Vaccines are considered as a therapeutic area for children; the scientific community focuses mainly on managing chronic disease when it comes to adults. There currently is an increase in the burden of vaccine preventable illnesses in adults. Adult vaccination has been shown to dramatically increase the health and quality of life of older populations. Therefore, adult vaccinations need to be approached as a public health issue, similar to smoking cessation programs, for example. According to the Kenya Non-Communicable Diseases and injuries poverty commission report, 2018. Kenya has a high percentage of disability adjusted life years (DALYs) from communicable diseases at 63%, while non-communicable diseases (NCDs) contribute 30% of the DALYs. Specific to pneumococcal pneumonia (PP) in adults, the Global burden of disease (GBD) study in 2016 found that 2,377,697 people of all ages died from lower respiratory tract infections (LRTI) in 2016. Of these, more people died from Streptococcus pneumonia(SP) than from all other studied respiratory pathogens combined. While the incidence of LRTIs in children under five years old was reducing, partly as a result of well-established vaccination programs in children, the incidence, morbidity and mortality of PP was increasing in older populations. The expert recommendations included the following; i) all individuals 65 years of age and above, and individuals with a predisposing comorbidity regardless of age, should receive the pneumococcal vaccine; ii) several systemic modules can be emulated from the successful childhood vaccines programs onto an adult vaccine program; iii) formulation of an effective vaccine program will require collaboration from the public, the government, healthcare providers, and the media, to create awareness; iv) stakeholders who need to be involved in vaccine policy development and implementation include medical professional associations, nurses, pharmacists, clinical officers, payers (private and public insurances), government, medical learning institutions and faith-based medical organizations. Burden of pneumococcal pneumonia in Kenya: Kenya has a high percentage of disability adjusted life years (DALYs) from communicable diseases at 63%, while non-communicable diseases (NCDs) contribute 30% of the DALYs [he DALYs . The Glohe DALYs . While the DALYs . Pneumoche DALYs .A rise in the aging population in Kenya is increasing the need for pneumococcal adult vaccination in Kenya. Following an episode of pneumococcal pneumonia, the mortality is increased for up to 10 years, compared to the expected 10 year survival of an average 63-year-old American male . The mosImpact of adult pneumococcal vaccination: the community-acquired pneumonia immunization trial in adults (CAPiTA) study was a phase 4, randomized, placebo-controlled clinical trial of the 13-valent pneumococcal conjugate vaccine efficacy in prevention of vaccine-serotype pneumococcal community-acquired pneumonia and invasive pneumococcal disease, which yielded the following results: 46% efficacy in prevention of vaccine-type (VT) CAP, and 75% efficacy in prevention of VT IPD [f VT IPD . Post hof VT IPD . Furtherf VT IPD . There if VT IPD .Challenges in attaining adequate adult vaccination coverage for pneumococcal pneumonia in Kenya: vaccination advice for adults is hereditary coproporphyria (HCP) initiated. The majority of the HCPs are under-informed or uninformed of the existence and indications of PP vaccines for adults. The existing policies and protocols from the Ministry of Health are non-specific, not recently updated, and not widely disseminated to the HCPs. There are no local studies illustrating the burden of non-vaccination in adults or the benefits of vaccination. Members of the public are not aware of the huge impact of adult pneumococcal vaccinations, with the belief that vaccines “only exist” for children. In addition, the “anti-vaxxer” movements have gained momentum in causing pensiveness towards vaccines, making uptake of vaccines in general challenging. Adult pneumococcal vaccines are costly, making them inaccessible to a great majority of the population. There are no programs in Kenya that provide finance or reimbursements for adult vaccines . The vaccines are not freely available in the government-run health facilities, which is where the majority of patients are treated. There is insufficient infrastructure in the country to reliably maintain the cold chain required of vaccines. Poor inventory management leads to regular stock-outs of vaccines in the country. There is no national registry for adult vaccinations in Kenya at the moment.Recommendations/framework for developing and implementing pneumococcal adult vaccine program in Kenya: all key stakeholders must be involved in the process of developing and implementing the pneumococcal vaccine program in Kenya as illustrated in Development of the vaccines program could borrow from the already established and successful paediatric vaccination program. Local data should be collected via surveys, research and interventional studies to determine the burden of PP in Kenya, the burden of non-vaccination of PP and the benefit of adult vaccination in Kenya. This data should be shared with the intended financiers and reimbursement bodies to illustrate the need for adult PP vaccination programs in the country. With involvement of the MOH and the named stakeholders, the existing guidelines on pneumococcal vaccination need to be updated, approved and disseminated to all relevant HCPs and the public. HCPs, directly and through the respective associations, need to be trained on the significance and administration of the PP vaccine. Training should be conducted directly to all the aforementioned HCP cadres via seminars, conferences, advisory boards and dissemination of education material on the subject matter. There should be an establishment of an electronic medical register by the ministry of health recording pneumococcal adult vaccinations in Kenya.


There are multiple diseases or conditions such as hereditary hemochromatosis, hemophilia, thalassemia, sickle cell disease, aging, and estrogen deficiency that can cause iron overload in the human body. These diseases or conditions are frequently associated with osteoarthritic phenotypes, such as progressive cartilage degradation, alterations in the microarchitecture and biomechanics of the subchondral bone, persistent joint inflammation, proliferative synovitis, and synovial pannus. Growing evidences suggest that the conditions of pathological iron overload are associated with these osteoarthritic phenotypes. Osteoarthritis (OA) is an important complication in patients suffering from iron overload-related diseases and conditions. This review aims to summarize the findings and observations made in the field of iron overload-related OA while conducting clinical and basic research works. OA is a whole-joint disease that affects the articular cartilage lining surfaces of bones, subchondral bones, and synovial tissues in the joint cavity. Chondrocytes, osteoclasts, osteoblasts, and synovial-derived cells are involved in the disease. In this review, we will elucidate the cellular and molecular mechanisms associated with iron overload and the negative influence that iron overload has on joint homeostasis. The promising value of interrupting the pathologic effects of iron overload is also well discussed for the development of improved therapeutics that can be used in the field of OA. Osteoarthritis (OA) is a common degenerative and progressive joint disease that is the primary cause of joint pain, joint dysfunction and deformity, and limb disability. This disease negatively affects the quality of life. . The terStudies reported in the past decades have revealed the association between iron homeostasis and OA. Diseases or conditions with diverse etiologies can result in iron overload . Iron ov.This review presents the relationship between iron overload and OA progression. Herein, the progress made in the field has also been presented. We have also discussed the clinical significance and cellular mechanisms of iron overload-associated OA to determine novel prophylactics, therapies, and predictive values that can be used for the treatment of OA .Clinical observations revealed that osteoarthritic phenotypes such as progressive cartilage degradation, altered microarchitecture and biomechanics of subchondral bone, persistent joint inflammation, proliferative synovitis, and synovial pannus are the common characteristics associated with iron overload . The ostThe term hemochromatosis encompasses a group of disorders caused by iron overload. HH is the most common disorder belonging to this group that is caused by the mutation of the homeostatic iron regulator (HFE) gene . Most paHFE gene mutations are primarily characterized by systemic iron overload in multiple tissues, such as the tissues in the liver, heart, and kidney . It has Iron overload-linked anemia is characterized by ineffective erythropoiesis that causes hepcidin inhibition. This, in turn, results in a high degree of absorption of dietary iron and secondary iron overload . A typicThalassemia-associated arthritic manifestations are one of the most common co-morbidities in thalassemia patients . It has SCD is one of the most common autosomal recessive blood hereditary diseases, affecting approximately 300,000 newborns every year . Single Although clinical findings have revealed that osteoarthritic phenotypes are one of the common complications in patients with hemophilia , relatedAlthough age, mechanical load, and joint injury are the primary risk factors, pathophysiology and internal mechanisms associated with OA have not been fully explored . During Estrogen deficiency, observed during menopause, is currently considered a critical cause of menopausal manifestations and symptoms . During Iron metabolism and homeostasis dysregulation are commonly observed in multiple inherited blood diseases. These are also observed in the elderly and patients suffering from estrogen deficiency. However, there may exist more commonalities or non-commonalities in the changes in iron metabolism and its subsequent influence and the manifestation or progression of OA caused by these different diseases. In terms of iron metabolism regulation, HH, aging, and estrogen deficiency are characterized by abnormal processes of iron acquisition and efflux. This dysregulation is largely attributed to the involvement of the hepcidin-ferroportin (FPN) axis. HH results in inappropriately low hepcidin levels and unregulated FPN activity. Under these conditions, the inability to inhibit the absorption of iron from the diet and the release of iron from macrophages are also observed. This results in the accumulation of iron in various tissues . In patiOsteoarthritic phenotypes have been noticed in multiple animal models subjected to conditions of iron overload. This indicated the adverse effect of