case helps to accumulate the experience of avapritinib in treating KIT D816V-mutant SM. Mastocytosis, a unique and orphan disease, refers to a clonal and neoplastic proliferation of mast cells in one or more organ(s) . The cliThe diagnosis of intestinal SM is challenging due to its rarity and nonspecific symptoms, requiring integration of clinical, laboratory, morphological, immunohistochemical, and molecular genetic data. SM with immunoreactivity for key markers of blastic plasmacytoid dendritic cell neoplasm (BPDCN), including CD123, CD4, and CD56 has rarely been documented. SM is considered incurable, while recent studies have revealed encouraging responses following treatment with tyrosine kinase inhibitors, such as imatinib and the 2nd generation agent avapritinib [A 44-year-old man presented to his primary physician with complaints of right lower abdomen discomfort for 4 years and diarrhea for 5 months. The symptoms were aggravated within 1 week.The colonoscopy examination showed a 3.0 cm × 3.0 cm protuberant lesion in the cecum with erosion, necrosis, and ulcer formation on the surface Fig. A. The tiLaboratory examinations identified increased serum tryptase level . PET/CT showed local cecum wall thickening with increased FDG uptake Fig.  and mildA final diagnosis of KIT D816V-mutant aggressive SM involving intestinal tract was established based on the combination of morphologic, immunohistochemical, molecular, and clinical findings.The patient was given avapritinib at an initial dosage of 200 mg once daily. After a month of treatment, the symptoms of diarrhea and abdomen discomfort ceased and the level of serum tryptase returned to normal ranges. Meanwhile, the patient’s memory was impaired, which recovered by gradually adjusting the drug dosage to 75 mg once daily. The patient underwent a routine ultrasound examination once a month by one designated doctor. Ultrasound results showed that the intestinal lesions and adjacent lymphadenopathy subsided after 1 month of treatment. The patient was followed up for 12 months and no recurrence was observed at the adjusted avapritinib dose (75 mg once daily).Mast cells are derived from hematopoietic stem cell precursors and play an important role in the genesis and manifestations of allergic response . Mast ceSM, a subtype of mastocytosis, is a diagnosis made by integrating clinical, laboratory, morphological, immunohistochemical, and molecular genetic data. According to the WHO classification of tumors of hematopoietic and lymphoid tissues , the diaUp to 80% of patients with SM are found to have gastrointestinal symptoms if a thorough medical history is taken . The gasMorphologically, there exists diversity in the intestine involvement of SM , 13. In The diagnosis of SM is difficult due to its rarity and atypical clinical presentation. The similarity of the clinical and histopathological features between BPDCN and our case makes the diagnosis further challenging. Clinically, both diseases are rare hematologic malignancies with heterogeneous clinical presentation and have a high frequency of cutaneous and bone marrow involvement, as well as lymph node and visceral organ involvement . MicroscA majority of adult SM patients carry somatic gain-of-function mutations of KIT, most are at amino acid 816 in exon 17, where aspartic acid is substituted by valine (D816V) (>90%) . Other rSM is considered incurable, and patients with aggressive SM have a worse survival rate due to organ damage, with an overall median survival of 41 months . The treIn conclusion, SM is very rare, and therefore, confirmation of a diagnosis can pose a significant challenge. The pathologist and clinician must have a high degree of suspicion, particularly in patients presenting with long-term diarrhea symptoms and hematopoietic/lymphoid-appearing tumors. SM with CD123, CD4 and CD56 co-expression has rarely been reported. The rare side-effect of memory impairment in this case helps to accumulate the experience of avapritinib in treating KIT D816V-mutant SM.


Parkinson’s disease (PD) is associated with a 3-fold mortality risk, which is closely related to advancing age. Evidence is lacking regarding the factors associated with the risks of mortality or nursing-home (NH) admission, in elderly patients with PD. We aimed at identifying the clinical characteristics associated with these outcomes, in older community-dwelling patients with late-onset PD.Retrospective, observational analysis of data from geriatric day hospital patients. Motor assessment included Unified Parkinson Disease Rating Scale (UPDRS) part III score, Tinetti Performance Oriented Mobility Assessment (POMA) balance and gait tests, and gait speed. Levodopa equivalent dose, comorbidity, cognitive performance, Activities of Daily Living performance were examined. Cox proportional hazards models were performed to identify the factors associated with mortality and NH admission rate (maximum follow-up time = 5 years).p = .023) and older age (HR = 1.12 95%CI (1.01–1.25), p = .044) were the only variables significantly associated with increased mortality risk. A Tinetti balance score below 11/16 was associated with a 6.7 hazard for mortality (p = .006). No specific factor was associated with NH admissions.We included 98 patients, mean age 79.4 (SD = 5.3) of whom 18 (18.3%) died and 19 (19.4%) were admitted into NH, over a median follow-up of 4 years. In multivariate Cox models, poor balance on the Tinetti POMA scale (HR = 0.82 95%CI (0.66–0.96), Age and the Tinetti POMA score were the only factors independently associated with mortality. The Tinetti POMA scale should be considered for balance assessment and as a screening tool for the most at-risk individuals, in this population.The online version contains supplementary material available at 10.1186/s12877-023-03776-7. Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s Disease, and represents the leading cause of motor disability in older adults . More thSubjects with PD are likely to experience a shorter life span compared to healthy individuals of the same age, and this risk of dying increases with aging –7. Thus,Individuals with PD might also face a greater risk of limitations in daily living activities and nursing-home (NH) admission, compared to the general population, although evidence remains heterogeneous and controversial , 12. WomHowever, there is limited available evidence relating to the predictors of survival and nursing home (NH) admission, in adults older than 70 years with late-onset Parkinson’s disease (PD), as they are less likely to participate in clinical research . More inThis is a retrospective, monocentric, observational analysis of data from community- dwelling older adults with PD, admitted between July 2007 and March 2019, in the geriatric day hospital of Bretonneau . This hospital is a referral center for geriatric care in the northern Parisian district. PD diagnosis was based on clinical examination by the referring neurologist, positive response to Levodopa treatment  and clinAge at PD diagnosis of 65 years and older (i.e. late-onset PD),Comprehensive assessment performed by our multidisciplinary day hospital staff Absence of available follow-up information for at least 12 months after the first evaluationPresence of clinical symptoms suggestive of others Parkinson syndromes, according to the American Academy of Neurology recommendations Evidence for another neurodegenerative disease (e.g. Alzheimer’s disease), at the time of the first evaluation or during the period of follow-upAbsence of consent to the use of their medical dataInsufficient fluency in French to understand and perform the tests or legal guardianshipAge at first day hospital assessment, gender,PD duration,Number and severity of comorbidities, using the Cumulative Illness Rating Scale  ,ability to use telephone; mode of transportation; responsibility for own medications; ability to handle finances; score 0–4) [Performance in Activities of Daily Living (ADL) (score 0–6)  and instore 0–4) ,Cognitive performance according to the Mini Mental State Examination (MMSE) (score 0–30) ,Weight measurement and Body Mass Index calculation,Handgrip strength of the dominant hand, measured by hydraulic dynamometer Number of drugs taken per day and daily Levodopa equivalent dose calculated .All patients underwent an initial comprehensive geriatric assessment along their first stay in the day hospital including as follows:UPDRS part III score (0–108)  and UPDRTinetti Performance Oriented Mobility Assessment (POMA) balance (score 0–16) and gait (score 0–12) tests; higher scores on Tinetti balance and gait subscales indicating better performance .Timed Up and Go (TUG) and Cognitive Timed Up and Go . Both tests were timed in seconds .Gait speed was measured on a 10-m distance, asking the patient to walk at his/her usual pace, starting from a standing still position, with or without the use of auxiliary aids. Time was measured with a digital stopwatch, from when instructed to start until crossing the 10-m marking.A physiotherapist performed the following tests for all included participants:The primary endpoint of the study was survival status . The secondary endpoint was NH admission.Survival status and housing status (i.e. occurrence of NH admission) were retrospectively collected every 6 months, over a maximum follow-up period of 5 years, using data available on the professional medical database of the hospital (ORBIS® software), completed by phone interviews with the patients, their general physician, specialists or staff of rehabilitation care units or NH. The date of data censoring was set as March 1st 2020.p values less than 0.05. Variables showing an association with mortality with a significance level of p < 0.2 in univariate analysis were analyzed using a multivariate Cox proportional hazard model and hazard ratios are reported with a 95% confidence interval. Data from patients lost to follow-up were censored. All statistical analyses were performed using R software (version 1.2.5).Demographic and clinical characteristics of patients at inclusion were subjected to descriptive statistics. Continuous variables were compared according to the survival status and to the housing status of patients during follow-up, and the differences between groups were calculated using Student’s t-test and Wilcoxon test, and by Fischer’s exact test for gender, the only categorical variable. The threshold of statistical significance was set for The research database was approved by the National Commission for Information Technology and Civil Liberties , since 2006. Consistent with the European General Data Protection Regulation, all patients were provided written and oral information about the data management explaining how their health data could be used anonymously for clinical research. The study protocol was also approved by the Regional Ethics Committee in Geriatric Medicine . According to the latter statements, despite full data availability in our records, sharing the clinical data of our patients would compromise the ethical standards mentioned above.One hundred eleven patients with an initial diagnosis of PD were referred to Bretonneau day hospital between July 2007 and March 2019. Thirteen patients were excluded from our analysis  years. Survival status and housing status (i.e. occurrence or not of NH admission) during follow-up was confirmed in 58 patients (59.2%), after complete 5-year monitoring. Point censoring occurred for 29 patients (29.6%) included after March 2015, when death or NH admission were not observed within the study duration (less than 4 years). Twenty-nine patients (29.6%) were lost to follow-up between 1 and 5 years after inclusion , ranging from 68 to 94 years old. The mean PD duration was 3.8 (3.6) years. Our sample comprised 57% of males. Few patients had severe motor impairment; rigidity, bradykinesia and postural instability were common, whereas resting tremor was absent in half of the population Fig. . Eighteep = .038). Tinetti balance score, on admission, was also lower in deceased participants than in those who survived .In univariate analyze Table , a slowep = .023). To compare the mortality risk of patients with poor balance to those with normal balance skills, we performed a post-hoc multivariate Cox proportional hazard model analysis, including age and gender, considering the Tinetti balance score in tertiles (Table p = .006), See Table After exclusion of eight subjects from our initial sample, due to missing data, 90 patients were included in the multivariate Cox model Table . The onlability to maintain balance with eyes closed was associated with a significant reduction in mortality HR = 0.26 [0.07–0.95, p = .038), with a sensitivity of 22.2% (CI 6.41–47.64%) and a specificity of 93.75% (CI 86.01–97.94%). This association was no longer significant after Bonferroni correction for multiple comparisons.All the single items of the Tinetti balance test were included in a multivariate model to explore their association with mortality (data not shown). The A total of 19 patients (19.4%) were admitted to a NH, within the study duration. No single factor was significantly associated with the odds of NH admission, in our study.In this retrospective, observational study of older patients with late-onset PD, we observed a significant association between poor performance on the Tinetti POMA balance test and increased mortality. Moreover, individuals from the lowest tertile (score of less than 11/16) experienced 6-fold higher mortality than their counterparts with the best performance (score greater than 14/16). This association was independent of age, gender or multimorbidity. No other single factor was associated with mortality risk or NH admission rate, at the end of follow-up.To our knowledge, there are no risk-assessment tools for clinicians to identify older patients with PD at risk of poor clinical outcomes, such as mortality or NH admission. Although the comprehensive assessment of motor and cognitive performances play a key role in routine assessment, none of them demonstrated a predictive value for adverse outcomes in this population , 29. In The severity of motor impairment was suggested as a prognostic factor for disease progression, disability or impaired quality of life in several studies , 11, 34.p = 0.19), despite a significant correlation between the two variables (r = 0.52 p < 0.001). However, several studies supported an association between gait speed and survival in elderly subjects [We did not find any other factor associated with mortality in our population. In our multivariate model, gait speed, although significantly lower in participants who died during the follow-up period in our study, was no longer significantly associated with mortality. The interaction between the Tinetti score and gait speed was non-significant  were not associated with mortality risk in our study population. There is conflicting evidence in the literature regarding the influence of gender on disease progression , 43. CogWe did not find any single factor associated with the risk of NH admission. This result is in contrast with results from Hosking et al. who identified, in NH residents with parkinsonism, a higher symptom burden, in particular cognitive impairment, increased disease severity on the UPDRS scale or disability compared to patients with a similar condition but living in their own home . HoweverThe main strength of our study is that, to our knowledge, it is the first one carried out specifically in elderly PD patients, focusing on factors associated with survival status or NH admission rate, and using data systematically recorded for more than 10 years. However, our study also has several limitations such as the fact that there was a limited number of events (deaths and NH admissions) due to the small size of our population, which potentially undermines its power. The inclusion criterion of an age at diagnosis of 65 and older may have skewed the results, since late-onset PD per se is an established mortality risk factor . The undOlder individuals with late-onset PD experience various patterns of motor and non-motor symptoms associated with an overall increased mortality risk. Among multiple assessment tools, the Tinetti POMA test may be an accurate instrument for identifying the older individuals with late-onset PD at higher risk of dying. This instrument should be considered in clinical practice, both by physiotherapists and geriatricians, to improve the care of older adults with late-onset PD. Future prospective studies are warranted to confirm the predictive value of the Tinetti POMA in this population.Additional file 1: Supplementary table. Comparison of the characteristics of patients included in the multivariate analysis vs those excluded.


