Mechanism of damage of HIF-1 signaling in chronic diabetic foot ulcers and its related therapeutic perspectives.

Diabetic foot ulcer (DFU) is a chronic complication of diabetes. Wound healing in patients with DFU is generally very slow, with a high recurrence rate even after the ulcer healed. The DFU remains a major clinical challenge due to a lack of understanding of its pathogenesis. Given the significant impact of DFU on patient health and medical costs, enhancing our understanding of pathophysiological alterations and wound healing in DFU is critical. A growing body of research has shown that impaired activation of the HIF-1 pathway in diabetics, which weakens HIF-1 mediated responses to hypoxia and leads to down-regulation of its downstream target genes, leading to incurable diabetic foot ulcers. By analyzing and summarizing the literature in recent years, this review summarizes the mechanism of HIF-1 signaling pathway damage in the development of DFU, analyzes and compares the application of PHD inhibitors, VHL inhibitors, biomaterials and stem cell therapy in chronic wounds of diabetes, and proposes a new treatment scheme mediated by participation in the HIF-1 signaling pathway, which provides new ideas for the treatment of DFU.

Botulinum Toxin Type A Alleviates Androgenetic Alopecia by Inhibiting Apoptosis of Dermal Papilla Cells via Targeting circ_0135062/miR-506-3p/Bax Axis.

Botulinum toxin type A (BTXA) has the potential to treat androgenetic alopecia (AGA); however, its impact on the apoptosis of dermal papillary cells (DPCs) is not yet fully understood. Noncoding RNAs play a crucial role in AGA. In this study, we investigated the potential mechanism by which BTXA alleviates apoptosis induced by dihydrotestosterone (DHT) in DPCs. We assessed the mRNA levels of circ_0135062, miR-506-3p, and Bax using qRT-PCR. Binding interactions were analyzed using RNA pulldown and dual-luciferase assays. Cell viability was determined using a cell counting kit-8 assay, and cell apoptosis was assessed using flow cytometry, TUNEL assays, and western blotting. Our findings revealed that BTXA inhibited the apoptosis of DPCs treated with DHT. Moreover, circ_0135062 overexpression counteracted the protective effect of BTXA on DHT-treated DPCs. MiR-506-3p was found to interact with Bax and inhibit apoptosis in DPCs by suppressing Bax expression in response to DHT-induced damage. Furthermore, circ_0135062 acted as a sponge for miR-506-3p, thereby inhibiting the targeting of Bax expression by miR-506-3p. In conclusion, BTXA exhibited an antiapoptotic effect on DHT-induced DPC injury via the circ_0135062/miR-506-3p/Bax axis.Level of Evidence II This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

N6-Methyladenosine Modification of lncCCKAR-5 Regulates Autophagy in Human Umbilical Cord Mesenchymal Stem Cells by Destabilizing LMNA and Inhibits Diabetic Wound Healing.

Long noncoding RNAs are pivotal contributors to the development of human diseases. However, their significance in the context of diabetic wound healing regulated by human umbilical cord mesenchymal stem cells (hUCMSCs) remains unclear. This study sheds light on the involvement of lncCCKAR5 in this process. We found that hUCMSCs exposed to high glucose conditions exhibited a significant downregulation of lncCCKAR5 expression, and lncCCKAR5 played a critical role in modulating autophagy, thus inhibiting apoptosis in hUCMSCs. In addition, the reduction of lncCCKAR5 in cells exposed to high glucose effectively thwarted cellular senescence and facilitated filopodium formation. Mechanistically, lncCCKAR5 served as a scaffold that facilitated the interaction between MKRN2 and LMNA, a key regulator of cytoskeletal function and autophagy. The lncCCKAR5/LMNA/MKRN2 complex played a pivotal role in promoting the ubiquitin-mediated degradation of LMNA, with this effect being further augmented by N6-adenosine methylation of lncCCKAR5. Consequently, our findings underscore the critical role of lncCCKAR5 in regulating the autophagic process in hUCMSCs, particularly through protein ubiquitination and degradation. This intricate regulatory network presents a promising avenue for potential therapeutic interventions in the context of diabetic wound healing involving hUCMSCs.

