Sclerocarya birrea (A. Rich) Hochst (Anacardiaceae) is a plant widely used by traditional healers in several African countries to treat numerous illnesses such as Alzheimer’s disease, schizophrenia, inflammation, infections, arterial hypertension, headaches, and others. This study aimed to determine the therapeutic efficacy of Sclerocarya birrea (S. birrea) against glutamate-induced neurotoxicity.

Thirty naïve white mice (Mus musculus Swiss, Muridae), of both genders and weighing between 18 and 25 g, were used in the experiments. Different doses (102.5, 205, and 410 mg/kg) of the extract and vitamin C (100 mg/kg) were administered to the animals one hour before administration of monosodium glutamate (4 mg/kg) for 15 consecutive days. T-maze and Y-maze tests were conducted over three days to assess the animals’ behavioral performance. After behavioral testing, the animals were sacrificed and their brains removed for analysis of oxidative stress parameters.

S. birrea extract reversed glutamate-induced behavioral alterations by significantly (P < 0.001) reducing the latency to reach the platform in the T-maze and significantly increasing the percentage of spontaneous alternation in the Y-maze. The extract also significantly counteracted (P < 0.001) glutamate-induced oxidative stress parameters. The 102.5 and 205 mg/kg doses of the extract significantly (P < 0.001) reduced catalase and reduced glutathione levels, as well as the increase in malondialdehyde levels induced by glutamate.

S. birrea root bark extract exhibits neuroprotective properties that facilitate memory and ameliorate glutamate-induced cognitive deficits in white mice. The results provide partial justification for the traditional medicinal use of S. birrea extract.

Acromegaly requires multimodal management. While surgery is first-line, many patients have persistent/recurrent disease. Gamma knife radiosurgery (GKRS) offers precise radiation, but data on its use as initial therapy remain limited. This study aimed to review the outcomes and report on our experience in treating patients with acromegaly using initial GKRS.

We retrospectively identified 33 patients with acromegaly who underwent GKRS from 1993 until 2016 at the Department of Radiotherapy, the Second Affiliated Hospital of Guangzhou Medical University. These patients had complete endocrine, radiological, and imaging data before and after GKRS. Furthermore, univariate and multivariate analysis was utilized to analyze the potential prognostic factors of endocrine remission and new-onset hypopituitarism.

Thirty-three patients were enrolled in the study. Fifteen patients (45.5%) were males and 18 (54.5%) were females. The median age was 44.0 years (range, 24.9–66.2 years). During a median follow-up of 65.6 months (range, 12.9–297.6), the median margin dose for GKRS was 15.0 Gy (range, 10.8–20.3 Gy). Endocrine remission was achieved in nine of the 33 patients (27.3%) over a mean follow-up of 85.1 months (range, 12.9–161.3). No prognostic factors demonstrated a significant association with endocrine remission. New-onset hypopituitarism occurred in eight patients (24.2%) after GKRS. The tumor control rate was 100%. Only one patient developed worsening visual dysfunction. No new cranial neuropathy was noted.

Initial GKRS for acromegaly provided effective tumor control and partial endocrine remission with a favorable safety profile, notably a low rate of new-onset hypopituitarism, representing a viable treatment option.

Circular RNAs (circRNAs) are non-coding RNAs characterized by a strictly closed-loop covalent structure. They are abundantly detected in various cells due to their conserved nature. Studies have reported their potential association with chronic liver disease (CLD), including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), with possible roles as diagnostic and prognostic markers. This study aimed to analyze the potential use of serum-derived hsa_circ_101555 as a diagnostic tool for CLD without HCC, and to compare it with other known non-invasive parameters for liver disease severity and inflammation. Additionally, it aimed to evaluate its expression among non-HCC CLD patients, CLD with HCC cases reported in our published (phase I) study, and healthy controls.

A cross-sectional study (phase II) was conducted involving 30 clinically, laboratory, and radiologically diagnosed Egyptian non-HCC CLD patients and 30 healthy subjects. The serum expression level of hsa_circ_101555 was measured using real-time polymerase chain reaction. The diagnostic accuracy was assessed through receiver operating characteristic curve analysis, calculating the area under the curve to determine sensitivity and specificity. The study also compared hsa_circ_101555 levels with established non-invasive parameters such as the Child-Turcotte-Pugh and model for end-stage liver disease scores, as well as inflammatory markers like the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.

hsa_circ_101555 demonstrated high diagnostic accuracy (area under the curve of 0.970) at a cutoff point of 2.088 for differentiating non-HCC CLD patients from healthy controls. Elevated circRNA levels were noted in patients with hepatic encephalopathy and ascites, correlating with advanced liver disease scores (Child-Turcotte-Pugh/model for end-stage liver disease scores). Mean circRNA values were highest in HCC cases, followed by non-HCC CLD patients, and lowest in healthy controls.

Serum-derived hsa_circ_101555 demonstrates high diagnostic accuracy in differentiating non-HCC CLD patients from healthy controls. These findings suggest that hsa_circ_101555 has the potential to serve as a reliable non-invasive biomarker for the early diagnosis of CLD, correlating with disease severity and inflammation markers. Further research with larger sample sizes is warranted to validate its clinical utility and enhance the management of CLD.

