Relieving Macrophage Dysfunction by Inhibiting SREBP2 Activity: A Hypoxic Mesenchymal Stem Cells-Derived Exosomes Loaded Multifunctional Hydrogel for Accelerated Diabetic Wound Healing.

Macrophage dysfunction is one of the primary factors leading to the delayed healing of diabetic wounds. Hypoxic bone marrow mesenchymal stem cells-derived exosomes (hyBMSC-Exos) have been shown to play an active role in regulating cellular function through the carried microRNAs. However, the administration of hyBMSC-Exos alone in diabetic wounds usually brings little effect, because the exosomes are inherently unstable and have a short retention time at the wounds. In this study, a multifunctional hydrogel based on gallic acid (GA) conjugated chitosan (Chi-GA) and partially oxidized hyaluronic acid (OHA) is prepared for sustained release of hyBMSC-Exos. The hydrogel not only exhibits needs-satisfying physicochemical properties, but also displays outstanding biological performances such as low hemolysis rate, strong antibacterial capacity, great antioxidant ability, and excellent biocompatibility. It has the ability to boost the stability of hyBMSC-Exos, leading to a continuous and gradual release of the exosomes at wound locations, ultimately enhancing the exosomes' uptake efficiency by target cells. Most importantly, hyBMSC-Exos loaded hydrogel shows an excellent ability to promote diabetic wound healing by regulating macrophage polarization toward M2 phenotype. This may be because exosomal miR-4645-5p and antioxidant property of the hydrogel synergistically inhibit SREBP2 activity in macrophages. This study presents a productive approach for managing diabetic wounds.

Detection and analysis of angiogenesis pathway­associated lncRNA expression profiles in human skin fibroblasts under high­glucose conditions.

Accumulating evidence has indicated that long non­coding RNAs (lncRNAs) have crucial roles in wound healing and that vascular lesions in diabetic wounds are frequently difficult to heal. However, the role of angiogenesis pathway­associated lncRNAs in wound healing in diabetic patients has remained to be fully elucidated. In the present study, human skin fibroblasts were cultured under high­glucose conditions in vitro to mimic a diabetic environment and the angiogenesis pathway­associated lncRNA expression profile in the high­ and normal­glucose groups was examined. The microarray data indicated that 14 lncRNAs and 22 mRNAs were differentially expressed. Several candidate lncRNAs and mRNAs were then analyzed by reverse transcription­quantitative PCR and the results were consistent with the microarray data. Furthermore, the University of California Santa Cruz Genome Browser was used to identify mRNAs linked to angiogenesis pathways near the transcriptional region of lncRNAs. The results suggested that lncRNAs RP4­791C19.1 and CTD­2589O24.1 may act on their target genes epidermal growth factor receptor and p21 (RAC1) activated kinase 1, respectively, as enhancers and cis­regulate their expression. Therefore, the present study confirmed that several angiogenesis pathway­associated lncRNAs were differentially expressed under high­glucose conditions, which may have a key role in wound healing in patients with diabetes.

Impact of inclusive leadership on employee innovative behavior: Perceived organizational support as a mediator.

Despite extensive literature on leadership and its impact employee innovative behavior, few studies have explored the relationship between inclusive leadership and employee innovative behavior. To address this gap, this study aimed to investigate how inclusive leadership influenced employee innovative behavior by examining perceived organizational support (POS) as a mediator. We used multi-wave and multi-source data collected at 15 companies in China to test our theoretical model. Results revealed that inclusive leadership had significantly positive effects on POS and employee innovative behavior. Furthermore, POS was positively related to employee innovative behavior and partially mediated the relationship between inclusive leadership and employee innovative behavior. We discussed implications and limitations of this study as well as avenues for future research.

Differential miRNA expression profiles in human keratinocytes in response to protein kinase C inhibitor.

Aberrant expression of microRNAs (miRNAs) is widely accepted to be involved in keratinocyte differentiation and to be dependent on activation of the protein kinase C (PKC) pathway. However, the miRNA profiles and biological characteristics of keratinocytes induced by specific inhibitors of PKC have yet to be elucidated. The present study aimed to explore the differential miRNA expression profiles in keratinocytes treated with the PKC inhibitor GF109203X, by conducting a bioinformatics analysis. Parts of the GF109203X­induced keratinocytes formed distinct clones after 2 days of culture, and the expression of intergrin ß1, cytokeratin (CK)19 and CK14 were positive, whereas CK10 expression was negative. A total of 79 miRNAs were differentially expressed in keratinocytes treated with GF109203X, among which 45 miRNAs were upregulated and 34 were downregulated. The significantly upregulated microRNAs includedhsa­miR­1­3p and miR­181c­5p, whereas hsa­miR­31­5p and hsa­let­7c­3p were significantly downregulated. In addition, the results of reverse transcription­quantitative polymerase chain reaction exhibited consistency with the microarray results. An enrichment analysis demonstrated that certain target genes of the differentially expressed miRNAs serve an important role in cell proliferation and differentiation, cell cycle progression and apoptosis, etc. These results revealed that GF109203X induced the differential expression of certain miRNAs when keratinocytes began showing the characteristics of epidermal­like stem cells, which may provide a novel approach for wound healing and regeneration of skin tissues.

