Role of resident memory T cells in neuroinflammatory and neurodegenerative diseases in the central nervous system

The immune system has been attracting increasing attention in the field of chronic neurological disorders in the central nervous system(CNS).Autoreactive T cells targeting CNS antigens play a crucial role in the development of various autoimmune diseases,such as multiple sclerosis(MS)and neuromyelitis optica spectrum disorder(NMOSD).Moreover,T cells are now recognized as a pivotal contributor to the pathology of neurodegenerative disorders,including Alzheimer's disease(AD),Parkinson's disease(PD),and multiple system atrophy.

New insights into the immunology and evolution of HIV

Fewer than one million HIV infected individuals are currently receiving anti-retroviral therapy. Thelimitations of such treatment have underscored the need to develop more effective strategies to control thespread and pathogenesis of HIV. Typically, naturally occurring protective immune responses provide theparadigm for such development. It is now clear however that HIV can utilise the millieu of an activatedimmune system to its own replicative advantage. Mobilisation of the immune response, intended to thwartof HIV contributes to lack of immune control and the development of progressive disease in the majority ofinfected, untreated individuals. Further delineation of the intimate interactions between the HIV and theimmune system will be critical and recent advances in this direction are discussed.

A retrospective analysis of mature T-and NK-cell lymphomas

Mature T-and natural killer(NK)-cell lymphomas are heterogeneous groups of malignant lymphoid neoplasms arising from T and NK cells. The incidence of mature T-and NK-cell lymphomas is 2.1 per 100,000 people, according to a US report~1.

Role of the clinical immunology laboratory in disease monitoring

Immunological investigations provide useful informa-tion to guide diagnosis of several disorders. Many such tests are also commonly repeated at intervals, in an effort to facilitate disease monitoring. In general how-ever, immunology test results are often slow to alter. Furthermore, audit activity has indicated that repeated testing accounts for a substantial workload in many immunology services, which may waste resources and compromise the effcient completion of necessary tests. Consequently, the need and appropriate mini-mum interval between repeated testing requires critical evaluation. In this review, the clinical utility of repeat-ed performance of several common immunology inves-tigations has been evaluated, based upon published evidence. In some cases （ e.g. , paraprotein quantifca-tion, or measurement of anti-glomerular basement membrane antibodies）, repeated testing provides vital clinical information and can be justifed on a frequent and individualized basis. However, many other investi-gations provided by immunology services provide less valuable information when used to aid disease moni-toring rather than diagnosis. It is hoped that the data summarized here will facilitate a more evidence-based approach to repeated testing. Such information may also assist with the local implementation of demand management strategies based upon setting of mini-mum retesting intervals for these investigations.

Global burden of HIV-negative multidrug-and extensively drug-resistant tuberculosis based on Global Burden of Disease Study 2021

Background:Tuberculosis(TB),caused by Mycobacterium tuberculosis,remains the second leading cause of death from a single infectious disease globally and poses a significant economic and clinical burden in the world in 2022.Of particular concern is the emergence of drug-resistant TB,accounting for 15%-20%of TB deaths.It is imperative to delve into the global trends of incidence and death rate for multidrug-resistant tuberculosis(MDRTB)and extensively drug-resistant tuberculosis(XDR-TB),drawing upon the comprehensive Global Burden of Disease(GBD)2021 drug-resistant tuberculosis dataset.Methods:From the GBD 2021,data on incidence,prevalence,disability-adjusted life years(DALYs),and death of MDR-TB and XDR-TB from 1990 to 2021 were collected.We calculated the estimated annual percentage changes in age standardized incidence rate(ASIR)and age-standardized death rate(ASDR),segmented by age,sex,and socio-demographic index(SDI).The impacts of various risk factors on MDR-TB and XDR-TB were also analyzed.Results:In 2021,there were an estimated 443,680(95%uncertainty interval[UI]:259,196-766,545)incident cases of MDR-TB,and an estimated 106,818(95%UI:41,612-211,854)death cases of MDR-TB,while there were an estimated 24,036(95%UI:17,144-34,587)incident cases of XDR-TB and 7,946(95%UI:3,326-14,859)death cases of XDR-TB.The incidence and death cases of MDR-TB were lowest in high SDI regions,whereas the incidence rates of XDR-TB in high-middle SDI regions were higher than those in middle SDI and high SDI regions.Conclusion:This study reported the disease burden of drug-resistant TB from 1990 to 2021.Until 2021,drugresistant TB is still a serious problem in low SDI countries,especially for high-risk age populations with highrisk factors.Controlling drug-resistant TB requires effective control strategies and healthcare systems.

