Chuxiao Shao

Hypertrophic scars (HSs) are a prevalent skin condition that imposes substantial functional, financial, and aesthetic burdens, with existing treatments often leading to recurrence, pain, and adverse effects. To address these issues, we propose a first-in-class fast-dissolving sodium alginate-based microneedle patch (sMN) that achieves sequential, dual-release kinetics by integrating tranilast (TS) and glabridin (GL)-loaded nanoparticles (GLNPs), termed TS+GLNPs@sMN. Our system uniquely integrates rapid TS release for immediate “OFF” switching, suppression of fibroblast activation, stabilization of mast cells, and relief of pruritus, with sustained GL release from GLNPs for prolonged “ON” switching, which promotes fibroblast apoptosis and modulates scar matrix deposition. This sequential “OFF-to-ON” paradigm mirrors the temporal progression of HS pathophysiology, with early inflammatory events preceding fibrotic remodeling. The cone-shaped microneedle patch (~565 μm) demonstrated efficient skin penetration/recovery, even drug distribution, fast dissolution (180 ± 20 s), high loading capacity, and desirable release kinetics. In vitro evaluations confirmed promising anti-proliferative, anti-migratory, and anti-angiogenic effects. Preliminary in vivo biocompatibility in mice was satisfactory, with no skin irritation and normal complete blood count, renal, and hepatic function. In vivo studies in a rabbit ear HS model demonstrate accelerated HS healing, reduced HS thickness, epidermal thickness index (ETI), scar elevation index (SEI), and collagen deposition, along with decreased profibrotic markers, inflammatory cytokines, and angiogenic factors. Overall, the TS+GLNPs@sMN patch offers a minimally invasive, self-administrable, dual-action therapeutic strategy for enhanced HS management, with safety and efficacy in preclinical models.

Background Arthritis is an inflammatory disease which causes inflammation, damages joint, and increases the risk of cardiovascular disorders like atherosclerosis. Quinic acid, a naturally occurring compound, exhibits anti-inflammatory and antioxidant potential. Method The current study was aimed to estimate the pharmacological effects of quinic acid in Freund complete adjuvant-induced arthritis and its possible impact on associated predisposing biomarkers of atherosclerosis development. Quinic acid at various doses (25, 50, and 100 mg/kg) and methotrexate as reference drug were administered, with one group receiving combination treatment. Body weight changes, paw size, arthritic and joint stiffness score, hematological parameters, lipid profile, asymmetric dimethylarginine, homocysteine, oxidative stress, inflammatory biomarkers, and histopathological evaluation of ankle joint and heart tissues were performed to ascertain the severity of arthritis and predisposing biomarkers of atherosclerosis. Results The findings indicated that combination treatment significantly improved (p < 0.001) body weight, hematological parameters, high density lipoprotein levels, antioxidant enzyme concentrations, and expressions of dimethyl arginine dimethyl amino hydrolase and cortistatin. Simultaneously, it substantially reduces (p < 0.001) paw size, joint stiffness, arthritic score, platelets and leucocyte count, lipid markers, asymmetric dimethylarginine, homocysteine, malondialdehyde, and nitrite levels, whereas downregulation of mRNA expression of inflammatory markers (interleukin-6, interleukin-1β, tumor necrosis factor-α) was observed. It also significantly (p < 0.001) improves the histopathological parameters of ankle joint and heart tissue. Conclusion It was concluded that quinic acid possessed hypolipidemic, anti-inflammatory, and antioxidant properties and may be an effective therapeutic substance for the management of polyarthritis and predisposing markers of atherosclerosis.