VvWRKY22 was influenced by climate conditions and was relative to saccharide accumulation. MYB-related transcription factors (TFs) were highly correlated with volatiles that accumulated during fruit ripening, especially decanal. Terpenoids showed correlations with a gene module that contained ERFs and HSFs. The findings support the hypothesis that fruit maturity and volatile formations vary in grape berries under different climates. Moreover, specific TFs could participate in volatile accumulations. The given results not only serve to enrich theoretical knowledge on the regulatory mechanism of volatiles in grapes, but also provide guidance for enhancing grape flavor and aroma by modulating cultivational conditions.With unique flavor and nutritional value, grapes are popular for eating and for the byproducts obtained in their processing. This study cultivated a popular grape variety, ‘Red Globe’, in two regions with different climates to investigate the discrepancies in their volatiles in response to climate. Saccharides, organic acids and transcriptomic and volatile metabolic analyses were studied separately via GC-FID, RNA sequencing and GC-MS/MS methods during the development of grape berries. In total, 83 volatiles were determined in samples, with (E)-2-hexenal the most abundant. Fatty acid derivatives and terpenoids in grapes showed discrepancies in different climates, and some of them were correlated to specific transcription factors.  Vitis vinifera L.), are widely planted in arid and semi-arid areas [As commercial fruits with popular flavor, grapes  grapes selected for investigation were separately cultivated at the experiment bases of Xinjiang Institute of Agricultural Sciences in Turpan and Urumqi, China. The cultivated environment was reported in a recent study [−2·s−1. By contrast, growing conditions in Urumqi included an average temperature of about 30 °C, average humidity of about 50% and light intensity of around 900–1200 μmol·m−2·s−1. In contrast to the temperate continental climate of Urumqi, Turpan possesses an arid, warm continental climate owing to its basin topography with longer sun exposure time. Fifteen grapevines with the same ages and growth trends that had been cultivated at the experimental bases of each district were selected for experimental use. At each stage, a bunch of grapes with similar growth trends from each grapevine was selected for sample collection. Five to ten well-developed berries without worms were collected from each of the bunches. Collected berries were divided into three parts for three replicates. Then the berries were immediately frozen by liquid nitrogen and stored at −80 °C until use. Berries collected at 45 days after flowering were labelled in accordance with their collection time as Stage 1 (S1). Then, berries were collected at intervals of fourteen days and labelled as Stages 2 to 5 (S2 to S5). External profiles of the selected grape berries are shown in The ‘Red Globe’ (nt study . In brie−1 fresh weight (FW) (n = 3).The saccharide and organic acid contents were analyzed by GC-FID and quantified with an internal standard method . Samples−1 FW (n = 3).The determination was processed in a gas chromatography–triple quadrupole mass spectrometer (GC-MS/MS) as previously reported . Grape bGrape berries were quickly frozen by liquid nitrogen and stored at −80 °C. Samples were sent to Beijing Genomics Institution  for RNA extraction, construction of the cDNA corpus and RNA sequencing. In brief, the total RNA was enriched by the mRNA enrichment method, as previously reported . The conVvUBI was used as a reference gene. Primers used in the present study were listed in −ΔΔCt method according to Ct value, as previously used [The validation of TFs was conducted by the real time quantitative PCR (RT-qPCR) method. Summarily, the extracted RNA from the grapes was reversed to cDNA by FastKing gDNA Dispelling RT SuperMix Kit  and RT-qPCR was completed with a SuperReal PreMix Plus Kit  in a CFX96 Real-Time PCR System . sly used . ResultsWGCNA was operated according to the previously published method . The difhttp://www.bioinformatics.com.cn (accessed on 16 August 2021). with modification. The Tukey method was conducted for analyzing significant differences (p < 0.05) and the Pearson correlation method was performed for correlation analysis on IBM SPSS Statistics 25 . Samples were collected with three parallels, and the results of the gene validations were expressed as mean ± SE, while others were exhibited as mean ± SD.Heatmap cluster, time cluster pattern, principal component analyses and fold change analyses were performed by MetaboAnalyst 5.0. Figures were depicted in Origin 2018 and an online website: Two monosaccharides and three organic acids, including fructose, glucose, malic acid, tartaric acid and citric acid were identified and quantified by GC-FID, as presented in In total, 83 kinds of volatiles were determined by GC-MS/MS in grapes, including phenylpropanoid/benzenoid derivatives; terpenoids; fatty acid derivatives, such as alcohols, aldehydes and esters; and so on. The time-accumulating patterns of volatiles from S1 to S5 in both TS and US grapes were determined and the top 25 positively and negatively correlated compounds are listed in Principal component analysis (PCA) was also conducted. As exhibited in p < 0.01). Notably, 1-hexanol was around 23-fold higher in TS than in US at S2. At all stages, the contents of decanal and 2,6,10,15-tetramethylheptadecane in TS were generally higher than in US. US had the higher nonadecane content at early stages, while TS possessed more nonadecane at later stages. Apart from the above components, low contents of terpenoids such as α-cadinene, δ-amorphene, α-muurolene, α-calacorene and linalool were detected in TS.Vitis vinifera reference genome (GCF_000003745.3_12X) via HISAT. Basic information of RNA sequencing was listed in In order to understand the effects of climate on grape volatiles at transcriptional levels, the RNA sequencing method was conducted on grape samples. After raw quality filtering, the results comprised about 185.73 Gb of clean sequence data with 40 to 45 million clean reads of each sample. Altogether, 77.33% to 91.23% reads were successfully mapped on p < 0.01) and are listed in DnaJ in TS was higher than that in US at S4, but it was upregulated in US at other stages as compared to TS. Validated by RT-qPCR, the expressions of PCC13-62 in US were higher than in TS from S2 to S4.The analyses of DEGs were completed in TS and US at each stage. Results are shown in p < 0.01). The two groups of DEGs were annotated into 192 and 206 pathways, respectively , was less highly expressed in desiccation-sensitive species when compared with desiccation-tolerant species [The chaperone protein DnaJ (HSP40) family was shown to have a unique function under heat stress in bidopsis . PCC13-6 species . TherefoVvWRKY22 was highly expressed in TS at later stages. Therefore, we inferred that the high expressional pattern of VvWRKY22 in TS was the outcome of high light intensity and long sunshine duration, and consequently induced the accumulation of saccharides.As mentioned with regard to TFs, a novel essay demonstrated that VvWRKY22 could regulate saccharide accumulation in grapes by interacting with VvSnRK1.1 or VvSnRK1.2 proteins . MoreoveAtPGR and act as a positive regulator of glucose [SlbHLH95 in tomato fruit ripening resulted in the accumulation of glutathione, soluble saccharides and starch [bHLH95 exhibited a negative correlation (r = −0.975) with (E)-2-hexenal -2-Hexenal was the principal component in the ‘Red Globe’ grape variety, and declined during fruit ripening. We inferred that the high temperature and long sunlight duration in Turpan enhanced the expression of


Shen-Shi-Jiang-Zhuo formula (SSJZF) exhibits a definite curative effect in the clinical treatment of non-alcoholic fatty liver disease (NAFLD).To explore the therapeutic effect and mechanism of SSJZF on NAFLD.Sprague Dawley rats were randomly divided into control, NAFLD, positive drug (12 mg/kg/day), SSJZF high-dose (200 mg/kg/day), SSJZF middle-dose (100 mg/kg/day), and SSJZF low-dose (50 mg/kg/day) groups. After daily intragastric administration of NAFLD rats for 8 weeks, lipid metabolism and hepatic fibrosis were evaluated by biochemical indices and histopathology. Then we uncovered the main active compounds and mechanism of SSJZF against NAFLD by integrating RNA-sequencing and network pharmacology, and PI3K/AKT pathway activity was verified by western blot.total triglycerides (58%), cholesterol (62%), aspartate aminotransferase (57%), alanine aminotransferase (41%) andγ-glutamyl transpeptidase (36%), as well as the expression of ACC (5.3-fold), FAS (12.1-fold), SREBP1C (2.3-fold), and CD36 (4.4-fold), and significantly reduced collagen deposition (67%). Then we identified 23 compounds of SSJZF that acted on 25 key therapeutic targets of NAFLD by integrating RNA-sequencing and network pharmacology. Finally, we also confirmed that high dose SSJZF increased p-PI3K/PI3K (1.6-fold) and p-AKT/AKT (1.6-fold) in NAFLD rats.High dose SSJZF had the best inhibitory effect on hepatic lipid accumulation and fibrosis in rats with NAFLD, which significantly down-regulated We found for first time that SSJZF improved NAFLD in rats by activating the PI3K/Akt pathway. These findings provide scientific support for SSJZF in the clinical treatment of NAFLD and contribute to the development of new NAFLD drugs. