Yan Bai

Background and aim: Gut-liver axis dysfunction drives metabolic associated fatty liver disease (MAFLD), but effective therapeutic strategies remain limited. Bletilla striata oligosaccharides (BSO) have immunomodulatory potential, yet their role in MAFLD via the gut-liver axis is unclear. This study aimed to investigate whether and how BSO ameliorates MAFLD by modulating gut microbiota, intestinal barrier function, and hepatic inflammation. Results: MAFLD was induced in mice by 8-week high-fat diet followed by 12-week BSO (150, 300, 600 mg/kg) or metformin treatment via oral gavage. Compared with the MAFLD model, high-dose BSO reduced body weight gain, lowered fasting glucose, and decreased hepatic triglycerides. BSO also attenuated liver injury, hepatic steatosis, inflammation. Mechanistically, BSO restored gut barrier integrity, upregulated colonic tight junction proteins, activated colonic LXRα/ABCA1 signaling, while suppressing the hepatic TLR4/NF-κB pathway. BSO remodeled gut microbiota, enriching beneficial Lachnospiraceae and Oscillospiraceae, and modulated hepatic metabolites, as shown by decreased confertifoline along with increased D-myo-inositol-4-phosphate. Additionally, BSO activated the intestinal FXR/FGF15 axis and ameliorated bile acid metabolism disorders, evidenced by reduced tauro-ω-muricholic acid and cholic acid. Conclusion: This study provides systematic evidence that BSO alleviates MAFLD through a multi-target gut-liver axis mechanism involving gut microbiota remodeling, barrier restoration, activation of LXRα/ABCA1 and FXR/FGF15 signaling, and subsequent suppression of hepatic TLR4/NF-κB-driven inflammation. Compared to previous approaches, BSO offers a favorable safety profile with combined regulatory effects. These findings support BSO as a promising candidate for MAFLD treatment, with potential applications as a dietary supplement or prebiotic agent.

Background/Objectives: Chitooligosaccharide (COS) is a marine-derived natural product obtained from shrimp and crab shells. Although its anti-inflammatory and antioxidant activities are documented, its potential effects on obesity and metabolic syndrome remain largely unclear. This study aimed to investigate the efficacy of COST (MW ≈ 1000 Da) against high-fat diet (HFD)-induced obesity and metabolic syndrome in Bama pigs. Methods: Bama pigs were fed a HFD for 12 weeks to establish an obesity model, followed by 12 weeks of oral COST administration. Serum biochemical parameters, tissue indicators, histopathology, and gene/protein expression related to cholesterol metabolism were analyzed. Fecal bile acid (BA) profiles, gut microbiota composition, and short-chain fatty acid (SCFA) levels were also examined. Results: COST treatment significantly attenuated weight gain and improved multiple components of metabolic syndrome, including insulin resistance, dyslipidemia, and inflammation. Mechanistically, COST upregulated intestinal ABCG5/ABCG8 to promote cholesterol excretion, increased ABCA1 expression in intestine and liver to enhance reverse cholesterol transport (RCT), and upregulated hepatic LDL-R to facilitate LDL-C clearance from circulation while modulating hepatic cholesterol synthesis via SREBP2 downregulation and RNF145 upregulation. These transcriptional changes were confirmed at the protein level for LXR, LDL-R, and ABCA1. Additionally, COST decreased fecal secondary BA levels, reshaped gut microbiota composition, and increased SCFA production, with significant correlations among these factors. Conclusions: COST ameliorates protective effects against HFD-induced obesity and metabolic syndrome, potentially through the regulation of cholesterol metabolism and the modulation of the gut microbiota-BA-SCFA network.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental endocrine disruptors (EDCs) that enter the human body through respiratory, digestive, and dermal exposure. Prolonged exposure has been associated with adverse health outcomes, including carcinogenicity, mutagenicity, and reproductive toxicity. However, whether genetic variation in apoptosis-related pathways modifies the reproductive effects of PAH exposure remains unclear. To investigate gene-environment interactions between urinary PAH metabolites and polymorphisms in apoptosis-related genes in relation to sperm apoptosis, we conducted a cross-sectional study involving 176 male participants from an infertility clinic in Wuhan, China, who completed structured questionnaires and provided biological samples. Ten OH-PAH metabolites in repeated urine samples were measured, along with genotyping of single-nucleotide polymorphisms (SNPs) at apoptosis-related genes (Fas, FasL, and caspase-3) in whole blood DNA, and sperm apoptosis. Multivariable linear regression evaluated the interaction between urinary OH-PAH levels and apoptotic gene SNPs on apoptotic sperm, with genotype-stratified analyses. PAH exposure appeared to interact with SNPs in FasL rs763110, Fas rs2234767, and caspase-3 rs12108497 to jointly influence sperm cell apoptosis. Specifically, for the FasL rs763110, higher 9-OHFlu was associated with fewer viable sperm and more apoptotic sperm, and this association was more pronounced among CC genotype homozygotes. For the caspase-3 rs12108497, higher 2-OHFlu was associated with more dead sperm, and this association was significant among TC and TC/CC genotypes. These findings suggest that genetic variation in apoptosis-related genes may modify susceptibility to PAH-induced sperm apoptosis, highlighting the importance of gene–environment interactions in male reproductive toxicity.

