IL-17 in wound repair: bridging acute and chronic responses.

Chronic wounds, resulting from persistent inflammation, can trigger a cascade of detrimental effects including exacerbating inflammatory cytokines, compromised blood circulation at the wound site, elevation of white blood cell count, increased reactive oxygen species, and the potential risk of bacterial infection. The interleukin-17 (IL-17) signaling pathway, which plays a crucial role in regulating immune responses, has been identified as a promising target for treating inflammatory skin diseases. This review aims to delve deeper into the potential pathological role and molecular mechanisms of the IL-17 family and its pathways in wound repair. The intricate interactions between IL-17 and other cytokines will be discussed in detail, along with the activation of various signaling pathways, to provide a comprehensive understanding of IL-17's involvement in chronic wound inflammation and repair.

Mono-phosphorylation at Ser4 of barrier-to-autointegration factor (Banf1) significantly reduces its DNA binding capability by inducing critical changes in its local conformation and DNA binding surface.

Barrier-to-autointegration factor (Banf1) is a small DNA-bridging protein. The binding status of Banf1 to DNA is regulated by its N-terminal phosphorylation and dephosphorylation, which plays a critical role in cell proliferation. Banf1 can be phosphorylated at Ser4 into mono-phosphorylated Banf1, which is further phosphorylated at Thr3 to form di-phosphorylated Banf1. It was observed decades ago that mono-phosphorylated Banf1 cannot bind to DNA. However, the underlying molecular- and atomic-level mechanisms remain unclear. A clear understanding of these mechanisms will aid in interfering with the cell proliferation process for better global health. Herein, we explored the detailed atomic bases of unphosphorylated Banf1-DNA binding and how mono- and di-phosphorylation of Banf1 impair these atomic bases to eliminate its DNA-binding capability, followed by exploring the DNA-binding capability of mono- and di-phosphorylation Banf1, using comprehensive and systematic molecular modelling and molecular dynamics simulations. This work presented in detail the residue-level binding energies, hydrogen bonds and water bridges between Banf1 and DNA, some of which have not been reported. Moreover, we revealed that mono-phosphorylation of Banf1 causes its N-terminal secondary structure changes, which in turn induce significant changes in Banf1's DNA binding surface, thus eliminating its DNA-binding capability. At the atomic level, we also uncovered the alterations in interactions due to the induction of mono-phosphorylation that result in the N-terminal secondary structure changes of Banf1. Additionally, our modelling showed that phosphorylated Banf1 with their dominant N-terminal secondary structures bind to DNA with a significantly lower affinity and the docked binding pose are not stable in MD simulations. These findings help future studies in predicting effect of mutations in Banf1 on its DNA-binding capability and open a novel avenue for the development of therapeutics such as cancer drugs, targeting cell proliferation by inducing conformational changes in Banf1's N-terminal domain.

NCF2, MYO1F, S1PR4, and FCN1 as potential noninvasive diagnostic biomarkers in patients with obstructive coronary artery: A weighted gene co-expression network analysis.

This study aims to explore the predictive noninvasive biomarker for obstructive coronary artery disease (CAD). By using the data set GSE90074, weighted gene co-expression network analysis (WGCNA), and protein-protein interactive network, construction of differentially expressed genes in peripheral blood mononuclear cells was conducted to identify the most significant gene clusters associated with obstructive CAD. Univariate and multivariate stepwise logistic regression analyses and receiver operating characteristic analysis were used to predicate the diagnostic accuracy of biomarker candidates in the detection of obstructive CAD. Furthermore, functional prediction of candidate gene biomarkers was further confirmed in ST-segment elevation myocardial infarction (STEMI) patients or stable CAD patients by using the datasets of GSE62646 and GSE59867. We found that the blue module discriminated by WGCNA contained 13 hub-genes that could be independent risk factors for obstructive CAD (P < .05). Among these 13 hub-genes, a four-gene signature including neutrophil cytosol factor 2 (NCF2, P = .025), myosin-If (MYO1F, P = .001), sphingosine-1-phosphate receptor 4 (S1PR4, P = .015), and ficolin-1 (FCN1, P = .012) alone or combined with two risk factors (male sex and hyperlipidemia) may represent potential diagnostic biomarkers in obstructive CAD. Furthermore, the messenger RNA levels of NCF2, MYO1F, S1PR4, and FCN1 were higher in STEMI patients than that in stable CAD patients, although S1PR4 showed no statistical difference (P > .05). This four-gene signature could also act as a prognostic biomarker to discriminate STEMI patients from stable CAD patients. These findings suggest a four-gene signature (NCF2, MYO1F, S1PR4, and FCN1) alone or combined with two risk factors (male sex and hyperlipidemia) as a promising prognostic biomarker in the diagnosis of STEMI. Well-designed cohort studies should be implemented to warrant the diagnostic value of these genes in clinical purpose.

