The digital implant impression technique (DIT) and conventional implant impression technique (CIT) workflows in implant-supported fixed partial dentures (FPDs) have not been extensively compared in prior studies. Moreover, there is no agreement on the more accurate method that entails less time in the laboratory and during the clinical phases of fabrication and delivery of the prosthesis, respectively. This review aimed to assess the precision of the imaging procedure and overall fabrication time of the DIT and CIT for the implant-supported FPDs. An electronic search was performed using PubMed, Scopus, EMBASE, Cochrane Oral Health Group, and Dentistry and Oral Science Source databases through EBSCO for relevant studies from January 2014 to April 2023. Following the preliminary screening, the studies that met the inclusion criteria underwent full-text review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Cochrane Collaboration risk of bias appraisal tool and Newcastle-Ottawa scale were applied to assess the quality of randomized controlled trials (RCTs) and non-randomized prospective clinical studies, respectively. The initial search yielded 332 studies, and after excluding duplicates, 241 papers were available for screening. Titles and abstracts were reviewed, and 97 articles were chosen for full-text review by two authors independently. Furthermore, 89 articles were excluded in compliance with the PICOS question, and eight studies were chosen for qualitative analysis. Hence, the review comprised two RCTs and six prospective clinical studies. The time efficiency of the implant-supported FPDs was examined in four investigations, three of which used the Trios 3 scanner and one used the Intero scanner. The three-dimensional accuracy of DIT and CIT was compared in six clinical comparative studies. One of the RCTs was rated to have a high risk of bias and the other with a moderate quality of evidence. The six prospective studies were rated to have high-quality of evidence. The findings of this review indicate the prospective applicability of future intraoral scanning systems. The DIT was reported to be outstanding in terms of patient preferences and total fabrication time efficiency. Additional in vivo studies are needed to establish the therapeutic usefulness and time efficiency of integrating DIT in more comprehensive settings. The degree of trueness and precision of implant impressions is especially important in prosthetic rehabilitation, which usually entails capturing the bodily structure and the precise positioning of endosseous implants, and the morphology of the peri-implant tissues. This, in turn, influences the degree of accuracy of the final prostheses ,2. MechaThe digital implant impression technique (DIT) has resolved most of the limitations of the CIT by removing prerequisites for impression materials, enhancing patient comfort, curbing the amount of time needed, and providing the capability to retain digital data ,7. When Complete DIT includes the real-time three-dimensional (3D) capture of the unique patient scenario within the oral cavity using IOS, computer-aided design (CAD) using dental software systems for swift prototyping such as milling or 3D printing (computer-aided manufacturing (CAM)), and professional delivery of dental prostheses. The construction, transfer, and subsequent analysis of the obtained IOS information into a Standard Tessellation Language (STL) file are essential measures in DIT. The digital approach is generally related to the fabrication of physically robust and precise manufacture of the monolithic zirconia prosthesis in an expedited process with a decreased requirement for physical human contact ,9. CurreThe impression accuracy of DIT in vivo has not been extensively studied yet ,11. FurtMethodologyThe review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards . A strucThe study population included partially edentulous patients with an implant-supported FPD. Studies involving DIT/IOS methods were included as the intervention. Studies discussing the CIT were included as the comparison. Study outcomes included measurement of accuracy, precision, or trueness of impression and total fabrication time taken to make the impression. Randomized controlled trials (RCT) or prospective clinical studies were considered for inclusion.Focused QuestionIs IOS a more accurate and less time-consuming method for fabricating the final prosthesis than CIT employed during implant-supported FDP rehabilitation?Search StrategyAn electronic search was conducted using PubMed, Scopus, EMBASE, Cochrane Oral Health Group, and Dentistry and Oral Science Source databases through EBSCO for relevant studies published in the English language from January 2014 to April 2023. The following Medical Subject Headings phrases were applied:  AND  AND . A manual search of journals for relevant publications was also conducted. Google Scholar was used to search for any studies that were not selected in the aforementioned databases.Selection Criteria for Eligible StudiesThe following were the inclusion criteria to be fulfilled for studies to be considered eligible for inclusion in this systematic review: RCT or non-randomized prospective clinical studies (in vivo) encompassing patients receiving implant-supported FDPs who were partially edentulous; studies evaluating the workflows of DIT and CIT strategies, accuracy, precision, or trueness of the IOS; and/or studies evaluating the speed of DIT and DIT of FPDs. Studies that were published before 2014 were eliminated, including in-vitro studies, expert comments, review articles, technical reports, studies on animal models, and case reports/series.Study SelectionTwo reviewers independently reviewed each title and abstract during the initial evaluation. Following the preliminary screening, studies that met the inclusion criteria underwent full-text analysis. Additionally, the lists of references of the selected studies were explored for any relevant published articles. If there were any discrepancies between the reviewers, a third reviewer was consulted to validate the review process.Quality AssessmentApplying the Cochrane Collaboration assessment tool for evaluating the risk of bias (RoB) for RCTs, two independent investigators executed a quality evaluation . The tooThe Newcastle-Ottawa scale (NOS) was utilized to appraise the quality of the reviewed non-randomized prospective clinical studies . The NOSData ExtractionTwo reviewers retrieved data independently from the included studies based on the predefined outcomes of interest for further qualitative analysis. The author names, publication year, the study design, sample size, demographic traits such as age and gender, the number of impressions or implants used, the purpose of the study, the type of IOS employed for scanning, the CIT material utilized, the number of implants used, the workflows of CIT and DIT, and the outcome assessment were extracted from the included studies. The review focused on the time required for the overall fabrication and completion of the CIT and DIT workflows, as well as the outcome measures of scan accuracy/precision/trueness in terms of measurement of variances in distance deviations or implant angulation. As previously stated, disagreements were resolved through discussion. In cases where additional details about the study methodology or any specific data were needed, the corresponding authors of the studies were communicated with.ResultsStudy SelectionThe preliminary electronic search resulted in 311 articles, as shown in the PRISMA flow diagram (Figure The manual search resulted in the selection of 21 relevant articles from a total of 332 articles for the process of the review. After removing the duplicate records, 241 publications were subjected to the initial screening. The abstracts of 144 articles were discarded after a review of the titles and abstracts. Further, 97 articles were selected for full-text review by two investigators independently. Finally, eight studies were chosen for qualitative review -22. Out Characteristics of Included StudiesSix prospective clinical trials and two RCTs were included in the review. The time efficiency of the implant-supported FPDs was examined in four investigations, three of which used the Trios 3 IOS ,17 and oThe objectives and detailed workflow of each study are presented in Table Scan AccuracyAccording to Hashemi et al., the CIT and DIT workflows had comparable characteristics in terms of impression accuracy, framework adaption, and reconstruction aesthetics . The RCTThe inconsistency of the scanned surface of the scan bodies of the DIT, on the other hand, was found to be double that of the CIT by Rutkunas et al. Particularly angular and vertical shift and positional discrepancies of the scan bodies in both approaches had substantial clinical significance . GedrimiAlsharbaty et al. recorded measurements of linear and angular displacement in three planes using a coordinate measuring device to assess the accuracy of a DIT employing Trios 3 Shape IOS, pick-up and transfer procedures, and between the CIT themselves. The DIT showed that there were angulation errors of 5° to 8.5°, inter-implant distance errors of 160 to 270 μm, and linear displacement errors of 270 to 450 μm. Thus, it was determined that the DIT was too inaccurate to be utilized to generate implant impressions for partially edentulous subjects .Time EfficiencyFour studies included in the review employing DIT and CIT showed the entire fabrication time of implant-supported FPDs. The fabrication time employing the DIT compared to the CIT was considerably reduced, according to Hashemi et al. and Joda et al. ,16. AccoOn the contrary, two further studies revealed that the total amount of time required for CIT was less than the DIT workflow ,22. AccoQuality Assessment of the Included StudiesTable One study was determined to have a high RoB as it showed a high risk for detection bias and an unclear RoB for allocation concealment . AnotherDiscussionThe literature on the most recent data on scan accuracy and turnaround time for comparing IOS to CIT was analyzed in this systematic review. Clinical expertise did not have any major influence on the effectiveness of IOS, but novice clinicians may find CIT to be more challenging and time-consuming, which may have an impact on the final results. Another benefit of DIT utilizing an IOS is that it works well for patients who have profound vomiting reflexes and allows for selective overwriting of areas when the impression is unclear . The ovePrecision refers to the similarity of the findings gathered from various measurements, whereas accuracy relates to trueness, expressing the degree to which a measurement corresponds to the actual value ,26. SeveThere was variation in time efficiency among the several studies. There was a definite trend for IOS to have less working time compared to CIT in two ,16 of thThe dearth of a standardized protocol for gauging the precision of intraoral impression techniques may be the primary impediment to accomplishing in vivo experiments. To obtain a reference model, the intraoral orientation of dental implants ought to be accurately captured and replicated in a model by employing any impression techniques. However, the approach for obtaining a reference model has been associated innately with inaccuracy, which generates a bias in the evaluation of the impression procedure that is to be evaluated. The variability of CIT outcome measures of in vivo studies illustrates that even the methods and materials used, namely, the design of the impression trays, implant coping, impression material, and splinting, contribute to the accuracy level of the reference frameworks. In vitro investigations, on the other hand, comprise reference and test models that are calibrated with the same tools, such as coordinate measuring machines, microscopes, digital micrometers, and standardized images. The accuracy is calculated as the difference between the test and reference framework models. The investigators of in vivo studies used diverse methods of evaluation to acquire data from the in vivo handling of CIT and DIT. A majority of in vivo studies did not provide quantitative information for determining the level of accuracy of impression techniques .Trios, iTero, Cerec, and True Definition are the most frequently utilized intraoral scanners described in the literature for measuring completely and partially edentulous models. Trios was shown to have the best trueness score for the partially edentulous model, followed by True Definition, iTero, and Cerec . VariousIn the majority of the reviewed studies, DIT was captured utilizing a Trios 3 IOS. The juxtaposition of discrepancies between the two methodologies indicates that DIT was more accurate than CIT in only a few of the clinical studies reviewed ,17,18. IAlthough DIT will broaden its scope of applications to provide superior results, CIT will continue to play an essential role in prosthetic rehabilitation, and clinicians must evaluate each circumstance of the working environment ,31. CareThe usage of IOS in clinical practice is highly demanding owing to its time efficiency and accuracy level in the fabrication of implant-supported FDPs with a more favorable patient perception. The findings of this review indicate the prospective applicability of future IOS systems. This, in turn, warrants continued development, and DIT could eventually replace CIT. The IOS was reported to be outstanding in terms of patient preferences and total fabrication time efficiency. Additional in vivo studies are needed to establish the therapeutic usefulness and time efficiency of integrating IOS in more comprehensive settings.