Treatment of Chin Retrusion With Botulinum Toxin Plus Hyaluronic Acid Filler in Comparison With Hyaluronic Acid Filler Alone: A Randomized, Evaluator-Blinded, Controlled Study.

BACKGROUND: Hyaluronic acid (HA) has already been widely administered for chin augmentation. Patients with chin retrusion frequently present with increased chin hypertonia. Monotherapy with HA falls short in addressing the multifaceted cosmetic concerns associated with chin retrusion. OBJECTIVES: This study aimed to investigate the clinical efficacy and safety of the combination therapy involving botulinum toxin (BTX) and HA in the treatment of chin retrusion. METHODS: We enrolled patients with moderate to severe chin retrusion for 9 months of follow-up after they received either combined treatment with BTX plus HA or monotreatment with HA. We also calculated the surface-volume coefficient with 3-dimensional digital scanning technique, and evaluated outcomes based on the Allergan Chin Retrusion Scale (ACRS), the Global Aesthetic Improvement Scale (GAIS), and treatment-related adverse events (TRAEs). RESULTS: A total of 50 patients were recruited and randomized to the treatment group (BTX plus HA) or control group (HA alone) in a 1:1 ratio. Patients in the treatment group exhibited significantly higher surface-volume coefficients during the first 6 months (P < .05). ACRS scores and responder rates in the 2 groups remained similar throughout the follow-up (P > .05). Within the initial 3 months, the GAIS responder rate in the treatment group was significantly higher than that in the control group (P < .05). Mild TRAEs were observed in both groups, and subsided within 7 days. There was no increase in adverse effects with the combined treatment. CONCLUSIONS: In comparison to monotherapy, the combined treatment not only improved the surface-volume coefficient of hyaluronic acid but also achieved similar ACRS scores with less HA volume. Furthermore, the combination treatment yielded superior treatment outcomes for individuals with chin retrusion.

Effect of a New Hyaluronic Acid Hydrogel Dermal Filler Cross-Linked With Lysine Amino Acid for Skin Augmentation and Rejuvenation.

BACKGROUND: Hyaluronic acid (HA) fillers are the most popular filler agents for skin rejuvenation. Although 1,4-butanediol diglycidyl ether is regarded as a relatively safe cross-linker, it still exhibits certain cytotoxicity. OBJECTIVES: We presented here an amino acid-cross-linked HA (ACHA) which was obtained by an amidation reaction with lysine and HA. This study aimed to investigate ACHA's efficacy and safety for skin augmentation and rejuvenation. METHODS: Rheology, compressive tests, and swelling experiments were conducted to investigate ACHA's mechanical and viscoelastic properties. The effects of ACHA on the human keratinocytes (HaCaT) cells and the human dermal fibroblast (HDF) were investigated by Transwell and wound healing assays. Its impacts on the epithelial thickness and collagen synthesis were further examined in a mouse experimental model. We recruited 50 patients with moderate to severe nasolabial folds (NLFs). The patients were randomly allocated to receive ACHA or Restylane injections. The resulting retention rates of HA and the Wrinkle Severity Rating Scale and Global Aesthetic Improvement Scale outcomes were evaluated and compared. RESULTS: ACHA exhibited good viscoelasticity. It not only promoted migration and proliferation of HaCat and HDF and secretion of various growth factors but also increased skin thickness and promoted the generation of collagen. Patients who received ACHA had more residual volume 12 months after treatment. ACHA exhibited a promising augmentation effect in NLF correction with few adverse reactions. CONCLUSIONS: ACHA has shown promise as a biomaterial with excellent biocompatibility and viscoelastic characteristics in both research and the clinic.See the abstract translated into Hindi, Portuguese, Korean, German, Italian, Arabic, Chinese, and Taiwanese online here: https://doi.org/10.1093/asj/sjad169.

Exosomes derived from Nr-CWS pretreated MSCs facilitate diabetic wound healing by promoting angiogenesis via the circIARS1/miR-4782-5p/VEGFA axis.