Rutaecarpine ameliorates hyperlipidemia and hyperglycemia in fat-fed, streptozotocin-treated rats via regulating the IRS-1/PI3K/Akt and AMPK/ACC2 signaling pathways.

AIM: We have shown that rutaecarpine extracted from the dried fruit of Chinese herb Evodia rutaecarpa (Juss) Benth (Wu Zhu Yu) promotes glucose consumption and anti-inflammatory cytokine expression in insulin-resistant primary skeletal muscle cells. In this study we investigated whether rutaecarpine ameliorated the obesity profiles, lipid abnormality, glucose metabolism and insulin resistance in rat model of hyperlipidemia and hyperglycemia. METHODS: Rats fed on a high-fat diet for 8 weeks, followed by injection of streptozotocin (30 mg/kg, ip) to induce hyperlipidemia and hyperglycemia. One week after streptozotocin injection, the fat-fed, streptozotocin-treated rats were orally treated with rutaecarpine (25 mg·kg(-1)·d(-1)) or a positive control drug metformin (250 mg·kg(-1)·d(-1)) for 7 weeks. The body weight, visceral fat, blood lipid profiles and glucose levels, insulin sensitivity were measured. Serum levels of inflammatory cytokines were analyzed. IRS-1 and Akt/PKB phosphorylation, PI3K and NF-κB protein levels in liver tissues were assessed; pathological changes of livers and pancreases were examined. Glucose uptake and AMPK/ACC2 phosphorylation were studied in cultured rat skeletal muscle cells in vitro. RESULTS: Administration of rutaecarpine or metformin significantly decreased obesity, visceral fat accumulation, water consumption, and serum TC, TG and LDL-cholesterol levels in fat-fed, streptozotocin-treated rats. The two drugs also attenuated hyperglycemia and enhanced insulin sensitivity. Moreover, the two drugs significantly decreased NF-κB protein levels in liver tissues and plasma TNF-α, IL-6, CRP and MCP-1 levels, and ameliorated the pathological changes in livers and pancreases. In addition, the two drugs increased PI3K p85 subunit levels and Akt/PKB phosphorylation, but decreased IRS-1 phosphorylation in liver tissues. Treatment of cultured skeletal muscle cells with rutaecarpine (20-180 µmol/L) or metformin (20 µmol/L) promoted the phosphorylation of AMPK and ACC2, and increased glucose uptake. CONCLUSION: Rutaecarpine ameliorates hyperlipidemia and hyperglycemia in fat-fed, streptozotocin-treated rats via regulating IRS-1/PI3K/Akt signaling pathway in liver and AMPK/ACC2 signaling pathway in skeletal muscles.

[A new bibenzyl compound from Dendrobium nobile].

In this study, seven bibenzyl compounds were isolated from the stem of Dendrobium nobile by silica gel, MCI column chromatographic and preparative HPLC technology. By using spectroscopic techniques including NMR and MS, these compounds were identified as 4,α-dihydroxy-3,5,3'-trimethoxybibenzyl (1), 4,5-dihydroxy-3,3',α-trimethoxybibenzyl (2), 4,4'-dihydroxy-3,5,3'-trimethoxybibenzyl (3), 4,5-dihydroxy-3,3'-dimethoxybibenzyl(4), 4,3'-dihydroxy-3,5-dimethoxybibenzyl (5), 5,4'-dihydroxy-3,3'-dimethoxybibenzyl (6) and 5,3'-dihydroxy-3-methoxybibenzyl (7). Compound 1 is a new compound and compound 4 was isolated from this plant for the first time.

[Effects of rutaecarpine on inflammatory cytokines in insulin resistant primary skeletal muscle cells].

