The rate of functional cure (HBsAg loss) remains unsatisfactory following pegylated interferon (PEG-IFN) treatment in chronic hepatitis B. To optimize PEG-IFN administration, this study aimed to evaluate virological markers to predict functional cure and/or hepatitis B e antigen (HBeAg) loss.

Relevant studies assessing virologic markers for predicting functional cure and HBeAg loss after PEG-IFN therapy were systematically retrieved from PubMed, Embase, the Cochrane Library, and Web of Science up to November 2023. Predictive effectiveness was evaluated via the summary receiver operating characteristic curve.

We analyzed 38 studies (6,179 patients). HBsAg decline at week 24 had the greatest discriminative ability according to the area under the receiver operating characteristic curve (AUROC) (0.89) and sensitivity (0.88) for predicting functional cure, whereas baseline HBsAg had a comparable AUROC (0.86) and highest specificity (0.79), with both being significantly better than baseline hepatitis B core-related antigen and hepatitis B virus (HBV) RNA (all P < 0.001). For HBeAg loss or seroconversion, HBV RNA, HBV DNA, HBeAg, and HBeAg decline at week 12, as well as HBV DNA and HBeAg decline at week 24, all exhibited comparable predictive values (AUROC = 0.75–0.78). HBV RNA and HBeAg levels at week 24 showed optimal sensitivity (0.87), and HBeAg decline at week 12 had the highest specificity (0.83).

HBsAg decline at week 24 and baseline HBsAg levels are better predictors of functional cure than novel virologic markers, while on-treatment HBV RNA and HBeAg levels and dynamic changes are the most reliable indicators for HBeAg loss.

N6-methyladenosine (m6A), the most prevalent internal RNA modification in eukaryotic cells, is a dynamic regulator of RNA metabolism and cancer biology. In colorectal cancer (CRC), dysregulated m6A reshapes transcriptomic programs that control tumor growth, metastasis, immune evasion, and therapeutic resistance. However, the context-dependent functions of individual m6A regulators remain incompletely defined, the integration of m6A with canonical oncogenic signaling remains incomplete, and its role in metabolic reprogramming lacks a systematic overview. This review aims to integrate current evidence on m6A regulatory machinery in CRC, clarify its coordination with oncogenic signaling and metabolic pathways, and highlight emerging translational implications. The key players regulating m6A in CRC progression are m6A “writers”, including methyltransferase-like 3 and methyltransferase-like 14; m6A “erasers”, including fat mass and obesity-associated protein and AlkB homolog 5; and m6A “readers”, including the YTH m6A RNA-binding protein family and the insulin-like growth factor 2 mRNA-binding protein family. m6A modification coordinates key oncogenic pathways, including Wnt/β-catenin, PI3K/Akt, MAPK, and p53 signaling. Moreover, m6A-dependent regulation of metabolic enzymes such as hexokinase 2, pyruvate kinase M2, and fatty acid synthase promotes the reprogramming of glucose, amino acid, and lipid metabolism, linking epitranscriptomic control to bioenergetic adaptation. We also discuss context-dependent and paradoxical functions of m6A regulators and advances in m6A-targeted therapies. In conclusion, m6A modification functions as a central regulatory hub in CRC by integrating signaling networks and metabolic pathways. Deeper mechanistic insights into spatiotemporal m6A regulation may accelerate the development of biomarkers and targeted therapies for precision CRC management.

Given the lack of efficient biomarkers for hepatocellular carcinoma (HCC) diagnosis, this study aimed to develop an HCC diagnostic strategy based on serum protein glycosylation signatures. We characterized differential N-glycosylation patterns of serum IgG to differentiate HCC from healthy controls and liver cirrhosis, and elucidated the molecular mechanisms driving aberrant Neu5Gc elevation in HCC to provide a theoretical basis for clinical application and differential diagnosis of HCC.

LIP-ELISA was applied to quantify serum Neu5Gc in 6,768 healthy individuals for baseline establishment. IgG was purified and subsequently analyzed by RPLC-MS/MS for glycosylation profiling in HCC and healthy samples. Bioinformatic analysis of CMAH and related gene clusters modulating Neu5Gc synthesis was conducted.

In a cohort of 1,114 participants, the LIP-ELISA platform achieved 80.21% sensitivity, 96.01% specificity, and 92.46% accuracy for primary HCC diagnosis. Serum IgG from HCC patients displayed multi-branched N-glycans modified with core fucose and Neu5Gc. Key molecules involved in glycan modification were identified, enabling the development of multiplexed gene detection for HCC, LC, and chronic hepatitis B. In vitro assays confirmed hypoxia-induced sialic acid accumulation in HCC cells. Meanwhile, CMAH-knockout mouse experiments verified that an exogenous high-sialic-acid diet compensates for endogenous Neu5Gc synthesis deficiency, revealing a dietary-mediated compensatory mechanism for Neu5Gc elevation.

