Diabetes mellitus represents a major independent risk factor for developing fatal cardiovascular diseases (CVDs) presumably through accelerating atherosclerosis; the underlying cause of most CVDs. Notably, this relative risk is reported to be higher in women than men. Endeavors directed towards identifying novel reliable predictive biomarkers are immensely thereby urged to improve the long-term outcome in these diabetic female patients. Sclerostin (SOST) is a Wnt signaling antagonist whereas irisin is a muscle-derived factor released after exercising which enhances browning of white adipose tissue. Emerging lines of evidence hint at potential crosstalk between them and CVDs. The present study aimed to assess the serum levels of SOST and irisin in Egyptian type 2 diabetic (T2DM) female patients with and without atherosclerosis and explore the possible relationship between both markers and other studied parameters among the studied cohorts. In this case-control study, 69 female subjects were enrolled; 39 type 2 diabetes patients with atherosclerosis (T2DM+ATHR), 22 type 2 diabetes patients without atherosclerosis (T2DM-ATHR) and 8 healthy controls. Their serum levels of SOST and irisin were assessed using ELISA. Significant increase in SOST levels were found in T2DM+ATHR compared to T2DM-ATHR and control (259.9 ±17.98 vs. 165.8±13.12 and 142.0±13.31 pg/mL respectively, P<0.001). Conversely, irisin levels were significantly lower in T2DM+ATHR (P<0.001) and T2DM-ATHR (P<0.01) compared to the control group (32.91±2.545 and 58.55±13.19 vs. 473.6±112.7 pg/mL). Interestingly, significant correlations between the levels of SOST and both irisin and fasting blood glucose were noticed in T2DM+ATHR group (r = 0.3754 and 0.3381 respectively, P<0.05). In conclusion, to the best of our knowledge, this study is the first to demonstrate the correlation between SOST and irisin levels in atherosclerotic T2DM female patients implying their potential implication in diabetic cardiovascular pathophysiology and supporting their use as reliable diagnostic/prognostic biomarkers for monitoring and preventing CVDs progression of T2DM female patients.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used to treat malaria and autoimmune diseases for more than 70 years; they also have immunomodulatory and anticancer effects, which are linked to autophagy and autophagy-independent mechanisms. Herein, we review the pharmacokinetics, preclinical studies and clinical trials investigating the use of CQ and HCQ as adjuvant agents in cancer therapy. We also discuss their safety profile, drug–drug and drug–disease interactions. Systematic studies are required to define the use of CQ/HCQ and/or their analogues in cancer treatment and to identify predictive biomarkers of responder subpopulations.

Herbal medicine is used by millions of diabetic patients due to economic and cultural factors. The current study investigates the antidiabetic potential of fenugreek (Trigonella foenum-graecum) seed extract at a dose of 100 mg/kg in a Streptozocin-induced diabetic model. Male Sprague-Dawley rats received either intraperitoneal fenugreek [daily (ED) or every other day (EOD)] or oral fenugreek supplement daily, for four weeks. Results show that fenugreek significantly reduced blood glucose. Urea levels were reduced after daily intraperitoneal injection, and creatinine levels dropped after oral treatment, respectively. AST and ALT levels were reduced following fenugreek treatment, while protein levels significantly increased. High-density lipoprotein (HDL) increased after daily injections, while triglycerides decreased significantly in all groups. Glutathione S-transferase and catalase increased with treatment, while peroxidase antioxidant enzyme levels were reduced. Glutathione peroxidase levels increased only after daily injection. Histologically, fenugreek mildly protected hepatic, renal, and pancreatic tissues. In conclusion, the current study shows some potential benefits of fenugreek use. Oral and injectable fenugreek showed improvement in blood glucose, renal and liver functions. Although triglyceride levels decreased significantly, no significant changes in cholesterol levels were seen after fenugreek use. Higher doses and longer fenugreek treatment duration are recommended for the optimum protection of the liver, kidneys, and pancreatic tissues.

Lysine specific demethylase-1 (LSD1) has been shown to be critical in acute myeloid leukemia pathogenesis and this has led to the development of LSD1 inhibitors which are currently tested in clinical trials. Nonetheless, preclinical studies reported that acute myeloid leukemic cells frequently exhibit intrinsic resistance to LSD1 inhibition, and the molecular basis for this phenomenon is largely unknown. We explored the potential involvement of mammalian target of rapamycin (mTOR) in mediating the resistance of leukemic cells to LSD1 inhibitors. Strikingly, unlike sensitive leukemias, mTOR complex 1 (mTORC1) signaling was robustly triggered in resistant leukemias following LSD1 inhibition. Transcriptomic, chromatin immunoprecipitation and functional studies revealed that insulin receptor substrate 1/extracellular-signal regulated kinase signaling critically controls LSD1 inhibitor induced mTORC1 activation. Notably, inhibiting mTOR unlocked the resistance of acute myeloid leukemic cell lines and primary patient-derived blasts to LSD1 inhibitors both in vitro and in vivo. In conclusion, mTOR activation might act as a novel pro-survival mechanism of intrinsic as well as acquired resistance to LSD1 inhibitors, and combination regimens co-targeting LSD1/mTOR could represent a rational approach in acute myeloid leukemia therapy.