It is now well established that inflammation plays an important role in the development of numerous chronic metabolic diseases including insulin resistance (IR) and type 2 diabetes (T2DM). Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Our pre- vious study has shown that rutaecarpine (Rut) can benefit blood lipid profile, mitigate inflammation, and improve kidney, liver, pan- creas pathology status of T2DM rats. However, the effects of Rut on inflammatory cytokines in the development of IR-skeletal muscle cells have not been studied. Thus, our objective was to investigate effects of Rut on inflammatory cytokines interleukiri (IL)-1, IL-6 and tumor necrosis factor (TNF)-α in insulin resistant primary skeletal muscle cells (IR-PSMC). Primary cultures of skeletal muscle cells were prepared from 5 neonate SD rats, and the primary rat skeletal muscle cells were identified by cell morphology, effect of ru- taecarpine on cell proliferation by MTT assay. IR-PSMC cells were induced by palmitic acid (PA), the glucose concentration was measured by glucose oxidase and peroxidase (GOD-POD) method. The effects of Rut on inflammatory cytokines IL-1, IL-6 and TNF-α in IR-PSMC cells were tested by enzyme-linked immunosorbent assay (ELISA) kit. The results show that the primary skeletal muscle cells from neonatal rat cultured for 2-4 days, parallel alignment regularly, and cultured for 7 days, cells fused and myotube formed. It was shown that Rut in concentration 0-180. 0 µmol x L(-1) possessed no cytotoxic effect towards cultured primary skeletal muscle cells. However, after 24 h exposure to 0.6 mmol x L(-1) PA, primary skeletal muscle cells were able to induce a state of insulin resistance. The results obtained indicated significant decrease (P < 0.05 to P < 0.001) IL-1, IL-6 and TNF-α production by cultured IR-PSMC cells when incubating 24 hours with Rut, beginning from 20 to 180.0 µmol x L(-1). IL-1, IL-6 and TNF-α in the Rut treated groups were dose-dependently decreased compared with that in the IR-PSMC control group. Our results demonstrated that the Rut promoted glucose consumption and improved insulin resistance possibly through suppression of inflammatory cytokines in the IR-PSMC cells.

[Probe excavations about using gene chip to identify original plants in Chinese pharmacopoeia based on NCBI sequence database].

OBJECTIVE: Based on the DNA fragments of medicinal plants of NCBJ database, the DNA Probe,which can be used to identify original plants in the Chinese Pharmacopoeia (2010 edition), was got. METHODS: First of all, get the Latin name of the original plants by collating the Chinese Pharmacopoeia. Next,download the medicinal plants' DNA fragments from the NCBI database, including ITS, matK, rbcL, psbK-psbI and trnH-psbA, then design probe by using Array Designer 4. 2. Finally, analyze each probe's versatility in the same kind of original plant and conservatism in different kinds of original plants by using Matlab, then determine the specificity of the probe. RESULTS: Regarding the Latin name of 586 original plants in the Chinese Pharmacopoeia (2010 edition) and the above five gene fragments as retrieval condition, 7 613 sequences were downloaded from NCBI, then 315 436 probes were got in total by analyzing. What's more, after analyzing versatility and conservatism of the probes,13 814 specific probes were got. Furthermore,in theory, 376 kinds of original plants could be detected. Because there existed the lack of related gene fragments in the NCBI database,or the sequences were short of specificity,210 species of original plants which were involved in the Chinese Pharmacopoeia didn't receive the corresponding probe. CONCLUSION: The results of the study can provide the further development of medicinal plants' identification chip with vital information support,and the excavation methods of probe can be widely used. Furthermore,the results of the study indicate the original plants which need sequencing importantly in the future.

The Role of p53 in Regulating Chronic Inflammation and PANoptosis in Diabetic Wounds.

