Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chin...Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.展开更多
Prostate cancer has gradually risen to become the second most common cancer threatening men’s health, and prostate-specific antigen (PSA), as the main screening indicator for prostate cancer, has the defects of low s...Prostate cancer has gradually risen to become the second most common cancer threatening men’s health, and prostate-specific antigen (PSA), as the main screening indicator for prostate cancer, has the defects of low specificity and insufficient diagnostic efficacy. As a novel inflammatory index based on neutrophil, lymphocyte and platelet counts, the systemic immune-inflammation index (SII) has recently become a more powerful biomarker for predicting the occurrence and progression of various malignancies. SII reflects the systemic inflammatory response of prostate cancer patients in a more balanced manner, and has higher predictive value than neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). High SII values are often associated with cancer progression and poor prognosis. This article reviews the research progress of SII in prostate cancer, in order to provide guidance for clinical practice.展开更多
Immune reconstitution inflammatory syndrome(IRIS)is a collection of inflammatory disorders characterized by the paradoxical worsening of preexisting infections processes following the initiation of antiretroviral ther...Immune reconstitution inflammatory syndrome(IRIS)is a collection of inflammatory disorders characterized by the paradoxical worsening of preexisting infections processes following the initiation of antiretroviral therapy in human immunodeficiency virus(HIV)-infected individuals.Diagnosing IRIS accurately and promptly remains challenging in areas with limited medical resources.Herpes simplex virus-2(HSV-2)is highly endemic in sub-Saharan Africa and is one of the primary opportunistic pathogens underlying IRIS,manifesting as mucocutaneous lesions.Here,we report a case of HSV-2-associated IRIS presenting as a genital ulcer,confirmed through nanopore high-throughput sequencing and successfully treated with acyclovir antiviral therapy.This study emphasizes the importance of clinicians maintaining proficiency in recognizing IRIS manifestations and being aware of region-specific opportunistic pathogens,both essential for timely diagnosis and etiology-directed therapy.展开更多
Aortic dissection(AD) is a cardiovascular emergency with a high mortality rate, and the risk of death is estimated to increase by 1%-2% per hour. AD is complicated by variable clinical manifestations, and early detect...Aortic dissection(AD) is a cardiovascular emergency with a high mortality rate, and the risk of death is estimated to increase by 1%-2% per hour. AD is complicated by variable clinical manifestations, and early detection and treatment can give more time for the treatment of patients.Hypertension is the most common cause of AD. In China, 65%-75% of patients with AD have poor blood pressure control. Patients with AD who are less than40 years of age are more likely to suffer from genetic diseases. Connective tissue disease(CTD) plays a dominant role in genetic diseases. Recently, inflammatory immunity, oxidative stress, obstructive sleep apnea-hypopnea syndrome(OSAHS), and other risk factors are being further studied. The new pathogenic factors should be explored to provide an accurate and effective prevention and treatment basis and new diagnostic methods and targets for drug therapy for AD.展开更多
Background Aortic dissection remains one of the most acute and critical diseases in cardiac surgery,with high mortality and disability rates.In the 1960s,DeBakeyfirst proposed the classification of aortic dissection.S...Background Aortic dissection remains one of the most acute and critical diseases in cardiac surgery,with high mortality and disability rates.In the 1960s,DeBakeyfirst proposed the classification of aortic dissection.Subsequently,various classifications of aortic dissection have been proposed.To facilitate clinicians and medical staff involved in the treatment of aortic dissection to make better assessment of the condition of aortic dissection patients and to make reasonable clinical decisions,we reviewed several current mainstream classification schemes.We hope that this paper inspires other researchers to propose a new,more suitable classification scheme for use in the clinical setting.展开更多
Toll-like receptor 3 protein expression has been shown to be upregulated during cerebral ische- mia/reperfusion injury in rats. In this study, rat primary cortical neurons were subjected to oxy- gen-glucose deprivatio...Toll-like receptor 3 protein expression has been shown to be upregulated during cerebral ische- mia/reperfusion injury in rats. In this study, rat primary cortical neurons were subjected to oxy- gen-glucose deprivation to simulate cerebral ischemia/reperfusion injury. Chemically synthesized small interfedng RNA （siRNA）-1280, -1724 and -418 specific to toll-like receptor 3 were transfected into oxygen-glucose deprived cortical neurons to suppress the upregulation of toll-like receptor 3 protein expression. Western blotting demonstrated that after transfection with siRNA, toll-like re- ceptor 3 protein expression reduced, especially in the toll-like receptor 3-1724 group. These results suggested that siRNA-1724 is an optimal sequence for inhibiting toll-like receptor 3 expression in cortical neurons following oxygen-glucose deprivation.展开更多
Hematopoietic cell transplantation（HCT） is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen（HLA）-matched...Hematopoietic cell transplantation（HCT） is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen（HLA）-matched donor（allogeneic） or from the patient（autologous）. Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease（Gv HD）. Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, Gv HD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT：（1） early complications（in the first month）-related to harvesting of stem cells, during conditioning（drug toxicity, posterior reversible encephalopathy syndrome）, related to pancytopenia,（2） intermediate phase complications（second to sixth month）-central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus,（3） late phase complications（after sixth month）-neurological complications of Gv HD, second neoplasms and relapses of the original disease.展开更多
