Recent studies have highlighted a link between amyotrophic lateral sclerosis (ALS) and gut microbiota. This prospective study aimed to evaluate the effects of electroacupuncture combined with Chinese herbal medicine on gut microbiota and metabolomics in ALS patients.

Ten ALS patients were randomly assigned to either a treatment group (electroacupuncture with Chinese herbal medicine, n = 6) or a control group (waiting treatment, n = 4). Healthy controls (age- and sex-matched, n = 10) were also included. Data were collected after 12 sessions of electroacupuncture and follow-ups at three and six months. ALS functional rating scale scores were documented pre- and post-treatment. Stool samples were collected at two time points (T0 and T4 weeks) and analyzed, and metabolomic profiles from urine samples were analyzed post-treatment. Heatmap correlation analysis was used to explore relationships between microbiota, metabolomics, and clinical outcomes.

Treatment with electroacupuncture reduced Eisenbergiella abundance in the treatment group. A significant positive correlation was found between Lachnospiraceae and ALS functional rating scale scores (P < 0.005 and P < 0.001, respectively). Differential expression of purine metabolism was observed in ALS patients (P = 0.0017).

Imbalances in the gut microbiome and metabolic disorders have been found among patients with ALS. These imbalances appear to be partially mitigated by treatment with electroacupuncture combined with Chinese herbal medicine. Our research suggests that Eisenbergiella might be a diagnostic biomarker and a potential therapeutic target for ALS.

Wilson’s disease (WD) is a rare autosomal recessive genetic disorder that can be treated with medications. The lack of a single, specific diagnostic indicator leads to diagnostic difficulties, which may result in disease progression to cirrhosis and even liver cancer. Thus, this study aimed to analyze the clinical data, imaging, histopathological manifestations, genetic testing results, and treatment effects of patients with WD hepatic type, and to explore the factors related to WD cirrhosis.

A single-center retrospective study was performed. 48 WD patients with a Leipzig score ≥ 4 were divided into a cirrhosis group and a non-cirrhosis group based on the presence of cirrhosis. Logistic regression analysis and odds ratios were used to describe the strength of association between risk factors and cirrhosis. The predictive value of the model for cirrhosis occurrence was evaluated by calculating the area under the receiver operating characteristic curve and the cutoff value.

All 48 patients diagnosed with WD had liver damage, with males accounting for 54.17%. The median age at diagnosis was 28 years (range: 10.25–40.5 years), and 39.58% of patients had cirrhosis. The most prevalent mutation was c.2333G>T (p.Arg778Leu), found in 41.30% (19/46) of cases. Imaging revealed fatty liver in 31.25% (15/48) of patients and “honeycomb-like” cirrhosis nodules in 73.68% (14/19). Compared with the non-cirrhosis group, the cirrhosis group had a higher positive rate for the Kayser-Fleischer (K-F) ring, older age at diagnosis, and higher levels of immunoglobulin G, but lower levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, white blood cells, and platelets (p < 0.05). Age at diagnosis (odds ratio = 1.072, 95% confidence interval = 1.007–1.142, p = 0.03) and the K-F ring (odds ratio = 18.657, 95% confidence interval = 1.451–239.924, p = 0.025) were independent risk factors for WD-related cirrhosis. The best values of area under the receiver operating characteristic curve for age at diagnosis combined with the K-F ring in predicting WD cirrhosis were 0.909. The average follow-up time for 33 patients was 48.6 months (range: 12–72 months). The biochemical recovery rate was over 60% after 12–72 months of treatment with zinc gluconate and/or penicillamine.

Age at diagnosis, combined with the K-F ring, is a simple and effective risk factor for WD-related cirrhosis. Zinc gluconate and penicillamine are safe and effective treatments.

With progress in basic and clinical research on hepatic encephalopathy in cirrhosis worldwide, the Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise the 2018 “Chinese Guidelines on the Management of Hepatic Encephalopathy in Cirrhosis.” The updated guidelines provide recommendations for the clinical diagnosis, treatment, and both primary and secondary prevention of hepatic encephalopathy in cirrhosis.

Ischemic colitis has been previously associated with the use of certain medications; however, no cases have been reported in connection with zolmitriptan. This study aimed to describe a case of ischemic colitis associated with zolmitriptan use. A 56-year-old female patient taking zolmitriptan presented to the hospital with complaints of abdominal pain, bloody diarrhea, and emesis. Colonoscopy and abdominal imaging with computed tomography revealed findings consistent with ischemic colitis. After recognizing the association between ischemic colitis and zolmitriptan use, the medication was discontinued, and the patient recovered with supportive therapy. This is the first reported case of ischemic colitis associated with zolmitriptan.

Cholesterol synthesis and gallstone formation are promoted by trimethylamine-N-oxide (TMAO), a derivative of trimethylamine, which is a metabolite of gut microbiota. However, the underlying mechanisms of TMAO-induced lithogenesis remain incompletely understood. This study aimed to explore the specific molecular mechanisms through which TMAO promotes gallstone formation.