Diabetic wounds represent a formidable challenge in the clinical management of diabetes mellitus, markedly diminishing the patient's quality of life. These wounds arise from a multifaceted etiology, with the pathophysiological underpinnings remaining elusive and complex. Diabetes precipitates neuropathies and vasculopathies in the lower extremities, culminating in infections, ulcerations, and extensive tissue damage. The hallmarks of non-healing diabetic wounds include senescence, persistent inflammation, heightened apoptosis, and attenuated cellular proliferation. The TP53 gene, a pivotal tumor suppressor frequently silenced in human malignancies, orchestrates cellular proliferation, senescence, DNA repair, and apoptosis. While p53 is integral in cell cycle regulation, its role in initial tissue repair appears to be deleterious. In typical cutaneous wounds, p53 levels transiently dip, swiftly reverting to baseline. Yet in diabetic wounds, protracted p53 activation impedes healing via two distinct pathways: i) activating the p53-p21-Retinoblastoma (RB) axis, which halts the cell cycle, and ii) upregulating the cGAS-STING and nuclear factor-kappaB (NF-κB) cascades, instigating ferroptosis and pyroptosis. Furthermore, p53 intersects with various metabolic pathways, including glycolysis, gluconeogenesis, oxidative phosphorylation, and autophagy. In diabetic wounds, p53 may drive metabolic reprogramming, thus potentially derailing macrophage polarization. This review synthesizes case studies investigating the therapeutic modulation of p53 in diabetic wounds care. In summation, p53 modulates chronic inflammation and cellular aging within diabetic cutaneous wounds and is implicated in a novel cell death modality, encompassing ferroptosis and pyroptosis, which hinders the reparative process.

The cGAS-STING pathway: a therapeutic target in diabetes and its complications.

Diabetic wound healing (DWH) represents a major complication of diabetes where inflammation is a key impediment to proper healing. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has emerged as a central mediator of inflammatory responses to cell stress and damage. However, the contribution of cGAS-STING activation to impaired healing in DWH remains understudied. In this review, we examine the evidence that cGAS-STING-driven inflammation is a critical factor underlying defective DWH. We summarize studies revealing upregulation of the cGAS-STING pathway in diabetic wounds and discuss how this exacerbates inflammation and senescence and disrupts cellular metabolism to block healing. Partial pharmaceutical inhibition of cGAS-STING has shown promise in damping inflammation and improving DWH in preclinical models. We highlight key knowledge gaps regarding cGAS-STING in DWH, including its relationships with endoplasmic reticulum stress and metal-ion signaling. Elucidating these mechanisms may unveil new therapeutic targets within the cGAS-STING pathway to improve healing outcomes in DWH. This review synthesizes current understanding of how cGAS-STING activation contributes to DWH pathology and proposes future research directions to exploit modulation of this pathway for therapeutic benefit.

Development of polysaccharide-coated layered double hydroxide nanocomposites for enhanced oral insulin delivery.

Oral insulin (INS) is predicted to have the most therapeutic advantages in treating diabetes to repress hepatic glucose production through its potential to mimic the endogenous insulin pathway. Many oral insulin delivery systems have been investigated. Layered double hydroxide (LDH) as an inorganic material has been widely used in drug delivery thanks to its appealing features such as good biocompatibility, low toxicity, and excellent loading capability. However, when used in oral drug delivery, the effectiveness of LDH is limited due to the acidic degradation in the stomach. In this study, to overcome these challenges, chitosan (Chi) and alginate (Alg) dual-coated LDH nanocomposites with the loading of insulin (Alg-Chi-LDH@INS) were developed by the layered-by-layered method for oral insulin delivery with dynamic size of ~ 350.8 nm, negative charge of ~ - 13.0 mV, and dispersity index 0.228. The insulin release profile was evaluated by ultraviolet-visible spectroscopy. The drug release profiles evidenced that alginate and chitosan coating partially protect insulin release from a burst release in acidic conditions. The analysis using flow cytometry showed that chitosan coating significantly enhanced the uptake of LDH@INS by Caco-2 cells compared to unmodified LDH and free insulin. Further in the in vivo study in streptozocin-induced diabetic mice, a significant hypoglycemic effect was maintained following oral administration with great biocompatibility (~ 50% blood glucose level reduction at 4 h). This research has thus provided a potential nanocomposite system for oral delivery of insulin.

[Effects of four kinds of Chinese medicine monomer on growth of PANC-1 xenograft tumor and studying of molecular mechanism].

OBJECTIVE: The antitumor effects of icarisid II, timosaponin A-III, neferine and salidroside were studied in PANC-1 xenograft tumor. METHOD: To establish of the nude mice xenograft tumor model, PANC-1 cells were injected. When the tumor major diameter was reached 3-5 mm, the treatment was initiated. The mice were randomized into vehicle control and treatment groups of six animals per each. Chinese medicine monomer was injected intraperitoneally every day. In 23th day, mice were killed once a day, tumor tissue were isolated and weighed and divided into two parts. One part was fixed with formaldehyde for tissue section and immunohistochemistry, the another of tissue was frozen in liquid nitrogen then in - 80 degrees C refrigerator for gene and protein expression analysis. RESULT: In PANC-1 tumor xenograft experiment, compared with model group, timosaponin A-III (1.0 mg x kg (-1)) exerted significant inhibitory effects on tumor growth. Timosaponin A-III suppressed mRNA expressions of VEGF (P < 0.05), reduced protein expressions of VEGF (P < 0.05), activated Caspase-3 protein. Icarisid II, neferine and salidroside had not an excelled antitumor effect. CONCLUSION: Timosaponin A-III exerted an excelled antitumor effect. The antitumor mechanisms include anti-angiogenesis, apoptosis promotion.

