Does Smoking Weaken the Immune System: A Narrative Review

Smoking has a complex impact on the immune system, affecting both innate and adaptive immunity. It can exacerbate pathogenic immune responses and attenuate defensive immunity, leading to a higher susceptibility to infections and certain diseases. The chemicals in cigarette smoke, such as nicotine and carbon monoxide, can alter immune cell functions and inflammatory responses. Smoking can also have long-term effects on the immune system, with some changes persisting even after quitting [1]. According to a Penn Medicine Physician, the Medical Oncologist Dr. David Porter, “People who are smokers tend to get sicker from infections”, “It may be that smoking impacts the immune system’s ability to respond appropriately”. Thus, such individuals within smoking exposure history might be considered as immunocompromised due to the altered and weakened immune system. Cigarette smoking is a prevalent habit with far-reaching health implications. Among its many adverse effects, smoking significantly alters the immune system’s functionality [1].

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

Unraveling colorectal cancer prevention:The vitamin D-gut flora-immune system nexus

Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D may play a pivotal role in the development of CRC.Vitamin D,primarily obtained through sunlight exposure,dietary sources,and supplements,has long been recognized for its essential functions in maintaining health,including immune regulation.This article delves into the intricate relationship between vitamin D,the immune system,gut flora,and the prevention of CRC.It presents a synthesis of epidemiological data,experimental studies,and clinical trials,highlighting the mechanisms by which vitamin D influences immune cell function,cytokine production,and inflammation.By enhancing the immune system’s surveillance and antitumor activity,vitamin D may offer a promising avenue for CRC prevention.Furthermore,this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain.Additionally,the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC,emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms,encompassing antineoplastic mechanisms,influences on the immune system,and modulation of the gut microbiome.

Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR) as Systemic Inflammatory Predictors in the Diagnosis of Bullous Pemphigoid and Pemphigus Vulgaris

Introduction: Autoimmune blistering skin disorders such as Bullous Pemphigoid and Pemphigus Vulgaris present diagnostic challenges. The Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), are inflammatory markers used to assess the body’s immune-inflammatory response. Objectives: The study aims to evaluate the significance of hematologic markers, specifically the Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), as diagnostic predictors of bullous pemphigoid (BP) and pemphigus vulgaris (PV). Methods: A retrospective study of 64 patients (36 with BP and 28 with PV). Patient clinical data: age, gender, complete blood count, autoimmune antibody levels (Dsg1, 3 and BP180, 230), IgE and C-reactive protein, and history of hypertension, diabetes, brain infarction, and coronary heart disease. The data was analyzed using SPSS. Results: The study involved 36 (56.3%) diagnosed with bullous pemphigoid (BP) and 28 (43.75%) with pemphigus vulgaris (PV). The average age in BP was 71 ± 8 and 52 ± 13 in PV. Laboratory findings showed high levels of Dsg1, Dsg3, neutrophil count, and lymphocyte count in PV, while high levels of eosinophils with a significant increase in C-reactive protein (CRP) in BP. Blood biomarkers, including NLR, PLR, SII, MPV, CRP, and IgE, proved an overall of 84.4% in disease prediction. Dsg1, Dsg3, BP180, and BP230 showed an overall of 88.1%. No significant relationship was noted between NLR, SII, and patients with comorbidities. Conclusion: The study highlights the diagnostic potential of SII and NLR in addition to hematologic markers in BP and PV, emphasizing their role in early diagnosis and therapeutic interventions, requiring further validation in larger patient cohorts.

Correlation between preoperative systemic immune inflammation index, nutritional risk index, and prognosis of radical resection of liver cancer

