Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a rapidly increasing global health concern, driven by metabolic stress, chronic inflammation, and progressive fibrotic remodeling. Myeloid-derived suppressor cells (MDSCs) have emerged as pivotal yet context-dependent modulators of MAFLD pathogenesis. This review summarizes the biological characteristics of MDSCs, their immunosuppressive mechanisms, and their multifaceted roles in MAFLD progression, including hepatic steatosis, chronic inflammation, and fibrogenesis. Quantitative synthesis reveals that murine models demonstrate MDSC expansion (∼3-fold with a high-fat diet, P < 0.05) and suppression of MDSC-associated proinflammatory mediators (e.g., MitoTEMPO reduced hepatic S100A8 mRNA by 5.9-fold, P < 0.001). In one human cohort (n = 98), hepatic CD33+/HLA-DR− MDSC density correlated with inflammation grade (Spearman r = 0.610, P < 0.001) and fibrosis stage (r = 0.687, P < 0.001), though this cross-sectional dataset lacked MAFLD-specific stratification and longitudinal validation. We further discuss emerging MDSC-targeted strategies and explicitly acknowledge current translational gaps. Collectively, this review provides a mechanistic and critically appraised framework positioning MDSCs as both promising therapeutic targets and potential biomarkers for MAFLD.

Pegylated interferon alpha (PegIFNα) has been associated with altered lipid metabolism, but long-term lipid trajectories in chronic hepatitis B remain poorly characterized. We evaluated lipid profiles and virological parameters during 144 weeks of PegIFNα-based therapy.

This single-center retrospective cohort study included 129 patients with chronic hepatitis B who completed 144 weeks of PegIFNα monotherapy, PegIFNα plus tenofovir alafenamide, or PegIFNα plus entecavir. Serum lipids, hepatitis B surface antigen (HBsAg), hepatitis B e antigen, and hepatitis B virus DNA were assessed at baseline and weeks 24, 48, 72, 96, and 144. Within-patient changes were analyzed with paired tests. Associations between early lipid changes and on-treatment HBsAg seroclearance at week 144 were examined with logistic regression.

From baseline to week 144, mean high-density lipoprotein cholesterol (HDL-C) increased by 0.10 ± 0.25 mmol/L (95% confidence interval, 0.06 to 0.15; P < 0.001) and mean total cholesterol decreased by 0.15 ± 0.41 mmol/L (95% confidence interval, −0.22 to −0.08; P < 0.001). Changes in triglycerides, low-density lipoprotein cholesterol, and the triglyceride-to-HDL-C ratio were not significant. HDL-C declined early and later recovered above baseline. At week 144, 37 patients (28.7%) achieved on-treatment HBsAg seroclearance (≤ 0.05 IU/mL). Of the 34 patients with HBsAg seroclearance at week 96, 13 had detectable HBsAg again at week 144. Early lipid changes were not associated with this endpoint.

HDL-C shows an early decline followed by recovery above baseline, whereas total cholesterol decreases modestly, with no significant net changes in triglycerides, low-density lipoprotein cholesterol, or the triglyceride-to-HDL-C ratio. Early lipid changes are not significantly associated with on-treatment HBsAg seroclearance. The durability of HBsAg loss requires post-treatment follow-up.

We compared logistic regression, random forest, and extreme gradient boosting (XGBoost) for classifying current colorectal cancer screening status among U.S. adults aged 45–75 years.

We analyzed 2024 Behavioral Risk Factor Surveillance System data for 227,647 adults aged 45–75 years with determinable screening status. Data were split into stratified training and held-out test sets before imputation. Missing predictors were handled with 20 multiply imputed datasets; imputation and preprocessing were fitted in training data and applied to held-out data. Model performance was assessed using five-fold cross-validation and the held-out test set.

In the test set, areas under the receiver operating characteristic curve were 0.771 for logistic regression, 0.778 for random forest, and 0.781 for XGBoost; corresponding areas under the precision-recall curve were 0.884, 0.888, and 0.890. Brier scores were 0.152, 0.153, and 0.149, respectively. At model-specific Youden thresholds, sensitivity ranged from 75.5% to 78.6% and specificity from 62.5% to 66.3%.

XGBoost has the highest discrimination and lowest Brier score, but differences among models are small. The models classify current screening status in this analytic cohort; external validation is needed before use in screening outreach.