iron overload on the development and progression of OA. Firstly, osteoarthritic phenotypes were studied in some genetic iron overload animal models. Camacho et al. used Hfe knockout (KO) mice suffering from HH and explored the progression of OA in mice under conditions of iron overload. The results suggested that iron overload accelerated the progression of OA . In anotTo elucidate the direct effect of iron overload on osteoarthritic phenotypes, iron-overload mouse models were developed by injecting iron dextran. Lindsey et al. established a close relationship between iron overload and OA by injecting iron dextran into guinea pigs characterized by a low incidence of OA . Excessiin vitro. The results will be discussed in this chapter  to establish an excess iron condition, and they reported that the presence of excess iron accelerated chondrocyte apoptosis, resulting in the expression of matrix-degrading enzymes such as MMP-3 and MMP-13 . ResultsRecently, the role of oxidative stress and mitochondrial dysfunction in OA development has gradually attracted the attention of researchers . HoweverAlthough cartilage loss is considered the primary cause of OA, an increasing number of research works have revealed that the integrity of the subchondral bone structure and subchondral bone homeostasis play indispensable roles in the occurrence and development of OA . Under nin vitro study illustrated that lactoferrin, an iron-binding glycoprotein, effectively suppressed the process of osteoclast differentiation of monocytes and significantly increased the extent of bone formation in adult mice  are adult stem cells present in the bone marrow cavity. They are capable of self-renewal and multidirectional differentiation and significantly affect human development, the onset of aging, and the occurrence of diseases . OsteogeOA is a degenerative inflammatory disease, leading to multiple joint and peri-joint damage . Inflammin vivo study of hemophilia indicated that iron-overloaded synovial tissue released pro-inflammatory cytokines (such as IL-1β and TNF-α) that stimulated catabolic activities in chondrocytes and accelerated the degenerative pathological changes in cartilages associated with OA , OA, and HH tissues and found that neutrophil invasion was significantly high under conditions of HH-related arthropathy. This was pronounced in joints containing high levels of iron deposits. These results suggested that the accumulation of neutrophils could potentially regulate the production of stromal enzymes, resulting in cartilage degradation and rapid progression of joint injury . MoreoveAs reported in the literature, diverse pathologies or conditions, such as HH, hemophilia, thalassemia, SCD, aging, and estrogen deficiency, could result in iron overload in the human body. Changes that result in iron overload in the joints increase the chances of developing osteoarthritic phenotypes. These results revealed the significance of iron overload on the process of OA onset. Richette et al. observed that patients suffering from HH had a higher chance of suffering from OA than patients belonging to the control group . PatientAs iron overload accelerates the progression of OA under various conditions, early reduction of iron intake (such as diet adjustment) or the daily temperate promotion of iron excretion can potentially be a prophylactic intervention. Under conditions of aging, HH, hemophilia, etc., iron promotes the progression of OA as the presence of iron triggers the production of free radicals . It has in vitro study was conducted recently, and the results revealed that the protein levels of MMP-3 and -13 in primary chondrocytes increased significantly following IL-1β treatment. Pretreatment with iron-chelating DFO effectively reversed the process of upregulation (Iron chelation therapy can potentially be an effective method of treating patients with systemic iron overload . The effgulation . These rgulation . Jing etgulation . In addigulation .Subchondral bone integrity and bone remodeling also played important roles in the physiopathology of OA. Iron chelation therapy for abnormal subchondral bone remodeling under iron overload conditions can also be an effective therapeutic strategy. Cornish et al. demonstrated that iron-binding lactoferrin effectively suppressed osteoclast differentiation of monocytes and significantly increased the extent of bone formation in adult mice . Iron ovWe discuss further literature from the perspective of therapeutic measures in iron metabolic kinetics. Systemic iron homeostasis is maintained by delicately regulating the process of iron acquisition, storage, and export . These pin vivo experiments reveal that an excess of iron is directly associated with the pathological processes associated with the tissues present in the joints in iron-loaded models. In this review, apart from the discussion on the relationship between hereditary blood diseases and iron overload-induced OA, we have also discussed the recent findings reported on aging- and estrogen deficiency-associated OA. We have attempted to understand and uncover the mechanism associated with iron overload. OA is a heterogeneous disorder with different etiologies and is characterized by various subtypes. Further research should be conducted to explore the role of iron overload on the progression of different types of OA. The origin of iron overload and its relation with inflammation, mechanical stress, and energy metabolism should also be studied. It is yet to be ascertained if an increase in the iron level is the only factor that results in pathological arthropathies in patients suffering from OA. Therefore, the influence of other contributing factors such as mechanical loading, altered metabolism, and oxidative stress should also be considered.Results from clinical and basic studies reveal that iron overload significantly influences the progression of OA. Results from Apart from descriptive investigations, cellular and mechanistic explorations are required to help translate the results into strategies for OA treatment. The articular cartage, subchondral bone, and synovial lining of the joint cavity were also studied . Under cOA refers to inflammatory diseases that occur in the joint and surrounding tissues of the human body and are caused by inflammation, degeneration, trauma, or other metabolic factors . The cli


In addition to being key pathogens in plants, animals, and humans, fungi are also valuable resources in agriculture, food, medicine, industry, and the environment. The elimination of pathogenic fungi and the functional enhancement of beneficial fungi have been the major topics investigated by researchers. Non-thermal plasma (NTP) is a potential tool to inactivate pathogenic and food-spoiling fungi and functionally enhance beneficial fungi. In this review, we summarize and discuss research performed over the last decade on the use of NTP to treat both harmful and beneficial yeast- and filamentous-type fungi. NTP can efficiently inactivate fungal spores and eliminate fungal contaminants from seeds, fresh agricultural produce, food, and human skin. Studies have also demonstrated that NTP can improve the production of valuable enzymes and metabolites in fungi. Further studies are still needed to establish NTP as a method that can be used as an alternative to the conventional methods of fungal inactivation and activation. Fungi are the second-most abundant group of organisms after insects  and theyDespite the fact that some fungi are harmful, many fungi are used in industries, including the food and feed, pharmaceutical, paper and pulp, textile, detergent, and biofuel industries . For cenAs fungi exert both beneficial and harmful effects, it would help to functionally enhance beneficial fungi, while inactivating harmful fungi. Several technologies have been developed and tested to control pathogenic and spoiling fungi and improve the functional aspects of beneficial fungi ,12. DuriNTP is an ionized gas—the fourth state of matter—that generates reactive chemical species, such as reactive oxygen and nitrogen species, electrons, atoms, neutral molecules, charged species, and ultraviolet radiation . NTP canThe non-thermal nature of NTP has enabled its biological applications ,23. NTP The type of sample and the purpose of treatment determine the plasma device and treatment settings used. NTP has demonstrated dual effects (activation and inactivation) on cells, tissues, and organisms depending on the applied dose and species . Plasma The antimicrobial activities of non-thermal atmospheric and low-pressure plasma have been demonstrated in many studies. The fungicidal effects of NTP can be evidenced by the killing or inactivation of fungal spores and cells in vitro .Candida albicans  and Saccharomyces cerevisiae (model yeast) have been targeted using various plasma sources  and ultimately led to cell apoptosis associated with cell cycle arrest at G1 phase through depolarization of mitochondrial membrane potential and fragmentation of nuclear DNA . In. In20]. Fungi exert a significant impact on human life as agents threatening human health and the ecosystem or by providing benefits to industry. The efficient control and use of fungal resources are advantageous for the economy and industry. Studies performed over the past decade demonstrate that NTP offers great potential as a universal tool for inactivating harmful fungi or activating the functions of beneficial fungi. An enormous amount of data support that NTP can be an efficient and eco-friendly remover of fungi without marked damage on the quality of contaminated and infected objects, thereby replacing chemical fungicides. However, further research is still needed to fine-tune the conditions of NTP to support optimal fungal control on foods and agricultural products and restrain human and animal fungal pathogens. Safety issues related to NTP treatment, such as the generation of genetically and phenotypically modified unfavorable fungal strains, as well as the protection of nearby cells and tissues from plasma treatment, also require further detailed investigations.A limited number of studies are available on the application of NTP to activating the functional aspects of beneficial fungi. The majority of these studies are focused on using NTP to generate functionally improved mutant strains. Enhancing the functional aspects of fungi without mutations may make NTP a safe and reliable technology. Therefore, future research should focus on addressing this aspect of NTP. In addition, the application of NTP technology to improving the functions of beneficial fungi could create a potential emerging, low-competition market in the food and agriculture industries.For the productive application of NTP technology, the establishment of a database of fungal responses to various plasma intensities may be essential because a broad spectrum of effects can be obtained based on the different doses or intensities of NTP used.


