Ammonia, a by-product of glutamine metabolism, has emerged as a key immunometabolic regulator in the tumor microenvironment. Recent studies reveal that excessive ammonia accumulation impairs effector CD8⁺ T cell viability through a distinct form of organelle-centered cell death, characterized by lysosomal alkalinization, mitochondrial dysfunction, and autophagy inhibition. This phenomenon, termed ammonia-induced cell death (AICD), contributes to immune suppression and tumor progression. Here, we comprehensively review the molecular pathways governing ammonia production, transport, and detoxification, with a focus on the roles of GLS1, CPS1, Rh-family transporters, and associated solute carriers. We further highlight advances in chemical biology tools—such as ammonia-sensitive probes and isotope-labeled metabolomics—that enable the functional dissection of ammonia metabolism in immune and tumor cells. Emerging therapeutic strategies that combine ammonia metabolism modulators with immune checkpoint inhibitors offer promising avenues to enhance anti-tumor immunity. Despite recent progress, key challenges remain, including the incomplete understanding of ammonia clearance in T cells, limited data on other immune cell types, and concerns about metabolic toxicity. Targeting AICD thus represents a chemically tractable and clinically relevant approach at the interface of metabolism, immunity, and cancer therapy.

This study proposes the implementation of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) technology for gene therapy targeting genetic mutations in human lymphocytes affected by chronic lymphocytic leukemia (CLL), offering new opportunities for effective treatment of this heterogeneous disease. It focuses on the application of CRISPR-Cas9-mediated targeted sequencing to systematically characterize the biological effects of monoallelic and biallelic TP53 gene lesions, aiming to replace mutant TP53 genes in CLL cells through this technology. CRISPR-Cas9 technology employs a specific enzyme guided by a designed guide RNA (gRNA) to a DNA target. The enzyme first introduces a cut at the target site, and following this cleavage event, it can further disrupt the TP53 gene. The gRNA plays a crucial role by directing the Cas9 protein to the DNA sequence of interest. The gRNA consists of CRISPR RNA (crRNA) and trans-activating CRISPR RNA (tracrRNA) sequences, responsible for target recognition and Cas9 binding, respectively. Examination of the predicted secondary structure of the tracrRNA-crRNA duplex suggests that the features required for Cas9-catalyzed DNA cleavage at specific sites can be captured within a single chimeric RNA. Although the natural tracrRNA-crRNA mechanism operates efficiently, the use of a single RNA-guided Cas9 system is particularly attractive due to its potential for programmed DNA cleavage and genome editing. Importantly, Cas9 can bind and cleave a target sequence only if it is adjacent to a protospacer adjacent motif. Once the gRNA-Cas9 complex binds to the target DNA, Cas9 induces a double-strand break at the specified site. In conclusion, CRISPR-Cas9 technology represents a powerful genetic engineering tool capable of inserting, deleting, or replacing DNA within an organism’s genome using these “molecular scissors.”

Interleukin-17B (IL-17B) and its receptor IL-17 receptor B (IL-17RB) are implicated in several cancers. However, data on their expression profile and clinical significance in laryngeal squamous cell carcinoma (LSCC) remain unavailable. This study aimed to explore the expression profile of IL-17B/IL-17RB in LSCC and to evaluate their predictive and prognostic value in LSCC patients. Tumor and serum samples from 30 LCSS patients and 30 controls were analyzed. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry (IHC) assessed IL-17RB expression on T helper type 2 (Th2) cells and monocytes, and IL-17B/IL-17RB in serum and tissues. Target gene expression levels at the mRNA and protein levels and their correlation with overall survival (OS) were further analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA; 519 head and neck squamous cell carcinoma [HNSCC] and 44 normal tissues) and the Human Protein Atlas (HPA; 492 RNA samples and 183 HNSCC and normal samples). Result showed weak IL-17RB expression on Th2 cells and monocytes and negative immunoreactivity of IL-17B/IL-17RB in LSCC tissues, consistent with GEPIA and HPA databases. No differences in IL-17B/IL-17RB levels in serum were found in LSCC patients compared with healthy controls. Neither IL-17B nor IL-17RB was correlated with OS. This study provides the first comprehensive evaluation of IL-17B/IL-17RB in LSCC, combining patient samples with bioinformatics datasets. Findings indicate that IL-17B and IL-17RB are not prognostic markers in LSCC, and their potential as serum markers in clinical practice is limited. Further studies are warranted to validate these negative findings and explore alternative roles of IL-17B/IL-17RB in LSCC.