The huge burden of type 1 diabetes mellitus (T1DM) has been a source of concern globally since the Industrial Revolution in the 18th–19th centuries. To this end, studies have shown that certain environmental changes that accompanied the Revolution may have increased the risk and burden of the disease in genetically predisposed individuals. However, documented studies that synthesize these environmental triggers are scarce. As a result, the current study was conceived to synthesize the environmental triggers of T1DM to boost public awareness. Relevant information was retrieved from reputable academic databases; namely, Scopus, PubMed, SpringerLink, and Embase. The results showed that chemical exposure, viral infection, gut microbiome disruption, vitamin and mineral deficiencies, inadequate or exclusive breastfeeding, as well as early exposure to infant feeding formulas could increase the risk and burden of T1DM in genetically predisposed individuals. As a consequence, these triggers could compromise the expression of certain genes involved in insulin synthesis and immune function, such as the human leukocyte antigen (HLA), insulin (INS), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and protein tyrosine phosphatase non-receptor type 22 (PTPN22) genes. This would result in a dysfunctional immune system in which immune cells, such as T-cells and B-cells and molecules, such as cytokines would attack self-tissues, thus causing autoimmunity of the pancreatic beta cells. Environmental triggers could also induce the T1DM pathophysiology by modifying the epigenome of the mentioned genes. Furthermore, some epigenetic changes could be reversed, which would infer that treatment procedures that would include the pathophysiology of the environmental triggers could be more effective.

Emerging evidence suggests that RNA-binding motif (RBM) proteins are involved in hepatocarcinogenesis and act either as oncogenes or tumor suppressors. The objective of this study was to investigate the role of RBM34, an RBM protein, in hepatocellular carcinoma (HCC).

We first examined the expression of RBM34 across cancers. The correlation of RBM34 with clinicopathological features and the prognostic value of RBM34 for HCC was then investigated. Functional enrichment analysis of RBM34-related differentially expressed genes (DEGs) was performed to explore its biological function. RNA sequencing (RNA-seq) was applied to identify downstream genes and pathways affected upon RBM34 knockout. The correlation of RBM34 with immune characteristics was also analyzed. The oncogenic function of RBM34 was examined in in vitro and in vivo experiments.

RBM34 was highly expressed in hepatocellular carcinoma and correlated with poor clinicopathological features and prognosis. RBM34 was positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. A positive correlation was also observed between RBM34, T cell exhaustion, and regulatory T cell marker genes. Knockout of RBM34 significantly inhibited cell proliferation, migration, and xenograft tumor growth, and sensitized HCC cells to sorafenib treatment. RBM34 inhibition reduced FGFR2 expression and affected PI3K-AKT pathway activation in HCC cells.

Our study suggests that RBM34 may serve as a new prognostic marker and therapeutic target of HCC.

Naringenin is an anti-inflammatory flavonoid that has been studied in chronic liver disease. The mechanism specific to its antifibrosis activity needs further investigation This study was to focused on the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) pathway in hepatic stellate cells and clarified the antifibrosis mechanism of naringenin.

The relationship between the cGAS-stimulator of interferon genes (STING) pathway and liver fibrosis was analyzed using the Gene Expression Omnibus database. Histopathology, immunohistochemistry, fluorescence staining, Western blotting and polymerase chain reaction were performed to assess gene and protein expression levels associated with the cGAS pathway in clinical liver tissue samples and mouse livers. Molecular docking was performed to evaluate the relationship between naringenin and cGAS, and western blotting was performed to study the expression of inflammatory factors downstream of cGAS in vitro.

Clinical database analyses showed that the cGAS-STING pathway is involved in the occurrence of chronic liver disease. Naringenin ameliorated liver injury and liver fibrosis, decreased collagen deposition and cGAS expression, and inhibited inflammation in carbon tetrachloride (CCl4)-treated mice. Molecular docking found that cGAS may be a direct target of naringenin. Consistent with the in vivo results, we verified the inhibitory effect of naringenin on activated hepatic stellate cells (HSCs). By using the cGAS-specific agonist double-stranded (ds)DNA, we showed that naringenin attenuated the activation of cGAS and its inflammatory factors affected by dsDNA. We verified that naringenin inhibited the cGAS-STING pathway, thereby reducing the secretion of inflammatory factors by HSCs to ameliorate liver fibrosis.

Interrupting the cGAS-STING pathway helped reverse the fibrosis process. Naringenin has potential as an antihepatic fibrosis drug.