Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), leading to a high incidence of surgical interventions and significant disability. Despite its clinical relevance, no targeted pharmacological therapies are currently available. This review aims to explore the underlying mechanisms driving intestinal fibrosis and address unresolved scientific questions, offering insights into potential future therapeutic strategies. We conducted a literature review using data from PubMed up to October 2024, focusing on studies related to IBD and fibrosis. Intestinal fibrosis results from a complex network involving stromal cells, immune cells, epithelial cells, and the gut microbiota. Chronic inflammation, driven by factors such as dysbiosis, epithelial injury, and immune activation, leads to the production of cytokines like interleukin (IL)-1β, IL-17, and transforming growth factor (TGF)-β. These mediators activate various stromal cell populations, including fibroblasts, pericytes, and smooth muscle cells. The activated stromal cells secrete excessive extracellular matrix components, thereby promoting fibrosis. Additionally, stromal cells influence the immune microenvironment through cytokine production. Future research would focus on elucidating the temporal and spatial relationships between immune cell-driven inflammation and stromal cell-mediated fibrosis. Additionally, investigations are needed to clarify the differentiation origins of excessive extracellular matrix-producing cells, particularly fibroblast activation protein (FAP) + fibroblasts, in the context of intestinal fibrosis. In conclusion, aberrant stromal cell activation, triggered by upstream immune signals, is a key mechanism underlying intestinal fibrosis. Further investigations into immune-stromal cell interactions and stromal cell activation are essential for the development of therapeutic strategies to prevent, alleviate, and potentially reverse fibrosis.
Humans ; Fibrosis/metabolism* ; Inflammatory Bowel Diseases/pathology* ; Animals ; Transforming Growth Factor beta/metabolism* ; Intestines/pathology*

OBJECTIVES: The major histocompatibility complex class I chain-related gene A (MICA), a component of the human leukocyte antigen (HLA) gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among MICA gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism. METHODS: Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. MICA genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of MICA alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined. RESULTS: Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified MICA alleles. The most common alleles in the rosacea group were MICA*010:01, MICA*008:04, and MICA*019:01. The frequencies of MICA*002:01 and MICA*027 were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and MICA*010:01 were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all P<0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of MICA-A4 and MICA-A9 were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas MICA-A6 was higher (10.12% vs 4.03%; all P<0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C₃₆+M₁₂₉+K₁₇₃+G₂₀₆+W₂₁₀+S₂₁₅) and Type II (Y₃₆+V₁₂₉+E₁₇₃+S₂₀₆+R₂₁₀+T₂₁₅). Type I MICA variants were significantly associated with rosacea susceptibility. CONCLUSIONS MICA gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the MICA gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.
Humans ; Polymorphism, Single Nucleotide ; Histocompatibility Antigens Class I/genetics* ; Rosacea/genetics* ; Genetic Predisposition to Disease/genetics* ; Female ; Male ; Adult ; Middle Aged ; Genotype ; Alleles ; Gene Frequency ; Haplotypes ; Case-Control Studies ; Aged ; High-Throughput Nucleotide Sequencing

ObjectiveTo investigate the association of particulate matter and ozone with the prevalence of non-alcoholic fatty liver disease (NAFLD) in a district of Shanghai, and to provide epidemiological evidence for the further identification of early health hazards of air pollution and for the prevention and control of NAFLD. MethodsBased on Songjiang Sub-cohort of Shanghai Natural Population Cohort, a cross-sectional survey design was used to recruit participants from 2016 to 2017. Annual average exposure levels to air pollution from 2009 to 2017 were matched to the participant’s residential address using a high-resolution and high-quality ambient air pollutants dataset in China. NAFLD was diagnosed according to the “Guidelines for the prevention and treatment of metabolism⁃associated (non⁃alcoholic) fatty liver disease” by the Chinese Medical Association. Multivariate logistic regression models were employed to analyze the association between air pollution and the prevalence of NAFLD, and stratified analyses were used to compare differences by age, gender, obesity, and lifestyle habits within subgroups. ResultsA total of 32 791 individuals were included in the study. The prevalence of NAFLD among community residents in suburban Shanghai was 38.88%. For every 1 μg·m^-3 increase in PM₁, PM_2.5, PM₁₀, or O₃, the risk of NAFLD increased correspongdinglt, with the odds ratios (95%CI) of 1.071 (1.043‒1.099), 1.065 (1.042‒1.089), 1.041 (1.027‒1.055), or 1.061 (1.032‒1.091), respectively. There were differences in effects across different gender, age, and obesity status subgroups. ConclusionPM₁, PM_2.5, PM₁₀, and O₃ are positively associated with an increased risk of NAFLD. Stratified analyses reveal that individuals aged 65 years old or above exhibited greater susceptibility to PM₁, PM_2.5, and O₃, whereas those aged less than 65 years old are more vulnerable to PM₁₀. Males are more sensitive to PM₁ and O₃, and females are more susceptible to PM_2.5 and PM₁₀. The association between air pollutant exposure and NAFLD risk is more pronounced among obese participants compared to that in non-obese counterparts.