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease characterised by excess lipid accumulation in liver without alcohol consumption  DC. (Compositae), Poria cocos (Schwein) F.A. Wolf (Polyporaceae), Magnolia officinalis (Rehder & E. H. Wilson) N. H. Xia & C. Y. Wu (Magnoliaceae), Rhizoma Pinelliae (Thunb.) Breit. (Araceae), Talcum (Silicates), Tetrapanax papyriferus (Hook.) K. Koch , Radix Bupleuri (Umbelliferae), Citrus aurantium L. (Rutaceae), Radix Paeoniae rubra (Ranunculaceae), Panax notoginseng (Burkill) F.H. Chen , Rubia cordifolia Linn (Rubiaceae), Fructus Broussonetiae (Moraceae), and Pinellia ternate (Thunb.) Ten. ex Breitenb (Araceae). Our previous research found that SSJZF could alleviate the symptoms of NAFLD patients through improving liver function, as well as reducing the lipid levels of NAFLD patients , as an important complementary and alternative medicine approach, has been shown efficacy and safety in treating complex diseases, including NAFLD -induced NAFLD to explore whether the protective effect of SSJZF on NAFLD was realised by improving hepatic lipid accumulation in clinical practice. Further, we used comprehensive analysis of mRNA-sequencing data mining, network pharmacology and bio-informatics to investigate the underlying mechanisms and effective compounds SSJZF against NAFLD, which provided theoretical basis for the application of SSJZF in clinical treatment of NAFLD.Atractylodes lancea , Poria cocos , Magnolia officinalis , Rhizoma Pinelliae , Talcum , Tetrapanax papyriferus , Radix Bupleuri , Citrus aurantium , Radix paeoniae rubra , Panax notoginseng , Rubia cordifolia , and Fructus Broussonetiae .SSJZF consists of In accordance with the dose ratio of SSJZF , the mixEpidemiological and animal model studies have shown that female sex hormone oestrogen is protective against NAFLD/NASH : normal control group (NC), fed with normal diet; NAFLD group (NAFLD), fed with HFD for 16 weeks; NAFLD + polyene phosphatidylcholine capsule group , after 8 weeks of HFD feeding, rats were orally treated with polyene phosphatidylcholine  at a dose of 12 mg/kg/day via a lavage needle and fed on HFD feeding for 8 weeks; NAFLD + low dose SSJZF group (L-SSJZF), after 8 weeks of HFD feeding, rats were orally treated with solid SSJZF at a dose of 50 mg/kg/day via a lavage needle and fed on HFD feeding for 8 weeks; NAFLD + middle dose SSJZF group (M-SSJZF), after 8 weeks of HFD feeding, rats were orally treated with solid SSJZF at a dose of 100 mg/kg/day via a lavage needle and fed on HFD feeding for 8 weeks; NAFLD + high dose SSJZF group (H-SSJZF), after 8 weeks of HFD feeding, rats were orally treated with solid SSJZF at a dose of 200 mg/kg/day via a lavage needle and fed on HFD feeding for 8 weeks. Raw drug dose of rats was obtained according to the conversion of body surface area and man-mouse dose, and the medium dose of crude drug given to rats was the clinical dose of human. After 4 weeks intervention, rats were sacrificed to collect blood samples and live tissues samples according to previously described protocols  for 24 h at 4 °C, following by dehydration in alcohol gradients. And then fixed samples were processed into paraffin-embedded 4 μm sections and stained with H&E .For hepatic lipogenesis observation, fresh liver tissues were dehydrated with a sucrose gradient and then frozen in OCT embedding medium  using liquid nitrogen. After freezing, the frozen liver tissues were sectioned at 10 μm in a freezing microtome and stained with Oil Red O  in dark. Subsequently, the sections were differentiated and washed. The nucleus was stained for 3 min with haematoxylin, and sealed with glycerol gelatine for observation.The degree of hepatic fibrosis was assessed by Masson staining. Briefly, fresh liver tissue was fixed in 4% paraformaldehyde overnight, dehydrated, paraffin-embedded, and sectioned. The sections were stained using Masson kits  according to the instructions. The collagen deposition was observed using a light microscope and analysed by the Image-Pro Plus software for relative quantification.HYP content was used to analyse by Hydroxyproline Content Assay Kit  following the instructions. In brief, the liver samples (0.2 g) were digested with 2 mL Extract solution in 110 °C oven for 6 h. After cooling, adjust the PH to 7 with 10 mol/L NaOH constant volume to 4 mL with distilled water and then centrifuged at 16,000 rpm for 20 min. After centrifugation, the supernatant was taken and measured by visible spectrophotometry. Hydroxyproline content was corrected to liver weight and expressed as µg hydroxyproline/mg liver.2O2 for blocking endogenous peroxidase. Then antigen retrieval was performed by microwave heating. After blocking non-specific antigen binding with 5% BSA at 37 °C for 1 h, the sections were incubated with a specific primary antibody against α-SMA, collagen I, collagen IV, and fibronectin  at 4 °C overnight. After incubating with the corresponding secondary antibodies at 37 °C for 1 h, the sections were stained with diaminobenzidine and counterstained with haematoxylin. Representative images were taken using an Olympus light microscope and analysed by the Image-Pro Plus software for relative quantification.Immunostaining was performed to determine the subcellular localisation and expression pattern of fibrosis related protein  in HCC tissues of mice in each group. Briefly, the paraffin-embedded sections were dewaxed, rehydrated, and incubated with 3% HThe levels of total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transpeptidase (γ-GT) in serum were accessed by an automatic biochemistry analyser  according to the manufacturer’s instructions. In addition, the levels of TC, TG, AST, ALT, and γ-GT in liver tissues were detected using Total cholesterol assay kit , Triglyceride assay kit , Aspartate aminotransferase Assay Kit , Alanine aminotransferase Assay Kit , and γ-glutamyl transferase Assay Kit , respectively.® Fast qPCR Mix  on the ABI 7500 Fast Real-Time PCR system (Applied Biosystems). GAPDH was used as an internal control for mRNAs. The relative mRNA expression of genes was calculated through the 2−ΔΔCt method. All the primer sequences used in this study are shown in Total RNA from liver tissues was extracted with Trizol (Invitrogen) according to the manufacturer’s instructions. Then cDNA synthesis was performed using PrimeScript™ RT reagent Kit with gDNA Eraser . RT-qPCR was performed to determine the relative mRNA level using the TB Greenp-value < 0.05 and |log2 FC| > 0.5. Unsupervised hierarchical clustering and the visualisation of heatmap were performed using the R platform (http://www.r-project.org/).The next generation sequencing experiments were performed by Shanghai Biotechnology . Briefly, total RNAs from rat livers were extracted by Trizol , and the purity and integrity of RNA were detected by agarose gel electrophoresis analysis. Then, the purity of RNA (OD 260/280) was detected using Nanodrop , and the RNA concentration was accurately quantified using Qubit 2.0 . Finally, the integrity of RNA was accurately detected by Agilent 2100 . The cDNA library was constructed using NEBNext1 UltraTM RNA Library Prep Kit for Illumina , and high-throughput sequencing was then performed using the HiSeqTM 2500 system (Illumina). Clean data was aligned to the rat reference genome by TopHat software and gene expression levels were assessed using fragments per kilobase of transcript per million mapped fragments (FPKM). The limma package in R was used to analyse the difference of expression matrix of sequencing data. Differentially expressed genes were identified with the threshold of https://tcmspw.com/tcmsp.php) database was used to identify the compounds in SSJZF. The screened the potential active compounds of the formula with the characteristics of oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18. OB indicates the drug-like nature of molecules as therapeutic agents and represents the relative amount of orally administered drug that reaches the blood circulation, shown by the convergence of the adsorption, distribution, metabolism, and excretion (ADME) process. ‘DL’ is a qualitative concept used in drug design to determine how drug-like a prospective compound is to describe and optimise pharmacokinetic and pharmaceutical properties , GeneCards (https://www.genecards.org), MalaCards   . In the network, the nodes represented the compounds and targets, and the edges represented the interactions between the targets and compounds.https://www.r-project.org/) installed on the Bioconductor, KEGG pathway analysis can be conducted, which can be used to explore the functional spectrum of genes or gene clusters  were screened out and visualised.Based on the clusterProfiler R package  containing proteinase inhibitor cocktail  and phosSTOP phosphatase inhibitor cocktail  from homogenised liver tissues. Then the proteins were separated by SDS - PAGE electrophoresis, and were transferred to polyvinylidene fluoride (PVDF) membranes . The membranes were blocked with 5% slim milk and incubated with primary antibodies including p-PI3K , PI3K , p-Akt , Akt  and GAPDH . After incubation with secondary antibodies, protein bands were visualised using an ECL detection kit . Protein expression levels were quantified by densitometry using ImageJ software  and normalised to GAPDH .t-test was used for comparison between two groups and one-way ANOVA for more than two groups. The p-values < 0.05 were considered as statistically significant.The data were represented as the mean ± SD. All statistical analysis and plotted images were performed using GraphPad Prism 6.0 . The paired or unpaired Student’s To confirm the efficiency of SSJZF for NAFLD treatment, rats were fed with high-fat diet (HFD) for 8 weeks to induce NAFLD and then subjected to treatment with or without SSJZF or PC by gavage for 8 weeks. The pathological changes of rat liver tissues were detected by H&E staining and Oil Red O staining . CompareTo elucidate the therapeutic mechanism of SSJZF against NAFLD, we performed mRNAs - sequencing on livers tissues obtained from control rats, NAFLD rats, and NAFLD rats treated with SSJZF. Differentially mRNA expression was obtained with the threshold of P-value < 0.05 and |log FC| > 1. A total of 1224 differentially expressed genes were identified by comparing the NAFLD rats with the control rats, of which 687 were up-regulated and 537 were down-regulated . A totalSSJZF consists of complexity of compounds and TCMSP was used to retrieve the potential compounds. With the limitation of OB ≥ 30% and DL ≥ 0.18, a total of 159 potential compounds of SSJZF were collected after deleting the duplicates . The tarTo further examine the signalling pathways and functions of these target genes, we performed functional enrichment analysis using KEGG pathways. The result indicated that 25 genes were mainly enriched in PI3K/Akt signalling pathway, endocrine resistance, TNF signalling pathway, lipid and atherosclerosis, Rap1 signalling pathway, MAPK signalling pathway, etc. . Taken tPI3K/Akt signalling pathway has also been demonstrated to play a critical role in the regulation of liver lipid metabolism in NAFLD  is a key factor leading to the occurrence and development of NAFLD ], could decrease TNF level in serum and improve NASH in patients  is a pivotal modulating component of the immune system, which regulates innate and adaptive immunity and implicates different inflammatory diseases such as tumour and inflammatory bowel disease  was not used to further identify these compounds in SSJZF and blood-absorbed compounds. In future study, these parts will be included in our experiments.In the present study, our data revealed that SSJZF ameliorated HLF-induced NAFLD via activating the PI3K/AKT pathway signalling. Importantly, we screened out 23 chemical compounds as the potential effective ingredients of SSJZF which acted on 25 targets of NAFLD by the comprehensive analysis of network pharmacology, mRNA-sequencing data mining and bioinformatics. This study not only provided theoretical basis for the application of SSJZF in clinical treatment of NAFLD, but also screened out some major compounds of SSJZF and their potential targets which will facilitate the development of new drugs for NAFLD.All authors made substantial contributions to the conception, study design, acquisition of data, analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to take responsibility and be accountable for the contents of the work.


