Exosomes from circ-Astn1-modified adipose-derived mesenchymal stem cells enhance wound healing through miR-138-5p/SIRT1/FOXO1 axis regulation

BACKGROUND Wound healing impairment is a dysfunction induced by hyperglycemia and its effect on endothelial precursor cells(EPCs)in type 2 diabetes mellitus.There is increasing evidence showing that exosomes(Exos)derived from adipose-derived mesenchymal stem cells(ADSCs)exhibit the potential to improve endothelial cell function along with wound healing.However,the potential therapeutic mechanism by which ADSC Exos contribute to wound healing in diabetic mice remains unclear.AIM To reveal the potential therapeutic mechanism of ADSC Exos in wound healing in diabetic mice.METHODS Exos from ADSCs and fibroblasts were used for high-throughput RNA sequencing(RNA-Seq).ADSC-Exo-mediated healing of full-thickness skin wounds in a diabetic mouse model was investigated.We employed EPCs to investigate the therapeutic function of Exos in cell damage and dysfunction caused by high glucose(HG).We utilized a luciferase reporter(LR)assay to analyze interactions among circular RNA astrotactin 1(circ-Astn1),sirtuin(SIRT)and miR-138-5p.A diabetic mouse model was used to verify the therapeutic effect of circ-Astn1 on Exo-mediated wound healing.RESULTS High-throughput RNA-Seq analysis showed that circ-Astn1 expression was increased in ADSC Exos compared with Exos from fibroblasts.Exos containing high concentrations of circ-Astn1 had enhanced therapeutic effects in restoring EPC function under HG conditions by promoting SIRT1 expression.Circ-Astn1 expression enhanced SIRT1 expression through miR-138-5p adsorption,which was validated by the LR assay along with bioinformatics analyses.Exos containing high concentrations of circ-Astn1 had better therapeutic effects on wound healing in vivo compared to wild-type ADSC Exos.Immunofluorescence and immunohistochemical investigations suggested that circ-Astn1 enhanced angiopoiesis through Exo treatment of wounded skin as well as by suppressing apoptosis through promotion of SIRT1 and decreased forkhead box O1 expression.CONCLUSION Circ-Astn1 promotes the therapeutic effect of ADSC-Exos and thus improves wound healing in diabetes via miR-138-5p absorption and SIRT1 upregulation.Based on our data,we advocate targeting the circ-Astn1/miR-138-5p/SIRT1 axis as a potential therapeutic option for the treatment of diabetic ulcers.

Invited Review Reduction,reuse and recycle of spent Li-ion batteries for automobiles:A review

The demand for Li-ion batteries (LIBs) for vehicles is increasing. However, LIBs use valuable rare metals, such as Co and Li, aswell as environmentally toxic reagents. LIBs are also necessary to utilize for a long period and to recycle useful materials. The reduction, reuse,and recycle (3R) of spent LIBs is an important consideration in constructing a circular economy. In this paper, a flowsheet of the 3R of LIBs isproposed and methods to reduce the utilization of valuable rare metals and the amount of spent LIBs by remanufacturing used parts and designingnew batteries considering the concept of 3R are described. Next, several technological processes for the reuse and recycling of LIBs are introduced.These technologies include discharge, sorting, crushing, binder removal, physical separation, and pyrometallurgical and hydrometallurgicalprocessing. Each process, as well as the related physical, chemical, and biological treatments, are discussed. Finally, the problem of developedtechnologies and future subjects for 3R of LIBs are described.

Electrochemical recycling of Pd and Ag from simulated high-level liquid waste

For the recycling of Pd and Ag from high-level liquid waste(HLLW), the electrochemical behaviors of Pd and Ag in the simulated HNO_(3) solutions were investigated by cyclic voltammetry and potentiostatic deposition.Scanning electron microscopy(SEM) and X-ray diffraction(XRD) were used to-observe the deposits morphology and to evaluate their composition. The results indicate that the formation of NO_(2)^(-)electrodeposited. When Pd and Ag are electrodeposited together, more metals are gained in the same time, and the deposited Ag does not dissolve in this situation. The metals are electrodeposited completely at the potentials from -0.4 to -0.6 V(vs MSE) and the deposits contai-n Ag and PdHx. The electrodeposition of Pd can boost h-ydrogen evolution,and then the reaction between H;and NO_(2)^(-)is sped up, thereby lowering the concentration of NO_(2)^(-)and inhibiting the dissolution of Ag.