Since the discovery of certain synthetic organic pesticides in the 1940s, such as dichloro-diphenyl-trichloroethane (DDT) and hexachlorocyclohexane (BHC), many highly efficient chemical pesticides have been largely produced and are widely used to control field weeds, plant pathogens, and agricultural pests  reduction by PQ01, and the presence of sucrose significantly enhanced biotransformation. P. geniculate had much more potential applications in the field of environmental protection. This information might provide an in-depth understanding of the environmental functions of humic-reducing microorganisms involving inorganic pollutants.Herbicide paraquat accumulation is emerging as a problem in an ever-growing portion of agricultural land. Whittington et al. used a packed-bed microbial bioreactor to assess the role of the natural soil microbial communities during biodegradation of the triazolopyrimidine fungicide ametoctradin. The authors demonstrated the ability of a naturally sourced microbial consortium to degrade ametoctradin and generate metabolite profiles in vitro. The results of high-throughput sequencing showed that biodegradation of ametoctradin in both ex vivo soils and in vitro in the bioreactor correlated with an increase in the relative abundance of Burkholderiales, which is a genus of well-characterized microbial degraders of xenobiotic compounds.Jaiswal and Shukla provided an outlook of alternative strategies for bioremediation via synthetic biology. Mainly, this review presented how to utilize gene-editing tools, TALEN, CRISPR-Cas, and ZFNs, to obtain a host with target gene sequences that are responsible for the degradation of recalcitrant compounds. A genetic approach can increase the perspective of enzyme-based bioremediation. Notably, the ecological safety of bioremediation bacteria should be considered because it will be performed in an open environment rather than in a closed fermentation tank.Novel bioremediation methods are still waiting to be discovered. Zhang et al. summarized the latest reports regarding lindane biodegradation mechanisms and metabolic pathways by degrading microbes, as well as the microbial remediation technologies of lindane-contaminated soils, for instance, plant-microbe association and genetic engineering technologies. In addition, the migration and transformation of lindane in the soil were also analyzed. These novel understandings and bioremediation technologies aided the rapid removal of lindane from the soil and water system.Lin et al. reviewed the poisonous effects of acephate and methamidophos on aquatic and land animals. Their physicochemical degradation mechanisms and pathways were also explained. In this review, the mechanisms and degradation pathways of acephate and methamidophos were summarized to provide a new pathway for the study of acephate and methamidophos degradation.Long-term exposure to acephate and methamidophos in non-target organisms results in serious toxic impacts. Bacillus, Mycobacterium, Pseudoxanthomonas, Rhizobium, and Rhodococcus, have been isolated and characterized. However, the microbial degradation mechanisms of neonicotinoids have rarely been reported. Pang et al. summarized the microbial degradation and biochemical mechanisms of several neonicotinoid insecticides. The potential of neonicotinoid-degrading microbes for the bioremediation of contaminated sites was also discussed. The detailed essential work still needs to be carried out before large-scale application of neonicotinoid-degrading microorganisms for the bioremediation of contaminated soil.Some neonicotinoid-degrading microorganisms, i.e., This Research Topic highlights that microorganisms play significant roles in the bioremediation of pesticide contaminated soil. Microbial consortia have a more dominant impact on the bioremediation of contaminated soils compared with a single strain. Plant-microbe associated bioremediation techniques are effective and cost-efficient methods of cleaning polluted sites, which is a promising method and could be used widely to significantly remove pesticides from the soil. Synthetic biology addresses the decontamination and remediation strategies for pesticides from the environment. Microbial synthetic biology remediation strategies not only increase the efficiency of microbial bioremediation processes for a particular contaminant but also provide the best methodologies for researchers. Given the health risks and the environmental impact of chemical pesticide polluted soils, microbial elimination-based bioremediation approaches, and associated technologies should be widely developed and applied in the future.In summary, this Research Topic will expand our knowledge regarding the recent development in the field of bioremediation of chemical pesticides polluted soil. We sincerely hope more scientists will be inspired by our Research Topic to make contributions to tackle the global challenges caused by chemical pesticide pollution.All authors contributed to the writing and approval of this editorial.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating, and dose-limiting side effect of many chemotherapy regimens yet has limited treatments due to incomplete knowledge of its pathophysiology. Research on the pathophysiology of CIPN has focused on peripheral nerves because CIPN symptoms are felt in the hands and feet. However, better understanding the role of the brain in CIPN may accelerate understanding, diagnosing, and treating CIPN. The goals of this review are to (1) investigate the role of the brain in CIPN, and (2) use this knowledge to inform future research and treatment of CIPN. We identified 16 papers using brain interventions in animal models of CIPN and five papers using brain imaging in humans or monkeys with CIPN. These studies suggest that CIPN is partly caused by (1) brain hyperactivity, (2) reduced GABAergic inhibition, (3) neuroinflammation, and (4) overactivation of GPCR/MAPK pathways. These four features were observed in several brain regions including the thalamus, periaqueductal gray, anterior cingulate cortex, somatosensory cortex, and insula. We discuss how to leverage this knowledge for future preclinical research, clinical research, and brain-based treatments for CIPN. Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and severe toxicity of many widely used chemotherapy drugs including platinum-based agents , taxanes , vinca alkaloids, proteasome inhibitors, and thalidomide analogues . These nWe use the term CIPN to encompass patient-reported symptoms, clinical signs, and mechanistic features , as opposed to a narrower definition referring only to the damage, dysfunction, and death of peripheral neurons. The symptoms of CIPN are primarily felt in the hands and feet with some combination of numbness, tingling, shooting or stabbing pain, burning pain, cramping, and hypersensitivity to cold temperatures  . The cliThere are only minimally effective methods to treat or prevent CIPN despite over 20 years of research and nearly 100 clinical trials in humans . In factThe majority of research on CIPN mechanisms has focused on primary afferents of the peripheral nervous system. This rapidly growing body of research is rigorous and utilizes a variety of preclinical non-human animal models of CIPN. Typically, this involves rats or mice without cancer who repeatedly receive chemotherapy  across several days or weeks to mimic how chemotherapy is delivered to human patients with cancer. This is combined with assessments of clinical signs of CIPN in the paws such as cold allodynia, mechanical allodynia, and mechanical hyperalgesia . Collectl carnitine was a promising agent that reduced CIPN and improved peripheral nerve function in rodents via known effects on mitochondria , and particularly the brain, has a previously under-recognized role in the pathophysiology of human CIPN . This nory input . In addiry input . Severalry input , and in ry input ). Yet, tdoes the brain play a prominent or even causal role in the pathophysiology of CIPN ? and (2) how can we leverage knowledge of the brain’s role in CIPN to accelerate basic research, clinical research, and diagnostics, treatment, and prevention of CIPN? We performed a scoping review  g review  to synthWe conducted a literature review on brain interventions in CIPN using PubMed. Our criteria were as follows: each study (1) measured CIPN signs or symptoms, (2) included human or non-human primate imaging OR an intervention delivered to the brain or spinal cord, (3) was written in English, and (4) was published before January 2021. We began with two PubMed searches: (1)  AND  NOT kidney NOT renal NOT nephrotoxicity, and (2) (ICV or intracerebroventricularly) AND neuropathy AND , and then we identified additional papers of interest by searching papers that cited the papers from our PubMed search.We conducted exhaustive searches of the literature on the role of the human/primate brain in CIPN and of brain interventions in CIPN. However, we did not conduct an exhaustive search of all spinal cord intervention papers; rather, we selected papers that also mentioned the role of the brain, per our literature search criteria.Our literature search found three published studies of the brain and CIPN in humans, and two studies in macaque monkeys  is positively correlated with CIPN severity. However, because of the observational nature of these studies,ex-vivo slices from a specific brain region. All studies in Overall, we identified four themes: brain hyperactivity, reduced GABAergic inhibition, inflammation, and GPCR/MAPK signaling. We discuss how these themes are supported by the studies and their implications for clinical research and ultimately treating and preventing CIPN in patients.p-Erk-IR neurons, a marker of neuronal activity  was reported after oxaliplatin treatment in rats that was accompanied by signs of CIPN . One stuactivity . Another monkeys . Similaractivity . GABAerg-Choline .B receptor antagonist, further suggesting that GABA is required for oxycodone to reduce CIPN symptoms. Lastly, injecting pro-inflammatory IL-17 into the spinal cord also decreased inhibitory signals that GABA produced, indicating that inflammation might be an upstream pathway for the inhibition of GABA  or only centrally (ICV), suggesting a role of these GPCRs in the CNS in modulating CIPN . However, GPCRs have become the focus of research attention for treating