Search Results (1,837)

Efficient treatment of diabetic wounds (DW) remains a major clinical challenge worldwide owing to vascular insufficiency, multiple bacterial infections, and overactivation of pro-inflammatory M1 macrophages caused by hyperglycemia. The development of novel pharmaceutical agents with multiple biological functions is urgently needed. Coptis chinensis Franch. (CC) has been used to treat diabetes for thousands of years in China, but the curative effects and underlying mechanisms of CC in DW remain uncertain. Herein, a homogeneous heteropolysaccharide component, namely CCP, was isolated and purified from CC, which exhibited a molecular weight of 39,697 Da and was primarily composed of Glc, GalA, Ara, Gal, and Xyl. CCP has a light yellowish color and is distributed in a block shape with small surface granulations. In vitro experiments revealed that CCP dose-dependently mitigated high glucose-induced suppression of viability, migration, and tube formation in HUVECs. Meanwhile, CCP promotes the polarization of M1 macrophages toward the M2 phenotype to exert anti-inflammatory effects, while possessing certain antibacterial properties. In addition, a composite hydrogel system was successfully constructed by introducing sodium carboxymethyl cellulose and carbomer 940 for CCP delivery. The obtained hydrogels exhibited reasonable moisturizing, swelling, and drug release capacities, along with favorable rheological behaviors and certain antibacterial activity. More importantly, the in vivo wound healing model evaluation in diabetic rats demonstrated that CCP hydrogel dressings could effectively promote wound healing by reducing inflammation, accelerating collagen deposition, upregulating the expression of VEGF and key angiogenesis-related factors. In addition, composite hydrogels demonstrated excellent cytocompatibility and hemocompatibility, which holds great promise for clinical application in DW treatment. Full article

Macrophages play a central and multifaceted role in the pathogenesis of rheumatoid arthritis (RA). This review synthesizes current understanding, emphasizing how M1/M2 polarization imbalance drives RA progression. Specifically, M1 promotes synovial inflammation, joint destruction, and pannus formation via pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and dysregulated angiogenesis. Conversely, functional impairment of anti-inflammatory M2 macrophages contributes to defective immune regulation. Beyond the classical M1/M2 dichotomy, macrophages exert their pathogenic influence through complex networks: activating adaptive immunity by phagocytosis and antigen presentation, secreting cytokines to regulate synovial tissue immune microenvironment and sustaining inflammation by metabolic reprogramming. Critically, heterogeneous macrophage subsets exhibit divergent roles. Recent studies have identified novel populations, such as pro-fibrotic SPP1⁺ macrophages and interferon-responsive STAT1⁺CXCL10⁺ macrophages. Future research may focus on reprogramming macrophage polarization, modulating metabolic pathways, targeting epigenetic regulators, or selectively manipulating specific pro-resolving subsets. The development of multi-target biologics, small molecules, and nanocarrier-based delivery systems could pave the way for personalized RA therapeutics. Full article

Cancer progression is driven by early dysregulation of the immune system and tumor-intrinsic mechanisms. Hypoxia, lactate accumulation and IL-6 signaling induce highly overlapping tumor-promoting effects, including angiogenesis, epithelial–mesenchymal transition, metastasis, immune evasion and treatment resistance, suggesting that these pathways interact and amplify one another. This parallel activation complicates therapeutic targeting, as inhibition of one pathway may be compensated for by another. Increased proteolytic activity emerges early during tumor development and profoundly alters immune regulation. We recently identified a protease-generated albumin fragment, the IL-6-inducing factor (IL-6IF), which triggers pathological IL-6 production. IL-6 in turn enhances both HIF-1α expression and nuclear translocation, promotes glycolysis and lactate production, and forms positive feedback loops with STAT3 and multiple signaling pathways. Together, these mechanisms integrate into a self-sustaining IL-6/HIF-1α/STAT3 axis that drives tumor progression and suppresses anti-tumor immunity. The strong overlap among IL-6, its enhancing loops and hypoxia-driven mechanisms highlights IL-6 as a central regulator of metabolic and immunological reprogramming in cancer. However, a broad IL-6 blockade can impair physiological immune function. Selective inhibition of IL-6IF offers a novel strategy to prevent pathological IL-6 production while preserving physiological IL-6-dependent immune function required for effective tumor control. Reducing pathologically enhanced IL-6 synthesis by targeting IL-6IF, therefore, might represent a potential therapeutic approach to disrupt multiple tumor-promoting pathways simultaneously and may thereby improve responsiveness to cancer immunotherapy. Full article