Effect of hydrogen intervention on refractory wounds after radiotherapy:A case report

BACKGROUND Patients with keloids who receive radiotherapy(RT)after surgery can develop refractory wounds that cannot be healed by the patient's own repair system.Such chronic wounds are uneven and complex due to persistent abscess and ulceration.Without external intervention,they can easily result in local tissue necrosis or,in severe cases,large area tissue resection,amputation,and even death.CASE SUMMARY This article describes the use of hydrogen to treat a 42-year-old female patient with a chronic wound on her left shoulder.The patient had a skin graft that involved implanting a dilator under the skin of her left shoulder,and then transferring excess skin from her shoulder onto scar tissue on her chest.The skin grafting was followed by two rounds of RT,after which the shoulder wound had difficulty healing.For six months,the patient was treated with 2 h of hydrogen inhalation(HI)therapy per day,in addition to application of sterile gauze on the wound and periodic debridement.We also performed one deep,large,sharp debridement to enlarge the wound area.The wound healed completely within 6 mo of beginning the HI treatment.CONCLUSION After HI therapy,the patient showed superior progress in reepithelialization and wound repair,with eventual wound closure in 6 mo,in comparison with the previous failures of hyperbaric oxygen and recombinant bovine basic fibroblast growth factor therapies.Our work showed that HI therapy could be a new strategy for wound healing that is cleaner,more convenient,and less expensive than other therapies,as well as easily accessible for further application in clinical wound care.

Hyperbaric oxygen therapy improves the effect of keloid surgery and radiotherapy by reducing the recurrence rate

Objective： Keloids are exuberant cutaneous scars that form due to abnormal growth of fibrous tissue fol- lowing an injury. The primary aim of this study was to assess the efficacy and mechanism of hyperbaric oxygen therapy （HBOT） to reduce the keloid recurrence rate after surgical excision and radiotherapy. Methods： （1） A total of 240 patients were randomly divided into two groups. Patients in the HBOT group （O group） received HBOT after surgical excision and radiotherapy. Patients in the other group were treated with only surgical excision and radiotherapy （K group）. （2） Scar tissue from recurrent patients was collected after a second operation. Hematoxylin and eosin （H＆E） staining was used to observe keloid morphology. Certain inflammatory factors （interleukin-6 （IL-6）, hypoxia-inducible factor-1α （HIF-1α）, tumor necrosis factor-α （TNF-α）, nuclear factor KB （NF-κB）, and vascular endothelial growth factor （VEGF）） were measured using immunohistochemical staining. Results： （1） The recurrence rate of the O group （5.97%） was significantly lower than that of the K group （14.15%）, P〈0.05. Moreover, patients in the O group reported greater satisfaction than those in the K group （P〈0.05）. （2） Compared with the recurrent scar tissue of the K group, the expression levels of the inflammatory factors were lower in the recurrent scar tissue of the O group. Conclusions： Adjunctive HBOT effectively reduces the keloid recurrence rate after surgical excision and radiotherapy by improving the oxygen level of the tissue and alleviating the inflammatory process.

Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap

Objective: Skin damage induced by ischemia/reperfusion (I/R) is a multifactorial process that often occurs in plastic surgery. The mechanisms of I/R injury include hypoxia, inflammation, and oxidative damage. Hydrogen gas has been reported to alleviate cerebral I/R injury by acting as a free radical scavenger. Here, we assessed the protective effect of hydrogen-rich saline (HRS) on skin flap I/R injury. Methods: Abdominal skin flaps of rats were elevated and ischemia was induced for 3 h; subsequently, HRS or physiological saline was administered intraperitoneally 10 min before reperfusion. On postoperative Day 5, flap survival, blood perfusion, the accumulation of reactive oxygen species (ROS), and levels of cytokines were evaluated. Histological examinations were performed to assess inflammatory cell infiltration. Results: Skin flap survival and blood flow perfusion were improved by HRS relative to the controls. The production of malondialdehyde (MDA), an indicator of lipid peroxidation, was markedly reduced. A multiplex cytokine assay revealed that HRS reduced the elevation in the levels of inflammatory cytokines, chemokines and growth factors, with the exception of RANTES (regulated on activation, normal T-cell expressed and secreted) growth factor. HRS treatment also reduced inflammatory cell infiltration induced by I/R injury. Conclusions: Our findings suggest that HRS mitigates I/R injury by decreasing inflammation and, therefore, has the potential for application as a therapy for improving skin flap survival.