Mesenchymal stem cell (MSC)-derived exosomes (Exos) were reported to a prospective candidate in accelerating diabetic wound healing due to their pro-angiogenic effect. MSCs pretreated with chemistry or biology factors were reported to advance the biological activities of MSC-derived exosomes. Hence, this study was designed to explore whether exosomes derived from human umbilical cord MSCs (hucMSCs) preconditioned with Nocardia rubra cell wall skeleton (Nr-CWS) exhibited superior proangiogenic effect on diabetic wound repair and its underlying molecular mechanisms. The results showed that Nr-CWS-Exos facilitated the proliferation, migration and tube formation of endothelial cells in vitro. In vivo, Nr-CWS-Exos exerted great effect on advancing wound healing by facilitating the angiogenesis of wound tissues compared with Exos. Furthermore, the expression of circIARS1 increased after HUVECs were treated with Nr-CWS-Exos. CircIARS1 promoted the pro-angiogenic effects of Nr-CWS-Exos on endothelial cellsvia the miR-4782-5p/VEGFA axis. Taken together, those data reveal that exosomes derived from Nr-CWS-pretreated MSCs might serve as an underlying strategy for diabetic wound treatment through advancing the biological function of endothelial cells via the circIARS1/miR-4782-5p/VEGFA axis.

Prospective, Randomized, and Controlled Study of a Human Umbilical Cord Mesenchymal Stem Cell Injection for Treating Diabetic Foot Ulcers.

With the development of society and the economy, the incidence of diabetic foot ulcers continues to increase. Currently, conventional debridement with dressing changes, hyperbaric oxygen, and vacuum sealing drainage are the main conservative treatments in clinical practice, and large wounds often require skin grafts or skin flap grafts. However, the treatment effects are not ideal, and many complications exist. Due to its complex pathogenesis, long treatment time, significant associated difficulties, and high disability rate, diabetic foot ulcers cause a heavy burden to patients, society, and medical care. According to our previous study, the pharmacological effects of human umbilical cord blood stem cells include nonspecific immune regulation; increased secretion of growth factors, vasoactive factors, and anti-inflammatory factors; enhanced anti-infectious ability of the human body; elimination of inflammation; and promotion of angiogenesis and ulcer healing. These effects suggest stem cells may be useful as an autologous or allogeneic treatment for refractory wounds. Therefore, we are conducting a clinical trial to treat refractory diabetic wounds with human umbilical cord stem cells in our clinic for diabetic foot ulcer patients who meet the inclusion criteria.

CircAGK regulates high dihydrotestosterone-induced apoptosis in DPCs through the miR-3180-5p/BAX axis.

The incidence of androgen alopecia (AGA), also known as seborrheic alopecia, has surged in recent years, and onset is occurring at younger ages. Dermal papilla cells (DPCs) are key to maintaining hair cycling, and apoptosis-driven processes in DPCs are closely related to hair follicle regeneration. Circular RNAs (circRNAs) are widely present in the human body and are closely related to the occurrence and development of many diseases. Currently, the biological functions of circRNAs in AGA are largely unknown. Whole-transcriptome sequencing was used to screen differential circRNA expression profiles between AGA patients and non-AGA patients. We found that hsa_circ_0002980 (circAGK) was significantly highly expressed in the AGA group. CircAGK promoted DPC apoptosis in the presence of high dihydrotestosterone (DHT) (15 nmol/L). By regulating the miR-3180-5p/BAX axis, circAGK promotes DPC apoptosis in a high DHT environment in vitro and inhibits hair growth in AGA mice in vivo, indicating that circAGK is a potential target for the clinical treatment of AGA.

Application of lncRNA-miRNA-mRNA ceRNA network analysis in the treatment of androgenic alopecia.

