Search Results (4,650)

Microbial fertilizers may improve phosphorus availability and pH in acidic soils, but field evidence linking these changes with medicinal plant biomass and specialised metabolite accumulation remains limited. Here, a one-season field experiment was conducted in acidic yellow soil in Guizhou Province, China, using four fertilization regimes for Lonicera macranthoides: an organic fertilizer plus compound fertilizer control (CK), a bacterial consortium (T1), a simplified bacterial combination (T2), and a fungal agent (T3). Soil chemical properties, soil aggregate composition, flower-bud biomass, and chlorogenic-acid-related compounds were measured. T1 and T3 increased soil available phosphorus and pH at the pre-flowering stage and increased the proportion of water-stable macroaggregates (>5 mm). Both treatments also increased fresh and dry biomass. T1 showed the highest numerical chlorogenic acid content, whereas T3 was more favourable for the accumulation of isochlorogenic acids A and C. Across plot-level observations, available phosphorus was positively correlated with fresh weight (r = 0.804) and dry weight (r = 0.781), and pH was positively correlated with chlorogenic acid (r = 0.687). Univariate regression and redundancy analysis further indicated that available phosphorus and pH were the soil factors most closely associated with biomass and chlorogenic acid accumulation. These findings provide preliminary field indications that microbial fertilizers may improve yield and medicinal quality in acidic-soil L. macranthoides production. However, the single-season, single-site nature of the experiment warrants cautious interpretation and further validation across broader conditions. The observed associations are consistent with, but do not prove, a mechanistic pathway involving microbe-mediated phosphorus transformation and acidity regulation. Full article

Cancer remains one of the leading causes of global mortality, with its incidence continuing to rise due to population growth, aging, lifestyle factors, and environmental exposures. Despite significant advances in early diagnosis and therapeutic strategies, the clinical management of cancer is still hindered by drug resistance, limited selectivity, and treatment-related toxicity. Consequently, increasing attention has been directed toward natural products as sources of novel anticancer agents with improved efficacy and reduced adverse effects. Pogostemon cablin (patchouli), a medicinal plant widely used in traditional medicine, has emerged as a promising candidate owing to its diverse bioactive constituents and broad pharmacological properties. This review systematically summarizes and critically evaluates current evidence on the anticancer potential of patchouli leaves, with particular emphasis on molecular mechanisms and translational relevance. Based on available experimental and preclinical studies, patchouli and its major phytochemicals exhibit notable anticancer activity against a wide range of malignancies, including endometrial, ovarian, liver, skin, nasopharyngeal, prostate, hematological, colorectal, and lung cancers. Mechanistically, these effects are primarily associated with the modulation of apoptosis, cell cycle regulation, oxidative stress, and key oncogenic signaling pathways, as well as potential synergistic interactions with conventional chemotherapeutic agents. Overall, this review highlights the therapeutic promise of patchouli leaves as a source of anticancer agents, identifies current knowledge gaps, and outlines future research directions to facilitate their development and clinical translation. Full article