The anti-neoplastic effects of metformin modulate the acquired phenotype of fbroblast cells in the breast cancer-normal fbroblast co-culture system

Intracellular communications between breast cancer and fibroblast cells were reported to be involved in cancer proliferation,growth,and therapy resitance.The hallmarks of cancer fibroblast interactions,consisting of caveolin 1(Cav1)and mono-carboxylate ransporter 4(MCT4)(metabolic coupling markers),along with IL-6,TGFB,and lactate secretion,are considered robust biomarkers predicting recurrence and metastasis.In order to promote a novel phenotype in normal fibroblasts,we predicted that breast cancer cells could be able to cause loss of Cavl and increase of MCT4,as well as elevate IL 6 and TGF in nearby nomal fibroblasts.We created a co culture model using breast cancer(4T1)and normal fibroblast(NIH3T3)cell lines cultured under specific experimental conditions in order to directly test our theory.Moreover,we show that long-term co-culture of breast cancer cells and normal fibroblasts promotes loss of Cavl and gain of MCT4 in adjacent fibroblasts and increase lactate secretion.These results were validated using the monoculture of each group separately as a control.In this system,we show that me tformin inhibits IL-6 and TGFB secretion and re expresses Cavl in both cells.However,MCT4 and lactate stayed high after treatment with metformin.In conclusion,our work shows that co-culture with breast cancer cells may cause signifcant alterations in the phenotype and secretion of normal fibroblasts.Metformin,however,may change this state and affect fibroblasts'acquired phenotypes.Moreover,mitochondrial inhibition by metformin after 8 days of treatment,signi ficantly hinders tumor growth in mouse model of breast cancer.

Unveiling the intricacies of irritable bowel syndrome

Irritable bowel syndrome(IBS)remains a challenging condition both for patients and clinicians,characterized by its chronic nature and the elusive complexity of its underlying mechanisms.The multifaceted relationship between the neuroendocrine axis,gut microbiota,and inflammatory response has emerged as a focal point in recent research,offering new insights into the pathophysiology of IBS.The neuroendocrine axis plays a crucial role in maintaining the delicate balance between the brain and the gut,often referred to as the“gut-brain axis”.This bidirectional communication is essential for regulating gastrointestinal function,stress responses,and overall homeostasis.Dysregulation of this axis,as highlighted by elevated cortisol and serotonin levels in IBS patients,suggests that neuroendocrine imbalances may significantly contribute to the severity of gastrointestinal symptoms.These findings underscore the need for a broader understanding of how stress and emotional factors influence IBS,potentially guiding more effective,personalized treatment approaches.Equally important is the role of the gut microbiota,a diverse and dynamic ecosystem that directly impacts gut health.This dysbiosis disrupts gut function and appears to exacerbate the neuroendocrine and inflammatory responses.These findings align with the growing recognition that gut microbiota is a critical player in IBS,influencing both the disease's onset and progression.

Effects of heat stress and long photoperiod on the prostate of rats

Objective:To examine light and heat effects on the morphological,histological,and micrometric structure of the prostate of rats.Methods:Thirty adult male rats were divided into three groups.The control group was kept under 20℃-22℃ and an artificial 12 h/12 h day/night cycle;the temperature group was under normal light and at(42±1)℃ heat for 4 to 5 h daily,and the light group was exposed to 8 h/16 h day/night cycle with 20℃-22℃.Rats were weighed five times(at the beginning of the study and every seven days).Five milliliters(mL)of their peripheral blood were taken.The tissue staining was performed using the hematoxylin-eosin(H&E)stain and periodic acid-Schiff(PAS).In the following,tissue and cellular reactions to the PAS were examined.Results:Folds were located entirely on the surface of the anterior lobe and periphery of the other lobes.The secretory units in the anterior lobe were more than the lateral lobe.A strong reaction of the secretory cells to the PAS was observed.Testosterone serum levels of the light group also significantly increased compared to the control group(P<0.05).The most histometric changes of the lobes were established in the lateral lobes.Heat stress resulted in a significant decrease in testosterone levels and transformed prostate tissue.The epithelium and parenchyma to scaffold ratio in the temperature group decreased.Conclusions:Maximum and minimum changes in the ventral lobe happened under the ascent of temperature and light,respectively.The ventral lobe in the study of prostatic hyperplasia should be more considered.

Interferon-gamma release assays as a tool for differential diagnosis of gastrointestinal tuberculosis

In this editorial,we comment on an article published in a recent issue of the World Journal of Clinical Cases.There is a pressing need for reliable tools for diagnosing tuberculosis(TB)of the gastrointestinal tract.Despite advancements in the diagnosis and treatment,TB remains a global health challenge.Ali et al demon-strated that TB may mimic gastrointestinal conditions,such as gastric outlet obstruction,causing a delay in the diagnosis.Furthermore,the latter complication is frequently observed during infections,including Helicobacter pylori,and rarely is related to TB,as in the presented case.In line with this,we think that laboratory tests based on interferon-gamma release assays can be a helpful tool for diagnosing latent TB paced in the gastrointestinal tract.Innovative strategies and approaches for diagnosing latent/active extra pulmonary TB are crucial for establishing the diagnosis early and enhancing treatment strategies to mitigate the global burden of TB.