Despite rapid advances in computational biology and regulatory reforms encouraging the reduction of animal use, a clear synthesis of how artificial intelligence (AI)-driven polypharmacology can function as a scientific and ethical bridge between traditional in vivo pharmacology and human-relevant drug development remains lacking. The shift from cage-based experimentation to code-based predictive modeling presents both opportunities and unresolved challenges in biological interpretation, regulatory acceptance, and pharmacology education. Therefore, this review aims to critically examine the transition toward AI-enabled, human-centric drug discovery within the framework of the 3R principles (Replacement, Reduction, and Refinement). Specifically, it explores (i) the global regulatory and ethical drivers accelerating non-animal methodologies, (ii) the scientific and educational gaps emerging from reduced dependence on animal models, and (iii) the role of AI and deep learning in reconstructing biological complexity through multi-omics integration and predictive toxicity modeling. By analyzing emerging AI platforms and computational strategies, this review highlights how AI-driven polypharmacology may offer a scalable, ethical, and precision-oriented framework for future pharmacological research.

Primary biliary cholangitis (PBC) is a chronic cholestatic disorder in which symptoms exert a direct influence on patients’ quality of life. Beyond pruritus and fatigue, patients with PBC are also prone to developing osteoporosis (OP). This skeletal condition not only heightens the likelihood of fractures but is also associated with elevated mortality. With the overall prevalence of PBC rising, a parallel increase in OP incidence among these patients can be anticipated. Early recognition, preventive strategies, and appropriate therapeutic approaches are essential for preserving patients’ quality of life. Nevertheless, current data on the management of OP in PBC remain limited. Most existing recommendations are extrapolated from studies on postmenopausal OP. However, these findings have not been effectively adapted into practical management protocols for PBC-related OP, largely due to distinct pathophysiological mechanisms between the two conditions. The absence of well-established preventive and therapeutic measures continues to represent a major obstacle in addressing OP among patients with PBC. This review offers a detailed synthesis of the epidemiology, underlying mechanisms, and therapeutic considerations of OP linked to PBC.

As the leading cause of chronic liver disease globally, metabolic dysfunction-associated steatotic liver disease (MASLD) lacks effective therapies. This study aimed to investigate the therapeutic potential and molecular mechanisms of oxytocin (OXT) in MASLD.

Integrated bioinformatics analysis of MASLD datasets was carried out to identify OXT-related metabolic disturbances. Serum OXT levels were quantified using an enzyme-linked immunosorbent assay in 113 MASLD patients and 63 healthy controls. Mechanistic assays were conducted using oleic acid (OA)-induced, lipid-loaded HepG2 cells and high-fat diet-fed C57BL/6 mice, and OXT was administered intraperitoneally in vivo and supplemented in vitro.

Bioinformatics analysis revealed significant changes in OXT expression levels, particularly in fatty acid metabolism. Elevated OXT expression levels in MASLD patients were identified as an independent prognostic factor. In vitro, OXT significantly reduced OA-induced lipid accumulation in HepG2 cells, while in vivo, it decreased body weight, liver injury, and serum cholesterol levels in high-fat diet-fed mice. Mechanistically, OXT enhanced the expression level of phosphorylated AMP-activated protein kinase (AMPK) and suppressed the levels of sterol regulatory element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS). Blockade of AMPK with the chemical inhibitor Compound C reversed the ability of OXT to suppress the SREBP1c/FAS axis and reduce lipid accumulation in hepatocytes. Additionally, OXT inhibited the nuclear translocation of SREBP1c in OA-treated cells.

The findings demonstrate that OXT may serve as a potential therapeutic agent for MASLD by regulating the AMPK/SREBP1c/FAS pathway in lipid metabolism.

Primary hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, with curative options still limited for patients with advanced disease. As an emerging modality of cancer immunotherapy, tumor vaccines represent a promising approach that activates the host immune system to recognize and eliminate malignant cells. Multiple vaccine platforms, including peptide vaccines, dendritic-cell vaccines, nucleic-acid vaccines, and viral-vector vaccines, have been explored for HCC. Among these, peptide- and dendritic-cell-based vaccines are supported by the most extensive clinical data, demonstrating favorable safety and immunogenicity profiles. The advent of personalized therapeutic cancer vaccines based on tumor-specific antigens has further refined the precision of vaccine design. Nevertheless, several major challenges persist, including immune suppression within the tumor immune microenvironment, marked tumor heterogeneity, immune-escape mechanisms, and limited vaccine immunogenicity, all of which hinder clinical efficacy. In addition, issues related to standardization, large-scale production, and regulatory oversight remain unresolved. Recent advances in sequencing technology, nanotechnology, and artificial intelligence have opened new avenues for optimizing vaccine platforms and delivery strategies. Combination therapies that integrate cancer vaccines with immune checkpoint inhibitors, chemotherapy, or locoregional treatments are also being actively investigated to improve patient outcomes. In summary, although vaccine-based immunotherapy for HCC is still at an early stage, its integration with personalized medicine and multimodal therapeutic strategies holds great potential for improving the long-term prognosis of patients with HCC. Therefore, this review aims to systematically summarize current advances in tumor vaccine–based immunotherapy for hepatocellular carcinoma, with a particular focus on vaccine platforms, target antigens, clinical trial outcomes, and future challenges for clinical translation.

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.

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.