Asiaticoside Prevents Oxidative Stress and Apoptosis in Endothelial Cells by Activating ROS-dependent p53/Bcl-2/Caspase-3 Signaling Pathway.

BACKGROUND: Asiaticoside (AC) is a triterpenoid saponin found in Centella asiatica (L.) urban extract that has a wide range of pharmacological properties. Our previous study demonstrated that AC could promote angiogenesis in diabetic wounds, but the specific mechanisms remain unknown. OBJECTIVE: This study aimed to examine the effectiveness and mechanism of AC on human umbilical vein endothelial cells (HUVECs) exposed to tert-butyl hydroperoxide (t-BHP) toxicity. METHODS: Senescence was confirmed using senescence-associated betagalactosidase (SA-ß-gal) activity and expression of the cell cycle phase markers p16 and p21. The levels of SOD, NO, MDA, GSH-Px, and ROS were tested. Furthermore, several cell death-related genes and proteins (p53, Bax, Bcl-2 and Caspase-3) were assessed with RT-qPCR and Western blotting. RESULTS: AC significantly reduced SA-ß-gal activity, with both the suppression of cellcycle inhibitors p16 and p21. We also found that the induced oxidative stress and apoptosis caused by t-BHP treatment resulted in the decrease of antioxidant enzymes activities, the surge of ROS and MDA, the up-regulation of p53, Bax and caspase-3, and the decrease of SOD, NO, GSH-Px and Bcl-2. These biochemical changes were all reversed by treatment with varying doses of AC. CONCLUSION: AC alleviates t-BHP-induced oxidative injury and apoptosis in HUVECs through the ROS-dependent p53/Bcl-2/Caspase-3 signaling pathway. It may be a potential antioxidant applied in metabolic disorders and pharmaceutical products.

SOX family transcription factors as therapeutic targets in wound healing: A comprehensive review.

The SOX family plays a vital role in determining the fate of cells and has garnered attention in the fields of cancer research and regenerative medicine. It also shows promise in the study of wound healing, as it actively participates in the healing processes of various tissues such as skin, fractures, tendons, and the cornea. However, our understanding of the mechanisms behind the SOX family's involvement in wound healing is limited compared to its role in cancer. Gaining insight into its role, distribution, interaction with other factors, and modifications in traumatized tissues could provide valuable new knowledge about wound healing. Based on current research, SOX2, SOX7, and SOX9 are the most promising members of the SOX family for future interventions in wound healing. SOX2 and SOX9 promote the renewal of cells, while SOX7 enhances the microvascular environment. The SOX family holds significant potential for advancing wound healing research. This article provides a comprehensive review of the latest research advancements and therapeutic tools related to the SOX family in wound healing, as well as the potential benefits and challenges of targeting the SOX family for wound treatment.

Preventive effect of Ya'an Tibetan tea on obesity in rats fed with a hypercaloric high-fat diet revealed by gut microbiology and metabolomics studies.

