BACKGROUND:Cancer chemotherapy often results in severe side effects due to its non-selective cytotoxicity toward rapidly dividing normal cells. These adverse effects are largely driven by oxidative stress resulting from elevated reactive oxygen species (ROS) production. Riboceine (RIB), a synthetic precursor of glutathione (GSH), and N-acetylcysteine (NAC), a clinically used antioxidant, hold promise in mitigating oxidative damage; however, their impact on chemotherapy efficacy and the molecular mechanisms involved remain incompletely understood. AIM:This study aimed to evaluate the cytoprotective potential of RIB and NAC against methotrexate (MET)- and docetaxel (DOC)-induced toxicity in normal and cancer cells, and to explore mechanistic pathways using integrative network pharmacology and molecular docking approaches. METHODOLOGY:Cytotoxic effects of MET and DOC, alone or in combination with RIB or NAC, were assessed in normal prostate epithelial (PNT-2), prostate cancer (PC3), and breast cancer (MCF-7) cell lines using the Resazurin assay. Intracellular ROS and GSH levels were quantified using DCF and OPA fluorescence assays, respectively. Network pharmacology, protein-protein interaction (PPI) analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and molecular docking were conducted using SwissTargetPrediction, STRING, ShinyGO, Cytoscape, and AutoDock Vina platforms. RESULTS:MET and DOC showed dose-dependent cytotoxicity in PNT-2 and PC3 cells, but limited efficacy in chemoresistant MCF-7 cells. RIB and NAC significantly reduced ROS and restored GSH levels in PNT-2 cells, protecting them against oxidative injury. These antioxidants preserved anticancer effects in PC3 cells but reduced chemotherapy efficacy in MCF-7 cells, likely due to elevated redox buffering and transporter expression. Network analyses identified BCL-2, MAPK8, and SOD among key antioxidant and apoptotic targets. However, no direct experimental validation of these mechanisms was performed, and apoptotic markers such as Annexin V or caspase-3 were not assessed. CONCLUSION:RIB and NAC provide selective cytoprotection to normal prostate cells during chemotherapy while maintaining anticancer effects in sensitive prostate cancer cells. However, their concurrent use in resistant cancers like MCF-7 may reduce drug efficacy, warranting cautious clinical application. Time-shifted antioxidant administration (e.g., post-chemotherapy) could be explored as a strategy to balance protection and efficacy. Future studies should include in vivo validation, apoptosis profiling, and protein-level mechanistic assays to confirm the predicted pathways.

ETHNOPHARMACOLOGY RELEVANCE:Cancer is a major global public health concern with significant ramifications on quality of life and treatment outcomes. Medicinal plants such as Tetrapleura tetraptera (TT) are key sources of bioactive compounds with therapeutic potential, yet their efficacy and underlying molecular mechanisms remain largely unexplored. AIM OF THE STUDY:To investigate the anti-prostate cancer potential, antioxidant activity, and underlying mechanism of TT. MATERIALS AND METHODS:Crude extracts were obtained through the sequential extraction of powdered TT (whole fruit, pulp, and seed). TT extracts were assessed for their antioxidant activity, total phenolic content and antiprostate cancer activity using the DPPH radical scavenging assay, Folin-Ciocalteu method and tetrazolium-based colorimetric assay, respectively. Bioactive compounds from TT and prostate cancer-related targets were identified through literature mining and public databases. Network pharmacology, molecular docking and molecular dynamics were employed to elucidate TT's potential mechanisms of action. RESULTS:Aqueous whole fruit extract exhibited potent antioxidant activity with EC50 = 83.46 ± 1.07 μg/mL, while the ethyl acetate fruit extract showed the strongest anti-prostate cancer activity (PC3 IC50 = 5.39 ± 1.24 μg/mL, SI = 7.72; LNCaP IC50 = 8.38 ± 1.27 μg/mL, SI = 4.97). Network pharmacology revealed that TT compounds targeted key proteins within the prostate cancer pathway, implicating MAPK, PI3K/AKT and P53 signaling cascades. Molecular docking and dynamics simulations further supported these findings, demonstrating strong, stable and flexible binding interactions between luteolin with MMP9/AR and Scopoletin with ERBB2. CONCLUSIONS:Whole TT fruit demonstrates promising anti-prostate cancer activity through the multitargeted modulation of key proteins involved in pivotal signaling pathways. However, further in vitro, in vivo and clinical studies are required to validate these findings and fully explore TT's therapeutic potential.

