Morroniside repairs atrazine-induced skin damage by ameliorating lipid metabolism disorders and inhibiting ferroptosis.

Morroniside (MOR) has shown great potential in treating atrazine (ATZ)-induced skin damage. This study aims to elucidate MOR's mechanism of action in mitigating lipid metabolism disorders and inhibiting ferroptosis to repair ATZ-induced skin damage. Twenty C57BL/6 mice were divided into four groups: the control group, the ATZ group, the MOR-H group and the MOR-L group, each comprising five mice. Following a one-month intervention, mouse skin tissues were harvested for untargeted lipid metabolomics analysis. Subsequently, the samples were assessed for indices related to ferroptosis. Untargeted lipid metabolomics analysis showed 127 differential metabolites in the ATZ vs. Ctrl group. There were 57 differential metabolites in the MOR-L vs. ATZ group. 34 differential metabolites in the MOR-H vs. ATZ group. the most obvious lipid reversal occurred after MOR-L administration, which primarily involved phospholipids, ceramides, and sphingomyelins. The levels of GPX4, Ferritin, MDA, SOD and GSH-PX, ferroptosis-related indicators, and the levels of p21 and p53, apoptosis-related indicators, were most significantly regressed in the MOR-L group (all P < 0.05). MOR may delay cellular aging and correct skin damage by reversing ATZ-induced lipid metabolism disorders, inhibiting ferroptosis and excessive oxidative stress occurrence.

Electroacupuncture promotes skin wound repair by improving lipid metabolism and inhibiting ferroptosis.

Lipid metabolism plays an important role in the repair of skin wounds. Studies have shown that acupuncture is very effective in skin wound repair. However, there is little knowledge about the mechanism of electroacupuncture. Thirty-six SD rats were divided into three groups: sham-operated group, model group and electroacupuncture group, with 12 rats in each group. After the intervention, local skin tissues were collected for lipid metabolomics analysis, wound perfusion and ferroptosis-related indexes were detected and finally the effect of electroacupuncture on skin wound repair was comprehensively evaluated by combining wound healing rate and histology. Lipid metabolomics analysis revealed 37 differential metabolites shared by the three groups, mainly phospholipids, lysophospholipids, glycerides, acylcarnitine, sphingolipids and fatty acids, and they could be back-regulated after electroacupuncture. The recovery of blood perfusion and wound healing was faster in the electroacupuncture group than in the model group (p < 0.05). The levels of GPX4, FTH1, SOD and GSH-PX, which are related to ferroptosis, were higher in the electroacupuncture group than in the model group (p < 0.05). The levels of ACSL4 and MDA were lower in the electroacupuncture group than in the model group (p < 0.05). Electroacupuncture may promote skin wound repair by improving lipid metabolism and inhibiting ferroptosis in local tissues.

Feasibility of repairing skin defects by VEGF165 gene-modified iPS-HFSCs seeded on a 3D printed scaffold containing astragalus polysaccharide.

The preparation of biodegradable scaffolds loaded with cells and cytokine is a feature of tissue-engineered skin. IPSCs-based tissue-engineered skin treatment for wound repair is worth exploring. Healthy human skin fibroblasts were collected and reprogrammed into iPSCs. After gene modification and induction, CK19+ /Integrinß1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP were obtained and identified by a combination of immunofluorescence and RT-qPCR. Astragalus polysaccharide-containing 3D printed degradable scaffolds were prepared and co-cultured with VEGF165 gene-modified iPS-HFSCsGFP , and the biocompatibility and spatial structure of the tissue-engineered skin was analysed by cell counting kit-8 (CCK8) assay and scanning electron microscopy. Finally, the tissue-engineered skin was transplanted onto the dorsal trauma of nude mice, and the effect of tissue-engineered skin on the regenerative repair of total skin defects was evaluated by a combination of histology, immunohistochemistry, immunofluorescence, RT-qPCR, and in vivo three-dimensional reconstruction under two-photon microscopy. CK19+ /Integrinß1+ /CD200+ VEGF165 gene-modified iPS-HFSCsGFP , close to the morphology and phenotype of human-derived hair follicle stem cells, were obtained. The surface of the prepared 3D printed degradable scaffold containing 200 µg/mL astragalus polysaccharide was enriched with honeycomb-like meshwork, which was more conducive to the proliferation of the resulting cells. After tissue-engineered skin transplantation, combined assays showed that it promoted early vascularization, collagen and hair follicle regeneration and accelerated wound repair. VEGF165 gene-modified iPS-HFSCsGFP compounded with 3D printed degradable scaffolds containing 200 µg/mL astragalus polysaccharide can directly and indirectly participate in vascular, collagen, and hair follicle regeneration in the skin, achieving more complete structural and functional skin regenerative repair.