Coronavirus disease 2019(COVID-19)poses an extremely serious global impact on public healthcare for individuals of all ages,including children.Increasing evidence has shown that liver abnormalities are commonly found ...Coronavirus disease 2019(COVID-19)poses an extremely serious global impact on public healthcare for individuals of all ages,including children.Increasing evidence has shown that liver abnormalities are commonly found in children with COVID-19,and age-related features in innate and adaptive response have been demonstrated.However,there are few reports and studies on COVID-19 related liver injury in children,and the data are scattered.So that many contradictions have arose.This situation is not only due to the serious ethical issues in studying pediatric patients with COVID-19,but also because of the short duration and wide coverage of the COVID-19 epidemic,the severity and complexity of clinical cases varied,as did the inclusion criteria for case reporting and patient outcomes.Therefore,we totaled the incidences,characteristics and pathomechanism of liver injury in children since the COVID-19 outbreak.The etiology of COVID-19-related liver injury is divided into three categories:(1)The direct mechanism involves severe acute respiratory syndrome coronavirus 2 binding to angiotensin-converting enzyme 2 in the liver or bile duct to exert direct toxicity;(2)the indirect mechanisms include an inflammatory immune response and hypoxia;and(3)COVID-19-related treatments,such as mechanical ventilation and antiviral drugs,may cause liver injury.In summary,this minireview provides fundamental insights into COVID-19 and liver dysfunction in children.展开更多
Objective:To observe the relationship between the distribution of TCM Syndromes of primary Sjogren's syndrome(pSS)and the changes of erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis fact...Objective:To observe the relationship between the distribution of TCM Syndromes of primary Sjogren's syndrome(pSS)and the changes of erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM.Methods:157 diagnosed PSS patients were divided into dampness heat obstructing collaterals syndrome,dryness evil invading lung syndrome,Qi blood stasis syndrome,liver kidney yin deficiency syndrome and Qi Yin deficiency syndrome according to TCM syndrome differentiation standard.The age,course of disease,general health score in international universal quality of life scale,self rating Anxiety scale(SAS),self rating Depression Scale(SDS)and erythrocyte sedimentation rate were observed and detected(ESR,C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM and other immune inflammatory indexes were detected.The relationship between different TCM Syndromes of PSS and molecular level changes of immune inflammatory indexes was analyzed and compared,as well as the impact on quality of life and mental emotion.Results:The overall health score of patients with Qi Yin deficiency syndrome was significantly lower than that of patients with dampness heat obstructing collaterals and dampness evil invading lung syndrome(P<0.01),while the SAS and SDS scores of patients with Qi Yin deficiency syndrome were significantly higher than those of patients with dampness heat invading lung syndrome and dampness heat obstructing collaterals syndrome(P<0.05,P<0.01);ESR,CRP,RF,TNF-α,IL-6,IgA,IgG and IgM related laboratory indexes of patients with dampness heat obstructing collaterals syndrome were significantly higher than those of patients with dry evil invading lung syndrome,liver kidney yin deficiency syndrome and liver kidney yin deficiency syndrome Qi Yin deficiency syndrome and Qi blood stasis syndrome(P<0.05,P<0.01).Correlation test found that the above five syndrome types were positively correlated with hs-CRP,IL-6,TNF-ɑindicators(P<0.05).Conclusion:The overall health,SAS,SDS and related hs-CRP,IL-6,TNF-ɑand some others indexes of SS patients are associated with TCM syndromes.展开更多
Objective This study was conducted to evaluate the effects of postoperative immune enhancing enteral nutrition on the immune system,inflammatory responses,and clinical outcome of patients undergoing major abdominal su...Objective This study was conducted to evaluate the effects of postoperative immune enhancing enteral nutrition on the immune system,inflammatory responses,and clinical outcome of patients undergoing major abdominal surgery. Methods This study was designed as a multicenter,prospective,randomized and controlled clinical trial. One hundred twenty-four patients undergoing major abdominal surgery were randomly assigned to receive either an immune enhancing enteral diet or an isocaloric and isonitrogenous control enteral diet for seven days. Enteral feeding was initiated 24 hours after surgery. Host immunity was evaluated by measuring levels of IgG,IgM,IgA,CD4,CD8,and CD4/CD8,and the inflammatory response was determined by assessing IL-1α, IL-2, IL-6, IL-10, and TNF-α levels. Infectious complications were also recorded. Results One hundred twenty patients completed the study and four patients were excluded. On postoperative day 9,among patients receiving an immune enhancing diet,IgG,IgA,CD4 and CD4/CD8 levels were significantly higher and TNF-α and IL-6 concentrations were significantly lower compared to the control group. Moreover,among patients receiving an immune enhancing diet,when comparing preoperation to day 9 postoperation levels,increases in IgA,CD4,and CD4/CD8 levels were significantly higher than in control patients and increases in TNF-α concentrations were significantly lower. No statistically significant differences were found between the two groups with regard to infectious complications. Conclusions Postoperative administration of immune enhancing enteral nutrition in patients undergoing major abdominal surgery can positively modulate postoperative immunosuppressive and inflammatory responses.展开更多
Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Method...Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Methods We retrieved data from sepsis patients who underwent Th1/Th2 cytokine testing in Nanfang Hospital,Southern Medical University from June 1,2020,to February 1,2022.An unsupervised K-means clustering method classified participants based on Th1/Th2 cytokine levels,with the primary outcome being the 7-day mortality rate post-ICU admission.Cox proportional hazards and Restricted Mean Survival Time(RMST)analyses were utilized to explore survival outcomes.Results A total of 321 sepsis patients were included.IL-6(HR 1.69,95%CI:1.22,2.34)and IL-10(HR 1.81,95%CI:1.37,2.40)emerged as independent predictors of 7-day mortality.Unsupervised K-means clustering revealed 3 inflammatory/immune subgroups:Cluster 1(n=166,low inflammatory response),Cluster 2(n=99,moderate inflammatory response with immune suppression),and Cluster 3(n=56,strong inflammatory and immune suppression).Compared to Cluster 1,Clusters 2 and 3 had higher 7-day mortality risks(14.4%vs 23.2%,HR=4.30,95%CI:1.51-12.26;14.4%vs 35.7%,HR=7.32,95%CI:2.57-20.79).Conclusion Septic patients in a protective immune response state(Cluster 1)exhibit better short-term prognoses,suggesting the importance of understanding inflammatory/immune states for precise treatment and improved outcomes.展开更多