The intestine is a vital organ of the digestive system, with its function largely reliant on the continuous regeneration of mucosal epithelial cells by healthy intestinal stem cells (ISCs). However, as we age, the regenerative potential of ISCs declines, primarily due to deleterious aging processes, such as cellular senescence, which contribute to the development of various chronic gut diseases. A growing body of evidence indicates that both healthy ISCs, which maintain intestinal homeostasis, and aging-associated senescent ISCs are profoundly influenced by epigenetic mechanisms. At the molecular level, dynamic and often reversible epigenetic modifications including chromatin remodeling, histone modifications, DNA methylation, N6-methyladenosine (m6A) modifications, and non-coding RNAs (long non-coding RNAs, circular RNAs, and microRNAs) play a pivotal role in modulating ISCs gene expression and function. This review explores the role of epigenetics in regulating ISCs stemness, proliferation, differentiation, and plasticity to maintain epithelial homeostasis, as well as the impact of aging-associated epigenetic changes on these processes. A deeper understanding of these mechanisms may inform researchers on the development of translational approaches, therapeutic strategies, and effective interventions aimed at enhancing the regenerative capacity of gut ISCs and mitigating the onset of age-related gut disorders.

Bergamot essential oil (BEO) is an extract of the bergamot fruit with significant neuroprotective effect. This study was to investigate the effects and the underlying mechanism of BEO in mitigating depression. GC-MS were used to identify its constituents. Antidepressive properties of BEO were evaluated by sucrose preference test (SPT), force swimming test (FST) and open field test (OFT). Nissl staining was used to determine the number of Nissl bodies in hippocampus (HIPP) of rats. Changes in HIPP dendritic length and dendritic spine density were detected by Golgi-Cox staining. Immunohistochemistry and Western blot were used to detect the postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the HIPP of rats. The enzyme-linked immunosorbent assay was used to determine the 5-hydroxytryptamine (5-HT), insulin-like growth factor 1 (IGF-1) and interleukin-1β (IL-1β) in the HIPP, serum and cerebrospinal fluid (CSF) of rats. Inhaled BEO significantly improved depressive behaviour in chronic unpredictable mild stress (CUMS) rats. BEO increased Nissl bodies, dendritic length and spine density, PSD-95 and SYP protein in the HIPP. Additionally, BEO upregulated serum 5-HT, serum and CSF IGF-1, while downregulating serum IL-1β. Collectively, inhaled BEO mitigates depression by protecting the plasticity of hippocampal neurons, hence, providing novel insights into treatment of depression.

The modification of RNA through the N6-methyladenosine (m6A) has emerged as a growing area of research due to its regulatory role in gene expression and various biological processes regulating the expression of genes. m6A RNA methylation is a post-transcriptional modification that is dynamic and reversible and found in mRNA, tRNA, rRNA, and other non-coding RNA of most eukaryotic cells. It is executed by special proteins known as "writers," which initiate methylation; "erasers," which remove methylation; and "readers," which recognize it and regulate the expression of the gene. Modification by m6A regulates gene expression by affecting the splicing, translation, stability, and localization of mRNA. Aging causes molecular and cellular damage, which forms the basis of most age-related diseases. The decline in skeletal muscle mass and functionality because of aging leads to metabolic disorders and morbidities. The inability of aged muscles to regenerate and repair after injury poses a great challenge to the geriatric populace. This review seeks to explore the m6A epigenetic regulation in the myogenesis and regeneration processes in skeletal muscle as well as the progress made on the m6A epigenetic regulation of aging skeletal muscles.

Globally, age-related diseases represent a significant public health concern among the elderly population. In aging, healthy organs and tissues undergo structural and functional changes that put the aged adults at risk of diseases. Some of the age-related diseases include cancer, atherosclerosis, brain disorders, muscle atrophy (sarcopenia), gastrointestinal (GIT) disorders, etc. In organs, a decline in stem cell function is the starting point of many conditions and is extremely important in GIT disorder development. Many studies have established that aging affects stem cells and their surrounding supportive niche components. Although there is a significant advancement in treating intestinal aging, the rising elderly population coupled with a higher occurrence of chronic gut ailments necessitates more effective therapeutic approaches to preserve gut health. Notable therapeutic strategies such as Western medicine, traditional Chinese medicine, and other health-promotion interventions have been reported in several studies to hold promise in mitigating age-related gut disorders. This review highlights findings across various facets of gut aging with a focus on aging-associated changes of intestinal stem cells and their niche components, thus a deviation from the normal to repercussion, as well as essential therapeutic strategies to mitigate intestinal aging.

Multiple epigenetic factors play a regulatory role in maintaining the homeostasis of cutaneous components and are implicated in the aging process of the skin. They have been associated with the activation of the senescence program, which is the primary contributor to age-related decline in the skin. Senescent species drive a series of interconnected processes that impact the immediate surroundings, leading to structural changes, diminished functionality, and heightened vulnerability to infections. Geroprotective medicines that may restore the epigenetic balance represent valid therapeutic alliances against skin aging. Most of them are well-known Western medications such as metformin, nicotinamide adenine dinucleotide (NAD+), rapamycin, and histone deacetylase inhibitors, while others belong to Traditional Chinese Medicine (TCM) remedies for which the scientific literature provides limited information. With the help of the Geroprotectors.org database and a comprehensive analysis of the referenced literature, we have compiled data on compounds and formulae that have shown potential in preventing skin aging and have been identified as epigenetic modulators.

