The intestinal barrier is the primary defense that separates the host from the external environment, possessing several crucial physiological functions, including nutrient digestion, absorption, and protection against potentially harmful dietary antigens and pathogenic microorganisms. Nevertheless, various factors, such as diet, medications, circadian rhythm disturbances, gut microbiota, microbial metabolites, and genetic predisposition, can disrupt the intestinal barrier. Such disruption may lead to bacterial translocation, subsequently triggering enterohepatic and systemic inflammation. Impaired intestinal barrier has been implicated in the pathogenesis of numerous diseases, particularly chronic gut and liver diseases. In this review, we will summarize the fundamental functions of intestinal barrier and discuss clinical correlations between intestinal barrier dysfunction and diseases such as colitis, colorectal cancer, and chronic liver diseases including metabolic dysfunction-associated steatohepatitis, alcohol-associated liver disease, and primary sclerosing cholangitis. Additionally, we will also highlight some potential therapeutic strategies aimed at restoring barrier integrity to improve disease management.

With the rapid development and expansion of the scale of the industry of Chinese materia medica,a large number of by-products in the process industrialization of Chinese materia medica have been produced,among which,the solid by-products of Chinese materia medica have been favoured by researchers due to the fact that they are rich in a large number of proteins,cellulose,hemicellulose,lignin,etc.,which can be used in the preparation of high value-added products.Therefore,the authors elaborated on the research on biochemical conversion,thermochemical conversion,resource oriented chemical components,preparation of biomass fuel,new composite materials and high-efficiency adsorbent of solid by-products in the process of industrialization of Chinese materia medica in recent years,aiming to provide theoretical basis for the comprehensive and high-value utilization of the solid by-products of Chinese materia medica and extension of the industrial chain.

Bone diseases, such as osteoporosis and osteoarthritis, have emerged as pressing public health concerns requiring immediate attention and resolution. Cellular therapy and tissue engineering techniques are among the most promising therapeutic approaches for such conditions. Human induced pluripotent stem cells (hiPSCs) possess remarkable capacity for indefinite self-renewal in vitro and the ability to differentiate into all somatic cell types originating from the three germ layers, thereby making them a promising source of osteoblasts. Consequently, it is crucial to establish a well-delineated system for osteogenic differentiation of hiPSCs in vitro, with the aim to generate osteoblast-like cells that conform to clinical application standards. Numerous research teams have achieved substantial advancements in both the direct osteogenic differentiation of hiPSCs and the indirect pathway via mesenchymal stem cells. In this article, we provide a comprehensive review of these two osteogenic differentiation pathways and their current applications, with the aim of serving as a valuable reference for bone regeneration technologies. Current research efforts have relied on embryoid body formation and monolayer induction methods utilizing biomaterials to develop a system that facilitates in vitro culture and osteogenic differentiation of hiPSCs. However, the existing research is primarily constrained by unclear system components and low efficiency. Therefore, the development of a stepwise and three-dimensional induction system based on stringent regulation by specific compounds is a primary research direction for the future.

BACKGROUND: The addition of growth factiors is commonly applied to improve the osteogenic differentiation of stem cells. However, for human pluripotent stem cells (hPSCs), their complex differentiation processes result in the unknown effect at different stages. In this study, we focused on the widely used bone forming peptide-1 (BFP-1) and investigated the effect and mechanisms of its addition on the osteogenic induction of hPSCs as a function of the supplementation period. METHODS: Monolayer-cultured hPSCs were cultured in osteogenic induction medium for 28 days, and the effect of BFP-1 peptide addition at varying weeks was examined. After differentiation for varying days (0, 7, 14, 21 and 28), the differentiation efficiency was determined by RT–PCR, flow cytometry, immunofluorescence, and alizarin red staining assays. Moreover, the expression of marker genes related to germ layers and epithelial-mesenchymal transition (EMT) was investigated at day 7. RESULTS: Peptide treatment during the first week promoted the generation of mesoderm cells and mesenchymal-like cells from hiPSCs. Then, the upregulated expression of osteogenesis marker genes/proteins was detected in both hESCs and hiPSCs during subsequent inductions with BFP-1 peptide treatment. Fortunately, further experimental design confirmed that treating the BFP-1 peptide during 7–21 days showed even better performance for hESCs but was ineffective for hiPSCs. CONCLUSION The differentiation efficiency of cells could be improved by determining the optimal treatment period.Our study has great value in maximizing the differentiation of hPSCs by adding osteogenesis peptides based on the revealed mechanisms and promoting the application of hPSCs in bone tissue regeneration.