Olfactory neuroblastoma (ONB), also known as esthesioneuroblastoma, is a rare malignant tumor arising from the olfactory epithelium of the sinonasal tract. Surgery combined with radiotherapy remains the standard treatment for localized disease, whereas chemotherapy is mainly used in advanced or recurrent cases. However, recurrent and metastatic ONB continues to present major therapeutic challenges, and traditional staging and histological grading systems cannot fully explain the marked differences in clinical behavior among patients. The primary objective of this review is to summarize recent advances in the molecular pathology, tumor microenvironment (TME), and emerging targeted therapeutic strategies in ONB. Emerging genomic and transcriptomic studies suggest that ONB comprises biologically heterogeneous tumors with distinct molecular and transcriptional programs associated with proliferation, neuroendocrine differentiation, angiogenesis, and stromal remodeling. Furthermore, we explore the increasing attention directed toward the TME, including immune-cell infiltration, angiogenic signaling, and immune checkpoint expression, which may influence therapeutic response. These molecular findings have generated interest in several potential targeted treatment strategies, including peptide receptor radionuclide therapy (PRRT), anti-angiogenic therapy, epigenetic-targeted therapy, immunotherapy, and DNA-damage-response-targeted approaches. Ultimately, although the current evidence remains limited because of the rarity of the disease, novel therapeutic strategies for ONB are emerging. In addition to summarizing the current landscape, this review discusses the translational challenges and future directions for precision oncology and biomarker-driven therapy, aiming to provide insights for improving individualized patient management. Full article

Diabetic foot ulcers (DFUs) affect 19–34% of diabetic patients with a five-year mortality rate of 50–70%. It is characterized by a high infection risk, chronic inflammation, oxidative stress, and poor angiogenesis, rendering existing therapies inadequate, which causes antimicrobial resistance and amputations. Bioactive compounds, such as curcumin, flavonoids, tannins, polyphenols, and proteins, found in natural product extracts (NPEs) have antibacterial, anti-inflammatory, antioxidant, and regenerative properties but are prone to variability and instability. Conventional drugs can be applied for targeted infection management and metabolic modulation, but lack regenerative capacity. The combined and synergistic potential of these two agents has not received much attention, especially when integrated into advanced drug delivery systems (DDSs), such as microneedles, hydrogels, nanofibers, and smart bandages. This review discusses NPEs, conventional drugs, combinations, and integration into DDSs, based on wound characteristics. These include depth, infection status, exudate level, and perfusion, as recommended by the 2023 IWGDF guidelines. Three combinations have shown promise in preclinical studies: propolis-charcoal bandages, propolis-oregano microneedles, and Centella-ZnO nanocomposites. However, none have yet been validated in clinical settings, and barriers to clinical adoption persist—standardization, stability, and regulatory issues. This work aims to pave the way for more accessible, sustainable, and efficacious DFU therapeutics by bridging natural and conventional approaches. Full article

Myeloid-derived growth factor (MYDGF) is a monocyte- and macrophage-secreted protein with anti-apoptotic and pro-angiogenic properties that has demonstrated protective effects in models of myocardial ischemia, but its role in peripheral ischemic injury has not been evaluated. We investigated the effects of recombinant human MYDGF (hMYDGF) in a murine hindlimb ischemia model. Male C57BL/6 mice underwent femoral artery ligation and were treated with continuous subcutaneous infusion of recombinant hMYDGF, vehicle control, or vascular endothelial growth factor (VEGF) as a positive control. Limb perfusion was assessed longitudinally using laser speckle contrast imaging, and functional recovery was evaluated using standardized limb function scoring. Recombinant hMYDGF significantly improved blood flow recovery in the ischemic limb compared with vehicle at all post-surgical time points, achieving levels of perfusion comparable to VEGF. Improved perfusion translated into accelerated early functional recovery, with a greater proportion of recombinant hMYDGF-treated mice retaining normal toe flexion. Immunohistochemical analyses revealed significantly increased CD34⁺ endothelial cell staining in both quadriceps and gastrocnemius muscles in recombinant hMYDGF-treated mice, consistent with enhanced angiogenesis, while alpha-smooth muscle actin staining did not differ between groups. Collectively, these findings demonstrate that recombinant hMYDGF restores blood flow and accelerates functional recovery following ischemic injury, supporting its therapeutic potential for ischemic diseases. Full article