BACKGROUND: Long noncoding RNAs (lncRNAs) can be used as competitive endogenous RNAs (ceRNAs) to bind to microRNAs (miRNAs) to regulate gene expression. Previous studies have demonstrated that ceRNAs play an important role in the development of tumors. However, it is not clear whether the lncRNA-miRNA-mRNA ceRNA network plays a role in androgenic alopecia (AGA). METHODS: The hair follicles of three AGA patients and three healthy individuals were collected for high-throughput whole transcriptome sequencing to screen for differentially expressed lncRNAs. Differentially expressed lncRNA target genes were subjected to databases to predict miRNA-mRNA and lncRNA-miRNA relationship pairs, and a ceRNA network was constructed using Cytoscape software. Relative expression was verified by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: 84 lncRNAs were significantly differentially expressed between the hair follicles of AGA patients and those of healthy individuals; 30 were upregulated, and 54 were downregulated. The top 10 upregulated lncRNAs were ENST00000501520, ENST00000448179, ENST00000318291, ENST00000568280, ENST00000561121, ENST00000376609, ENST00000602414, ENST00000573866, ENST00000513358, and ENST00000564194. The top 10 downregulated lncRNAs were ENST00000566804, ENST00000561973, ENST00000587680, ENST00000569927, ENST00000340444, ENST00000424345, ENST00000589787, NR_024344, NR_073026, and NR_110001. The qRT-PCR validation results and receiver-operating characteristic curve analysis indicated that one upregulated lncRNA, LOXL1-AS1 (ENST00000564194), had the most significant clinical diagnostic potential. After further analysis, it was concluded that LOXL1-AS1 could be used as a sponge to target hsa-miR-5193, thereby regulating TP53 expression. CONCLUSION: The ceRNA network-regulating AGA was constructed through high-throughput sequencing. Our study also identified a key lncRNA that is possibly related to the AGA pathological process.

Correction of breast asymmetry by autologous fat grafting with the aid of 3D laser-scanning technology.

BACKGROUND: Currently, the lack of clinically accurate measurement and evaluation methods for breast asymmetry has considerably limited the use of autologous fat grafting in the correction of breast asymmetry. OBJECTIVE: This study calculated the volume difference in the bilateral breasts by three-dimensional (3D) laser scanning technology, established a bridge between digitalization and surgery to guide the correction of breast asymmetry by autologous fat grafting, and evaluated the surgical effect. METHODS: In the experimental group (3D group), the measurement range was defined by standardized methods, the algorithm to calculate the volume difference in the bilateral breasts was determined by the established software instructions, and the volume of intraoperative autologous fat grafting was guided by personalized data. In the control group, the volume of intraoperative autologous fat grafting was determined based on the surgeon's visual assessment and surgical experience. RESULTS: The volume difference in the bilateral breasts was less at 12 months after surgery (P < 0.05), the satisfaction of patients was higher (P < 0.05), and the reoperation rate was lower (P < 0.05). The incidence of postoperative complications was low in both groups (P > 0.05). CONCLUSIONS: 3D laser scanning technology can be used as a bridge between digitalization and surgery to significantly improve the surgical effect of autologous fat grafting in the correction of breast asymmetry, with high patient satisfaction and high clinical application value.

Smart thermosensitive poloxamer hydrogels loaded with Nr-CWs for the treatment of diabetic wounds.

The treatment of diabetic wound is a focus issue. At present, the Nocardia rubra cell wall skeleton (Nr-CWS) has been proved proven to promote angiogenesis and wound repair. Unfortunately, the high-glucose diabetic wound environment makes many drugs unable to be released effectively, and soon be removed. Smart thermosensitive poloxamer hydrogel (TH) is an ideal and adjustable drug delivery platform compatible with most living tissues. Here, a multifunctional composite thermosensitive hydrogel was developed. A mixture of poloxamers 407 and 188 as the gel matrix, and then it was physically mixed with Nr-CWS. The delivery vehicle not only controlled its release stably, preventing degradation in vitro, but also showed good affinity in vitro. In vivo, compared with thermosensitive poloxamer hydrogel alone or the direct use of Nr-CWS, the thermosensitive poloxamer hydrogel loaded with Nr-CWS promoted the proliferation of vascular endothelial cells effectively, resulting in increased expression of derma-related structural proteins and enhanced angiogenesis and wound healing. This study indicated that the angiogenesis and skin regeneration brought by Nr-CWS hydrogel are related to the activation of phosphatidylinositol 3 kinase and protein kinase B, Janus kinase/signal transducer and activator of transcription, and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways.

