The pathogenic role of MIR142 genetic abnormalities in the development of primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is unexplored. The objective of this study was to investigate the frequency, spectrum, and functional significance of mutations in the MIR142 gene in primary CNS DLBCL.

Direct Sanger sequencing of the MIR142 gene was performed in tumor tissue from 35 patients with primary DLBCL of the CNS. In silico prediction of microRNA (miRNA)–target interactions, enrichment analysis of target gene ontologies, and prediction of the secondary structure and minimum free energy of the miRNA hairpin were performed.

The mutation frequency was 37.1% (95% confidence interval: 23.2–53.7%). The vast majority of the identified single-nucleotide variants were located outside the regions encoding mature miRNA chains. In silico analysis showed that the n.29A>G mutation located in the seed sequence of miR-142-5p resulted in a significant reduction in the number of potential targets and alterations to the interaction spectrum. All single-nucleotide variants identified in the study patients caused a change in minimum free energy and affected the shape and length of the hairpin stem of pri-miRNA. The results indicate the fragility of the pri-miR-142 hairpin.

The frequency of gene mutations in primary DLBCL of the CNS significantly exceeds that reported for systemic DLBCL.

Liver fibrosis is a pivotal and reversible stage in the progression of chronic liver disease. However, the mechanisms underlying fibrosis reversal remain unclear, and effective diagnostic biomarkers are lacking in clinical practice. In this study, we aimed to elucidate the role and molecular mechanisms of glutathione S-transferase Mu 3 (GSTM3) in liver fibrosis reversal, and preliminarily determine whether GSTM3 can serve as a novel biomarker for liver fibrosis reversal.

Carbon tetrachloride-induced mouse models of liver fibrosis and spontaneous reversal were established. Proteomic analysis was used to identify proteins shared between liver tissue and serum that were continuously downregulated during fibrosis reversal. The expression of GSTM3 was evaluated in the livers of mice undergoing fibrosis reversal and in clinical samples from patients with liver fibrosis. Hepatic stellate cells (HSCs) were transfected with Gstm3-silencing RNA or an overexpression plasmid to assess the effects on fibrosis markers. RNA sequencing analyses were performed, and the underlying molecular mechanisms were investigated.

Proteomic analysis revealed significantly decreased GSTM3 levels in both hepatic tissue and serum in mice undergoing fibrosis reversal, and its expression was negatively correlated with the extent of reversal. GSTM3 levels were markedly increased in the hepatic tissue and serum of patients with liver fibrosis. GSTM3 expression was upregulated in transforming growth factor-β-stimulated HSCs. GSTM3 knockdown inhibited the expression of fibrosis markers, such as collagen type I α1 and tissue inhibitor of metalloproteinase 1, whereas its overexpression promoted their expression. Mechanistic studies indicated that GSTM3 knockdown activated peroxisome proliferator-activated receptor γ (PPARγ) signaling and downregulated its downstream targets, cluster of differentiation 36 and fatty acid-binding protein 4, thereby suppressing HSC activation.

GSTM3 knockdown promotes liver fibrosis reversal via PPARγ signaling-mediated inhibition of HSC activation. Therefore, GSTM3 is a promising therapeutic target and diagnostic biomarker for liver fibrosis.

Vulvovaginal candidiasis, an infection caused by an abnormal proliferation of Candida species in the vagina and vulva, is particularly relevant, affecting up to 75% of women of reproductive age. Because of antifungal drug resistance, a significant number of plants are used to treat vaginal candidoses in Cameroon. Thus, the scientific validation of the use of these plants in treating candidiasis is valuable. This study sought to identify medicinal plants used to treat vaginal infections in the Dschang district and evaluate the antifungal activity of the most promising plants on five Candida species.

The ethnobotanical survey was conducted in Dschang (Menoua Division, West Cameroon) through individual interviews using a semi-structured questionnaire. Extracts from seventeen plants were obtained by maceration using water or a water–ethanol solution (3:7; v/v). Antifungal activity was evaluated using the microdilution method.

Forty-eight plants belonging to 33 families were identified as treating vaginal infections. Decoction and formulation of ovules were the prevalent modes of plant preparation, with leaves and bark being the predominant plant organs used. Out of thirty-four extracts tested, two (CSEHAlc and MIEHAlc) showed antifungal activity, with minimum inhibitory concentrations ranging from 0.315 to 2.5 mg/mL. The determination of the minimum fungicidal concentrations revealed the fungicidal orientation of these bioactive extracts.