Testicular histological evaluation and spermatogenic process was also performed. The results showed that oxidative, inflammatory, and metabolic factors significantly increased in obese rats. The testicular expression of aromatase, NF-κB, Bax, and caspase 3 increased and Nrf2 expression decreased in obese rats, while (pre) treatment with garlic powder significantly decreased the expression of these genes in obese rats. These results were also confirmed by the findings of the histological evaluation and sperm analysis. It can be concluded that garlic powder could improve reproductive dysfunction in obese rats.Today, adolescent obesity is recognized as an epidemic and a cause of reproductive disorders. Decreased testosterone levels occur due to functional defects in the hypothalamus-pituitary axis, excessive activity of cytochrome P450 aromatase enzyme, and testicular dysfunction in these people. Oxidative damage, inflammation, and apoptosis are also the main mechanisms of testicular damage during obesity. The use of herbal products such as garlic can improve this disorder due to its anti-inflammatory and antioxidant properties. Therefore, the aim of this study is to investigate the effect of pretreatment and treatment of garlic powder on the expression of cytochrome P450 aromatase enzyme and the expression of genes involved in testosterone synthesis, inflammation, oxidative damage, apoptosis in testicular tissue, and metabolic function of liver tissue in young male obese rats. Eighty male Wistar rats were divided into the controlled and treated groups. Serum levels of lipid, glucose, and insulin as metabolic factors were measured along with the testicular antioxidant and inflammation markers. The expression of Bcl2, Bax, and caspase-3 along with NF- The number of adults over 18 years of age affected by obesity and its complications exceeds 1.9 billion worldwide [κB pathway is activated and increased the release of proinflammatory factors like IL-1β, IL-6, and TNF-α, which can induce cell apoptosis [Obesity refers to abnormal and considerable body fat accumulation with a harmful effect on health. According to the definition of the World Health Organization (WHO), obesity is when the body mass index (BMI) is higher than 30 kg/morldwide . Obesityorldwide . Obesityorldwide , 7. The orldwide . ROS proorldwide –13. The orldwide , 13. Mororldwide , 15 and orldwide  significpoptosis , 18. Thipoptosis . In addipoptosis –22. Therpoptosis –29.Allium sativum L.) is an annual plant that uses as a medicinal plant and spice and has been used for centuries to protect the body against infections [The medicinal plants and the products are preferred by many, when given the low cost, availability, and low side effects , 31. Garfections . Recentlfections –37. Morefections . El-Akabfections  also repfections . Sheweitfections  showed tfections . Lai et fections  also repfections . AlthougAllium sativum) was procured from a local market by a botanist, and it was identified and checked on https://www.theplantlist.org. Normal saline was used for dose preparation.Garlic  and the total antioxidant capacity, Folin–Ciocalteu spectrophotometric method  and the Eighty male Wistar rats  were kept based on the standard conditions from animals in the lab . The subjects were allowed free access to the standard diet and water. The “Guidelines for the Care and Use of Laboratory Animals” was used for animal care and for observing ethics. The Ethics Commission with ethical number EC20210006558 approved the study.  Group 1: control rats were provided with distilled water orally as a vehicle using gavage (12 weeks)  Group 2: obese rats were provided with distilled water orally as a vehicle using gavage (12 weeks)  Group 3: healthy rats were orally fed with garlic powder (50 mg/kg/day) using gavage (12 weeks)  Group 4: healthy rats were orally fed with garlic powder (100 mg/kg/day) using gavage (12 weeks)  Group 5: obese rats were orally fed with garlic powder (50 mg/kg/day) using gavage (12 weeks)  Group 6: obese rats were orally fed with garlic powder (100 mg/kg/day) using gavage (12 weeks)  Group 7: animals were orally protected by gavage for 12 weeks during induction of obesity with garlic powder (50 mg/kg/day)  Group 8: animals were orally protected by gavage for 12 weeks during induction of obesity with garlic powder (100 mg/kg/day)To cause obesity, the subjects were fed a high-fat diet (HFD) for 12 weeks and it was checked using the HOMA-IR evaluation test . After oβ and TNF-α were determined using ELISA by a rat-specific kit . The concentration of protein in testes was measured using Bradford and bovine serum albumin was used as the standard [Following the final treatment session fasting for one night, blood samples were taken through cardiac puncture. After centrifuging , the collected serums were tested to determine insulin, lipid profile, and glucose. The parameters except for insulin were measured using Hitachi 912. To determine the serum level of insulin, the ELISA method was utilized along with a rat-specific kit . Following the sampling, the testis tissue was separated and weighed. Testicular and serum testosterone levels were measured by ELISA using an existing commercial kit . The CAT activity of tissue was examined in terms of the degradation rate of hydrogen peroxide using CAT read at 230 nm . The totstandard .β-actin expression. In addition, the method 2−ΔΔCT was used to determine the relative expression level.To assess reproductive damage caused by obesity, testicular expression of genes that had a role in the production of testosterone and P450Aromatase was measured along with oxidative stress, apoptosis, and inflammation. Total RNA extract kit was used to extract total RNA . Primer Script reverse transcriptase was used to synthesize complementary DNA (cDNA) from RNA samples . Here, the primers of target genes were selected following the references , 48.  Taμm thick were made using a microtome. After staining, using hematoxylin and eosin (H&E), the evaluation of the prepared cross-sections was done based on the study of Memudu et al. [The left testicles were fixed in 4% formaldehyde solution. After at least a week, they were embedded in paraffin and incisions approximately 5 u et al. . The stau et al. . 50 sperp < 0.05 was considered as the minimum statistically significant level.The data were recorded in SPSS 18. One-way analysis of variance (ANOVA) and Tukey post hoc test were used to compare the differences between the groups. The results were presented as the means ± standard deviation (SD). μg/mL). In addition, total phenol content was determined using the calibration curve of the equation and reported as μg of gallic acid equivalents per mg of sample (μg of GAE/mg of the sample) equal to 6863.59 μg GAE/mg sample.p < 0.05, p < 0.05, p < 0.05, p < 0.05, p < 0.05, The results showed that consuming a high-fat diet for 12 weeks significantly improved food intake and weight gain (μU/L) level, and HOMA-IR index significantly increased in the obesity group  in the liver in HFD-fed mice” [Clearly, the improvement of hepatic lipid metabolism in obesity by the consumption of medicinal plants is associated with the reduction of local and systemic inflammation and oxidative damage , 42, 55.pathways , 87. Theresponse . TNF-α iithelium . NF-κB i pathway . In line pathway –92. Thestivities , 94. Anotivities . It is ativities . In linetivities  showed ted mice” . These fβ HSD, and CYP19A1 in the testes tissue of HFD-fed rats. In line with these results, the findings of the histological analysis of the testicular tissue in the control and HFD groups (pre)treated with garlic indicated that the morphology of the seminiferous tubules was not changed and kept its normal cycle of spermatogenesis. However, morphological abnormalities including increased abnormal spermatogenesis and degeneration of sperm tubes are clearly evident in the testicular tissue of obese rats, which is consistent with what has been previously reported [α and IL-6, which also improves production of aromatase, acting in an autocrine or paracrine fashion [βHSD in the testis tissues. These effects can be inhibiting local or systemic inflammation and inhibiting apoptosis and oxidative damage in the testicular tissue, improving the activity of the pituitary-gonadal axis and improving the metabolic state of glucose or lipids in the liver tissue. These findings can provide a new window for the therapeutic use of garlic powder or its products as a modifier of metabolic and reproductive disorders in obese people. An achievement is well demonstrated by many studies related to alternative and complementary medicine [Our findings demonstrated that using a variety of doses of garlic as pretreatment and treatment improved the activity of the pituitary-gonadal axis and the expression genes that have a role in synthesis of testosterone, i.e., StAR, P450Scc, 17reported . Oi et areported  reportedreported . These rreported . Memudu reported  also shoreported . Our resreported . In factreported , 98. Morreported  also shoreported . Garlic reported . Moreovereported  showed treported . Howeverreported . In addi fashion –103. In  fashion . In line fashion , 106. Asmedicine , 48, 107


