DNA polymerase epsilon catalytic subunit A (POLE) gene plays a crucial role in DNA repair and chromosomal replication. Mutations in the POLE gene have been linked to cancer, particularly colorectal carcinoma (CRC). However, the genomic landscape and pathological significance of POLE mutant CRC remain underreported. This study aimed to characterize the clinicopathologic features and genomic landscape of CRC harboring POLE mutations and to investigate the implications of co-occurring genetic alterations.

We identified thirty-four CRC cases with POLE mutations from our institution’s database using the next-generation sequencing gene panels including 161-gene panel for the cases of 2016–2021 and the 505-gene panel for the case of 2022–2023. We collected clinicopathologic data (age, sex, tumor site, and grading) and conducted comprehensive next-generation sequencing. Survival outcomes were assessed by reviewing patients’ medical records at the time of data collection, with survival status determined based on the most recent clinical follow-up available with overall survival as the primary endpoint and a median follow-up time of 20.5 months. Statistical analyses, including chi-squared testing and CoMutation plotting, were performed using Python.

The enrolled 34 patients had a median age of 60.5 years (range: 37–84); tumors were in the colon (26 cases, 77%) and rectum (8 cases, 23%), with a mismatch repair deficiency rate of 29%. Next-generation sequencing analysis of a 505-gene panel revealed that POLE mutations were predominantly missense (89%). The mutations were distributed across various domains: 11.4% in the exonuclease domain, 25.7% in the catalytic domain, 20% in an unknown functional domain, and 42.9% in a nonfunctional domain. The average number of genomic mutations per case was 12.1 ± 12.3. CoMutation analysis identified two subsets: genomic mutation high (>5 mutations, range 6–60 mutations, n = 22) and mutation low (. Notably, TP53 mutations occurred in 55% of cases, and defects in double-stranded DNA repair proteins occurred in 47% of cases. POLE mutant CRC with co-occurring DNA repair mutations exhibited a significantly higher total number of genomic mutations (19.9 ± 14.4, range 7–60 mutations; chi-squared = 5.1, p-value = 0.02). Although a survival comparison between TP53 wild-type and TP53 mutant subgroups of POLE-mutant CRC is not statistical significant (p = 0.37), it showed a trend toward better survival in the TP53 wild-type group.

Our findings reveal unique genomic landscapes in POLE mutant CRC, particularly with co-occurring TP53 or double-stranded DNA repair mutations, which are critical in colorectal carcinogenesis. These tumors demonstrate increased genetic instability, highlighting potential for immunotherapy.

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.

ATP-binding cassette (ABC) transporters are transmembrane proteins involved in the translocation of bilirubin, bile acids, phospholipids, and cholesterol into bile canaliculi. Mutations in particular genes encoding these transporters—including BSEP (ABCB11 gene), MDR3 (ABCB4 gene), sterolin-1 and sterolin-2 (ABCG5/8 genes), and MRP2 (ABCC2 gene)—result in a wide spectrum of liver diseases, ranging from benign conditions such as Dubin-Johnson syndrome to more severe presentations like progressive familial intrahepatic cholestasis. The severity of disease is influenced by many factors, including zygosity, mutation type, and environmental modifiers such as hormones, consanguinity, and founder effects. Homozygous and compound heterozygous mutations typically result in severe and early-onset diseases, while heterozygous single-allelic mutants generally result in milder diseases. Next-generation genetic testing has proven to have high diagnostic value and is important for prognostication. With knowledge of the underlying specific mutations, there is also potential for future targeted therapy for many severe diseases. The aim of this review is to update and discuss the hepatic diseases associated with ABC transporter mutations, the genetic and environmental effects that influence the severity of disease, typical presentations of these cholestatic hepatic diseases, diagnostic considerations, and treatment options.

Synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies, and multiple system atrophy (MSA), are a group of neurodegenerative diseases characterized by the oligomerization of α-synuclein protein in neurons or glial cells. Various splicing isoforms of α-synuclein have been described, each with different aggregation properties. The α-synuclein gene (SNCA) has been identified as a highly significant genetic risk locus associated with various synucleinopathies across populations. This study aimed to assess the association of SNCA genetic variants with MSA and the levels of SNCA transcripts in peripheral blood mononuclear cells (PBMCs) from MSA and PD patients.

In this retrospective case–control study, 96 MSA patients, 1086 PD patients, and 485 healthy volunteers were included. PCR followed by restriction endonuclease analysis was used to detect four SNCA single-nucleotide polymorphisms (rs356219, rs3756063, rs11931074, and rs356168) in these individuals. In addition, RT-qPCR was performed to detect the levels of α-synuclein transcripts (SNCA mRNA isoforms -140, -126, and -112) in PBMCs of 24 MSA patients (including parkinsonian (MSA-P) and cerebellar (MSA-C) variants), 31 PD patients, and 32 healthy volunteers.