Ya'an Tibetan Tea (YATT) is a classic dark tea variety fermented with a unique geographical environment and traditional craftsmanship. Previous research indicates that it is beneficial for obesity and related metabolic disorders, but no systematic research currently reveals its precise mechanisms. This work investigated the preventive effect of YATT on obesity and the corresponding potential mechanisms by performing 16S rRNA gene sequencing and metabolomics studies. Our results demonstrated that YATT could significantly improve the body weight and fat deposition in hypercaloric high-fat diet (HFD)-induced obese rats, enhance antioxidant enzymes activity and reduce inflammation, and reverse the liver damage caused by an HFD. Moreover, 16S rRNA analysis showed that YATT could improve the intestinal microbial disorders caused by the HFD by significantly reversing the increase in Firmicutes/Bacteroidetes（F/B）ratio and the relative abundance of flora associated with the HFD, such as unclassified_Lachnospiraceae and Romboutsia flora. In addition, metabolomic analysis of cecum contents identified 121 differential metabolites, of which 19 were common to all experimental rats fed with and without a high-fat diet. Strikingly, 17 of the most prevalent 19 differential metabolites, including Theobromine, L-Valine, and Diisobutyl phthalate, were considerably reversed by YATT. Enrichment analysis of the metabolic pathways of these differential metabolites indicated that Caffeine metabolism, Phenylalanine metabolism, and Lysine degradation are the potential metabolic pathways responsible for the obesity prevention effect of YATT. Collectively, this work revealed that YATT has good potential for obesity prevention and the improvement of intestinal microbial communities, potentially due to the YATT-induced alterations in the metabolic pathways and functional metabolite levels of caffeine and amino acids. These results inform the material basis of YATT for obesity prevention and its mechanisms and provide essential insights for developing YATT as a healthy beverage for obesity prevention.

Targeting DNA methylation and demethylation in diabetic foot ulcers.

BACKGROUND: Poor wound healing is a significant complication of diabetes, which is commonly caused by neuropathy, trauma, deformities, plantar hypertension and peripheral arterial disease. Diabetic foot ulcers (DFU) are difficult to heal, which makes patients susceptible to infections and can ultimately conduce to limb amputation or even death in severe cases. An increasing number of studies have found that epigenetic alterations are strongly associated with poor wound healing in diabetes. AIM OF REVIEW: This work provides significant insights into the development of therapeutics for improving chronic diabetic wound healing, particularly by targeting and regulating DNA methylation and demethylation in DFU. Key scientific concepts of review: DNA methylation and demethylation play an important part in diabetic wound healing, via regulating corresponding signaling pathways in different breeds of cells, including macrophages, vascular endothelial cells and keratinocytes. In this review, we describe the four main phases of wound healing and their abnormality in diabetic patients. Furthermore, we provided an in-depth summary and discussion on how DNA methylation and demethylation regulate diabetic wound healing in different types of cells; and gave a brief summary on recent advances in applying cellular reprogramming techniques for improving diabetic wound healing.

Protective effect of solanesol in glucose-induced hepatocyte injury: Mechanistic insights on oxidative stress and mitochondrial preservation.

Solanesol is a tetra sesquiterpene enol with various biological activities. Modern medical studies have confirmed that solanesol has the function of lipid antioxidation and scavenges free radicals. This study aimed to investigate the protective effect of solanesol against oxidative damage induced by high glucose on human normal hepatocytes (L-02 cells) and its possible mechanism. The results showed that solanesol could effectively improve the decrease of cell viability induced by high glucose, decrease the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in the extracellular medium, increased the enzyme activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), balanced the level of reactive oxygen species (ROS) in cells, inhibited lipid peroxidation of all kinds of biological membranes, and restored mitochondrial membrane potential (MMP). In addition, Solanesol also inhibited the expression of Keap1, promoted the nuclear translocation of Nrf2 by hydrogen bonding with Nrf2, and activated the expression of downstream antioxidant factors NQO1 and HO-1. Altogether, these findings suggest that solanesol may be a potential protectant against diabetic liver injury.

Piezo1 in skin wound healing and related diseases: Mechanotransduction and therapeutic implications.

Skin wound healing is a multifaceted and intricate process involving inflammation, tissue proliferation, and scar formation, all of which are accompanied by the continuous application of mechanical forces. Mechanotransduction is the mechanism by which the skin receives and reacts to physical signals from the internal and external environment, converting them into intracellular biochemical signals. This intricate process relies on specialized proteins known as mechanotransducers, with Piezo1 being a critical mechanosensitive ion channel that plays a central role in this process. This article provides an overview of the structural characteristics of Piezo1 and summarizes its effects on corresponding cells or tissues at different stages of skin trauma, including how it regulates skin sensation and skin-related diseases. The aim is to reveal the potential diagnostic and therapeutic value of Piezo1 in skin trauma and skin-related diseases. Piezo1 has been reported to be a vital mediator of mechanosensation and transduction in various organs and tissues. Given its high expression in the skin, Piezo1, as a significant cell membrane ion channel, is essential in activating intracellular signaling cascades that trigger several cellular physiological functions, including cell migration and muscle contraction. These functions contribute to the regulation and improvement of wound healing.