To investigate the efficacy of donepezil hydrochloride plus olanzapine for senile dementia and its effect on the recovery of cognitive function.  A total of 60 patients with senile dementia admitted to our hospital from April 2020 to July 2021 were recruited and assigned to receive either olanzapine alone (observation group) or donepezil hydrochloride plus olanzapine  via the random number table method, with 30 patients in each group. P < 0.05). Before treatment, the difference in the scores of cognitive function between the two groups did not come up to the statistical standard (P > 0.05). Donepezil hydrochloride plus olanzapine was associated with significantly higher scores of cognitive function in patients versus olanzapine alone (P < 0.05). The two groups had a similar incidence of adverse reactions (P > 0.05).  The combined therapy resulted in significantly higher clinical efficacy versus monotherapy of olanzapine ( Donepezil hydrochloride plus olanzapine substantially enhances the recovery of cognitive function of patients with senile dementia and features a manageable safety. Further trials are, however, required prior to clinical promotion. Alzheimer's disease (AD) is a common clinical neurological disease in the elder population and is characterized by mental retardation, cognitive dysfunction, and behavioral dysfunction, severely compromising quality of life . MedicatOlanzapine is a common antipsychotic drug for psychiatric diseases that acts on various receptor systems and exerts various pharmacological activities . NeverthA total of 60 patients with senile dementia admitted to our hospital from April 2020 to July 2021 were recruited and assigned to receive either olanzapine alone (observation group) or donepezil hydrochloride plus olanzapine  via the random number table method, with 30 patients in each group. Undersigned informed consent was obtained from all the eligible patients, and the study protocol was approved by the hospital ethics committee, with the ethics number: SH-SY20200402. All procedures complied with the Declaration of Helsinki's ethical guidelines for clinical research.Inclusion criteria were as follows: (1) patients who were clinically diagnosed with Alzheimer's disease and (2) the patients and their families were informed and voluntarily participated in this study.Exclusion criteria were as follows: (1) patients who have recently received psychotropic drugs; (2) patients with other psychiatric diseases; and (3) patients and their families who were not willing to comply and cooperate reasonably with the present study.The patients in the two groups received 5 mg of olanzapine  daily at the beginning of administration, and the dose was increased according to disease severity, with a maximum of 20 mg daily .The patients in the experimental group additionally received 5 mg of donepezil hydrochloride (H20070181) daily before bed. The dose was increased according to disease severity, with a maximum of 10 mg daily . The durTCM Adjuvant Therapy. The two groups received Jieyu Yizhi Decoction. The ingredients of the decoction include 12 g of Bupleuri Radix and Polygalae Radix, 30 g of Codonopsis Radix, Angelicae Sinensis Radix, Poria, Atractylodis Macrocephalae Rhizoma, and Schisandrae Chinensis Fructus, 9 g of Pinelliae Rhizoma, 15 g of Paeoniae Radix Alba and Acori Tatarinowii Rhizoma, and 10 g of Licorice. The herbs were decocted with water to obtain 200 mL of filtrate and administered twice daily. Benzodiazepines were prevented during TCM treatment.  Cured: the patient's BEHAVE-AD score decreased by less than 75% after treatment.  Markedly effective: the patient's BEHAVE-AD score decreased by 50–75% after treatment.  Effective: the patient's BEHAVE-AD score after treatment decreased by 25–50%.  Ineffective: the patient's BEHAVE-AD score after treatment decreased by less than 25%.Wechsler Adult Intelligence Test and Clinical Memory Scale were used to evaluate the cognitive function of patients, including image-free recall, recognition of meaningless images, pointing memory, memory of portrait characteristics, learning association, memory IQ, speech IQ, operational IQ, and total IQ. The higher the score of each index, the better the recovery of the cognitive function of the patient.Adverse reactions during treatment include insomnia, lethargy, nausea and vomiting, and abnormal liver function.T test. Count data were expressed as the number of cases (rate) and analyzed using the chi-square test. Statistical significance was indicated by P < 0.05.SPSS 21.0 was the software used for data analyses. Measurement data were expressed as P > 0.05)  years, with disease duration of 1 to 7 (3.82 ± 0.58) years. There were 22 males and 8 females in the experimental group, aged 61 to 83 (73.44 ± 3.42) years. The patient characteristics of the two groups were comparable ( > 0.05) .P < 0.05)  .P > 0.05). Donepezil hydrochloride plus olanzapine was associated with significantly higher scores of cognitive function in patients versus olanzapine alone (P < 0.05)  .P > 0.05)  .Senile dementia, also known as Alzheimer's disease, is a common central nervous system degenerative disease in the elderly . It is aOlanzapine is a new clinical atypical neuroleptic drug  with a sP < 0.05), indicating a favorable treatment efficiency of donepezil hydrochloride plus olanzapine for senile dementia. It effectively increases the concentration of acetylcholine in the relevant areas of the patient's brain, which positively affects the cognitive status of the patient's body function [The results of the present study showed that the donepezil hydrochloride plus olanzapine was associated with significantly higher clinical efficacy and scores of cognitive function in patients versus olanzapine alone (function . The reafunction . MoreoveDonepezil hydrochloride plus olanzapine herein significantly improved the cognitive function of patients and considerably relieved the disease condition of patients with Alzheimer's disease . There wIn conclusion, donepezil hydrochloride plus olanzapine substantially enhances the recovery of cognitive function of patients with senile dementia and features a manageable safety. Further trials are, however, required prior to clinical promotion.


This study assessed the preventive properties of naringin and naringenin on paclitaxel-induced nephrotoxicity and cardiotoxicity in adult male Wistar rats. Intraperitoneal injection of paclitaxel 2 mg/kg body weight, two days/week on the 2nd and 5th days of each week, with or without oral administration of naringin and/or naringenin 10 mg/kg body weight every other day, was continued for six weeks. Treatment of rats with naringin and/or naringenin significantly reversed elevated serum creatinine, urea, and uric acid levels caused by paclitaxel, reflecting improved kidney function. Similarly, heart dysfunction induced by paclitaxel was alleviated after treatment with naringin and/or naringenin, as evidenced by significant decreases in elevated CK-MB and LDH activities. After drug administration, histopathological findings and lesion scores in the kidneys and heart were markedly decreased by naringin and/or naringenin. Moreover, the treatments reversed renal and cardiac lipid peroxidation and the negative impacts on antioxidant defenses via raising GSH, SOD, and GPx. The preventive effects of naringin and naringenin were associated with suppressing oxidative stress and reestablishing antioxidant defenses. A combination of naringin and naringenin was the most efficacious in rescuing organ function and structure. Taxus brevifolia (Pacific yew). The chemical is a taxane, an intermediary metabolite that displays potent anticancer activity [Paclitaxel is a natural tricyclic diterpenoid isolated from the bark of activity –3. Taxanactivity –7. Moreoactivity . Paclitaactivity . Unfortuactivity .A paclitaxel formulation using Cremophor EL (CrEL) as a solvent (Taxol) induced cumulative sensory-dominant peripheral nephrotoxicity in humans, clinically characterized by numbness and paresthesia of the extremities. This toxicity was a result of CrEL exposure. Serum creatinine levels increased in association with increased damage –15. AddiPaclitaxel produces cytotoxicity by enhancing the formation of reactive oxygen species (ROS), thus inducing oxidative stress , 19. Henin vitro and in vivo [Natural therapeutics have been investigated to prevent the side effects of anticancer drugs –28, high in vivo . Flavono in vivo . Naringi in vivo . Additio in vivo .Concerning previous studies, using plant constituents with antioxidant and anti-inflammatory properties will be our strategy to counteract and treat the side effects of anticancer drugs. As a result, this investigation was carried out to assess the renal and cardiac toxicity prevention by naringin and naringenin coincident with paclitaxel-treated Wistar rats. We assessed toxicity by examining kidney and heart function, oxidative stress, and antioxidant defense systems, as well as histopathology.ad libitum. All animal-related procedures were performed, complying with the recommendations and instructions of the Experimental Animal Ethics Committee, Faculty of Science, Beni-Suef University, Egypt  We did everything we could to lessen animals' pain and suffering.Fifty adult male Wistar rats with weights of ∼130–150 g were collected from the VACSERA Vaccination Centers' Animal House in Dokki, Giza, Egypt. In order to rule out any concurrent infections, animals were watched for 15 days before the experiment began. Rats were housed in polypropylene cages with ventilated stainless steel lids at a standard air temperature of (25 ± 5°C) and with a 12-hour light cycle. Animals had free access to water and received a sufficiently balanced standard diet on a daily basis L 16 A/1916/1212/13), 1,1,3,3 tetra-methoxy propane was obtained from Sigma-Aldrich  , metaphosphoric acid was obtained from ALPHA CHEMIKA Company (India) (batch code: M 21519), 5,5- dithiobis nitrobenzoic acid was obtained from Sigma-Aldrich  (batch code: 40K3652), GSH was obtained from PanReac AppliChem ITW Companies (Spain) (batch code: 3W010085), and pyrogallol was obtained from Research Lab Company (India) (batch code: 1280B251114).Paclitaxel (Taxol®) was obtained from the Bristol–Myers Squibb global biopharmaceutical company (batch code: 7E05628). Naringin (batch code: BCBM4171 V) and naringenin (batch code: