Microbiome: Role in Inflammatory Skin Diseases.

As the body's largest organ, the skin harbors a highly diverse microbiota, playing a crucial role in resisting foreign pathogens, nurturing the immune system, and metabolizing natural products. The dysregulation of human skin microbiota is implicated in immune dysregulation and inflammatory responses. This review delineates the microbial alterations and immune dysregulation features in common Inflammatory Skin Diseases (ISDs) such as psoriasis, rosacea, atopic dermatitis(AD), seborrheic dermatitis(SD), diaper dermatitis(DD), and Malassezia folliculitis(MF).The skin microbiota, a complex and evolving community, undergoes changes in composition and function that can compromise the skin microbial barrier. These alterations induce water loss and abnormal lipid metabolism, contributing to the onset of ISDs. Additionally, microorganisms release toxins, like Staphylococcus aureus secreted α toxins and proteases, which may dissolve the stratum corneum, impairing skin barrier function and allowing entry into the bloodstream. Microbes entering the bloodstream activate molecular signals, leading to immune disorders and subsequent skin inflammatory responses. For instance, Malassezia stimulates dendritic cells(DCs) to release IL-12 and IL-23, differentiating into a Th17 cell population and producing proinflammatory mediators such as IL-17, IL-22, TNF-α, and IFN-α.This review offers new insights into the role of the human skin microbiota in ISDs, paving the way for future skin microbiome-specific targeted therapies.

Evaluation of two laboratory model methods for diarrheal irritable bowel syndrome.

BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder, and the underlying pathogenic mechanism is still unclear. Animal models that mimic the pathological state of IBS-D patients were constructed to provide a reference for later drug research and model development. METHODS: The IBS-D model was induced using restraint stress and chemical stimulation (rhubarb), and rats were divided into normal control group (NC), chemically stimulated group (CS), and restraint stress group (RS). Visceral motility responses to Colorectal Balloon Dilation (CRD) were measured by Abdominal Withdrawal Reflex (AWR); evaluation of faecal properties and water content; determination of colonic tissue tight junction (TJ) mRNA expression by RT-PCR; measurement of inflammatory cytokines by ELISA; and intestinal flora and short chain fatty acids. RESULTS: Compared to NC group, CS and RS group rats showed increased intestinal sensitivity and Bristol stool score, significant diarrheal symptoms and weight loss. Mucin 2, ZO-1, OCLN, CLDN4 mRNA expression was reduced and the intestinal mucosal barrier function was diminished. In addition, the levels of inflammatory factors IL-1ß, IL-6, IL-8, IL-10 and TNF-α increased, the abundance and diversity of intestinal flora decreased, the content of beneficial bacteria such as Bifidobacteria decreased, and SCFAs such as acetic acid, propionic acid and butyric acid decreased to different degrees. Although, no significant difference was observed for any molecular and inflammatory marker, but compared to CS group, RS group had less water in the stool, higher visceral sensitivity, and higher relative abundance of beneficial intestinal bacteria such as Actinobacteria. CONCLUSION: In conclusion, restraint stress combined with chemical stimulation can mimic the pathological state of diarrhoea symptoms, visceral hypersensitivity, reduced intestinal mucosal barrier permeability, immune regulatory dysfunction and dysbiosis in IBS-D patients. However, herbs with antibacterial effects such as rhubarb and senna, for example, are not suitable as the first choice for chemical stimulation, as they may lead to a decrease in harmful bacteria and an increase in beneficial bacteria in the intestinal fraction and do not perfectly mimic the imbalanced state of intestinal flora in IBS-D patients, while restraint stress may be a key factor in modelling.

Effect of Shenling Baizhu powder on immunity to diarrheal disease: A systematic review and meta-analysis.