Objective:Human leukocyte antigen(HLA)B27 is a susceptibility allele of ankylosing spondylitis(AS),and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS,but current typing methods such as sequence specific primer polymerase chain reaction(PCR-SSP)still possess limitation.Therefore,this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing(PCR-SBT). Methods:Peripheral blood of 116 patients with suspected AS(suspected AS group)and 121 healthy volunteers(control group)admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT.Among the patients in the suspected AS group,23 patients were finally diagnosed with AS(confirmed AS group),and the remaining 93 undiagnosed patients served as the non-confirmed AS group.PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS,and the results of the 2 methods were compared. Results:The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group[11.63%vs 2.48%;P<0.001,odds ratio(OR)=5.18,95%confidence interval(CI)2.097 to 12.795].B*27:04,B*27:05,B*27:06,and B*27:07 were detected in the suspected AS group and the control group.The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group(9.48%vs 1.24%;P<0.001,OR=8.346,95%CI 2.463 to 28.282).The positive rate of B27 in the suspected AS group and the confirmed AS group(B27+/+ and B27+/-)was significantly higher than that in the control group(χ2=16.579,P<0.001;χ2=94.582,P<0.001,respectively).Among the confirmed AS group,21 were HLA-B27 carriers,and the B27 positive rate in the confirmed AS group was 91.3%.PCR-SBT could achieve high resolution typing of the HLA-B gene locus,with higher sensitivity,specificity,positive predictive value,negative predictive value,and accuracy than PCR-SSP. Conclusion:PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province.The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

Organ transplantation is the effective method to replace the function of the patient failed organ. But it is very disappoint that recipients have to receive the long-term immunosuppression regimens for prevention of allograft rejection. To induce allograft immune tolerance without immunosuppressant is in great demand. Although several tolerance strategies for organ transplant have been proposed, even some has already been tested in the 1st clinical trial, these strategies haven ' t approached to ideal efficacy. Helminths are remarkably successful parasites to achieve immunological tolerance to host immune response. It is now well established that the parasites′ success is the result of active immunomodulation of their hosts ' immune response. We suggest that injecting B cells from donor spleen and helminth soluble antigens, recipient might become tolerance to donor organ, but not tolerated to other antigens. Research based on this approach has great translated value for future clinic practice.

Objective To investigate the extraction and purification methods of serum specific endothelial cell antibody of renal transplant recipients with rejection after renal transplantation.Methods Human umbilical vein endothelial cell (HUVEC)was isolated and cultured.The serum samples of the renal transplant recipients with poor renal function after renal transplantation were collected.Specific endothelial cell antibody was screened out with flow cytometry;antibodies against human leukocyte antigen (HLA)and major histocompatibility complex class Ⅰ-related chain A (MICA)were detected by Luminex platform.After the existence of specific endothelial cell antibody in the serum sample was confirmed,specific endothelial cell antibody was absorbed with HUVEC.The cell was washed and then the absorbed antibody was eluted from the cell membrane.Antibody IgG in the eluent was purified and concentrated again with Protein-A /G magnetic beads.Antibody activity in the eluent was detected by flow cytometry and the purified specific endothelial cell antibody (IgG)was identified by SDS-polyacrylamide gel (SDS-PAGE)and Western blot.Results In the serum of 386 renal transplant recipients,the serum samples of 5 renal transplant recipients with serum creatinine (Scr) >400 μmoI /L,negative anti-HLA antibody,negative anti-MICA antibody and median fluorescence intensity (MFI) >16 were selected.Purified specific endothelial cell antibody IgG showed immunoglobulin heavy chain (purity > 95%)by SDS-PAGE gel.Flow cytometry showed that the purified antibody had the feature of rebinding with the surface antigen of vascular endothelial cell.Conclusions The purification method of using human umbilical vein endothelial cell to absorb specific endothelial cell antibody in the serum of renal transplant recipients may obtain good effect.

OBJECTIVETo review the role of polymorphism of major histocompatibility complex class I-related chain A (MICA) gene and antibodies against MICA antigens in transplant immunology.

DATA SOURCESThe data used in this review were mainly from our own results and from the relevant English language literatures published from 1999 to 2010. Some data presented in this review are in press.

STUDY SELECTIONArticles regarding MICA gene discovery and pioneering finding of antibodies against MICA antigen and allograft rejection were selected. This review chronicles the development of our understanding of the role that MICA antigens and antibodies may play in organ transplantation.

RESULTSPolymorphic glycoprotein MICA antigens were detected on freshly isolated human umbilical cord endothelial cells, but not on peripheral lymphocytes. Antibodies were found and typing of recipients and donors by sequencing the MICA alleles has established that de novo antibodies produced in kidney transplant recipients are directed at mismatched MICA epitopes and are associated with acute rejection and chronic transplant failure. The specificity of antibodies against the epitopes of MICA antigens were well characterized by donor MICA typing, single antigen array testing with antibody absorption and elution. Acute graft-versus-host disease was observed in stem-cell recipients who were mismatched for MICA.

CONCLUSIONSImmunization against mismatched MICA epitopes encountered in donor organs after transplantation may result in antibodies against MICA alleles. Testing for MICA donor-specific antibodies (DSA) which are associated with early failure of kidney transplants may be helpful for identifying some of the targets of antibodies against antigens other than the human leukocyte antigen (HLA) and for improving transplantation outcome.

Antibodies ; immunology ; Graft Rejection ; immunology ; Histocompatibility Antigens Class I ; immunology ; Humans ; Organ Transplantation

OBJECTIVE:To establish an HPLC method for the determination of the content of Indirubin in Banlangen granules. METHODS: The choromatographic separation was performed on C18 column (250 mm?4.6 mm,5 ?m) with column temperature set at 30 ℃. The mobile phase consisted of methanol-water(76∶24) at a flow rate of 1.0 mL?min-1.The dete-ction wavelength was set at 289 nm.RESULTS:The calibration curve of Indirubin was linear in the range of 0.073 5～0.612 5 ?g (r=0.999 9) and the average recovery was 98.78%(RSD=0.74%,n=9).CONCLUISON: The method is rapid and accurate, and it can be used for quality control of Banlangen granules.