Sepsis is a leading life-threatening problem in intensive care medicine. The recent studies have given insights into the transition from inflammation to long-term immunosuppression in sepsis. This condition might cause physiological changes that comprise the lipopolysaccharide (LPS) tolerance. Most studies about the LPS tolerance focus on the reduced ability of macrophages to secrete pro-inflammatory cytokines. Although this method has identified various molecular changes, it remains ambiguous since changes in the whole cell population are measured as an average and markers are required for cell recognition. A fast and label-free method is in demand to detect cell tolerance and screen therapeutic agents that might reverse the process. In this study, direct current insulator-based dielectrophoresis (DC-iDEP) was used to characterize the biophysical properties (EKMr) of inflamed cells, LPS-tolerant cells, and cells treated with therapeutic agents. The results showed that the EKMr of these cells was 4.28×10⁸, 3.13×10⁸, and 4.25×10⁸ V/m², respectively, suggesting that the established method was useful in distinguishing LPS-tolerant cells. The device holds the promise to be applied in medical diagnosis and medicine screening.
Lipopolysaccharides/pharmacology* ; Animals ; Mice ; Macrophages/metabolism* ; Immune Tolerance/drug effects* ; RAW 264.7 Cells ; Drug Evaluation, Preclinical

In order to reduce the disease burden of chronic hepatitis B (CHB) and improve the treatment rate of CHB, the indications for anti-viral therapy have been gradually expanded and simplified in guidelines for the prevention and treatment of CHB released by Chinese Medical Association from 2005 to 2022. This article elaborates on the evolution in the indications for anti-viral therapy in CHB from the five aspects of converging indications of HBeAg-positive and HBeAg-negative CHB, reduction in the treatment threshold of HBV DNA, reduction in the treatment threshold of serum alanine aminotransferase, emphasis on the risk factors for disease progression, and gradual loosening of the requirements for virological indicators in patients with liver cirrhosis.

Glaucoma is the first irreversible blinding eye disease in the world, and vision loss due to glaucoma is related to the obstruction of the aqueous humor drainage channel, which leads to increased intraocular pressure and damage to the optic nerve.The relationship between the ocular lymphatic system and the aqueous humor drainage pathway is of important significance.Exploration of the generation and development of ocular lymphatic vessels and identification of the markers of ocular lymphatic vessels (LVs) are important for researching whether lymphatic pathways are involved in the aqueous humor outflow in glaucoma.Relationship between aqueous humor drainage system and ocular lymphatic drainage pathway can be elucidated from following aspects: (1)podoplanin is highly expressed in trabecular meshwork endothelial cells, while no expression of platelet-endothelial cell adhesion molecule (CD31) is found, suggesting that there is a close relationship between trabecular meshwork and LVs; (2)there are similarities in morphology, molecules and function between Schlemm canal and LVs, and Schlemm canal not only has some characteristics of LVs and blood vessels, but also some undiscovered characteristics of blood vessels and lymphatic endothelial cells; (3)the bulbar conjunctiva is rich in LVs, suggesting that the bulbar conjunctiva has active tissue drainage and immunoregulatory functions; (4)the sclera is mainly composed of collagen fibers and lacks real LVs, but many lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE-1)-positive macrophages around the scleral vessels are regulated by tissue-specific factors; (5)multiple lymphatic markers can be detected in ciliary body, and suspected LVs can be observed by electron microscopy; (6)various lymphatic markers can be expressed in a single choroidal cell, with LYVE-1 expressed highest.Research progress in the lymphatic system of LVs, lymphatic markers, and aqueous humor outflow was reviewed in this article.

Objective:Our study aims to determine histological regression and clinical improvement after long-term antiviral therapy in hepatitis B virus-related cirrhosis patients.Methods:Treatment-na?ve chronic hepatitis B patients with histologically or clinically diagnosed liver cirrhosis were enrolled. Liver biopsies were performed after 5 years entecavir-based antiviral treatment. Patients were followed up every 6 months. Cirrhosis regression was evaluated based on Metavir system and P-I-R score. Clinical improvement was evaluated before and after the long-term treatment. Kruskal Wallis test and Wilcoxon signed-rank test were used for continuous variables, Fisher's exact test was used for categorical variables and multivariate analysis was performed using logistic regression analysis.Results:Totals of 73 patients with HBV-related liver cirrhosis were enrolled. Among them, 30 (41.1%) patients were biopsy proved liver cirrhosis and the remaining 43 (58.9%) cirrhotic patients were diagnosed by clinical features. Based on Metavir system and P-I-R score, 72.6% (53/73) patients attained histological regression. Furthermore, 30.1% (22/73) were defined as significant regression (Metavir decrease ≥2 stage), 42.5% (31/73) were mild regression (Metavir decrease 1 stage or predominantly regressive by P-I-R system if still cirrhosis after treatment) and 27.4% (20/73) were the non-regression. Compared to levels of clinical characteristics at baseline, HBV DNA, ALT, AST, liver stiffness(decreased from 12.7 to 6.4 kPa in significant regression, from 18.1 to 7.3 kPa in mild regression and from 21.4 to 11.2 kPa in non-regression)and Ishak-HAI score significantly decreased after 5 years of anti-HBV treatment, while serum levels of platelets and albumin improved remarkably ( P<0.05). In multivariate analysis, only the pre-treatment liver stiffness level was associated with significant regression ( OR=0.887, 95% CI: 0.802-0.981, P=0.020). Conclusions:After long-term antiviral therapy, patients with HBV-related cirrhosis are easily to attain improvements in clinical parameters, while a certain percentage of these patients still cannot achieve histological reversal.