Obesity and type 2 diabetes (T2D) are multifactorial metabolic disorders characterized by progressive dysfunction of multiple organs and biological systems. Although mitochondrial dysfunction is a hallmark of disease progression, the mechanisms linking metabolic stress to coordinated tissue dysfunction remain incompletely understood. Comparative proteomic studies have consistently identified coordinated remodeling of oxidative phosphorylation, fatty acid oxidation, tricarboxylic acid cycle activity, redox regulation, mitochondrial proteostasis, and adaptive signaling across metabolically affected organs, revealing conserved organizational principles underlying mitochondrial adaptation. However, these findings have largely been interpreted within reductionist, pathway-centered frameworks. Here, we integrate evidence from comparative proteomics, mitochondrial biology, bioenergetics, redox biology, signaling, and systems biology to propose the concept of mitochondrial-centered biological networks (MCBNs), in which mitochondria function as dynamic regulatory hubs coordinating interconnected processes that collectively determine metabolic adaptation and tissue resilience. Building on this framework, we introduce the Mitochondrial Homeostasis Hypothesis, which proposes that preservation or restoration of mitochondrial homeostasis depends on coordinated regulation of MCBNs and constitutes a fundamental systems-level mechanism underlying resistance to obesity, T2D, and hypercaloric diet-induced metabolic dysfunction. Curcumin represents a well-studied network-modulating intervention that coordinately influences mitochondrial bioenergetics, metabolic flexibility, redox homeostasis, proteostasis, inflammatory signaling, and adaptive stress responses, supporting the concept that mitochondrial homeostasis is preserved through coordinated network regulation rather than isolated modulation of individual molecular pathways. Finally, we discuss how emerging technologies, including functional proteomics, redox proteomics, spatial and single-cell proteomics, acetylomics, integrated multi-omics, and artificial intelligence-assisted network analysis, provide unprecedented opportunities to quantitatively characterize MCBNs, validate the proposed hypothesis, identify network-based biomarkers, and accelerate the development of network-guided precision mitochondrial medicine. Full article

Background: This review aims to systematically summarize the lineage origins, subtype classification, and functional dynamics of endometrial macrophages, clarify their mechanisms of action in normal reproductive physiology (menstrual cycle, pregnancy) and common reproductive diseases, integrate cognitive breakthroughs brought by cutting-edge research technologies, and provide theoretical support for basic research and clinical translation in reproductive medicine. Methods: Recent basic and clinical research studies related to endometrial macrophages were retrieved, with a focus on incorporating findings from technologies such as single-cell sequencing and multi-omics. The reviewed content covers core aspects including macrophage origins (embryonic-derived, bone marrow-derived), subtype classification (M1/M2 and novel metabolism-related subtypes), cycle- and pregnancy-specific functions, and disease-associated mechanisms. A comprehensive analysis of the regulatory networks of endometrial macrophages under physiological and pathological conditions was conducted. Results: Endometrial macrophages, by virtue of their phenotypic plasticity and functional heterogeneity, play a central role in cyclical endometrial remodeling, pregnancy establishment, and the regulation of reproductive immune homeostasis. Dysregulation of their function is closely associated with various reproductive disorders such as recurrent spontaneous abortion and endometriosis. In-depth exploration of their biological characteristics and regulatory mechanisms holds great significance for filling knowledge gaps in the field of reproductive immunology and advancing precise prevention and treatment of related diseases. Conclusions: Endometrial macrophages are core regulators of the reproductive immune microenvironment, and their spatiotemporal dynamic functions are closely linked to reproductive health. The revelation of novel classification systems and regulatory mechanisms provides new perspectives for in-depth understanding of reproductive physiological and pathological processes, as well as important targets for immune-targeted therapy of reproductive-related diseases. This holds great clinical translational significance for promoting the precision development of reproductive medicine. Full article

Indole alkaloids are major bioactive compounds in Strobilanthes cusia. Although methyl jasmonate treatment can promote the accumulation of indole alkaloids in S. cusia, the transcriptional regulation remains unclear. In this study, the jasmonic acid responsive bHLH transcription factor ScMYC2 was cloned and characterized. It encodes a protein containing 477 amino acids, which features typical bHLH-MYC_N and HLH domains. ScMYC2 localized in the nucleus, showed tissue specific expression consistent with indole alkaloid accumulation, and was significantly induced by methyl jasmonate. Furthermore, the coding sequence of ScMYC2 was cloned into an expression vector and overexpressed in Arabidopsis thaliana via Agrobacterium-mediated transformation technology. Alkaloid metabolic analysis was performed on three homozygous A. thaliana lines (ScMYC2-OE1, OE2, OE3) stably transformed using UPLC-MS/MS. The results indicated that, compared with wild-type, 14 differential metabolites were detected in the A. thaliana lines overexpressing ScMYC2. Among them, the content of indole increased to 2.83-fold that of the wild-type, while the indole glycoside component indole-3-cyano-6-O-glucoside increased to 2.35-fold. Yeast two-hybrid screening identified 35 ScMYC2-interacting proteins, including UDP-glycosyltransferase, TOPLESS-related proteins, and E3 ubiquitin-protein ligase. BiFC assays further confirmed the in vivo interaction between ScMYC2 and ScUGT1. These findings suggest that ScMYC2 is associated with methyl jasmonate-responsive regulation of indole alkaloid biosynthesis and provides genetic resources for the cultivation of S. cusia with high medicinal value. Full article