BCBJ2179 V) were obtained from Sigma . The creatinine reagent kit  and the urea reagent kit  were purchased from Biosystem S.A. (Spain). Uric acid, CK-MB, and LDH reagent kits were purchased from Spin React (Spain), with catalog numbers MD41001, MD41254, and MX41214, respectively. Chemicals of oxidative stress including trichloroacetic acid were obtained from PanReac AppliChem ITW Companies (Spain) (batch code: 5O011689), thiobarbituric acid was obtained from Sd Fine Chem Limited(SDFCL) Company (India)  kg body weight (b.wt) orally every other day and 2 mL saline twice per week intraperitoneally for six weeks.Paclitaxel-administered control group: rats were administered paclitaxel intraperitoneally at a dose level of 2 mg/kg b.wt  twice wePaclitaxel-administered group treated with naringin: rats were administered paclitaxel intraperitoneally as in group 2 and received oral naringin 10 mg/kg b.wt treatment  every otPaclitaxel-administered group treated with naringenin: rats were treated as above but were administered naringenin at a dose level 10 mg/kg b.wt  (dismantPaclitaxel-administered group treated with a combination of naringin and naringenin: rats were treated as above but received both naringin and naringenin at dose levels of 10 mg/kg (dismantled in 5 mL 1% CMC) b.wt every other day for six weeks.In this study, adult male Wistar rats were divided into five groups, each with ten rats.Using diethyl ether inhalation anesthesia before decapitation and dissection and at the end of the experiment, blood samples were taken from each animal's jugular vein into gel and clot activator tubes, allowed to coagulate at room temperature, and then centrifuged at 3,000 rpm for 15 min. Clearly, nonhemolyzed sera were aspirated quickly, divided into four aliquots, and kept at 30°C until they were needed for biochemical testing. Each animal's kidney and heart tissues were rapidly removed and weighed after decapitation and dissection. A portion of tissue of each organ was preserved in phosphate-buffered formalin (10%) for 24 h before being transferred to 70% alcohol for histological analysis. About 0.5 g of each tissue was homogenized in 5 mL saline (0.9% NaCl) with a Teflon homogenizer . After the homogenates had been centrifuged for 15 minutes at 3,000 rpm, the supernatants were aspirated from the homogenates and kept in a deep freezer at −20°C for determination of oxidative/antioxidant status.Creatinine and urea levels in serum were measured as previously described by Fabiny and Ertingshausen  and TabaCK-MB and LDH activities in serum were assayed as described by Young  and YounμL of 76% trichloroacetic acid (TCA) to 0.5 mL of the kidney or heart homogenate. Then, 175 μL of 1.07% thiobarbituric acid (TBA) was added. After 30 minutes in a water bath at 80°C, the formed faint pink color was detected at 532 nm. The standard was MDA .Kidney and heart lipid peroxidation (LPO) was estimated as previously described by Preuss et al. . BrieflyKidney and heart GSH content was estimated by following the findings reported by Beutler et al.  with modμL of the homogeneous supernatant was placed in a Wasserman tube containing 350 μL Tris buffer (pH 7.6), 50 μL GSH solution (2 mM), and 50 μL H2O2 (3.38 mM). The residual GSH content was determined after a 10-minute incubation period, as indicated previously. A standard was made by substituting 50 μL distilled water for 50 μL of the sample, and a blank was made by substituting 100 μL distilled water for 50 μL of the sample and 50 μL GSH solution. The amount of GSH transformed to GSSG was then determined using the residual GSH content, and the enzyme activity was calculated.Kidney and heart glutathione peroxidase (GPx) activity was measured as previously described by Matkovics et al. . This meThe activity of superoxide dismutase (SOD) in the kidney and the heart was measured as previously described by Marklund and Marklund . The proμm sections were cut from paraffin wax tissue blocks with a sliding microtome. For regular examination under an electric light microscope, the tissue sections were fixed on glass slides, dewaxed, and hematoxylin and eosin stained (H&E) [Parts of the kidneys and hearts of rats were collected and fixed in 10% neutral buffered formalin for 24 h. Tissues were then washed with water and dehydrated in a series of ethyl alcohol dilutions . Specimens were cleaned with xylene before being embedded in paraffin wax for 24 hours at 56°C in a furnace. Four ed (H&E) . Score sp < 0.05.All data were presented as the mean ± standard error of the mean (SEM). For statistical analysis, Statistical Package for the Social Sciences (SPSS) programme (version 22)  was utilized. Tukey's post hoc test was used to compare mean values pairwise. Differences were deemed significant at p < 0.05) in serum urea, creatinine, and uric acid levels. Percentage changes were +52.43, +106.98, and +352.46%, respectively, compared to normal controls.Administration of paclitaxel to rats for 6 weeks produced a significant increase (p > 0.05). The naringin and naringenin combination seemed to be the most efficacious for normalizing elevated serum levels. Percentage decreases in urea, creatinine, and uric acid were −28.75, −47.19, and −40.22%, respectively, compared with paclitaxel alone  and SOD (−8.19%) and GPx (−23.23%) activities in comparison to the normal control group. The oral dose of naringin and naringenin and their combination improved kidney LPO significantly. Additionally, treatment with naringin and naringenin or their combination resulted in a significant increase in kidney GSH content. Also, these treatments reversed the decline in activities of kidney SOD and GPx.As outlined in In a similar way as in the kidney, paclitaxel administration resulted in a significant increase in LPO in heart tissue, whereas heart GSH content, SOD activity, and GPx activity decreased significantly. Naringin and naringenin and their combination significantly increased cardiac LPO. Additionally, heart GSH content was significantly increased as a result of the treatment with naringin and the combination. However, the treatment with naringenin resulted in a nonsignificant rise in heart GSH content. Moreover, all three treatments significantly enhanced heart SOD and GPx activities .Renal lesions are illustrated in Cardiac pathological lesions are described in Paclitaxel is largely effective for ancillary treatment of tumors in ovarian  and breaThe current study showed the impact of serial intraperitoneal injections of paclitaxel over a period of six weeks at the dose level of 2 mg/kg b.wt 2 days/week. These injections induced nephrotoxicity evidenced biochemically by a significant elevation of serum urea, creatinine, and uric acid levels. Thus, the drug impairs renal function and may compromise urinary excretion of toxic metabolites. Our data are consistent with those reported by Adikwu et al. . Ahmed ein vivo and in vitro [Citrus flavonoids naringin and naringenin have anti-inflammatory and antioxidant effects both in vitro . In compin vitro –69. In oin vitro  who repoin vitro , and narin vitro . Quercetin vitro .in vitro [In the present study, paclitaxel administration also induced cardiotoxicity, evidenced biochemically by a significant increase in serum activity of CK-MB and LDH. Histopathological findings supported these changes in serum enzyme activities. The hearts of the paclitaxel-administered group exhibited several adverse histological changes and lesions, including severe degenerative changes and necrosis of cardiac muscles accompanied by the presence of inflammatory and apoptotic cells. These findings concur with those of Saad et al.  who indiin vitro . Besidesin vitro . Paclitain vitro .in vivo and in vitro [In the current study, treatment of paclitaxel-administered rats with naringin and/or naringenin resulted in improvement in cardiac biomarkers and histological integrity. These outcomes are in line with those of Rajadurai and Prince  who showin vitro –80. Morein vitro  reportedvia ROS generation, resulting in oxidative stress [Renal and cardiac toxicity in paclitaxel-administered rats was correlated with a noticeable rise in kidney and heart LPO and a reduction in nonenzymatic antioxidant GSH content and enzymatic antioxidant (SOD and GPx) activities. These findings corroborate the findings of several other researchers –84 who re stress , 85. Alse stress . Moreovee stress .via its OH group and that this scavenging was responsible for reduced hepatic and renal damage.The current study's findings showed that administering naringin and/or naringenin decreases LPO, increases GSH content, and augments SOD and GPx activities in kidney and heart tissue after six weeks of treatment. This improvement may be attributed to scavenging ROS and free radicals induced by paclitaxel intoxication. These findings are consistent with those of the research by Fukui et al.  who provNaringin and naringenin and their combination prevent many adverse impacts on renal and cardiac function and histological integrity induced by paclitaxel in Wistar rats. This action is due to suppressing oxidative stress and enhancing antioxidant defense systems in both organs. The combination of naringin and naringenin was the most efficacious for protecting kidney and heart function and structural integrity. An important limitation of the study is the shortage of kidney and heart samples to perform Western blot analysis for determination of various mediators of apoptosis and inflammations due to their exhaustion in detection of oxidative stress/antioxidants biomarkers and histological investigations. Furthermore, clinical studies are required to assess the safety and efficacy of naringin and naringenin and their combination against paclitaxel-deteriorated effects on the heart and kidneys in human beings.