Necroptosis was found in a rat ischemia/reperfusion injury flap model

Background:Necroptosis is a new form of cell death that has been identified as a third pathway causing cell death.In this study,necrostatin-1 (Nec-1) was used to determine whether necroptosis exists in a rat ischaemia/reperfusion injury flap model.Methods:In this study,twenty male Sprague-Dawley rats were divided randomly into two groups:a control group (CTL group) and a Nec-1 group.Each abdominal skin flap underwent 3 h of ischaemia and then reperfusion.Fifteen minutes before and after reperfusion,phosphate buffer saline (PBS) was administered intraperitoneally to the CTL group,while Nec-1 was administered intraperitoneally to the Nec-1 group.Twenty-four hours after reperfusion,the whole flap was divided equally into 54 sections.Flap blood perfusion was measured.One sample was taken randomly from each row.Morphological changes,apoptosis,receptor-interacting protein-1 (RIP-1) expression and caspase-3 activity were observed and detected.The measurements between the two groups were compared with the independentt-test,and aPvalue of <0.05 was considered statistically significant.Results:Compared to flaps in the CTL group,flaps in the Nec-1 group showed longer survival rates,better blood perfusion and less inflammatory infiltration.The total flap area considered to have survived was 70.88 ± 10.28% in the CTL group,whereas 80.56 ± 5.40% of the area was found to be living in the Nec-1 group (Nec-1 vs.CTL,t= –2.624,P<0.05).For some rows,there were significant differences in cell apoptosis between the two groups,the apoptosis index (AI) in rows "9 cm","7 cm","6 cm" and "5 cm" was significantly lower in the Nec-1 group than that in the CTL group (Nec-1 vs.CTL,P<0.05).RIP-1 expression was much lower in the Nec-1 group than that in the CTL group in rows "5 cm" to "9 cm" (Nec-1 vs.CTL,P<0.05).No significant differences in caspase-3 activity were found.Conclusion:According to the results,necroptosis was present in a rat abdominal ischaemia/reperfusion injury flap model.

Hyperbaric oxygen treatment on keloid tumor immune gene expression

Background:Hyperbaric oxygen treatment(HBOT)has been demonstrated to influence the keloid recurrence rate after surgery and to relieve keloid symptoms and other pathological processes in keloids.To explore the mechanism of the effect of HBOT on keloids,tumor immune gene expression and immune cell infiltration were studied in this work.Methods:From February 2021 to April 2021,HBOT was carried out on keloid patients four times before surgery.Keloid tissue samples were collected and divided into an HBOT group(keloid with HBOT before surgery[HK]group,n=6)and a non-HBOT group(K group,n=6).Tumor gene expression was analyzed with an Oncomine Immune Response Research Assay kit.Data were mined with R package.The differentially expressed genes between the groups were compared.Hub genes between the groups were determined and verified with Quantitative Real-time PCR.Immune cell infiltration was analyzed based on CIBERSORT deconvolution algorithm analysis of gene expression and verified with immunohistochemistry(IHC).Results:Inflammatory cell infiltration was reduced in the HK group.There were 178 upregulated genes and 217 downregulated genes.Ten hub genes were identified,including Integrin Subunit Alpha M(ITGAM),interleukin(IL)-4,IL-6,IL-2,Protein Tyrosine Phosphatase Receptor Type C(PTPRC),CD86,transforming growth factor(TGF),CD80,CTLA4,and IL-10.CD80,ITGAM,IL-4,and PTPRC with significantly downregulated expression were identified.IL-10 and IL-2 were upregulated in the HK group but without a significant difference.Infiltration differences of CD8 lymphocyte T cells,CD4 lymphocyte T-activated memory cells,and dendritic resting cells were identified with gene CIBERSORT deconvolution algorithm analysis.Infiltration levels of CD4 lymphocyte T cell in the HK group were significantly higher than those of the K group in IHC verification.Conclusion:HBOT affected tumor gene expression and immune cell infiltration in keloids.CD4 lymphocyte T cell,especially activated memory CD4+T,might be the key regulatory immune cell,and its related gene expression needs further study.

Inflatable pressure garment device for pressure therapy after chest wall keloid operation and radiotherapy

Aim: Keloids often occur on the chest wall, with high recurrence rates despite surgery and radiotherapy. Garment pressure therapy is commonly used to treat hypertrophic scars and keloids. Irregularity of the chest wall surface can inhibit the effects of the garment pressure therapy. This clinical study is to determine the effect of inflatable pressure garment in preventing keloid recurrence after keloid operation and radiotherapy. Methods: Chest wall keloid was removed and radiotherapy was administered at the surgical sites on the 1st and 7th postoperative days in 61 patients. An inflatable pressure garment device was designed and its pressure effect was confirmed by comparing it with the general pressure garment at the sites of the right and left infraclavicular area, manubrium and sternal area between breasts. The keloid patients were treated with inflatable pressure garment device 1 month after the operation. The clinical results were observed. Results: The detected pressures were 0.26 ± 0.21, 0.49 ± 0.16, 0.53 ± 0.10 and 0.91 ± 0.17 kPa at the sites of the right infraclavicular area, the manubrium area, the left infraclavicular area and sternal area between breasts with the general pressure garment. These were obvious lower (P < 0.05) than that generated with the inflatable pressure garment device of which the average pressures were 7.26 ± 0.41, 7.6 ± 0.32, 9.02 ± 0.54 and 10.31 ± 0.14 kPa at the corresponding sites.Sixty-one patients were treated with this device after keloid surgical excision and radiotherapy. Satisfactory results were observed. Conclusion: Appropriate and effective pressure can be generated with inflatable pressure garment on the chest wall. This device may be useful in preventing chest wall keloid recurrence after keloid operation and radiotherapy.