Graphene oxide accelerates diabetic wound repair by inhibiting apoptosis of Ad-MSCs via Linc00324/miR-7977/STK4 pathway.

Many studies have shown that graphene oxide (GO) promotes proliferation and differentiation of a variety of stem cells. However, its effect on adipose-derived mesenchymal stem cell (Ad-MSCs) apoptosis is still unclear. Apoptosis is a significant factor affecting stem cell-based treatment of diabetic wounds. Therefore, we explored the effect of GO on Ad-MSC apoptosis and diabetic wound healing. In this study, qRT-PCR was used to detect Ad-MSC expression of LncRNAs, miRNAs, and mRNAs under high-glucose environment. RNA immunoprecipitation (RIP), RNA pull-down, and luciferase assays were used to detect interactions of specific lncRNAs, miRNAs, and mRNAs. The effects of GO on Ad-MSC apoptosis were explored by flow cytometry, TUNEL assay, and Western blot. A diabetic wound model was used to explore the function of Linc00324 on Ad-MSC reparative properties in vivo. As a result, GO inhibited high glucose-induced apoptosis in Ad-MSCs, and Linc00324 contributed to the anti-apoptotic effect of GO. RIP and RNA pull-down confirmed that Linc00324 directly interacted with miR-7977, functioning as a miRNA sponge to regulate expression of the miR-7977 target gene STK4 (MST1) and downstream signaling pathways. In addition, GO reduced the apoptosis of Ad-MSCs in wounds and promoted wound healing. Taken together, these findings suggest GO may be a superior auxiliary material for Ad-MSCs to facilitate diabetic wound healing via the Linc00324/miR-7977/STK4 pathway.

Palliative radiotherapy combined with stent insertion to relieve dysphagia in advanced esophageal carcinoma patients: A systematic review and meta-analysis.

Introduction: Esophageal cancer is one of the most aggressive malignancies with limited treatment options, thus resulting in high morbidity and mortality. For patients with advanced esophageal cancer, the median survival is 3-6 months, with the majority requiring intervention for dysphagia. Objective: To compare the relief of dysphagia in patients with incurable esophageal cancer treated with stenting alone or a combination of stenting and palliative radiotherapy. Methods: The protocol of this study was pre-registered on PROSPERO (CRD42022337481). We searched PubMed, Wan Fang, Cochrane Library, Embase, and Web of Science databases. The literature search, quality assessment, and data extraction were conducted by two reviewers independently. The primary endpoints included median overall survival and dysphagia scores. Bleeding events, stent migration, and pain events were secondary outcomes. The meta-analysis results (the primary and secondary outcomes) were pooled by means of a random-effect model or a fixed-effects model. Results: Nine studies with a total of 851 patients were included in this meta-analysis, consisting of 412 patients in the stenting alone group and 439 patients in the palliative radiotherapy after esophageal cancer stenting (ROCS) group. The ROCS group could significantly improve dysphagia scores (SMD: -0.77; 95% CI: -1.02 to -0.51) and median overall survival (SMD: 1.70; 95% CI: 0.67-2.72). Moreover, there were no significant differences between the two groups in bleeding events, pain events, and stent migration. Conclusion: Patients with dysphagia in advanced esophageal cancer may benefit further from ROCS in median overall survival and dysphagia scores. However, there was no significant advantage in improving bleeding events, pain events, and stent migration. Therefore, it is urgent to find a better therapy to improve adverse events in the future. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022337481.

Three-Dimensional Rapid Printing-Assisted Individualized Total Nasal Reconstruction Based on a Database of Normal External Noses.