multiple other brain-mediated conditions such as anxiety and depression , and the2+ channel inhibitor, decreased paclitaxel-induced mechanical hypersensitivity and pain aversiveness in a dose-dependent manner .findings . This isfindings , 16 papefindings , and eigfindings  and we hfindings . Second,findings  and thatfindings . BlockinOur review has the potential to shift the theoretical paradigm of CIPN as not exclusively a peripheral phenomenon and help focus more research attention on the brain. This shift can help advance preclinical and clinical research on CIPN to inform additional and more impactful studies of the brain in CIPN, which are urgently needed according to the 2017 National Cancer Institute Clinical Trials Planning Meeting on CIPN . This fuThe possibility of direct and indirect effects of chemotherapy on the brain in CIPN. It is possible but unlikely that brain changes summarized here  are caused by chemotherapy entering the brain. Indeed, the idea that chemotherapy accumulates in the human brain has been debated, and likely depends on the type of chemotherapy, the dose density, and other factors that may compromise the blood brain barrier , and the remaining themes should be studied to gain a better understanding of the role of the human brain in CIPN. Second, knowledge of those brain mechanisms can inform brain biomarkers of CIPN, for which there are currently none. If a highly accurate and reliable biomarker for CIPN is identified, it can help increase sensitivity and reduce bias in clinical trials of CIPN treatments, and it might also serve as a risk factor for predicting which patients will experience the worst CIPN or experience the best recovery of CIPN symptoms after completion of chemotherapy. In addition, the biomarker might be related to the brain but could be measured peripherally, such as a recent study finding that serum levels of brain-derived neurotrophic growth factor predicted CIPN and overall survival in 91 patients with multiple myeloma receiving bortezomib and/or thalidomide ; fatigurocesses ). Distrerocesses . In addirocesses ; in factrocesses . Nausea rocesses , and hasrocesses . Finallyrocesses . Cognitirocesses , but resrocesses . HoweverIf our hypothesis is false, and the brain does not play a prominent or causal role in the development and treatment of CIPN, then there are alternative implications for future work. First, CIPN interventions that affect the brain  could merely mask symptoms of CIPN rather than treating factors that are part of the pathophysiological mechanism per se. Second, it suggests that researchers should continue to focus on mechanisms and treatments for peripheral damage to stop CIPN at its peripheral source. However, the lack of successful treatments for CIPN thus far despite significant research suggests that researchers should include more work with animal models that better translate to CIPN in humans , the emerging literature in this area reflects only a small number of papers supporting each theme. Second, our review does not include all possible explanations on the role of the brain in CIPN and there are likely other factors involved that simply have not been studied yet. Moreover, some of the brain-based interventions might also affect other regions of the brain or body, and perhaps systemically, or vice versa . Third, all the evidence suggesting that the brain plays a prominent or causal role in CIPN is based in non-human animals, and these methods are unethical in humans. However, even given these limitations, our review is important because it highlights gaps in the literature and opportunities for future research to further test the contributing role of brain mechanisms to CIPN.Conclusion The vast majority of research on CIPN has focused on peripheral nerve damage but has yet to produce significant advances in the prevention and treatment of CIPN despite nearly 100 clinical trials for CIPN (for CIPN . Herein,


The application of mesenchymal stromal cells (MSCs) from different sources, including bone marrow , adipose tissue (atMSCs), and human term placenta (hPSCs) has been proposed for various clinical purposes. Accumulated evidence suggests that the activity of the different MSCs is indirect and associated with paracrine release of pro-regenerative and anti-inflammatory factors. A major limitation of bmMSCs-based treatment for autologous application is the limited yield of cells harvested from BM and the invasiveness of the procedure. Similar effects of autologous and allogeneic MSCs isolated from various other tissues were reported. The easily available fresh human placenta seems to represent a preferred source for harvesting abundant numbers of human hPSCs for allogenic use. Cells derived from the neonate tissues of the placenta (f-hPSC) can undergo extended expansion with a low risk of senescence. The low expression of HLA class I and II on f-hPSCs reduces the risk of rejection in allogeneic or xenogeneic applications in normal immunocompetent hosts. The main advantage of hPSCs-based therapies seems to lie in the secretion of a wide range of pro-regenerative and anti-inflammatory factors. This renders hPSCs as a very competent cell for therapy in humans or animal models. This review summarizes the therapeutic potential of allogeneic applications of f-hPSCs, with reference to their indirect pro-regenerative and anti-inflammatory effects and discusses clinical feasibility studies. The definition of stem cells is not straightforward. The relevant qualities of such cells depend initially on their proliferative potential and the expectations for their trans-differentiation to mature cells of different target tissues . The posThe high interest in stem cells rose based on early experiments and relevant clinical application, based on harvesting and implanting BM hematopoietic stem cells (HSC) ,4. The IRegenerative cell therapies in the fast-emerging field of tissue engineering are based on the anticipation that delivered cells rebuild the affected tissues ,13,14,15One of the major promising breakthroughs in stem cells research was the introduction of multipotent embryonic stem cells (ES cells), isolated from the gastrula at an early stage of human fetal development ,33. ThesThe fibroblast-like matrix-adherent colony-forming cells, referred to as mesenchymal stromal or stem cells (both under the widely used abbreviation MSCs), were initially described several decades ago. The bona fide description of bmMSCs as stem cells is based on their self-renewal capability and their ability to differentiate to cells of mesodermal tissues, mainly osteoblasts, chondrocytes, and adipocytes ,62,63. TbmMSCs and stromal cells harvested from other tissues have been tested for regenerative medicine in various animal disease models. Though the bmMSCs differentiated into several mesodermal cell phenotypes in vitro, in vivo studies reported that bmMSCs contributed to bone formation, while differentiation to other cells such as chondrogenesis remains questionable ,67,68,69In general, all MSCs seem to share a typical set of common mesenchymal cell surface antigens, which are in part different from the markers of other cell lineages, such as hematopoietic and endothelial cells ,89,90,91Major efforts along the last few decades identified alternative tissue sources for isolating MSCs for regenerative therapy application , includiMSCs isolated from these tissues by standard techniques may present in a blend of different cell types, enriched by cell adhesion and the choice of expansion medium. By definition, matrix adhering cells expressing the MSCs’ markers without expression of any of the specific hematopoietic and endothelial cells’ markers are categorized as MSCs ,128,129.In their gene expression level, cells classified as bmMSCs expressed 425 genes at significantly different levels compared with non-MSC fibroblasts . A panelMSCs isolated from different tissue sources seem to have similar a secretome, with variations in the amount and proportions of the different components ,138,139.Recent studies have attempted to overcome the limited ability of identifying and discriminating between different types of MSCs by using advanced molecular transcriptome and proteasome analyses ,146,147.Since most cell surface molecules investigated so far seem not unique to specific MSCs populations, they could not be used for enrichment of any specific type of MSCs from a mixture of mesenchymal cell preparations. Still, differences in cell attachment properties could be used to differentiate between MSCs from different sources. For instance, culturing hPSCs on fibrin-coated dishes yielded low cell attachment to the surface and the hPSCs stayed compact and round, while bmMSCs, under the same conditions, showed a flat, spindle-shaped appearance . This coThe cloning and systematic expansion of human bmMSCs and detailed analyses showed differences in phenotype plasticity characteristics in vitro . The curInterestingly, extracellular vesicles from different sources may also have different clinical potential. The atMSCs seemed to have superior regeneration potential for angiogenesis due to secretion of IGF-1, VEGF, and TGF-β1. In vitro release of such vesicles induces the expression of angiopoetin-1 in endothelial cells. One may hypothesize that PSCs-derived micro-vesicles will contribute to angiogenesis as well . A majorA major field of MSCs is dedicated to investigating their effects on the immune system in various preclinical and clinical studies. This includes graft-versus-host disease  and autoIn early studies it was noted that MSCs, unless specifically activated, express very few MHC class I antigens and no MHC class II molecules . They wePreliminary data suggest that human MSCs express additional immune-checkpoint antigens, which further augment their anti-inflammatory action. Activation of immune cells through toll-like receptors (TLR) activates the different paths of the innate and adaptive immune responses, but activation of TLR on MSCs enhanced their immunosuppressive potential . Their aAnother interesting emerging direction in cell therapy relates to the role of mitochondria in the regenerative process. It was suggested that implanted cells may not only contribute to the health of the mitochondria in the cells of the target tissue but may even transfer healthy mitochondria to the repaired failing tissues ,171,172.Unlike the BM, the