Search Results (2,315)

Cisplatin-induced acute kidney injury (AKI) remains a dose-limiting complication in cancer chemotherapy with restricted preventive measures. Carthamus tinctorius L. (safflower) is known to exhibit effective antioxidant and anti-inflammatory properties; however its potential in renoprotective mechanisms remains poorly understood. The present study utilized a cisplatin-induced AKI mouse model to evaluate the renoprotective potential of CT (Carthamus tinctorius) extract. Integrated multi-omics along with in silico and in vivo approaches were used to elucidate the underlying mechanisms of action. The results initially demonstrated a rich phytochemical profile of CT extract characterized by abundant polysaccharides and flavonoids, with Hydroxysafflor Yellow A as a dominant bioactive constituent. In a cisplatin-induced acute kidney injury (AKI) mouse model, CT extract noticeably ameliorated the abnormalities of renal injury, as suggested by improved histopathology, reduced serum creatinine and BUN levels, and regulation of redox homeostasis. Metabolically, CT extract partially reversed AKI-associated disturbances by affecting 21 key metabolites, likely associated with histidine and alanine-aspartate-glutamate biosynthesis, and modulating amino acid and energy metabolism pathways. Concurrently, CT extract improved gut microbial homeostasis, increasing microbial diversity, normalizing the Firmicutes/Bacteroidota ratio, suppressing pathogens, and enriching beneficial Ligilactobacillus. Network pharmacology and molecular docking identified AKT1, RELA, MAPK, and TP53 as central targets of core compounds (rutin and kaempferol derivatives), apparently targeting the PI3K-AKT and RELA (NF-kappaB) hubs. These results suggested that the renoprotective effects of CT extract are associated with transcriptional upregulation of the PI3K/Akt/Nrf2 pathway-related genes, increased expression of antioxidant genes (Ho-1, Sod1), and reduced expression of pro-inflammatory mediators (RelA, Cdk2) in the cisplatin-induced AKI mouse model. Full article

Exposure to high altitudes for hours or days is defined as acute hypobaric hypoxia (AHH) condition, which rapidly engages adjustments such as signaling pathways involving inflammation, immune modulation and oxidative stress, whose dysregulation has been described as contributing to the pathophysiology of high-altitude illnesses, due to insufficient acclimatization, such as developing acute mountain sickness (AMS). Given its traditional high-altitude use and bioactive properties, Senecio nutans (S. nutans) extract, or chachacoma (CH), has emerged as a potential therapeutic strategy to mitigate high-altitude related pathobiology. The aim of this study was to evaluate the effects of S. nutans on acclimatization, regarding the status of oxidative stress, inflammation, immune and symptoms associated with AMS in an animal model exposed to AHH. Twenty-eight female Wistar rats (≈3 months old) were randomly allocated into four experimental groups (n = 7 each): normobaric normoxia (NX), normobaric normoxia plus S. nutans administration (NX+CH), acute hypobaric hypoxia (AHH; 48 h exposure), and acute hypobaric hypoxia plus S. nutans administration (AHH+CH). S. nutans was administered subcutaneously at a dose of 80 mg/kg, one hour prior to hypoxic exposure. Outcomes included body weight, food intake, hematological parameters, lung histopathology, pulmonary mRNA expression of HIF-1α, NF-κB, TNF-α, IL-1β, IL-6, and VEGF, and lipid peroxidation in lung tissue assessed by malondialdehyde (MDA) levels. After 48 h of AHH, animals exhibited a decrease in body weight and food intake, increase in hematocrit level and total leukocytes, as well as lung injury characterized by thickening of alveolar walls and inflammatory infiltrates. In addition, AHH induced an increase in pulmonary IL-6 and IL-1β mRNA expression. In contrast, S. nutans administration partially attenuated hypoxia-induced body weight loss, mitigated the rise in hematocrit levels, and reduced lung damage, while returning total leukocyte counts to control levels. Notably, S. nutans also decreased the hypoxia-induced overexpression of IL-6 and IL-1β. Regarding lipid peroxidation, no significant differences were observed among groups. These findings suggest that S. nutans exerts a protective effect against acute hypobaric hypoxia by attenuating inflammatory responses and preserving pulmonary structure, thereby supporting its potential as a preventive strategy to mitigate early pathophysiological alterations associated with high-altitude exposure. Full article

