Xiahong Dai

Metabolic syndrome (MetS) represents a growing global health burden characterized by obesity, insulin resistance, dyslipidemia, and hypertension. Increasing evidence suggests that gut microbiota-associated mediators may serve as signaling intermediates involved in host metabolic regulation. However, the mechanisms by which these mediators interact with host signaling pathways and influence metabolic responses remain incompletely understood. This review summarizes current advances in gut microbiota-associated mediators, focusing on short-chain fatty acids, bile acids, lipopolysaccharide, trimethylamine N-oxide, and branched-chain amino acids. We discuss their interactions with host metabolic and inflammatory pathways, including pathways implicated in FFAR2/3-mediated signaling, FXR/TGR5 signaling, TLR4/NF-κB-mediated inflammatory signaling, and mTORC1-associated nutrient-sensing. Furthermore, we propose a microbiota–mediator–host signaling network framework as an emerging conceptual model to integrate these molecular interactions and highlight the utility of multi-omics approaches in characterizing complex microbiota–host communication. Despite mechanistic advances, substantial challenges remain, including heterogeneous microbial signatures across populations, limited causal evidence, inter-individual variability in therapeutic responses, and barriers to clinical translation of microbiota-targeted interventions. A better understanding of microbiota-associated signaling networks may provide new insights into metabolic regulation and contribute to the rational development of microbiota-targeted strategies that complement established lifestyle interventions for MetS management.

Backgroud The role of HIV infection in precipitating different clinical features in Cryptococcal meningitis (CM) patients remains controversial. Methods One hundred and twelve CM patients living with HIV/AIDS (CM+HIV+ patients) and 112 CM patients living without HIV/AIDS (CM+HIV- patients) were enrolled after propensity score matching. Demographic characteristics, symptoms, routine blood tests, biochemical and cerebrospinal fluid (CSF) profiles were compared between the two groups. Kaplan–Meier analysis and Cox proportional hazards model was used to assess 10-week mortality. Results CM+HIV+ patients frequently occurred in young (mean age 40.3±10.5) and male (89.3%) populations who also experienced leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, and hypoalbuminemia, less headaches (66.9%) and higher cryptococcemia (23.2%) (all P < 0.050); they also had higher glucose (2.6±1.1 mmol/L), increased smear positivity (78.8%) and decreased white blood cells [8.0 (2.0-28.0)×106/L] in initial CSF assay (all P< 0.050). The 10-week cumulative survival rate was 84.6% for CM+HIV+ patients and 88.5% for CM+HIV- patients (P = 0.345). Age < 35.0 years old (Hazard ratio (HR) 3.0 (1.0-8.9), P=0.046), intracranial pressure (ICP) > 250.0 mmH2O (HR: 4.8(1.1-21.6), P=0.041) and treatment lacking amphotericin B [HR: 6.5(1.9-21.4), P=0.003] were independent risk factors for 10-week mortality in CM+HIV+ patients. Conclusions There are significant clinical differences in cryptococcal meningitis patients living with or without HIV/AIDS. However, the 10-week survival rate was similar between the two groups. Younger population, high ICP and treatment lacking amphotericin B were independent risk factors for 10-week mortality of Chinese CM+HIV+ patients.