human placentae are an easily available tissue source of fully differentiated human mesenchymal cells . Figure The hPSCs are often termed “placental mesenchymal stem cells” (pMSCs) based on the tendency to label any mesenchymal stromal cells isolated from various other tissue sources as “MSC”. Such an assumption is based on the expectation that all MSCs share some properties and could serve as alternative for bmMSCs in cell therapies ,185,186.Early studies expected the hPSCs to serve as building blocks of damaged tissues ,192,193,A major cellular component of the placental tissues is the multinuclear syncytium of trophoblasts mixed with supporting cells. Only isolated trophoblast stem cells in early gestation could be cultured in vitro as organoids for the study of different trophoblast sub-populations. Nevertheless, it is not feasible to culture and expand trophoblasts from a mature full-term placenta ,205.The hPSCs isolated from the fetal versus maternal placenta and expanded separately differ in some features of their phenotype, their secretome, and activity. The shape of both types of hPSCs also differs from fibroblasts or bmMSCs . The hPSThe identification of fetal hPSCs is not straightforward ,213,214.When isolating hPSCs from adjacent fetal and maternal tissues, even when the source of fetal tissues is carefully dissected from the chorionic plate, a mixture of maternal and fetal hPSCs and cells with heterogeneous properties can be anticipated. We assume that one of the subpopulations may overgrow the culture and thus reduce the proportion of the other . NeverthAccumulated data support the observation that most stem and stromal cells therapies, leading to the repair of compromised tissues and organs, are not necessarily associated with their physical integration in the repaired organs or with replacing cells in the damaged tissues, as some studies seem to propose ,231,232.Many studies used commercially produced hPSCs, such as the PLX cells produced by Pluristem or PDA-1 cells by Celgene. Commercial companies purposely do not fully disclose in peer-reviewed scientific publications the exact methods of isolation, quality measures, and production of such cells. However, production methods employed will have an impact on cell characteristics. This tendency of corporate entities to disclose as little as possible critical information on the cells is a major drawback for the comprehension of their activity and exact composition, which may be crucial for understanding their mode of action. In general, the f-hPSCs provide systemic effects when applied in highly vascularized tissues ,206. NevBM regeneration in ARS has been a therapeutic challenge. Since hematopoietic stem cells are dependent of the support of BM stromal cells, the administration of bmMSCs was proposed to help recover severe radiation-induced damage ,236. IntBased on these results, Gorodetsky’s group disclosed a simple procedure for the direct isolation and expansion of pure population of f-hPSCs, which contained only cells from the chorionic plate . The intVarious types of MSCs and PSC have been claimed to have anti-inflammatory effects. Most of these studies related to inflammatory lung failure ,244,245..Accumulating evidence suggests that the diseased tissue targeted by MSCs or the current health condition of the patient treated—in pre-clinical situations this would be the stage of a disease/defect induced in the experimental model—may modulate the regenerative potential of such cells. MSCs applied during flare of inflammation, in different stages of an (autoimmune) disease seem to act differently from MSCs applied during remission or injected in a healthy environment .Secondary inflammatory processes may derive from various disorders such as diabetes mellitus. The hPSCs were shown to be useful in treating the inflammatory complications of diabetes ,254,255.Typical to placental stromal cells, the f-hPSCs were found to express mesenchymal stromal cell markers , as wellThe biological rational for the expectation of better responses from f-hPSCs is that these cells, which originate of the chorionic plate, share and connect to the fetus’ circulation. This may explain the apparent higher activity of f-hPSCs, which can respond to the fetal stress signals carried in the fetal circulation along the development of the pregnancy, in confronting various acute stress messages, such as depleted function of the hematopoietic system ,262,263.The mainstream approach of attempting to use stem cells implants for the reconstruction of degenerated tissue and for the replacement of cells in failing organs has so far yielded disappointing results. This diverted the focus of cell therapy from dealing with the differentiation potential (“stemness”) of the cells while attempting to develop treatments based on the indirect and paracrine regenerative effect of this cell therapy. For this goal, MSCs from different sources seem to pose as preferred candidates based on their role in wound healing and tissue regeneration in many disorders. The most studied cells are the bmMSCs, isolated from BM in low numbers and expanded to high numbers by passaging. A wide range of projects demonstrated that MSCs isolated from various other tissues may have pro-regenerative, anti-inflammatory, and immune-modulating activity that surpasses the effects observed initially with bmMSCs.The mature, full-term fresh placenta is an easily available disposable healthy bulk organ. It contains cells from comparably young donors. Such cells are sensitive to different stimuli and seem to adapt their secretome to the regenerative need of the donor. The f-hPSCs seem to be the most potent candidates for PSCs-based therapies. The rational for this difference may lie in the role of the fetal part of the placenta in the direct support and nourishment of the developing fetus. Another advantage of f-hPSCs is their lower rejection rates, since they derive from the fetal placenta, which is in a very tight interaction with the allogeneic maternal tissue and blood that would otherwise reject a foreign tissue. This renders the f-hPSCs an ideal source of allogeneic cells for (pre-) clinical studies.In continuation of earlier studies on the use of MSC for regenerative medicine, m-hPSCs and f-hPSCs have demonstrated very impressive activities in treating severe complications associated with tissue degeneration and severe inflammation. The mechanistic explanation of their activity and their diverse applications deserve further thorough investigation.


Field-washing decontamination of equipment is an effective way for firefighters to reduce their risk of secondary contamination. No study has yet clarified the factors influencing effective field decontamination of equipment such as self-contained breathing apparatuses (SCBAs). This study sought to examine factors that influence the SCBA washing and decontamination behavior of firefighters. We conducted a questionnaire using the web-based Seoul Metropolitan Electronic Questionnaire System. As of May 2021, the survey had been sent to 3626 of 7198 Seoul career firefighters, and 1940 subjects were selected to participate in the study. Binomial logistic regression and χ2-test analyses were performed. We confirmed that previous training in SCBA washing was an important factor in effective field decontamination of SCBAs. Firefighters should be trained to perform field decontamination procedures systematically and regulations to perform field decontamination before leaving the scene of a fire should be introduced. Cancer is a leading cause of death among firefighters. Occupational exposure to polycyclic aromatic hydrocarbons (PAHs), organophosphate flame retardants (OPFRs), and polybrominated diphenyl ethers (PBDEs) places firefighters at increased risk for several diseases or cancers ,2,3,4,5.PPE is essential for firefighters working in hazardous environments . A systeDecontamination of equipment can be achieved by scrubbing with water and dish soap, which can remove PAHs by as much as 85% . Post-fiDespite the dangers inherent in firefighting, there is currently a lack of information regarding policies for the occupational health and safety of firefighters. Very little remains known about the factors that influence effective field decontamination of firefighters’ PPE, as few studies have focused directly on this topic. One recent study used the Health Belief Model (HBM) to investigate factors affecting decontamination behavior . To the This study examined factors that influence SCBA washing and decontamination behavior among firefighters.In this questionnaire survey, we focused on the SCBA and the SCBA charger among the PPE and grasped the actual situation. By deriving problems in the fields of human resources, equipment, budgets, and systems through the results of the questionnaire, it was conducted to seek improvements in fire scenes by field.In the Fire Science Research Center, Seoul Metropolitan, Fire Service Academy, a questionnaire survey was conducted in seven major domains for people in charge of fire suppression and rescue operations working in Seoul metropolitan. The specific contents of the questionnaire survey are as follows;(1)Storage, use, washing, charging, training, repair, management status and safety management manual recognition of SCBA set (bombe and mask)(2)Risk awareness of the generation of hazardous substances at the fire scene and the level of occupational exposure(3)Usage, management of SCBA charger and SCBA charging room installation environment(4)SCBA bombe inspection and SCBA repair room operation system(5)Health belief in the use and management of SCBA: Perceived Susceptibility, Perceived severity, Perceived benefits, Perceived barriers, Self-efficacy(6)Fire incidence and dispatch status(7)Demographic and sociological information of questionnaire participantsIn South Korea, the purchase and distribution of SCBA sets is carried out collectively by the fire department of each province. The central governing body, the National Fire Agency, holds the authority to enact and revise the safety management manual for PPE and the legal provisions for firefighting equipment. The Safety Management Manual and the Fire Equipment Law include information on the use and washing SCBAs, and the installation environment of SCBA charging rooms, but enforcement remains the responsibility of each provincial fire