Mimosa pudica found wildly in the Terai region of Nepal and assess its physicochemical properties, such as total phenolic content (TPC) and total flavonoid content (TFC).  The study aimed to evaluate the in vitro antioxidant and antimicrobial potency of Mimosa pudica (EAMP), such as extractive value, total ash content, loss on drying, and phytochemical screening, were calculated using standard protocols. The TPC was determined by using the Folin–Ciocalteu method taking gallic acid as standard, and TFC was conducted by using the AlCl3 colorimetric method, using a 96-well plate reader. The in vitro antibacterial activity of different concentrations of the extract against four bacterial ATCC strains was determined by the agar well diffusion method in the Mueller Hinton agar (MHA) medium. The in silico molecular docking model was used to ascertain the antibacterial potency of L-mimosine against the selected strains of bacteria used for the in vitro study by calculating the binding affinity towards the protein of bacteria.  The physicochemical properties of ethyl acetate extract of µg/mL. The plant extract also demonstrated the antibacterial activity against both Gram-positive bacteria Staphylococcus aureus (15 mm) and Bacillus cereus (22 mm) and Gram-negative bacteria Escherichia coli (17 mm) and Klebsiella pneumoniae (16 mm) at 200 mg/mL concentration of extract. There was a noteworthy binding affinity of antibiotics with almost all selected bacterial proteins with binding energy against Escherichia coli DNA gyrase subunit B , Staphylococcus aureus DNA gyrase subunit B , Bacillus cereus metallothiol transferase , and Klebsiella pneumoniaebeta-lactamase , respectively, with the L-mimosine.  The preliminary screening of the extract showed the presence of several phytochemicals. The total ash content (7.67%), loss on drying (2.30%), and extractive value (8.966%) were determined by analyzing the crude sample. The total phenolic and flavonoid contents were 418.640 ± 0.018 mg GAE/g (dried extract) and 14.126 ± 0.021 mg QE/g (dried extract), respectively. The extract showed a potent free radical scavenging activity with an IC50 value of 158.95 ± 1.12 Mimosa pudica from the Terai region of Nepal is rich in phenolic and flavonoid compounds, has a significant impact on bacterial growth inhibition, and has a notable potential to scavenge free radicals (DPPH). According to the in silico analysis, L-mimosine is a potent antibacterial compound that might be utilised to discover novel antibacterial drugs to combat antibiotic resistance. The findings of the current study suggest that  Mimosa pudica (Family: Fabaceae), a neglected weed, has been studied for its numerous ethnobotanical uses. It is a perennial or annual creeping herb and has been identified as Lajjalu in Ayurveda. It is one of the sought-after plants for its pharmacological properties, which include antidiabetic, antitoxin, antihepatotoxin, antioxidant, and wound-healing properties [Mimosa are used to relieve several illnesses and health discomfort. The root decoction of this plant is used to relieve toothache. Mimosa pudica is reported to stop the bleeding and speed up the healing of the wound. It is mostly utilised in herbal remedies for gynecological conditions [Nature has been a source of medicine for thousands of years. The phytochemical constituents and the potency of plants against several diseases attracted scientists to explore natural resources for discovering novel drugs. WHO has reported that 80% of the world population still relies on traditional medicine for primary health care . Scientioperties . The planditions .Mimosa pudica, estimate the phenolic and flavonoid content, and assess the in vitro antioxidant and antimicrobial effectiveness against gram-positive and negative bacterial strains. Furthermore, A molecular docking model was used to ascertain the affinity of L-mimosine for bacterial protein and to assess the antimicrobial property of the compound.The phytochemicals of plants are attributed to multiple pharmacological activities, and they can be screened with some in vitro assays believing that they have the same in vivo potency. Free radicals are highly reactive moieties produced by cells during respiration and cell-mediated immunological responses. Free radicals, such as unpaired electrons or reactive oxygen species (ROS), which contain different oxygen species, such as hydrogen peroxide, can cause a variety of damages, eventually leading to the development of multiple human health disorders, including cancer. Antioxidants, being molecules that impede the oxidation of other molecules by donating electrons that can neutralize radical production can alleviate ROS-induced cell damage. The secondary metabolites such as polyphenol and flavonoids with at least one hydroxyl group exhibit free radical inhibition, peroxide breakdown, metal inactivation, and oxygen scavenging and play a critical role in multiple biological activities , 5. In bM. pudica were collected in October 2021 from Haripurwa Municipality located in Sarlahi district of province no. 2 of Nepal. The herbarium of the plant was prepared successfully, and the plant was identified and certified by the National Herbarium and Plant Laboratory (KATH), Godawari, Lalitpur, and a voucher specimen (06/078–079) was deposited.The leaves of M. pudica were kept in the shade and dried for a week and then the leaves were grounded into a powder. The powdered sample was subjected to the first maceration in ethyl acetate for 2 days, followed by the second maceration for another 2 days. The extract from successive maceration was then filtered and concentrated using the Rota-evaporator. Thus, the obtained extract was kept inside the vacuum desiccators for complete loss of water and finally transferred in a bottle, labeled, and stored in a refrigerator.The maceration process was employed for extraction of leaf samples using ethyl acetate as a solvent. Firstly, the collected leaves of The dried extract of the sample then proceeded for phytochemical screening and solvent-solvent fractionation was conducted using hexane, ethyl acetate, and water to identify the constituents, using standard phytochemical methods as described by Trease and Evans as well as Harborne , 10. TheThe leaf sample was grounded and physicochemical parameters  were analyzed using the standard quality control guideline of WHO .Mimosa pudica was determined using the Folin–Ciocalteu method, taking gallic acid as standard for the calibration curve as described by Singleton et al. with a few modifications [µl extract (5 mg/mL) was pipetted in a triplicate manner and was then mixed with 158 µL distilled water and 10 µL of 10% w/v Folin–Ciocalteu reagent (FCR) in a 96-well plate. The mixture was then left for 8 minutes at room temperature, and the initial reading was taken at 765 nm. Subsequently, after that, 30 µL of 20% (w/v) Na2Co3 was added to each well and was incubated for 30 min at 40°C. The final absorbance was taken at 765 nm using a 96-well plate reader . The amount of total phenolic content was calculated using a gallic acid calibration curve and reported as gallic acid equivalent in mg per gram of dry extract (mg GAE/g DE).The total phenolic content of ications . BrieflyM. pudica extract was quantified using a 96-well plate reader employing the Dowd technique with a little modification [µl of extract solution (5 mg/ml) was mixed with 110 µl distilled water and 60 µl methanol was pipetted in a well. The solution was then kept shaking for 5 min to let the reaction happen. The initial reading was taken at 415 nm. The reaction was then quenched by adding 5 µL of 10% AlCl3 and 5 µL CH3COOK (1M) and was incubated for 30 min at 25°C. The final reading was taken after incubation at 415 nm. Quercetin standard (0–100 ppm) was used to prepare the calibration curve. The total flavonoid content was calculated and expressed as mg quercetin equivalent per gram of dry extract (mg QE/g DE).The flavonoid content in fication . An aliqMimosa pudica leaves was determined using the DPPH free radical scavenging assay method described by Brand-Williams et al. with a little modification [µL extract or reference quercetin of different concentrations were pipetted in triplicate in a 96-well plate, initial reading was taken at 517 nm, and 100 µL of 0.1 mM DPPH was added to each well and incubated at room temperature for 30 min in the dark. A control was prepared by mixing 100 µL methanol and 100 µL DPPH solution. Finally, the absorbance of the solutions was measured by using a 96-well plate reader at 517 nm. The percentage of inhibition was calculated by using the following formula:control is the absorbance of the control and A sample is the absorbance of the sample.In vitro antioxidant activity of the extract of fication . To do tMimosa pudica was determined by the agar well diffusion method in Mueller Hinton agar (MHA) medium. The ATCC cultures of bacteria, namely, Staphylococcus aureus (ATCC 6538 P), Bacillus cereus (ATCC 14579), Escherichia coli (ATCC 8739), and Klebsiella pneumoniae (ATCC 700603), were taken for the antibacterial test. The selected bacterial strains were cultured overnight and used to assess the inhibitory potency of plant extract. The bacteria were first tallied with 0.5 MacFarland solution. Wells were made of agar plates using a cork borer of 6 mm diameter. Then, 100uL of each extract was placed in the wells made of the inoculated plates; the process also included the same volume of ethyl acetate, which served as the negative control. Likewise, for positive control, three antibiotics  were taken. All the plates were incubated for 24 hours at 37°C. The zone of inhibition (ZOI) was measured the following day.Antibacterial activity was evaluated according to the method described by Satish et.al. and Joshi et al. . AntibacMimosa pudica. Research and review papers published in several databases  were explored to collect information. The relevant keywords having an entry on medical subject headings (MeSH) database, and which are already indexed, were used as the precursor for backward and forward search strategy. The articles not complying with the review protocol were excluded.A detailed systematic literature review was conducted for the exploration of L-mimosine as the one of constituents found in ethyl acetate extract of Escherichia coli, and DNA gyrase subunit B (PDB:4uro) was selected for Staphylococcus aureus, metallothiol transferase (PDB: 4jh5) was selected for Bacillus cereus, and beta-lactamase (PDB: 4pm9) was selected for Klebsiella pneumoniae.Docking of L-mimosine (PubChem Id: 440473) was conducted in four protein structures selected from four different bacteria . DNA gyrase subunit B (PDB: 1KZN) was selected for Escherichia coli, Staphylococcus aureus, Bacillus cereus, and Klebsiella pneumoniae selected proteins, respectively.For positive control, four different antibiotics were used, clorobiocin (PubChem Id: 54706138), novobiocin (PubChem Id: 54675769), fosfomycin (PubChem Id: 446987), and cefotaxime (PubChem Id: 5742673) against For the preparation of the protein, the AutoDock tool's graphic interface was used. First, the water molecules were removed, then the addition of polar hydrogen was conducted after that nonpolar hydrogen was merged, and finally, the Kollman charge was added .In the case of ligands, SDF files were converted to pdbqt files, and energy minimization was conducted by applying Universal Force Filed in an Open Babel (Open Babel Development Team) software .Docking of ligands to the protein active site was performed in AutoDock and Vina  conjugatPymol software was used for visualization of the 3D structure of docked files and the ligPlot+ (European Bioinformatics Institute) software  was for Mimosa pudica (EAMP) showed the presence of flavonoids, saponins, coumarins, tannins, terpenoids, and alkaloids  of gallic acid . The hydroxyl groups in the phenolic compounds of plant extracts are vital with redox properties responsible for antioxidant activity channelizing by facilitating free radical scavenging . As a balic acid  and exprlic acid . Comparia albida . Patro ea leaves . The datMimosa pudica (EAMP) was determined in the term of quercetin equivalent (QE). As a basis for the quantitative determination, flavonoid contents in Mimosa extracts were determined using aluminum chloride in a colorimetric method. The results were derived from the calibration curve  of quercetin  and Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae), and the positive and negative control was taken for standard drug inhibition comparative study. The ethyl acetate solvent was used to prepare the plant extract in five different concentrations . As expected, the highest concentration; i.e., 200 mg/ml, showed the maximum inhibition against each bacterial strain  on the same plant extract, the antibacterial activity against Staphylococcus aureus and Bacillus subtilis was noted. The zone of inhibition (ZOI) given by Mimosa extract against these bacteria was found to be 13 mm and 10 mm, respectively [The study shows us that the extract has antibacterial activity against Gram-positive bacteria (n Tables  and 7. Tectively .Mimosa pudica contains several marker compounds. The different fractions were found to have varied proportions and composition of constituents [Mimosa pudica were isolated in a study conducted by Patel and Bhutani [M. pudica were greatly enhanced by the presence of crocetin, crocin, jasmonic acid, L-mimosine , caffeic acid, ethyl gallate, and gallic acid in the ethyl acetate fraction of the whole plant. This may be partially due to