Objective To investigate the regulatory effect of Jiedu Huayu Tongfu prescription on intestinal homeostasis in patients with hepatitis B cirrhosis with liver-gallbladder damp-heat syndrome, as well as its effect on endotoxin, inflammatory factors, and cellular immune function. Methods A total of 72 patients who attended The First Affiliated Hospital of Henan University of Chinese Medicine from June 2019 to January 2021 and met the diagnostic and inclusion criteria were enrolled as subjects and then randomly divided into observation group and control group, with 36 patients in each group. In the treatment group, 2 patients were lost to follow-up, 2 patients were excluded, and 32 patients completed the study; in the control group, 2 patients were lost to follow-up, 1 patient was excluded, and 33 patients completed the study. In addition to the basic treatment including antiviral therapy and liver-protecting treatment, the patients in the observation group were given Jiedu Huayu Tongfu granules, and those in the control group were given oral administration of Bifidobacterium tetravaccine tablets; the course of treatment was 4 weeks for both groups. The 16S rDNA sequencing technique was used for sequencing of fecal flora, and the two groups were measured in terms of the changes in liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and albumin (Alb)], endotoxin (ET), levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and T lymphocyte subsets (CD3 + T, CD4 + T, CD8 + T, and CD4 + /CD8 + ) after treatment. For normally distributed continuous data with homogeneity of variance, the paired t -test was used for comparison within each group, and the independent samples t -test was used for comparison between two groups; the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data. The chi-square test was used for comparison of categorical data. Results The observation group had a significantly higher overall response rate than the control group (87.5% vs 60.6%, χ 2 =-2.299, P =0.022). After treatment, both groups had significant reductions in ALT, AST, and TBil and a significant increase in Alb (all P < 0.05), and compared with the control group, the observation group had a significantly greater reduction in TBil ( Z =-2.165, P =0.030). After treatment, both groups had significant improvements in the levels of CD3 + T, CD4 + T, and CD4 + /CD8 + , and the observation group had significantly greater improvements than the control group ( Z =-2.146, -2.940, and 3.157, P =0.032, 0.003, and 0.002). After treatment, both groups had significant reductions in the levels of TNF-α, IL-6, and ET, and the observation group had significantly greater reductions than the control group ( Z =-2.139, -1.982, and -2.062, P =0.032, 0.048, and 0.043). Both groups had an increase in the number of operational taxonomic units after treatment. As for the abundance of intestinal flora at the phylum level, the observation group had a significant increase in the abundance of Firmicutes and a significant reduction in the abundance of Bacteroidetes after treatment ( Z =-3.181 and -2.215, P =0.001 and 0.027); compared with the control group, the observation group had significantly greater increases in the abundance of Firmicutes and Cyanobacteria and significantly greater reductions in the abundance of Bacteroidetes, Cercozoa, and ε-Proteobacteria (all P < 0.05). At the genus level, the observation group had a significant increase in the abundance of Bifidobacterium after treatment ( Z =-2.045, P =0.041). The alpha-diversity analysis showed that the observation group had significant increases in Chao1 and Ace indices after treatment ( t =-4.263 and -3.328, P =0.001 and 0.005) and a significantly greater increase in Ace index than the control group ( t =2.292, P =0.030). The beta-diversity analysis showed that the two groups had a similar composition of flora without significant difference (all P > 0.05). Conclusion Jiedu Huayu Tongfu prescription, in combination with etiological and basic treatments, can alleviate clinical symptoms, reduce liver injury, and improve cellular immune function in patients with hepatitis B cirrhosis with liver-gallbladder damp-heat syndrome. Jiedu Huayu Tongfu prescription can improve the imbalance of intestinal flora by increasing the abundance of the probiotic bacteria such as Firmicutes, Lactobacillus, and Bifidobacterium and the pathogenic bacteria such as Bacteroidetes and Cercozoa, and its effect in further improving liver and immune function may be associated with the regulation of intestinal microecology.

Coronary artery disease (CAD) is a chronic disease but causes the highest mortality and morbidity among the cardiovascular diseases worldwide. Correlations between CAD and gut microbiota have been observed. This suggests that the gut microbiota could become a vital diagnostic marker of CAD, and restoring the gut habitat may become a promising strategy for CAD therapy. The elevated level of trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, was found to be associated with the increased risk of cardiovascular disease and the all-cause mortality. Preclinical studies have shown that it has pro-arteriosclerosis properties. It is likely that regulating the production of TMAO by gut microbiota may become a promising strategy for anti-atherosclerosis therapy. This review summarizes the clinical and preclinical researches on the intervention of CAD by regulating the gut microbiota and the microbiota-derived metabolite TMAO, with the aim to provide new target for the therapy of CAD.
Coronary Artery Disease ; Gastrointestinal Microbiome ; Humans ; Methylamines ; Oxides