department. Therefore, the personnel in charge, the budget, the system, and detailed operational matters differ depending on the fire department.The design of this study is cross-sectional. We conducted a questionnaire using the web-based Seoul Metropolitan Electronic Questionnaire System. As of May 2021, the survey had been sent to 3626 shift workers engaged in fire and rescue operations out of a total of 7198 career firefighters working in the Seoul metropolitan area. Of these, 2031 responded, showing a survey participation rate of 56.0%. The questionnaire was completed via an electronic questionnaire system using a computer or cell phone. First, we sent official text messages to the institutions where survey subjects were employed, and second, we sent e-mails and SMS messages so that the survey participants could actively participate. As a result, at least 30% of respondent fire departments participated in the survey.In this study, firefighters answered questions regarding SCBA washing, training, and information management used at disaster scenes, including fires. To reflect the firefighting scene, we developed questionnaire items through a process of prior research and interviews with experts in the relevant field. Finally, we evaluated the survey items through a pilot survey. The questionnaire was conducted for a total of 19 days from 13 May to 31 May 2021. By explaining the purpose and importance of the questionnaire through official texts, e-mails, and SMS messages, we encouraged the survey participants to enroll. The survey was sent to 3626 shift workers engaged in fire and rescue operations out of a total of 7198 career firefighters working in the Seoul metropolitan area. Of these, 2031 responded, showing a survey participation rate of 56.0%. Of the 2031 survey respondents, only 1940 people who agreed to participate in the study and responded to the survey were analyzed .The main data collected by the questionnaire survey were demographic and sociological information , fire incidence and dispatch status of participants’ work department , and training experience in SCBA use and washing.The dependent variable was SCBA decontamination behavior, which was measured by whether participants had engaged in the practice of bombe washing and mask washing over the past year. The independent variables were the following demographic and work-related characteristics: sex, age, job ranking, job duties, total years of fire service, total years of shift work in the fire service, monthly numbers of emergency dispatches in the past year, monthly numbers of dispatches to incipient-stage or free-burning fires in the past year, previous training in SCBA use, and previous training in SCBA washing.2-test analysis to confirm the subjects’ characteristics and associations between the independent variables and decontamination behavior. Binomial logistic regression analysis was performed to confirm factors influencing SCBA washing. All statistical analyses were performed using the IBM SPSS 27.0 program .We performed a χSCBAs is one of the personal protective equipment devices that supplies oxygen to firefighters at all fire scenes. To promote the occupational health of firefighters, various factors related to SCBAs should be considered ,18. WashAccording to a survey study on the use and management of turnout gear among metropolitan firefighters in South Korea, 9.1% answered that they had removed their turnout gear before boarding a fire fighting vehicle at the scene of a fire after completing firefighting activities. In addition, 41.6% and 48.3% of the respondents answered that they removed their turnout gear in the fire fighting vehicle and garage of the fire department . This meIn this study, we first explored the SCBAs decontamination behavior of firefighters and confirmed previous training in SCBA washing to be a key factor. Firefighters who used SCBAs and were trained in SCBA washing were more likely to wash their gear, and pre-training in SCBA washing was an influencing factor while pre-training in SCBA use was not. These findings imply that pre-training in SCBA washing is more important than pre-training in SCBA use regarding SCBA washing behavior. Based on the study sample group, female firefighters were more likely to practice bombe washing than their male counterparts. Firefighters dispatched to five or more insipient-stage or free-burning fires per month in the past year were more likely to have washed their masks than those who had not been dispatched to a fire. While our study observed that sex influenced the practice of bombe washing, the proportion of female firefighters was far smaller than that of male firefighters at only 2.8%. Future studies should use robust evidence to investigate whether sex represents a significant factor influencing SCBA washing behavior. The results of this study imply a possible need for intervention to increase SCBA washing among firefighters.A previous study reported that the constructs of the Health Belief Model influenced the individual safety behavior of farmers . Among tThe main limitation of this study is a lack of generalizability. The study used firefighter data from only the city of Seoul, in Korea. Research conducted elsewhere using the tools of this study may produce different results. In addition, due to the cross-sectional nature of the study, the time of investigation may have skewed the study results. In future studies, it is necessary to investigate and gather data concerning contamination during the use of SCBA .The significance of this study is that, to the best of our knowledge, it is the first to propose training in field decontamination for the occupational health of firefighters. The findings show the necessity of training based on the collection of firefighters’ demographic information and work history at a national level. This study serves as an example of occupational health research among firefighters.This study confirmed that previous training in SCBA washing is an important factor in decontamination of SCBAs while previous training in SCBA use is not. When distributing firefighting equipment, it is necessary to train personnel in field decontamination according to standard operating procedures. Moreover, it will be necessary to introduce regulations to perform field-washing procedures prior to returning from the scene of fire-related incidents. The large-scale Firefighter’s SCBA Survey could promote firefighters’ health with greater accuracy. Currently, there is no regular large-scale survey related to the job of firefighters except for mental health surveys. In the future, it will be necessary to investigate the work environment in consideration of the occupational characteristics of firefighters.


Cardiovascular disease has been and will continue to be a leading cause of morbidity and mortality, contributing to substantial social and economic burdens worldwide. Aging and obesity have been identified as two common risk factors of cardiovascular disease . AlthougUnfortunately, the elderly obese population has risen globally, most probably due to the failure of weight control in young and middle-aged obese individuals, as well as the increased risk of obesity that comes with aging. These may contribute to increased incidence, prevalence, and severity of cardiovascular disease among the elderly. Therefore, attenuation of the aged-obese condition would be extremely beneficial in mitigating the burden of cardiovascular disease. Extensive research has been done to explore cardioprotective benefits of pharmacological interventions. It has been shown that anti-diabetic drugs such as metformin, and DPP4 and SGLT2 inhibitors are effective in alleviating cardiac dysfunction partly due to restoration of the obese associated impaired mitochondrial function, resulting in a decreased risk of obesity-induced cardiovascular disease . LifestyCardiorespiratory fitness is defined as the ability of the circulatory, respiratory, and muscular systems to supply oxygen during sustained physical activity. Although exercise training can increase cardiorespiratory fitness, this effect is not permanent since ∼72% of cardiorespiratory fitness is determined by genetics . PreviouThe molecular mechanisms underlying the predictive effects of cardiorespiratory fitness on the development of obesity and cardiovascular disease have been widely studied in rats selectively bred for high and low intrinsic running capacity. The results from these studies suggest that high cardiorespiratory fitness decreases risk of obesity via alleviation of insulin resistance and disruptive nutrient oxidation . The impCurrently, the relationships between the protective effect of high cardiorespiratory fitness and the detrimental effect of the combined aged-obese condition on the development of cardiovascular disease are not completely understood and further investigations are needed prior to the establishment of novel targeted therapies. Mitochondria play an important role in the pathophysiology of cardiovascular disease, therefore cardiac mitochondrial alterations which mediate the predictive effect of cardiorespiratory fitness on the incidence of cardiovascular disease should be holistically evaluated. These mechanisms include mitochondrial metabolism, mitochondrial oxidative phosphorylation and respiration, mitochondrial dynamics, mitochondrial oxidative stress, mitochondrial membrane potential change, mitochondrial swelling, and mitophagy. Additionally, a future study directly comparing the effect of cardiorespiratory fitness on a variety of cardiac parameters under various conditions including physiological condition, obesity, and aging should be performed. The results from such studies will reveal the strength of predictive effects of cardiorespiratory fitness on the development of cardiovascular disease in each condition. The use of cardiorespiratory fitness as a predictor of the incidence of cardiovascular disease should also be determined in subjects who receive either caloric restriction or exercise training. This will help identify the interactions between intrinsic cardiorespiratory fitness, caloric restriction, and exercise training. These results may be valuable on transference to future clinical practice to increase intrinsic cardiorespiratory fitness, further reducing the burden of cardiovascular disease, especially in the era when this is an issue across the world.