Aerobic exercise promotes beneficial effects in the brain including increased synaptic plasticity and neurogenesis and regulates neuroinflammation and stress response via the hypothalamic-pituitary-adrenal axis. Exercise can have therapeutic effects for numerous brain-related pathologies, including major depressive disorder (MDD). Beneficial effects of aerobic exercise are thought to be mediated through the release of “exerkines” including metabolites, proteins, nucleic acids, and hormones that communicate between the brain and periphery. While the specific mechanisms underlying the positive effects of aerobic exercise on MDD have not been fully elucidated, the evidence suggests that exercise may exert a direct or indirect influence on the brain via small extracellular vesicles which have been shown to transport signaling molecules including “exerkines” between cells and across the blood-brain barrier (BBB). sEVs are released by most cell types, found in numerous biofluids, and capable of crossing the BBB. sEVs have been associated with numerous brain-related functions including neuronal stress response, cell-cell communication, as well as those affected by exercise like synaptic plasticity and neurogenesis. In addition to known exerkines, they are loaded with other modulatory cargo such as microRNA (miRNA), an epigenetic regulator that regulates gene expression levels. How exercise-induced sEVs mediate exercise dependent improvements in MDD is unknown. Here, we perform a thorough survey of the current literature to elucidate the potential role of sEVs in the context of neurobiological changes seen with exercise and depression by summarizing studies on exercise and MDD, exercise and sEVs, and finally, sEVs as they relate to MDD. Moreover, we describe the links between peripheral sEV levels and their potential for infiltration into the brain. While literature suggests that aerobic exercise is protective against the development of mood disorders, there remains a scarcity of data on the therapeutic effects of exercise. Recent studies have shown that aerobic exercise does not appear to influence sEV size, but rather influence their concentration and cargo. These molecules have been independently implicated in numerous neuropsychiatric disorders. Taken together, these studies suggest that concentration of sEVs are increased post exercise, and they may contain specifically packaged protective cargo representing a novel therapeutic for MDD. Major depressive disorder (MDD) is one of the leading causes of disability worldwide . The WorExercise is one of the most effective non-pharmacological therapeutic means to sustain a healthy mind , and hasPhysical exercise (PE) is classified into aerobic and anaerobic PE depending on the level of intensity, the types of muscle fibers used, and the recruited metabolic energy system . AerobicRecent studies show that after a single bout of aerobic physical activity, skeletal muscles release EVs into circulation  that areIn this perspective review, we demonstrate the potential of aerobic exercise as an adjunct treatment option for major depression. We delve into the mechanisms by which exercise affects brain health, including its impact on synaptic plasticity, neuroinflammation, and monoamine neurotransmission. While other manuscripts have focused on the triad of exercise, EVs, and depression , here, wMoreover, we emphasize the significance of sex as a crucial biological variable in understanding the interplay between exercise, sEVs, and MDD. Most importantly, our review takes an additional step in this novel field by exploring the different mechanisms underlying the passage of sEVs across the BBB, going beyond the current focus on exercise, sEVs, and MDD. This discussion aims to provide a more nuanced understanding of the relationship between exercise and sEV-mediated effects on the nervous system.Research into the beneficial effects of exercise on depression dates to the early 1900s, with studies by The exercise regimens used in research vary widely across studies leading to inconsistent findings or interpretations of the data. Nonetheless, there have been numerous studies looking at the therapeutic role of aerobic exercise in the context of MDD which have provided consistent, comparable, and measurable outcomes . AerobicExercise-induced benefits on MDD are most commonly associated with certain neuro-molecular mechanisms including; increasing the levels of serotonin and norepinephrine , increasThere have been many excellent reviews focusing on the efficacy of different exercise variables such as intensity , duratioPostmortem human studies of individuals with depression and/or who have died by suicide show reduced BDNF protein levels in the hippocampus and other brain regions, contrary to individuals receiving antidepressant treatment (Met/Met)  , or whenMet/Met) .fibronectin type III domain-containing protein 5 (FNDC5)  , and lac (FNDC5) .Met/Met) inhibits the beneficial effects of exercise-induced increase in the hippocampal mRNA levels of FNDC5 and BDNF  in response to muscle contractions . There iIn vivo research on sEVs originating from skeletal muscle is challenging due to the current inability to specifically label and monitor sEVs released from this tissue. However, multiple in vitro studies have clearly shown that myoblasts and myotubes release proteins using sEVs  may use modified small extracellular vesicles loaded with exerkines, which have been shown to reduce obesity and T2DM and positively affect metabolic health . These rThe data summarized in in vivo and ex vivo studies concluded that aerobic exercise increases sEV markers , and stimulates their release into circulation without changing its vesicle size or concentration  is disrupted in individuals with depression  with stusEVs released from depolarized neurons have been found to regulate synaptic plasticity. For example, proteomic analysis of neuron-derived sEVs found the synaptic-plasticity-associated protein MAP1b to be enriched in these vesicles . SpecifiThere is evidence that sEVs are regulators of neuroinflammation, for example, monocytes activated by interferon-alpha secrete sEVs carrying altered miRNA profiles, subsequently activating the nuclear factor-κB, and increasing the inflammatory response . LikewisPrevotella 2 and Ruminococcaceae UCG-002) in their bacteria-derived sEVs from serum  via decreasing the expression of rab7 in brain endothelial cells and enhancing their transport.sEVs follow a complex journey from being secreted by parental cells in the periphery to crossing the blood-brain barrier and infiltrating into the brain . Underst the BBB . Using hIn vivo and in vitro studies have shown that peripheral sEVs interact with the BMECs of the BBB under stroke-like conditions, and enter the brain via different mechanisms such as: micropinocytosis, receptor-mediated transcytosis, and adsorptive-transcytosis (scytosis . Morad escytosis .Given that, crossing the blood-brain barrier facilitates the connection between the brain and the periphery, sEVs play a critical role in some of the systemic alterations reported in neuropsychiatric disorders . In indiMore research is needed to fully understand the underlying mechanisms of the bi-directional transfer of sEVs across the BBB, particularly as brain-derived sEVs may reflect physiological changes in psychiatric disorders.Exercise has been identified as an effective preventative and treatment strategy for a variety of neuropsychiatric disorders . HoweverAerobic exercise is a promising and evidence-based treatment for MDD, and the discovery that exercise-induced sEVs can promote intercellular communication by delivering cargo, acting on neighboring and distant cells, promoting healthier physiological status is an important new advance in the field of exercise. Knowing that both, the effects of exercise and the prevalence of MDD are influenced by sex, sex as a biological variable should be taken into consideration in future studies. The role of sEVs in the context of exercise and depression has yet to be investigated, however, based on the evidence summarized here, we identify common biological features between exercise and depression, exercise and sEVs, and sEVs and depression. We suggest that exercise’s effect on depression is mediated by altered peripheral sEV cargo signatures that influence neural pathways associated with the etiopathogenesis of major depression, such as neural plasticity and neuroinflammation. Future studies, including examining the effects of exercise-induced sEV cargo on depression and better understanding the mechanisms of bi-directional sEV transfer, as well as investigating the extent and type of sEVs released in different types, intensity, duration, and frequency of exercise, would provide important missing links across all three research domains.