The frequency of the ‘T’ allele (of rs11931074) was significantly higher in MSA patients than in the healthy controls. The level of SNCA-140 mRNA was significantly decreased in MSA and PD patients compared with the controls, while the level of SNCA-112 mRNA was significantly increased in MSA-P patients than in PD patients and the controls. SNCA-112 mRNA/SNCA-140 mRNA and SNCA-112 mRNA/SNCA-126 mRNA ratios were significantly increased in MSA patients than in the controls.

The SNCA rs11931074 polymorphism is associated with MSA. There is a pronounced alteration in the expression of SNCA transcripts in PBMCs of MSA and PD patients.

Chronic hepatitis B (CHB) poses a major global health burden, with China particularly affected. Effective antiviral therapy is crucial to prevent disease progression, but responses may vary by Hepatitis B virus (HBV) genotype. This prospective study aimed to compare genotype-specific responses to 144-week entecavir (ETV) therapy in HBeAg-positive CHB patients, with particular emphasis on histological improvement assessed through paired liver biopsies.

We enrolled 49 treatment-naïve CHB patients (HBV DNA ≥ 20,000 IU/mL, alanine transaminase (ALT) > 2× ULN, and Scheuer system G ≥ 2) who received ETV 0.5 mg/day. HBV genotyping was performed using Polymerase Chain Reaction and fragment length analysis. The primary endpoint was histological improvement (i.e., ≥ 2-grade reduction in necroinflammatory activity without fibrosis progression), evaluated via paired biopsies (baseline and week 144) by blinded pathologists. Secondary endpoints included virological response (i.e., serum HBV DNA < 100 IU/mL), HBeAg seroconversion, and ALT normalization.

The cohort included 24 genotype B and 24 genotype C patients (one genotype A patient was excluded from genotype-specific analyses). Genotype B showed significantly higher histological improvement rates (91.3% vs. 63.2%, P = 0.027) and greater inflammation resolution (0 ≤ G < 1: 56.5% vs. 26.3%, P = 0.048). Virological suppression was excellent in both groups (100% vs. 100%). HBeAg seroconversion trended higher in genotype C (29.2% vs. 50.0%, P = 0.140). All patients achieved ALT normalization by week 48, with no safety concerns.

HBV genotype B demonstrates superior histological responses to ETV therapy compared with genotype C, supporting the clinical value of HBV genotyping for personalized CHB management. These findings highlight the importance of considering viral genotype when evaluating treatment outcomes.

Mediastinal germ cell tumors (GCTs) are rare malignant neoplasms that occasionally develop somatic-type malignancies (SMs), such as sarcomas, carcinomas, and hematologic malignancies.

We report a unique case of a 16-year-old male patient with a mediastinal GCT that simultaneously developed two different SMs: well-differentiated angiosarcoma and acute megakaryoblastic leukemia (AML). The patient initially presented with left shoulder pain and intermittent shortness of breath. The imaging study demonstrated a 12.5 × 9.0 × 8.5 cm heterogeneous mass in the left anterior mediastinum. The mediastinal mass was resected and showed a cystic mature teratoma with somatic transformation into well-differentiated angiosarcoma and AML. A subsequent bone marrow biopsy confirmed the diagnosis of AML, and next-generation sequencing demonstrated the presence of PTEN and TP53 gene mutations in the AML. Despite aggressive chemotherapy and allogeneic stem cell transplantation, the patient died 10 months after diagnosis.

Our report demonstrates the unique capability of mediastinal GCTs to simultaneously develop two different SMs. The presence of two different SMs in mediastinal GCTs is associated with extremely aggressive behavior and a poor prognosis.

Terahertz (THz) radiation is increasingly explored for biomedical applications, however, its non-thermal effects on cellular metabolism and regulatory networks remain insufficiently characterized. This study aimed to investigate how 2.3 THz radiation affects metabolic pathways and membrane-associated signaling in human melanoma cells.

SK-MEL-28 melanoma cells were exposed to 2.3 THz radiation for 45 min using the 1st Novosibirsk free-electron laser. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays. Metabolic alterations were detected by targeted metabolomics using liquid chromatography–tandem mass spectrometry. Gene network analysis was performed using the ANDSystem platform to reconstruct gene and protein interaction networks linking altered metabolites to membrane receptors, lipid raft proteins, and signaling pathways. Overrepresentation analysis of biological processes was applied to identify enriched functional categories.