Kansui Radix, the root of Euphorbia kansui, was first described in Shen Nong Ben Cao Jing as a traditional Chinese medicine, known for its effects of expelling water, reducing edema, and dissipating masses. It is traditionally indicated for conditions such as “watery accumulation” and “abdominal masses (zheng-jia)”, which share certain similarities with the clinical manifestations of renal cell carcinoma (RCC), including renal masses, edema, and body cavity effusion. Despite the recognized antitumor effects of Kansui Radix, the pharmacological basis and specific molecular mechanisms underlying its inhibition of RCC progression remain unclear. The goal of this study was therefore to evaluate the antitumor efficacy of Kansui-DCM in RCC and to explore its potential mechanism. To this end, the chemical composition of the dichloromethane fraction of Kansui Radix (Kansui-DCM) was characterized by UPLC-MS. The antiproliferative effects of Kansui-DCM on 786-O and RENCA cells were evaluated using the CCK-8 assay. Apoptotic morphology, apoptosis rate, cell migration and invasion abilities were assessed. An RCC mouse model was established, and tumor growth and histopathological staining were evaluated after drug administration. Immunohistochemistry, transcriptomic analysis, WGCNA (weighted gene co-expression network analysis), network pharmacology, and immunofluorescence were employed to investigate the molecular pathway. Protein and gene expression were analyzed by Western blot and qRT-PCR, respectively. Finally, the interactions between the active components and key targets were substantiated through molecular docking and molecular dynamics simulations. A total of 1397 compounds were detected in Kansui-DCM by UPLC-MS. In vitro experiments demonstrated that Kansui-DCM inhibited the proliferation of 786-O and RENCA cells in a dose-dependent manner, induced apoptosis, and suppressed cell invasion and migration in RENCA cells. Treatment with Kansui-DCM markedly suppressed tumor growth in vivo, as reflected by a reduction in tumor volume. Immunohistochemical analysis indicated that the expression levels of CD31, COX-2, and Ki67 were markedly decreased, while the expression level of CD8 was significantly increased. Integrated analysis using WGCNA and network pharmacology predicted that Kansui-DCM may exert its effects through the regulation of the HIF/VEGF signaling pathway, which was further validated by immunofluorescence, Western blot, and qRT-PCR assays. Molecular docking and molecular dynamics simulations demonstrated stable interactions between multiple active components of Kansui-DCM and key targets such as VEGFR2 and HIF-2α. In conclusion, these findings suggested that Kansui-DCM exerts anti-RCC effects associated with regulation of the HIF/VEGF pathway. Full article

Background: Diabetic foot ulcers (DFUs) are chronic wounds characterized by persistent inflammation, oxidative stress, impaired angiogenesis, and defective extracellular matrix remodeling. Current therapeutic approaches remain insufficient for refractory diabetic wounds due to limited drug retention and inadequate regulation of the wound microenvironment. This study aimed to develop a centipede-derived protein fraction-loaded nanocapsule hybrid hydrogel for sustained bioactive delivery and diabetic wound repair. Methods: A bioactive protein fraction was isolated from processed medicinal centipede material and screened using cellular compatibility assays. The selected tropomyosin-containing protein fraction was incorporated into nanocapsules and subsequently integrated into a gallic acid-modified polyacrylamide hydrogel matrix. The physicochemical properties, antioxidant activity, rheological behavior, and protein release characteristics of the nanocapsule-hydrogel system were systematically evaluated. A streptozotocin-induced diabetic rat wound model was established to assess therapeutic efficacy through wound closure analysis, histological staining, and immunohistochemical evaluation. Results: The prepared nanocapsules exhibited a spherical morphology, nanoscale size distribution, and sustained protein delivery capability. The PAM-GA hydrogel demonstrated antioxidant activity, injectability, shear-thinning behavior, self-healing ability, and enhanced retention of protein release. In vivo experiments showed that the PT@NC@PAM-GA hydrogel significantly accelerated wound closure and promoted tissue regeneration, accompanied by enhanced angiogenesis, collagen deposition, and reduced inflammatory responses. Conclusions: The centipede-derived protein fraction-loaded nanocapsule hybrid hydrogel effectively integrates bioactive protein delivery with a multifunctional hydrogel matrix, providing a potential strategy for sustained treatment of diabetic foot ulcers. Full article

