PPARγ deficiency results in severe, accelerated osteoarthritis associated with aberrant mTOR signalling in the articular cartilage

Objectives: We have previously shown that peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor, is essential for the normal growth and development of cartilage. In the present study, we created inducible cartilage-specific PPARγ knockout (KO) mice and subjected these mice to the destabilisation of medial meniscus (DMM) model of osteoarthritis (OA) to elucidate the specific in vivo role of PPARγ in OA pathophysiology. We further investigated the downstream PPARγ signalling pathway responsible for maintaining cartilage homeostasis. Methods: Inducible cartilage-specific PPARγ KO mice were generated and subjected to DMM model of OA. We also created inducible cartilage-specific PPARγ/mammalian target for rapamycin (mTOR) double KO mice to dissect the PPARγ signalling pathway in OA. Results: Compared with control mice, PPARγ KO mice exhibit accelerated OA phenotype with increased cartilage degradation, chondrocyte apoptosis, and the overproduction of OA inflammatory/catabolic factors associated with the increased expression of mTOR and the suppression of key autophagy markers. In vitro rescue experiments using PPARγ expression vector reduced mTOR expression, increased expression of autophagy markers and reduced the expression of OA inflammatory/catabolic factors, thus reversing the phenotype of PPARγ KO mice chondrocytes. To dissect the in vivo role of mTOR pathway in PPARγ signalling, we created and subjected PPARγ-mTOR double KO mice to the OA model to see if the genetic deletion of mTOR in PPARγ KO mice (double KO) can rescue the accelerated OA phenotype observed in PPARγ KO mice. Indeed, PPARγ-mTOR double KO mice exhibit significant protection/reversal from OA phenotype. Significance PPARγ maintains articular cartilage homeostasis, in part, by regulating mTOR pathway

Haplotype Analysis of Seven Non-Syndromeic Autosomal Recessive Hearing Loss Loci in Iranian Families

Objective: Hearing impairment is the most frequent sensorineural defect in 2 forms, syndromic and non–syndromic. The aim of this study is haplotype analysis of seven loci of non–syndromic autosomal recessive hearing loss in Iranian families. Materials & Methods: In this descriptive study, forty one Iranian families with 2 or more affected individuals segregating as an autosomal recessive non–syndromic hearing loss were selected simply and conveniently. The patients have been tested negative for the following loci, DFNB1, DFNB2, DFNB3, DFNB4, DFNB6, DFNB7/11, DFNB8/10, DFNB9, DFNB12, DFNB16, DFNB18, DFNB21, DFNB23, DFNB29 and DFNB4 previously. The subjects have been investigated additional 7 loci (DFNB22, DFNB28, DFNB30, DFNB31, DFNB36, DFNB37 and DFNB67) , to determine the prevalence of these genes involve in these loci. Homozygosity mapping was applied using number of STR (Short Tandem Repeat) markers. Results: Three families linked to the following loci DFNB28, DFNB30 and DFNB 31. Conclusion: In this research, the cause of additional 7% of non–syndromic hearing loss was determined in Iranian population

Complementary Therapies for Idiopathic Hirsutism: Topical Licorice as Promising Option

Hirsutism is one of the most prevalent health problems in women. The aim of the study was to compare the effect of 755 nm alexandrite hair removal laser with that of alexandrite laser plus topical licorice on the improvement of idiopathic hirsutism. A double-blind, randomized placebo-controlled study was performed on 90 female subjects. The patients were divided into two groups: alexandrite laser plus 15% licorice gel (group A) and placebo (group B). Each subject received one of both products over one side of the face, twice daily for 24 weeks on the hirsute locations. Each group underwent five sessions of alexandrite laser at 6-week intervals. To minimize the effects of confounding variables, the test was performed on two separate zones of patients’ skin. The mean ± SD numbers of terminal hairs in group A were 7.05 ± 4.55 for zone 1 and 6.06 ± 3.70 for zone 2. In group B, they were 3.18 ± 1.75 for zone 1 and 2.49 ± 1.63 for zone 2. The difference in the mean number of terminal hairs was statistically significant between the two groups (p<0.001), and there were no serious adverse reactions. The treatment of idiopathic hirsutism with 755 nm alexandrite laser plus topical licorice is more effective than alexandrite laser only