Breast cancer is one of the leading causes of mortality among women worldwide. Tumor necrosis factor α-induced protein 3-interacting protein 1 (TNIP1) is a ubiquitin-binding protein that is widely expressed, but its function in breast cancer cells remains unknown. This study aimed to elucidate the molecular mechanism of TNIP1 regulation in the proliferation and apoptosis of breast cancer cells.

A colony formation assay was conducted on MCF-7 and T47D cells stably transfected with TNIP1/cyclin G1 (CCNG1) short hairpin RNAs. Quantitative polymerase chain reaction was performed to assess the relative abundances of TNIP1, CCNG1, and cyclin D1 (CCND1) messenger RNAs. Immunoprecipitation and immunoblotting were used to detect the expression of TNIP1, CCNG1, CCND1, and related proteins. A dual-luciferase reporter assay was employed to explore the molecular mechanism of TNIP1 in signal transduction. Caspase activity in MCF-7 and T47D cells transfected with TNIP1 short hairpin RNAs was measured using the Caspase-Glo 3/7 assay.

Ablation of TNIP1 induced growth arrest in breast cancer cells. TNIP1 directly interacted with CCNG1, and TNIP1 knockdown increased the ubiquitination of CCNG1. CCNG1 knockdown also induced growth arrest in MCF-7 and T47D cells. Furthermore, TNIP1 knockdown activated the NF-κB pathway and induced apoptosis in these cells.

TNIP1 regulates the proliferation and apoptosis of breast cancer cells, suggesting that TNIP1 may serve as a potential biomarker for breast cancer.

Shenqi Fuzheng (SQ) is a widely used Chinese medicine formula known for its immune-enhancing and Qi-supplementing properties. However, the blood-absorbed components of SQ and their pharmacokinetics remain underexplored. This study aimed to comprehensively analyze the chemical constituents of SQ and investigate their absorption and pharmacokinetic behavior in rat plasma.

Ultra-performance liquid chromatography-triple quadrupole time-of-flight mass spectrometry (hereinafter referred to as UPLC-Triple-TOF/MS) is employed to identify the chemical components in SQ extract and quantify the components absorbed into the blood after oral administration in rats. This method provides fragmentation patterns of compounds and key pharmacokinetic profiles of blood-absorbed compounds.

A total of 105 compounds are identified from the SQ extract, and 40 are detected in the blood following oral administration. Organic acids and amino acids are found at higher concentrations in the bloodstream. Compounds such as Astragalosides promptly enter the bloodstream within 5 m after administration, with levels declining after 15 m. Flavonoids are absorbed within 15–30 m, and the peak of alkaloids occurs approximately 1 h after administration.

This study provides new insights into the chemical composition and pharmacokinetics of SQ, highlighting the dynamic changes in the content of absorbed compounds in the blood. It further promotes the comprehensive characterization of traditional Chinese medicine formulations through UPLC-Triple-TOF/MS. Future research should focus on elucidating the pharmacological activities of the identified compounds and investigating their potential synergistic effects within the formulation.

Exophiala, a genus of saprotrophic black fungi commonly found in the environment, is typically associated with cutaneous infections in immunocompromised hosts and rarely manifests as pneumonia. Here, we report the first case of Exophiala pneumonia in Pakistan, occurring in an immunocompetent, middle-aged female with interstitial lung disease.

A 56-year-old female presented with a two-week history of malaise and a cough productive of black sputum. On auscultation, fine crackles were heard in the bilateral posterior middle and lower lung fields. Chest radiography showed features of usual interstitial pneumonia with patchy and dense reticular opacities in the middle and lower lung lobes bilaterally. Bronchoscopy was performed, and bronchoalveolar lavage was sent to the microbiology laboratory for culture. Gram stain findings revealed numerous pus cells, primarily neutrophils, along with septate hyphae, which were also confirmed on potassium hydroxide smear. The results were communicated to the treating physician, and the patient was started on intravenous voriconazole. After four days of incubation at 25°C and 37°C, colonies of mold were observed on the culture, which were identified as Exophiala jeanselmei on Lactophenol Cotton Blue staining. After one week of treatment, the patient showed clinical improvement and was discharged on oral voriconazole with outpatient follow-up.

Our findings suggest that bronchoalveolar lavage with an elevated neutrophil count and abnormal pulmonary imaging should be evaluated as signs of both fungal and bacterial pneumonia. Additionally, fungal culture should be considered in such cases, as it employs specific techniques and prolonged incubation for the isolation of fungi. Since Exophiala jeanselmei is a rare yet severe cause of pneumonia, early detection and the knowledge gained from treated infections are crucial for effective management.