In modern societies, the renewed concept of food as medicine coexists with unprecedented consumption of highly processed foods, food additives, environmental xenobiotics, and pharmacological agents, contributing to the increasing prevalence of metabolic and degenerative diseases and accelerated aging. Although modern pharmacotherapies have transformed disease management, long-term drug exposure introduces additional metabolic burdens, off-target effects, and cumulative toxicities that are profoundly influenced by nutritional status. Collectively, dietary constituents, environmental chemicals, endogenous metabolic by-products, and therapeutic agents constitute a complex exposome that requires continuous recognition, utilization, detoxification, and clearance. Within this context, the liver sinusoidal clearance system (LSCS) emerges as a central regulator of systemic homeostasis. We propose a conceptual framework in which circulating molecules are classified as self (S), modified self (M), and foreign (F) molecules according to their physiological handling by the LSCS. Through coordinated hepatic utilization of S molecules and selective clearance of M and F molecules, fenestrated liver sinusoidal endothelial cells (LSECs) maintain metabolic homeostasis, immune tolerance, and physiological pharmacokinetics. Conversely, chronic dietary overload, poor dietary quality, food processing, and sustained exposure to pro-inflammatory and oxidative dietary and environmental molecules initiate chronic low-grade inflammation, which promotes LSEC capillarization, impairs hepatic clearance, increases the modification of S molecules into M molecules and establishes a feed-forward cycle that further amplifies chronic inflammation and metabolic dysfunction. Finally, we discuss recent advances in the programmable modulation of the LSCS, including its transient suppression to prolong therapeutic exposure and its activation to enhance the clearance of metabolically harmful M and F molecules through coordinated upregulation of the endoglin–stabilin-2–FcγRIIb axis and the LSEC markers Oit3 and Dnase1L3. We highlight dual-function supramolecular nanofiber platforms that enable bidirectional regulation of the LSCS through nanofiber complexes with therapeutic proteins, thereby expanding their therapeutic potential and enhancing efficacy in the treatment of metabolic, inflammatory, and age-related diseases. Full article

Hyperuricemia (HUA) is a key pathological basis for gout and uric acid (UA) nephropathy, and its increasing global prevalence presents a substantial public health challenge. Natural products (NPs) have emerged as a research hotspot due to their potential to reduce UA and favourable safety profile; however, comprehensive bibliometric analyses in this area remain limited. In this study, the English literature on NPs with anti-HUA activity published between 2004 and 2026 was retrieved from the Web of Science, Scopus, and PubMed, and analyzed using Bibliometrix (R package), VOSviewer, and CiteSpace. A total of 581 articles were identified, indicating a rapid increase in publication output across 53 countries, 870 institutions, 234 journals, and 3421 authors. China was found to lead the field, with Guangzhou University of Traditional Chinese Medicine contributing the highest number of publications. The Journal of Ethnopharmacology ranked first in publication volume, and Kong Ling-Dong emerged as the most prolific author. Major research foci included xanthine oxidase (XOD), UA metabolism, oxidative stress, inflammatory regulation, gut microbiota, and molecular docking. Perilla frutescens leaves and Terminalia chebula, together with six principal categories of bioactive compounds, demonstrated promising therapeutic potential. Overall, this study elucidates the developmental trends and research frontiers in the field, providing a valuable reference for future investigations. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