Nonalcoholic Fatty Liver Disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes and is closely associated with metabolic disturbances such as obesity, dyslipidemia, and insulin resistance. Despite its increasing prevalence and potential progression to severe liver conditions, there is currently no approved pharmaceutical intervention for NAFLD. Traditional Chinese Medicine (TCM) formulations, such as Xiaoyao San (XYS), have shown therapeutic efficacy in treating NAFLD, but the underlying mechanisms remain unclear. This study employed a multi-omics approach to elucidate the therapeutic mechanisms of XYS in NAFLD. A rat model of NAFLD was established using a high-fat diet (HFD). The chemical constituents of XYS were analyzed using UPLC-MS/MS. Transcriptomics and proteomics analyses were performed to identify potential biological targets and signaling pathways involved in the therapeutic effects of XYS. The results were validated using ELISA and Western blotting. UPLC-MS/MS identified 225 prototype chemical components of XYS in the blood. XYS significantly reduced body weight, liver index, and Lee’s index in NAFLD model rats. It ameliorated HFD-induced hepatic steatosis, down-regulated serum levels of ALT, AST, GGT, TG, TC, LDL-C, FBG, IL-1β, IL-6, TNF-α, and ROS, and up-regulated HDL-C levels. Transcriptomics and proteomics analyses revealed that XYS modulated key signaling pathways, including cAMP, TGF-β, NF-κB, and necroptosis. Specifically, XYS down-regulated the expressions of NF-κB, p-NF-κB, FOXO1, TGF-β1, RIP3, and p-MLKL, while up-regulating cAMP, PKA, p-PKA, and PPARα. XYS improves NAFLD by regulating the cAMP/PKA-mediated PPARα, FOXO1, and NF-κB signaling pathways. This study provides a comprehensive understanding of the molecular mechanisms underlying the therapeutic effects of XYS in NAFLD and supports its potential as a novel therapeutic intervention for this condition.

Neuroregulation during skin wound healing involves complex interactions between the nervous system and intricate tissue repair processes. The skin, the largest organ, depends on a complex system of nerves to manage responses to injury. Recent research has emphasized the crucial role of neuroregulation in maximizing wound healing outcomes. Recently, researchers have also explained the interactive contact between the peripheral nervous system and skin cells during the different phases of wound healing. Neurotransmitters and neuropeptides, once observed as simple signalling molecules, have since been recognized as effective regulators of inflammation, angiogenesis, and cell proliferation. The significance of skin innervation and neuromodulators is underscored by the delayed wound healing observed in patients with diabetes and the regenerative capabilities of foetal skin. Foetal skin regeneration is influenced by the neuroregulatory environment, immature immune system, abundant growth factors, and increased pluripotency of cells. Foetal skin cells exhibit greater flexibility and specialized cell types, and the extracellular matrix composition promotes regeneration. The extracellular matrix composition of foetal skin promotes regeneration, making it more capable than adult skin because neuroregulatory signals affect skin regeneration. The understanding of these systems can facilitate the development of therapeutic strategies to alter the nerve supply to the skin to enhance the process of wound healing. Neuroregulation is being explored as a potential therapeutic strategy for enhancing skin wound repair. Bioelectronic strategies and neuromodulation techniques can manipulate neural signalling, optimize the neuroimmune axis, and modulate inflammation. This review describes the function of skin innervation in wound healing, emphasizing the importance of neuropeptides released by sensory and autonomic nerve fibres. This article discusses significant discoveries related to neuroregulation and its impact on skin wound healing.

Introduction: Spinal cord injury (SCI) is a severe neurological disease characterized by significant motor, sensory, and autonomic dysfunctions. SCI is a major global disability cause, often resulting in long‐term neurological impairments due to the impeded regeneration and remyelination of axons. A SCI interferes with communication between the brain and the spinal cord networks that control neurological functions. Recent advancements in understanding the molecular and cellular mechanisms of remyelination have opened novel therapeutic interventions.Method: This review systematically sourced articles related to spinal chord injury, remyelination, regeneration and pathophysiology from major medical databases, including Scopus, PubMed, and Web of Science.Results: This review discusses the efficacy of targeted therapy in enhancing myelin repair after SCI by identifying key molecules and signaling pathways. This explores the effectiveness of specific pharmacological agents and biological factors in promoting oligodendrocyte precursor cell proliferation, differentiation, and myelin sheath formation using in vitro and in vivo models. Targeted therapies have shown promising results in improving remyelination, providing hope for functional recovery in SCI patients.Conclusions: This review demonstrates challenges and future perspectives in translating findings into clinical practice, emphasizing safety profiles, delivery method optimization, and combinatory therapy potential. This review also supports the possibility of targeted remyelination therapies as a promising strategy for SCI treatment, paving the way for future clinical applications.