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.

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 .

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.

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.

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.

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.

The expression of circ_0090049 in hepatocellular carcinoma and the molecular regulation mechanism of other biological functions.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in liver cancer. Circular RNA_0090049 (circ_0090049) has been shown to be involved in the advance of HCC. However, the interaction between circ_0090049 and microRNA (miRNA) in HCC has not been studied. Quantitative real-time PCR was used to detect the expression of related genes. Through detection of cell proliferation, migration, invasion, and rate of tumor sphere formation, the capping experiment was carried out to verify the regulatory relationship between miRNA and circ_0090049 or circ_0090049 and ubiquitin-conjugating enzyme E2 T (UBE2T). The expression of related proteins was detected by Western blotting. The interaction of miRNA with circ_0090049 or UBE2T was notarized by Dual-luciferase reporter assay. Xenotransplantation experiments confirmed the function of circ_0090049 in vivo. Circ_0090049 and UBE2T were upregulated in liver cancer. Silencing circ_0090049 reduced the proliferation, migration, invasion, and tumor spheroid formation rate of Huh7 and HCCLM3 cells. MiR-605-5p and miR-548c-3p were identified as targets of circ_0090049, and UBE2T was the target of miR-605-5p and miR-548c-3p. Anti-miR-605-5p, anti-miR-548c-3p or UBE2T overexpression restored the inhibitory effect of circ_0090049 knockdown on HCC cells. Animal experiments confirmed the antitumor effect of silence circ_0090049. Circ_0090049 regulates the expression of UBE2T by regulating miR-605-5p or miR-548c-3p, thereby promoting the development of HCC cells.

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.

Long noncoding RNA H19 act as a competing endogenous RNA of Let-7g to facilitate IEC-6 cell migration and proliferation via regulating EGF.

Intestinal mucosal injury is one of the most significant complications of burns. In our previous study, it was found that autophagy could alleviate burn-induced intestinal injury, but the underlying mechanisms are still unclear. Irregular expression of long noncoding RNAs (lncRNAs) is present in many diseases, including burns. However, the relationship between lncRNAs and intestinal mucosal injury requires further elucidation. In this study, we established a burn mice model and detected the expression level of autophagy-related proteins. Then, H19 content after autophagy intervention was tested in vitro and in vivo. The interaction of H19 with Let-7g and that of Let-7g with epidermal growth factor (EGF) were verified by dual-luciferase reporter assays. We found that the expression of the autophagy-associated proteins LC3-II and Beclin-1 was raised in the intestinal tract of the burn mice model. Similarly, the transfection of H19 raised autophagy levels. H19 was elevated after autophagy intervention in vitro and in vivo. H19 overexpression was able to promote IEC-6 cell migration and proliferation. Let-7g was suppressed by the overexpression of H19 and the combination of Let-7g mimic was able to abolish the physiological effect of H19. Moreover, the suppression of Let-7g increased the expression of EGF protein, which heightened IEC-6 cell migration and proliferation. Besides this, dual-luciferase assays revealed that Let-7g was a direct target of H19 as well as the EGF gene. Taken together, autophagy-mediated H19 increases in mouse intestinal tract after severe burn and functions as a sponge to Let-7g to regulate EGF, which suggests that H19 serves as a potential therapeutic target and biomarker for intestinal mucosal injury after burns.

Epidermal growth factor regulation by autophagy-mediated lncRNA H19 in murine intestinal tract after severe burn.

To investigate the regulation of epidermal growth factor (EGF) by autophagy-mediated long non-coding RNA (lncRNA) H19 in the intestinal tracts of severely burned mice. C57BL/6J mice received third-degree burns to 30% of the total body surface area. Rapamycin and 3-methyladenine (3-MA) were used to activate and inhibit autophagy, and the changes in LC3 and Beclin1 levels were assessed by Western blotting. The effect of autophagy on lncRNA H19 was detected by qRT-PCR. Adenovirus-mediated overexpression of lncRNA H19 in IEC-6 cells was used to assess the effects of lncRNA H19 on EGF and let-7g via bioinformatics analysis, Western blotting and qRT-PCR. let-7g mimic/inhibitor was used to overexpress/inhibit let-7g, and qRT-PCR and Western blotting were used to detect the effects of let-7g on EGF. The expression levels of LC3-II, Beclin1 and lncRNA H19 were increased in intestinal tissues and IEC-6 cells after rapamycin treatment but were reversed after 3-MA treatment. LC3-II, Beclin1 and lncRNA H19 levels increased in intestinal tissues after the burn, and these increases were more significant after rapamycin treatment but decreased after 3-MA treatment. The lncRNA H19 overexpression in IEC-6 cells resulted in increased and decreased expression levels of EGF and let-7g, respectively. Furthermore, overexpression and inhibition of let-7g resulted in decreased and increased expression of EGF, respectively. Taken together, intestinal autophagy is activated after a serious burn, which can increase the transcription level of lncRNA H19. lncRNA H19 may regulate the repair of EGF via let-7g following intestinal mucosa injury after a burn.

Effects of Frozen Stromal Vascular Fraction on the Survival of Cryopreserved Fat Tissue.