An mRNA sequencing analysis of the healing-promoting role of electroacupuncture a in rat skin wound model.

BACKGROUND: Many studies have confirmed that electroacupuncture can regulate the body's environment to treat a variety of diseases. However, there are few reports on the mechanism of electroacupuncture therapy for diseases involving skin injury. Transcriptome sequencing can reveal changes in gene expression within cells and the signaling pathways involved. In this study, we used transcriptome sequencing to study the molecular mechanisms by which electroacupuncture promotes the healing of skin lesions. METHODS: A total of 10 SD rats were divided into two groups of 5: a control group and an electroacupuncture treatment group. The wound-healing area was compared between the two groups after 3 and 14 days. Then, mRNA sequencing and bioinformatics were used to analyze the changes in gene expression profiles in skin tissue after electroacupuncture stimulation. RESULTS: (I) The wound area was significantly reduced after 3 and 14 days of electroacupuncture compared with the control group (P<0.05). (II) There was a total of 694 gene expression changes, 496 of which were upregulated and 198 of which were downregulated. Analysis of variable gene-related signaling pathways by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), identified immuneinflammatory response, cell proliferation, tissue remodeling, cell metabolism, graft-versus-host disease, antigen processing and presentation, Th17 cell differentiation, cytokine-cytokine receptor interaction, PPAR signaling pathway, Wnt signaling pathway and other signaling pathways were changed. CONCLUSIONS: Electroacupuncture can promote wound repair, as shown by the changes in gene expression profiles during the healing of skin wounds under electroacupuncture. This study provides a scientific basis that deepens the understanding of the mechanism underlying electroacupuncture.

Experimental vascular protective shield combined with vacuum sealing drainage prevents pressure on exposed vessels and accelerates wound repair.

BACKGROUND: The sustained negative pressure created by vacuum sealing drainage (VSD) on exposed vascular wounds can result in blood vessel compression, embolism, or necrosis. The objective of this research was to explore the ability of an experimental vascular protective shield combined with VSD to protect exposed vessels of the lower limbs and accelerate wound repair. METHODS: (I) The vascular protective shield was prepared; (II) the material was subjected to acute toxicity and hemolysis tests; (III) and 30 New Zealand rabbits were divided into three groups: the control, VSD-only, and combined shield-VSD groups (with ten rabbits in each group). The wound-healing rate, myocardial function, wound histopathology, expression of angiogenesis markers, and exposed vascular compression of these three groups were compared on day 7. RESULTS: (I) The internal structure of the material was smooth; and (II) no toxicity or death was observed in mice of any group. The hemolysis rate in the combined shield-VSD group was very low. (III) The combined shield-VSD group showed a higher wound-healing rate, and higher levels of cluster of differentiation 31 (CD31), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF), than the other groups (P<0.05), along with a better tissue healing rate. (IV) Left ventricular pressure fluctuations in the combined shield-VSD group were smaller than those in the VSD-only group (P<0.05). (V) Blood vessels in the control and combined shield-VSD group were not damaged, but were damaged in the VSD-only group. CONCLUSIONS: The experimental vascular protective shield exhibited exceptional biosafety. The combination of this shield with VSD reduces influences on systolic and diastolic capacities of myocardium and avoids multiple compressions of exposed vessels, thus contributing to early vascularization of wounds and wound repair.

Hair follicle stem cells combined with human allogeneic acellular amniotic membrane for repair of full thickness skin defects in nude mice.