Metabolic-associated fatty liver disease(MAFLD),a global health burden with limited therapeutic options beyond lifestyle changes,urgently needs novel strategies.We engineered exosome-like nanovesicles(HNVs)from dried ...Metabolic-associated fatty liver disease(MAFLD),a global health burden with limited therapeutic options beyond lifestyle changes,urgently needs novel strategies.We engineered exosome-like nanovesicles(HNVs)from dried honeysuckle(Lonicera japonica),exhibiting significantly more uniform size distribution than conventional herbal extracts and characteristic nanovesicle morphology.Orally delivered HNVs,enriched with bioactive metabolites,dramatically inhibited increased fat vacuoles,lipid droplet deposition,and collagen fibrosis in the livers of mice with MAFLD induced by high-fat diet(HFD).Mechanistically,HNVs orchestrate a dual gut-liver intervention:(1)restoring gut barrier integrity,slashing serum LPS by 1.58-fold and quelling hepatic inflammation;(2)remodeling gut microbiota to suppress bile salt hydrolase(BSH),elevating taurochenodeoxycholic acid(TCDCA)2.07-fold.This microbial shift reprograms enterohepatic signaling by inhibiting the FXR-FGF15-FGFR4 axis,thereby boosting hepatic cholesterol catabolism via bile acid synthases.Critically,efficacy is strictly microbiotadependent:abolished by antibiotics and fully transferable via fecal microbiota transplantation(FMT)from HNV-treated donors.Presenting the first natural nanovesicle platform that concurrently targets gut barrier repair and metabolic reprogramming,HNVs establish a pioneering,multi-targeted therapeutic paradigm for MAFLD,directly linking gut microbial ecology to hepatic pathophysiology with high translational potential.展开更多
Osteosarcoma,a prevalent primary malignant bone tumor,predominantly affects both elderly and adolescent populations and usually has an unfavorable prognosis.The specific mechanisms underlying its invasive progression ...Osteosarcoma,a prevalent primary malignant bone tumor,predominantly affects both elderly and adolescent populations and usually has an unfavorable prognosis.The specific mechanisms underlying its invasive progression remain unclear.The tumor microenvironment includes not only cancer cells but also bone-related cells,immune cells,tumor-associated nerve cells,and cell-secreted factors.The cooperative and competitive interactions among these cellular components contribute to the proliferation,progression,metastasis,and immune evasion of osteosarcoma.Alterations in bone-related cells,resulting from oncogenic changes,can rapidly increase bone density or aggravate bone loss,thereby promoting the survival of osteosarcoma cells.During the progression of osteosarcoma,genetic alterations in tumor cells lead to changes in extracellular matrix components,influencing the variation in cell-secreted factors,promoting immunosuppression within the tumor microenvironment,and consequently affecting tumor proliferation and progression.This review summarizes the roles of tumor microenvironment components in the pathogenesis of osteosarcoma and discusses existing therapeutic targets.The findings suggest potential research directions for further investigation of osteosarcoma,provide novel insights into the development of osteosarcoma,and may guide the development of more effective anti-tumor strategies.展开更多
Human bone marrow stem cells(hBMSCs)play an important role during the fracture healing phase.Previous clinical studies by our research group found that fracture healing time was obviously delayed in patients who under...Human bone marrow stem cells(hBMSCs)play an important role during the fracture healing phase.Previous clinical studies by our research group found that fracture healing time was obviously delayed in patients who underwent splenectomy,for combined traumatic fractures and splenic rupture,which is most likely related to the dysregulation of immune inflammatory function of the body after splenectomy.A large number of studies have reported that the inflammatory factor interleukin-1β plays an important role in the multi-directional differentiation ability and immune regulation of BMSC,but its specific regulatory mechanism needs to be further studied.Recently,long noncoding RNAs(lncRNAs)have attracted remarkable attention owing to their close relationship with stem cell osteogenesis and potential role in various bone diseases.In this study,we explored the molecular mechanism of a novel lncRNA,LncMSTRG.11341.25(LncMSTRG25),in terms of its effects on osteogenic differentiation of hBMSCs.Our results reveal significant up-regulation of LncMSTRG25,osteogenic differentiation markers during the osteogenic differentiation of hBMSCs,and decreased expression of miR-939-5p with an increase in differentiation time.LncMSTRG25 knockdown significantly inhibited the osteogenic ability of hBMSCs.When we knocked down PAX8 alone,we found that the osteogenic ability of hBMSCs was also significantly reduced.The interaction between LncMSTRG25 and PAX8 was verified using the RNA immunoprecipitation assay,RNA pull-down assays,silver staining,and the dual-luciferase reporter.The results show that LncMSTRG25 can function as a sponge to adsorb miR-939-5p,inducing the osteogenic differentiation of hBMSCs by activating PAX8.These findings deepen our understanding of the regulatory role of lncRNA-miRNA-mRNA networks in the immune microenvironment of bone marrow,and highlight the important role played by the spleen as an immune organ in fracture healing.展开更多
Atherosclerosis(AS)is a chronic inflammatory condition influenced by glucose and lipid disorders,oxidative stress,and thrombosis,reflecting the complexity of its pathological process.The development of accurate experi...Atherosclerosis(AS)is a chronic inflammatory condition influenced by glucose and lipid disorders,oxidative stress,and thrombosis,reflecting the complexity of its pathological process.The development of accurate experimental models that simulate human AS is essential for understanding its initiation and progression.This review summarizes the current AS research models and analyzes their specific application scenarios.We discuss tissue-engineered blood vessels(TEBVs)and vessels-on-a-chip(VoCs),which leverage tissue engineering and precise microenvironmental control to construct in vitro models that closely resemble the structure and function of human AS.Isolated vessel segments from live animals provide a valuable tool for investigating human AS due to their physiological similarity,controllability,and reproducibility.The review further outlines the construction of AS animal models through high-fat diets and gene-editing techniques,highlighting how immune-inflammatory responses,mechanical arterial injury,and hemodynamic changes accelerate model development.This comprehensive analysis highlights the potential of AS models to revolutionize theranostic applications in clinical translational research,paving the way for more personalized and effective treatments for AS in the near future.展开更多
Diabetic nephropathy （DN） is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomeruIar basement membrane, increased extracellular matrix formation,...Diabetic nephropathy （DN） is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomeruIar basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial-mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte-endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.展开更多