This study established an LIP-ELISA-based clinical diagnostic platform combining AFP and Neu5Gc, defined sialic acid–modified glycan structures, and preliminarily identified regulators of Neu5Gc biosynthesis, providing novel insights for HCC diagnosis and mechanism research.

Alpinia calcarata (A. calcarata) Roscoe (Family: Zingiberaceae) is a rhizomatous perennial herb used in traditional medicine to treat inflammatory conditions. This study aimed to develop a topical emulgel dosage form by incorporating the essential oil of A. calcarata rhizome and to investigate it’s in vitro anti-inflammatory activity. A thin-layer chromatographic fingerprint of the essential oil of A. calcarata rhizome was developed. Then, an emulsion base containing plant oil was formulated and incorporated within a Carbopol gel base. The physical characteristics of this formulation were evaluated subsequently. The anti-inflammatory mechanism of the emulgel was determined by in vitro blood cell membrane stabilization assay and thrombolytic activity assay. The results were statistically analyzed by one-way analysis of variance. The thin-layer chromatographic fingerprint of the test oil demonstrated several bands with unique retention factor values. The formulated herbal emulgel was white, viscous, and homogeneous in appearance. The spreadability was 118 g·cm/M, and the pH of the emulgel was 6.30 at 25°C. The A. calcarata emulgel significantly (p < 0.05) inhibited heat-induced in vitro hemolysis, with the highest activity at a 50 µg/mL dose (87.68 ± 0.35%) compared to the placebo. Furthermore, this activity was found to be dependent on the essential oil concentration (r2 = 0.99) of the emulgel. Therefore, it was concluded that the essential oil of A. calcarata rhizome is an effective active ingredient to be used in a topical emulgel formulation, whereas the diverse phytochemicals present in the essential oil would be the underlying source of its anti-inflammatory activity.

Liver transplant rejection significantly affects patient prognosis. Myeloid-derived suppressor cells (MDSCs), known for their potent immunoregulatory functions, represent a promising target for managing liver transplant rejection. This study aimed to systematically characterize the diversity of MDSC subsets and their context-dependent functions, particularly within the context of transplant tolerance.

We analyzed clinical and murine liver transplants using single-cell RNA sequencing, bulk RNA sequencing, flow cytometry, multiplex immunohistochemistry, and co-culture assays to phenotype MDSC subsets.

Single-cell RNA sequencing analysis of human and murine samples revealed MDSC involvement in transplant rejection. In mice, MDSC scores followed a normal distribution during the first week post-transplant and correlated with clinical flow cytometry data at one month. A distinct LDLR+ monocytic MDSC (M-MDSC) subset was identified and confirmed through spatial mapping by multiplex immunohistochemistry. Flow cytometry demonstrated dynamic changes in LDLR+ M-MDSCs across tissues (liver, spleen, peripheral blood, bone marrow, and lymph nodes), with a peak during acute rejection. Co-culture experiments showed that LDLR−/− M-MDSCs exhibited reduced Arg-1/iNOS expression and an impaired capacity to induce inhibitory receptors (TIGIT, PD1, CTLA-4) or suppress effector molecules (GZMB, IFN-γ, IL-2) in CD8+ T cells.

These findings highlight the critical role of MDSCs in liver transplant rejection. LDLR+ M-MDSCs exhibited enhanced immunosuppressive properties, underscoring their potential clinical relevance in mitigating rejection and promoting immune tolerance.

Chronic pancreatitis is an inflammatory disease and is difficult to manage despite advancements in medical science. This study examined the effect of water/ethanol extracts of Justicia carnea leaves on oxidative stress and glucagon expression in a mouse model of chronic pancreatitis induced by trinitrobenzenesulfonic acid (TNBS).

Twenty-five male Swiss albino mice were randomized and treated intrarectally with vehicle (the control group) or TNBS. Some TNBS-treated mice were treated orally with 200 mg/kg or 400 mg/kg J. carnea extracts, or with the positive control, 500 mg/kg sulfasalazine, every other day on three occasions. Oxidative stress markers and pancreatic glucagon expression were assessed.

Compared with the healthy control mice, treatment with TNBS significantly decreased the levels of pancreatic glutathione (0.89 µmol/g tissue vs. 7.16 µmol/g tissue in the control) and glutathione peroxidase activity, but significantly increased the levels of α-amylase and lipase activities, lipid peroxidation, total antioxidant capacity, and nitric oxide, as well as serum C-reactive protein (P < 0.05 for all), accompanied by severe inflammation and reduced glucagon expression in the pancreatic tissues. The toxic effects of TNBS were significantly mitigated by treatment with J. carnea extracts.

These findings provide evidence that treatment with J. carnea extracts inhibited oxidative stress and preserved glucagon expression in the pancreatic tissues of mice.