BACKGROUND: The nose is an unpaired facial structure. Applying three-dimensional rapid printing to total nose reconstruction is difficult because no paired structure is available for reference. In this study, three-dimensional laser scanning was used to create a database of normal external noses of Han Chinese individuals in East China to assist in total nose reconstruction. METHODS: Three-dimensional laser scanning was used to create a database of normal external noses. Patients scheduled for nasal reconstruction had their measurements scaled according to head circumference and facial proportions to simulate a new reconstructed shape for the residual nose using this database. The personalized new shape was produced using rapid three-dimensional printing for preoperative evaluation and surgical design. RESULTS: In the database of external noses, the medium nose type was the main type among Han adults in East China (64.15 percent), followed by the narrow nose type (26.34 percent). Quantitative analysis showed that blood loss and operative times were lower in the study group than in the traditional surgery group ( p < 0.05). A postoperative nasal appearance satisfaction questionnaire showed that the appearance satisfaction rate, daily life measures, and perioperative comfort were significantly better in the study group ( p < 0.05). CONCLUSIONS: The database of external noses can bridge three-dimensional printing with total nasal reconstruction. The database has important clinical significance for optimizing the shape of the nose, reducing intraoperative blood loss, shortening the operative time, and improving patient satisfaction. This study provides new insight for the application of computer-guided three-dimensional scanning and rapid printing in organ reconstruction.

Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis.

Damaged hyaline cartilage has no capacity for self-healing, making osteoarthritis (OA) "difficult-to-treat". Cartilage destruction is central to OA patho-etiology and is mediated by matrix degrading enzymes. Here we report decreased expression of miR-17 in osteoarthritic chondrocytes and its deficiency contributes to OA progression. Supplementation of exogenous miR-17 or its endogenous induction by growth differentiation factor 5, effectively prevented OA by simultaneously targeting pathological catabolic factors including matrix metallopeptidase-3/13 (MMP3/13), aggrecanase-2 (ADAMTS5), and nitric oxide synthase-2 (NOS2). Single-cell RNA sequencing of hyaline cartilage revealed two distinct superficial chondrocyte populations (C1/C2). C1 expressed physiological catabolic factors including MMP2, and C2 carries synovial features, together with C3 in the middle zone. MiR-17 is highly expressed in both superficial and middle chondrocytes under physiological conditions, and maintains the physiological catabolic and anabolic balance potentially by restricting HIF-1α signaling. Together, this study identified dual functions of miR-17 in maintaining cartilage homeostasis and prevention of OA.

Efficacy and safety of hyaluronic acid fillers for lip augmentation in a Chinese population.

BACKGROUND: Hyaluronic acid (HA) is an effective dermal filler for facial rejuvenation. This study aimed to observe the clinical efficacy of HA injection for lip augmentation in Chinese patients. METHODS: From May 2019 to April 2020, 70 patients with lip fullness scale (LPS) ≤3 underwent local HA injection using the "three-point" injection technique. All patients were followed up to observe the clinical efficacy, LPS, adverse events, and complications. RESULTS: All 70 patients were followed up for 12 months. Statistically significant improvements were observed in the height of lips within 6-9 months post-treatment (p < 0.05). The LFS improved significantly at follow-up compared with baseline (p < 0.05). Local redness occurred in two patients, and serious swelling occurred in three patients. These adverse events were generally tolerated and disappeared gradually within 1 week. No other serious adverse events and complications were reported in the remaining patients. CONCLUSIONS: Hyaluronic acid injection can be used for lip augmentation in the Chinese population. The "three-point" technique is simple, safe, and effective and does not cause serious complications.

Exosomal microRNA⁃93⁃3p secreted by bone marrow mesenchymal stem cells downregulates apoptotic peptidase activating factor 1 to promote wound healing.