Dairy cattle are frequently fed high-concentrate(HC)diets in modern intensive feeding systems,especially in the transition period.During this period,cows face many alterations that include hormonal changes and shiftin...Dairy cattle are frequently fed high-concentrate(HC)diets in modern intensive feeding systems,especially in the transition period.During this period,cows face many alterations that include hormonal changes and shifting to a lactating state.Switching to a HC diet that may disrupt the ruminal microbiota balance can lead to subacute ruminal acidosis(SARA).Moreover,the main factor shaping the rumen microbiota is dietary composition,especially the ratio of starch to fibrous carbohydrates.Feeding highly fermentable carbohydrate diets after adaptation to forage diets leads to a rumen fermentation rate that exceeds rumen absorption and buffering rates,resulting in a reduction in ruminal pH.As a result of Gram-negative bacterial cell lysis,an increase in harmful ruminal bacterial metabolites,including lipopolysaccharide,lactic acid,and histamine,is observed.The interactions between the host immune system and the ruminal microbiota play an essential role in many physiological processes and the development of the disorder.Progress in DNA sequencing and bioinformatics platforms provides new opportunities to investigate the composition of ruminal microbes and yields unique advances in understanding ecology of the rumen.Subacute ruminal acidosis is linked with a change in the ruminal microbiota structure and richness and with other metabolic disorders;such as rumenitis,milk fat depression,laminitis,and liver abscesses.Therefore,this review aims to explore a better understanding of the crosstalk between diet and microbiota in the prevalence of rumen acidosis and its consequences,which is crucial for control strategies such as feeding management,and supplementation with thiamine,prebiotics,and probiotics.展开更多
Wound healing is a highly orchestrated process involving a variety of cells,including immune cells.Developing immunomodulatory biomaterials for regenerative engineering applications,such as bone regeneration,is an app...Wound healing is a highly orchestrated process involving a variety of cells,including immune cells.Developing immunomodulatory biomaterials for regenerative engineering applications,such as bone regeneration,is an appealing strategy.Herein,inspired by the immunomodulatory effects of gastrodin(a bioactive component in traditional Chinese herbal medicine),a series of new immunomodulatory gastrodin-comprising biodegradable polyurethane(gastrodin-PU)and nano-hydroxyapatite(n-HA)(gastrodin-PU/n-HA)composites were developed.RAW 264.7 macrophages,rat bone marrow mesenchymal stem cells(rBMSCs),and human umbilical vein endothelial cells(HUVECs)were cultured with gastrodin-PU/n-HA containing different concentrations of gastrodin(0.5%,1%,and 2%)to decipher their immunomodulatory effects on osteogenesis and angiogenesis in vitro.Results demonstrated that,compared with PU/n-HA,gastrodin-PU/n-HA induced macrophage polarization toward the M2 phenotype,as evidenced by the higher expression level of pro-regenerative cytokines(CD206,Arg-1)and the lower expression of pro-inflammatory cytokines(iNOS).The expression levels of osteogenesis-related factors(BMP-2 and ALP)in the rBMSCs and angiogenesis-related factors(VEGF and BFGF)in the HUVECs were significantly up-regulated in gastrodin-PU/n-HA/macrophage-conditioned medium.The immunomodulatory effects of gastrodin-PU/n-HA to reprogram macrophages from a pro-inflammatory(M1)phenotype to an anti-inflammatory and pro-healing(M2)phenotype were validated in a rat subcutaneous implantation model.And the 2%gastrodin-PU/n-HA significantly decreased fibrous capsule formation and enhanced angiogenesis.Additionally,2%gastrodin-PU/n-HA scaffolds implanted in the rat femoral condyle defect model showed accelerated osteogenesis and angiogenesis.Thus,the novel gastrodin-PU/n-HA scaffold may represent a new and promising immunomodulatory biomaterial for bone repair and regeneration.展开更多
Microbes are increasingly being implicated in autoimmune disease.This calls for a re-evaluation of how these chronic inflammatory illnesses are routinely treated.The standard of care for autoimmune disease remains the...Microbes are increasingly being implicated in autoimmune disease.This calls for a re-evaluation of how these chronic inflammatory illnesses are routinely treated.The standard of care for autoimmune disease remains the use of medications that slow the immune response,while treatments aimed at eradicating microbes seek the exact opposite-stimulation of the innate immune response.Immunostimulation is complicated by a cascade of sequelae,including exacerbated inflammation,which occurs in response to microbial death.Over the past 8 years,we have collaborated with American and international clinical professionals to research a model-based treatment for inflammatory disease.This intervention,designed to stimulate the innate immune response,has required a reevaluation of disease progression and amelioration.Paramount is the inherent conflict between palliation and microbicidal efficacy.Increased microbicidal activity was experienced as immunopathology-a temporary worsening of symptoms.Further studies are needed,but they will require careful planning to manage this immunopathology.展开更多
Receptor for advanced glycosylation end products(RAGE)is an essential cell surface receptor that detects advanced glycation end products(AGEs)to mediate important inflammatory and immune processes.Inflammation can cau...Receptor for advanced glycosylation end products(RAGE)is an essential cell surface receptor that detects advanced glycation end products(AGEs)to mediate important inflammatory and immune processes.Inflammation can cause insulin resistance,in which the excess glucose in the blood that cannot be stored as fat induces hyperglycemia.Under these conditions,AGEs,high mobility group box 1,S100s,and other inflammatory factors induce the production of tumor necrosis factor-α,interleukin-1β,interleukin(interleukin-6),and other proinflammatory cytokines,inducing chronic inflammation.Herein,we reviewed the relationships between diabetes and RAGE-related inflammation and the associated signaling pathways.Recent progress in targeted therapy against RAGE has also been discussed.Since RAGE is involved in the progression of diabetes,it might be a promising therapeutic target for the prevention and management of this disorder and related complications.展开更多
基金supported by the National Natural Science Foundation of China(82230122,82025035,82104612)Shanghai Municipal Health Commission program(ZY(2021-2023)-0205-02)the Science Foundation for Young Scholars of Zhongshan Hospital,Fudan University(grant No.2021ZSQN70).