BACKGROUND Radical surgery is the most commonly used treatment for hepatocellular carcinoma(HCC).However,the surgical effect remains not ideal,and prognostic evaluation is insufficient.Furthermore,clinical intervention is rife with uncertainty and not conducive to prolonging patient survival.AIM To explore correlations between the systemic immune inflammatory index(SII)and geriatric nutritional risk index(GNRI)and HCC operation prognosis.METHODS This retrospective study included and collected follow up data from 100 HCC.Kaplan–Meier survival curves were used to analyze the correlation between SII and GNRI scores and survival.SII and GNRI were calculated as follows:SII=neutrophil count×platelet count/lymphocyte count;GNRI=[1.489×albumin(g/L)+41.7×actual weight/ideal weight].We analyzed the predictive efficacy of the SII and GNRI in HCC patients using receiver operating characteristic(ROC)curves,and the relationships between the SII,GNRI,and survival rate using Kaplan–Meier survival curves.Cox regression analysis was utilized to analyze independent risk factors influencing prognosis.RESULTS After 1 year of follow-up,24 patients died and 76 survived.The area under the curve(AUC),sensitivity,specificity,and the optimal cutoff value of SII were 0.728(95%confidence interval:0.600-0.856),79.2%,63.2%,and 309.14,respectively.According to ROC curve analysis results for predicting postoperative death in HCC patients,the AUC of SII and GNRI combination was higher than that of SII or GNRI alone,and SII was higher than that of GNRI(P<0.05).The proportion of advanced differentiated tumors,tumor maximum diameter(5–10 cm,>10 cm),lymph node metastasis,and TNM stage III-IV in patients with SII>309.14 was higher than that in patients with SII≤309.14(P<0.05).The proportion of patients aged>70 years was higher in patients with GNRI≤98 than that in patients with GNRI>98(P<0.05).The 1-year survival rate of the SII>309.14 group(compared with the SII≤309.14 group)and GNRI≤98 group(compared with the GNRI>98 group)was lower(P<0.05).CONCLUSION The prognosis after radical resection of HCC is related to the SII and GNRI and poor in high SII or low GNRI patients.

Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice

In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.

The Influence of Noni Fruit Juice on Immune System Function

Morinda citrifolia (noni) fruit juice has the potential to influence immune system function. This review discusses results from several human and animal studies that provide insight into the potential mechanisms of action by which noni juice exerts its immunomodulatory effects. Increased natural killer cell activity is a likely a major contributor to the improved health outcomes and increased survival times described in case reports and as observed in LLC and S180 tumor bearing mice. Increased interferon-gamma (IFN-γ) production is also an important mechanism of action through which noni improves immune function. IFN-γ promotes natural killer cell activity and phagocytosis, activities both seen in human and bovine studies as well as in rodents. Noni promotes regulatory cytokine expression, such as IL-2 which stimulates CD4+ T cell differentiation. Noni juice appears to influence this process via kinase 1/2 (ERK1/2), protein kinase B (Akt) and nuclear factor-kappa-beta signaling. As oxidative status is known to influence immune function, this review also discusses the notable antioxidant properties of noni juice that have been demonstrated in human trials.

Effects of rearing system and antibiotic treatment on immune function,gut microbiota and metabolites of broiler chickens

Background:In China,cage systems with a high space utilization have gradually replaced ground litter systems,but the disease incidence of chickens in cages is higher.Broilers in the ground litter pens may be stimulated by more environmental microbes during the growth process and show strong immune function and status,but knowledge of which microbes and their metabolites play an immunomodulatory role is still limited.This study aimed to explore the differences and correlations in the immune function,gut microbiota and metabolites and the importance of gut microbiota of broilers raised in cages and ground litter pens.Methods:The experiment involved a 2×2 factorial arrangement,with rearing systems(cages or ground litter pens)and antibiotic treatment(with or without broad-spectrum antibiotics in drinking water)as factors.Results:The results showed that,compared with the cage group,the ground litter broilers had stronger nonspecific immune function(Macrophages%and NO in blood),humoral immune function(IgG in blood,LPS stimulation index in ileum)and cellular immune function(T%,Tc%,ConA stimulation index and cytokines in blood).Antibiotic(ABX)treat-ment significantly reduced nonspecific immune function(Macrophages%and NO in blood,iNOS and Mucin2 mRNA expression in ileum),humoral immune function(IgG in blood and sIgA in ileum)and cellular immune function(T%and cytokines in blood,Th and Tc ratio,TLRs and cytokines mRNA expression in ileum).Furthermore,the ground litter broil-ers had higherαdiversity of microbiota in ileum.The relative abundance of Staphylococcus,Jeotgalicoccus,Jeotgalibaca and Pediococcus in the ileum of ground litter broilers were higher.ABX treatment significantly reduced theαdiversity of ileal microbiota,with less Chloroplast and Mitochondria.In addition,the levels of acetic acid,isobutyric acid,kynurenic acid and allolithocholic acid in the ileum of ground litter broilers were higher.Spearman correlation analysis showed that Jeotgalibaca,Pediococcus,acetic acid,kynurenic acid and allolithocholic acid were related to the immune function.Conclusions:There were more potential pathogens,litter breeding bacteria,short-chain fatty acids,kynurenine,allolithocholic acid and tryptophan metabolites in the ileum of broilers in ground litter pens,which may be the reason for its stronger immune function and status.

