Biomarkers for Impending Risk of Osteoporosis in Premenopausal Women.

OBJECTIVE: To compare 'cytokines' and 'bone turnover markers' in pre- and post-menopausal women and identify their relationship with bone mineral density (BMD) in both groups.  Study Design: A cross-sectional study. PLACE AND DURATION OF STUDY: Department of Biological & Biomedical Sciences, The Aga Khan University, Karachi, Pakistan, from June 2017 to August 2019. METHODOLOGY: Groups comprised of healthy premenopausal and postmenopausal women from the general population belonging to different ethnic groups and socio-economic status. Serum cytokines and bone turnover markers were assessed by solid-phase immunoassays, BMD (gm /cm2)] measurement was performed by dual-energy X-ray absorptiometry at the hip, lumbar spine, and proximal femur. Results were interpreted as a sum of T scores calculated by BMD of the above-mentioned sites. RESULTS: Cytokines and bone turnover markers were significantly high in post-menopausal women (p<0.001). A negative correlation (r = 0.32) of TNF α with BMD (total T scores) observed in premenopausal women was found to be significant, however, no significant association of BMD was detected in post-menopausal women. CONCLUSION: There is an increase in the production of cytokines and bone turnover markers after menopause. TNF-α follows this usual pattern of increase in post-menopausal women and can predict impending bone loss and osteopenia in premenopausal females. Therefore, estimation of this cytokine in pre-menopausal women can give a fair indication of a decline in BMD, bone health, and risk of future osteoporosis. Key Words: Bone mineral density, Cytokines, Bone turnover markers, Osteoporosis.

Endometriosis, infertility and MicroRNA's: A review.

The review aims to explore circulating small non- coding regulatory Ribonucleic Acids (miRNA) as biomarkers of endometriosis; a reproductive age group disorder. miRNA are linked with genetic, epigenetic and angiogenic factors, hormones, cytokines, chemokines, oxidative stress (OS) markers, mediators of inflammation, hypoxia, angiogenesis and altered immune system contributing to the pathogenesis of endometriosis. Hormonal imbalance occurs by decreased levels of miRNAs -23a and miRNAs -23b and increase in miRNAs -:135a, 135b, 29c and 194-3p. Angiogenesis by vascular endothelial growth factor is attributed to increased miRNAs -126, miRNAs -210, miRNAs -21, miRNAs -199a-5p and miRNAs 20A. OS upregulates miRNAs -302a by increased levels of Tumor Necrosis factor (TNF)-α, TNF- ß and Interleukin -1ß. Upregulation of miRNAs -199a and miRNAs -16 promotes inflammation and cell proliferation in the endometriotic lesions. The gold standard to diagnose endometriosis is laparoscopy, yet miRNA can be validated as diagnostic tool for detection, progression and prevention of endometriosis in large, independent cohorts of women, with and without endometriosis.

'Targeting the feast of a sleeping beast': Nutrient and mineral dependencies of encysted Acanthamoeba castellanii.

Acanthamoeba spp. cause a corneal infection, Acanthamoeba keratitis (AK), and a cerebral infection, granulomatous amoebic encephalitis (GAE). Though aggressive chemotherapy has been able to kill the active trophozoite form of Acanthamoeba, the encysted form of this parasite has remained problematic to resist physiological concentrations of drugs. The emergence of encysted amoeba into active trophozoite form poses a challenge to eradicate this parasite. Acanthamoeba trophozoites have active metabolic machinery that furnishes energy in the form of ATPs by subjecting carbohydrates and lipids to undergo pathways including glycolysis and beta-oxidation of free fatty acids, respectively. However, very little is known about the metabolic preferences and dependencies of an encysted trophozoite on minerals or potential nutrients that it consumes to live in an encysted state. Here, we investigate the metabolic and nutrient preferences of the encysted trophozoite of Acanthamoeba castellanii and the possibility to target them by drugs that act on calcium ion dependencies of the encysted amoeba. The experimental assays, immunostaining coupled with bioinformatics tools show that the encysted Acanthamoeba uses diverse nutrient pathways to obtain energy in the quiescent encysted state. These findings highlight potential pathways that can be targeted in eradicating amoebae cysts successfully.

Comparison of serum levels of vitamin D and vitamin D-binding protein in normal, osteopenic and osteoporotic postmenopausal women.

OBJECTIVE: To compare the serum levels of vitamin D, vitamin D binding protein (VDBP) calcium and phosphate in normal, osteopenic and osteoporotic postmenopausal women categorized on the basis of bone mineral density (BMD) scores. METHODS: A cross sectional study carried out from May 2017 to August 2018. BMD measured by Dual energy X-ray Absorptiometry categorized women (aged 20- 70 years) into normal (n=37) (T score ≥ -1.0) osteopenic (n=25) (-2.5< T score, < -1) and osteoporotic (n= 26) (T score < -2.5) according to WHO classification. Serum concentrations of vitamin D, VDBP, calcium, phosphate analyzed by enzyme linked immunosorbent assay were compared by Analysis of Variance. RESULTS: In normal females higher levels of vitamin D and VDBP were observed [15.82 (8 - 69.18), 469.9 (269.57 - 875.55)] vs. osteopenic [(7.45 (4.66 - 15.1), 296.05 (232.58 - 420.23)] and osteoporotic women [(7.25 (3.97 - 17.49), 272.94 (202.23 - 351.24)]; [median interquartile range]; p value < 0.0001. CONCLUSION: Vitamin D and VDBP are linked with bone health and estimation of VDBP appears to be a valuable tool for the assessment of increased bone loss and possible risks of bone fractures especially in postmenopausal women.