Hepatocellular carcinoma (HCC) lacks effective early diagnostic markers and is heavily driven by angiogenesis and hypoxia. Emerging evidence indicates that metabolic enzymes and noncoding RNAs coordinate these processes. Here, we reveal that phosphoserine phosphatase (PSPH), a serine biosynthesis enzyme, is significantly upregulated in HCC, correlating with angiogenic markers and poor prognosis. Clinical data and functional assays demonstrated that miR-101-3p directly targets the PSPH 3′ UTR to suppress its expression, while lncRNA GSEC acts as a competing endogenous RNA to sponge miR-101-3p. In vitro, GSEC knockdown or miR-101-3p overexpression decreased PSPH and HIF1α levels, strongly inhibiting HCC angiogenesis, migration, invasion, and proliferation. Crucially, these anti-tumor effects were reversed by restoring PSPH. In vivo, modulating the GSEC/PSPH axis significantly altered xenograft tumor growth and vascularization. Conclusively, the GSEC/miR-101-3p/PSPH regulatory axis drives HIF1α-dependent angiogenesis and HCC progression, highlighting PSPH as a promising diagnostic biomarker and therapeutic target. Full article

Chronic wounds constitute a major clinical and socioeconomic burden owing to prolonged inflammation, persistent bacterial infection, impaired angiogenesis, and defective extracellular matrix remodeling. Advanced wound dressings have traditionally been developed to promote tissue regeneration, control bacterial infection, and restore the wound microenvironment. Recent advances have focused on multifunctional biomaterials integrating regenerative, antibacterial, anti-inflammatory, antioxidant, and controlled drug-delivery properties. Within this context, antiviral biointerface engineering has emerged as a promising, although still exploratory, materials-engineering perspective rather than an established function of wound dressings. Hydrogel–metal–organic framework (MOF) hybrid polymer composites have emerged as versatile platforms for multifunctional wound dressings. Hydrogels provide hydrated three-dimensional matrices with tunable porosity, swelling behavior, mechanical compliance, and biocompatibility, whereas MOFs contribute high surface area, adjustable pore architectures, chemically tailorable active sites, and controlled ion release. Their integration generates synergistic systems whose performance is governed by structure–function relationships involving polymer crosslinking density, MOF dispersion, pore hierarchy, interfacial adhesion, swelling dynamics, and surface functionalization. Collectively, these parameters regulate mass transport, mechanical stability, therapeutic delivery, and cytocompatibility while potentially influencing virus–material interactions through engineered biointerfaces. Current evidence indicates that direct experimental demonstrations of antiviral performance in hydrogel–MOF wound dressing systems remain limited. Accordingly, antiviral biointerface functions should be regarded as emerging engineering opportunities requiring further experimental validation before clinical translation. This review critically analyzes the structure–function engineering principles governing hydrogel–MOF hybrid systems and examines how established regenerative functions may be integrated with emerging antiviral biointerface concepts. Unlike previous reviews focused primarily on drug delivery, antibacterial activity, or tissue engineering, this review emphasizes the relationships between polymer architecture, MOF chemistry, interfacial design, and transport phenomena while explicitly distinguishing experimentally supported evidence from prospective mechanistic concepts. Particular attention is given to current limitations, translational challenges, and future directions for the rational design of next-generation multifunctional hydrogel–MOF wound dressings. Full article

Hypoxia and the evolving concept of pseudohypoxia are critical in driving tumor angiogenesis, contributing to malignancy progression and therapeutic resistance. Angiogenesis, a common feature of many solid tumors, is promoted by hypoxia-induced overexpression of pro-angiogenic factors (e.g., VEGF, FGF) and genetic mutations (e.g., VHL, SDH) that stabilize hypoxia-inducible factors (HIF) even in normal oxygen conditions, a phenomenon known as pseudohypoxia. Recent experimental studies challenge the view that hypoxia universally enhances vessel growth. In certain models, severe oxygen deprivation impairs angiogenesis. Furthermore, tumor-mediated metabolic reprogramming can drive immune evasion via HIF stabilization in immune cells. These paradoxes, together with persistent therapy resistance and the limited effectiveness of current anti-angiogenic treatments, reveal critical gaps in our understanding of how hypoxic signaling modulates vascular and immune dynamics within the tumor microenvironment. These complexities demand more detailed exploration of underlying processes and the development of innovative therapeutic strategies. Here, we review recent mechanistic studies on tumor angiogenesis, summarizing therapeutic and diagnostic advances from both preclinical and clinical studies. We further discuss strategies to exploit hypoxic vulnerabilities, including HIF inhibitors, hypoxia-activated prodrugs, vascular normalization, combination regimens to restore immunity, biomarker-guided patient selection, and advanced hypoxia-targeted imaging to improve outcomes in angiogenesis-driven cancers. Full article