BACKGROUND: Nowadays, the use of cryopreserved fat tissue for soft tissue augmentation is common, except for its unpredictable fat graft absorption, and the toxicity of the cryoprotective agent remains a limitation. In this study, the effects of freezing stored fat tissue without a cryoprotector, and the addition of the stromal vascular fraction (SVF) on the survival of cryopreserved transplants was studied. METHODS: Lipoaspirates from six donors were processed and cryopreserved at - 20 °C, - 80 °C and - 196 °C, respectively. The authors evaluated the lipoaspirates in vitro, on the basis of fat tissue and SVF viability after cryopreservation. In vivo fat grafting was performed in nude mice. Six trenches were injected on the backs of mice. Cryopreserved tissues (- 20 °C, - 80 °C and - 196 °C) were injected on the right side, and the other side received the SVF combination. At 4 and 8 weeks after transplantation, the authors examined the weight, volume and morphology of the tissue and analyzed histochemical staining and immunohistochemistry (i.e., DIL, CD31 and VWF) to evaluate the survival of the fat grafts. RESULTS: After cryopreservation without the cryoprotective agent, adipose tissue maintained its morphology better in - 80 °C than - 20 °C and - 196 °C. SVF cells can retain their adhesive and proliferative properties after cryopreservation. Although cryopreservation caused damage to fat tissue, all explants showed intact adipocytes and vascular ingrowth. Most of all, the - 80 °C group had less graft resorption and fibrosis than the other temperature groups. There was increased survival of fat grafts in the SVF group compared with the control group. CONCLUSION: In this study, the authors demonstrated that the storage temperature of - 80 °C was promising for 3 months of adipose tissue cryopreservation without a cryoprotective agent, and SVF could increase the survival rate of cryopreserved fat tissue. NO LEVEL ASSIGNED: 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 .

High RNA-Binding Motif Protein 3 (RBM3) Expression is Independently Associated with Prolonged Overall Survival in Intestinal-Type Gastric Cancer.

BACKGROUND High expression of the RNA-binding motif protein 3 (RBM3) has previously been described as a favorable clinicopathological factor in several cancers, including ovarian cancer, colorectal cancer, prostate cancer, and breast cancer. The aim of this study was to examine the prognostic implications of RBM3 expression in gastric cancer. MATERIAL AND METHODS Immunohistochemical analysis of RBM3 expression from 123 patients showed that upregulated RBM3 was mainly found in intestinal-type (n=78, case=59) cancer compared to diffuse-type (n=15, case=8) and mixed-type (n=30, case=17). There were no significant differences in RBM3 expression in subgroups of clinicopathological parameters. RBM3 expression was strongly associated with p53 but not with Ki-67. Cox univariate analysis revealed that high RBM3 expression was closely associated with prolonged overall survival time (HR 0.504, 95% CI: 0.300-0.845, P=0.009). Multivariate analysis remained supporting these associations when adjusted for age, sex, tumor size, differentiation grade, TNM stage, lymphatic invasion, and Ki-67 and p53 expression (HR 0.541, 95% CI: 0.308-0.952, P=0.033), where Lauren grade was not included. Lauren grade was the only factor with independent prognostic significance in a model adjusted for all factors. These results were confirmed by Kaplan-Meier analysis. RESULTS Therefore, together with the upregulated RBM3 expression observed in intestinal-type of Lauren grade, we suggest that upregulation of RBM3 is partially responsible for the favorable overall survival in cases with intestinal Lauren grade, which is demonstrated by the box diagram and Kaplan-Meier analysis. Our results showed that high RBM3 expression in gastric cancer is mainly found in intestinal-type of Lauren grade and is associated with longer overall survival time. CONCLUSIONS We found that RBM3 is a potential biomarker of good prognosis and deserves further validation.

A novel label-free live-cell biosensor for G-protein-coupled receptor functional assay with enhanced sensitivity.

This study developed a surface plasmon resonance (SPR)-based live-cell biosensor with enhanced sensitivity for label-free ligand binding assay of G-protein-coupled receptors (GPCRs). The ß2-adrenoceptor was heterologously expressed in human embryonic kidney-293 cells. The specific ligand binding function of expressed ß2-adrenoceptor was monitored by SPR via refractive index measurement. The results indicate the expressed ß2-adrenoceptor can respond to isoprenaline with high specificity. The SPR signals can be enhanced more than three times by the use of LY294002. This biosensor can be applied in the functional assay of GPCRs by detecting the specific interactions between GPCRs and their target ligands.

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.

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.

The role of SDF-1-CXCR4/CXCR7 axis in biological behaviors of adipose tissue-derived mesenchymal stem cells in vitro.

Numerous studies have reported that CXCR4 and CXCR7 play an essential, but differential role in stromal cell-derived factor-1 (SDF-1)-inducing cell chemotaxis, viability and paracrine actions of BMSCs. Adipose tissue-derived mesenchymal stem cells (ADSCs) have been suggested to be potential seed cells for clinical application instead of bone marrow derived stroma cell (BMSCs). However, the function of SDF-1/CXCR4 and SDF-1/CXCR7 in ADSCs is not well understood. This study was designed to analyze the effect of SDF-1/CXCR4 and SDF-1/CXCR7 axis on ADSCs biological behaviors in vitro. Using Flow cytometry and Western blot methods, we found for the first time that CXCR4/CXCR7 expression was increased after treatment with SDF-1 in ADSCs. SDF-1 promoted ADSCs paracrine, proliferation and migration abilities. CXCR4 or CXCR7 antibody suppressed ADSCs paracrine action induced by SDF-1. The migration of ADSCs can be abolished by CXCR4 antibody, while the proliferation of ADSCs was only downregulated by CXCR7 antibody. Our study indicated that the angiogenesis of ADSCs is, at least partly, mediated by SDF-1/CXCR4 and SDF-1/CXCR7 axis. However, only binding of SDF-1/CXCR7 was required for proliferation of ADSCs, and CXCR7 was required for migration of ADSCs induced by SDF-1. Our studies provide evidence that the activation of either axis may be helpful to improve the effectiveness of ADSCs-based stem cell therapy.

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.

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.

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.