The impact of screen exposure on children’s language development has been widely debated. However, some characteristics of screen use, particularly the influence of the pandemic over the past three years have yet to be sufficiently investigated. To examine the association between screen exposure, particularly during the pandemic, and language development delays in children aged 18–72 months. A total of 2100 children who attended the children’s language development clinic at Guangzhou Women and Children’s Medical Center and Yuncheng Street Community Health Service Center in Guangzhou, China, were recruited into the study between January 2020 and September 2023. Children’s demographic and developmental characteristics were obtained through a structured questionnaire, and their language development delays were evaluated through the Sign-Significate Relations (S-S) assessment, which was subsequently validated by the China Developmental Scale for Children method based on the voluntary principle. Multivariate logistic regression models were employed to analyze the association between screen exposure and language development delay. In order to gain further insight, the data was stratified according to whether or not the children had experienced a period of social isolation due to the COVID-19 pandemic, the parenting environment and the quality of screen usage. More than half of the children (53.29%) were exposed to screens for over 1 h daily. After adjusting for potential confounders, a dose-response relationship was observed between children’s daily screen exposure exceeding 1 h and the risk of delayed language development. The stratified analyses confirmed the main findings, revealing stronger associations in children who had experienced at least one period of quarantine, whose primary language spoken at home was Cantonese, whose caregivers had an intermediate personality, whose daily outdoor activities were less than 2 h, who did not have interaction with caregivers during screen time, and who watched educational videos. This study suggested that excessive screen exposure in children was associated with a heightened likelihood of language development delays, especially among children who experienced COVID-19 quarantine with prolonged screen time.

Alcoholic liver disease (ALD) is a liver disorder resulting from excessive alcohol intake, and currently, there are no therapeutics approved by the FDA for its treatment. This study investigates the protective effects and underlying pharmacological mechanisms of two chitosan oligosaccharides, COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da), in mitigating alcohol-induced liver disease (ALD). In animal models, we evaluated the changes in ALD following treatment with COST and COSM. Histopathological analysis revealed that both COST and COSM interventions mitigated hepatic steatosis and inflammatory infiltration. Additionally, these compounds reduced various markers of liver injury, enhanced antioxidant enzyme levels, and significantly improved liver function. Western blot analysis demonstrated that COSM markedly decreased the expression of the hepatic metabolic enzyme CYP2E1, activated the Keap-1/Nrf-2/HO-1 pathway, and restrained the NF-κB and MAPK pathways. In an in vitro model of alcohol-induced hepatocyte L02 injury, both COST and COSM exhibited protective effects on hepatocytes, corroborating the findings from the animal studies. Collectively, in vivo and in vitro experiments confirmed that COST and COSM can reduce oxidative damage, enhance antioxidant capacity, and ameliorate steatosis and inflammatory damage in the liver, thereby significantly attenuating alcohol-induced injury. Notably, COSM exhibited slightly superior efficacy compared to COST.

Obesity is closely related to metabolic diseases, which brings a heavy burden to the health care system. It is urgent to formulate and implement effective treatment strategies. Glucagon-like peptide-1 (GLP-1) is a protein with seven transmembrane domains connected by type B and G proteins, which is widely distributed and expressed in many organs and tissues. GLP-1 analogues can reduce weight, lower blood pressure, and improve blood lipids. Obesity, diabetes, cardiovascular diseases, and other diseases have caused scientists’ research and development boom. Among them, GLP-1R agonist drugs have developed rapidly in weight-loss drugs. In this paper, based on the target of GLP-1, the mechanism of action of GLP-1 in obesity treatment was deeply studied, and the drugs approved and designed for obesity treatment based on GLP-1 target were elaborated in detail. Innovatively put forward and summarized the double and triple GLP-1 targeted drugs in the treatment of obesity with better effects and less toxic and side effects, and this can make full use of multi-target methods to treat other diseases in the future. Finally, it is pointed out that intestinal flora and microorganisms have many benefits in the treatment of obesity, and fecal bacteria transplantation may be a potential treatment for obesity with less harm to the body. This article provides some promising methods to treat obesity, which have strong practical value.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with metabolic syndrome. Also, the name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). We performed focused drug screening and found that Cilostazol effectively ameliorated hepatic steatosis and might offer potential for NAFLD treatment. Our aim was to investigate the therapeutic effects of Cilostazol on the glycolipid metabolism and intestinal flora in NAFLD mice and explore the specific mechanism. In this study, 7-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, and then treated with intragastric administration for 12 weeks. The results showed that Cilostazol inhibited liver lipid de novo synthesis by regulating the AMPK-ACC1/SCD1 pathway and inhibited liver gluconeogenesis by the AMPK-PGC1α-G6P/PEPCK pathway. Cilostazol improved the intestinal flora diversity and intestinal microbial composition in the NAFLD mice, and specifically regulated Desulfovibrio and Akkermansia. In addition, Cilostazol increased the level of short-chain fatty acids in the NAFLD mice to a level similar to that in the blank Control group. Cilostazol reduces liver lipid accumulation in NAFLD mice by improving glucose and lipid metabolism disorders and intestinal dysfunction, thereby achieving the purpose of treating NAFLD.

Endotoxin is a general term for toxic substances in Gram-negative bacteria, whose damaging effects are mainly derived from the lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria, and is a strong pyrogen. Obesity is a chronic, low-grade inflammatory condition, and LPS are thought to trigger and exacerbate it. The gut flora is the largest source of LPS in the body, and it is increasingly believed that altered intestinal microorganisms can play an essential role in the pathology of different diseases. Today, the complex axis linking gut flora to inflammatory states and adiposity has not been well elucidated. This review summarises the evidence for an interconnection between LPS, obesity, and gut flora, further expanding our understanding of LPS as a mediator of low-grade inflammatory disease and contributing to lessening the effects of obesity and related metabolic disorders. As well as providing targets associated with LPS, obesity, and gut flora, it is hoped that interventions that combine targets with gut flora address the individual differences in gut flora treatment.