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.

T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.

Early identification and multidisciplinary management of immune checkpoint inhibitors associated colitis can improve patient outcomes

Currently,the use of immune checkpoint inhibitors(ICIs)has shown notable clinical efficacy in treating various malignant tumors,significantly improving patient prognosis.However,while ICIs enhance the body’s anti-tumor effects,they can also trigger immune-related adverse events(irAEs),with ICI-associated colitis being one of the more prevalent forms.This condition can disrupt treatment,necessitate drug discontinuation,and adversely affect therapeutic outcomes.In severe cases,irAEs may even become life-threatening.A recent case report by Hong et al highlights the importance of vigilance for ICI-associated colitis in patients experiencing symptoms such as diarrhea and abdominal pain,which can arise both during and even after completion of ICI treatment.Early identification,multidisciplinary management,and continuous monitoring of patients are essential steps to further improve outcomes.

Immune indicators and depression in adolescents:Associations with monocytes,lymphocytes,and direct bilirubin

BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.

Nomogram based on a novel nutritional immune-inflammatory status score to predict postoperative outcomes in esophageal squamous cell carcinoma

BACKGROUND The relationship between patient nutritional,immune,and inflammatory status is linked to tumor progression and prognosis.However,there are limited studies on the prognosis of esophageal squamous cell carcinoma(ESCC)after surgery based on the comprehensive indicators of these factors.AIM To develop and validate a novel nomogram based on a nutritional immuneinflammatory status(NIIS)score for predicting postoperative outcomes in ESCC.METHODS This retrospective study examined 829 patients with ESCC who underwent radical surgery between June 2016 and June 2020,with 568 patients in the training cohort and 261 patients in the validation cohort.We incorporated comprehensive indicators related to nutrition,immunity,and inflammation to develop the NIIS score, using LASSO regression. Subsequently, a nomogram combining the NIIS score and other clinicopathologicalparameters was developed and validated using calibration curves, time-dependent area under curves, and decisioncurve analysis.RESULTSWe identified eight indicators that constitute the NIIS score. High-risk scores emerged as an independent riskfactor for overall survival [training set HR 2.497 (1.802, 3.458), P < 0.001]. A NIIS nomogram for personalizedprognostic prediction was developed by integrating the NIIS score with clinicopathological variables, yieldingenhanced predictive value relative to individual indicators and the UICC/TNM staging system.CONCLUSIONThe NIIS score provides strong predictive value for postoperative outcomes in ESCC, thus offering a valuable toolfor clinical decision-making.

CRAFITY score and nomogram predict the clinical efficacy of lenvatinib combined with immune checkpoint inhibitors in hepatocellular carcinoma

BACKGROUND The CRAFITY score is mainly utilized for hepatocellular carcinoma(HCC)patients receiving atezolizumab and bevacizumab,with little investigation in its predictive capacity for alternative regimens,such as lenvatinib and programmed cell death protein 1(PD-1)inhibitors,which are widely utilized in Chinese clinical practice.AIM To look at the predictive significance of the CRAFITY score in HCC patients taking lenvatinib and PD-1 inhibitors.METHODS The retrospective investigation consisted of 192 patients with incurable HCC who received lenvatinib and PD-1 inhibitors between January 2018 and January 2022.Patients were stratified according to CRAFITY score(based on baseline alphafetoprotein and C-reactive protein levels)into CRAFITY-low,CRAFITY-intermediate,and CRAFITY-high groups.Overall survival(OS)and progressionfree survival(PFS)were assessed using Kaplan-Meier analysis,and independent prognostic factors were identified through Cox regression analysis.Nomograms were created to forecast survival for a year.RESULTS The median PFS and OS were the longest for patients in the CRAFITY-low group,followed by those in the CRAFITY-intermediate and CRAFITY-high groups(median PFS:8.4 months,6.0 months,and 3.1 months,P<0.0001;median OS:33.4 months,19.2 months,and 6.6 months,P<0.0001).Both the objective response rate(5%,19.6%,and 22%,P=0.0669)and the disease control rate(50%,76.5%,and 80%,P=0.0023)were considerably lower in the CRAFITY-high group.The findings from the multivariate analysis showed that a nomogram which included the tumor number,prior transarterial chemoembolization history,and CRAFITY score predicted 12-month survival with an area under the curve of 0.788(95%confidence interval:0.718-0.859),which was in good agreement with actual data.CONCLUSION The CRAFITY score is a valuable predictor of survival and treatment outcomes in patients receiving lenvatinib and PD-1 inhibitors.