Mesenchymal stem cells (MSCs) are gaining the spotlight in research due to their abundant sources, immune privileges

Introduction Kidney stone disease (KS) is a complicated disease with an increasing global incidence. It was shown that Bushen Huashi decoction (BSHS) is a classic Chinese medicine formula that has therapeutic benefits for patients with KS. However, its pharmacological profile and mechanism of action are yet to be elucidated. Methods The present study used a network pharmacology approach to characterize the mechanism by which BSHS affects KS. Compounds were retrieved from corresponding databases, and active compounds were selected based on their oral bioavailability (≥30) and drug-likeness index (≥0.18). BSHS potential proteins were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, whereas KS potential genes were obtained from GeneCards and OMIM, TTD, and DisGeNET. Gene ontology and pathway enrichment analysis were used to determine potential pathways associated with genes. The ingredients of BSHS extract were identified by the ultra‐high‐performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q/Orbitrap MS). The network pharmacology analyses predicted the potential underlying action mechanisms of BSHS on KS, which were further validated experimentally in the rat model of calcium oxalate kidney stones. Results Our study found that BSHS reduced renal crystal deposition and improved renal function in ethylene glycol(EG)+ammonium chloride(AC)-induced rats, and also reversed oxidative stress levels and inhibited renal tubular epithelial cell apoptosis in rats. BSHS upregulated protein and mRNA expression of E2, ESR1, ESR2, BCL2, NRF2, and HO-1 in EG+AC-induced rat kidney while downregulating BAX protein and mRNA expression, consistent with the network pharmacology results. Discussion This study provides evidence that BSHS plays a critical role in anti-KS via regulation of E2/ESR1/2, NRF2/HO-1, and BCL2/BAX signaling pathways, indicating that BSHS is a candidate herbal drug for further investigation in treating KS.

Background: Fecal microbiota transplantation (FMT) based on the positive ion mode of metabonomics has a good therapeutic benefit for slow transit constipation (STC) patients. However, a piece of comprehensive metabolomics information is yet to be established. The aim of the study was to explore the efficacy and mechanism of FMT in the treatment of STC under metabonomics. Methods: Eight STC patients meeting the set inclusion and exclusion criteria were enrolled and treated with FMT (three times). The Patient Assessment of Constipation-Symptoms (PAC-SYM), weekly total defecation times, and defecation frequency scores of these STC patients were compared before and after treatment. Feces and serum of STC patients before and after treatment were analyzed using 16SrDNA and metabolomics. Results: After FMT treatment, the PAC-SYM score of constipated patients decreased [(5.00 ± 2.94) vs (5.20 ± 2.87)], while the number of complete defecations per week increased [(2.00 ± 1.79) vs (1.69 ± 1.80)]. The score of defecation frequency decreased [(0.83 ± 1.03) vs (0.86 ± 0.95)]. The metabolites in the feces and serum of patients receiving FMT changed significantly ( P < 0.05). The results from 16SrDNA analysis showed that the α and β diversity of the fecal microbiome changed significantly ( P < 0.05) after transplantation, and the contents of genera Lactobacillus , Bacillus , Succiniclasticum , Cellvibrio , and Escherichia increased in FMT treated patients. Conclusion: FMT may treat STC by increasing the beneficial intestinal flora and metabolites in the anion mode of metabolomics.

Background: Globally, interest in herbal medicines is increasing. In Ghana, most herbalist use herbal medicines for treatment of various ailments including prostate cancer, although no empirical evidence on their efficacies exists. Objective: The aim of the presentstudy was to test for antioxidant and anti-prostate cancer activities of Moringa oleifera, Phyllanthus amarusand Carica papaya. Methods: Plants parts used were air-dried, ground and sequentially extracted using solvents with increasing order of polarity (petroleum ether, dichloromethane, ethyl acetate, ethanol and aqueous). The 2, 2-diphenyl-1-picrylhydrazyl assay, Folin Ciocalteu method and tetrazolium-based calorimetric assay were used to determine total antioxidant capacities, total phenolic content of extracts and cytotoxicities of the extracts against LNCaP and PC3 prostate cancer cells, respectively. Results: Ethanolic extract of P. amaruspossessed the highest phenolic content while its aqueous extract showed the strongest antioxidant activity (EC50=19.32±1.13 μg/mL). Aqueous extract of C. papayaexhibited anti-prostate cancer activity with good selectivity towards PC3 cells [IC50= 45.68 ±1.16 μg/mL,selectivity index (SI) =18], whereas dichloromethane extract of P. amarusshowed the strongest anticancer activity against LNCaP cells (IC50= 43.97±1.14 μg/mL). Conclusion: These findings lend pharmacological credence to the anecdotal evidence of the anti-prostate cancer property of the plants. Further studies must be performed to identify the active principles in the bioactive plant components.