In the context of hematological malignancies, the strongest epidemiological correlations are with the emergence of lymphomas, in particular non-Hodgkin’s lymphoma (NHL)  and, more specifically, all NHL B subtypes . Questionable and unconfirmed associations are reported between HBV and NHL T subtypes  and leukemia. The presence of HBV DNA in peripheral blood mononuclear cells has been reported by numerous studies, and its integration in the exonic regions of some genes is considered a possible source of carcinogenesis. Some in vitro studies have shown the ability of HBV to infect, albeit not productively, both lymphomonocytes and bone marrow stem cells, whose differentiation is halted by the virus. As demonstrated in animal models, HBV infection of blood cells and the persistence of HBV DNA in peripheral lymphomonocytes and bone marrow stem cells suggests that these cellular compartments may act as HBV reservoirs, allowing replication to resume later in the immunocompromised patients (such as liver transplant recipients) or in subjects discontinuing effective antiviral therapy. The pathogenetic mechanisms at the basis of HBV carcinogenic potential are not known, and more in-depth studies are needed, considering that a clear correlation between chronic HBV infection and hematological malignancies could benefit both antiviral drugs and vaccines.HBV is one of the most widespread hepatitis viruses worldwide, and a correlation between chronic infection and liver cancer has been clearly reported. The carcinogenic capacity of HBV has been reported for other solid tumors, but the largest number of studies focus on its possible lymphomagenic role. To update the correlation between HBV infection and the occurrence of lymphatic or hematologic malignancies, the most recent evidence from epidemiological and  Several viruses, often causing chronic or persistent infections, are correlated with the occurrence of malignancy. Usually, the immune response, with its articulated actions, represents the best control against the emergence of neoplastic cells; however, the persistence of viruses with oncogenic characteristics represents the driver for immune evasion, facilitating poor control over malignancy emergence.Epstein−Barr virus, human papillomavirus, human herpesvirus-8, Merkel cell polyomavirus, and hepatitis B viruses (HBV) and hepatitis C virus (HCV) are commonly considered viruses with oncogenic properties. The correlation between these infections and the emergence of cancer has been clearly demonstrated; although, the development of malignancy is not common among infected subjects , 2. IndeHBV is one of the most widespread hepatitis viruses worldwide, with 296 million infected subjects, including over 6 million children under the age of 5 . The corThe positive correlation between chronic HBV infection and the emergence of lymphomas has been repeatedly reported in the literature. However, although several meta-analyses reported a positive correlation , others in vitro studies of HBV infection of hematopoietic and lymphatic cells have been reported, suggesting possible patterns of persistent infection and viral reactivation. Finally, some considerations on possible implications between HBV infection of blood cells and the possibility of new targets for eradication treatments are reported.The purpose of this review is to provide information on HBV lymphotropism and its potential impact on lymphomagenesis. With this aim, the epidemiological correlates between HBV infection and the occurrence of lymphatic or hematological tumors have been updated, and the results of The role of HBV in the field of oncogenesis is mainly related to the occurrence of HCC, and some studies have evaluated the protective effect of HBV vaccination and antiviral drugs on HCC emergence , 9. The Some recent studies have attempted to evaluate the impact of active HBV infection on the onset of all types of extrahepatic cancer . In a prLymphomas are the hematological tumors most epidemiologically associated with HBV infection , 14. NotA recent Chinese paper by Zhou et al.  investigThe influence of anti-HBV antiviral treatments and vaccinations on lymphomagenesis was also studied. Both variables are absent in most of the above cited study cohorts. One of the most relevant studies on this issue is that of Huang et al.  on a TaiIn conclusion, most cohort studies conducted in high HBV-prevalence countries have demonstrated a correlation between HBV infection and NHL, while the impact of HBV on the onset of leukemia, Hodgkin’s lymphoma and other hematological disorders is controversial. New studies are needed, including prospective clinical and virological studies that involve control groups, which are often lacking in retrospective and prospective epidemiological studies. Moreover, longer follow-up studies would allow us to better evaluate the influence of vaccination status and antiviral therapy on cancer development.The integration of HBV DNA into the genome of human hepatocytes is a recognized mechanism contributing to the onset of HCC . HBV DNAIn a similar fashion, some recent studies have also supported the role of HBV DNA integration into the genome of immune cells in driving the pathogenesis of immunoproliferative disorders such as NHL and leukemia  Figure –36 and iIn this regard, a recent study revealed that HBV DNA integration represents a common phenomenon in NHL tissues of patients with HBV infection . Indeed,In line with these data, another study has recently shown that HBV DNA integration profiles in PBMCs are superimposable to those observed in tumor liver tissues, since they mostly involve genes regulating cell survival and proliferation in both body compartments. This study also provided evidence of HBV DNA integration within an extrahepatic lymphoproliferative tumor in a patient with chronic hepatitis B. Overall findings further reinforce the role of HBV DNA integration in PBMCs in paving the way toward lymphomagenesis .Beyond PBMCs, HBV DNA integration has also been detected in the bone marrow hematological stem cells (HSCs) of chronically infected HBV patients . These iOverall, further studies are necessary to better explore the functional consequences of HBV DNA integration on immune cell function, malignant cell surveillance, and oncogenic transformation to finally elucidate the role of HBV DNA integration in immune cells and their precursors in hematological malignancies. Similarly, the limited knowledge of the kinetics, frequencies and specific mechanisms underlying HBV DNA integration in immune cells calls for further investigations to unveil these relevant issues.in vitro models of HBV infection, especially in blood mononuclear cells. However, over the years, several studies have demonstrated the presence of viral genomes or other replicative intermediates in cells such as B and T lymphocytes and monocytes  in immune cells   , 99. FurOverall findings support the importance of deepening the role of lymphoid cells as HBV reservoir and finely characterizing the intermediates of HBV replication in this compartment. In particular, the evaluation of the efficacy of these novel drugs should include the monitoring of HBV replication in lymphoid cells to verify whether the drug can induce cccDNA silencing in all compartments where the virus hides and replicates.Numerous studies have confirmed the possibility of finding HBV DNA inside cellular compartments outside the liver, such as the pancreas and kidney, with several data on cells of the hematopoietic system, such as circulating PBMCs, NK cells and bone marrow precursor stem cells. Little is known about the mechanisms of HBV entry into hematological cells; nevertheless, the role of PBMCs as an extrahepatic reservoir of HBV infection deserves further investigation, since it may contribute to persistent HBV production, potentially jeopardizing the success of the current and novel therapeutic approaches, aimed at achieving HBV functional cure.Furthermore, it is possible that the presence of HBV in immune cell precursors can promote uncontrolled cell proliferation and, possibly, malignancy.Data correlating HBV with other hematologic malignancies have been reported; however, they are not always confirmed and are often supported by limited studies. In particular, among hematological disorders so far investigated, a stronger association has been reported for B-cell NHL.There are no clear pathogenetic studies investigating the connections between chronic HBV infection and the onset of lymphatic and/or hematological malignancy, and it is possible that HBV acts more as an inflammatory driver than as a direct carcinogen.Nevertheless, it is known that HBV can frequently integrate its DNA into the genome of the infected cells. HBV DNA integration is recognized as a mechanism promoting neoplastic transformation by several mechanisms, including the direct dysregulation of oncogenes and onco-suppressors, the production of chimeric viral-human RNAs and proteins with transactivating properties, and the promotion of overall genome instability. Notably, HBV DNA integration represents a common phenomenon in NHL tissues, molecular data show its potential impact in carcinogenesis, and epidemiological evidence seems to confirm a possible correlation.In conclusion, although many epidemiological and laboratory studies have been produced in recent years, this remains a field of study due to the possible benefits of therapeutic or prophylactic strategies involving antivirals and vaccines.LS and VS: study conception and design. VS, VM, RS, MI, LP, and SD: literature revision. LS, VS, VM, RS, MI, LP, and SD: draft manuscript preparation. LS and VS: final manuscript revision. All authors contributed to the article and approved the submitted version.


Diabetic retinopathy (DR) is a complication of diabetes mellitus that can lead to vision loss and blindness. It is driven by various biochemical processes and molecular mechanisms, including lipid peroxidation and disrupted aldehyde metabolism, which contributes to retinal tissue damage and the progression of the disease. The elimination and processing of aldehydes in the retina rely on the crucial role played by aldehyde dehydrogenase (ALDH) and aldo-keto reductase (AKR) enzymes. This review article investigates the impact of oxidative stress, lipid-derived aldehydes, and advanced lipoxidation end products (ALEs) on the advancement of DR. It also provides an overview of the ALDH and AKR enzymes expressed in the retina, emphasizing their growing importance in DR. Understanding the relationship between aldehyde metabolism and DR could guide innovative therapeutic strategies to protect the retina and preserve vision in diabetic patients. This review, therefore, also explores various approaches, such as gene therapy and pharmacological compounds that have the potential to augment the expression and activity of ALDH and AKR enzymes, underscoring their potential as effective treatment options for DR. Diabetic retinopathy (DR) is a progressive disease that poses a serious threat to vision ,2,3. AlmThe etiology of DR is strongly associated with hyperglycemia and other factors commonly found in individuals with diabetes, such as hypertension and dyslipidemia ,8,9. TheDiabetic macular edema (DME) is the most common cause of vision loss in patients with DR . It is cPresently, there are no treatments for the early stages of DR, and the recommended approach is to regulate blood glucose levels and lipid profiles while maintaining proper control over blood pressure . The iniAlthough the clinical classification of DR primarily revolves around vascular pathologies, recent research has provided significant evidence indicating the involvement of the retinal neurovascular unit (NVU) in the development of this disease . The NVUDiabetes causes the breakdown of the inner BRB through the secretion of various substances by glial and immune cells within the NVU, including VEGF, pro-inflammatory cytokines , as well as components of the complement system . The dys+) in the extracellular space, which has been linked to retinal excitotoxicity benzene (TCPOBOP) leads to increased mRNA levels of AKR1b7, AKR1c6, AKR1c19, and AKR1d1 . On the In conclusion, DR is a progressive disease that significantly threatens vision globally. Specific lipid aldehydes  have strong associations with the onset and progression of DR. The retina possesses defense mechanisms that detoxify these lipid aldehydes produced during lipid peroxidation. Targeting ALDH and AKR enzymes, which are crucial for aldehyde detoxification, shows immense potential as a therapeutic approach for DR. These enzymes are expressed in the cells of retinal NVU and understanding their expression and functional roles in the retina, particularly in the context of diabetes, is crucial when unraveling the mechanisms underlying lipid aldehyde accumulation and DR development. Further research is needed to fully understand the cell-specific expression of various aldehyde detoxifying enzymes in the retina, which could be accomplished through the utilization of single-cell RNA sequencing techniques. Additionally, a deeper understanding of the substrate specificity of different aldehyde detoxifying enzymes could help identify the most suitable targets to enhance DR treatment. It is now imperative that we prioritize the translation of this research into therapeutic strategies that could be effectively implemented in a clinical setting.