Personalized nutritional care for immune function recovery in postoperative gastrointestinal surgery patients:An observational study

BACKGROUND Gastrointestinal(GI)surgery can significantly affect the nutritional status and immune function of patients.This study aimed to investigate the effects of personalized nutritional care on the recovery of immune function in patients who underwent postoperative GI surgery.AIM To study examines personalized nutritional care’s impact on immune function recovery,nutritional status,and clinical outcomes after GI surgery.METHODS This observational study included 80 patients who underwent GI surgery between 2021 and 2023.Patients received personalized nutritional care based on their individual needs and surgical outcomes.Immune function markers including lymphocyte subsets,immunoglobulins,and cytokines were measured preoperatively and at regular intervals postoperatively.Nutritional status,clinical outcomes,and quality of life were assessed.RESULTS Patients receiving personalized nutritional care showed significant improvements in immune function markers compared to baseline.At 4 weeks postoperatively,CD4+T-cell counts increased by 25%(P<0.001),while interleukin-6 levels decreased by 40%(P<0.001).Nutritional status,as measured by prealbumin and transferrin levels,improved by 30%(P<0.01).Postoperative complications reduced by 35%compared to historical controls.The quality-of-life scores improved by 40%at 3 months postoperatively.CONCLUSION Personalized nutritional care enhances immune function recovery,improves nutritional status,and reduces complications in patients undergoing postoperative GI surgery,highlighting its crucial role in optimizing patient outcomes following such procedures.

Genome-wide identification and characterization of putative effectors in Heterodera schachtii that suppress plant immune response

The sugar beet cyst nematode(Heterodera schachtii) is one of the most destructive pathogens in sugar beet production, which causes serious economic losses every year. Few molecular details of effectors of H. schachtii parasitism are known. We analyzed the genome and transcriptome data of H. schachtii and identified multiple potential predicted proteins. After filtering out predicted proteins with high homology to other plant-parasitic nematodes, we performed functional validation of the remaining effector proteins. 37 putative effectors of H. schachtii were screened based on the Nicotiana benthamiana system for identifying the effectors that inhibit plant immune response, eventually determines 13 candidate effectors could inhibit cell death caused by Bax. Among the 13 effectors, nine have the ability to inhibit GPA2/RBP1-induced cell death. All 13 effectortriggered immunity(ETI) suppressor genes were analyzed by qRT-PCR and confirmed to result in a significant downregulation of one or more defense genes during infection compared to empty vector. For in situ hybridization,13 effectors were specifically expressed and located in esophageal gland cells. These data and functional analysis set the stage for further studies on the interaction of H. schachtii with host and H. schachtii parasitic control.

Machine learning model using immune indicators to predict outcomes in early liver cancer

BACKGROUND Patients with early-stage hepatocellular carcinoma(HCC)generally have good survival rates following surgical resection.However,a subset of these patients experience recurrence within five years post-surgery.AIM To develop predictive models utilizing machine learning(ML)methods to detect early-stage patients at a high risk of mortality.METHODS Eight hundred and eight patients with HCC at Beijing Ditan Hospital were randomly allocated to training and validation cohorts in a 2:1 ratio.Prognostic models were generated using random survival forests and artificial neural networks(ANNs).These ML models were compared with other classic HCC scoring systems.A decision-tree model was established to validate the contri-bution of immune-inflammatory indicators to the long-term outlook of patients with early-stage HCC.RESULTS Immune-inflammatory markers,albumin-bilirubin scores,alpha-fetoprotein,tumor size,and International Normalized Ratio were closely associated with the 5-year survival rates.Among various predictive models,the ANN model gene-rated using these indicators through ML algorithms exhibited superior perfor-mance,with a 5-year area under the curve(AUC)of 0.85(95%CI:0.82-0.88).In the validation cohort,the 5-year AUC was 0.82(95%CI:0.74-0.85).According to the ANN model,patients were classified into high-risk and low-risk groups,with an overall survival hazard ratio of 7.98(95%CI:5.85-10.93,P<0.0001)between the two cohorts.INTRODUCTION Hepatocellular carcinoma(HCC)is one of the six most prevalent cancers[1]and the third leading cause of cancer-related mortality[2].China has some of the highest incidence and mortality rates for liver cancer,accounting for half of global cases[3,4].The Barcelona Clinic Liver Cancer(BCLC)Staging System is the most widely used framework for diagnosing and treating HCC[5].The optimal candidates for surgical treatment are those with early-stage HCC,classified as BCLC stage 0 or A.Patients with early-stage liver cancer typically have a better prognosis after surgical resection,achieving a 5-year survival rate of 60%-70%[6].However,the high postoperative recurrence rates of HCC remain a major obstacle to long-term efficacy.To improve the prognosis of patients with early-stage HCC,it is necessary to develop models that can identify those with poor prognoses,enabling stratified and personalized treatment and follow-up strategies.Chronic inflammation is linked to the development and advancement of tumors[7].Recently,peripheral blood immune indicators,such as neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and lymphocyte-to-monocyte ratio(LMR),have garnered extensive attention and have been used to predict survival in various tumors and inflammation-related diseases[8-10].However,the relationship between these combinations of immune markers and the outcomes in patients with early-stage HCC require further investigation.Machine learning(ML)algorithms are capable of handling large and complex datasets,generating more accurate and personalized predictions through unique training algorithms that better manage nonlinear statistical relationships than traditional analytical methods.Commonly used ML models include artificial neural networks(ANNs)and random survival forests(RSFs),which have shown satisfactory accuracy in prognostic predictions across various cancers and other diseases[11-13].ANNs have performed well in identifying the progression from liver cirrhosis to HCC and predicting overall survival(OS)in patients with HCC[14,15].However,no studies have confirmed the ability of ML models to predict post-surgical survival in patients with early-stage HCC.Through ML,a better understanding of the risk factors for early-stage HCC prognosis can be achieved.This aids in surgical decision-making,identifying patients at a high risk of mortality,and selecting subsequent treatment strategies.In this study,we aimed to establish a 5-year prognostic model for patients with early-stage HCC after surgical resection,based on ML and systemic immune-inflammatory indicators.This model seeks to improve the early monitoring of high-risk patients and provide personalized treatment plans.