More than 20 years after the discovery of lunasin, a clear shift in lunasin research is observable—from an initial focus on its direct in vitro anticancer effects toward strategies aimed at improving its bioavailability and repositioning it as a potential adjunct in cancer therapy. Lunasin, a soy-derived bioactive peptide, has been extensively studied for its antineoplastic properties. However, its limited oral bioavailability restrains its efficacy in clinical trials. Therefore, recent research on lunasin points towards the possibility of using it as an adjunct in cancer treatment, rather than as a stand-alone nutraceutical in humans. In preclinical models, in vitro and in vivo, lunasin can enhance the effects of standard anticancer drugs in breast and colon cancers. Research suggests that lunasin can potentiate the effects of drugs, such as tamoxifen, aspirin, cisplatin, and oxaliplatin, by sensitizing cancer cells to apoptosis, modulating cell cycle progression, reducing metastatic potential, and attenuating drug-resistance pathways, including PI3K/Akt, FAK/MAPK1/NF-κB, and integrin-mediated signaling. In combination with those drugs, lunasin exerts significant anticancer effects at concentrations substantially lower than those proven as effective in monotherapy, suggesting a potential role in dose reduction in conventional agents and, subsequently, mitigation of their adverse effects. Although the enhanced effect of those combinations has been shown in preclinical models, there is a distinct lack of human clinical trials in this matter. Available evidence supports a promising concept of lunasin as a molecular “priming” agent that might complement cytotoxic therapies rather than replace them. This combination-oriented paradigm may represent a shift in lunasin research and offer a novel direction for the use of bioactive peptides in precision oncology; however, further studies exploring this possibility, including human clinical trials, are needed to elucidate lunasin’s role in nutraceutical-assisted cancer therapy. Full article

Sleep deprivation is a recognized risk factor for neuroinflammatory and neurodegenerative disorders. Dopamine signaling through D2 receptors (DRD2) has emerged as a potential immunomodulatory pathway in the central nervous system. The present study investigated whether activation of DRD2 by quinpirole (QUIN) modulates astrocytic and microglial responses and NF-κB nuclear translocation in a murine model of rapid eye movement sleep deprivation (RSD). Male CD1 mice were subjected to 72 h of RSD and treated with QUIN (2 mg/kg/day). GFAP, Iba-1, and NF-κB expression were evaluated in hippocampal subregions (CA1, CA3, dentate gyrus) and the medial parietal cortex using immunofluorescence and confocal microscopy. RSD increased GFAP and Iba-1 expression and induced morphological changes consistent with glial activation. Notably, RSD increased NF-κB nuclear expression in microglia. QUIN administration reduced Iba-1 expression, attenuated microglial morphological alterations, and reduced NF-κB nuclear expression across all analyzed regions, even in RSD-subjected mice. These findings suggest that DRD2 activation exerts anti-inflammatory effects in the brain during REM sleep deprivation and that dopaminergic signaling may represent a key target for neuroinflammation associated with sleep loss. Full article

Hypogonadism is increasingly recognized as an independent cardiovascular risk factor, with testosterone deficiency associated with endothelial dysfunction, increased thrombotic risk, and adverse cardiovascular outcomes. Circulating biomarkers provide valuable insights into the vascular health status of hypogonadal men and the cardiovascular effects of testosterone replacement therapy (TRT). This comprehensive review examines the molecular basis of testosterone action on the cardiovascular system and synthesizes evidence on circulating cardiovascular biomarkers in hypogonadism, including endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), platelet markers, endothelial activators, adhesion molecules, and inflammatory/oxidative stress markers. We also compare the cardiovascular safety profiles of transdermal versus intramuscular testosterone formulations. Hypogonadal men exhibit reduced circulating EPCs, elevated EMPs, increased platelet reactivity, higher levels of endothelial activators (ICAM-1, VCAM-1, E-selectin, von Willebrand factor, endothelin-1, ADMA), and increased inflammatory markers (hsCRP, IL-6, TNF-α). TRT improves most of these biomarkers through androgen receptor (AR)-dependent and AR-independent mechanisms involving PI3K/Akt/eNOS signaling, VEGF upregulation, CXCL12/CXCR4 axis modulation, and NF-κB pathway suppression. Current evidence suggests that transdermal testosterone formulations may offer advantages regarding hematological safety and more stable testosterone exposure; however, definitive evidence demonstrating superior cardiovascular outcomes compared with intramuscular formulations remains limited. Circulating cardiovascular biomarkers are significantly altered in hypogonadism and improve with TRT. Available data suggest that transdermal testosterone formulations may offer a more favorable cardiovascular safety profile than intramuscular preparations, particularly with respect to erythrocytosis and pharmacokinetic stability, although head-to-head randomized trials with hard cardiovascular endpoints are still needed. Understanding the molecular mechanisms underlying these changes is essential for optimizing TRT in hypogonadal men with cardiovascular risk factors. The cardiovascular safety advantage of transdermal formulations is currently supported primarily by pharmacokinetic and hematological evidence; direct comparative evidence from randomized trials with hard cardiovascular endpoints remains unavailable. Full article