Cardiac paragangliomas (PGLs) are rare extra-adrenal tumors that arise from chromaffin cells of the sympathetic ganglia. PGLs are often diagnosed incidentally, in the absence of symptoms, or with symptoms related to cardiovascular dysfunction. Cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) can be used to accurately determine the lesion morphology and position as well as providing detailed tissue characterization. A multimodal imaging approach, not yet standardized, could be useful either in diagnosis and monitoring or in treatment planning. In the case reported here, CCT and CMR were performed to define lesion anatomy, and a reconstruction was generated using cinematic rendering (CR) to characterize the PGL angioarchitecture. According to the World Health Organization’s tumor classification scheme, paragangliomas (PGLs) are rare neuroendocrine tumors arising from extra-adrenal parasympathetic or sympathetic ganglia neural crest cells .Cardiac PGLs are extremely rare tumors  originating from visceral paraganglial cells of the left atrium or the aorta. Cardiac PGLs are most commonly observed in the left atrium and they are functional in 35%–50% of patients with symptoms related to catecholamine excess , 3. ClinThese lesions can be evolutive, leading to serious complications such as bleeding and cardiac failure. Radiologic findings acquired by computed tomography (CT) and magnetic resonance (MR) play an essential role in cardiac PGL management and can provide further anatomic and tissue characterization.Currently, the most commonly used tool to provide 3D images from CT data is volume rendering (VR). The cinematic rendering (CR) algorithm has recently been introduced; this supports interpretation for diagnosis of various cardiac pathologies and treatment planning by creating complex lighting effects such as refraction, providing high levels of detail in terms of shadowing and depth, and visualizing high-density and high-contrast structures .In this study, we report the case of a patient with severe rest dyspnea, on whom cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) imaging were performed to characterize a vascularized paracardiac mass suggested by a previous invasive coronary angiography (ICA) addressing a possible angioma.CR reconstruction using the CCT dataset was employed to better evaluate the anatomical details, including course and tortuosity of the vessels  involved in the mass vascular supply.2). The patient provided written informed consent for this study.A 46-year-old man, a candidate for aortic valve replacement, was referred to us after an invasive coronary angiogram ICA;  showed aCCT was performed  using a CCT showed a solid mass above the basal anterior wall of the left ventricle, characterized by intense, progressive, and inhomogeneous contrast enhancement, and a capsule; the core of the lesion was hypovascular/necrotic; in addition, the lesion showed complete encasing of the left main coronary artery, the proximal-middle segment of the left anterior descending (LAD) coronary artery, and the proximal segment of the left circumflex coronary artery. CR reconstruction of the CCT dataset was employed to better evaluate the anatomical details involved in the mass vascular supply.The patient also underwent CMR imaging  on a 1.5CMR findings were as follows: well-circumscribed ovoid/spherical lesions and typical hyperintensity on T2 imaging sequences, with the other features similar to CCT.The location and evidence on the morphological, functional, and metabolic features of the mass all pointed to a solid, hypervascular, capsulated, non-infiltrative, neuro-endocrine type of tumor; even though serum catecholamines were within normal ranges, the diagnosis was non-excreting cardiac PGL.The patient is now in follow-up, mainly with CMR for 2.5 years, and the morphological features of the mass are stable. Multimodality imaging of atypical cardiac masses is warranted for proper diagnosis and follow-up.Extra-adrenal PGLs are solid hypervascularized tumors originating from the chromaffin cells of the sympathetic ganglia. PGLs are exceptionally rare , and their diagnosis and treatment usually follow very different paths and approaches.In our case, the mass is attached to the left upper anterolateral portion of the heart and incorporates an important tract of the left coronary artery as well as having contiguity relationships with the majority of adjacent structures.These aspects, as also reported in the literature, make any surgical removal procedure extremely complex and risky, although the possibility of cardiovascular morbidity and mortality without treatment remains high, given the possible compression/invasion of neighboring structures.Prognostic factors are represented by tumor attenuation, contrast enhancement, detailed understanding of the feeding vessel, and close proximity to surrounding blood vessels and vital structures , 6.CCT and CMR, thanks to multiple 2D postprocessing techniques, are available to facilitate evaluation of the anatomy, which is often complex and challenging in patients with cardiac PGL.CCT, thanks to its high spatial resolution and contrast, was able to evaluate the entire solid nodular mass at the base of the LV and its relationship with the surrounding arterial and venous vessels. The lesion was found to have stretched and shifted both the anterior descending coronary artery and the left circumflex artery, which, however, was not providing vascular supply.In this context, to develop a clear understanding of the PGL angioarchitecture, CR reconstructions were generated.Briefly, under this approach, 2D reconstructed slices composed of isotropic voxels from standard clinical CT acquisitions are stacked to create a volume, and light is passed through the volume to create a 3D visualization. However, compared to VR, CR makes use of a more sophisticated lighting model that creates photorealistic images with improved detail and produces shadowing effects that allow for robust visualization of the relative positions of structures.3D visualizations of CT data can be invaluable in the investigation of complex anatomy and pathology, and pathological findings concerning neighboring structures can be identified and visualized .3D CR is helpful for surgeons because it provides information on spatial relationships and a subjective perspective on the relevant organ .Similar to VR, CR provides the best visualizations of high-density and high-contrast structures such as contrast-enhanced small vessels, but at the same time, it provides more natural and photorealistic illumination of the rendered data , highligThe applications of CR are numerous and varied, including medical education, easy disease detection, and improved description and classification of lesions. Recently, examples of the advantages of CR in the context of cardiovascular pathologies have been presented and this method has been qualitatively compared with other 3D postprocessing methods , 12. MorIn our case, multiplanar reconstruction images still represented the gold standard in classification and preoperative treatment planning; however, the 3D volume rendering and cinematic rendering images provided a more exhaustive global overview of the vascular complexity of the lesion.For morphological evaluation and tissue characterization, acquisition of a CMR scan is useful in the differential diagnosis and monitoring of cardiac masses. Through this investigation, the study of the cardiac planes enables localization of the lesion and determination of its relationship with the surrounding structures. The morphological characteristics of hyper/hypointensity are suitable to discriminate the lesion, and its relationships with other structures are much better highlighted.In this case, the lesion showed obvious signal restriction in DWI sequence, and furthermore, the use of gadolinium (LGE) highlighted capsular hyperenhancement of the mass in post-contrast PSIR-TFE sequences, emphasizing its high vascularity.CMR is now in routine use, but the examination process is lengthy, and it may not be available at every facility.Both CCT and CMR are useful for further evaluation of these masses. Attenuation on CCT, tissue characterization on CMR, pattern and degree of contrast enhancement, and presence or absence of blood flow on cine CMR images can help differentiate among pericardial masses.CMR provides incremental prognostic value over clinical factors such as left ventricular ejection fraction and coronary artery disease. In , CMR hadIn our case, CMR contributed useful information, such as the morphological characteristics of hyper/hypointensity, signal restriction in DWI, and enhancement postgadolinium injection.This case study shows the ability of a multimodal morphological imaging approach, using images obtained with CCT and CMR, to correctly identify, locate, and characterize cardiac PGLs and monitor non-operable lesions over time.In challenging circumstances, extra-adrenal PGL and metastases can be localized using nuclear medicine methods such as SPECT and MIBG with neurotransmitter analogs, and metabolic radiotracers represent the final step for accurate functional characterization of a PGL and exclusion of a malignant component.For this type of lesion with complex morphology, not only do additional visualization techniques such as CR provide descriptions and detailed representations of the lesion, its anatomy, and its relationship to the surrounding structures, but they also act as support for both diagnosis and management of complex cardiovascular lesions. In vitro analyses should be performed to characterize the functional status of PGLs, a feature that, combined with the vascular relationships of the lesion, deeply influences the management of these patients.In conclusion, no standalone scans allow for comprehensive diagnosis of PGLs, although PET/MR technology and, more recently, radiomics techniques can attempt to solve issues related to morpho-functional assessment and benign/malign differentiation. In order to accomplish the aim of establishing the optimal ways to make use of these techniques, more studies with larger samples are needed.