Background: Diarrhea is one of the leading causes of death worldwide and is associated with immune dysfunction. The modulatory effects of Shenling Baizhu powder (SLBZS) on immune function in diarrheal disease have been validated in various animal models. However, the results of these studies have not been systematically evaluated. This study aimed to evaluate the preclinical data on SLBZS for the treatment of diarrhea from an immunological perspective. Methods: PubMed, Embase, Cochrane Library, CNKI, Wanfang Database, VIP, and Chinese Medicine Database were searched for all animal trials on SLBZS for the treatment of diarrhea published up to April 2022. Standardized mean differences (SMD) were used as effect sizes in the meta-analysis of continuous variables, including immune organs, immune cells, and immune cytokines. Subgroup analysis was performed according to animal species and disease models. The GRADE was used to assess the quality of evidence. Results: A total of 26 studies were included. Meta-analysis showed that compared to those in the model group, SLBZS significantly increased body weight [SMD = 1.54, 95% confidence interval (CI) (1.06, 2.02)], spleen mass [SMD = 1.42, 95% CI (0.98, 1.87)], thymus mass [SMD = 1.11, 95% CI (0.69, 1.53)], macrophage phagocytic capacity (SMD = 1.07, 95% CI [0.59, 1.54]), sIgA [SMD = 1.04, 95% CI (0.33, 1.74)], RBC-C3b-RR [SMD = 1.16, 95% CI (0.65, 1.67)], IL-2 [SMD = 1.52, 95% CI (0.89, 2.14)] and decreased diarrhea scores [SMD = -1.40, 95% CI (-2.03, -0.87)], RBC-IC-RR [SMD = -1.40, 95% CI (-1.94, -0.87)], and IL-8 [SMD = -2.80, 95% CI (-3.54, -2.07)]. Subgroup analysis showed that SLBZS regulated TNF-α, IL-1ß, and IL-10 in rats and mice, and improved IL-6 and IL-10 in different diseases, with differences between subgroups (p < 0.05). Owing to heterogeneity, the reliability of the results remains to be verified. The quality of evidence was "very low". Conclusion: SLBZS improve diarrhea symptoms by enhancing immune function. It has curative effects with differences between different species and diseases, however, because the reporting in the original studies was too unclear to be assessed, the analysis was inconclusive. For higher quality evidences, future research should pay attention to the scientific rigor of the experimental design and the completeness of the reported results.

Comparison of the Efficacy of Danhong Injections at Different Time-points During the Perioperative Period of Acute Myocardial Infarction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Objectives: Danhong injections (DHI) are widely used in the treatment of acute myocardial infarction (AMI). As there are no guidelines for the timing of DHI in the peri-percutaneous coronary intervention (PCI) period for AMI, we investigated the effects of DHI timing. Methods: We reviewed reports published before September 30, 2020 in PubMed, embase, the Cochrane Central Register of Controlled Trials, the Chinese BioMedical database, Chinese VIP database, Wanfang database, and Chinese National Knowledge Infrastructure database. Only randomized controlled trials of DHI with percutaneous coronary intervention for AMI were included. Methodological quality was assessed using the Cochrane evaluation manual 5.3.3 criteria. A meta-analysis was performed, and forest plots were drawn. Results: We included 23 studies which all revealed that patients in DHI groups had better efficacy than control groups. Subgroup analysis revealed that DHI administered intraoperatively and continued postoperatively was more effective in increasing left ventricular ejection fraction when compared to other time-points (p < 0.001). The pre- and intraoperative use of DHI could improve reflow more effectively than conventional treatment, while the effect was not significant in the postoperative intervention study (p = 0.654). The 16 postoperative interventions revealed that the effect of DHI at 14 days was better than that at 7 and 10 days for hs-CRP (p = 0.013), the 10-days treatment produced better results for CK-MB than for the other treatments (p < 0.001) and a dosage of 30 ml proved most effective for IL-6 (p < 0.001). Conclusion: DHI proved to be superior to conventional Western medicine in reducing the incidence of adverse cardiac events, promoting reperfusion, improving cardiac function, reducing inflammatory factors, and protecting the myocardium. DHI should be administered early in the perioperative period and continued postoperatively because of its ability to improve cardiac function. Furthermore, in the PCI postoperative, 30 ml is recommended to inhibit IL-6 levels, for patients with high hs-CRP, a course of 14 days is most effective, for patients with obvious abnormalities of CK-MB, a 10-days course of treatment is recommended. However, due to the limited number and quality of the original randomized controlled trials, our conclusions need large, multi-centre RCTs to validation.