Macrophage polarization in cardiac transplantation:Insights into immune modulation and therapeutic approaches

The role and regulatory mechanisms of macrophage polarization in cardiac transplantation have gained significant attention.Macrophages can polarize into either the M1(pro-inflammatory)or M2(anti-inflammatory)phenotype in response to environmental cues.M1 macrophages facilitate transplant rejection by releasing inflammatory mediators and activating T cells,whereas M2 macrophages support graft survival by secreting antiinflammatory factors and promoting tissue repair.Mitochondrial quality control regulation plays a crucial role in macrophage polarization,which may influence graft survival and immune responses.This review provides an overview of the current understanding of mitochondrial quality control-regulated macrophage polarization in cardiac transplantation,its effects on graft outcomes,and potential therapeutic strategies to modulate this process to enhance transplant success rates.The review was conducted by systematically analyzing recent studies and integrating findings from key research articles to synthesize a comprehensive understanding of this emerging field.

Differentiating between immune checkpoint inhibitor-induced myocarditis and cardiac metastasis in a cardio-oncology patient presenting with myocardial infarction: A case report

BACKGROUND Cardiovascular diseases and cancer are leading causes of morbidity and mortality.Patients with malignancies are at increased risk for cardiovascular complications including acute coronary syndromes,chemotherapy or radiation therapy related complications and cardiac metastasis.CASE SUMMARY We present a case of a 47-year-old female with metastatic cancer on immuno-therapy presented with anterior ST elevation myocardial infarction followed by emergent percutaneous coronary intervention in the left anterior descending artery.Echocardiography after 72 hours showed thickening of inferior wall and cardiac magnetic resonance depicted inflammation and necrosis attributable to either cardiac metastasis or immunotherapy induced myocarditis.Biopsy was not performed because of treatment with antiplatelet drugs and a definite diagnosis was achieved after probationary administration of high-dose intravenous methyl-prednisolone that led to recovery.CONCLUSION In patients with malignancy,chemotherapy-induced cardiovascular complications and cardiac metastasis are common concerns and may coexist with common acute cardiovascular diseases including acute coronary syndromes.In such cases clinical suspicion aided by multimodality imaging is crucial for the diagnosis.A multidisciplinary team approach is required for prompt initiation of the appro-priate treatment.

Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration

Inflammation plays a crucial role in the regeneration of fish and avian retinas.However,how inflammation regulates Müller glia(MG)reprogramming remains unclear.Here,we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina.We first showed that two types of quiescent MG(resting MG1 and MG2)reside in the uninjured retina.Following retinal injury,resting MG1 transitioned into an activated state expressing known reprogramming genes,while resting MG2 gave rise to rod progenitors.We further showed that retinal microglia can be categorized into three subtypes(microglia-1,microglia-2,and proliferative)and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury.Analysis of cell–cell interactions indicated extensive crosstalk between immune cells and MG,with many interactions shared among different immune cell types.Finally,we showed that inflammation activated Jak1–Stat3 signaling in MG,promoting their transition from a resting to an activated state.Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair,and may provide valuable insights into future mammalian retina regeneration.

Reevaluating Calculus bovis:Modulating the liver cancer immune microenvironment via the Wnt/β-catenin pathway

In this article,we comment on the work published by Huang et al,which explores the mechanisms by which Calculus bovis(CB)modulates the liver cancer immune microenvironment via the Wnt/β-catenin signalling pathway.The study demon-strates that active components in CB effectively inhibit the activation of the Wnt/β-catenin pathway,significantly reducing the polarization of M2 tumor-associated macrophages.Both in vivo and in vitro experiments have validated the anti-tumour effects of CB,revealing its complex mechanisms of action through the modulation of immune cell functions within the tumour microenvironment.This article highlights CB’s therapeutic potential in liver cancer treatment and calls for further investigations into its mechanisms and clinical applications to develop safer,more effective options for patients.The study also revealed that key com-ponents of CB,such as bilirubin and bile acids,inhibit tumour cell proliferation and promote apoptosis through multiple pathways.Future research should explore the mechanisms of action of CB and its potential integration with existing treatments to improve the therapeutic outcomes of liver cancer patients.With multidisciplinary collaboration and advanced research,CB could become a key component of comprehensive liver cancer treatment,offering new hope for patients.

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.

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.

Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.

Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.

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.

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.