Cirrhotic cardiomyopathy (CCM) is a significant complication of cirrhosis, but its progression and underlying mechanisms remain incompletely understood. This study aimed to investigate dynamic changes in cardiac function, pathology, inflammation, and mitochondrial damage in a mouse model of CCM, and to compare echocardiographic characteristics in patients with cirrhosis.

Bile duct ligation was performed in male C57BL/6J mice to induce cirrhosis. Longitudinal analyses were conducted over eight weeks. Cardiac function was assessed using serum biomarkers, echocardiography, and electrocardiography. Pathology was examined with hematoxylin and eosin, Masson’s trichrome, Sirius Red, and wheat germ agglutinin staining. Western blotting and immunohistochemistry were used to detect markers of inflammation, fibrosis, apoptosis, and mitochondrial function. Cardiac and liver function markers were also evaluated in patients with cirrhosis.

Mice subjected to bile duct ligation developed progressive cardiac dysfunction, including reduced cardiac output and diastolic dysfunction (end-diastolic interventricular septal thickness, left ventricular internal diameters, stroke volume, and left ventricular end-diastolic volume decreased, whereas ejection fraction and fractional shortening increased), as well as cardiac atrophy. Myocardial apoptosis, inflammation (elevated tumor necrosis factor, interleukin-6, and p65), and fibrosis worsened over time. Mitochondrial injury was characterized by reduced carnitine palmitoyltransferase 1A and peroxisome proliferator-activated receptor alpha, with increased hexokinase 2, pyruvate kinase M2, and lactate dehydrogenase A. In patients with cirrhosis, impaired cardiac function and elevated brain natriuretic peptide levels correlated with total bilirubin.

The progression of CCM is closely associated with cirrhosis severity and appears to be driven by myocardial atrophy, apoptosis, inflammation, fibrosis, and mitochondrial dysfunction.

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.

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.

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.

Unlike the traditional staging treatment of tumors, the core of “Green Tumor Treatment” is to divide the treatment of tumors into three stages: Hegemony (directly targeting the cancer focus), Kingship (supporting the body’s vital energy and eliminating pathogenic factors), and Imperialism (improving the internal environment), based on the urgency of the tumor and the patient’s physical condition. This approach guides the clinical treatment of tumors. Its treatment system incorporates all minimally invasive and low-damage treatment methods, combining internal and external treatments, traditional Chinese medicine and Western medicine, as well as local and systemic treatments. It aims to maximize treatment outcomes while ensuring the patient’s quality of life, which is highly consistent with the treatment goals for primary liver cancer. This review aims to explore the integrated Traditional Chinese and Western medicine treatment model for primary liver cancer under the guidance of the Green Tumor Treatment concept.

The long-term clinical outcomes of patients with hepatitis B virus (HBV)-related cirrhosis receiving nucleos(t)ide analog (NA) therapy according to virological response patterns remain inadequately defined. This study aimed to investigate the association between virological response patterns and clinical outcomes in a large, long-term, real-world cohort.

This retrospective–prospective cohort study enrolled patients with HBV-related cirrhosis receiving NA therapy from 2009 to 2019. According to the serum HBV DNA levels during the initial two years of antiviral treatment, patients were categorized as having a complete (CVR) or partial virological response (PVR). Patients with CVR were further stratified according to their dynamic HBV DNA changes during follow-up into maintained virological response (MVR) or virological breakthrough (VBT) patterns. The primary clinical outcomes included hepatocellular carcinoma (HCC), acute-on-chronic liver failure, and liver-related death. Secondary endpoints included recompensation and progression to decompensation. Cox proportional hazards regression was used to assess the association between virological response patterns and clinical endpoints.