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide and is characterized by extensive vascularization, aggressive progression, and limited therapeutic responsiveness. Angiogenesis plays a central role in HCC development by supporting tumor growth, metabolic adaptation, invasion, and metastatic dissemination. Although anti-angiogenic therapies targeting the vascular endothelial growth factor (VEGF) pathway have improved clinical management, their overall survival benefit remains modest because of compensatory signaling, adaptive resistance, and the highly complex nature of the tumor microenvironment (TME). Astrocyte elevated gene-1/metadherin (AEG-1/MTDH) has emerged as a multifunctional oncogene that functions by orchestrating interconnected angiogenic, inflammatory, metabolic, and immune-regulatory programs within the hepatic tumor microenvironment. AEG-1 regulates angiogenesis through modulation of VEGF-family signaling, NF-κB activation, hypoxia-responsive pathways, PI3K/AKT signaling, endothelial remodeling, and translational control of pro-angiogenic mediators. Emerging evidence further implicates AEG-1 in hypoxia adaptation, immune evasion, extracellular vesicle signaling, and metabolic reprogramming, supporting its role as a systems-level regulator of HCC angiogenesis. This review summarizes the current understanding of the molecular mechanisms through which AEG-1 regulates angiogenesis in HCC, discusses its interactions with the TME and anti-angiogenic resistance pathways, and highlights future translational opportunities for developing multi-targeted therapeutic strategies beyond conventional VEGF-centric approaches. Full article

Redox homeostasis is the balance between oxidative processes and antioxidant defenses and is fundamental to cellular integrity. This review critically synthesizes current evidence on the phytochemical composition, redox-modulating mechanisms, and therapeutic bioactivities of Fagonia cretica L. (F. cretica), with the aim of evaluating its translational potential as a natural antioxidant and anticancer agent. F. cretica has emerged as a phytochemically rich candidate containing highly bioactive secondary metabolite for redox-targeted therapeutic applications. Its diverse secondary metabolite profile, including alkaloids, flavonoids, tannins, saponins, terpenoids, glycosides, and phenolic compounds, confers broad biological activity. Bioactive constituents, particularly kaempferol, catechin, quercetin, and arbutin, directly neutralize reactive oxygen species (ROS) and modulate inflammatory pathways through inhibition of COX-1, COX-2, and nitric oxide production. These compounds influence important major ROS-sensitive redox signaling pathways: activation of the Keap1/Nrf2/ARE axis to upregulate cytoprotective genes such as HO-1, NQO1, and GCL, suppression of the NF-κB pathway to attenuate pro-inflammatory cytokine transcription, including TNF-α, IL-1β, and IL-6, and interference with the MAPK-PI3K/Akt cascade to disrupt aberrant cancer cell survival and proliferation. Bioactive compound-rich extracts of F. cretica exhibit anticancer activity in MCF-7 breast cancer cells by inducing DNA damage, cell cycle arrest, and apoptotic signaling through the FOXO3a/p53 pathways. Similar effects have been reported in colorectal (HCT-116) and prostate (PC-3) cancer cells through DNA (cytosine-5)-methyltransferase 1 (DNMT1) downregulation, oxidative stress induction, and ER-β activation. Moreover, these extracts demonstrate cytotoxic effects in HepG2 and Caco-2 intestinal cancer cells, often associated with topoisomerase inhibition and caspase activation. Despite encouraging preclinical evidence, systematic studies encompassing pharmacokinetic profiling, toxicological characterization, and human clinical trials remain essential to translate these findings into safe, evidence-based therapeutic applications. Full article