Synergistic effect of hyperbaric oxygen preconditioning and hydrogen-rich saline in ameliorating rat flap ischemia/reperfusion injury

Aim:This study was conducted to evaluate the synergistic effects of hyperbaric oxygen(HBO)preconditioning and hydrogen-rich saline(HRS)treatment on skin flap survival and apoptosis in a rat ischemia/reperfusion(IR)skin flap model.Methods:Male Sprague-Dawley rats were randomly divided into five groups:one sham surgery group(sham group)and four surgery groups(IR group,HBO group,HRS group,and HBO+HRS group).An extended epigastric adipocutaneous flap(6 cm×9 cm)was raised over the abdomen in each animal of all five groups.The last four groups underwent 6 h of IR management and were treated,respectively,with normal saline,HBO,HRS(HRS,0.8 mmol/L),or a combined approach(HBO and HRS).On the 3rd postoperative day,flap survival rate and perfusion condition,apoptotic index,caspase-3 activity,protein expression of pASK1 and Bcl-2/Bax ratio,and Bcl-2 messenger RNA(mRNA)expression were assessed.Results:Prior studies have shown the protective effects of HBO and HRS,both of which have been associated with an increase in flap survival.Compared to the IR group,the flaps in the HBO,HRS,and HBO+HRS groups showed better perfusion and a larger survival area with a low number of apoptotic cells,low caspase-3 activity and pASK1 expression,and a high Bcl-2/Bax ratio and Bcl-2 mRNA expression.Of these groups,the HBO+HRS group showed the best flap survival.Conclusion:Both HBO and HRS treatments increase the rate of flap survival,while the synergistic application of HBO and HRS showed a higher survival rate as compared to individual treatments of each.The potential regulation of apoptosis with the use of these two modalities may improve skin flap survival.

Reconstruction of a large defect of the female chest following keloid excision with use of the rectus abdominis myocutaneous flap

Aim: This study aimed to investigate the efficacy of the myocutaneous flap of the rectus abdominis in the surgical treatment of a large defect on the female chest following keloid excision.Methods: According to the location and size of the keloid on the chest, a myocutaneous flap based on the left or right rectus abdominis muscle was designed and transferred for repair of a chest defect following keloid resection. Radiotherapy was performed in the surgical area on the first and seventh postoperative days.Results: From January 2015 to March 2016, rectus abdominis myocutaneous flap coverage and early radiotherapy were used to treat 7 cases of keloids on the female chest. A postoperative follow-up of 10-14 months (average 12 months) was conducted. All the flaps survived well without evidence of keloid recurrence, and all patients achieved an improved chest shape.Conclusion:The rectus abdominis myocutaneous flap is a viablemethod for wound closure following resection of large keloids on the female chest.

Keloid treatment: what will be the right choice?

I do not know the meaning of 'disease without satisfactory treatment method', but I know the principle the doctor should obey when he faces such patients. That is he should choose the most effective method for the patients, considering not the interest of himself, but the benefit of the patients, not the treatment method he can offer, but the method the patients need. Unfortunately, such principles are not followed sometimes. Patients in plight are often manipulated by evil hand and then drop into despair circumstance. They become suspicious of every doctor in this field in the end. The development in this field is then blocked forever.

The radiation therapy in keloids treatment: a comprehensive review of pathomechanism, damage mechanisms and cellular response

Keloid management has always been frustrating and challenging. The combination therapy of surgical excision and radiation therapy was deemed as the last resort for decades. The authors performed a thorough and comprehensive review over the mechanisms on how radiation therapy damages the keloid cells. The keloid cells' cellular response towards damage induced by irradiation was also studied based on original and current literatures. Mechanisms of damage generated by radiation therapy on keloid cells remained partially understood. However, direct damage was identified playing dominant role, in contrast to damage involved cancer cell apoptosis. Moreover, the p53 pathway and some inflammatory factors like interleukin-6 were believed to function in cellular response to irradiation. However, the transforming growth factor beta, which was the major dysregulated pathway involved in pathogenesis of keloid formation showed no apparent correlation with cellular response to irradiation damage. These pathways could partially explain radiation resistance in some refractory keloid lesions. The scientific basis and experimental proof in this field was still inadequate, which drove us to find more evidence to identify the key regulator response to damage engendered by radiation therapy. Further pathway identification may benefit the drug development to prevent keloid recurrence.