Autoimmune hepatitis and primary sclerosing cholangitis after direct-acting antiviral treatment for hepatitis C virus:A case report

BACKGROUND Chronic hepatitis C virus(HCV)infection is a major global health concern that leads to liver fibrosis,cirrhosis,and cancer.Regimens containing direct-acting antivirals(DAAs)have become the mainstay of HCV treatment,achieving a high sustained virological response(SVR)with minimal adverse events.CASE SUMMARY A 74-year-old woman with chronic HCV infection was treated with the DAAs ledipasvir,and sofosbuvir for 12 wk and achieved SVR.Twenty-four weeks after treatment completion,the liver enzyme and serum IgG levels increased,and antinuclear antibody became positive without HCV viremia,suggesting the development of autoimmune hepatitis(AIH).After liver biopsy indicated AIH,a definite AIH diagnosis was made and prednisolone was initiated.The treatment was effective,and the liver enzyme and serum IgG levels normalized.However,multiple strictures of the intrahepatic and extrahepatic bile ducts with dilatation of the peripheral bile ducts appeared on magnetic resonance cholangiopancreatography after 3 years of achieving SVR,which were consistent with primary sclerosing cholangitis.CONCLUSION The potential risk of developing autoimmune liver diseases after DAA treatment should be considered.

Efficacy of probiotics supplementation in amelioration of celiac disease symptoms and enhancement of immune system

Patients with celiac disease(CD)have a mucosal layer that is unable to regulate the gut microbiota,leaving the host vulnerable to dangerous infections and antigens.When compared to healthy people,this dysbiosis is marked by a decrease in intra-and intergeneric biodiversity,which demonstrates an imbalance between helpful bacteria and possibly harmful or proinflammatory species.The early gut microbiota is influenced by the genotype of newborns with the HLADQ2 haplotypes,and this may modify how gluten is handled in the intestinal lumen,polarize innate or adaptive immune responses,and result in glutensensitive enteropathy.The outcome of gluten digestion can vary depending on the composition of the intestinal gut bacteria and the partial conversion of gluten into peptides larger than ten amino acids in the small intestines,which can be immunogenic.In the small intestine,114 different bacterial strains belonging to 32 different species have 27 of them exhibiting peptidolytic activity.Thus,the individual risk of developing a gluten-related illness is further influenced by microbial composition and gluten degrading capacity.The conclusion that lactobacilli and Bifidobacterium spp.may be used as a probiotic supplement in CD patients is based on their shared possession of the most extensive peptidolytic and proteolytic activity thought to be engaged in the breakdown of gluten among all potential bacterial genera present in the gut microbiota.In children with CD autoimmunity,daily oral dose of Lactobacillus.plantarum HEAL9 and Lactobacillus.paracasei 8700:2 was found to modify the peripheral immune response.Bifidobacterium.breve strains have demonstrated a beneficial effect on reducing pro-inflammatory cytokine TNF-production in CD children on gluten-free diets.

Impact of exercise on markers of B cell-related immunity:A systematic review

Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Immune checkpoint inhibitor-associated gastritis:Patterns and management

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of ICIs.Although irAE gastritis is rarely reported,it may lead to serious complications such as gastrorrhagia.Furthermore,irAE gastritis is often difficult to identify early due to its diverse symptoms.Although steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains uncertain.In addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be considered.In this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

Immune consequences of exercise in hypoxia:A narrative review

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type,dose(frequency/duration,intensity),and individual characteristics.Similarly,reduced availability of ambient oxygen(hypoxia)modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia.How combined exercise and hypoxia(e.g.,high-altitude training)sculpts immune responses is not well understood,although such combinations are becoming increasingly popular.Therefore,in this paper,we summarize the impact on immune responses of exercise and of hypoxia,both independently and together,with a focus on specialized cells in the innate and adaptive immune system.We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia,then we discuss how they may be modulated by nutritional strategies.Mitochondrial,antioxidant,and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism,resilience,and overall immune functions by regulating the survival,differentiation,activation,and migration of immune cells.This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions.Appropriate acclimatization,training,and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state.

A Prognostic Biomarker for Bladder Cancer Correlated with Immune Infiltration Is PAEP

Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.

The early life immune dynamics and cellular drivers at single-cell resolution in lamb forestomachs and abomasum

Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.