Asthma is a heterogeneous chronic airway disease in which oxidative stress (OS) plays a central mechanistic role beyond classical immune-mediated inflammation. Reactive oxygen and nitrogen species (ROS/RNS), generated by recruited inflammatory cells and activated airway structural cells, drive epithelial injury, mucus hypersecretion, airway remodeling, and modulate key transcription factors including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. This review synthesizes current evidence on the multilevel redox-based determinants of asthma severity, spanning from genetic polymorphisms to circulating biomarkers. We examine serum antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxiredoxins (PRDXs), and the thioredoxin (Trx) system as dynamic indicators of systemic redox status and disease severity, alongside oxidative enzymes including NADPH oxidases and dual oxidases (NOX/DUOX), xanthine oxidase (XO), and myeloperoxidase (MPO) that serve as upstream sources of airway oxidant burden. Functional genetic polymorphisms in antioxidant genes (SOD2, CAT, glutathione S-transferase mu 1/glutathione S-transferase theta 1 (GSTM1/GSTT1), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/KEAP1)) and oxidative enzyme genes including nitric oxide synthase 1/2/3 (NOS1/2/3), MPO, cytochrome b-245 alpha chain (CYBA), and xanthine dehydrogenase (XDH) are reviewed as modulators of individual redox capacity and asthma susceptibility, with particular attention to gene–environment interactions. We further discuss oxidative damage biomarkers, including malondialdehyde (MDA), 8-isoprostanes, 4-hydroxynonenal, 8-oxo-7, 8-dihydro-2′-deoxyguanosine, protein carbonyls, 3-nitrotyrosine, and advanced oxidation protein products as indicators of lipid, DNA, and protein oxidation that correlate with disease activity and control. The roles of micronutrient cofactors in modulating antioxidant enzyme function and their potential as contextual biomarkers are also addressed. Additionally, emerging evidence on microRNAs (miRNAs) linked to OS biology in asthma is presented. Finally, we critically evaluate the challenges limiting clinical translation, including biomarker non-specificity, analytical variability, gene–environment complexity, and the absence of standardized reference ranges. This integrated framework supports the development of multilevel redox prognostic panels combining genetic, enzymatic, and oxidative damage readouts for improved asthma phenotyping, severity stratification, and personalized therapeutic approaches. Full article

Lichen sclerosus (LS) is a chronic inflammatory skin disorder with an incompletely understood molecular pathogenesis. This systematic review aimed to synthesize current evidence on key molecular mechanisms underlying the disease, with a particular focus on immune dysregulation, epigenetic modifications, and tissue remodeling. A structured literature search identified studies employing transcriptomic, epigenetic, and experimental approaches. The strongest evidence consistently supports a central role of immune activation, particularly T cell-mediated responses involving Th1- and Th17-related pathways, accompanied by increased expression of pro-inflammatory cytokines and activation of the NF-κB signaling pathway. Epigenetic and post-transcriptional mechanisms, including dysregulated microRNAs (notably miR-155-5p) and altered DNA methylation patterns, may sustain immune imbalance and fibroblast activation partly via modulation of the FOXO signaling pathway. In parallel, experimental and multi-omics studies highlight enhanced fibroblast activity and extracellular matrix remodeling, largely associated with the TGF-β signaling pathway, linking inflammation with progressive fibrosis. Emerging data also suggest interactions between immune signaling and metabolic alterations, although these findings remain preliminary. Overall, the available evidence indicates that LS may involve a complex interplay between immune, epigenetic, and fibrotic mechanisms. While several molecular pathways and candidate biomarkers have been identified, their clinical relevance requires further validation in larger, well-designed studies. Full article