This study identifies medicinal plants used to treat vaginal infections in Dschang and their modes of preparation. The in vitro antifungal screening of selected plants indicated Mangifera indica and Canarium schweinfurthii as the anti-Candida plants that can be further exploited for antifungal drug discovery.

Antimitochondrial antibody (AMA)-negative primary biliary cholangitis (PBC) is a rare presentation of PBC that comprises 5%–10% of all PBC patients. The pathogenesis of AMA-negative PBC appears to be similar to that of AMA-positive PBC. AMA-negative PBC presents similarly to AMA-positive PBC, with symptoms of cholestasis, fatigue, and pruritus most commonly reported. Defective bicarbonate production, resulting in acidification of bile and bile acids, has been proposed as the primary mechanism of damage to bile ducts and hepatocytes and is reflected in elevations of alkaline phosphatase and aminotransferases. Chronic damage can lead to the development of cirrhosis. The diagnosis is made by the finding of AMA negativity by ELISA or assays of similar sensitivity and a positive PBC-specific antinuclear antibody (ANA; anti-glycoprotein 210 and anti-speckled 100 kDa protein) test. In cases in which anti-glycoprotein 210 and anti-speckled 100 kDa protein assays are also negative, a liver biopsy is required to make the diagnosis after exclusion of other causes of cholestasis by magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography. Treatment for AMA-negative PBC is the same as for AMA-positive cases, with ursodeoxycholic acid as the first-line treatment. Current treatment is most effective in early stages, where it slows but does not eliminate progression. Risk stratification by validated tools such as the GLOBE and UK-PBC scores remains useful in AMA-negative PBC.

Pancreatic cystic neoplasms (PCNs) are increasingly detected in clinical practice, yet substantial variability exists in imaging interpretation and reporting, which may affect clinical decision-making. This guideline was developed to standardize diagnostic imaging evaluation and reporting for PCNs. A multidisciplinary expert panel conducted literature search and critical appraisal of domestic and international evidence, identified key clinical questions, and formulated recommendations using the Grading of Recommendations Assessment, Development and Evaluation framework. A modified Delphi consensus process and external review were performed to ensure the robustness of the recommendations. A total of 21 key questions were addressed, covering essential aspects of imaging evaluation and reporting for PCNs, including the preferred imaging modality for suspected lesions; standardized measurement of cyst size and mural nodules and their clinical significance; definitions of cyst wall and septal thickening; optimal imaging approaches for assessing the relationship between cystic lesions and the main pancreatic duct; measurement and evaluation of main pancreatic duct diameter and dilation; imaging-based classification of intraductal papillary mucinous neoplasms and serous cystic neoplasms; assessment of ductal obstruction, calcification, hemorrhage, and pancreatitis-related changes; criteria for suspicious lymph nodes; differentiation of PCNs from pancreatic pseudocysts or retention cysts; and recommended imaging modalities and follow-up intervals. This guideline provides a structured and evidence-based framework for imaging evaluation and reporting of PCNs, which may improve the consistency and clarity of imaging reports and support clinical decision-making.

Mitochondrial DNA (mtDNA) variability, especially heteroplasmy, is believed to affect cellular immunobiogenesis, particularly in monocytes in metabolic syndrome (MetS). This study aimed to identify associations of monocytic mtDNA variability with its phenotypic indices, including cytokine secretion and gene expression, and cardiometabolic parameters in patients with MetS.

The cross-sectional study recruited 87 adult participants, including 34 healthy blood donors (Control group), 21 obese patients (Obesity group), and 32 MetS patients (MetS group). Blood biochemistry tests were performed on venous blood samples, and monocytes (CD14+ cells) were isolated. Monocyte mtDNA was analyzed by next-generation sequencing to identify low (5–10%) and intermediate (10–95%) heteroplasmy, and homoplasmy (≥95%). Expression of genes related to mitochondrial biogenesis, mitochondrial uncoupling, oxidative stress system, and NF-κB signaling was assessed by quantitative real-time polymerase chain reaction. Monocytes cultured with and without lipopolysaccharide for 24 h were analyzed by enzyme-linked immunosorbent assay to assess the cytokine secretion stimulation index.