Atherosclerotic disease is nowadays one of the most important concerns of modern medicine because it is a major cause of morbidity and mortality worldwide. Atheromatous lesions of the lower limbs, known as peripheral arterial disease (PAD), can significantly affect the quality of life and lead to disability in a high proportion of patients. The number of peripheral catheter-based procedures for endovascular treatment of PAD, which represent a promising alternative therapeutic option, has increased over the past years. Indeed, several techniques have been improved over time and now contribute to modern concepts of endovascular repair. This special issue aimed to provide a comprehensive overview of this lively research field by gathering contributions covering imaging and technical endovascular features, clinical studies and practical applications.Rotzinger et al. reported the results of a randomized controlled study assessing different image acquisition techniques using computed tomography angiography (CTA) in lower limbs. The authors prospectively compared in 60 patients three image acquisition techniques: the “traditional” anterograde method (SA), the adaptive anterograde method (AA), and the retrograde acquisition method (RA). Quantitative and qualitative analysis were performed. In terms of qualitative and quantitative analysis, AA gave better results than SA and RA, reporting the best vascular enhancement in a high percentage of patients. The presence of stenotic or occlusive lesions did not significantly impact the attenuation values among all levels and acquisition methods. The authors showed that AA should be recommended as the method of choice, especially in the presence of aneurysms which had a significant impact on the vessel attenuation in AA (high attenuation) and RA (low attenuation) at the iliac artery (P = 0.03 and 0.04) and femoral artery levels (P = 0.02 and <0.01). Alternatively, the authors concluded that SA may be useful in patients with renal failure, since the test bolus can be avoided. The spreading availability of rapid computed tomography scans could likely overcome the limits of RA.The study of  Pescatori et al. conducted a systematic review of the different re-entry devices currently available for aortoiliac occlusive disease. Indeed, standard endoluminal revascularization fails in treating occlusions at the aortoiliac level in almost 20% of patients. In this setting, subintimal recanalization may be an option, but failure is reported in about 25% of patients as well. Several devices have been developed over the last decade, in order to facilitate the cross back within the true lumen, when conventional subintimal recanalization does not work or is at risk of occlusion of important collaterals. Pioneer, outback, offroad, and enteer catheters were described in this overview and the applications for those devices were fully revised.In this issue,  Saucy et al. emphasized the importance of vessel preparation for optimizing endovascular therapy of infrainguinal lesions and provided a review of the different techniques allowing to gain lumen before vascular stenting or angioplasty using drug-coated technology. Over the last 5 years, the use of self-expandable nitinol stents has permitted endovascular repair of long atherosclerotic lesions, allowing significant improvement of clinical outcomes as compared to plain balloon angioplasty. Drug-eluting balloons have also emphasized the ability of this technology to decrease the incidence of restenosis and to drive target repair. However, calcified lesions and elastic recoil of the arterial vessel wall are still considered as risk factors for early restenosis and failed procedure. Therefore, vessel preparation using focused atherectomy catheters has shown promising results in modifying vessel compliance and debulking obstructive calcifications in order to improve long-term patency, as nicely described in this review.In the same way,  Loffroy et al. conducted a review of safety, efficacy and outcomes of one of those debulking devices in patients with acute and subacute ischemia of the lower limbs. The authors described the use of Rotarex®S catheter as a percutaneous pure rotational mechanical atherectomy plus thrombectomy (MATH) device in such a setting as compared to rheolytic thrombectomy devices. MATH is a minimally invasive technique for rapidly recanalizing thrombotic lesions whatever the type and age of thrombus is. Indeed, many patients considered as chronic patients may present with critical limb ischemia, with occlusive lesions containing thrombus triggered by underlying atheromatous disease. The authors showed that MATH provides different advantages over surgery and catheter-directed thrombolysis, with faster revascularization, lower invasiveness, and the capacity to treat the underlying atherosclerotic lesions promptly. It is also associated with a lower rate of complications such as bleedings and avoids the need for intensive care unit hospitalization. Cost-effectiveness of the routine use of this device was also discussed here, with the existing evidence being favorable.More in detail, Loffroy et al. discussed the place of IVUS in PAD through a systematic overview, notably the main applications of IVUS technique during interventions including angioplasty, stenting, recanalization of complete occlusion, evaluation of residual stenosis and stent delivery and expansion, and atherectomy procedure. Over recent years, IVUS has gained acceptance as a useful adjunctive tool to conventional angiography in a high proportion of catheter-based interventions for PAD. IVUS allows evaluation of the plaque features, artery diameter, and the presence of dissections. In addition, the authors showed that IVUS has the capability to accurately guide the best choice of appropriate percutaneous angioplasty method, guide the deployment of several catheters and devices, and evaluate the immediate outcomes of any vascular procedure. Again, despite the cost of this catheter, most of studies evaluated in this review showed that the use of IVUS during endovascular interventions can be cost-effectiveness.Last, Qanadli). First, the development of disruptive innovations such as drug delivery technology. Second, the improvement of evidence-based techniques to guide treatments. Many modalities for image-guided therapies have become available and useful as adjunctive tools such as IVUS, image fusion, three-dimensional imaging, robotics, and virtual or enhanced reality. Last, the development of specific catheters for vessel preparation such as atherectomy and thrombectomy devices allowed to get back to an old concept called “leave nothing behind” that has never been so relevant to optimize outcomes. Without any doubt, the next decade should allow active research in percutaneous interventions with promising perspectives and progress in all these aspects, especially with the use of artificial intelligence. In this setting, it is of the utmost importance to remember that being innovative should in no way prevent vascular specialists and interventional radiologists from remaining dedicated clinicians.Several factors have driven the evolution of percutaneous interventions for PAD over the last decade (Each author has participated sufficiently in this manuscript to take public responsibility for its content. RL and SQ: conception and design of the study, or acquisition of data, or analysis, interpretation of data, drafting the article or revising it critically for important intellectual content, and final approval of the version to be submitted. Both authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Objective: This study focuses on whether vine tea contains potentially toxic components that trigger hepatotoxicity as a mechanism of action, which further provides some reference for the consumption and guides future product development of vine tea.Methods: The chemical components of vine tea were collected from the reported literature and the toxicological information matched with the CTD database was collected, and the dataset of potential toxic components was established. The toxic components were submitted to the PharmMapper server to obtain potential targets. At the same time, the relevant targets were searched in the CTD database and GeneCards database with keywords such as “Hepatic Toxicity,” “Liver Damage,” and “Drug-induced liver injury.” After intersection, the potential hepatotoxic targets of vine tea were obtained. The protein interactions of potential hepatotoxic targets of vine tea were analyzed by the STRING database. Protein–protein interaction (PPI) networks were constructed by Cytoscape3.6.1 software. The GO molecular function and KEGG pathway of hepatotoxic targets were enriched by the R package to screen the key targets. The role of the components and key targets was analyzed by the LEDOCK program. The data from GEO database were mined for the functional correlation characterized by cell transcriptional expression caused by vine tea as a disturbance factor.Results: This study has searched 34 potential toxic components and 57 potential hepatotoxic targets of vine tea, and the result showed that these targets were mainly involved in oxidative stress, cell metabolism, and apoptosis to affect the liver.Conclusion: Vine tea has the interrelationship of multi-components, multi-targets, and multi-pathways. At the cellular level, the toxic components of vine tea, mainly flavonoids, may promote oxidative stress, promote oxidation to produce free radicals, guide apoptosis, and affect cell metabolism and other cytotoxic mechanisms. However, this hepatotoxicity is related to the dose, duration of vine tea, and individual differences. This study revealed the potential hepatotoxic components of vine tea and provides a reference for further research and development of related functional products. Ampelopsis grossedentata (Hand. -Mazz.) W.T. Wang, a genus of Ampelopsis in the family Vitaceae, and the chemical composition of vine tea is mainly flavonoids and polyphenolic substances  module to observe the differences between the enrichment analysis results and the biological processes involved in the toxic targets acted by vine tea.The domestic and foreign literature  was lookThe 3D stereo structure of vine tea toxicity components dataset was submitted to the PharmMapper server  for the The potential hepatotoxic targets of vine tea were analyzed by the STRING online server  for protwww.bioconductor.org/) bioinformatics analysis package of R software (https://www.r-project.org/). Running the R 4.0.2 software, the R package (org.Hs.eg.db) was referenced, transforming potential hepatotoxic target gene names of vine tea toxic components for gene ID numbers, and the GO biomolecular functions and KEGG pathways of the targets were enriched by the clusterProfiler . The topological properties of the PPI network allowed the analysis of the interaction mechanism of the potential hepatotoxic targets of vine tea. The results were imported into Cytoscape 3.6.1 software for visualization, as shown in p-value cutoff to 0.05 and Q-value cutoff to 0.05. The top 20 GO molecular functions were plotted in a bar graph after enrichment. From p < 0.001, and all of these molecular functions were related to drug-induced liver injury, among which there were nine molecular functions with ≥6 hits. The coenzyme binding with the highest number of targets (19%) may lead to drug-induced liver injury or cirrhosis by binding to pyridoxal phosphate, flavin adenine dinucleotide, and nicotinamide adenine dinucleotide. In addition, molecular functions, such as heme binding, organic acid binding, fatty acid binding, carboxylic acid binding, oxygen binding, and heparin binding, may result in toxicity and damage to the liver by affecting the metabolism of drugs or alcohol by the liver, inducing the incidence of negative blood-related effects  pathway enrichment analysis was calculated by a Bioconductor package for potential hepatotoxic targets of vine tea with a Sixteen key target proteins of potential hepatotoxicity of vine tea were screened by the total conditions, and the corresponding protein crystal structures were obtained by the PDB database. Among them, nine protein crystal structures with natural ligands were extracted and pretreated for the docking task, and the specific docking parameter information is shown in The results of the aforementioned analysis obtained eight major toxic components of vine tea. When these components were used as perturbation factors to search the GEO database for relevant expression profiles, only a few components’ expression profiles such as