The increasing interest in microbiological food safety requires the development of sensitive and reliable analyses and technologies for preserving food products’ freshness and quality. Different types of packaging systems are one of the solutions for controlling microbiological activity in foods. During the last decades, the development of biopolymer-based active packaging with essential oil incorporation systems has resulted in technologies with exceptional application potential, primarily in the food industry. There is no doubt that this principle can facilitate food status monitoring, reduce food waste, extend the shelf life, improve the overall quality of food, or indicate a larger problem during the storage, production, and distribution of foodstuffs. On the other hand, most antimicrobial packaging systems are in the development phase, while the sensitivity, selectivity, complexity, and, above all, safety of these materials are just some of the essential questions that need to be answered before they can be widely used. The incorporation of essential oils as antimicrobial substances in biopolymer-based active packaging holds significant promise for enhancing food safety, extending shelf life, and offering more sustainable packaging solutions. While challenges exist, ongoing research and innovation in this field are likely to lead to the development of effective and environmentally friendly packaging systems with enhanced antimicrobial properties. Microbiological contamination is a significant concern in the food industry as it can lead to foodborne illnesses and the spoilage of products. There are several acute problems associated with microbiological contamination in the food industry: foodborne illness outbreaks, product recalls, regulatory compliance, consumer trust, economic loss, supply chain issues, etc. To address these acute problems, the food industry employs various strategies, including stringent sanitation practices, HACCP  systems, regular testing and monitoring, and compliance with food safety regulations. Additionally, advances in food processing technologies as well as new packaging technologies are continuously being developed to mitigate microbiological contamination risks and improve food safety. On the other hand, the global production of plastics has gradually increased since plastics’ industrialization in the 1950s, reaching 368 million tons in 2019, with the expectation that it will reach 1.1 billion tons by 2050 .Beside plastic waste, food waste and spoilage are globally recognized as environmental and economic problems that need an emerging solution. Only a small percentage of food is composted, and the rest of the unused food is the largest compound of solid municipal waste, which degrades, releasing methane and contributing to greenhouse emissions. The food can be spoiled in physical, chemical, biochemical, and microbial ways during distribution, storage, and consumption. It is estimated that the amount of wasted food per year can feed one-eighth of the world’s population and answer the global challenge of meeting the increased need for food . PackagiTherefore, the development of active biodegradable packaging with incorporated bio-based antimicrobial agents such as essential oils can address urgent challenges on a global level, such as reducing plastic and food waste and their harmful effects on the environment. This review includes information about biopolymer-based structures used for packaging systems and different approaches for the incorporation of essential oils in targeted structures. Additionally, the emergence of microbiological contamination in the food industry, the influence of the packaging system on the inactivation of microbiological contamination, the migration of the antimicrobial substance into the packaging system, and the proposal for comprehensive determination of the antimicrobial potential of biopolymer-based active packaging with incorporated essential oils were summarized.Campylobacter spp., Escherichia coli O157 (STEC and VTEC), Listeria monocytogenes, Salmonella spp. , Salmonella enteritica serotype Typhi, Shigella spp., and Yersinia enterocolitica. The mentioned bacteria are monitored in numerous countries and by a large number of health organizations for the prevention of foodborne diseases, determining the source and place of outbreaks, etc. [Diseases caused by the consumption of contaminated food, called foodborne diseases, represent a challenge to the entire system of food production and supply. The food supply line represents the processes of growing, harvesting, transporting, storing, and preparing food in an unhygienic environment, often without adequate environmental control measures. Therefore, this indispensable route represents an infection path for humans. Foodborne microorganisms often cause acute illness in humans but also significant economic losses during food production and processing. It should be noted that some groups of the human population are more at risk than others, such as children, pregnant women, elders with low immune status, persons with cancer, on chemotherapy, or/and infected with HIV . There aks, etc. .Salmonella bacteria, S. aureus, C. perfringens, and Campylobacter spp. are found in five prominent foodborne pathogens [In the last decade, the global food and beverage industry has seen significant growth. Following this trend, this industry is predicted to be worth more than 5700 billion dollars by the end of 2025 . The turathogens . Based oathogens . The mosathogens .Pseudomonas spp. and lactic acid bacteria (LAB), which are often involved in the spoilage of dairy and meat products. What distinguishes microbiological contamination in the food industry is that bacteria easily resist adverse environmental conditions, including high pH, low temperatures, and anaerobic environmental conditions [Microbiological contamination can enter the food chain in a production environment , process environment , preparation environment , and/or water used in any production-process phase . Althougnditions .E. coli, Salmonella spp., L. monocytogenes, Vibrio cholerae, and Pseudomonas spp., were isolated from water used in cases of agricultural production [L. monocytogenes. It is considered that bacteria are the main cause of spoilage in most food products, which causes a great economic loss in the process of food storage and preservation [Bacteria occupy a very important place among the microorganisms found in food. This is not only because many species can be present in food but also because of their fast growth and ability to use nutrients, as well as their ability to grow in different conditions . Various indicators of fecal contaminants, such as oduction . Also, fervation .E. coli, Salmonella spp., and Clostridium botulinum stand out in particular and are extensively studied by both the medical and scientific public. An unavoidable detail is the unpredictable nature of bacterial contamination due to the type of food in which they are found, the environment and storage conditions, and the possibility of toxin production. Some bacteria are found in food products as secondary contamination, while others live only in certain food environments, such as C. botulinum, which has been a problem for the canned food industry for decades due to its anaerobicity and sporogenicity [L. monocytogenes, which represents a major risk in RTE foods containing smoked meats and sausages [The presence of bacteria in food products is a matter of great importance. Bacterial motility, adaptability, sporogenicity, toxin production, and cell wall structure dictate the treatments involved in food preparation and processing. Although there are many ways to group bacteria, from the point of view of the food industry, the following division is the most important: non-pathogenic, conditionally pathogenic, and pathogenic bacteria, whereby the controversy that the mentioned groups may or may not be the cause of food spoilage must be added to the discussion . Pathogegenicity . Anothersausages . Non-patThe most common foodborne bacteria, coupled with food sources and health risks, are summarized in Due to their ability to contaminate and degrade food products by producing extracellular enzymes, mycelial fungi and molds are of great importance in the microbiological contamination of food . AccordiAspergillus and Penicillium species stand out. In addition to them, Mucor, Absidia, and Rhizopus genera stand out. Apart from representatives of Ascomycotina and Zygomycotina, xerophilic fungi whose growth is characteristic under conditions of reduced water activity (aw) also occur as food contaminants. Representatives of this group of fungi are Xeromyces and Vallemia [Deuteromycotina can also be food contaminants, with Alternaria, Botrytis, Cladosporium, and Fusarium species being the most prominent [Among the fungi that appear as food contaminants, Vallemia . Represerominent . The mosFungal contamination of food generally occurs first as contamination with spores that can be part of the sexual and asexual reproduction of fungi . In favoThe presence of microorganisms in food is one of the main problems for the food industry, scientific community, and global economy. This problem appears to be a global issue because it represents a constant threat to health. As a consequence of the solution to this problem, the food industry must constantly develop and prepare procedures that minimize the occurrence and persistence of microbiological contamination in food . This prModern methods for early detection of microbiological contamination include expensive genotyping and identifying the presence of microorganisms where possible and feasible in real-time . HoweverIn the last few decades, the resistance of microorganisms to antimicrobial agents has become a major environmental problem, and consequently, the number of broad-spectrum antimicrobial agents is decreasing. The acquired antimicrobial resistance, most microorganisms can transfer to new generations by simple, horizontal gene transfer. In addition, the abuse of antimicrobial agents, which is expressed in the veterinary and meat industries, has caused even specific antimicrobial agents to be no longer effective in the fight against pathogens in food. On the other hand, the pharmaceutical industry does not have a solution for the production of new antimicrobial agents, both due to the lack of sources and the high cost of production .Different materials have been used in food packaging, such as metal, glass, paper, and plastic. Environmental concerns and strivings to reduce the amount of solid waste, as well as consumers’ requirements for increasing food safety, have imposed a need for the development of biodegradable active packaging . The difBiopolymer-based structures for the encapsulation of essential oils can be divided into particles, fibers, and gels .They usually have nanodimensions, which classify them as nanostructures. Different biopolymers have been utilized for the preparation of nanoparticles—vesicles with sizes up to 100 nm, intended for the encapsulation of essential oils in active packaging applications. Proteins and polysaccharides, individually or together (in the form of complexes), are used for obtaining nanoparticles. For the production of protein, polysaccharides, and protein/polysaccharides-based nanoparticles, different methods have been utilized, such as nanospray drying and complex coacervation. Different proteins and polysaccharides such as zein, gelatin, soy protein, whey protein, milk proteins, alginate, pectin, chitosan, pullulan, starch, cellulose, gellan gum, and maltodextrin have been successfully used for the formation of nanoparticles or nanocapsules intended for the incorporation of essential oils as antimicrobial agents in active packaging with the aim to achieve their compatibilization with hydrophilic biopolymer matrix and protect them from evaporation, thermal degradation, and oxidation during film processing and product storage ,30. The Nanofibers are obtained by a process that implies the conversion of biopolymer solution into nanofibers using electrohydrodynamic techniques such as electrospraying (low-density polymer solution) and electrospinning (high-density polymer solution). The fibers are formed under an electrical field passing through the syringe. The first step in the preparation of nanofiber-loaded essential oils implies the formation of EO emulsion in a hydrophilic biopolymer solution using usually non-ionic surfactants from the group of Triton X or