Combinations of Tibetan tea and medicine food homology herbs: A new strategy for obesity prevention.

Obesity has become a significant global public health problem. Functional drinks have been an essential direction for obesity prevention research. The present study investigated the preventive effect and safety of winter melon and lotus leaf Tibetan tea (WLTT, a compound tea drink based on Ya'an Tibetan Tea and medicine food homology herbs) on obesity. The rats' hypercaloric high-fat diet (HFD) obesity model was established to evaluate obesity prevention and explored the mechanism through intestinal flora regulation. The results showed that in obese rats with the intervention of WLTT (400, 800, and 1600 mg/kg BW), the body weight, fat accumulation, adipocyte cell size, serum lipid levels, and antioxidant enzyme activity (SOD, GSH-Px, and MDA) were progressively improved. 16S rRNA high-throughput sequencing showed that WLTT could improve intestinal flora disorders due to HFD, which significantly reversed the relative abundance of Firmicutes and the F/B ratio associated with an HFD, and significantly upregulated the relative abundance of Verrucomicrobia. At the genus level, the downregulation of the relative abundance of Akkermansia and unclassified_Lachnospiraceae groups, and the upregulation of the relative abundance of Romboutsia, Ruminococcus, Corynebacteriume, and Saccharibacteria_genera_incertae_sedis groups brought about by the HFD were significantly reversed. The results of the above experiments were compared favorably with those of a parallel experiment with Bi -Sheng -Yuan slimming tea (BSY, a functional drink based on green tea and medicine food homology herbs). Overall, the findings have provided that WLTT can prevent obesity owing to an HFD by regulating intestinal flora and has a good safety profile, and combinations of Tibetan tea and medicine food homology herbs could be a new option for obesity prevention.

Neuropeptide substance P: A promising regulator of wound healing in diabetic foot ulcers.

In the past, neuropeptide substance P (SP) was predominantly recognized as a neuroinflammatory factor, while its potent healing activity was overlooked. This paper aims to review the regulatory characteristics of neuropeptide SP in both normal and diabetic wound healing. SP actively in the regulation of wound healing-related cells directly and indirectly, exhibiting robust inflammatory properties, promoting cell proliferation and migration and restoring the activity and paracrine ability of skin cells under diabetic conditions. Furthermore, SP not only regulates healing-related cells but also orchestrates the immune environment, thereby presenting unique and promising application prospects in wound intervention. As new SP-based preparations are being explored, SP-related drugs are poised to become an effective therapeutic intervention for diabetic foot ulcers (DFU).

Preparation and Safety Evaluation of Centella asiatica Total Glycosides Nitric Oxide Gel and Its Therapeutic Effect on Diabetic Cutaneous Ulcers.

Diabetic cutaneous ulcers (DCU) are a chronic and refractory complication of diabetes mellitus, which can lead to amputation or even death in extreme cases. Promoting the early healing of DCU and reducing the disability rate and treatment cost are important research topics in treating with integrated traditional Chinese and Western medicine. Centella asiatica total glycosides are extracted from the traditional Chinese medicine Centella asiatica and have angiogenic, anticancer, antioxidant, and wound healing effects. Nitric oxide (NO) is a critical component of wound healing. During the development of DCU, endogenous NO secretion is insufficient. It has been reported that exogenous nitric oxide can promote wound healing, but it is difficult to adhere to the skin because of its short half-life. Therefore, in this study, we used the polymer excipient hydroxyethyl cellulose as the matrix, combined with Centella asiatica total glycosides and NO, and developed a new type of topical gel that can promote wound healing. At the same time, we made a comprehensive research and evaluation on the preparation technology, quality standard, skin toxicity, reproductive toxicity, and pharmacodynamics against diabetic skin ulcers of the gel. According to our research results, the combination of Centella asiatica total glycosides and nitric oxide can accelerate the healing speed of DCU wounds, and 8% Centella asiatica total glycosides nitric oxide gel (CATGNOG) has the best effect in ulcer wound healing. CATGNOG has the advantages of feasible preparation method, controllable quality, good stability at low temperature, and no apparent skin toxicity and reproductive toxicity. It can effectively inhibit the growth of bacteria on the wound surface, relieve the inflammatory reaction of the wound surface, and promote the healing of ulcer wound, which provides a basis for further research of the preparation in the future.