From dichotomy to diversity:deciphering the multifaceted roles of tumor-associated macrophages in cancer progression and therapy

Macrophages are innate immune cells that are ubiquitously distributed throughout the vertebrate body.Macrophages orchestrate sophisticated processes in development,homeostasis,immunity,and disease1.Macrophages residing in tumor tissues are commonly known as tumor-associated macrophages(TAMs)and promote or inhibit tumor growth depending on the activation state2.

Synthesis of reduced graphene oxide nanosheets from sugarcane dry leaves by two-stage pyrolysis for antibacterial activity

Oxidative-exfoliation methods were in vogue in the production of rGO from graphite.Processing of such synthetic graphite needs high temperatures(2500℃).Thus,such process is not cost-effective.The present study is made on the dry leaves of sugarcane(Saccharum officinarum)as an alternative raw material so as to be economical and environmentally benign.The dry leaves are subjected to two-step pyrolysis without any catalyst or reducing agent in far divergent temperatures to produce as prepared and acid treated rGOs.They were evaluated by UV–Vis.,FTIR,XRD,Raman spectroscopy,TGA/DTG,BET,FESEM-EDS and TEM.The as prepared rGO has few layers with irregular and folded architecture whereas acid-treated rGO has thinly stacked crumpled sheets with many wrinkles on its surface.The prepared rGOs have multilayered graphitic structure due to the unique ratio between G and D bands.Acid treated rGO has poor thermal stability as compared to that of as-prepared rGO at high temperatures due to the variation in the oxygen-containing functional groups.Acid treated rGO has low antibacterial activity as compared to that of the as-prepared rGO due to the paucity of the functional groups.

IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

Unlocking the novel activation mechanism of human IL-18

Interleukin(IL)-18,a member of the IL-1 family,is commonly known as an interferon-γinducer and is expressed in both hematopoietic and non-hematopoietic cells,such as intestinal epithelial cells,keratinocytes,and endothelial cells.In the immune system,the mature IL-18 plays a critical role in eliminating tumors and infectious agents by activating NK cells and T-lymphocytes,and by synergizing with other cytokines like IL-12 and IL-1βto induce inflammation[1-2].

Early monitoring values of oncogenic signalling molecules for hepatocellular carcinoma

The prevention and early diagnosis of liver cancer remains a global medical challenge.During the malignant transformation of hepatocytes,a variety of oncogenic cellular signalling molecules,such as novel high mobility group-Box 3,angiopoietin-2,Golgi protein 73,glypican-3,Wnt3a(a signalling molecule in the Wnt/β-catenin pathway),and secretory clusterin,can be expressed and secreted into the blood.These signalling molecules are derived from different signalling pathways and may not only participate in the malignant transformation of hepatocytes but also become early diagnostic indicators of hepatocarcinogenesis or specific targeted molecules for hepatocellular carcinoma therapy.This article reviews recent progress in the study of several signalling molecules as sensitive biomarkers for monitoring hepatocarcinogenesis.

Caspase-11 mediated inflammasome activation in macrophages by systemic infection of A.actinomycetemcomitans exacerbates arthritis

Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A.actinomycetemcomitans)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly understood.Here,we show that systemic infection with A.actinomycetemcomitans triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages.The administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages.These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A.actinomycetemcomitans.This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A.actinomycetemcomitans.

Retrospective cohort study on the postoperative survival rate enhancement of patients with colorectal cancer using three traditional Chinese medicine formulations:evidence from 1,361 cases