the synergistic effects of these compounds. Moreover, multiple studies have demonstrated that the compound isolated from Mimosa pudica has substantial antibacterial, antioxidant, and antidiabetic properties [A thorough analysis of the literature found that tituents . The 14  Bhutani . The finoperties . This stEscherichia coli DNA gyrase subunit B with clorobiocin and L-mimosine was found to be −9.2 kcal/mol and −5.7 kcal/mol, respectively. Similarly, the binding energy of Staphylococcus aureus DNA gyrase subunit B with novobiocin and L-mimosine was found to be −8.2 kcal/mol and −6.1 kcal/mol, respectively. Likewise, the binding energy between Bacillus cereus metallothiol transferase with fosfomycin and L-mimosine was −4.3 kcal/mol and −5.2 kcal/mol, respectively, and the binding energy of Klebsiella pneumoniaebeta-lactamase, cefotaxime, and L-mimosine was found to be −7.5 kcal/mol and −6.1 kcal/mole, respectively.Four bacteria were used for the antibacterial activity of L-mimosine, binding energies were calculated against their specific protein with specific antibiotic and L-mimosine using molecular docking . The proEscherichia coli DNA gyrase subunit B were involved in forming a hydrogen bond with clorobiocin, whereas Tyr 26, Val43, Ala47, Asp49, Glu 50, Val 71, Gly 77, Ile 78, Pro79, Ile90, His 95, Val118, and Thr 165 amino acids were involved in forming hydrophobic interaction with the clorobiocin molecule (Figures Escherichia coli DNA gyrase subunit B.Asn46, Asp73, and Gly117 amino acids of  Figures . However Figures . There wStaphylococcus aureus DNA gyrase subunit B were forming hydrogen bonding with novobiocin and Ile 36, Try 35, Glu 50, Ser55, Asp 57, Gly 85, Ile86, Pro87, Gly 125, Val130, and Thr 173 were forming hydrophobic interaction (Figures Staphylococcus aureus DNA gyrase subunit B.Asn 54, Glu 58, Asp81, Gly 127, and Val 126 amino acids of  Figures , whereas Figures . There wBacillus cereus metallothiol transferase were forming a hydrogen bond with fosfomycin residue, and His 117 was forming hydrophobic interaction (Figures Bacillus cereus metallothiol transferase.His 66, Arg 94, Arg 96, Tyr 105, Glu 115, and Arg 124 amino acids of  Figures . Meanwhi Figures . Number Klebsiella pneumoniaebeta-lactamase were involved in the formation of hydrogen bond with cefotaxime, and Tyr 105, Thr 216, Gly 236, Ala 237, Gly 238, and Gly 242 were forming hydrophobic interaction with cefotaxime (Figures Klebsiella pneumoniaebeta-lactamase. There was a greater binding affinity of antibiotics with almost all selected bacterial proteins, except Bacillus cereus metallothiol transferase; however, the binding of L-mimosine was strong with the active sites of all the targeted protein. This suggests L-mimosine is likely to be a potent antibacterial compound.Asn 104, Ser 130, Asn 1332, Thr 235, Asp 240, and Ala 272 amino acid residues of  Figures . However Figures . There wMimosa pudica have potent antibacterial activity as well as significant antioxidant efficiency. Although the parameters chosen for this research were not disease-specific, the assessment of antioxidant potentials can be used as a benchmark for the application of Mimosa pudica for reactive oxygen species-mediated diseases. In addition, the minimal drying loss observed during the physiochemical analysis could be correlated with the extract's potential to prevent itself from eroding, while performing in silico molecular docking of L-mimosine against selected bacterial protein showcased noteworthy antibiotic binding affinities. This shows that L-mimosine could be a potent antibacterial compound and a compound of interest for novel antibacterial drug discovery to combat antibiotic resistance.The study revealed that the phytochemicals in an ethyl acetate extract of


Skeletal muscle index (SMI) is a promising predictor of clinical outcomes in patients with malignant diseases. As a simpler surrogate of sarcopenia-psoas muscle index (PMI), its predict value for overall survival (OS) after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) has not been reported. To determine if changes in the PMI predicted OS in individuals with HCC treated with TACE.A retrospective analysis was performed in HCC patients treated with TACE between January 2018 and March 2019. The survival curve according to PMI was estimated by the Kaplan–Meier method and then compared by the log-rank test. Cox proportional hazards models were conducted to identify the prognostic factors for OS. Furthermore, the predictive abilities of PMI and SMI were compared by using Harrell’s concordance index (C-index).p < .001). Multivariate analysis found that either PMI  or SMI  was significantly associated with OS. In the multivariate analysis, the C-index for PMI was 0.78 and 0.79 for SMI (p = .985).Two hundred and twenty-eight patients  were analysed. The OS was less in patients with low PMI than those with high PMI .Psoas-muscle index has advantages of being faster and easier to acquire, which thus makes it more likely to achieve widespread clinical application.PMI is a simple tool to predict OS in HCC patients treated with TACE. The predictive ability of PMI is comparable to that of SMI. For patients with unresectable hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) is a widely accepted treatment ,2. OveraComputed tomography (CT) is a well-established tool for diagnosing sarcopenia . For thiA single-muscle approach to be used clinically for the diagnosis of sarcopenia is a recent trend in the literature on CT-defined muscle quantification  Currentlsupplementary materials.The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional ethics committee of the institution and individual consent for this retrospective analysis was waived. The authors confirm that the data supporting the findings of this study are available within the article and its In this study, the clinical records of 285 patients with HCC who were initially treated with TACE at our institution were retrospectively reviewed between January 2018 and March 2019. The inclusion criteria were: (1) pathologically or radiologically confirmed HCC; (2) unresectable disease or intolerable resection; (3) Barcelona Clinic Liver Cancer (BCLC) stage A/B/C; and (4) availability of CT imaging. The exclusion criteria were: (1) Child–Pugh class C; (2) Eastern Cooperative Oncology Group (ECOG) performance status > 2; (3) patients who did not have a complete abdominal CT examination covering the level of L3; (4) spontaneous ruptured HCC; (5) patients received liver transplantation or surgical resection following initial TACE; and (6) missing data. Ultimately, we enrolled 228 patients in this study. Clinical data collected included age, gender, weight, height, aetiology, Child–Pugh class, α-Fetoprotein (AFP) level, portal vein thrombus (PVTT), BCLC stage, ALBI , SMI, PM2) by the square of the height (m2) was done to obtain the SMI (cm2/m2) [Skeletal muscle mass was assessed using CT images acquired for the purpose of HCC evaluation. For the analysis of SMI, venous-phase axial images of the abdomen were exported to a dedicated post-processing workstation , which enables tissue demarcation using Hounsfield unit (HU) thresholds. The muscles were quantified within a HU range of −29 to 150 HU  and tiss(cm2/m2) ,14. A revia the right femoral artery under local anaesthesia. A 5-F catheter was introduced, and angiography was conducted to assess the tumour number, size, localization, and tumour-feeding arteries. Embolization via a microcatheter was performed with lipiodol-based injectant.TACE was performed Patients were followed every 1–3 months until the patient died or until the end of the study. Tumour markers, imaging examinations, and liver function were tested. When residual viable tumours were identified or new lesions identified, the patients were treated according to their tumour status and general condition after multidisciplinary discussion. The OS time was defined as the period from initial TACE to death or 31 August 2021.r). Pearson’s r indicates linear correlation between PMI and SMI.Continuous data are presented as mean and standard deviation if normally distributed and median (range) if the distribution was skewed for continuous variables. Categorical data are presented as frequency and percentage. Interobserver agreement of the measurements of PMI was assessed using the intraclass correlation coefficient (ICC) and its 95% confidence interval (CI). ICC results were interpreted according to the following criteria: poor (0 to 0.5), moderate (0.50 to 0.75), substantial (0.75 to 0.9), and excellent (0.9 to 1) . CorrelaTo identify the cut-off points for PMI and SMI that would best predict the OS, maximally selected rank statistics were used ,17. Patip < .2 in the univariate analysis were considered potential predictors of OS and were further assessed by multivariate analysis. The predictive abilities of PMI and SMI were evaluated by using Harrell’s concordance index (C-index) [p value of less than .05 was considered statistically significant.Univariate and multivariate Cox’s proportional hazards models were used to evaluate the predictive factors of OS. Factors with C-index) . StatistA total of 773 TACE procedures were identified, with an average of 3.2 sessions per patient . The mean age was 58.9 years, and 76.8% of patients were male. The majority cause of liver disease was hepatitis B virus infection. Two hundred and one (88.2%) patients had Child-Pugh class A liver function. The BCLC stage distribution was as follows: stage A, 58 (25.4%); stage B, 112 (49.1%); and stage C, 58 (25.4%). Among the 58 patients with BCLC stage C, metastasis occurred in 30 cases. The details of patient characteristics are summarized in p < .001) and moderately strong relationship (r = 0.57) between PMI and SMI  than that in women . Given this, gender-specific cut-off values were established by using maximally selected rank statistics. The cut-off values for PMI in men and women were 42.28 and 37.42 mm/m2, respectively. Likewise, the cut-off values for SMI in men and women were 45.95 and 33.96 cm2/m2, respectively.Interobserver agreement of PMI measurements was excellent with an ICC of 0.96 . There was a significant linear , lower ALBI grade [Supplemental Table 2 shows the patient characteristics classified by SMI. Higher BMI (≥ 24 kg/m2), and BCLC stage (A) were more frequently in patients with high SMI. While older age, female, and large maximum tumour diameter (> 3 cm) were more frequently in patients with low SMI.Patients were followed up for a median of 22.3 months. As the last follow-up visit, 134 of the 228 patients (58.7%) had died. The median survival time was 24.2 months (range: 1–41.3 months).p < .001) and SMI .Survival curves for patients classified by cut-off values of PMI and SMI are shown in p = .014) and SMI  were significant independent prognostic factors associated with OS (p = .985).On univariate analysis, PMI, SMI, AFP level, Child-Pugh class, ALBI grade, number of tumours, maximum tumour diameter, portal vein thrombus and metastasis were all found to be associated with OS . The ind with OS . The preIn this present study, the prognostic role of PMI and SMI in HCC patients undergoing TACE was interrogated. We found PMI and SMI reliable in predicting OS. As well, owing to its simplicity and accessibility, PMI was more convenient for clinical use.Nutritional status assessment is valuable for patients with HCC, especially in the advanced stages of disease. Currently available laboratory tests are not sufficient to justify nutritional intervention for patients with HCC. However, sarcopenia by balancing performance and nutritional status may predict the prognosis in patients with malignancies ,6. The Ap = .985). Moreover, PMI has advantages compared to SMI being faster and easier to acquire, thus making it more likely to achieve widespread clinical application.Recently, several studies reported single muscle, rather than total skeletal muscle, mass for sarcopenia assessment ,21. The We propose that PMI can serve as a surrogate for the assessment of sarcopenia. The psoas muscle is the main flexor of the hip and also provides postural support of the lumbar spine, sacroiliac, and hip joints. Although it only accounts for approximately 10% of total skeletal muscle area at L3, the psoas is a key muscle for posture and core strength  and may Sarcopenia is a multifactorial condition related to age, reduced physical activity, and protein-energy malnutrition, but also to a severe wasting status due to malignant tumour or chronic disease ,25. In hIn the current study, AFP level, Child-Pugh class, maximum tumour diameter, metastasis, and BCLC stage were demonstrated to predict OS in HCC patients treated with TACE, which were similar to previously reported data ,27. Howepost hoc analysis will have unavoidable biases. As well, some patients were excluded if CT scans were not available, which may result in selection bias. Third, the manual determination of PMI is subject to measurement error. This is likely due to the asymmetry of the muscle making determination of the length and width challenging. However, our results showed an excellent interobserver agreement with an ICC of 0.96 for assessment of PMI, indicating that, at least in our hands, the technique was reliable.The current study has several limitations. First, it is a retrospective study and as such secondary to In conclusion, a retrospective analysis of PMI found that the approach was straightforward and accurate in predicting the long-term survival of HCC patients treated with TACE.Click here for additional data file.