Shahid Sadoughi University of Medical Sciences and Health Services

Mucopolysaccharidosis type VI (MPS VI), also known as Manteaux-Lamy syndrome, is an autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme arylsulfatase B(ARSB). This syndrome is progressive and affects many tissues and organs, leading to inflammation and scarring. The classic clinical features of Maroteaux-Lamy syndrome are significant impairment of the osteoarticular system with dysostosis multiplex, short stature and motor dysfunction. The rate at which symptoms appear and worsen can vary between affected individuals. Mutations in the ARSB gene are responsible for MPS VI. We investigated the clinical presentation and molecular basis of patients with MPS VI for the first time in Yazd province, Iran.

Of the 52 people who took part in this project, there were 13 probands. Whole exome sequencing (WES) was performed in 2 of them and the nominated mutation in the ARSB (c.430G > A) was verified by Sanger sequencing in the remaining patients.

All patients had parental consanguinity, except for one family in which the parents were unrelated. All patients were of Fars ethnicity and had characteristic phenotypes such as severe short stature, cardiac involvement, coarse facial features, and corneal opacities. Sequence analysis of the ARSB gene revealed a pathogenic homozygous missense mutation c.430G > A (p. Gly144Arg) in all patients. This type of mutation influenced the phenotypes of the severe patients.

These results expand the genetic databases of Iranian patients with MPS VI and would be very helpful for the high-risk families to accelerate the detection of carriers and to perform prenatal testing for the disorder in this population in a cost-effective manner. There is a possibility that other unknown mutations are responsible for the disease. The decision to screen for and detect carriers of this disease at a national level is awaited. The results of the present study could be an asset for married families in part of the city of Meybod. The results offer a way for early detection of patients and carriers of the disease.

Cardiac fibrosis is a pathological condition marked by the excessive accumulation of extracellular matrix (ECM) components, which leads to impaired cardiac function and heart failure. Despite its significant contribution to cardiovascular morbidity and mortality, no effective therapeutic drugs specifically target the inhibition of cardiac fibrosis, largely due to the complex etiological heterogeneity and pathogenesis of this disease. Sirtuins (SIRTs), a family of NAD + -dependent deacetylases, play a critical role in cellular processes such as oxidative stress, inflammation, energy metabolism, mitochondrial function, epithelial-to-mesenchymal transition (EMT), and ECM homeostasis, all of which are implicated in cardiac fibrosis. Growing clinical and experimental evidence suggests that SIRTs regulate the cellular and molecular mechanisms of cardiomyocytes through various biological pathways. Emerging evidence indicates that sirtuin activators, including resveratrol and NAD + precursors, hold therapeutic potential in mitigating cardiac fibrosis. However, the complex and context-dependent roles of sirtuins necessitate further research to fully elucidate their mechanisms and translational applications. As the role of SIRTs in relation to cardiac fibrosis and its associated mechanisms is rarely discussed in the literature, this review comprehensively addresses the roles of the seven mammalian sirtuins (SIRT1-SIRT7) in the pathogenesis and progression of cardiac fibrosis. It highlights the key role of SIRTs as molecular targets for innovative anti-fibrotic therapies, offering new avenues for the treatment of cardiac fibrosis and associated cardiovascular diseases.

Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. Crocin is known as the main component of saffron, which has antioxidant properties and has the ability to scavenge free radicals. Considering the pathophysiology of PCOS and also the anti-inflammatory and antioxidant properties of crocin in improving insulin resistance, we aimed to evaluate the efficacy of the combination of crocin and metformin compared to metformin alone in PCOS patients.

This study is a prospective, double-blind randomized controlled clinical trial. Fifty patients with PCOS and hirsutism were included from Baqaipour Obstetrics and Gynecology Clinic in Yazd and randomly assigned into the two study arms of control group [metformin and placebo (n = 25)] or intervention group [metformin and crocin (n = 25)]. Patients were administered crocin 15 mg tablets once a day in combination with metformin 500 mg twice a day for 12 weeks to complete three full periods of the monthly cycle. The studied endpoints were evaluated at the beginning and end of the study.

Crocin significantly improved the serum level of follicle-stimulating hormone (FSH) (P = 0.048) and Ferriman- Gallwey score (P = 0.042) at day 90. Furthermore, crocin group had a significant improvement in terms of acne severity at the end of the study (P = 0.03), so that none of the patients in the crocin group had severe acne at the end of the study. However, the comparisons between two groups were not statistically significant for other evaluated outcomes including fasting blood sugar (FBS), dihydroepiandrosterone-sulfate (DHEA-S), luteinizing hormone (LH), dermatology life quality index (DLQI), and blood pressure (BP) at the end of the study.

In the present study, concurrent use of crocin along with metformin was significantly effective in ameliorating the unpleasant side effects of PCOS, including hirsutism and acne, and increasing FSH sex hormone levels in patients with PCOS.

26/08/2021, Trial Registry number: IRCT20210730052027N1.