Enzyme-linked immunosorbent assays were used to compare serum concentrations of TMAO, apolipoprotein A4 (APOA4), and proprotein convertase subtilisin/kexin type 9 (PCSK9) between patients with cholelithiasis and normal controls. A murine model of TMAO-induced cholelithiasis was employed, incorporating assays of gallstone weight and bile cholesterol content, along with RNA sequencing of murine hepatic tissue. A TMAO-induced AML12 hepatocyte line was constructed and transfected with targeted small interfering RNAs and overexpression plasmids. In vivo and in vitro experiments were performed to determine the expression and regulation of genes related to cholesterol metabolism.

Serum TMAO and PCSK9 levels were elevated, whereas APOA4 levels were reduced in patients with cholelithiasis. Furthermore, our murine model demonstrated that TMAO upregulated hepatic expression of PCSK9, 3-hydroxy-3-methylglutaryl-CoA reductase, and ATP-binding cassette sub-family G member 5/8, while reducing APOA4 expression, thereby modulating cholesterol metabolism and promoting lithogenesis. PCSK9 and APOA4 were identified as key regulatory genes in the cholesterol metabolic pathway. PCSK9 knockdown increased APOA4 expression, while APOA4 overexpression led to reduced PCSK9 expression.

TMAO upregulated hepatic PCSK9 expression and reduced APOA4 expression, initiating a feedback loop that dysregulated cholesterol metabolism and promoted lithogenesis.

General transcription factor IIIC subunit 2 (GTF3C2) is one of the polymerase III transcription-related factors. Previous studies have revealed that GTF3C2 is involved in regulating cell proliferation. However, the role of GTF3C2 in hepatocellular carcinoma (HCC) remains unclear. This study aimed to determine its expression, biological function, and mechanism in HCC.

The expression of GTF3C2 in HCC and non-tumor tissues, along with its clinical significance, was investigated using public databases and clinical samples. Reverse transcription-quantitative polymerase chain reaction and Western blot assays were performed to detect the expression of GTF3C2, ubiquitin specific peptidase 21 (USP21), mitogen-activated protein kinase 2 (MEK2), extracellular signal-regulated kinase 1/2 (ERK1/2), and p-ERK1/2 in cells. A luciferase reporter assay was conducted to explore the regulatory effect of GTF3C2 on USP21 transcription. Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, and colony formation assays were performed to assess HCC cell proliferation. Subcutaneous injection of HCC cells into nude mice was used to evaluate tumor growth in vivo.

GTF3C2 expression was upregulated in HCC tissues and was positively correlated with advanced tumor stages and high tumor grades. HCC patients with high GTF3C2 expression had significantly worse survival outcomes. Knockdown of GTF3C2 suppressed the proliferation of Hep3B and HCCLM3 cells, while overexpression of GTF3C2 facilitated the proliferation of SNU449 and Huh7 cells. GTF3C2 promoted USP21 expression by activating its transcription, which subsequently increased the levels of MEK2 and p-ERK1/2 in HCC cells. Overexpression of both USP21 and MEK2 counteracted the GTF3C2 knockdown-induced inactivation of the ERK1/2 pathway. Moreover, GTF3C2 promoted HCC cell proliferation in vitro and tumor growth in vivo by regulating the USP21/MEK2/ERK1/2 pathway.

Upregulation of GTF3C2 is frequently observed in HCC tissues and predicts poor prognosis. GTF3C2 promotes HCC cell proliferation via the USP21/MEK2/ERK1/2 pathway.

Direct-acting antivirals (DAAs) have dramatically changed the landscape of chronic hepatitis C virus (HCV) treatment and significantly reduced the risk of HCV-related hepatocellular carcinoma (HCC) after achieving sustained virologic response. However, the risk of HCC persists, particularly in patients with pre-treatment cirrhosis or fibrosis stage 3 (F3), even after DAA-induced viral eradication. While professional guidelines agree on the need for surveillance in cirrhotic patients, there is no consensus regarding surveillance for the pre-treatment F3 population following HCV eradication. The risk of HCC in the F3 population falls below the threshold for cost-effective surveillance. However, co-existing risk factors—such as diabetes, hepatic steatosis, alcohol use, advanced age, and elevated alpha-fetoprotein levels—may warrant reconsideration of HCC surveillance in this group. This underscores the need for an individualized, risk-based approach to HCC surveillance. This review provided a simplified algorithm to assist clinicians in managing patients with HCV after DAA-induced sustained virologic response.