Hepatocellular carcinoma (HCC) represents the most prevalent malignancy in Egypt and globally. However, non-invasive diagnostic/prognostic biomarkers for early detection of HCC are still lacking. Circular RNAs (circRNAs) are one of the promising biomarkers. They are considered stable, long-stranded non-coding RNAs in a sealed circular form held together by covalent bonds. circRNAs have been observed in several genetic studies to play a vital role in the initiation and progression of malignancy. Our current cross-sectional study aimed to evaluate the potential role of serum-derived hsa_circ_101555 as a diagnostic biomarker for HCC, in addition to comparing its prognostic significance and predicting the response to therapy.

The serum expression level of hsa_circ_101555 was measured using real-time polymerase chain reaction in 62 clinically/radiologically diagnosed Egyptian HCC patients at baseline and three months after HCC treatment. These results were compared to those of 30 healthy subjects.

Our data showed that the mean circRNA value was highest in HCC cases (7.66 ± 3.74) compared to healthy controls (1.21 ± 0.96). Furthermore, the circRNA value showed excellent diagnostic accuracy in differentiating HCC patients from healthy controls at a cutoff point of 1.966, as indicated by an area under the curve of 0.984. In addition, it showed a prognostic role in differentiating between HCC progression and regression in these patients based on response evaluation criteria in solid tumors (RECIST)/ modified- RECIST (mRECIST) response categories at the cutoff point 5.1150, with an area under the curve of 0.891 and a standard error of 0.058. Interestingly, positive correlations between post-intervention circRNA levels and laboratory measurements were observed in our HCC patients, including the albumin-bilirubin score (r = 0.424, P = 0.001**), the neutrophil-to-lymphocyte ratio (r = 0.410, P = 0.001**), alpha-fetoprotein (r = 0.273, P = 0.032*), the aspartate aminotransferase/alanine aminotransferase ratio (r = 0.284, P = 0.025*), fibrosis-4 (r = 0.501, P = 0.000**), and the aspartate aminotransferase to platelet ratio score (r = 0.436, P = 0.000**), indicating an association with worsening liver inflammation, fibrosis, and disease progression. Lastly, post-intervention circRNA values were significantly correlated with clinical/pathological tumor key features, including larger tumors (>5 cm) (P = 0.019), multiplicity (tumor numbers > 3) (P = 0.031), vascular invasion (P = 0.030), Barcelona Clinic Liver Cancer stage C (P = 0.007), and advanced Tomur, Node, Metastasis stage (P = 0.012).

To our knowledge, this is the first study to highlight the expression levels of serum-derived hsa_circ_101555 in Egyptian HCC patients. Our data showed its upregulation in HCC cases compared to healthy subjects. Additionally, its increased levels were associated with tumor progression according to the RECIST/mRECIST categories. Furthermore, its significant correlation with markers/scores of liver inflammation, dysfunction, and tumor pathological features underscores its potential as a promising diagnostic/prognostic biomarker, aiding in better clinical decision-making for the management of hepatocellular carcinoma.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of hepatic fibrosis, yet its prevalence in asymptomatic populations remains unclear. This study aimed to assess the prevalence of steatosis and significant fibrosis in asymptomatic individuals without known liver disease in the Greater Vancouver Area.

Interested individuals voluntarily registered online via the Canadian Liver Foundation website or by telephone. Inclusion criteria included age ≥ 19 years, no known liver disease, and low alcohol intake (<30 g/day for men, <20 g/day for women). Demographic and clinical data were collected, and all participants underwent transient elastography after a 3-h fast. The study aimed to collect 4,500 analyzable scans while reflecting the region’s ethnic diversity.

A total of 4,193 participants were analyzed. The median age was 62 years, the median body mass index was 25.4, and 45% were male. Asian individuals comprised 42% of the cohort. Steatosis was present in 59.6% of participants, and 45.7% met diagnostic criteria for MASLD. Significant fibrosis (F2–F4) was found in 8.6%. Age, male sex, ethnicity, cardiac disease, diabetes, hypertension, and obesity were significantly associated with fibrosis. Logistic regression analysis confirmed age, weight, diabetes, dyslipidemia, hypertension, and obesity as independent predictors.

A substantial proportion of asymptomatic individuals in Greater Vancouver have undetected MASLD and significant fibrosis. Early identification of high-risk groups may support broader implementation of transient elastography screening. This study provides one of the first North American population-based estimates of MASLD and fibrosis stratified by ethnicity, offering new insights into liver disease distribution among Caucasian, Chinese, and South Asian populations.

