A Novel High-Throughput Screening Platform Identifies Itaconate Derivatives from Marine Penicillium antarcticum as Inhibitors of Mesenchymal Stem Cell Differentiation.

Worldwide diffused diseases such as osteoarthritis, atherosclerosis or chronic kidney disease are associated with a tissue calcification process which may involve unexpected local stem cell differentiation. Current pharmacological treatments for such musculoskeletal conditions are weakly effective, sometimes extremely expensive and often absent. The potential to develop new therapies is represented by the discovery of small molecules modulating resident progenitor cell differentiation to prevent aberrant tissue calcification. The marine environment is a rich reserve of compounds with pharmaceutical potential and many novel molecules are isolated from macro and microorganisms annually. The potential of small molecules synthetized by marine filamentous fungi to influence the osteogenic and chondrogenic differentiation of human mesenchymal stem/stromal cells (hMSCs) was investigated using a novel, high-throughput automated screening platform. Metabolites synthetized by the marine-derived fungus Penicillium antarcticum were evaluated on the platform. Itaconic acid derivatives were identified as inhibitors of calcium elaboration into the matrix of osteogenically differentiated hMSCs and also inhibited hMSC chondrogenic differentiation, highlighting their capacity to impair ectopic calcification. Bioactive small molecule discovery is critical to address ectopic tissue calcification and the use of biologically relevant assays to identify naturally occurring metabolites from marine sources represents a strategy that can contribute to this effort.

Gender Based Differences in Risk Factor Profile and Coronary Angiography of Patients Presenting with Acute Myocardial Infarction in North Indian Population.

INTRODUCTION: Coronary Artery Disease (CAD) among women presents atypically with atypical chest pain, neck pain, nausea, fatigue and dyspnoea. Co-existing co-morbidities such as Diabetes Mellitus (DM) and hypertension along with difference in risk factor prevalence makes it necessary to have a gender specific approach. AIM: To study gender specific differences in diagnosing and treating Acute Myocardial Infarction (AMI) in North Indian population. MATERIALS AND METHODS: Fifty consecutive men and women presenting with AMI were studied. A detailed history including symptoms, history of DM, hypertension, smoking and dyslipidaemia was obtained. ECG, evaluation of cardiac enzymes (CPK-MB, Troponin I), RBS, lipid profile, two dimensional transthoracic echocardiography and coronary angiography were performed. The data was statistically analysed. RESULTS: Among 100 patients (50 males and females each), we found a later age at presentation (62 y vs 56.5 y) and higher prevalence of diabetes (52% vs 24%, p=0.004) and hypertension (46% vs 28%) among females but more dyslipidaemia (34% vs 26%), smoking (44% vs 0%, p=0.0) and higher BMI (25.58 vs 23.74, p=0.019) among males. More females presented with atypical symptoms (16% vs 6%) and were detected to have insignificant CAD (14% vs 2%) than males. CONCLUSION: North Indian women with presentation at a later age, with atypical symptoms, more incidences of risk factors such as diabetes and hypertension along with lesser dyslipidaemia and BMI than males need a higher index of suspicion while evaluating them for CAD. Misdiagnosis is more likely because of atypical presentation. A milder disease on angiography and a lower incidence of multiple vessel disease is a common finding. We recommend more and larger Indian studies to acquire more data so that this growing prevalence of CAD in women can be curbed.

Gersemiols A-C and Eunicellol A, Diterpenoids from the Arctic Soft Coral Gersemia fruticosa.

Three new diterpenes named gersemiols A-C (1-3) and a new eunicellane diterpene, eunicellol A (4), have been isolated together with the known sesquiterpene (+)-α-muurolene (5) from the Arctic soft coral Gersemia fruticosa. The name gersemiane was assigned to the rare and unnamed diterpene skeleton of compounds 1-3 corresponding to 4-isopropyl-1,5,8a-trimethyltetradecahydrophenanthrene. The chemical structures were elucidated on the basis of extensive spectroscopic analysis (HR-ESIMS, 1D and 2D NMR) as well as coupling constant calculations for the determination of the relative configurations. All compounds were tested for their antimicrobial activity against several bacteria and fungi and eunicellol A was found to exhibit moderate and selective antibacterial activity.