Gliomas are the most common malignant brain tumors driven by genetic and microenvironmental factors, with newly recognized high-risk molecular subtypes requiring aggressive treatment. This study aims to address the limitations of biopsy-based molecular typing by developing a non-invasive multimodal magnetic resonance imaging habitat imaging model to predict high-risk subtypes, thereby improving early detection and guiding treatment. Data of 204 glioma patients retrieved from The Cancer Genome Atlas public database were retrospectively analyzed. Habitat imaging based on K-means clustering was applied to three habitat regions in pre-operative T1CE and T2FLAIR sequences, extracting 10,416 radiomics features. Analysis of variance was used to assess the correlation between features and labels, screening radiomics features significantly associated with high-risk molecular subtypes. A support vector machine classifier was employed to construct a habitat radiomics model. Logistic regression (LR) was used to identify relevant clinical features, and a clinical prediction model was established, followed by performance evaluation. A combined model was developed by integrating the habitat radiomics model and the clinical model using multivariate LR. The predictive performance of the three models was evaluated and compared using metrics such as the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration curves. The combined model achieved AUC = 0.943 and 0.912 in the training and test sets, respectively, outperforming the clinical model (training set: AUC = 0.830; test set: AUC = 0.841) and the habitat radiomics model (training set: AUC = 0.914; test set: AUC = 0.864). In DCA, the combined model demonstrated significantly higher and more stable net benefits within a reasonable clinical threshold range compared to the other two models. Calibration curves indicated that the combined model also exhibited superior calibration performance. This study shows that combining clinical and radiomics data improves glioma risk prediction, but multicenter validation of such approach for clinical use is warranted.

Women living with human immunodeficiency virus (HIV) have up to 6 times the risk of cervical cancer compared with HIV-negative women, with more than 60% of cervical cancer cases in Southern Africa occurring among HIV-positive women. Human papillomavirus (HPV) DNA self-sampling is a World Health Organization-recommended, cost-effective screening approach suitable for low-resource settings, particularly where healthcare worker availability and client mobility are constrained. With support from the Swedish Embassy, Population Services International Zimbabwe evaluated the feasibility and acceptability of HPV DNA self-sample collection among women of reproductive age, and assessed whether self-collected vaginal swabs yielded results comparable to provider-collected cervical samples. A quantitative cross-sectional crossover trial was conducted from May 2020 to December 2022 across three high-volume healthcare facilities. Women aged 30-65 were randomized into two arms: Arm 1 (self-collection followed by provider collection) and Arm 2 (provider collection followed by self-collection). Data were collected electronically using SurveyToGo and analyzed in STATA 13. Randomization checks assessed demographic comparability between arms. HPV positivity rates and 95% confidence intervals (CIs) were also computed. Among 609 self-collected samples, 26.9% were HPV-positive (95% CI: 23.5-30.6), compared with 29.3% positivity (95% CI: 25.8-33.0) among 611 provider-collected samples, showing statistically similar outcomes. Findings were consistent across study sites and participant age groups. Self-sample collection was widely acceptable among participants and deemed feasible by service providers. The results demonstrate that women can reliably self-collect samples for HPV DNA testing. This strategy offers a scalable, resource-efficient approach to expanding cervical cancer screening coverage in high-HIV-burden, low-resource settings, such as Zimbabwe, while reducing provider workload and facilitating earlier detection.

Breast cancer remains a major public health concern, especially in the female population, and its treatment remains challenging in the world. Targeted gene therapy might prove effective in curbing the prevalence. This Pilot study was to evaluate mutation patterns in Adenomatous Polyposis Coli (APC) And Myelocytomatosis (MYC) gene in benign and malignant breast lesions. The pilot study consisted the use of 10 formalin-fixed heterogenous paraffin-embedded tissue blocks, 5 fibroadenomas (FA) and 5 invasive ductal adenocarcinomas (IDA) from the pathological archives of Federal Teaching Hospital Ido-Ekiti. Nucleic acid amplification technique by using Dellaporta DNA extraction protocol. Polymerase chain reaction (PCR) technique was used to amplify the DNA fragments, sequenced using a Genetic Analyzer 3130xl sequencer from Applied Biosystems using the manufacturers’ manual, Bio-Edit software and Mega 6 were used for all genetic analysis. PCR optimization and Primer specificity, HGVSc, HGVSp, and VAF (%) were analysed. The results were reported that in fibroadenoma in the APC gene, single nucleotide polymorphism (SNP) mutation recorded transition in all samples, as well as in the invasive ductal adenocarcinoma it recorded. In functional mutation in the APC gene, fibroadenoma showed both silent and missense mutations while invasive ductal adenocarcinoma it recorded only missense mutation. The results reported in the MYC gene show that in SNPs mutation for fibroadenoma, showed both transversion and transition. In IDA, transition, InDel and transversion were observed. In functional mutation, fibroadenoma showed silent and missense while in IDA silent and missense were observed. This study carried out demonstrated missense mutation in both APC and MYC genes in fibroadenoma and invasive ductal adenocarcinoma singly.