quercetin, taxifolin, phloridzin, and kaempferol were found, whose database platform numbers were GSE62805, GSE59704, GSE38138, and GSE145665, respectively. At the same time, referring to the expression profile no. GSE5789, the experimental protocol for this data was obtained with the transcriptional data using toxic drugs  as perturbers that caused liver damage. After the expression profiles were enriched for the GO functional biological process (BP) modules separately, the BP modules corresponding to the enrichment of vine tea components were compared with the BP modules enriched for the reference expression profiles for similarity. Eight similar common BP modules were found, namely gland growth, angiogenesis, morphogenesis of blood vessels, epithelial cell differentiation, development of circulatory system, sprouting angingenesis, and muscle organ growth, which were more consistent with the gene functions of the important targets analyzed previously, and the results are shown in In this study, we analyzed the GO molecular functions and KEGG pathway of the same targets by integrating the action targets of the toxic components of vine tea and the hepatotoxicity-related targets and validated them by molecular docking techniques. By mining the expression profile of GEO, we analyzed the toxicological effects of the GO functional modules enriched by the transcriptional expression of vine tea components as perturbation factors at the cellular level, to predict the potential hepatotoxic action mechanism of vine tea. The liver is involved in the physiological processes of body metabolism, hormone balance, and toxin removal, and is an essential organ of the human body. Most drugs are absorbed orally through the gastrointestinal tract and then metabolized by the liver and excreted from the kidneys; if a few drugs are metabolized by the liver to form end-toxicants or transient active substances, then the drugs are exposed to the liver will lead to pharmacologic liver damage. Therefore, the active components of drugs should be actively concerned whether they can cause hepatotoxicity while exerting their medicinal effects, and some active components may cause hepatotoxicity through direct cellular toxicity, oxidative stress, immune response, and cellular metabolism . Althougin vivo is complex. Although there is a large body of literature supporting the antioxidant function of dietary polyphenol or flavonoid components in vivo, the antioxidant activity of these substances in vivo can be expressed by the substances themselves either directly as reactive oxygen radical scavengers or indirectly as regulators of intracellular antioxidant enzymes and pro-oxidant enzymes, when involved in peroxidases containing systems with redox metals, these substances have been shown to act as pro-oxidants, directing the formation of reactive oxygen radicals (ROS) and phenoxyl radicals, further promoting the destruction of lipids, DNA, or their biomolecules , glutathione S-transferase Mu 1 (GSTM1), whose involvement in phase II metabolism is considered as a pathway for cellular clearance of exogenous toxic substances, and it is important to note that inhibition of these enzymes may lead to accumulation of exogenous toxic substances. Among them affecting the glutathione metabolic pathway can lead to depletion of glutathione, thus affecting the content of components such as bilirubin and glutathione, which is consistent with the literature reporting that flavonoids cause glutathione oxidation in rat hepatocytes . On the  In summary, this work demonstrates that vine tea has a multi-component, multi-target, and multi-pathway interrelationships and that the flavonoid-based toxic components of vine tea may promote oxidative stress and pro-oxidative generation of free radicals and attack the mitochondria at the cellular level, causing cytotoxicity, triggering apoptotic mechanisms, or affecting the metabolic activities of cells. These adverse effects are dose-dependent toxic manifestations, and although the general population has a good degree of tolerance at certain doses and durations, the potential pitfalls hidden in a few healthy individuals with sensitive constitutions should not be overlooked. Such herb tea beverages do not require SFDA approval for market circulation, and their therapeutic functions and taste are increasingly favored by consumers worldwide, and the assessment of potential toxicity and drug interactions has not been definitional, so mixing and abuse with other herbs should be avoided, and it is recommended that a safe dosage standard for consumption of herbal-based tea beverages be established. This work is based on database mining and analysis to investigate whether vine tea is potentially hepatotoxic using a network toxicology and molecular dynamics approach. Although the method is becoming increasingly popular, its accuracy and reliability are related to the subjective choice of the user, together with drawbacks such as the limitations of the database, which require the user to have a deep basic knowledge of network toxicology and molecular dynamics theoretical approach. However, it also illustrates the important contribution of the method to the development of biology, which will become a core research technique in modern biology and further generate new interdisciplinary disciplines. Finally, the metabolic indexes and action targets predicted in this paper are informative but do not fully reflect the overall profile of vine tea. Because of the potential applications in material and pharmaceutical sciences for constituents containing therapeutic functions such as dihydromyricetin, vine tea is of increasing interest to researchers. Further follow-up studies and validation of the toxicological effects, serum pharmacology, and serum medicinal chemistry of various constituents of vine tea are essential to guide future product development and the possibility of reducing the cost of new formulations.


Parasites are diverse and challenging group of eukaryotes, including zoonotic pathogens naturally occurring in the environment, already significantly changed by globalization and anthropogenic impact. Climate changes can further modify fundamental features and transmission dynamics of zoonosis . The proximity of humans and animals in several settings, such as in the rural landscapes, as well as in fragmented sylvatic habitats, in the natural environment close to urban areas and for the companion relationship between human and animals, may represent additional risk factors.The Research Topic aims to gather the most updated studies on zoonotic neglected and foodborne parasites, taking into account two pivotal aspects: (i) challenging scenarios represented by climate change and anthropogenic impact and (ii) the “One-Health” concept.Toxoplasma, Leishmania, Cryptosporidium) to metazoans .The Research Topic collected 11 contributions including 3 reviews, 1 minireview, 1 brief research report and 6 original research articles, ranging from protozoans . Apart from the Mediterranean basin, the East African region remains one of the most globally impacted for leishmaniosis: Jones and Welburn underlined the necessity to implement surveillance and disease management measures, especially in low- and middle-income countries, expected to be most impacted by climate change (3).Vector-borne diseases are particularly interesting in the global change scenario, given the susceptibility of vectors to climatic variations and their large plasticity and adaptive features to several ecological contexts. In the review of Utaaker et al. highlighted the need to investigate epidemiological scenarios of cryptosporidiosis in goats, one of the most frequently bred species, especially in low-income countries. Despite the resulting negligible concern for zoonotic transmission in these areas, scant information is available for developing countries so far.Another protozoan disease affecting both humans and livestock, and having a huge impact in low-income countries, is cryptosporidiosis. Toxoplasma gondii was studied in host-parasite interplay by the means of CRISPR-Cas9 . The study excluded their involvement as virulence factors in vitro and in vivo experiments. This study evidenced the application of an innovative approach such as the CRISPR-Cas9 system to investigate biological functions of parasitic proteins and host-parasite interactions.Finally, the role of two thioredoxin proteins from Butala et al.).Several metazoans are included in the Neglected Tropical Diseases (NTDs) list and the World Health Organization (WHO) has recently launched its road map “Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021–2030,” as highlighted in the review about neurocisticercosis, a disease that represents a significant health burden to affected communities . By comparing the haplotypes obtained in the sample with homologous sequences from all over the world, the researchers observed a moderate genetic variation occurring in the sample, showing E. intermedius (G6) as the most commonly represented genotype in camels, followed by E. granulosus sensu stricto (G1). In addition, the Middle East isolates were more variable than the North/sub-Saharan isolates, suggesting an ancestrality for E. granulosus originating from the former region. The study offers a global outlook of the importance of camels in the molecular epidemiology of cystic echinococcosis in the main camel breeding areas of the world. Genetic diversity of the related species E. multilocularis, in which four distinct clades corresponding approximately to their continents of origin are described, was recently investigated . With molecular epidemiology, it is possible also to trace various records of genetic variants in atypical regions, which may be the result of introduction or natural migration of host animals. In this scenario, red foxes from Eastern Europe (Poland) harbor haplotypes of the typical European E. multilocularis, but also of the Asian cluster. The study presented the first large-scale investigation showing a zone of apparent overlap between European and Asian variants of E. multilocularis. Because the resolution from microsatellite EmsB analyzes and mitochondrial (mt) sequencing did not completely agree on allocation to Asian and European clusters, the authors suggested that cross-fertilization between worms of Asian origin and worms from the European Polish population might explain these conflicting results.Cystic and alveolar echinococcosis are two of the most important zoonotic parasites with public health and economic relevance, ranked in highest positions among the food-borne zoonoses according to the international food safety agencies. Their presence in wild and domesticated animals still pose a challenge for the disease control. In the study of Toxocara canis, a neglected zoonotic parasite, which threatens the health of dogs and humans worldwide . Considering the understudied and fascinating role of miRNas in host-parasite interplay, particularly in chronic infections induced by nematodes, this study is of great relevance for a better understanding of the adaptive and innate immune responses mechanisms associated with dog infections by T. canis.Regarding the phylum Nematoda, the role of microRNAs (miRNAs) was investigated in the infection progression caused by Riveiro et al. examined the current knowledge of Trichuris trichiura and its relationship to whipworm of other primates. This study contributes to the debate on the systematics of T. trichiura, in updating data supporting the existence of several taxonomic entities with different degree of host affiliation circulating in primates.Dirofilaria immitis in dogs and humans is updated for the Colombian region  reporting a considerable seropositivity in both dogs (around 11%) and humans (around 7%), indicating comparable transmission rates also in atypical hosts as humans.The epidemiological status of the cardiopulmonary dirofilariosis caused by Thanks to a broader and more comprehensive view of interacting factors characterizing a zoonotic disease, the scientific community could better understand major elements that contribute to the fundamental aspects of parasite transmission and how they are closely linked to the distribution and persistence of these diseases. This article collection emphasize how interdisciplinary collaboration is becoming an essential feature of epidemiological surveys, being of paramount importance in developing effective strategies for the control of zoonotic diseases.This editorial was authored by SC, with review and input by SG, VS, AG, and MP. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.