Tween. Active packaging based on nanofibers obtained from chitosan, gelatine, alginate, zein, chitosan/gellan, tragacanth, and sodium alginate/polyvinyl alcohol with different EOs has been proven effective in the protection of food products against foodborne pathogens ,44,45,463D networks are comprised of chemically or physically crosslinked hydrophilic or amphiphilic polymers, usually nano-sized (1–200 nm), called nanogels. According to affinity for certain solvents (water or hydrophobic ones), nanogels are divided into hydrogels and organogels. Hydrogels are obtained by the crosslinking of hydrophilic monomers or polymers, possess an affinity for water, and are suitable for the incorporation of hydrophilic compounds. On the other hand, organogels possess an affinity for a hydrophobic medium and are suitable for entrapping essential oils. Nanoorganogels have been proven to be promising systems for encapsulating and delivering EOs, improving their performance. They are obtained by a covalently crosslinked or self-assembly process. Nanogels based on chitosan/myristic acid and chitosan/benzoic acid have been shown to be efficient in the encapsulation of clove and rosemary essential oils, contributing to the better antimicrobial activity of active packaging toward food pathogens ,48. The Bacillus sp. and Klebsiella. The main types of cyclodextrins consist of 6, 7, and 8 glucopyranose units  connected by a (1–4) glycosidic bond. The inner cavity of CDs is hydrophobic, while the outer side has an affinity toward the aqueous phase. With hydrophobic substances, such as essential oils, CDs form host-guest inclusion complexes via secondary forces, enabling their compatibilization with a hydrophilic biopolymer matrix. The procedure of preparation of inclusion complexes implies the dispersion of CDs and essential oil in an aqueous medium, stirring in mild conditions, and the filtration of obtained inclusion complexes [Another example of a good carrier for antimicrobial substances are the cyclodextrins (CDs). CDs are cyclic oligosaccharides obtained as a result of the enzymatic conversion of starch by the action of the enzyme glycosyltransferase, produced by the bacteria omplexes . Active omplexes , formatiomplexes , or CD-Eomplexes .The ideal antimicrobial biopolymer packaging should meet several important criteria. To begin with, all phases (components) in their production must, following legal regulations, meet the conditions of direct contact with food . In addiThe basic division of packaging with antimicrobial action is biodegradable and non-degradable. Most synthetic polymers are not biodegradable, which is why they are often used as packaging materials. In addition, they are characterized by low cost, low density, internality, good protective properties, mechanical strength, a high degree of transparency, the ability to heat seal, and the possibility of labeling and printing . The mosEssential oils are hydrophobic liquids consisting of volatile aromatic compounds with diverse effects—antimicrobial, antioxidant, anti-inflammatory, analgetic, anti-depressive, relaxing, etc. They are highly recognized in the pharmaceutical industry and medicine, but also in the gastronomy and food packaging industries. EOs are obtained by extraction from different plant parts—seeds, stems, bark, buds, leaves, and flowers. The composition and yield are influenced by the conditions of plant growth and harvesting as well as extraction parameters . Among different extraction methods for EO, steam distillation is the most widely used method, resulting in a high yield (above 93%) . This meZingiber officinale), cinnamon oil, thyme oil (Thymus vulgaris), lemongrass oil (Cymbopogon citratus), oregano oil, tea tree oil , sage oil , catnip essential oil (Nepeta cataria), Satureja Khuzestanica, Helichrysum italicum, mustard (Brassica nigra), etc. [It can be summarized that essential oils play a crucial role in active packaging systems by virtue of their profound antimicrobial attributes, which synergistically enhance the protective capabilities of packaging materials against microbial threats. These oils, harnessed from botanical sources, contain a rich array of bioactive constituents, including phenols, terpenes, and aldehydes, that collectively exhibit potent inhibitory effects against a spectrum of microorganisms. The main compounds of essential oils belong to the class of monoterpenes, monoterpenoids, and phenylpropanoids  . Those ca), etc. . Mechania), etc. . This ina), etc. . DiffereWhen a biopolymer possesses a hydrophobic character, such as in the case of cellulose acetate , celluloIn order to achieve complete incorporation (solubility) of essential oils into hydrocolloids—water-soluble proteins and/or polysaccharides matrix, controlled release of EOs, their protection against oxidation, thermal degradation, and evaporation—with the aim of ensuring uniform dispersion into a hydrocolloid matrix, it is necessary to encapsulate them using different approaches such as emulsification, liposome formation, entrapping in biopolymers and clay-based nanocarriers, as well as in cyclodextrins. The advantages and limitations of each method of incorporation of essential oils in a biopolymer matrix are given in Encapsulation by emulsification is a simple method for the compatibilization of essential oils and hydrophilic biopolymers, which requires high mechanical energy incorporated in the system and the addition of amphiphilic molecules—emulsifiers or surfactants. After the formation of EO droplets in the aqueous medium under high-speed stirring, an emulsifying agent intended for the formation of oil-in-water emulsion is added. The droplet size is mostly between 20 and 200 nm; therefore, the obtained emulsion has the prefix nano . DiffereLiposomes are vesicles that consist of a hydrophilic core and an amphiphilic—phospholipids-based bilayer. Liposomes are categorized according to their size and lamellarity, such as small unilamellar vesicles (SUV)—with sizes in the range between 20 and 100 nm; large unilamellar vesicles (LUV)—with sizes above 100 nm; and multilamellar vesicles (MLV)—sizes above 500 nm . HydrophThe basic property of most antimicrobial packaging is based on the migration of the antimicrobial substance from the packaging matrix to the packaged food and/or the space around the food. In contrast to microbiological contamination, the migration of the active compound from the matrix is a deliberate, targeted, and necessary process to achieve the antimicrobial effect and protection of the antimicrobial package. Only proper and controlled migration of the antimicrobial substance can inhibit or reduce the proliferation of microorganisms and delay food spoilage and expiration .Unlike other types of active packaging materials where the migration of the target compound does not have to be efficient, this property of antimicrobial packaging is a critical point and is largely determined by the proper release of the antimicrobial compound from the active material. Only a gradual migration of the antimicrobial agent will maintain an effective antimicrobial concentration of the target substance in the packaging system during a longer period of storage . Behind However, there is one important but expected drawback of antimicrobial packaging. In addition to the desired migration of the active compound, antimicrobial packaging can also release other low-molecular-weight substances into the food. Volatile substances, polymer additives, residual monomers, or oligomers that are not bound to the packaging matrix can migrate into the packaged food . The migDiffusion of the substance from the packaging matrix;Desorption from the matrix surface;Sorption of the substance in the contact space;Desorption into food.The term “migration” refers to the transfer of low-molecular-weight compounds from the packaging matrix to the packaged food. In polymer packaging, the migration process is characterized by great complexity, which is strongly influenced by the interaction between the food components and the packaging material . Bhunia This migration mechanism can be twofold, depending on whether the packaged food is in direct contact with the packaging matrix or not . Namely,For antimicrobial packaging to be effective, the active compound must be released at a minimum inhibitory concentration (MIC) level. However, this reference concentration will not only depend on the antimicrobial activity of the compound incorporated in the polymer matrix but also on the matrix itself, given that the interaction between them strongly affects the release of the active substance . TherefoIt is important to emphasize that multi-layer systems provide numerous advantages in terms of the migration of the active substance in the packaging. As for the migration process, the combination of different layers achieves a controlled release of the active compound from the packaging. From an industrial point of view, this combination can affect packaging costs, which can be another disadvantage of active packaging .In the last decades, materials for food packaging have been improved in several different aspects, such as the development and selection of the best packaging option, prolongation of the shelf life of food, meeting environmental requirements, etc. Modified atmosphere-, smart-, and active packaging have become essential in the improvement of food storage and protection conditions from processing and production processes, through handling and storage, to the final consumer and disposal . InteresFurthermore, packaging materials should not be seen as waste but as a resource. One of the best ways to achieve this result is by recycling. Many food companies have been much more interested in another way of using packaging materials: biodegradable packaging. However, a major problem is excessive costs in proportion to the amount of biodegradable material that has to be used . EquallyToday’s trends in developed countries related to fresh, minimally processed, easy-to-prepare, and RTE foods represent major challenges in terms of the microbiological safety and quality of these foods. A similar problem arises in the course of globalization, i.e., the distribution of food from centralized industrial systems to the whole world . This flAlthough the primary idea of inactivating microbiological contamination was related to improvements in traditional food preservation methods , it was quickly realized that no single method is comprehensive and is not the right solution for inhibiting the growth of microorganisms and preventing food spoilage completely. One of the innovative strategies to extend the shelf life of food is the addition of antimicrobial substances to food, which has also had a limited effect given that most consumers want high-quality food without preservatives . Also, tAs already mentioned, the primary function of packaging is related to the protection of food from external influences, mechanical force, and spoilage by environmental microorganisms, moisture, gases, dust, odors, etc. . Also, tPackaging with antimicrobial activity is reflected in a physical combination of two or more chemically different phases, where one of the phases is the matrix of the packaging, while the other phases are in the form of embedded substances with antimicrobial properties . One impIn other words, the use of polymeric materials as a matrix phase (carrier) of antimicrobial agents has a consequent, threefold role, as presented in According to Radusin et al. , antimic2, ZnO, and MgO have antibacterial activity attributed to their effect on the cell’s respiratory system (creating reactive oxygen). Titanium dioxide is non-toxic and has been approved by the FDA for use in food, drugs, and food contact materials [2O3, and iron oxides) [It most often happens that a certain antimicrobial substance is effective only on one group of microorganisms. That is why silver ions are often used due to the wide spectrum of antimicrobial activity against gram-negative and gram-positive bacteria, fungi, protozoa, and certain viruses ,124. In aterials . On the aterials . For nowaterials . Antimic oxides) .In recent years, the use of inorganic nanoparticles as antimicrobial substances in packaging materials has particularly intensified. This is attributed to the good stability of these materials and their ability to withstand process conditions such as high pressures and temperatures in plastic manufacturing processes . In addiA wide variety of natural extracts, such as pigments, garlic, lemongrass, cinnamon, cloves, and