Prognostic scores are valuable tools for predicting survival in patients with chronic liver disease. Recently, the albumin-bilirubin (ALBI) score has emerged as a potential prognostic indicator in liver-related conditions. This study aimed to compare the prognostic efficacy of the ALBI score with the Model for End-stage Liver Disease (MELD), MELD-Na+, and Child-Turcotte-Pugh (CTP) scores in predicting survival among patients with alcohol-associated liver disease (ALD).

This study included consecutive ALD patients admitted to the Medicine and Gastroenterology wards of MKCG Medical College and Hospital, Berhampur, Odisha, India, between November 2019 and November 2022. Upon hospitalization, baseline characteristics, clinical and laboratory parameters, ALBI, MELD, MELD-Na+, and CTP scores were recorded. The accuracy of these scores in predicting survival up to three years was compared.

A total of 490 ALD patients were included. Higher ALBI scores were observed in patients who died during hospitalization (p < 0.001), at 28 days (p < 0.001), 90 days (p < 0.001), six months (p < 0.001), one year (p < 0.001), two years (p < 0.001), and three years (p < 0.001), compared to those who survived. However, the area under the receiver operating characteristic (AUROC) curves showed that the ALBI score was inferior to MELD, MELD-Na+, and CTP scores in predicting survival at admission [AUROC: ALBI (0.719), MELD-Na+ (0.823), MELD (0.817), CTP (0.770)] and at three years [AUROC: ALBI (0.755), MELD-Na+ (0.787), MELD (0.758), CTP (0.784)]. Furthermore, Cox regression analysis revealed that components used in the MELD, MELD-Na+, and CTP scores—such as serum creatinine, serum sodium, and hepatic encephalopathy—were independent predictors of mortality, whereas the components of the ALBI score (serum albumin and serum bilirubin) were not.

All hospitalized ALD patients had a grade 3 ALBI score, with significantly higher scores observed among non-survivors compared to survivors. However, MELD, MELD-Na+, and CTP scores were superior to the ALBI score in predicting survival both during hospitalization and over a three-year follow-up period.

Neurodegenerative diseases (NDs) represent a major global health challenge in aging populations, with their incidence continuing to rise worldwide. Although substantial progress has been made in elucidating the clinical features and molecular underpinnings of these disorders, the precise mechanisms driving neurodegeneration remain incompletely understood. This review examines the increasing significance of the gut–brain–immune triad in the pathogenesis of NDs, with particular attention to Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. It explores how disruptions in gut microbiota composition and function influence neuroinflammation, blood–brain barrier integrity, and immune modulation through microbial-derived metabolites, including short-chain fatty acids, lipopolysaccharides, and bacterial amyloids. In both Alzheimer’s and Parkinson’s diseases, a reduced abundance of short-chain fatty acid-producing bacterial taxa has been consistently associated with heightened pro-inflammatory signaling, thereby facilitating disease progression. Although detailed mechanistic understanding remains limited, experimental evidence—primarily from rodent models—indicates that microbial metabolites derived from a dysbiotic gut may initiate or aggravate central nervous system dysfunctions, such as neuroinflammation, synaptic dysregulation, neuronal degeneration, and disruptions in neurotransmitter signaling via vagal, humoral, and immune-mediated pathways. The review further highlights how gut microbiota alterations in amyotrophic lateral sclerosis and multiple sclerosis contribute to dysregulated T cell polarization, glial cell activation, and central nervous system inflammation, implicating microbial factors in disease pathophysiology. In addition to identifying critical knowledge gaps, the review emphasizes the need for sustained, multifactorial research efforts, including the development of physiologically relevant brain–gut organoid models and the implementation of standardized experimental protocols. A major limitation in the field remains the difficulty of establishing causality, as clinical manifestations often arise after extended preclinical phases—lasting years or decades—during which aging, dietary patterns, pharmacological exposures, environmental factors, and comorbidities collectively modulate the gut microbiome. Finally, the review discusses how microbial influences on host epigenetic regulation may offer innovative avenues for modulating neuroimmune dynamics, underscoring the therapeutic potential of targeted microbiome-based interventions in neurodegenerative diseases.

Inflammatory bowel disease (IBD) is a chronic condition with significant health implications worldwide. In Nigeria, data on its prevalence and characteristics are limited, highlighting the need for comprehensive studies to better understand its epidemiology and clinical features in the region. This study aimed to assess the clinical presentation, endoscopic findings, and management challenges of IBD among patients undergoing colonoscopy in Nigeria.

Over five years (2019–2024), a multicenter, cross-sectional survey was conducted involving clinicians across Nigeria’s six geopolitical zones. It included a retrospective review of records from 18 centers. Data collection was conducted in two phases via Google Forms, focusing on care practices and detailed case information, including demographics, clinical features, histology, and treatment. Data analysis used descriptive statistics and tests for associations, with significance set at p < 0.05.

