Hepatocellular carcinoma (HCC) remains challenging to treat in advanced stages, primarily due to the development of resistance to sorafenib. There is an urgent need for novel therapeutic strategies to overcome this resistance. This study aimed to investigate the potential of oleanolic acid (OA), a natural hepatoprotective compound, in mitigating sorafenib resistance and elucidate its underlying molecular mechanisms.

Sorafenib-resistant Huh7 and HepG2 cell lines were established to mimic the resistant phenotype. The effects of OA on these cells were evaluated by assessing cell invasion, migration, and sensitivity to sorafenib. Gene expression analysis was conducted to identify molecular changes induced by OA treatment, with a focus on fabp3 expression.

Oleanolic acid significantly inhibited the invasive and migratory capabilities of sorafenib-resistant Huh7 and HepG2 cells (p < 0.01). Furthermore, OA treatment downregulated fabp3 expression and restored the cells’ sensitivity to sorafenib.

Oleanolic acid shows promise as an adjunct therapy for overcoming sorafenib resistance in HCC. By reducing cell aggressiveness and restoring drug sensitivity, OA may enhance the therapeutic efficacy of current treatments for advanced HCC.

Gastrointestinal endoscopy has revolutionized the entire practice of gastroenterology worldwide, including Nigeria. Endoscopy was introduced in Nigeria more than four decades ago, and it has been a story of varying successes and challenges. This study explored the various experiences of endoscopists, the challenges they face, and the efforts put in place to maintain the practice in Nigeria.

This cross-sectional survey was conducted from October to December 2023 among endoscopists practicing in Nigeria. It involved a 30-part self-administered online questionnaire that inquired about individual experiences in endoscopy practice. These included qualifications, competency, facility settings, challenges faced, and innovations employed to address them. At the end of the survey, responses were analyzed using descriptive statistics, Chi-square, and likelihood ratios at the 0.05 level of significance.

A total of 41 respondents participated in the survey from 19 states across the six geopolitical zones of Nigeria, with a mean age ± standard deviation of 43 ± 7 years. Male respondents made up 80.5%, with Nigerian-trained gastroenterologists via the residency program constituting the predominant population, and an average endoscopy experience of five to nine years (39.02%). Most of the respondents work in public institutions (73.17%), with 43.9% working in at least two centers. There was an average of five endoscopists and three to seven endoscopy centers per state. Most centers perform 11–12 upper and four to five lower GI endoscopies per week, respectively, with a predominance of diagnostic procedures. The most common endoscopic intervention was variceal band ligation. The most common challenge faced was the high cost of procedures, accessories, and maintenance of endoscopes.

Endoscopy practice cuts across all the zones and most states of the federation. Both diagnostic and therapeutic procedures are available in most centers. However, the practice is faced with a myriad of challenges, mainly poor financing and inadequate training, among others. As a result, some innovations were locally developed to ease the practice and prevent it from collapsing.

Endometrial cancer is a common malignant tumor of the female reproductive system, and its incidence is increasing worldwide. The underlying causes of endometrial cancer are multifactorial. In recent years, the role of diet and lifestyle has received considerable attention and has become a key area of research for cancer prevention. Available literature suggests that different dietary patterns, such as the Mediterranean diet or a plant-based diet, along with moderate physical activity, are associated with a reduced risk of this cancer. Despite these findings, significant gaps in knowledge remain, particularly regarding the specific foods, lifestyle choices, and mechanisms of action that can help mitigate the risk of cancer. Furthermore, the effects of cultural and genetic differences among subpopulations make this issue even more complex. In this context, this review aimed to assess the existing literature on the potential role of diet and lifestyle factors in preventing endometrial cancer, evaluate the available data, and highlight areas that require further investigation to provide concrete evidence and recommendations for prevention.

Tumors are complex systems characterized by variations across genetic, transcriptomic, phenotypic, and microenvironmental levels. This study introduced a novel framework for quantifying cancer cell heterogeneity using single-cell RNA sequencing data. The framework comprised several scores aimed at uncovering the complexities of key cancer traits, such as metastasis, tumor progression, and recurrence.

This study leveraged publicly available single-cell transcriptomic data from three human breast cancer subtypes: estrogen receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative. We employed a quantitative approach, analyzing copy number alterations (CNAs), entropy, transcriptomic heterogeneity, and diverse protein-protein interaction networks (PPINs) to explore critical concepts in cancer biology.

We found that entropy and PPIN activity related to the cell cycle could distinguish cell clusters with elevated mitotic activity, particularly in aggressive breast cancer subtypes. Additionally, CNA distributions varied across cancer subtypes. We also identified positive correlations between the CNA score, entropy, and the activities of PPINs associated with the cell cycle, as well as those linked to basal and mesenchymal cell lines.

This study addresses a gap in the current understanding of breast cancer heterogeneity by presenting a novel quantitative approach that offers deeper insights into tumor biology, surpassing traditional marker-based methods.