Wounds are soft tissue injuries, which are difficult to heal and can easily lead to other skin diseases. Bone marrow mesenchymal stem cells (BMSCs) and the secreted exosomes play a key role in skin wound healing. This study aims to clarify the effects and mechanisms of exosomes derived from BMSCs in wound healing. Exosomes were extracted from the supernatant of the BMSCs. The expression of the micro-RNA miR-93-3p was determined by qRT-PCR analysis. HaCaT cells were exposed to hydrogen peroxide (H2O2) to establish a skin lesion model. MTT, flow cytometry, and transwell assays were conducted to determine cellular functions. The binding relationship between miR-93-3p and apoptotic peptidase activating factor 1 (APAF1) was measured using a dual luciferase reporter gene assay. The results showed that BMSC-derived exosomes or BMSC-exos promoted proliferation and migration and suppressed apoptosis in HaCaT cells damaged by H2O2. However, the depletion of miR-93-3p in BMSC-exos antagonized the effects of BMSC-exos on HaCaT cells. In addition, APAF1 was identified as a target of miR-93-3p. Overexpression of APAF1 induced the dysfunction of HaCaT cells. Collectively, the results indicate that BMSC-derived exosomes promote skin wound healing via the miR-93-3p/APAF1 axis. This finding may help establish a new therapeutic strategy for skin wound healing.

CircARHGAP12 Triggers Mesenchymal Stromal Cell Autophagy to Facilitate its Effect on Repairing Diabetic Wounds by Sponging miR-301b-3p/ATG16L1 and miR-301b-3p/ULK2.

Circular RNAs have been confirmed to play vital roles in the development of human diseases. Nevertheless, their effects on modulating mesenchymal stromal cells (MSCs) to heal diabetic wounds are still elusive. In this study, our data revealed that MSCs treated with high glucose displayed an evident reduction in circARHGAP12 expression, whereas autophagy mediated by circARHGAP12 suppressed high glucose-triggered apoptosis of MSCs. Mechanistically, circARHGAP12 was capable of directly interacting with miR-301b-3p and subsequently sponged microRNA to modulate the expression of the miR-301b-3p target genes ATG16L1 and ULK2 and the downstream signaling pathway. Moreover, circARHGAP12 promoted the survival of MSCs in diabetic wounds in vivo and accelerated wound healing. Collectively, these results suggest that circARHGAP12/miR-301b-3p/ATG16L1 and circARHGAP12/miR-301b-3p/ULK2 regulatory networks might be an underlying therapeutic target for MSCs in diabetic wound healing.

The potential role of hsa_circ_0001079 in androgenetic alopecia via sponging hsa-miR-136-5p.

BACKGROUND: Androgenetic alopecia (AGA) is an androgen-dependent polygenic hereditary disease. METHODS: Diseased hair follicles from 5 AGA patients and normal hair follicles from 5 healthy individuals were selected as specimens to carry out whole transcriptome sequencing. Multiple high-expression circular RNAs (circRNAs) were screened from the diseased group. We further verified the presence of the circRNAs in the clinical specimens by real-time fluorescence quantitative PCR (qRT-PCR). RESULTS: In total, 100 circRNAs were significantly upregulated, and 184 circRNAs were significantly downregulated. The top 10 upregulated circRNAs were hsa_circ_0101041, hsa_circ_0001578, hsa_circ_0135062, hsa_circ_0002980, hsa_circ_0005062, hsa_circ_0072688, hsa_circ_0133954, hsa_circ_0001079, hsa_circ_0005974, hsa_circ_0000489. The top 10 downregulated circRNAs were hsa_circ_0001278, hsa_circ_0031482, hsa_circ_0008285, hsa_circ_0003784, hsa_circ_0077096, hsa_circ_0001148, hsa_circ_0006886, hsa_circ_0000638, hsa_circ_0084521, and hsa_circ_0101074. Among top 10 upregulated circRNAs, hsa_circ_0001079 showed significantly high expression via large-sample verification and clinical application potential. Based on a database comparison and base pairing analysis, we found that has-miR-136-5p bound to hsa_circ_0001079 and that hsa-miR-136-5p had potential binding sites with Wnt5A. CONCLUSION: In summary, through high-throughput sequencing and bioinformatic analysis, a potential diagnostic marker for alopecia and a key circRNA that might adsorb microRNA (miRNA) through a sponging mechanism, thus mediating alopecia, were discovered in this study.