Monocyte mtDNA showed low variability, but alternative homoplasmies were significantly more common. Intermediate and low heteroplasmy from the protein-coding locus correlated with stenosis (r = 0.396; 95% confidence interval (CI) 0.067–0.647) and low-density lipoprotein levels (r = −0.258; 95% CI −0.45 – −0.043). Intermediate heteroplasmy from the rRNA locus correlated with blood insulin levels (r = −0.228; 95% CI −0.424 – −0.019). D-loop low heteroplasmy correlated with fasting blood glucose (r = 0.275; 95% CI 0.062–0.464). Homoplasmies were associated with creatinine, blood urea nitrogen, and alkaline phosphatase. Intermediate heteroplasmy in mtDNA was associated with the monocyte cytokine secretion stimulation index (R2 = 0.156, P = 0.003). However, there was no significant association between mtDNA variability and the expression of the various genes.

Monocyte mtDNA shows relatively low variability. Low and Intermediate heteroplasmy are associated with cardiometabolic parameters, and intermediate heteroplasmy is associated with the monocyte cytokine secretion stimulation index.

Hepatic ischemia–reperfusion (HIR) injury impairs outcomes post–liver transplantation. Therefore, we aimed to investigate the role and mechanism of miR-381-3p in HIR.

The study enrolled 150 healthy controls, 82 non-HIR-injured patients, and 68 patients with HIR injury following liver transplantation. Clinical data were analyzed. Multivariate analysis identified HIR risk factors; the predictive value of miR-381-3p was assessed via receiver operating characteristic analysis. An in vitro hypoxia/reoxygenation (H/R) model was established and employed. The cellular effects of miR-381-3p and JAK2 were evaluated using CCK-8, flow cytometry, ELISA, luciferase, RIP, and bioinformatics.

Serum miR-381-3p was significantly elevated in HIR compared with the other groups. miR-381-3p was the strongest independent HIR risk factor, which was confirmed by receiver operating characteristic analysis. H/R upregulated miR-381-3p. Inhibiting miR-381-3p counteracted H/R-induced decreased viability and increased apoptosis, inflammation, and oxidative stress. miR-381-3p directly bound to and suppressed JAK2 via its 3′ untranslated region (validated by luciferase and RIP). Transfection of si-JAK2 abolished the protective effects of miR-381-3p inhibition.

miR-381-3p exacerbates post-transplant HIR by directly targeting JAK2, amplifying inflammation and oxidative stress. Thus, our findings nominate serum miR-381-3p as a promising non-invasive biomarker and suggest its potential as a therapeutic target for mitigating HIR injury.

Extrahepatic cancers have been recognized as a significant outcome of metabolic dysfunction–associated steatotic liver disease (MASLD), which involves five cardiometabolic risk factors, including hypertension, and is associated with the tumorigenesis of several cancers or with anti-cancer treatment. We aimed to investigate the association between hypertension, liver fibrosis, and extrahepatic cancers in the MASLD population.

This multicenter cross-sectional study was based on a MASLD population from hospital-based databases across 11 centers nationwide in China, according to MASLD diagnostic criteria identified using keywords and ICD-10 codes. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between risk factors and extrahepatic cancers.

A total of 103,652 individuals with MASLD were identified, among whom 6,605 were diagnosed with extrahepatic cancers. The primary outcome revealed that hypertension was significantly associated with extrahepatic cancers (OR 1.14, 95% CI: 1.08–1.21), and its combination with hyperglycemia further increased this association (OR 1.36, 95% CI: 1.22–1.51). Risk factors for extrahepatic cancers included being over 40 years of age and female sex. Conversely, certain metabolism-based treatments were found to have potentially protective effects, including angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, fibrates, GLP-1 receptor agonists, and thiazolidinediones. After adjusting for confounding factors, the fibrosis-4 (FIB-4) score was associated with extrahepatic cancers. In the hypertension subgroup, FIB-4 scores of 1.30–2.66, 2.67–3.47, and ≥ 3.48 were associated with extrahepatic cancers in individuals aged 35–64 years, consistent with findings in those aged ≥ 65 years of age with FIB-4 ≥ 2.

Hypertension combined with liver fibrosis is associated with extrahepatic cancers in patients with MASLD.