Bioactive food ingredients that regulate the gut microbiota are promising dietary strategies for supporting systemic health, but their roles in skin photoaging remain insufficiently defined. Qiongyu Gao (QYG), a classical food–medicine homologous formula composed of Rehmanniae Radix, Panax ginseng, and Poria cocos, was evaluated as an oral functional food candidate for UV-induced skin photoaging. QYG was chemically characterized by HPLC and UPLC–QTOF–MS/MS. Young and aged mice were subjected to D-galactose plus UVA/UVB exposure and orally administered QYG, followed by skin transcriptomics, gut microbiota sequencing, serum metabolomics, and validation in UVB-injured primary dermal fibroblasts. QYG alleviated wrinkle formation, epidermal thickening, oxidative stress, inflammation, extracellular matrix degradation, collagen disorganization, and hyaluronic acid loss. Multi-omics analysis showed that QYG selectively remodeled gut microbiota, enriching Lactobacillus-, Bifidobacterium-, and Akkermansia-associated taxa, regulated serum metabolites related to energy and lipid metabolism, and enriched mitochondrial energy metabolism-related pathways in photoaged skin. In fibroblasts, QYG-containing serum restored mitochondrial membrane potential, reduced ROS accumulation and cellular senescence, and regulated AMPK/PGC-1α-associated markers. These findings support QYG as a promising food–medicine homologous functional food candidate for skin health maintenance through gut microbiota-associated systemic metabolic regulation. Full article

The BMP2-Smad signaling pathway serves as a central regulator of osteoblast differentiation and bone formation, rendering it a promising target for the discovery of osteogenic agents from natural sources. Nonetheless, direct BMP2-binding ligands derived from complex herbal extracts remain poorly characterized. In the present study, surface plasmon resonance (SPR)-based target fishing against BMP2, in conjunction with UPLC-Q-TOF-MS identification, was employed to screen for bioactive ligands from Periploca forrestii, a traditional Miao medicinal plant used for bone-related conditions. Six caffeoylquinic acid derivatives, namely neochlorogenic acid (NCA), 3-O-caffeoyl-4-O-sinapoylquinic acid, chlorogenic acid (CA), cryptochlorogenic acid (CCA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC), were captured as direct BMP2-binding ligands. All six compounds promoted osteoblast differentiation and mineralization in MC3T3-E1 Subclone 14 cells, with IB displaying the strongest binding affinity and bioactivity. Mechanistically, IB failed to rescue the osteogenic suppression induced by the BMP type I receptor inhibitor LDN-193189, indicating its dependence on BMP signaling. In an LPS-induced inflammatory model, IB significantly reversed the downregulation of key proteins in the BMP2-Smad pathway (p-Smad1, Smad4, and Runx2) and osteogenic marker genes (Osterix, COL1A1, and OCN), demonstrating its capacity to restore osteogenic function under compromised conditions. Collectively, these findings establish that caffeoylquinic acid derivatives, particularly IB, function as BMP2-targeting osteogenic constituents of P. forrestii that activate BMP2-Smad signaling to promote osteoblast differentiation, thereby offering a pharmacological basis for the development of natural product-derived osteogenic agents. Full article

Immunosenescence is a major contributor to age-associated morbidity, yet microbiota-directed strategies capable of restoring immune homeostasis remain insufficiently validated. Medicinal plant polysaccharides (MPPs) are structurally diverse macromolecules that often resist host digestion and undergo microbial transformation in the colon, but their effects cannot be interpreted as those of a homogeneous intervention class. In this structured narrative review, we critically synthesize evidence across structural carbohydrate biology, microbial ecology, metabolite signaling, and immune aging and propose a structure–microbiota–metabolite–immunity framework for evaluating how MPPs may influence immunosenescence. Monosaccharide composition, glycosidic linkages, molecular-weight distribution, branching, uronic acid content, chemical substitutions, and higher-order conformation can shape microbial carbohydrate-active enzyme activity, polysaccharide utilization, and ecological cross-feeding. The resulting changes in short-chain fatty acids, secondary bile acids, tryptophan-derived indoles, and other metabolites may affect epithelial barrier integrity, regulatory T-cell/T helper 17-cell (Treg/Th17) balance, macrophage polarization, nuclear factor-κB (NF-κB) signaling, NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, and systemic inflammatory tone. However, evidence from in vitro systems and young disease models primarily supports mechanistic plausibility and should not be treated as direct evidence of immunosenescence modification. Translation will require structurally defined preparations, causal validation in aging-relevant models, comparison with established fermentable fibers, identification of responder phenotypes, and adequately powered trials in older adults. Full article