Cancer continues to be a primary cause of death globally, necessitating the constant development of effective and less toxic therapeutics. Cucurbitacins belong to the tetracyclic triterpenoids found mainly in the Cucurbitaceae family. Cucurbitaceae plants exert various biological activities such as anti-diabetic, anti-cancer and anti-inflammatory properties, which make them beneficial in addressing metabolic disorders. This review focuses on cucurbitacins namely A, B, C, D, E, I, IIa, which have been explored in cancer research. Cucurbitacins suppress tumor progression by activating cell death pathways, including apoptosis, autophagy, pyroptosis and ferroptosis. They are known to target multiple crucial biomolecular key players, such as STAT3, AKT, mTOR, ERK, EGFR and TLR4. Additionally, they disrupt cytoskeletal proteins and inhibit cell proliferation, invasion, migration, angiogenesis, and cell-cycle arrest. Cucurbitacins have been demonstrated to modulate tumor microenvironment, leading to enhanced host immune surveillance that reverses traditional therapy resistance from cisplatin, doxorubicin, and paclitaxel. In this review, we highlight the strong potential of cucurbitacins as anti-cancer agents, either as monotherapy or in combination, for the development of safer, cost-effective drugs with improved patient treatment outcomes. Full article

Cancer remains a major global health challenge and is the second leading cause of death worldwide. Targeted therapy has emerged as one of the most promising strategies for cancer treatment. However, current targeted therapies highlight the urgent need for novel therapeutic targets and strategies. The provirus integration site for Moloney murine leukemia virus 1 (PIM1) kinase has been identified as a key factor in tumor progression and poor prognosis. This review systematically summarizes and analyzes the diverse mechanisms of PIM1 in promoting tumor progression, including cell programmed death, cell cycle progression, DNA damage response, metastasis, cell stemness, metabolic reprogramming, tumor angiogenesis, anti-cancer immune response and therapeutic resistance, and comprehensively evaluates its potential as a therapeutic target. Moreover, PIM1 contributes to the development of resistance to various anticancer therapies. Based on the advances and limitations in PIM1-targeted cancer therapy, we propose that future research should focus on combination strategies involving PIM1 inhibitors and agents targeting parallel or upstream/downstream pathways regulated by PIM1. Our review highlights the therapeutic value and potential of PIM1 in cancer treatment, providing new insights and theoretical bases for the development of novel anti-tumor strategies targeting PIM1. Full article

Chronic wounds are associated with long-standing inflammation, impaired angiogenesis, oxidative stress, microbial load and defective remodelling of the extracellular matrix, impairing tissue repair. Conventional dressings offer protection and moisture regulation but do not sufficiently address the biological failures. Electrospun nanofibrous wound dressings offer a more active regenerative platform due to their architecture, which resembles the extracellular matrix, allowing cell adhesion and migration and facilitating the localised delivery of therapeutic agents. Marine-derived polysaccharides, such as alginate, chitosan, carrageenan, fucoidan, glycosaminoglycans, and ulvan, are particularly attractive in this area due to their biocompatibility, biodegradability, sustainability, and intrinsic haemostatic, antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory properties. This review critically discusses the mechanistic and translational relevance of marine polysaccharide-based nanofibres in wound healing with a focus on inflammation resolution, polarisation of macrophages, responses of keratinocytes and fibroblasts, angiogenesis, collagen deposition, redox balance and matrix remodelling. Biofabrication strategies, especially electrospinning and related nanofibre-forming strategies, are reviewed from the aspects of scaffold architecture, drug-loading capacity, controlled release, and wound microenvironment modulation. The review also discusses current shortcomings such as heterogeneity in the composition of marine polymers, mechanical fragility, sterilisation and storage issues, scalability, regulatory uncertainty and limited translation from preclinical models to clinical evidence. Overall, marine-derived polysaccharide nanofibers are a promising class of multifunctional wound dressings, but their clinical translation needs stronger standardisation, comparative in vivo evidence, safety validation and manufacturable designs. Full article