文摘Background:Numerous long RNAs were detected in extracellular vesicles(EVs),some of which were related with the tissue origins and immune cell types.This study examined the molecular basis of different traditional Chinese medicine syndrome diagnoses(also called syndrome differentiation)in pancreatic ductal adenocarcinoma.Methods:128 pancreatic ductal adenocarcinoma patients with different syndrome diagnoses were retrospectively reviewed in this study.Long RNA sequencing was conducted to analyze the EV long RNA profile of plasma samples.Differentially regulated EV long RNAs were annotated and assessed for Gene Ontology pathway enrichment using DAVID.The online program xCell were used to perform the cell-type enrichment analysis.Results:An average of 15,000 annotated genes,mainly including messenger RNAs,were stably detected per sample.Different syndrome diagnoses exhibited unique EV mRNA expression profiles and therefore different enriched pathways.Gene Set Enrichment Analysis discovered transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation as the hallmarks of cancer with Shi-Re syndrome.Cell-type enrichment analysis also revealed a varied inflammation/immune cell type distribution among patients with or without Shi-Re diagnosis.Mast cells,platelets and Tregs were significantly enriched but basophils,common lymphoid progenitors,dendritic cells,and conventional dendritic cells were decreased in patients with Shi-Re diagnosis compared with patients without Shi-Re diagnosis.Conclusion:We identified the hallmarks of cancer with different syndrome diagnoses based on plasma EV long RNA sequencing.In particular,transforming growth factor-βand kirsten rat sarcoma viral oncogene homolog signaling activation were the hallmarks of Shi-Re syndrome,which contribute to shape an inflammatory/immune-suppressive tumor microenvironment in pancreatic ductal adenocarcinoma.
文摘Prostate cancer has gradually risen to become the second most common cancer threatening men’s health, and prostate-specific antigen (PSA), as the main screening indicator for prostate cancer, has the defects of low specificity and insufficient diagnostic efficacy. As a novel inflammatory index based on neutrophil, lymphocyte and platelet counts, the systemic immune-inflammation index (SII) has recently become a more powerful biomarker for predicting the occurrence and progression of various malignancies. SII reflects the systemic inflammatory response of prostate cancer patients in a more balanced manner, and has higher predictive value than neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). High SII values are often associated with cancer progression and poor prognosis. This article reviews the research progress of SII in prostate cancer, in order to provide guidance for clinical practice.
基金supported by National key R&D Program of China(2024YFC2311100)the National Social Science Fund of China(2022-SKJJ-B-069).
文摘Immune reconstitution inflammatory syndrome(IRIS)is a collection of inflammatory disorders characterized by the paradoxical worsening of preexisting infections processes following the initiation of antiretroviral therapy in human immunodeficiency virus(HIV)-infected individuals.Diagnosing IRIS accurately and promptly remains challenging in areas with limited medical resources.Herpes simplex virus-2(HSV-2)is highly endemic in sub-Saharan Africa and is one of the primary opportunistic pathogens underlying IRIS,manifesting as mucocutaneous lesions.Here,we report a case of HSV-2-associated IRIS presenting as a genital ulcer,confirmed through nanopore high-throughput sequencing and successfully treated with acyclovir antiviral therapy.This study emphasizes the importance of clinicians maintaining proficiency in recognizing IRIS manifestations and being aware of region-specific opportunistic pathogens,both essential for timely diagnosis and etiology-directed therapy.
基金National Key Research and Development Program of China(NO.2018YFA0108700,NO.2017YFA0105602)NSFC Projects of International Cooperation and Exchanges(NO.81720108004)
文摘Aortic dissection(AD) is a cardiovascular emergency with a high mortality rate, and the risk of death is estimated to increase by 1%-2% per hour. AD is complicated by variable clinical manifestations, and early detection and treatment can give more time for the treatment of patients.Hypertension is the most common cause of AD. In China, 65%-75% of patients with AD have poor blood pressure control. Patients with AD who are less than40 years of age are more likely to suffer from genetic diseases. Connective tissue disease(CTD) plays a dominant role in genetic diseases. Recently, inflammatory immunity, oxidative stress, obstructive sleep apnea-hypopnea syndrome(OSAHS), and other risk factors are being further studied. The new pathogenic factors should be explored to provide an accurate and effective prevention and treatment basis and new diagnostic methods and targets for drug therapy for AD.
基金supported by the Medical Science and Technology Research Fund of Guangdong Province(No.A2022113)。
文摘Background Aortic dissection remains one of the most acute and critical diseases in cardiac surgery,with high mortality and disability rates.In the 1960s,DeBakeyfirst proposed the classification of aortic dissection.Subsequently,various classifications of aortic dissection have been proposed.To facilitate clinicians and medical staff involved in the treatment of aortic dissection to make better assessment of the condition of aortic dissection patients and to make reasonable clinical decisions,we reviewed several current mainstream classification schemes.We hope that this paper inspires other researchers to propose a new,more suitable classification scheme for use in the clinical setting.
基金supported by the National Natural Science Foundation of China,No.30970995the Postgraduate Science Research Innovation Project of Higher Learning University of Jiangsu Province in China,No.CXLX11_0735
文摘Toll-like receptor 3 protein expression has been shown to be upregulated during cerebral ische- mia/reperfusion injury in rats. In this study, rat primary cortical neurons were subjected to oxy- gen-glucose deprivation to simulate cerebral ischemia/reperfusion injury. Chemically synthesized small interfedng RNA （siRNA）-1280, -1724 and -418 specific to toll-like receptor 3 were transfected into oxygen-glucose deprived cortical neurons to suppress the upregulation of toll-like receptor 3 protein expression. Western blotting demonstrated that after transfection with siRNA, toll-like re- ceptor 3 protein expression reduced, especially in the toll-like receptor 3-1724 group. These results suggested that siRNA-1724 is an optimal sequence for inhibiting toll-like receptor 3 expression in cortical neurons following oxygen-glucose deprivation.
文摘Hematopoietic cell transplantation（HCT） is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen（HLA）-matched donor（allogeneic） or from the patient（autologous）. Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease（Gv HD）. Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, Gv HD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT：（1） early complications（in the first month）-related to harvesting of stem cells, during conditioning（drug toxicity, posterior reversible encephalopathy syndrome）, related to pancytopenia,（2） intermediate phase complications（second to sixth month）-central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus,（3） late phase complications（after sixth month）-neurological complications of Gv HD, second neoplasms and relapses of the original disease.