THz exposure did not affect cell viability but induced significant alterations in purine metabolism, pantothenate/CoA biosynthesis, and the pentose phosphate pathway. Network analysis revealed that these metabolic changes were associated with membrane raft reorganization and receptor-mediated signaling involving epidermal growth factor receptor and G-protein subunits. Additional effects were observed in pathways related to chromatin organization and post-translational regulation.

THz radiation induces coordinated remodeling of metabolic and regulatory networks in melanoma cells without cytotoxicity. These findings highlight the role of membrane-associated signaling in mediating THz-induced cellular responses and provide insight into potential biomedical applications of THz technologies.

Mild traumatic brain injury (mTBI) represents the majority of head injury presentations in emergency departments (EDs), yet only a minority of patients have acute intracranial lesions on computed tomography (CT). This leads to widespread use of unnecessary CT scans. Point-of-care (POC) biosensing, defined as analytical testing performed at or near the site of patient care, offers a promising solution to this dilemma by enabling rapid biomarker quantification to inform CT decision-making. This review aims to evaluate POC-compatible biosensing strategies for ultra-early mTBI triage, with emphasis on platforms, matrix effects, and benchmarking aligned with CT-based decision-making. Two key precedents support this approach: (1) the integration of S100B into Scandinavian Neurotrauma Committee guidelines, which has demonstrated the potential for safe reduction of CT scans, and (2) the regulatory clearance of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) testing to rule out the need for head CT in adults with suspected mTBI (Glasgow Coma Scale 13–15) when serum is collected within 12 hours of injury. Accordingly, this review focuses on the most implementable use case for mTBI, namely CT triage/rule-out. It synthesizes the current biomarker landscape (S100B, GFAP, UCH-L1), analyzes POC-suitable sensing modalities, and proposes a practical validation and benchmarking framework aligned with this intended use. A critical component is interference testing and real-world sample robustness, including vulnerabilities such as hemolysis-related elevation of UCH-L1. In conclusion, the most reliable path for biosensor translation in mTBI is to anchor development and validation to the ED CT-triage use case, emphasizing decision-point robustness and resilience to real-world sample variability over pure analytical sensitivity.

Gliomas remain a major challenge in brain cancer treatment. Although genetic mutations have been widely studied, recent research indicates that epigenetic changes, which alter gene activity without changing the DNA sequence, also contribute significantly to tumor growth and treatment resistance. This review seeks to elucidate the principal drivers and modulators of brain tumor development, emphasizing the complex interaction between tumor metabolism and epigenetic regulation. It highlights how metabolic intermediates influence chromatin structure and transcriptional events driving glioma progression. Metabolic intermediates, such as acetyl-CoA and S-adenosylmethionine, serve as essential epigenetic cofactors, directly impacting chromatin structure and gene expression. Additionally, metabolic disorders like diabetes not only frequently coexist with gliomas but also exacerbate tumor progression through mechanisms such as inflammation, oxidative stress, and epigenetic reprogramming. Tumors located near brain regions controlling heart function may also increase the risk of sudden death, particularly in diabetic patients. The review proposes a comprehensive framework to understand glioma development by linking metabolism, epigenetics, and overall health. This integrated perspective leads to novel personalized treatment approaches, targeting both the tumor and the patient’s broader metabolic health, with the potential to improve survival rates and quality of life for glioma patients.

Alpha-1 antitrypsin deficiency (AATD) is an autosomal codominant genetic disorder caused by mutations in the SERPINA1 gene. It results in reduced circulating levels of alpha-1 antitrypsin (AAT), a serine proteinase inhibitor (PI) primarily produced by hepatocytes. The most common deficient alleles are PI*S and PI*Z, with PI*ZZ homozygotes having the most severe deficiency and highest risk for lung and liver disease. While AATD is well established as a cause of early-onset emphysema and liver cirrhosis, emerging evidence suggests a potential association with the formation of arterial aneurysms. The pathophysiological rationale for this association centers on protease-antiprotease imbalance and potential extracellular matrix degradation of elastin in arterial vessel walls. Several studies have reported increased frequencies of AATD alleles in patients with abdominal aortic aneurysms and intracranial aneurysms compared to the general population, with some demonstrating statistically significant associations. Additionally, patients with the PI*ZZ genotype have been shown to have larger aortic diameters, greater aortic stiffness, and reduced distensibility compared to controls. However, the evidence is inconsistent, as several large studies have failed to demonstrate significant associations between AATD and aneurysm formation. Overall, current evidence suggests an association of AATD with the development of arterial aneurysms. However, it is also clear that the presence of AATD alone is not sufficient to increase the risk of developing new-onset arterial aneurysms.