Cancer continues to pose a substantial public health problem in Nigeria, characterized by rising rates of occurrence and mortality. While there is increasing interest in using natural products for cancer treatment, comprehensive data on the specific bioactive compounds in these plants and how they modulate different types of cancer are still lacking. Additionally, although traditional knowledge about these food plants is rich and valuable, it has not been fully integrated with modern scientific research to create standardized treatment protocols. Scientific databases like PubMed, ScienceDirect, Google Scholar, and ResearchGate were explored to retrieve empirical data. The key plants discussed are Spondias mombin, Xanthosoma sagittifolium, Elaeis guineensis, Irvingia gabonensis, Allium cepa, Blighia sapida, Dioscorea dumetorum, Psidium guajava, and Talinum triangulare. These plants demonstrate a wide range of anticancer properties, including the ability to induce apoptosis (cell death), halt the cell cycle, inhibit angiogenesis, and regulate inflammatory responses. They contain a variety of phytochemicals, such as flavonoids, tannins, terpenoids, alkaloids, and organosulfur compounds, which contribute to their anticancer effects. For example, Spondias mombin contains flavonoids that inhibit the formation of tumors, whereas Xanthosoma sagittifolium exhibits cytotoxic effects against leukemia cells. Additionally, Elaeis guineensis exhibits antioxidant properties that counteract oxidative stress, a crucial factor in cancer progression. This review highlights the significance of these plants in developing complementary cancer therapies that can be used alongside conventional treatments. By combining traditional knowledge with contemporary scientific methods, these medicinal plants have the potential to provide innovative approaches to cancer prevention and treatment, addressing the pressing demand for safer and more efficient therapeutic alternatives.

Oral contraceptive pills (OCPs) are commonly used for contraception, but their long-term effects on oxidative stress, lipid profiles, and liver function remain unclear. This study aimed to evaluate the impact of intermediate-term OCP use (Yasmin) on oxidative stress, lipid profile, and liver function, with particular emphasis on antioxidant markers, lipid metabolism, and hepatic enzyme activity, to better understand the potential metabolic and hepatic effects.

A case-control study was conducted in Maysan Governorate, Iraq, involving 150 women (100 OCP users and 50 non-users). Blood samples were collected from Al-Sadr Teaching Hospital and a specialized clinic between February and April 2023. Serum levels of antioxidants, lipids, and liver enzymes were measured using biochemical assays.

OCP users had significantly lower levels of glutathione peroxidase vitamin E and uric acid (p < 0.001) compared to non-users. Lipid profiles showed that OCP users had higher levels of triglyceride and low-density lipoprotein (p < 0.05), whereas total cholesterol was significantly higher in non-users (p < 0.05). Liver enzyme activity, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total serum bilirubin, did not show statistically significant differences (p > 0.05). Longer duration of OCP use was significantly negatively correlated with vitamin E levels (r = −0.67), glutathione peroxidase activity (r = −0.56), uric acid levels (r = −0.45) and high-density lipoprotein (r = −0.54). Positive correlations were found between the duration of OCP use and total cholesterol (r = 0.62), triglyceride (r = 0.58), low-density lipoprotein (r = 0.60), and liver enzymes alanine aminotransferase (r = 0.66) and aspartate aminotransferase (r = 0.64).

Intermediate-term OCP use was associated with changes in oxidative stress and lipid metabolism, potentially increasing cardiovascular and metabolic risks. Regular monitoring of these parameters is recommended for OCP users.

Protein disulfide isomerases (PDIs) are essential enzymes that facilitate the proper folding of proteins and maintain protein quality within the endoplasmic reticulum. Dysregulation of PDIs has been correlated with numerous disorders, including cancer and rheumatoid arthritis (RA). E64FC26 (EFC), a small molecule that inhibits a wide range of PDI family members, has shown promise as a therapeutic agent in oncology. However, its effects on RA have not yet been studied. This research investigates the efficacy of EFC as a potential treatment for RA.

To investigate EFC’s effects on RA fibroblast-like synoviocytes, several assays were employed, including Cell Counting Kit-8 for cell viability, EdU for cell proliferation, Transwell for migration and invasion, TUNEL for apoptosis, and in vitro tube formation assays for angiogenesis. Flow cytometry was used to assess apoptosis in detail. Cytokine production was analyzed using ELISA and real-time polymerase chain reaction. In vivo, a collagen-induced arthritis model was developed in DBA mice to evaluate EFC’s effects on inflammation, disease progression, and bone damage. RNA sequencing was utilized to identify the molecular pathways influenced by EFC treatment.

EFC exhibited significant anti-inflammatory effects on RA fibroblast-like synoviocytes, reducing cell proliferation, migration, invasion, angiogenic activity, and cytokine secretion, while simultaneously promoting apoptosis. In vivo experiments using the collagen-induced arthritis mouse model showed that EFC alleviated inflammation, slowed disease progression, and preserved joint and bone integrity. RNA sequencing data suggested that EFC acts through pathways associated with inflammation and apoptosis regulation.

The findings of this research underscore EFC’s therapeutic potential in managing RA. These results pave the way for the development of inhibitors targeting the PDI family as innovative treatments for RA.