Repair of large skin defects caused by burns, trauma, or tumor operations is a clinical challenge. Hair follicle stem cells (HFSCs) are involved in epithelialization of wounds, formation of new hair follicles and promote vascularization in the newly formed skin, and human acellular amniotic membrane (hAAM) is a promising scaffold for skin substitute. Here, we investigated the ability of rat HFSCs (rHFSCs) combined with an hAAM to repair full thickness skin defects in nude mice. The effect of the rHFSC-hAAM composite on the repair of skin defects in nude mice was assessed by hematoxylin and eosin staining, immunohistochemistry, and EdU-labeled cell tracking. Isolated and cultured rHFSCs had strong cloning and proliferation potentials. Immunofluorescence staining and flow cytometry assays showed that rHFSCs expressed high levels of integrin α6, CK15, p63, and Sox9. Cells cultured in hAAM showed flaky and cluster-like morphology and were able to adhere and grow effectively. After transplantation, the rHFSC-hAAM composite promoted wound healing in nude mice. Moreover, cells in the rHFSC-hAAM composite were directly involved in hair follicle formation and angiogenesis of tissue around the hair follicle. These results provide an experimental and theoretical basis for the clinical application of HFSCs in repair of human skin defects and a new approach for skin tissue engineering.

[Effects on urinary retention after spinal cord injury treated with acupuncture at Zhibian (BL 54) and Shuidao (ST 28) with elongated needle].

OBJECTIVE: To explore the clinical effects of acupuncture with elongated needle on urinary retention after spinal cord injury. METHODS: A total of 66 patients with urinary retention after spinal cord injury were randomized into an elongated needle group (34 cases) and a filiform needle group (32 cases). In both of the groups, the routine orthopedic treatment and the bladder function training were adopted. Additionally, in the elongated needle group, the acupuncture at Zhibian (BL 54) and Shuidao (ST 28) was used with the elongated needle. In the filiform needle group, the acupuncture with filiform needle was used at Zhibian (BL 54) and Shuidao (ST 28). In both of the groups, acupuncture treatment was provided once every two days, for 2 months consecutively. Separately, before treatment and after 1, 2 month treatment, the residual urine volume, urodynamic parameters (bladder capacity, peak urinary flow rate and bladder pressure) and safety indicators were observed in the patients of the two groups. The clinical therapeutic effects were compared between the two groups. RESULTS: As compared with the results before treatment, the residual urine volume was reduced obviously (all P<0.01), bladder capacity, peak urinary flow rate and bladder pressure were improved obviously (all P<0.01) after 1, 2 month treatment in the two groups. After 1, 2 month treatment, the residual urine volume in the elongated needle group was lower than the filiform needle group (both P<0.01). The improvements in bladder capacity, peak urinary flow rate and bladder pressure in the elongated needle group were superior to the filiform needle (all P<0.01). The total effective rate was 94.1% (32/34) in the elongated needle group, higher than 71.9% (23/32) in the filiform needle group (P<0.01). During treatment, there was no damage of kidney function, no fainting or broken needle happened in the two groups. CONCLUSION: Acupuncture with elongated needle achieves the significant effects on urinary retention after spinal cord injury. This therapy is better than acupuncture with filiform needle and safe in operation.

[Urodynamic effects of elongated needle on patients with urinary retention after spinal cord injury].

OBJECTIVE: To explore the clinical significance of elongated needle in the treatment of urinary retention after spinal cord injury. METHODS: From January 2016 to June 2018, 60 patients with urinary retention after spinal cord injury were divided into elongated needle acupuncture group and needle acupuncture group, 30 cases in each group. The Shuidao(ST28) and Zhibian(BL54) were selected as the treatment of acupoints. In the elongated needle group, there were 23 males and 7 females, with a mean age of(52±9) years old. The patients in this group were treated on both sides, and the electro-acupuncture apparatus was used for 30 minutes at frequencies of 3 Hz for 30 minutes. In needle group, there were 24 males and 6 females, with a mean age of (56±10) years old. After treatment, the needles were retained for 30 minutes. The treatment frequencies of both groups were once every other day and passed for 2 months. After 2 months of treatment, the clinical significances of the treatment of the disease were explored by analyzing the time between the two groups of patients to reach the equilibrium bladder, diary urinary diary, urodynamics and urinary tract infection between the two groups. RESULTS: (1)Time to reach the equilibrium bladder:(39.5±1.2) days in elongated needle group and (46.5±2.1) days in needle group; the time to reach the equilibrium bladder in the two groups was significantly different(P<0.05). (2)Comparison of urination diary between the two groups:the daily number of catheterization, the amount of each catheterization, the number of daily urination, and the amount of urine per urination after treatment were better than those before treatment by intra-group comparison(P<0.05); the number of daily catheterization, the amount of daily catheterization, the number of daily urination, and the amount of urine output per patient in elongated needle group were better than those in needle group by comparison between two groups(P<0.05). (3)Comparison of improvement of urinary tract infection between the two groups:the urinary tract infection were better than that before treatmant in each group by intra-group comparison; the improvement rate of urinary tract infection in awn needle group (1/3.3%) was higher than that in needle group(5/16.7%), with significantly differences. (4)Comparison of urodynamic index between two groups:by intra-group comparison, the VH2O, Pves, Pdet, Qave, Qmax, and BC of the two groups were better than those before treatment(P<0.05); By comparison between two groups, the improvement of VH2O, Pves, Pdet, Qave, Qmax and BC were better than those of the needle group (all P<0.05). CONCLUSIONS: The elongated needle is better than conventional needle in improving urinary retention, urinary tract infection and urodynamic index in patients with urinary retention after spinal cord injury. It has positive significance in improving patients' quality of life and is worth applying to clinical.