Ovarian cancer is one of the most lethal gynecological diseases and remains a formidable challenge because of its high mortality and intrinsic resistance to conventional treatment approaches. Recent advances in molecular biology and drug discovery have identified several proteins, such as interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), heat shock proteins (HSPs), epidermal growth factor (EGF), and matrix metalloproteinases (MMPs), as potential therapeutic targets. Tetrahydrocannabinol (THC), cannabinol, elasterol, and 2-methylenecholestan-3-ol are among the substances that have shown promise in modulating these targets. This study aims to evaluate, in silico, the potential of 2-methylenecholestan-3-ol, elastrol, THC, and cannabinol to modulate IL-2, TNF-α, HSPs, EGF signaling, and MMPs in ovarian cancer. Bioinformatics databases were used to identify potential therapeutic agents for ovarian cancer. Molecular docking, protein-ligand complex analysis, SwissADME, admetSAR, and toxicity prediction were performed as key components of the workflow. Overall, the in silico analyses suggest that these compounds may interact with key proteins implicated in ovarian cancer progression. Particularly, elasterol and 2-methylenecholestan-3-ol showed good therapeutic properties against OC targeting HSP70 and HSP90, whereas THC and cannabinol show adequate interactions with MMPs and TNF-α. These findings suggest potential therapeutic relevance, opening up a promising avenue for improving ovarian cancer treatment.

Artificial intelligence (AI) plays a crucial role in advancing head-and-neck cancer diagnosis and treatment, significantly impacting patient outcomes and healthcare efficiency. We explore how AI-driven technologies are revolutionizing clinical practices. AI-driven surgical robotics enables highly accurate, minimally invasive procedures by providing real-time intraoperative guidance and analyzing complex imaging data, thus improving surgical success rates and reducing complications. Similarly, AI-driven remote monitoring systems facilitate continuous, non-invasive tracking of disease progression, treatment adherence, and early detection of recurrence, allowing for timely interventions and personalized care adjustments. These innovations enhance diagnostic accuracy, therapeutic precision, patient engagement, and resource utilization, leading to a better quality of life. However, several challenges hinder widespread AI adoption, including concerns over data privacy and security, algorithm bias due to unrepresentative datasets, variability in data quality, and regulatory and ethical issues regarding accountability and transparency. Implementation barriers, such as that in integration with existing workflows, clinician acceptance, and resource limitations, further complicate deployment, especially in low-resource settings. Despite these hurdles, we demonstrate that the potential benefits of AI—improved diagnostic accuracy, personalized treatment, and proactive disease management—are substantial. Addressing these challenges through robust data governance, validation, and ethical frameworks is essential for safe and equitable AI integration. We conclude that ongoing technological and methodological advancements will continue to enhance the efficacy and accessibility of AI in head cancer care. We emphasize the importance of collaborative efforts, regulatory support, and ethical standards to fully realize AI’s transformative potential, ultimately leading to more precise, patient-centered, and effective head-and-neck cancer management.

Lactic acidosis is classified into type A and type B. In cases of type B lactic acidosis, it is important to consider underlying lymphomas, mostly B-cell types, such as intravascular large B-cell lymphoma (IVLBCL) or diffuse large B-cell lymphoma. Cluster of differentiation (CD) 5⁺ large B-cell lymphoma (LBCL) is well-known for its aggressive nature. We report here two cases of CD5⁺ LBCL that showed severe lactic acidosis (11.2 mmol/L and 15.9 mmol/L, respectively; reference range: 0.6-1.7) with hypoglycemia. Case 1 was a 79-year-old female who presented with multiple organ failure. CD5⁺ IVLBCL was diagnosed through a random skin biopsy in this patient. Case 2 was a 78-year-old female with bone marrow involvement by CD5⁺ LBCL cells and liver failure. The patient was also diagnosed pathologically as IVLBCL by liver biopsy. Both patients were under ventilator management and high-flow continuous hemodialysis and filtration. Plasma exchange was also employed. An anti-lymphoma regimen (a 50% dose-reduced etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) was introduced on day 11 and day 2 of hospitalization for cases 1 and 2, respectively. In Case 1, lactic acidosis was normalized within day 17, and the patient survived longer than 8 weeks, while in Case 2, lactic levels did not improve until her death on day 16 of hospitalization. In conclusion, prompt recognition of type B lactic acidosis and early diagnostic biopsy are essential for improving outcomes in aggressive CD5⁺ IVLBCL, highlighting the need for novel therapeutic strategies.

We report a rare case of Plummer-Vinson syndrome (PVS) in a 55-year-old female with no known premorbid condition who presented to the hospital with a chief complaint of dysphagia for 1 month, weight loss, and a history of fever (high grade up to 40°C) associated with occasional rigors and chills. Laboratory testing showed iron-deficiency anemia, together with dysphagia, raising clinical suspicion for PVS. She was further examined with upper gastrointestinal endoscopy to evaluate the cause of dysphagia, which revealed a Schatzki ring in the esophagus at 38 cm from the incisors, near the gastroesophageal junction. The ring was dilated endoscopically, and the rest of the stomach and duodenum were normal. The computed tomography scan presented hepatosplenomegaly and lymphadenopathy. Findings were consistent with a myeloproliferative disorder and non-Hodgkin lymphoma. Oral iron supplementation (150-200 mg) was recommended, and dysphagia should be evaluated with gastroduodenal endoscopy as indicated.