基金National Natural Science Foundation of China,No.22004063Natural Science Foundation of Jiangsu Province,No.20200303+3 种基金Program for Innovative Talents and Entrepreneur in Jiangsu,No.021413006001Fundamental Research Funds for the Central Universities,No.021414380504State Key Laboratory of Analytical Chemistry for Life ScienceNo.5431ZZXM2206。
文摘Coronavirus disease 2019(COVID-19)poses an extremely serious global impact on public healthcare for individuals of all ages,including children.Increasing evidence has shown that liver abnormalities are commonly found in children with COVID-19,and age-related features in innate and adaptive response have been demonstrated.However,there are few reports and studies on COVID-19 related liver injury in children,and the data are scattered.So that many contradictions have arose.This situation is not only due to the serious ethical issues in studying pediatric patients with COVID-19,but also because of the short duration and wide coverage of the COVID-19 epidemic,the severity and complexity of clinical cases varied,as did the inclusion criteria for case reporting and patient outcomes.Therefore,we totaled the incidences,characteristics and pathomechanism of liver injury in children since the COVID-19 outbreak.The etiology of COVID-19-related liver injury is divided into three categories:(1)The direct mechanism involves severe acute respiratory syndrome coronavirus 2 binding to angiotensin-converting enzyme 2 in the liver or bile duct to exert direct toxicity;(2)the indirect mechanisms include an inflammatory immune response and hypoxia;and(3)COVID-19-related treatments,such as mechanical ventilation and antiviral drugs,may cause liver injury.In summary,this minireview provides fundamental insights into COVID-19 and liver dysfunction in children.
基金National key research and development plan of ministry of science and technology for Chinese medicine modernization research key special project(No.2018YFC1705204)Construction project of famous Chinese medicine doctor Liu Jian studio in Anhui province(No.[2018]11)+1 种基金Anhui province’s 12th batch of“115”innovation team(No.[2019]1)National training project for key talents of TCM clinical characteristic technical inheritance(No.[2019]36)。
文摘Objective:To observe the relationship between the distribution of TCM Syndromes of primary Sjogren's syndrome(pSS)and the changes of erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM.Methods:157 diagnosed PSS patients were divided into dampness heat obstructing collaterals syndrome,dryness evil invading lung syndrome,Qi blood stasis syndrome,liver kidney yin deficiency syndrome and Qi Yin deficiency syndrome according to TCM syndrome differentiation standard.The age,course of disease,general health score in international universal quality of life scale,self rating Anxiety scale(SAS),self rating Depression Scale(SDS)and erythrocyte sedimentation rate were observed and detected(ESR,C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM and other immune inflammatory indexes were detected.The relationship between different TCM Syndromes of PSS and molecular level changes of immune inflammatory indexes was analyzed and compared,as well as the impact on quality of life and mental emotion.Results:The overall health score of patients with Qi Yin deficiency syndrome was significantly lower than that of patients with dampness heat obstructing collaterals and dampness evil invading lung syndrome(P<0.01),while the SAS and SDS scores of patients with Qi Yin deficiency syndrome were significantly higher than those of patients with dampness heat invading lung syndrome and dampness heat obstructing collaterals syndrome(P<0.05,P<0.01);ESR,CRP,RF,TNF-α,IL-6,IgA,IgG and IgM related laboratory indexes of patients with dampness heat obstructing collaterals syndrome were significantly higher than those of patients with dry evil invading lung syndrome,liver kidney yin deficiency syndrome and liver kidney yin deficiency syndrome Qi Yin deficiency syndrome and Qi blood stasis syndrome(P<0.05,P<0.01).Correlation test found that the above five syndrome types were positively correlated with hs-CRP,IL-6,TNF-ɑindicators(P<0.05).Conclusion:The overall health,SAS,SDS and related hs-CRP,IL-6,TNF-ɑand some others indexes of SS patients are associated with TCM syndromes.
文摘Objective This study was conducted to evaluate the effects of postoperative immune enhancing enteral nutrition on the immune system,inflammatory responses,and clinical outcome of patients undergoing major abdominal surgery. Methods This study was designed as a multicenter,prospective,randomized and controlled clinical trial. One hundred twenty-four patients undergoing major abdominal surgery were randomly assigned to receive either an immune enhancing enteral diet or an isocaloric and isonitrogenous control enteral diet for seven days. Enteral feeding was initiated 24 hours after surgery. Host immunity was evaluated by measuring levels of IgG,IgM,IgA,CD4,CD8,and CD4/CD8,and the inflammatory response was determined by assessing IL-1α, IL-2, IL-6, IL-10, and TNF-α levels. Infectious complications were also recorded. Results One hundred twenty patients completed the study and four patients were excluded. On postoperative day 9,among patients receiving an immune enhancing diet,IgG,IgA,CD4 and CD4/CD8 levels were significantly higher and TNF-α and IL-6 concentrations were significantly lower compared to the control group. Moreover,among patients receiving an immune enhancing diet,when comparing preoperation to day 9 postoperation levels,increases in IgA,CD4,and CD4/CD8 levels were significantly higher than in control patients and increases in TNF-α concentrations were significantly lower. No statistically significant differences were found between the two groups with regard to infectious complications. Conclusions Postoperative administration of immune enhancing enteral nutrition in patients undergoing major abdominal surgery can positively modulate postoperative immunosuppressive and inflammatory responses.
文摘Objective Sepsis patients exhibit diverse immune states,making it crucial to identify subtypes with distinct inflammatory profiles through Th1/Th2 cytokine data for personalized treatment and improved prognosis.Methods We retrieved data from sepsis patients who underwent Th1/Th2 cytokine testing in Nanfang Hospital,Southern Medical University from June 1,2020,to February 1,2022.An unsupervised K-means clustering method classified participants based on Th1/Th2 cytokine levels,with the primary outcome being the 7-day mortality rate post-ICU admission.Cox proportional hazards and Restricted Mean Survival Time(RMST)analyses were utilized to explore survival outcomes.Results A total of 321 sepsis patients were included.IL-6(HR 1.69,95%CI:1.22,2.34)and IL-10(HR 1.81,95%CI:1.37,2.40)emerged as independent predictors of 7-day mortality.Unsupervised K-means clustering revealed 3 inflammatory/immune subgroups:Cluster 1(n=166,low inflammatory response),Cluster 2(n=99,moderate inflammatory response with immune suppression),and Cluster 3(n=56,strong inflammatory and immune suppression).Compared to Cluster 1,Clusters 2 and 3 had higher 7-day mortality risks(14.4%vs 23.2%,HR=4.30,95%CI:1.51-12.26;14.4%vs 35.7%,HR=7.32,95%CI:2.57-20.79).Conclusion Septic patients in a protective immune response state(Cluster 1)exhibit better short-term prognoses,suggesting the importance of understanding inflammatory/immune states for precise treatment and improved outcomes.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(No.KLZ25H280004 to X.Z.M.).