A total of 459 suspected IBD cases (9.7%) were identified among over 4,700 colonoscopies, with histological confirmation in 208 cases (4.4%), indicating the prevalence of IBD in the Nigerian patient population. The most common subtype was ulcerative colitis (53.9%), followed by Crohn’s disease (21.0%) and indeterminate colitis (25.0%). Regional variations were observed, with higher diagnosis rates in some zones (North-West: 14.9%; South-East: 1.4%). The predominant clinical feature was rectal bleeding. Endoscopic findings frequently showed pan-colitis (62%), with significant regional differences (p < 0.001), and management mainly involved medications such as acetylsalicylic acid derivatives (60.0%), with surgical options rarely employed (0.6%). Challenges included high medication costs and limited availability, which affected nearly half of the patients (49.4%; 46.2%).

IBD, though under-recognized, is present in the Nigerian population, with notable regional variation in prevalence and presentation. The primary clinical features align with global patterns, and significant barriers, such as medication costs and availability, hinder effective management. Increasing awareness, improving diagnostic infrastructure, and addressing treatment challenges are essential to enhance care and outcomes for patients with IBD in Nigeria.

Despite significant advances in Parkinson’s disease (PD) treatment, it remains incurable, with limited therapeutic options. Currently, repurposing already tested, safe drugs has emerged as an effective therapeutic strategy against various neurodegenerative diseases, including PD. Using a drug-repurposing approach, the current study investigated the neuroregenerative potential of polysialic acid mimicking compounds, 5-nonyloxytryptamine oxalate (5-NOT) and Epirubicin (Epi), an anti-cancer drug, in 1-methyl-4-phenylpyridinium (MPP+)-treated human neuroblastoma SH-SY5Y cells as a PD model.

The excitotoxic model was established by exposing SH-SY5Y cells to 500 µM of MPP+ and subsequently treating them with the test compounds. The effect of MPP+-induced toxicity on cellular and nuclear morphology, as well as on the expression of neuroplasticity and cell survival proteins, were studied by immunostaining, gelatin zymogram, and Western blot assays.

Treatment with 5-NOT and Epi significantly promoted the survival of MPP+-challenged SH-SY5Y cells and prevented changes in their cellular and nuclear morphology by regulating the expression of microtubule-associated protein (MAP-2) and polysialylated-neural cell adhesion molecule (PSA-NCAM) and NCAM synaptic plasticity proteins. Further, 5-NOT and Epi treatment also protected SH-SY5Y cells by restoring levels of nitric oxide, matrix metalloproteinase, and stress response proteins. Interstingly, 5-NOT attenuated MPP+-induced toxicity in SH-SY5Y cells by regulating the intrinsic protein kinase AKT/BAD apoptotic pathway and the P-38 MAP kinase synaptic plasticity pathway.

These preliminary findings suggest that 5-NOT, as a potential polysialic acid glycomimetic, may serve as a promising drug candidate for targeting neurodegeneration of dopaminergic neurons, a hallmark feature of PD.

Spinal cord injury (SCI) significantly impacts the central nervous system, with limited effective treatments available. Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuronal growth, survival, and regeneration after SCI. MicroRNAs, particularly miR-124-3p, have been implicated in SCI pathophysiology. However, the relationship between miR-124-3p and BDNF in the context of SCI remains unclear. This study aimed to investigate the correlation between miR-124-3p expression and BDNF levels in a rat model of spinal cord injury and to assess how the timing of injury affects this relationship.

This study included 72 male Wistar rats divided into three groups: intact (n = 8), sham (n = 32), and SCI (n = 32). SCI diagnosis was confirmed through behavioral-motor function analysis using the Basso, Beattie & Brenham score and histological examination with crystal violet staining. The expression levels of miR-124-3p and BDNF were assessed using real-time polymerase chain reaction in all groups at four time points (one hour, one day, three days, and seven days post-injury).

In the SCI group, a marked reduction in miR-124-3p expression was observed relative to both the sham and intact groups. Conversely, there was a substantial elevation in BDNF expression within the SCI group in comparison to the sham and intact groups. The findings underscore a negative association between miR-124-3p expression and BDNF messenger RNA levels.

The downregulation of miR-124-3p and concurrent upregulation of BDNF suggest a potential regulatory role of miR-124-3p in modulating BDNF expression during SCI. These findings provide new insights into the molecular mechanisms underlying SCI and suggest that miR-124-3p and BDNF could serve as potential therapeutic targets. Further research is needed to explore the translational potential of these findings for developing novel diagnostic and therapeutic strategies for SCI.