Breast cancer is the most common cancer among women, with hormone receptors playing a crucial role, not only in cancer cell growth but also as primary targets in breast cancer treatment. This systematic literature review aimed to summarize the current evidence on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) discordance rates between primary and recurrent breast cancer. Additionally, it seeks to identify how discordance affects prognosis, metastasis, and the potential evidence of primary tumor heterogeneity.

The databases Web of Science, Scopus, MEDLINE, and PubMed were searched for publications of original research in English from 2013 to 2023. Studies with paired histopathology from primary and recurrent breast cancer that employed immunohistochemistry and fluorescence in situ hybridization were included. Ten studies were deemed eligible for inclusion.

Concordance between primary and recurrent breast cancer was high for ER (80%), PR (65%), and HER2 (85%). Average discordance rates were: ER 19%, PR 34%, and HER2 15%, with PR discordance consistently being the highest. Loss of ER and PR receptors was observed more frequently than gain, while the opposite trend was noted for HER2. Loss of ER and PR was associated with a worse prognosis. Discordance was also observed in cases of tumor metastasis.

Discordance in receptor expression between primary and recurrent breast cancer was common, highlighting the importance of re-biopsy in recurrent or metastatic breast cancer, if possible. Patients who lost hormone receptors experienced worse outcomes, suggesting the development of treatment-resistant tumor clones.

Chronic hepatitis B virus (HBV) infection remains a major cause of liver diseases, including cirrhosis and hepatocellular carcinoma. Reliable biomarkers for assessing viral replication, liver damage, and predicting clinical outcomes are essential for effective patient management. This review focuses on two promising biomarkers: serum HBV RNA and hepatitis B core-related antigen, both of which show strong correlations with viral replication and disease progression. Serum HBV RNA levels reflect the quantity and transcriptional activity of intrahepatic covalently closed circular DNA, providing insights into viral replication. They also correlate with other markers of replicative activity and have predictive value for key clinical outcomes, including hepatitis B e antigen and hepatitis B surface antigen seroconversion, relapse after therapy cessation, and liver fibrosis. Similarly, hepatitis B core-related antigen is closely associated with covalently closed circular DNA levels, correlates with markers of viral replication, and shows promise in predicting liver fibrosis, cirrhosis, and the risk of hepatocellular carcinoma. This review highlights the potential of both biomarkers for monitoring disease progression and guiding therapeutic decisions, particularly in the context of personalized treatment strategies and risk assessment for liver-related complications.

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.

Data regarding risk factors and long-term outcomes of U.S. patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD) are limited. This study aimed to investigate the role of clinical and histologic risk factors on long-term outcomes in patients with MASLD.

A retrospective cohort study of 451 adults with biopsy-proven MASLD was conducted at a U.S. academic hospital from 2012 to 2020. An experienced pathologist evaluated the index liver biopsy. Patients with a prior liver transplant or alternative etiologies of chronic liver disease were excluded. The duration of the risk exposure was determined from the date of the index liver biopsy to an outcome event or the last follow-up examination. Outcome events of interest included incident liver-related events, liver decompensation, and all-cause mortality.

In the final cohort of 406 patients followed for a median of 3.7 years (interquartile range: 4.8 years), 35 patients died, 41 developed hepatic decompensation, and 70 experienced a liver-related event. Among histologic risk factors, stage 3 (adjusted Hazard ratio (aHR) 2.68, 95% confidence interval (CI) 1.18–6.11) and stage 4 (aHR 6.96, 95% CI 3.55–13.64) fibrosis were associated with incident liver-related events compared to stage 0–1 fibrosis. Stage 4 (aHR 8.46, 95% CI 3.26–21.99) fibrosis alone was associated with incident liver decompensation events compared to stage 0–1 fibrosis. Among clinical risk factors, hypertension (aHR 2.58, 95% CI 1.05–6.34) was associated with incident liver decompensation.

In a U.S. single-center cohort of patients with biopsy-proven MASLD, advanced fibrosis was the primary risk factor for incident liver decompensation and liver-related events.

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.

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.

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.

The effect of tenofovir amibufenamide (TMF) on blood lipid profiles in patients with chronic hepatitis B (CHB) remains unclear. This study aimed to explore whether TMF affects blood lipids during 48 weeks in patients with CHB.

A total of 91 patients with CHB undergoing TMF treatment for 48 weeks were divided into two groups: Lipid Normal (n = 42) and Lipid Abnormal (n = 49), based on baseline blood lipid levels. Lipid indices, virological responses, and biochemical indicators were compared between the two groups. Clinical observations were further verified through in vitro experiments.

After an average follow-up of 373 ± 121 days, lipid indices in all 91 patients had not significantly changed compared with baseline (total cholesterol: 4.67 vs. 4.69 mmol/L, P = 0.2499; triglycerides: 1.08 vs. 1.04 mmol/L, P = 0.4457; high-density lipoprotein cholesterol: 1.25 vs. 1.25 mmol/L, P = 0.3063; low-density lipoprotein cholesterol: 3.03 vs. 3.02 mmol/L, P = 0.5765). Subgroup comparisons showed lipid indices remained stable. Among treatment-naïve patients (n = 82), complete viral suppression rates were 23.2%, 59.8%, 70.7%, and 86.6% at four, 12, 24, and 48 weeks, respectively. Cellular experiments revealed that TMF did not promote lipid metabolism in primary hepatocytes and AML12 cells.

Regardless of baseline blood lipid characteristics, 48 weeks of antiviral treatment with TMF in patients with CHB had no significant lipid-raising effect.

Macromolecular-based gene delivery systems have emerged as viable alternatives to non-viral vectors for gene therapy due to their versatility, biocompatibility, and capacity to efficiently deliver therapeutic cargo. These systems, primarily based on synthetic and natural polymers, offer significant advantages in terms of safety, controlled gene release, and targeted delivery. This review explores the design and synthesis of macromolecular carriers, focusing on their chemical and physical architectures, which play a key role in improving gene delivery. Catanionic polymers and their derivatives (comb, brush, and star polymers) have been extensively researched for their capacity to condense and protect genetic material. Furthermore, natural polymers like chitosan and hyaluronic acid have been modified to enhance gene delivery capabilities. These macromolecular carriers are engineered to boost circulation time, increase cellular uptake, and facilitate the controlled release of genetic material at the target site. Strategies such as incorporating targeting ligands, stimuli-responsive elements, and reducing cytotoxicity are being pursued to improve the overall efficiency and specificity of these systems. This review highlights the current state of macromolecular gene delivery systems, their applications, and the ongoing research aimed at overcoming existing challenges, paving the way for more effective non-viral gene therapies.

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.