Portal hypertension can cause serious complications such as upper gastrointestinal bleeding, primarily due to esophageal and gastric varices. The risk of mortality from variceal hemorrhage is significant, particularly when the hepatic venous pressure gradient exceeds 12 mmHg. Established treatments generally include endoscopic variceal band ligation and cyanoacrylate glue for gastric varices; however, challenges such as limited availability and a lack of technical expertise can hinder the use of glue, leading to preventable complications. This study investigates the efficacy of using a 50% glucose solution for injection sclerotherapy in cases of gastric varices. We present three unique patient cases. The first case involves a 21-year-old with persistent upper gastrointestinal bleeding and a portal vein thrombus, who experienced temporary relief after receiving injection sclerotherapy but tragically succumbed to significant bleeding later. The second case describes a 24-year-old who successfully managed his bleeding with the same treatment but was subsequently lost to follow-up. Lastly, a 72-year-old patient with recurrent painless hematemesis remained free of symptoms following injection sclerotherapy. Overall, while cyanoacrylate glue remains the preferred treatment, injection sclerotherapy with 50% dextrose shows promise as an effective alternative, particularly in settings where conventional treatments are not readily available, potentially reducing the risks associated with untreated variceal bleeding.

End-stage liver disease is associated with disruptions in gut microbiota composition and function, which may facilitate gut-to-liver bacterial translocation, impacting liver graft integrity and clinical outcomes following liver transplantation. This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.

This single-center, non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion (NMP). Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3, 6, and 12. Stool microbiota was profiled via 16S rRNA gene sequencing, stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry, and breath volatile organic compounds (VOCs) were analyzed with selected-ion flow-tube mass spectrometry.

Both cohorts experienced a loss of microbiota diversity and dominance by single taxa. The NMP cohort demonstrated enrichment of several beneficial gut taxa, while the static cold storage cohort showed depletion of such taxa. Various gut bacteria were found to correlate with stool short-chain fatty acids (e.g., lactic acid, butyric acid) and several VOCs.

Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation. However, notable differences in microbiota composition and function were observed between liver graft preservation methods. Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.

Surgical management of supratentorial spontaneous intracerebral hemorrhage (sICH) remains controversial. Craniotomy (CT) reduces mortality but offers limited functional benefits. Neuroendoscopic surgery (NE) has emerged as a viable alternative, providing improved outcomes. Recent randomized controlled trials (RCTs) strengthen ongoing comparisons between these approaches. This meta-analysis systematically evaluates the efficacy and safety of NE versus CT for supratentorial sICH.

RCTs comparing NE versus CT for supratentorial sICH were systematically identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science databases. Evaluated outcomes included functional outcome (favorable or unfavorable), hematoma evacuation rate, mortality, intraoperative blood loss, operation time, rebleeding, infection (including pulmonary and intracranial), and total complications. Cochrane’s Risk of Bias-2 tool was employed to assess the risk of bias across the included studies.

Eight RCTs were included, comprising 1,354 patients. NE demonstrated a significant advantage in achieving a favorable functional outcome (risk ratio: 1.43; 95% confidence interval (CI) 1.22, 1.68; p < 0.001) and a notably higher hematoma evacuation rate (mean difference (MD): 7.60; 95% CI 3.59, 11.61; p < 0.001). Additionally, NE was associated with a marked reduction in intraoperative blood loss (MD: −152.95; 95% CI −261.68, −44.22; p = 0.006) and a substantial reduction in operative time (MD: −118.49; 95% CI −147.30, −89.67; p < 0.001). The incidences of unfavorable functional outcome and total complications, including pulmonary infection, were significantly lower in the NE group. However, NE did not lead to an improvement in the mortality rate, and there were no significant differences in the incidences of postoperative rebleeding or intracranial infection between the two groups.

These findings suggest that NE offers distinct advantages in terms of functional outcomes and surgical efficiency for patients with supratentorial sICH. Future studies should involve larger, higher-quality RCTs, and neuroendoscopic techniques should be continuously optimized.

Cardiovascular diseases (CVDs) remain the leading cause of global morbidity and mortality, highlighting the urgent need for innovative diagnostic and prognostic approaches to address their complex pathophysiology. Recent advances in molecular cardiology have unveiled immune-derived microRNAs (miRNAs), or immuno-miRs, as pivotal regulators in the interplay between immune responses and cardiovascular pathology. Secreted by immune cells such as T lymphocytes, macrophages, and neutrophils, these small non-coding RNAs modulate critical signaling pathways by regulating gene expression. Immuno-miRs influence essential processes, including inflammation, endothelial dysfunction, and fibrotic remodeling—core mechanisms underlying conditions such as atherosclerosis, myocardial infarction, and heart failure. Moreover, their presence in systemic circulation within extracellular vesicles underscores their role in intercellular communication, impacting both immune and non-immune cardiovascular cells, such as cardiomyocytes and endothelial cells. This dual functionality renders immuno-miRs promising candidates as diagnostic biomarkers for early disease detection and as prognostic tools for assessing disease progression and therapeutic efficacy. Furthermore, emerging miRNA-based interventions—such as miRNA mimics and inhibitors—show considerable promise in modulating immune dysregulation in CVDs, although clinical translation remains a significant challenge. In this review, we comprehensively examine the regulatory roles of immuno-miRs in both innate and adaptive immune responses and explore recent advancements in miRNA-based therapies. By consolidating current knowledge and identifying existing gaps, we provide a comprehensive overview of the transformative potential of immuno-miRs in CVD management. Integrating these molecules into personalized medicine may pave the way for more effective, targeted, and minimally invasive strategies to combat one of the world’s most pressing health challenges.