Histopathologic melanoma diagnosis extends beyond melanocytic cytology to encompass non-melanocytic features: solar elastosis patterns, stromal regression, adnexal relationships, epidermal reaction patterns, and the host inflammatory response. These “old school” low-power clues are particularly valuable on sun-damaged skin, where benign nevi, reactive melanocytic hyperplasia, and melanoma in situ share overlapping features. Quantitative data support two elastosis-based signs: the “umbrella sign” (reduced elastosis beneath the lesion’s central third; PPV (Positive Predictive Value) for nevus, 96%, and NPV (Negative predictive Value) for melanoma, 74%; calculated from raw cohort data) and the “purple fiber sign” (100% specificity, 30% sensitivity for nevus), both from a cohort of 81 actinically damaged lesions. Regression—identified by compressed elastic layers displaced to the reticular dermis, fibrosis, melanophages, and inflammation—aids diagnosis but complicates distinction from surgical scar. The maturation state of tertiary lymphoid structures (TLSs) within the regression zone, ranging from immunosuppressive immature aggregates to anti-tumoral mature structures with germinal centers, may explain the variable prognostic significance of histologic regression. Epidermal hyperplasia over thick melanomas reflects angiogenesis-related changes, while effacement is a practical red flag in spitzoid lesions. Ancillary tests are most productive when morphology has already framed the differential. These non-melanocytic clues remain indispensable as the foundation for rational ancillary testing. Full article

Diabetic oral mucosal wounds exhibit impaired healing and require biomaterials with strong wet adhesion, favorable biocompatibility, and adequate mechanical stability. In this study, an in situ photocurable adhesive hydrogel (ATDS) based on sulfonated chitosan was developed for diabetic oral mucosal wound repair. ATDS exhibited a tensile strength of 50 kPa, an elongation at break of 320%, and an adhesive strength of 0.605 MPa, while also displaying a porous microstructure without obvious cytotoxicity. Compared with hyaluronic acid (HA) gel, which was completely lost by day 3, ATDS provided more durable wound coverage in the oral environment. In a diabetic rat model of oral mucosal defect, ATDS significantly accelerated wound closure, with wounds nearly completely healed by day 6, promoted re-epithelialization as early as day 3, and increased epidermis thickness by approximately 50% compared with the control group. In addition, ATDS enhanced angiogenesis and reduced the expression of the inflammatory cytokines TNF-α and IL-1β. Collectively, these findings demonstrate that ATDS effectively promotes diabetic oral mucosal wound healing through its barrier-protective, pro-angiogenic, and anti-inflammatory effects, highlighting its potential as a promising biomaterial for oral tissue engineering and regenerative applications. Full article

Infectious wounds are plagued by persistent infection, uncontrolled inflammation, and delayed repair, while traditional therapies suffer from the poor solubility of natural drugs, low bioavailability, and bacterial drug resistance. To address these issues, this study developed a photo-responsive chitosan composite hydrogel (BBR-AS@Ce6@Matrix) cross-linked by chitosan (CS) and oxidized sodium alginate (OSA), co-loaded with Berberine–Asiaticoside cocrystal (BBR-AS) and chlorin e6-loaded chitosan nanoparticles (Ce6@CS NPs). The BBR-AS co-crystal was prepared by solvent method and verified to significantly improve the solubility and dissolution of asiaticoside. The Ce6@CS NPs were fabricated via non-solvent-assisted counterion complexation, showing high encapsulation efficiency, uniform particle size, and efficient singlet oxygen generation under irradiation. The hydrogel exhibited a three-dimensional porous network, favorable rheology, high water content, pH-dependent swelling and erosion behaviors, and significantly promoted BBR/AS release in vitro. In vitro experiments demonstrated strong antibacterial activity against Escherichia coli and Staphylococcus aureus, good cytocompatibility, and enhanced migration of L929 and Hacat cells. In a rat infectious wound model, the hydrogel combined with light irradiation markedly accelerated wound closure, promoted collagen deposition and angiogenesis, upregulated VEGF/CD31, and downregulated TNF-α/IL-6. In conclusion, BBR-AS@Ce6@Matrix integrates co-crystal solubilization, nanoparticle-facilitated release, and photodynamic synergy to achieve antibacterial, anti-inflammatory, pro-angiogenic and tissue remodeling effects, providing a promising multifunctional platform for infectious wound repair. Full article