Breast cancer is considered as one of the most aggressive types of cancer. Acquired therapeutic resistance is the major cause of chemotherapy failure in breast cancer patients. To overcome this resistance and to improve the efficacy of treatment, drug combination is employed as a promising approach for this purpose. The synergistic cytotoxic, apoptosis inducing, and cell cycle effects of the combination of LY294002 (LY), a phosphatidylinositide-3-kinase (PI3K) inhibitor, with the traditional cytotoxic anti-estrogen drug tamoxifen (TAM) in breast cancer cells (MCF-7) were investigated. LY and TAM exhibited potent cytotoxic effect on MCF-7 cells with IC₅₀ values 0.87 µM and 1.02 µM. The combination of non-toxic concentration of LY and TAM showed highly significant synergistic interaction as observed from isobologram (IC₅₀: 0.17 µM, combination index: 0.18, colony formation: 9.01%) compared to untreated control. The percentage of early/late apoptosis significantly increased after treatment of MCF-7 cells with LY and TAM combination: 40.3%/28.3% (p < 0.001), compared to LY single treatment (19.8%/11.4%) and TAM single treatment (32.4%/5.9%). In addition, LY and TAM combination induced the apoptotic genes Caspase-3, Caspase-7, and p53, as well as p21 as cell cycle promotor, and significantly downregulated the anti-apoptotic genes Bcl-2 and survivin. The cell cycle assay revealed that the combination induced apoptosis by increasing the pre-G₁: 28.3% compared to 1.6% of control. pAKT and Cyclin D1 protein expressions were significantly more downregulated by the combination treatment compared to the single drug treatment. The results suggested that the synergistic cytotoxic effect of LY and TAM is achieved by the induction of apoptosis and cell cycle arrest through cyclin D1, pAKT, caspases, and Bcl-2 signaling pathways.

Background: Vitamin D (VD) deficiency is associated with insulin function and secretion. It is linked with diabetes mellitus (DM) progression, and complications were also recorded. Therefore, the current study aimed to investigate serum VD level in Type 2 DM (T2DM) patients and its association with diabetic nephropathy and cardiovascular diseases (CVD). Materials and Methods: In this cross-sectional study, 205 patients with Type 2 diabetes age ranged from 39 to 75 years old were enrolled. Serum VD, high-sensitivity C-reactive protein (hs-CRP), and hemoglobin A1c (HbA1c) were measured. In addition, urinary albumin:creatinine ratio (ACR) was estimated. Results: Patients with Type 2 diabetes had a 78.5% VD level <30 ng/m. ACR and hs-CRP levels were significantly increased in patients with diabetes with VD <30 ng/m (P = 0.011 and P = 0.008, respectively). Female had significantly lower VD level than male P < 0.001. Patients exposed to sunlight had significantly higher VD level and lower hs-CRP levels compared with less-exposed, P value (0.001 and <0.001), respectively. Exercise significantly increased VD and decreased ACR levels in DM patients, P value (0.046 and 0.002), respectively. VD was positively associated with age (r = 0.355 P = 0.040) and negatively correlate with BMI (r = −0.502 P = 0.009), duration of disease (r = −0.498 P = 0.003), ACR (r = −0.384 P = 0.015), and HbA1c (r = −0.327 P = 0.032). Conclusion: The evidence from this study suggest that patients with Type 2 diabetes with VD deficiency are at higher risk for developing CVD and nephropathy.

Acetyleugenol is a phytochemical compound with broad effects against infectious diseases and tumors. Here, we extracted, characterized, and elucidated the structure of acetyeugenol, for the first time, from the leaves of Acacia nilotica (L.)—a well-known medicinal plant. The broad antibacterial potential of acetyleugenol was first confirmed against seven bacterial clinical isolates, which reveal a strong activity against Proteus sp., Salmonella typhi, Staphylococcus aureus, and Streptococcus pneumonia with similar or better zone of inhibition comparing to that of the control amoxicillin. To further investigate its effect against Mycobacterium tuberculosis, acetyleugenol and its indole and phenyl analogues were subjected to molecular docking experiments against two potential tuberculosis drug targets—MtPknE and MtPknB Ser/Thr protein kinases. The results reveal that all of the analogs have improved docking scores compared to the acetyleugenol. The indole analogues EUG-1 and EUG-3 were more effective with better docking scores for MtPknE with −11.08 and −10.05 kcal/mol, respectively. Similar results were obtained for the MtPknB. In contrast, only the EUG-2 phenyl analogue has given rise to similar docking scores for both targets. This opens the door for further comprehensive studies on these acetyleugenol analogues with in vitro and in vivo experiments to validate and get more insights into their mechanisms of action.

Diabetes mellitus (DM) and thyroid dysfunction (TD) are the two most common endocrine disorders in clinical practice. The study aim to find out the prevalence of thyroid disorders in type 2 diabetes mellitus patients. In a cross-sectional study 369 diagnosed type 2 DM patients, of which 203 are males and 166 are females, age reneged from (18 to 73) were enrolled, from July 2016 to July 2016. Their demographic data were obtained by through a questionnaire. Serum FT3, FT4, TSH and thyroid Antibodies (Tg-Ab, AM-Ab and TR-Ab) were measured using TOSOH, ELISA and enzymatic methods respectively. Out the 369 type 2 DM patients, of whom 9.5% are thyroid disorders, 2.3% have hypothyroidism, 5.0% subclinical hypothyroidism and 2.2% hyperthyroidism. Thyroid disorders are more common in female’s 16.5:1 fold. Compared with the control group, hypothyroid and subclinical hypothyroid DM patients have significant increase in TSH while significant decreases were observed in FT3 and FT4. TSH was significantly lower while FT3 and FT4 were significantly higher in hyperthyroidism DM patients. Moreover 23.3% of hypothyroidism has positive Tg-Ab, 23.3% has AM-Ab and 100% of hyperthyroidism has positive TR-Ab. The data suggested that, the prevalence of thyroid diseases is common in type 2 DM Libyan patients. Autoantibodies are the main causes of thyroid dysfunction, therefore, could predict and increase risk of thyroid disease, especially in females.

Objective. To investigate the antioxidant and hepatoprotective effects of ethanolic Mangifera indica (M. indica) seed extract on carbon tetrachloride (CCl₄)‐induced hepatotoxicity in albino rats. Methods. Forty‐eight albino rats weighing (100–150 g) were used for hepatoprotective and toxicity experiments. Antioxidant activity was determined using the 2, 2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay. The toxicity of M. indica seeds on the liver was evaluated by examining wellness parameters, body weight, and liver histological sections. The protective effects of 50 mg/kg and 100 mg/kg of seed extract on CCl₄‐induced hepatotoxicity were investigated by evaluating hematological, renal, and liver function parameters, body weight, and liver histological sections. Results. The antioxidant activity of the M. indica ethanolic extract was (92 ± 0.03 RSA %) compared with (91 ± 0.01 RSA %) of propyl gallate, and the IC₅₀ was (8.3 ± 0.01 µg/ml) and (14.1 ± 0.01 µg/ml). No changes were observed in the health indicators, body weights, and liver histological sections following oral administration of 50 mg/kg and 100 mg/kg of M. indica seed extracts. Treatment with M. indica seed extract significantly reduced alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), blood sugar, and urea levels compared with those in the CCl₄‐treated group. Conclusion. The IC₅₀ of the M. indica ethanolic extract was 8.3 µg/ml, and the M. indica extract is a potential source of natural antioxidants that protect against CCl₄‐induced hepatotoxicity.