Heme oxygenase 1 (HO-1) has an influential yet insufficiently investigated effect on Sirtuin 1 (SIRT1), a histone deacetylase activated by nicotinamide adenine dinucleotide, which may impact the transforming growth factor-β (TGF-ß)/Smad3 pathway in nonalcoholic fatty liver disease (NAFLD)-related liver fibrosis. This study aimed to elucidate the regulation of NAFLD-related liver fibrosis induced by HO-1 through the SIRT1/TGF-ß/Smad3 pathway.

HO-1 induction and inhibition were established in C57BL/6J mice fed a methionine- and choline-deficient (MCD) diet. Additionally, wild-type mice were fed either a normal diet or an MCD diet. Hematoxylin and eosin, Masson’s trichrome, and Sirius Red staining were used to assess hepatic steatosis, inflammation, and fibrosis. In vitro, plasmid overexpression and small interfering RNA silencing of HO-1 were performed in LX-2 cells. Cell viability was assessed using the Cell Counting Kit-8, and apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick-end labeling and immunofluorescence. Flow cytometry was employed to assess apoptosis and reactive oxygen species production. Western blot and real-time quantitative reverse transcription polymerase chain reaction were used to analyze the mRNA and protein expression of genes related to HO-1, SIRT1, the TGF-ß signaling pathway, and fibrosis.

MCD-fed mice developed significant liver damage, including steatosis, inflammatory infiltration, and pericellular fibrosis. Zinc protoporphyrin treatment exacerbated these conditions. Corroborating these findings, silencing HO-1 in LX-2 cells increased the expression of fibrosis-related genes. Furthermore, HO-1 overexpression not only increased SIRT1 expression but also reduced the activity of key regulatory factors in the TGF-ß signaling pathway, suggesting a potential interaction between HO-1 and the SIRT1/TGF-ß pathway.

HO-1 inhibits the activation of the TGF-ß/Smad3 pathway in NAFLD-related liver fibrosis through SIRT1. These findings provide insights into new therapeutic strategies for treating NAFLD-associated liver fibrosis.

T lymphocytes play a pivotal role in resolving hepatitis B virus infection. This study aimed to investigate the dynamics of peripheral blood T lymphocyte subsets during peginterferon alpha (peg-IFN-α) therapy and their association with hepatitis B surface antigen (HBsAg) clearance in inactive HBsAg carriers (IHCs).

This prospective observational study enrolled 197 IHCs treated with peg-IFNα-2a/2b for 48 weeks and followed for 24 weeks (treatment group), and 221 IHCs who were regularly monitored for 72 weeks without treatment (IHC control group). Peripheral blood T lymphocyte subsets were evaluated using flow cytometry at baseline, and at 12, 24, 48, and 72 weeks in both groups. At 72 weeks, IHCs in the treatment group were categorized into an HBsAg clearance group and an HBsAg persistence group. Differences in T lymphocyte subsets among these groups were compared, and correlations between T lymphocyte subsets and HBsAg clearance were analyzed.

At 72 weeks, intention-to-treat analysis showed significantly higher HBsAg clearance (46.7%) and seroconversion rates (34.5%) in the treatment group compared to the IHC control group (HBsAg clearance rate of 1.4%, seroconversion rate of 0.9%; both p < 0.001). The median absolute counts of CD3+, CD4+, and CD8+ cells significantly decreased at 12, 24, and 48 weeks in both the HBsAg clearance and persistence groups, returning to baseline at 72 weeks (all p < 0.001). IHCs with HBsAg clearance had higher median percentages of CD3+ CD8+ cells and lower median percentages of CD3+ CD4+ cells and CD4+/CD8+ ratios at 12, 24, and 48 weeks compared to the HBsAg persistence and IHC control groups (all p < 0.001). Baseline HBsAg levels (below 2.0 log10 IU/mL) and hepatitis B virus DNA levels (below 20 IU/mL), alanine aminotransferase elevation at 12 weeks (greater than 2×upper limit of normal), and CD4+/CD8+ ratios (less than 1.5 at 12 weeks and below 1.4 at 24 weeks) were predictive of HBsAg clearance.

Peripheral blood CD4+/CD8+ ratios at 12 and 24 weeks may serve as predictive markers for HBsAg clearance in IHCs treated with peg-IFN-α.