The Mechanism of MAPK Signal Transduction Pathway Involved with Electroacupuncture Treatment for Different Diseases.

The mitogen-activated protein kinase (MAPK) signal transduction pathway plays an important role in the regulation of various diseases, such as cardiovascular and cerebrovascular diseases, and takes part in anti-inflammatory effects, analgesic effects, protection against injury, and maintenance of gastrointestinal functions. Electroacupuncture therapy is an external therapy used in traditional Chinese medicine. By adding external electrical stimulation to traditional acupuncture, the stimulus gets doubled and the therapeutic efficacy gets enhanced accordingly. It combines the benefits of both acupuncture and electrical stimulation. In recent years, some studies have explored the molecular mechanisms of MAPK signal pathways involved with electroacupuncture treatment. Based on these recent studies, this article summarizes the mechanisms of MAPK signal transduction pathways involved with electroacupuncture treatment. This adds great value to the studies of molecular mechanisms of electroacupuncture treatment and also provides an effective reference for its clinical use.

[The metabolic profilings study of serum and spinal cord from acute spinal cord injury rats ¹H NMR spectroscopy].

OBJECTIVE: To establish the rat model of acute spinal cord injury, followed by aprimary study on this model with ¹H NMR based on metabonomics and to explore the metabonomics and biomarkers of spinal cord injury rat. METHODS: Twenty eight-week-old adult male SD rats of clean grade, with body weight of (200±10) g, were divided into sham operation group and model group in accordance with the law of random numbers, and every group had 10 rats. The rats of sham operation group were operated without damaging the spinal cord, and rats of model group were made an animal model of spinal cord incomplete injury according to the modified Allen's method. According to BBB score to observate the motor function of rats on the 1th, 5th, and 7th days after surgery. Postoperative spinal cord tissue was collected in order to pathologic observation at the 7th day, and the metabolic profilings of serum and spinal cord from spinal cord injury rats were studied by ¹H NMR spectroscopy. RESULTS: The hindlimb motion of rats did not obviously change in sham operation group, there was no significant difference at each time point;and rats of model group occurred flaccid paralysis of both lower extremities, there was a significant difference at each time; there was significant differences between two groups at each time. Pathological results showed the spinal cord structure was normal with uniform innervation in shame group, while in model group, the spinal cord structure was mussy, and the neurons were decreased, with inflammatory cells and necrotic tissue. Analysis of metabonomics showed that concentration of very low density fat protein (VLDL), low density fat protein (LDL), glutamine, citric acid, dimethylglycine (DMG) in the serum and glutathione, 3-OH-butyrate, N-Acetyl-L-aspartic acid (NAA), glycerophosphocholine (GPC), glutamic acid, and ascorbate in spinal cord had significant changes(P<0.05). CONCLUSIONS: There are significant differences in metabolic profile from serum and spinal cord sample between model group and sham operation group, it conduces to explain the changes of small molecular substances in serum and spinal cord tissue after spinal cord injury, this provides the research basis for targeted research on the role of metabolic markers in patients with acute spinal cord injury.