文摘Metabolic-associated fatty liver disease(MAFLD),a global health burden with limited therapeutic options beyond lifestyle changes,urgently needs novel strategies.We engineered exosome-like nanovesicles(HNVs)from dried honeysuckle(Lonicera japonica),exhibiting significantly more uniform size distribution than conventional herbal extracts and characteristic nanovesicle morphology.Orally delivered HNVs,enriched with bioactive metabolites,dramatically inhibited increased fat vacuoles,lipid droplet deposition,and collagen fibrosis in the livers of mice with MAFLD induced by high-fat diet(HFD).Mechanistically,HNVs orchestrate a dual gut-liver intervention:(1)restoring gut barrier integrity,slashing serum LPS by 1.58-fold and quelling hepatic inflammation;(2)remodeling gut microbiota to suppress bile salt hydrolase(BSH),elevating taurochenodeoxycholic acid(TCDCA)2.07-fold.This microbial shift reprograms enterohepatic signaling by inhibiting the FXR-FGF15-FGFR4 axis,thereby boosting hepatic cholesterol catabolism via bile acid synthases.Critically,efficacy is strictly microbiotadependent:abolished by antibiotics and fully transferable via fecal microbiota transplantation(FMT)from HNV-treated donors.Presenting the first natural nanovesicle platform that concurrently targets gut barrier repair and metabolic reprogramming,HNVs establish a pioneering,multi-targeted therapeutic paradigm for MAFLD,directly linking gut microbial ecology to hepatic pathophysiology with high translational potential.
基金supported by the National Natural Science Foundation of China(No.82274559,81904231).
文摘Osteosarcoma,a prevalent primary malignant bone tumor,predominantly affects both elderly and adolescent populations and usually has an unfavorable prognosis.The specific mechanisms underlying its invasive progression remain unclear.The tumor microenvironment includes not only cancer cells but also bone-related cells,immune cells,tumor-associated nerve cells,and cell-secreted factors.The cooperative and competitive interactions among these cellular components contribute to the proliferation,progression,metastasis,and immune evasion of osteosarcoma.Alterations in bone-related cells,resulting from oncogenic changes,can rapidly increase bone density or aggravate bone loss,thereby promoting the survival of osteosarcoma cells.During the progression of osteosarcoma,genetic alterations in tumor cells lead to changes in extracellular matrix components,influencing the variation in cell-secreted factors,promoting immunosuppression within the tumor microenvironment,and consequently affecting tumor proliferation and progression.This review summarizes the roles of tumor microenvironment components in the pathogenesis of osteosarcoma and discusses existing therapeutic targets.The findings suggest potential research directions for further investigation of osteosarcoma,provide novel insights into the development of osteosarcoma,and may guide the development of more effective anti-tumor strategies.
基金supported by the National Natural Science Foundation of China(81672166).
文摘Human bone marrow stem cells(hBMSCs)play an important role during the fracture healing phase.Previous clinical studies by our research group found that fracture healing time was obviously delayed in patients who underwent splenectomy,for combined traumatic fractures and splenic rupture,which is most likely related to the dysregulation of immune inflammatory function of the body after splenectomy.A large number of studies have reported that the inflammatory factor interleukin-1β plays an important role in the multi-directional differentiation ability and immune regulation of BMSC,but its specific regulatory mechanism needs to be further studied.Recently,long noncoding RNAs(lncRNAs)have attracted remarkable attention owing to their close relationship with stem cell osteogenesis and potential role in various bone diseases.In this study,we explored the molecular mechanism of a novel lncRNA,LncMSTRG.11341.25(LncMSTRG25),in terms of its effects on osteogenic differentiation of hBMSCs.Our results reveal significant up-regulation of LncMSTRG25,osteogenic differentiation markers during the osteogenic differentiation of hBMSCs,and decreased expression of miR-939-5p with an increase in differentiation time.LncMSTRG25 knockdown significantly inhibited the osteogenic ability of hBMSCs.When we knocked down PAX8 alone,we found that the osteogenic ability of hBMSCs was also significantly reduced.The interaction between LncMSTRG25 and PAX8 was verified using the RNA immunoprecipitation assay,RNA pull-down assays,silver staining,and the dual-luciferase reporter.The results show that LncMSTRG25 can function as a sponge to adsorb miR-939-5p,inducing the osteogenic differentiation of hBMSCs by activating PAX8.These findings deepen our understanding of the regulatory role of lncRNA-miRNA-mRNA networks in the immune microenvironment of bone marrow,and highlight the important role played by the spleen as an immune organ in fracture healing.
基金supported by the National Key Research&Development Program of China(grant nos.2021YFA1201000 and 2023YFC2605000)National Natural Science Foundation of China(grant no.82302364)+6 种基金NSFC International Collaboration Key Project(grant no.51861135103)the support by the China Postdoctoral Science Foundation(grant no.2023M730589)the Chongqing Municipal High-Level Medical Talents Program for Young and Middle-Aged Professionals(grant no.YXGD202401-58)Program for Youth Innovation in Future Medicine,Chongqing Medical University(grant no.W170)Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University(grant nos.KRYC-GG-2213 and KRYC-YQ-2201)the Kuanren Talents Enhancement Program(grant no.2024krpy02)the Doctoral Supervisor Cultivation Program of the Second Affiliated Hospital of Chongqing Medical University.