oregano, have shown antimicrobial activity in packaging material against a large number of bacterial pathogens . The mosFinally, it should be emphasized that the direct addition of an antimicrobial substance to food can reduce food quality, changing the organoleptic and textural qualities of food . ConsequPreliminary antimicrobial analysis of the selected essential oils by disc-diffusion method;Determination of the minimal inhibition concentration (MIC) of the selected essential oils;In vitro assessment of the antimicrobial activity of active packaging systems;In vivo assessment of the antimicrobial activity of active packaging systems;Sensory analysis.While in vitro studies provide valuable insights into the antimicrobial properties of biopolymer-based active packaging, they have limitations and should be complemented with in vivo experiments on the specific food products the packaging is designed for. Generally, when it comes to testing the antimicrobial potential of newly designed biopolymer-based active packaging with incorporated essential oils, researchers should follow these steps:6 CFU/mL; (iii) homogenization of 1 mL of cell suspension with 9 mL of melted and tempered culture medium, which should be poured into Petri dishes; (iv) after the solidification, the sterile discs (6 mm in diameter) should be placed onto the inoculated medium; (v) on each disc, an aliquot of 15 μL of the tested essential oil and suitable positive and negative controls is applied; and (vi) after the incubation period, the diameter of the halo zone can be measured for each disc and expressed in mm [As presented in ed in mm .cN is a number of cells in a positive control and tN is a number of cells after the contact of essential oil dilution and microbial cells. This method seems to be indispensable when testing compounds with promising antimicrobial effects [In order to obtain the minimal inhibitory concentration (MIC) of the selected essential oil capable of inhibiting microbial growth up to 90%, the microdilution method is usually employed. The preparation of cell suspension is performed in the same manner as the previously described disc diffusion method. Afterwards, the serial dilutions of the tested essential oil were prepared, and equal volumes (100 μL) of each dilution and inoculated media were transferred to a sterile flat-bottom, 96-well microtiter plates. After the period of incubation, 100 μL of mixture from each well was poured into Petri dishes and homogenized with suitable culture media. Petri dishes are commonly incubated under the same conditions as microtiter plates, and the grown colonies are enumerated by viable count. The final results of the MIC determination are calculated as follows: effects ,138,139.In vitro assesment of antimicrobial activity of active packaging systems involves conducting laboratory experiments to evaluate the effectiveness of each packaging layer in inhibiting the growth of microorganisms that can spoil or contaminate food products. In this step, it is very important to test each layer individually and their combinations to ensure their activity against the selected microorganisms . Also, tIn vivo assessment of the antimicrobial activity of active packaging systems involves conducting experiments in real-life conditions to evaluate the effectiveness of packaging materials in inhibiting the growth of microorganisms and preserving the quality and safety of food products. Unlike in vitro assessments, which are conducted in controlled laboratory settings, in vivo assessments provide a more realistic understanding of how active packaging systems perform in practical situations. After choosing the relevant microorganisms or pathogens that are likely to affect the quality and safety of the specific food being packaged, their suspension should be made, and the selected food should be artificially contaminated with them. Afterwards, the active packaging materials with antimicrobial agents can be placed on the selected food, ensuring direct contact with it. The packaged food is then stored under the conditions that simulate the intended storage environment , and periodically, the samples of the packaged food are performed to assess microbial populations over time. The common microbial analyses that are conducted for this purpose are colony counting by using standardized methods , PCR  and quantify the intensity of these attributes using a trained panel;Consumer Acceptance Test—Assess consumer preferences and overall acceptance of the food products with active packaging systems compared to controls.Sensory analysis of active packaging systems involves evaluating how the packaging materials affect the sensory attributes  of the packaged food products. This type of analysis helps determine whether the active packaging materials introduce any changes in the sensory qualities of the food, which can influence consumer perception and acceptance. In order to perform sensory tests, a panel of trained sensory analysts or consumers who are skilled in evaluating food products should be recruited . The senThe results obtained by the sensory panel should be interpreted and analyzed to determine if there are any noticeable sensory changes introduced by the active packaging system, taking into account whether these changes are acceptable to consumers or if they may impact the marketability of the product. Moreover, the results of sensory analysis can be compared with the data obtained during microbial analysis in order to understand if any changes in sensory attributes correspond to changes in microbial populations.Sensory analysis of active packaging systems is crucial for ensuring that the packaging materials do not adversely affect the sensory characteristics of the food products. This information is essential for product development, quality control, and consumer acceptance.The incorporation of essential oils as antimicrobial substances within biopolymer-based active packaging has demonstrated the packaging material’s antimicrobial efficacy. The bioactive compounds inherent in essential oils exhibit pronounced inhibitory effects against a spectrum of pathogenic and spoilage microorganisms, thereby manifesting a tangible extension of the shelf life of packaged commodities. This innovative approach offers a more sustainable alternative by mitigating reliance on conventional synthetic antimicrobial additives, thereby aligning with the contemporary drive for sustainable packaging modalities. The strategic incorporation of essential oils into biopolymeric matrices constitutes a propitious intervention, effectively attenuating the reliance on chemical preservatives and satisfying the increasing demand for environmentally based packaging solutions. The consequential elongation of product shelf life is a noteworthy outcome of this integration, notably benefiting perishable commodities encompassing many food items. The noticeable inhibition effect on spoilage microorganism proliferation is crucial in solving the perishability predicament that compromises product quality. Moreover, the incorporation of essential oils can offer ancillary advantages, particularly in the realm of flavor preservation. The aromatic origin of essential oils imparts a natural flavor profile to packaged foods, thereby augmenting their sensorial allure.By addressing these critical fronts, the integration of essential oils within biopolymer-based active packaging is poised to substantiate its role as a pivotal stride towards efficacious and sustainable food preservation patterns. However, the journey is not without challenges, especially concerning essential oil volatility and compatibility within diverse biopolymer matrices. The vulnerability of essential oils to gradual volatilization underscores the need for meticulous considerations to ensure sustained antimicrobial efficacy. Furthermore, the homogenous dispersion or encapsulation of essential oils within packaging materials necessitates precise techniques due to the intricate nature of the process. The regulatory landscape also requires attention, as the utilization of essential oils in active packaging calls for adherence to rigorous safety and food contact standards. The variability in permissible concentrations across jurisdictions accentuates the need for strict regulatory compliance. The exploration of synergistic interactions among essential oils and other antimicrobial agents offers a promising avenue to enhance antimicrobial potency further. Understanding the mechanistic nuances underlying these interactions opens novel avenues to fortify the antimicrobial efficacy of active packaging materials. Moving forward, research endeavors should focus on optimizing formulation techniques, refining processing methodologies, and elucidating the long-term stability and controlled release kinetics of essential oil-infused packaging materials under varying storage conditions. Addressing these critical aspects will underpin the integration of essential oils within biopolymer-based active packaging as a pivotal step toward effective and sustainable food preservation strategies. The symbiotic alliance between essential oils and biopolymers holds immense potential for redefining packaging’s role in ensuring food safety and longevity while aligning with evolving environmental paradigms. Sensory evaluations discerning alterations in sensory attributes and preferences are imperative in refining the formulation of biopolymer-based packaging fortified with essential oils. Prospective research trajectories should endeavor to optimize formulation methodologies, augment processing techniques, and illuminate the long-term stability and controlled release kinetics of essential oil-infused packaging across varying storage conditions.In conclusion, the integration of essential oils as potent antimicrobial agents within biopolymer-based active packaging materials represents a transformative advancement in the realm of food preservation and packaging. The incorporation of essential oils and biopolymers synergistically marries the innate antimicrobial attributes of the former with the structural advantages and eco-friendliness of the latter. This convergence not only bolsters packaging’s role in safeguarding product quality and shelf life but also resonates with the global call for sustainable packaging solutions. Crucially, the selection of appropriate biopolymers is an essential determinant of the success of active packaging systems. Different biopolymers bring distinct mechanical, barrier, and compatibility properties to the table, influencing the overall performance and practicality of the packaging. The adaptability of essential oils to diverse biopolymers is a testament to their versatility, with each combination offering a unique and tailored approach to combating microbial proliferation. Furthermore, the dynamic landscape of consumer preferences underscores the need for a holistic evaluation of the sensory attributes imparted by essential oils in packaged products. As consumers increasingly seek natural and minimally processed alternatives, the interplay between essential oils, flavors, and product quality gains paramount significance. Looking ahead, continued research is indispensable in fine-tuning the formulation and processing techniques of essential oil-infused packaging materials. The optimization of factors like essential oil concentrations, release kinetics, and shelf stability will pave the way for robust and scalable applications. Collaboration across multidisciplinary domains, encompassing chemistry, packaging engineering, microbiology, and consumer studies, holds the potential to yield comprehensive solutions that address both technical and consumer-driven challenges. The alignment of industry efforts and academic exploration will drive innovation in antimicrobial active packaging, propelling it from a nascent concept to a standard practice in ensuring food safety and extending shelf life. In summary, the integration of essential oils within biopolymer-based active packaging encapsulates a dynamic convergence of science, sustainability, and sensory appeal. By harnessing the power of nature’s antimicrobial arsenal and the ingenuity of biopolymers, this interdisciplinary approach forges a path toward safer, longer-lasting, and more environmentally conscious food products. The journey is ongoing, but the strides made so far signify a promising future where essential oil-infused packaging stands as a cornerstone in the modern food packaging landscape.