Background:Prior studies have affirmed the safety and effectiveness of traditional Chinese medicine in treating colorectal cancer patients.However,definitive evidence regarding whether traditional Chinese medicine can significantly enhance the survival of colorectal cancer patients remains elusive.This study seeks to provide conclusive insights by examining the postoperative administration of Xihuang capsules,Pingxiao capsules,and Zilongjin tablets and its impact on the 5-year overall survival(OS)and disease-free survival(DFS)rates among colorectal cancer patients.Methods:A retrospective study was conducted,involving 1,361 patients selected from the medical center.This retrospective study was carried out at a medical center in Tianjin,China.We assessed differences in postoperative OS and DFS between the control group and the medication group using Kaplan–Meier survival analysis and Cox proportional hazards modeling.Additionally,propensity score matching was used to mitigate imbalances in baseline characteristics among patients.Results:Before propensity score matching,Xihuang capsules could prolong the 5-year OS(79.9%vs.81.4%,P=0.0480)and 5-year DFS(74.9%vs.79.5%,P=0.0046)of patients after surgery.Similar conclusions were obtained after propensity score matching:OS(74.8%vs.78.3%,P=0.0084),DFS(72.7%vs.78.9%,P=0.008).Patients taking Pingxiao capsules showed improved 5-year OS(77.2%vs.84.0%,P=0.0383)and 5-year DFS(69.9%vs.80.0%,P=0.0157)after propensity score matching.Patients taking Zilongjin tablets showed improvement in the 2-year OS(84.2%vs.93.1%,P=0.0390)and 1-year DFS(88.2%vs.92.0%,P=0.0320)after propensity score matching.Conclusion:Xihuang capsules and Pingxiao capsules significantly improved the 5-year OS and DFS of patients with colorectal cancer after surgery.Zilongjin tablets showed improvement in the 2-year OS and 1-year DFS after surgery for patients.

Dietary exposure assessment of perchlorate and chlorate in infant formulas marketed in Shanghai,China

Perchlorate and chlorate are ubiquitous pollutants that can adversely affect the thyroid function in humans.This study assessed the potential health risks associated with the dietary exposure of infants and young children to perchlorate and chlorate present in infant formulas available in Shanghai.The assessment was based on risk monitoring data from 150 samples of infant formulas in Shanghai between 2020 and 2022,along with the dietary consumption data of infants and young children.The detection rates of perchlorate and chlorate in infant formulas were 46.0%and 98.7%,with mean contents of 9.98μg/kg and 112.01μg/kg,and the maximum values of 151.00μg/kg and 1475.00μg/kg,respectively.The mean and 95th percentile(P95)values of daily perchlorate exposure of 0-36-month-old infant and young children via infant formulas were 0.07 and 0.17μg/kg body weight(bw)per day,respectively,which were lower than the tolerable daily intake(TDI)of perchlorate(0.3μg/kg bw per day).The mean and P95 values of chlorate exposure via infant formulas in 0-36-month-old infants and young children were 0.83 and 1.89μg/kg bw per day,which were lower than the TDI of chlorate(3μg/kg bw per day).The P95 exposure of different age groups(0-6 months,7-12 months and 13-36 months)of infants and young children to perchlorate and chlorate in infant formulas was below the TDI.Therefore,the risk associated with the exposure of 0-36-month-old infants and young children to perchlorate and chlorate from infant formulas in Shanghai is considered acceptable.Prioritizing environmental pollution control efforts to reduce the levels of perchlorate and chlorate in food products is important to safeguard the health of the infants and children under the One Health concept.

Markers of Oocyte Quality to Enhance Human IVF Outcomes: A Bibliographic Review

The markers of oocyte quality have remained a major controversy in the field of embryology due to the subjectivity of the different methods of oocyte assessment. Various scholars use oocyte quality and oocyte competence interchangeably. Oocyte quality can be defined as the overall health of an oocyte whereas oocyte competence refers to the ability of an oocyte to be fertilized and develop into a healthy embryo. Diminished oocyte quality is believed to be a result of alterations in oocyte growth and maturation processes that stem from several pelvic and systemic factors before and after oocyte retrieval. In this review, we focus on the morphological and nonmorphological markers of oocyte quality. Strict restrictions that limit the number of oocytes fertilized in various countries have triggered researchers around the world to come up with the most appropriate and noninvasive markers that enhance oocyte selection and optimize IVF outcomes. PubMed, Google Scholar, and the Cochrane Library were used to search for peer-reviewed, original articles about oocyte quality markers. The review was written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Morphological markers are commonly used, but they are subjective, and no single marker can be used exclusively to predict oocyte competence and subsequent embryonic development potential. Furthermore, transcriptomics of differentially expressed genes in cumulus cells and assessment of metabolomics and other contents of follicular fluid have shown greater precision. However, their specificity to the different quality determinants needs further research.

Structural insights of poly(butylene adipate-co-terephthalate)depolymerases

Poly(butylene adipate-co-terephthalate),PBAT,is one of the most popular plastics nowadays and is becoming a large burden to the environment when PBAT waste is accumulated.Biodegradation of PBAT is an environmentally friendly method to treat PBAT waste.In the past two decades,a couple of microbial strains or mixed strains have been chemically characterized.From this,many PBAT depolymerases have been isolated and further structurally determined.The review we focused on the PBAT depolymerases that have been structurally characterized,including lipases,esterases,and cutinases.We also discussed which shape of the substrate-binding tunnels is beneficial for recognizing and decomposing polymer chains of PBAT,which would be important guidance in directing the designation of PBAT depolymerases.

Activation and signaling of the p38 MAP kinase pathway

The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.