This comprehensive literature review delves into the multifaceted roles of RNA-binding motif protein 3 (RBM3) in cellular processes, disease pathogenesis, and therapeutic potential. RBM3 has been implicated in shaping cell morphology, synaptic protection in neurodegenerative conditions, and regulating gene expression through binding to specific RNA sequences. In cancer, RBM3 exhibits contrasting effects, influencing cell proliferation, tumorigenic potential, and RNA splicing. Clinical studies suggest RBM3 as a predictive biomarker in chemotherapy response for muscle-invasive bladder cancer. Despite promising therapeutic implications in neuroprotection and cancer, challenges persist in understanding the regulatory mechanisms and clinical behavior of RBM3. Further research is warranted to elucidate the molecular mechanisms underlying RBM3’s diverse functions and its significance as a potential target for personalized medicine in cancer therapy. This review underscores the pivotal role of RBPs, particularly RBM3, in disease progression and highlights the need for continued investigation to harness their therapeutic potential effectively. This review evaluates evidence available through December 2025, with particular emphasis on studies published between 2010 and 2025. Full article

Hyperlipidemia (HL) is a major metabolic disorder and a critical risk factor for cardiovascular diseases, closely associated with oxidative stress, inflammation, and disrupted cholesterol homeostasis. Freeze-dried Poecilobdella manillensis powder (FDPMP), a traditional medicinal product, has shown therapeutic potential against hyperlipidemia; however, its underlying mechanisms remain largely unclear. In this study, HL was induced in ApoE⁻/⁻ mice by feeding a high-fat diet (HFD) for eight weeks, during which FDPMP or simvastatin (positive control) was orally administered daily. Concurrently, an in vitro foam cell model was established by exposing RAW264.7 macrophages to oxidized low-density lipoprotein (ox-LDL, 80 μg/mL) for 24 h, with FDPMP pretreatment applied 30 min prior to ox-LDL stimulation. Following intervention, serum lipid profiles, hepatic oxidative stress markers, histopathological changes, and cholesterol metabolism-related gene and protein expression were systematically evaluated. FDPMP administration significantly improved serum lipid profiles by reducing triglycerides, total cholesterol, and low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol levels. Additionally, FDPMP alleviated histopathological damage in the liver, kidney, and heart, enhanced antioxidant enzyme activities, and attenuated oxidative stress. Untargeted metabolomic analysis revealed that FDPMP markedly modulated key metabolic pathways, including choline metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism. Mechanistically, FDPMP restored cholesterol homeostasis through dual regulation of cholesterol metabolism, characterized by upregulation of cholesterol 7α-hydroxylase (CYP7A1) to promote bile acid-mediated cholesterol excretion, alongside downregulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and synthase (HMGCS1) to inhibit cholesterol biosynthesis. In vitro, FDPMP effectively suppressed ox-LDL-induced foam cell formation, reduced intracellular lipid accumulation, and mitigated oxidative stress in macrophages. Collectively, these findings demonstrate that FDPMP ameliorates hyperlipidemia through coordinated regulation of cholesterol synthesis and excretion, coupled with systemic metabolic reprogramming and antioxidative effects. This study provides mechanistic insights supporting FDPMP as a promising natural therapeutic candidate for hyperlipidemia and related metabolic disorders. Full article