文摘Atherosclerosis(AS)is a chronic inflammatory condition influenced by glucose and lipid disorders,oxidative stress,and thrombosis,reflecting the complexity of its pathological process.The development of accurate experimental models that simulate human AS is essential for understanding its initiation and progression.This review summarizes the current AS research models and analyzes their specific application scenarios.We discuss tissue-engineered blood vessels(TEBVs)and vessels-on-a-chip(VoCs),which leverage tissue engineering and precise microenvironmental control to construct in vitro models that closely resemble the structure and function of human AS.Isolated vessel segments from live animals provide a valuable tool for investigating human AS due to their physiological similarity,controllability,and reproducibility.The review further outlines the construction of AS animal models through high-fat diets and gene-editing techniques,highlighting how immune-inflammatory responses,mechanical arterial injury,and hemodynamic changes accelerate model development.This comprehensive analysis highlights the potential of AS models to revolutionize theranostic applications in clinical translational research,paving the way for more personalized and effective treatments for AS in the near future.
文摘Diabetic nephropathy （DN） is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomeruIar basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial-mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte-endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.
基金the National Natural Science Foundation of China(NSFC No.31872988No.31572429)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PADA).
文摘Dairy cattle are frequently fed high-concentrate(HC)diets in modern intensive feeding systems,especially in the transition period.During this period,cows face many alterations that include hormonal changes and shifting to a lactating state.Switching to a HC diet that may disrupt the ruminal microbiota balance can lead to subacute ruminal acidosis(SARA).Moreover,the main factor shaping the rumen microbiota is dietary composition,especially the ratio of starch to fibrous carbohydrates.Feeding highly fermentable carbohydrate diets after adaptation to forage diets leads to a rumen fermentation rate that exceeds rumen absorption and buffering rates,resulting in a reduction in ruminal pH.As a result of Gram-negative bacterial cell lysis,an increase in harmful ruminal bacterial metabolites,including lipopolysaccharide,lactic acid,and histamine,is observed.The interactions between the host immune system and the ruminal microbiota play an essential role in many physiological processes and the development of the disorder.Progress in DNA sequencing and bioinformatics platforms provides new opportunities to investigate the composition of ruminal microbes and yields unique advances in understanding ecology of the rumen.Subacute ruminal acidosis is linked with a change in the ruminal microbiota structure and richness and with other metabolic disorders;such as rumenitis,milk fat depression,laminitis,and liver abscesses.Therefore,this review aims to explore a better understanding of the crosstalk between diet and microbiota in the prevalence of rumen acidosis and its consequences,which is crucial for control strategies such as feeding management,and supplementation with thiamine,prebiotics,and probiotics.
基金supported by the National Natural Science Foundation of China(82160175/81860326)Department of Science and Technology of Yunnan Province of China(2017FF117(-062)/202101AY070001-078)100 Talents Program of Kunming Medical University(Limei Li).
文摘Wound healing is a highly orchestrated process involving a variety of cells,including immune cells.Developing immunomodulatory biomaterials for regenerative engineering applications,such as bone regeneration,is an appealing strategy.Herein,inspired by the immunomodulatory effects of gastrodin(a bioactive component in traditional Chinese herbal medicine),a series of new immunomodulatory gastrodin-comprising biodegradable polyurethane(gastrodin-PU)and nano-hydroxyapatite(n-HA)(gastrodin-PU/n-HA)composites were developed.RAW 264.7 macrophages,rat bone marrow mesenchymal stem cells(rBMSCs),and human umbilical vein endothelial cells(HUVECs)were cultured with gastrodin-PU/n-HA containing different concentrations of gastrodin(0.5%,1%,and 2%)to decipher their immunomodulatory effects on osteogenesis and angiogenesis in vitro.Results demonstrated that,compared with PU/n-HA,gastrodin-PU/n-HA induced macrophage polarization toward the M2 phenotype,as evidenced by the higher expression level of pro-regenerative cytokines(CD206,Arg-1)and the lower expression of pro-inflammatory cytokines(iNOS).The expression levels of osteogenesis-related factors(BMP-2 and ALP)in the rBMSCs and angiogenesis-related factors(VEGF and BFGF)in the HUVECs were significantly up-regulated in gastrodin-PU/n-HA/macrophage-conditioned medium.The immunomodulatory effects of gastrodin-PU/n-HA to reprogram macrophages from a pro-inflammatory(M1)phenotype to an anti-inflammatory and pro-healing(M2)phenotype were validated in a rat subcutaneous implantation model.And the 2%gastrodin-PU/n-HA significantly decreased fibrous capsule formation and enhanced angiogenesis.Additionally,2%gastrodin-PU/n-HA scaffolds implanted in the rat femoral condyle defect model showed accelerated osteogenesis and angiogenesis.Thus,the novel gastrodin-PU/n-HA scaffold may represent a new and promising immunomodulatory biomaterial for bone repair and regeneration.
文摘Microbes are increasingly being implicated in autoimmune disease.This calls for a re-evaluation of how these chronic inflammatory illnesses are routinely treated.The standard of care for autoimmune disease remains the use of medications that slow the immune response,while treatments aimed at eradicating microbes seek the exact opposite-stimulation of the innate immune response.Immunostimulation is complicated by a cascade of sequelae,including exacerbated inflammation,which occurs in response to microbial death.Over the past 8 years,we have collaborated with American and international clinical professionals to research a model-based treatment for inflammatory disease.This intervention,designed to stimulate the innate immune response,has required a reevaluation of disease progression and amelioration.Paramount is the inherent conflict between palliation and microbicidal efficacy.Increased microbicidal activity was experienced as immunopathology-a temporary worsening of symptoms.Further studies are needed,but they will require careful planning to manage this immunopathology.
基金supported by the National Natural Science Foundation of China(No.22177030).
文摘Receptor for advanced glycosylation end products(RAGE)is an essential cell surface receptor that detects advanced glycation end products(AGEs)to mediate important inflammatory and immune processes.Inflammation can cause insulin resistance,in which the excess glucose in the blood that cannot be stored as fat induces hyperglycemia.Under these conditions,AGEs,high mobility group box 1,S100s,and other inflammatory factors induce the production of tumor necrosis factor-α,interleukin-1β,interleukin(interleukin-6),and other proinflammatory cytokines,inducing chronic inflammation.Herein,we reviewed the relationships between diabetes and RAGE-related inflammation and the associated signaling pathways.Recent progress in targeted therapy against RAGE has also been discussed.Since RAGE is involved in the progression of diabetes,it might be a promising therapeutic target for the prevention and management of this disorder and related complications.