Background/Objectives: Atherosclerotic plaque instability is driven by complex interactions among inflammatory, structural, and cellular remodeling programs. While bulk RNA sequencing provides insight into tissue-level transcriptional states and single-cell RNA sequencing (scRNA-seq) defines cellular heterogeneity, integration across these transcriptomic layers remains limited. We aimed to identify coordinated transcriptional programs associated with stable and unstable plaque phenotypes and map these programs to specific cellular compartments and regulatory networks. Methods: Paired bulk RNA-seq data from stable and unstable human carotid plaques (GSE120521) and scRNA-seq data from human coronary atherosclerotic lesions (GSE131778) were analyzed. Differential expression and Hallmark gene set enrichment analyses were performed using limma and clusterProfiler. Bulk-derived inflammatory and structural signatures were projected onto single-cell data using Seurat module scoring. Compartment-level transcriptional scores, an inflammatory–structural endotype index, and transcription factor activity inference using decoupleR and DoRothEA were used to characterize plaque-associated transcriptional states. Results: Unstable plaques demonstrated enrichment of inflammatory pathways, including interferon gamma response, inflammatory response, TNFα/NF-κB signaling, IL6/JAK/STAT3 signaling, complement activation, and reactive oxygen species pathways. In contrast, stable plaques demonstrated relative enrichment of myogenesis and structural remodeling programs. Projection of bulk-derived signatures onto single-cell data localized inflammatory programs predominantly to TREM2hi and inflammatory macrophage populations, whereas structural programs localized to smooth muscle cell and fibromyocyte-like compartments. Compartment-level analyses showed increased myeloid and adaptive immune signatures in unstable plaques and increased smooth muscle cell/fibro-remodeling signatures in stable plaques. Transcription factor activity analysis identified increased SPI1, NFKB1, RELA, and STAT1 activity in unstable plaques and higher SRF and TEAD1 activity in stable plaques. Conclusions: Integrative analysis of bulk and single-cell transcriptomic data identified distinct inflammatory and structural plaque transcriptional states associated with unstable and stable plaque phenotypes, respectively. These findings support a systems-level framework linking tissue-level plaque behavior to specific cellular and regulatory programs and provide evidence for inflammatory and structural plaque endotypes in human atherosclerosis. Full article

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and is increasingly driven by cardiometabolic disease, including type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. These conditions promote atrial electrical instability and a permissive substrate through mitochondrial dysfunction, oxidative stress, inflammation, calcium-handling abnormalities, and profibrotic signaling, culminating in atrial fibrosis and conduction heterogeneity. Metformin, the foundational glucose-lowering therapy for T2DM, exerts pleiotropic actions that intersect with these upstream pathways. Beyond glycemic control, metformin induces mild mitochondrial complex I modulation with reduction of reverse electron transfer-derived reactive oxygen species, activates adenosine monophosphate (AMP) activated protein kinase, and attenuates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated cytokine signaling; experimental data further suggest favorable effects on adiponectin–sarcoendoplasmic reticulum calcium adenosine triphosphatase (SERCA) 2a-dependent calcium cycling, connexin expression, small-conductance Ca²⁺-activated K+ channel remodeling, lipid handling, and transforming growth factor-β (TGF)-β-associated fibrotic remodeling. Observational cohort studies have reported associations between metformin exposure and a modest reduction in incident AF, particularly with longer treatment duration and in higher-risk metabolic phenotypes; device-based surveillance cohorts support a preventive association for new-onset AF rather than reduction of established AF burden. Data after catheter ablation suggest improved freedom from recurrence in metformin-treated patients, whereas evidence in postoperative AF is largely neutral, likely reflecting distinct acute mechanisms. Collectively, metformin may be best conceptualized as a potential substrate-modifying, upstream therapy candidate; however, confounding, exposure misclassification, and heterogeneity in comparators limit causal inference, underscoring the need for prospective randomized trials with AF endpoints. In practice, integration with comprehensive risk-factor modification (blood pressure, weight, sleep apnea, and glycemic optimization) remains essential when considering AF prevention strategies. Full article

This paper presents a miniaturized ultra-wideband high-pass filter integrated with a notch function based on low-temperature co-fired ceramic (LTCC). The design motivation is to realize continuous wideband high-pass transmission while rejecting a narrow in-band interference/leakage component in compact RF front-end modules. The proposed design employs a cascaded structure of a seventh-order quasi-elliptic HPF and a three-section $\lambda /4$ stub notch filter in a single multilayer LTCC chip. Multiple transmission zeros (TZs) are introduced to improve the lower-stopband selectivity, while the three-section coupled-line NF produces a tunable localized rejection band. The LTCC implementation further integrates multilayer capacitors, three-dimensional helical inductors, shielded strip-line coupling stubs, a grounding compensation capacitor, and an isolation wall to balance compactness, impedance matching, and parasitic suppression. The fabricated chip achieves an ultra-wide bandwidth of 2.35 octaves, a notch 20 dB FBW of 8.5%, an insertion loss below 2 dB, a 60 dB roll-off rate of 154.1 dB/GHz within the lower stopband, and a voltage standing wave ratio (VSWR) less than 2. Experimental results validate that the proposed compact chip meets communication requirements and is suitable for 5G base stations, radar systems, and other applications. The chip dimensions are 4.5 mm × 3.2 mm × 2.5 mm. Full article