[Screening and bioinformatics analysis of differentially expressed genes in hyperplastic scar].

OBJECTIVE: To screen differentially expressed genes in hyperplastic scar to explore the pathogenesis of hyperplastic scar and identify new therapeutic targets. METHODS: Three pairs of surgical specimens of hyperplastic scar and adjacent normal skin tissues were collected to investigate the differentially expressed genes in hyperplastic scar using Agilent gene oligonucletide microarray and clustering analysis. DAVID Bioinformatics Resources 6.7 was used for GO analysis and pathway analysis. RESULTS AND CONCLUSION: Distinctly different gene expression profiles were found between hyperplastic scar tissues and normal skin tissues. Compared with normal skin tissue, hyperplastic scar tissues showed 3142 up-regulated and 2984 down-regulated genes by two folds and 28 up-regulated and 44 down-regulated genes by 5 folds after repeating the experiment once; after repeating the experiment twice, 3004 genes were found up-regulated and 3038 down-regulated by 2 folds and 25 up-regulated and 38 down-regulated by 5 folds in hyperplastic scars. In all the 3 specimens, 1920 genes were up-regulated and 1912 down-regulated by 2 folds and 18 up-regulated and 29 down-regulated by 5 folds. The dysregulated genes in hyperplastic scar were involved in cell cycles, cell proliferation, immune response and cell adhesion (CDKN1C, CDKN2A, CTNNA3, COL6A3, and HOXB4) and in signaling pathway of focal adhesion, TGF-beta signaling pathway, p53 signaling pathway, cell cycle, and tumor-associated pathways (TGFß1, CDKN1C, CDKN2A, CDC14A , ITGB6, and EGF).

Congenital arhinia: A rare case.

PATIENT: Male, 4 months FINAL DIAGNOSIS: Congenital arhynia Symptoms: Absence of the nose Medication: - Clinical Procedure: - Specialty: Pediatrics and Noenatology • Genetics. OBJECTIVE: Congenital defects. BACKGROUND: Congenital nasal absence (arhinia) is an extremely rare malformation. Arhinia causes severe airway obstruction and poor feeding in the affected neonate. There is an association with other facial anomalies, especially defects of the eyes, ears, palate, and midline defects. CASE REPORT: A full-term boy was born via an uncomplicated vaginal delivery. The mother was 40 years old and had a normal pregnancy. The mother had 4 previous uncomplicated pregnancies. There was no history of drug use during pregnancy. CONCLUSIONS: Congenital arhinia is a rare defect of embryogenesis, often associated with other anomalies that significantly influence the immediate and long-term outcomes of the neonate. It is a potentially life-threatening condition and requires the presence of a highly skilled neonatal resuscitation team at the time of delivery. Parental counseling is vital and a multidisciplinary team approach is required to optimize neonatal outcome.

[Expression of microRNA-203 and P63 in human epidermal stem cells and keratinocytes].

OBJECTIVE: To observe the changes in expression of microRNA-203 and P63 in human epidermal stem cells and KCs, and to investigate their effects and significance in the epidermal proliferation and differentiation. METHODS: (1) Five normal foreskin tissue specimens were collected from 5 patients by circumcision in Department of Urinary Surgery of the First Affiliated Hospital of Nanchang University from March to June in 2013. Then single cell suspension was obtained by separating epidermis with trypsin digestion method. The cells were divided into quick adherent cells and non-quick adherent cells by type IV collagen differential adherent method. The biological characteristics of cells were observed by inverted phase contrast microscope immediately after isolation and on post culture day (PCD) 3. The expression of CD29, keratin 19, keratin 1, and keratin 10 was identified by immunocytochemical staining. The expression of microRNA-203 and mRNA of P63 was determined by real-time fluorescent quantitative RT-PCR. The protein expression of P63 was determined by Western blotting. Data were processed with t test and Pearson correlation analysis. RESULTS: (1) Immediately after isolation, quick adherent cells were small, round, and dispersed uniformly. On PCD 3, the cells adhered firmly, and they grew in clones. Immediately after isolation, non-quick adherent cells appeared in different shapes and sizes, and dispersed unevenly. On PCD 3, the cells adhered precariously and did not show clonal growth. Quick adherent cells showed positive expression of CD29 and keratin 19, while non-quick adherent cells showed positive expression of keratin 1 and keratin 10. Quick adherent cells were identified as epidermal stem cells, and non-quick adherent cells were identified as KCs. (2)The expression level of microRNA-203 in epidermal stem cells (0.74 ± 0.20) was lower than that in KCs (3.66 ± 0.34, t =16.582, P <0.001). The mRNA expression level of P63 in epidermal stem cells (4. 16 ± 0.28) was higher than that in KCs (2.90 ± 0.39, t =5. 850, P =0.001). The protein expression level of P63 in epidermal stem cells (1.42 ± 0.05) was higher than that in KCs (0.73 ± 0.03, t =26.460, P <0. 001). (3) The expression level of microRNA-203 was in significantly negative correlation with the expression levels of mRNA and protein of P63 (with r values respectively - 0. 94 and -0.98 , P values below 0.05). CONCLUSIONS: The expression levels of microRNA-203 and P63 in human epidermal stem cells and KCs were significantly different, which might be related to the different characteristics of proliferation and differentiation of the cells.