In total, 1,869 patients were enrolled. During a median follow-up of seven years, the MVR, VBT, and PVR rates were 65.4%, 26.5%, and 8.1%, respectively. The cumulative serum hepatitis B surface antigen (HBsAg) clearance rate was 9.8%. Moreover, 34.9% of patients with HBsAg < 100 IU/mL at baseline experienced HBsAg clearance. Compared with patients with VBT and PVR, those with MVR had a lower five- and ten-year cumulative incidence of HCC in both the compensated (five-year: 10.1% vs. 17.0%; ten-year: 14.2% vs. 33.6%; P < 0.001) and decompensated cirrhosis subgroups (five-year: 19.5% vs. 36.7%; ten-year: 25.7% vs. 49.7%; P < 0.001). Similarly, patients with MVR also had a lower cumulative incidence of liver-related death. Additionally, a higher hepatic recompensation rate was observed in patients with MVR than in those with VBT (34.1% vs. 22.5%, P < 0.001). Importantly, patients achieving HBsAg clearance and undetectable serum HBV DNA levels (“functional cure” during ongoing NA therapy) had the lowest five- and ten-year cumulative incidence of HCC (3.9% and 8.7%, respectively).

Patients with long-term MVR exhibited a lower incidence of HCC and liver-related death in both compensated and decompensated HBV-related cirrhosis subgroups, especially those achieving “functional cure.” However, more than 30% of patients experienced PVR or VBT during long-term NA antiviral therapy. These findings highlight the importance of long-term, rigorous monitoring after initial CVR to optimize outcomes and support clinical decision-making.

Thalassemia is a group of anemias that result from inherited defects in the production of the beta chain of hemoglobin. It is stabilized by gamma globin, which combines to form fetal hemoglobin. One therapeutic approach is to target histone deacetylase (HDAC), which plays an important role in controlling beta thalassemia. This study sought to identify a natural inducer for treating this disease.

Twenty-five Andrographis paniculata compounds were screened using Schrödinger Suite 2020 (Maestro 12.3) for ligand preparation, grid generation, glide extra precision docking and molecular mechanics/generalized born surface area scoring. The HDAC2 crystal structure (Protein Data Bank ID: 4LXZ) was prepared by removing crystallographic water molecules and performing restrained minimization. Top-scoring complexes were subjected to 5-ns molecular dynamics simulations in GROMACS 2019 using the optimized potentials for liquid simulations force field, three interaction site point charge solvation, and standard neutralization and equilibration protocols. Absorption, distribution, metabolism, and excretion properties were predicted using QikProp.

Among the twenty five screened compounds, SRJ09 derivative of andrographolide, ranked among the top candidates based on glide extra precision docking and molecular mechanics/generalized born surface area scores and was therefore selected for further analysis. SRJ09 showed favorable binding to the HDAC2 active site, with interactions comparable to the reference inhibitor 20Y. Absorption, distribution, metabolism, and excretion predictions indicated acceptable drug-likeness, and molecular dynamics simulations demonstrated stable SRJ09–HDAC2 complex behavior over 5 ns.

We concluded that beta thalassemia may benefit from the use of andrographolide, and SRJ 09 as prospective HDAC2 inhibitor drugs that are favourable and efficacious and that generate fetal hemoglobin. Therefore, this bioactive compound is worth further investigation using in vitro and in vivo studies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor for cardiovascular disease (CVD). While gut bacteria have been linked to CVD, the role of intestinal fungi in subclinical coronary atherosclerosis (SCA) remains unclear. In this study, we aimed to investigate the association between the gut mycobiome and SCA in MASLD.

A cross-sectional study was conducted among 103 MASLD patients without established CVD. Fibrosis and steatosis were assessed using magnetic resonance elastography (MRE) and proton density fat fraction, respectively. SCA was defined by coronary artery calcification (CAC). Fecal fungal composition was analyzed via internal transcribed spacer sequencing.

Mean age was 60.8 ± 11.2 years; 51.5% were men; 20.4% had cirrhosis. CAC correlated with MRE (r = 0.489, p < 0.001), interleukin-6 (r = 0.407, p < 0.001), and tumor necrosis factor-α (r = 0.254, p = 0.018), but not proton density fat fraction. Cirrhosis patients had higher CAC than F0–F3 (456.9 vs. 205.9, p = 0.033). Candida albicans (C. albicans) abundance was greater in cirrhosis and correlated with CAC (r = 0.403, p < 0.001) and MRE (r = 0.212, p = 0.032). In multivariate analysis, older age, diabetes, obesity, cirrhosis, and enriched C. albicans independently predicted CAC ≥ 100 AU in MASLD.

In MASLD, cirrhosis and C. albicans enrichment are independently associated with higher SCA burden, suggesting advanced liver disease and a potential fungal contribution to CVD pathogenesis.