Background: Cisplatin-induced cardiotoxicity is associated with oxidative stress, inflammation, and apoptosis; however, the role of CD38-Sirt3 signaling remains unclear. This study investigated whether apigenin protects against cisplatin-induced cardiac injury via modulation of CD38-Sirt3 signaling. Methods: Male Sprague Dawley rats were assigned to three groups, (1) Control, (2) Cisplatin (5 mg/kg), and (3) Pretreatment with apigenin (50 mg/kg/day) plus cisplatin groups. Then, left ventricular (LV) function, cardiac injury, oxidative stress, inflammation, apoptosis, and CD38-Sirt3 signaling-related proteins were assessed. Results: Cisplatin impaired LV function and induced cardiac injury, oxidative stress, inflammation, and apoptosis in rats. These changes were accompanied by increased cardiac CD38 and decreased cardiac Sirt3 and SOD2 expression. Apigenin significantly improved LV function (%LVEF and %LVFS), reduced cardiac injury (LDH, CK-MB), attenuated oxidative stress, suppressed inflammatory responses (TNF-α, IL-1β, p-NF-κB, TLR-4), and inhibited apoptosis (Bax/Bcl-2, cleaved caspase-3). Notably, apigenin improved cardiac SOD2 expression and reversed the alteration of CD38-Sirt3 signaling in cisplatin-treated rats. Conclusions: This study provides evidence that cisplatin-induced cardiotoxicity is associated with alterations in CD38-Sirt3 signaling. Apigenin attenuated LV dysfunction and cardiac injury, reduced oxidative stress, inflammation, and apoptosis, potentially through CD38-Sirt3 signaling. These findings highlight the cardioprotective potential of apigenin against cisplatin-induced cardiotoxicity. Full article

Muscle wasting associated with gastric cancer represents a complex, multifactorial systems disorder involving inflammatory, anabolic, mechanosensory, calcium-regulatory, mitochondrial, and proteostatic disruption. This review synthesizes current evidence regarding the cellular and physiological mechanisms involved in skeletal muscle dysfunction in gastric cancer and provides a unifying framework centered on loss of signaling coherence. Specifically, it examines IL-6/STAT3 and NF-κB inflammatory signaling, the myostatin–activin–ACVR2B–SMAD pathway, PI3K/Akt/mTOR signaling, mechanotransduction, excitation–metabolism coupling, calcium homeostasis, mitochondrial function, and proteostasis. Although individual components of these pathways have been implicated in muscle wasting associated with chronic disease, current evidence suggests that they interact through positive feedback loops. Inflammation, anabolic resistance, impaired force-to-signal conversion, mitochondrial stress, altered intracellular calcium homeostasis, and disrupted protein quality control may reinforce one another, contributing to metabolic, structural, and transcriptional instability. Within this context, muscle wasting reflects not only loss of muscle mass or strength, but also loss of functional integrity resulting from disrupted integration of mechanical, metabolic, inflammatory, and anabolic signals. Given the systemic nature of these effects, this review proposes kinesitherapy as a potentially useful nonpharmacological adjunctive strategy that may modulate inflammation, restore responsiveness to mechanical stimuli, support calcium homeostasis and mitochondrial function, improve anabolic sensitivity, and maintain protein quality control. Overall, this review presents a systems-biology model of gastric cancer-associated muscle wasting and supports further investigation of exercise-based therapies for this condition. Full article

Natural products like the isoprenylated flavonoid Kuwanon G (KWG), isolated primarily from Morus alba, offer promising pleiotropic effects against multifactorial diseases, overcoming the limitations of conventional single-target synthetic drugs. This study aims to systematically review the pharmacological activities of KWG and evaluate its underlying molecular mechanisms. A comprehensive literature review was integrated with network pharmacology, protein–protein interaction (PPI) profiling, and KEGG/GO pathway enrichment analyses to identify shared targets across different pathologies. Experimental data demonstrate that KWG exhibits antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, anti-obesity, and anticancer properties. Bioinformatics analyses revealed that KWG exerts these effects by modulating core targets (e.g., TNF, IL-6, SRC, RELA) and key signaling pathways, including NF-κB, PI3K/AKT/mTOR, and Toll-like receptors, which govern inflammation, oxidative stress, and metabolic regulation. In conclusion, KWG is a potent, multi-target compound with significant therapeutic potential for managing chronic and infectious diseases. However, future structure–activity relationship studies and clinical trials are required to address its pharmacokinetic limitations, such as low bioavailability, to facilitate its clinical translation. Full article