BACKGROUND. HBV-related acute-on-chronic liver failure (HBV-ACLF) is hallmarked by high short-term mortality rates, calling for accurate prognostic biomarkers for initial risk stratification. METHODS. Three tandem mass tag–labeled (TMT-labeled) quantitative proteomic studies were performed on 10 patients with HBV-related acute hepatic decompensation and on 20 patients with HBV-ACLF. Candidate biomarkers were preliminarily verified in a cross-sectional cohort (n = 144) and further confirmed in 2 prospective cohorts (n = 207 and n = 148). RESULTS. Plasminogen, a potential prognostic biomarker for HBV-ACLF, was identified by TMT quantitative proteomics and preliminarily verified in the cross-sectional cohort. Further validation with a prospective cohort (n = 207) showed that plasminogen levels at admission were significantly lower (P < 0.001) in HBV-ACLF nonsurvivors than in survivors. The cumulative survival duration of patients with high plasminogen levels was significantly longer (P < 0.001) than that of patients with low plasminogen levels. During hospitalization, plasminogen levels significantly decreased (P = 0.008) in the deterioration group but significantly increased (P < 0.001) in the improvement group. Additionally, plasminogen levels gradually increased in survivors but gradually decreased in nonsurvivors. The P5 score, a prognostic panel incorporating plasminogen levels, hepatic encephalopathy occurrence, age, international normalized ratio (INR), and total bilirubin, was significantly superior to the Child-Pugh, Model for End-stage Liver Disease (MELD), Chronic Liver Failure Consortium ACLF (CLIF-C ACLF), Chinese Group on the Study of Severe Hepatitis B (COSSH), and HINT (a prognostic score based on hepatic encephalopathy occurrence, INR, neutrophil count, and thyroid-stimulating hormone) scores (all P < 0.05). The performances of the plasminogen level and P5 score were validated in a second multicenter, prospective cohort (n = 148). CONCLUSIONS. Plasminogen is a promising prognostic biomarker for HBV-ACLF, and sequential plasminogen measurements could profile the clinical course of HBV-ACLF. P5 is a high-performance prognostic score for HBV-ACLF. FUNDING. The National Key Research and Development Program (2017YFC1200204); the National Natural Science Foundation of China (81400589, 81600497); the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81121002); the Chinese High-Tech Research and Development Programs (2012AA020204); the National S&T Major Project (2012ZX10002004); and the Zhejiang Provincial Medicine and Health Science and Technology Project (2016147735).

Indoleamine 2, 3-dioxygenase (IDO) is a key enzyme in the degradation of tryptophan (Trp) to kynurenine (Kyn). We measured IDO activity as the Kyn to Trp ratio, and investigated whether IDO could be used to assess prognosis of acquired immune deficiency Sydrome (AIDS) patients with pneumocystis pneumonia (PCP). The Kyn and Trp concentration were measured by UPLC-MS/MS in plasma samples. A total of 49 AIDS-PCP patients were included in the analysis. Clinical characteristics and Kyn/Trp ratio were compared between survivors and non-survivors. Kyn/Trp ratio was significantly lower after anti-PCP treatment in AIDS patients with PCP (P < 0.0001). Plasma Kyn/Trp ratio was higher in patients with PaO2/FiO2 ≤ 300 mmHg than in those with PaO2/FiO2 > 300 mmHg (P = 0.007). Kyn/Trp ratio, D-dimer and CRP showed much higher AUC for predicting death of AIDS-PCP patients. Kyn/Trp ratio was useful for predicting the mortality of AIDS-PCP due to a significantly higher Kyn/Trp ratio in the non-survivors (P = 0.002). And the high Kyn/Trp ratio group had higher mortality rate than low Kyn/Trp group (32.1% vs. 9.1%, respectively, p = 0.024). Activation of the kynurenine pathway is associated with the severity and fatal outcomes of AIDS patients with pneumocystis pneumonia.

N this study, levels of plasma α2-Heremans-Schmid glycoprotein, serum tumor necrosis factor-α, serum liver function parameters and short-term mortality were measured in 100 hepatitis B patients. Release of interleukin-6 and tumor necrosis factor-α from the lipopolysaccharide-stimulated peripheral blood mononuclear cells in the presence/absence of spermine and α2-Heremans-Schmid glycoprotein were analyzed by enzyme-linked immunosorbent assay to determine the significance and potential mechanism of α2-Heremans-Schmid glycoprotein in hepatitis B virus-associated liver damage. Results showed that serum α2-Heremans-Schmid glycoprotein levels in acute-on-chronic liver failure patients were significantly lower than that in chronic hepatitis B patients or healthy controls (p < 0.05). A negative dependence between serum human α2-Heremans-Schmid glycoprotein and tumor necrosis factor-α levels was observed. Interleukin-6 and tumor necrosis factor-α levels in the lipopolysaccharide-induced peripheral blood mononuclear cell supernates were significantly reduced by spermine and/or α2-Heremans-Schmid glycoprotein. The latter two proteins jointly inhibited cytokine release. These observations suggest that plasma α2-Heremans-Schmid glycoprotein is an independent marker of liver damage and a prognostic indicator of hepatitis B virus chronicity. It may reduce liver inflammation by partially inhibiting release of inflammatory factors from activated peripheral blood mononuclear cells.