Cancer, the second leading cause of mortality worldwide, has been the subject of extensive and quickly changing scientific study and practice. Cancer remains a mystery despite the enormous effort put into understanding the genesis of cancerous cells, the development of malignant tissues, and the process by which they propagate and recur. Cells from humans that have been recruited by cancer and, to some extent, changed into pathogenic organisms or the foundation of tumors serve as agents of destruction. Understanding cancers leads to challenging philosophical issues since they undermine and use multicellular organization processes. Cancer metastasizing cells adopt new phenotypes while discarding previous behaviors. The absence of comprehensive knowledge of this has hampered the development of therapeutics for metastatic illness. For systems-level experimental and computational metastasis modeling, integrating these complex and interconnected features continues to be a problem because metastasis has typically been studied in separate physiological compartments. Lung, breast, and prostate cancers accounted for the bulk of the 18 million new cases of cancer that were diagnosed in 2018. The most frequent cancer in women is breast cancer. Animal experimentation plays a significant role in primary and translational breast cancer research. In theory, such breast cancer models should be comparable to breast cancer in humans in terms of tumor etiology, biological behavior, pathology, and treatment response. Epidemiologic research has dramatically benefited the current understanding of genetic and environmental carcinogenic factors for breast cancer. Breast cancer risk factors include race, familial history of the disease, ethnicity, genetics, and modifiable exposures such as increasing alcohol use, inactivity, exogenous hormone use, and unique female reproductive variables . CarcinoThe effects of hormone replacement therapy (HRT) on breast tissue may vary depending on the kinds of estrogen or progestogen, as well as the formulations, dosages, and durations. Conjugated equine estrogen (CEE) appears to have a lower profile risk when compared to astro-progestin treatment , whereas progestins with a structural affinity for testosterone are associated with a greater risk . The relationship with progestins, particularly in continuous combination regimens, seems to lower the risk of hyperplasia of the endometrium and cancer. In contrast, prolonged unopposed endometrial interaction with estrogen raises those risks  [Impact of neoadjuvant chemotherapy (NACT) on the hypothalamic-pituitary axis and the resulting change in gonadotropin levels in premenopausal breast cancer patients. The outcomes for postmenopausal women having breast cancer who received NACT, namely the considerable drop in gonadotropin hormone-releasing hormone (GnRH) and follicle-stimulating hormone (FSH) concentrations comparable to control postmenopausal women, are different from those for premenopausal women . Breast PlacentaHuman Placental Lactogen (HPL)Placental lactogen levels may be less than controls in the early stages of pregnancy  and more significant compared to authorities in the later stages of pregnancy ; however, there is no direct correlation between absolute HPL concentrations and maternal glycaemic results in gestational diabetes mellitus (GDM) or pre-gestational diabetes mellitus (PGDM), nor with GDM status or risk. Additionally, in pregnancies impacted by GDM or PGDM, HPL is probably favorably associated with placental mass and child birthweight and may play a functional role in the control of fetal development. Despite being out of common clinical usage in recent years, HPL may be worth looking at again as a potential antenatal indication for diagnosing macrosomia . AccordiHuman Chorionic Gonadotropin (hCG)Testing for hCG shows that this enzyme is involved in many functions. While its primary job is to sustain early gestation, the findings of testing may result in inaccurate inferences about the pregnancy status. This might have significant emotional and monetary repercussions for patients in various circumstances. Additionally, hCG testing might detect another disease, such as cancer . EctopicUterusProlactin (PRL)Although it has been linked to several bodily processes, including metabolism and energy balance, PRL is named for its critical role in stimulating milk production during lactation. Many of the physiological adaptations of the mother's body to cope with the physiological needs during lactation and pregnancy, including the high energy requirements of the developing fetus, followed by the production of milk to support the child after birth, have been attributed to PRL . PRL plaRelaxinA class of peptide hormone/neuromodulators known as relaxins (RLNs) can control various physiological functions, including brain function and reproduction . In pathHypothalamic and pituitaryGonadotropin-Releasing Hormone (GnRH)Human reproductive capability is initiated and maintained by the pulsatile production of the hypothalamic hormone GnRH. Congenital hypogonadotropic hypogonadism (CHH) is an uncommon condition that causes delayed puberty and infertility by impairing average episodic GnRH production . The oveLuteinizing Hormone (LH)Many females experience infertility due to reproductive dysfunction, which has drawn the interest of several researchers due to its complicated pathophysiology. Ovulation problems resulting from various pathogenic reasons are a defining feature of female infertility. Through decreased LH, p62 deficiency in the pituitary caused female infertility . Eighty Follicle-Stimulating Hormone (FSH)The pituitary gland produces FSH as part of a synchronized hypothalamic-pituitary-gonadal (HPG) axis event; it is crucial for fertility because it is essential for reproduction and the development of germ cells at various stages of reproductive development . The dissociable components comprise the heterodimeric glycoprotein hormone FSH . To presOxytocin (OT)A pleiotropic peptide hormone called oxytocin extensively affects social behavior, development, reproduction, and overall health. Endogenous oxytocin promotes patterns of growth, resiliency, and healing, as does activation of the oxytocin receptor. An anti-inflammatory, antioxidant, and stress-coping chemical, oxytocin has protective benefits, particularly when faced with hardship or trauma . Even whOvaryProgesteroneA vital steroidogenic precursor for various non-gonadal and gonadal hormones, including aldosterone, estradiol, cortisol, and testosterone, progesterone is known to have a significant physiological role in both the menstrual cycle and pregnancy . AccordiAndrostenedioneDehydroepiandrosterone (DHEA), testosterone, dehydroepiandrosterone sulfate dihydrotestosterone, androstenedione are all naturally occurring androgens in females. Acne, hirsutism, and androgen-mediated cutaneous diseases (AMCDs) associated with female pattern hair loss (FPHL) are only a few of the frequent cutaneous problems that these androgens are crucial in the development . The mosEstrogensDuring pregnancy, the breast undergoes morphological and physiological changes that prepare it for lactation. The ductal system enlarges and branches into the fat tissue in response to the surge in estrogen throughout the first trimester. Another consequence of elevated estrogen levels is decreased adipose tissue and ductal proliferation and elongation . The preInhibinThe transforming growth factor beta (TGFb) superfamily includes activins and inhibins, which include the isoforms of activin C, A, B, AB, and E, and inhibin A and B, respectively. They control various biological processes, such as cellular differentiation, proliferation, and invasiveness, to improve the synthesis and operation of several tissues in humans and organs . AccordiReflects the predisposing and overall effect of placental, uterine, hypothalamic and pituitary, and ovarian hormones on breast cancer. We are dealing with the hormones somehow linked with the female reproductive system. HPL is supposed to mainly affect the breast. It involves the development of breasts and is believed to reduce the growth of breast cancer and is considered a protective hormone, thus its effect is protection from the development of breast cancer in the life of a female. The second hormone secreted from the placenta is human chorionic gonadotropin. This hormone does not have enough research data to prove its role in breast cancer but is supposed to increase the risk of development of breast cancer in females with higher levels of hGC and if the levels persist for a longer time in the body. The hormone prolactin is supposed to increase the risk of breast cancer development in a female's life. The increased levels of prolactin are supposed to be harmful to females and thought to increase the risk of development of breast cancer in the life of females. Thus disregulation of the hormone prolactin increases the risk of the development of breast cancer in the life of a female. Relaxin is the second hormone secreted by the uterus, which is supposed to have a preventive role against the development of breast cancer in the life of females. Still, the data is insufficient for it to be proved. However, this hormone relaxin is supposed to be considered a protective role for breast cancer. Hypothalamic and pituitary secret hormones gonadotropin-releasing hormone increases the risk of breast cancer development in a female's life, but it has insufficient data to prove its role; it is not a protective hormone for breast cancer. The following hormone, luteinizing hormone, secreted during the menstrual cycle, is supposed to help in the development of tumors in the breast. This tumorigenesis action of this LH hormone is considered to promote the growth of breast cancer in the life of a female. A follicle-stimulating hormone secreted during the menstrual cycle is supposed to prevent the action of certain drugs and causes chemoresistance; however, the data is insufficient to prove this. The fourth hormone, oxytocin, is believed to be protective against developing breast cancer. It causes alterations in the breast tissue and thus has a protective hormone effect in breast cancer. Ovaries secret progesterone during the life of a female. This hormone, if secreted in a limited amount, helps the breast protect against breast cancer. The critical part of this hormone is that its small amount helps cure breast cancer. Androstenedione's role is uncertain but is linked to breast cancer development. Estrogen, due to its encouraging role in the development of tumors, helps organs have the potential of turning malignant, and this increases the risk of breast cancer. Inhibin is a hormone of disregulated levels, which may increase the development of breast cancer in females; however, the role is uncertain and yet to be proved Table .Cancer is the leading cause of death worldwide. Cancer is a malignant growth of cells that takes up the nutrition from the surrounding tissue and starves them to death. Cancer cells have escaped the normal cell cycle and do not undergo apoptosis. Cancer cells can spread all over the body from the primary site to the secondary site using various channels of our human body spreading through the blood, spreading through the body's lymphatic drainage, and many more. The factors that cause cancer are known as carcinogens. These carcinogens are the reason for the occurrence of cancer at the primary site in the human body. Carcinogens are major of three types chemical mutagens, physical mutagens, and biological mutagens. The physical mutagens include factors like radiation, and the natural mutagens include microorganisms like viruses. The chemical mutagens include carbon compounds, hormones, and other factors. This review article presents the hormonal effect on cancer predisposition and its overall development. We are dealing with the hormones somehow linked with the female reproductive system.