| 1 | Curcumin preconditioning enhances the efficacy of adipose-derived mesenchymal stem cells to accelerate healing of burn wounds显示文摘Background:Following recent findings from our group that curcumin preconditioning augments the therapeutic efficacy of adipose-derived stem cells in the healing of diabetic wounds in rats,we aimed to investigate the regenerative effects of curcumin preconditioned adipose-derived mesenchymal stem cells(ASCs)for better recovery of acid inflicted burns in this study.Methods:ASCs were preconditioned with 5μM curcumin for 24 hours and assessed for proliferation,migration,paracrine release potential and gene expression comparative to naive ASCs.Subsequently,the healing capacity of curcumin preconditioned ASCs(Cur-ASCs)versus naive ASCs was examined using acidic wounds in rats.For this,acid inflicted burns of 20 mm in diameter were made on the back of male Wistar rats.Then,2×10^(6) cells of Cur-ASCs and naive ASCs were intradermally injected in the wound periphery(n=6)for comparison with an untreated saline control.Post-transplantation,wounds were macroscopically analysed and photographed to evaluate the percentage of wound closure and period of re-epithelization.Healed wound biopsies were excised and used for histological evaluation and expression analysis of wound healing markers at molecular level by quantitative PCR and western blotting.Results:We found that Cur-ASCs exhibited greater proliferation,migration and paracrine potential in vitro.Further,Cur-ASCs showed more effective recovery than naive ASCs as exhibited by gross morphology,faster wound closure and earlier re-epithelialization.Masson’s trichrome and hematoxylin and eosin staining demonstrated the improved architecture of the healing burns,as evidenced by reduced infiltration of inflammatory cells,compact collagen and marked granulation in Cur-ASC treated rats.Corroborating these findings,molecular assessment showed significantly reduced expressions of pro-inflammatory factors(interleukin-1 beta,interleukin-6,tumor necrosis factor alpha)a with striking upsurge of an oxidative marker(superoxide dismutase 1),proangiogenic factors(vascular endothelial growth factor,hepatocyte growth factor,hypoxia-inducible factor-1 alpha)and collagen markers(transforming growth factor beta 1,fibroblast growth factor-2,collagen type 1 alpha 1),verifying that Cur-ASCs modulate the regulation of pro-inflammatory and healing markers at burn sites.Conclusions:Treatment with Cur-ASCs resulted in faster re-epithelization of acid inflicted burns compared to the treatment with naive ASCs.Based on observed findings,we suggest the transplantation of Cur-ASCs is a valuable therapy for the potent clinical management of acidic burns. | Maryam Azam Hafiz Ghufran Hira Butt Azra Mehmood Ramla Ashfaq Asad M.Ilyas Muhammad R.Ahmad Sheikh Riazuddin | 2021 | Burns & Trauma2021，9，1： | 2 |
| 4 | Two novel variants in CYP1B1 gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients显示文摘AIM: To find the CYP1 B1 mutations associated with primary congenital glaucoma(PCG) in Pakistani consanguineous pedigrees. METHODS: After getting informed consent, 11 consanguineous pedigrees belonging to different ethnic groups were enrolled. Detailed medical history was recorded and pedigrees were drawn. The standard ophthalmological examination was done to characterize the phenotype. Genomic DNA was extracted from 10 mL whole blood and coding exons and exon intron boundaries of CYP1 B1 gene were directly sequenced. Bioinformatics tools were used to model the mutant protein and predict the effect of novel variants on protein structure and function. RESULTS: Sequencing analysis revealed 5 different CYP1 B1 variants in 7 families(7/11; 64%), including two novel variants. A common mutation, p.R390 H was found in four families, whereas p.P437 L was found once in a family. Two novel variants, a homozygous non sense variant p.L13* and a compound heterozygous variant, p.P350 T along with p.V364 M were segregating with PCGin two families. All the patients had the variable onset and severity of the disease. The success rate of early clinical interventions was observed dependent on mutation types and position. Two different haplotypes were associated with frequently found mutation, p.R390 H. CONCLUSION: Identification of novel CYP1 B1 variants reassert the genetic heterogeneity of Pakistani PCG patients. The patients with missense mutations show severe phenotypic presentations and poor vision after surgical interventions as compare to patients with null variants. This may help to better understand the role of CYP1 B1 mutations in the development of PCG and its course of pathogenicity. | Yar Muhammad Waryah Muhammad Iqbal Shakeel Ahmed Sheikh Muhammad Azhar Baig Ashok Kumar Narsani Muhammad Atif Munir Ahmad Bhinder Attiq Ur Rahman Azam Iqbal Memon Muhammad Suleman Pirzado Ali Muhammad Waryah | 2019 | International Journal of Ophthalmology(English edition)2019，12，1： | 0 |
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