Objective: To determine spatial distribution of sand flies (Diptera: Psychodidae; Larroussius group), the vectors of visceral leishmaniasis in Ardabil province, Northwest of Iran. Methods: Sand flies were collected using sticky traps from the 30 selected points in Ardabil province, during May-November 2017. The MaxEnt model in GIS software was used for modeling. Results: A total of 2 794 specimens of sand flies were collected, of which 33% were Larroussius subgenus sand flies. Phlebotomus kandelakii and Phlebotomus wenyoni were the highest and lowest collected species respectively. Based on the modeling, four areas in the province were identified with more than 70% probability of the presence of Larroussius group vectors which were at risk of visceral leishmaniasis disease transmission. Conclusions: The distribution of Larroussius subgenus sand flies was observed in all parts of Ardabil. But the northern parts of the province (Germi and Bilesavar counties) as well as central part (Ardabil and Meshkinshahr counties) were of great importance in terms of the presence of Larroussius subgenus sand flies and the possibility of transmission of the visceral leishmaniasis.

Objective: To investigate the maturity development of miracidia in uterine eggs from four portions of the Opisthorchis viverrini uterus and environmental factors possibly affected in maturation and infectivity of distal part uterine eggs. Methods: Uteri of adult worms were divided into 4 equal parts. Development of eggs was determined under light microscope. Only embryonated eggs were used to evaluate the effects of physicochemical factors: temperature, salinity, acidity, ultraviolet A, B, C. Infection success was evaluated by feeding treated eggs to intermediate host snails and determining by using a PCR approach. Results: Eggs obtained from the uterus closest to the ovary (regions 1 and 2) failed to develop in vitro. Eggs from region 4 of the uterus (close to the genital pore) were used to study effects of physicochemical factors. The highest survival and infection success was in groups of eggs kept at 30 °C (95.20%). The calculated period of loss infection success (LI₅₀ and LI₉₅) on miracidia in distal uterine eggs by exposure to UV-A, UV-B and UV-C were 73 and 1 523 d; 8 and 20 d; 1 and 2 d, respectively. Lethal concentrations (LC₅₀ and LC₉₅) of salinity, HCl and NaOH on miracidia in distal uterine eggs were 45.43 and 120.09 ppt, 0.01 and 0.25 M; 0.01 and 0.11 M, respectively, after 24 h exposure. Conclusions: Opisthorchis viverrini eggs display a high tolerance to environmental conditions, especially after snail host eating for infection.

Objective: To identify mutually regulated proteins in PC-3 and DU145 androgen-independent prostate cancer cell lines treated with 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17), and to study the molecular pathways that contributed to the anticancer activity of MS17. Methods: PC-3 and DU145 cells were treated with 3 × EC₅₀ (15 μM) concentration of MS17 for 24 h and were subjected to protein expression profiling using two-dimensional gel electrophoresis and protein identification by mass spectrometry. Selected differentially expressed proteins with significant P-value of P<0.05 and fold change over 1.5-folds were filtered through and ontologically classified. Mutually regulated proteins were ranked by fold change and identified as common protein targets of MS17. Results: Profiling data revealed that, the mutually down-regulated proteins included ACTB and ACTG associated with structural molecule activity, ACTN1 with cell cycle, ACTN4 with cell migration, HNRPK with apoptosis, PLST with morphogenesis and TERA with proteolysis. However, the expressions of CH60 and HS71A respectively associated with response to unfolded protein demonstrated opposing regulation in PC-3 and DU145 cells. Pathway analysis of the differentially expressed proteins in PC-3 cells demonstrated the modulation of top pathways associated with cell-cell adhesion and cytoskeletal organization while in DU145 cells the pathways were associated with proteosomal degradation, regulation of electrolytes and water, regulation control of germ cells and organization of filament assembly/disassembly. Conclusions: The findings of the present study provide an understanding on the anti-tumorigenic activity of MS17 at the proteome level and warrant further research for its potential application for the management and treatment of androgen-independent prostate cancer.

Objective: To assess the safety and efficacy of herbal formulation rich in standardized fenugreek seed extract (IND-2) add-on therapy in type 2 diabetes mellitus (T2DM) patients who were on insulin treatment in prospective, single arm, open-label, uncontrolled, multicentre trial. Methods: T2DM patients (n=30) with aged 18-80 years who were stabilized on insulin treatment with fasting blood sugar (FBS) level between 100-140 mg/dL received IND-2 capsules (700 mg, thrice a day) for 16 weeks. The primary endpoints were an assessment of FBS at week 2, 4, 6, 8, 12 and 16. Secondary end-points include post-prandial blood sugar level, glycosylated Hb (HbA1c), reduction in the dose of insulin and number of hypoglycemic attacks, and improvement in lipid profile at various weeks. Safety and adverse events (AEs) were also assessed during the study. Results: Study was completed in twenty T2DM patients, and there was no significant reduction in FBS and post-prandial blood sugar level after addon therapy of IND-2. However, add-on therapy of IND-2 significantly reduced (P<0.01) the HbA1c values, requirements of insulin and hypoglycemic events as compared with baseline. Total cholesterol, high-density lipoproteins-cholesterol, and low-density lipoprotein-cholesterol levels were significantly increased (P<0.01) after IND-2 add-on therapy. Body weight and safety outcomes did not differ significantly in IND-2 add-on therapy group at week 16. Additionally, add-on therapy of IND-2 did not produce any serious adverse events. Conclusions: The results of present investigation suggest that add-on therapy of IND-2 with insulin in T2DM patients improves glycaemic control through a decrease in levels of HbA1c and number of insulin doses needed per day without an increase in body weight and risk of hypoglycemia. Thus, IND-2 may provide a safe and well-tolerated add-on therapy option for the management of T2DM.

Objective: To evaluate the anticancer activity of crude acetone and water leaf extracts of Tulbaghia violacea on a human oral cancer cell line (KB). Methods: The antioxidant activity of the leaf extracts was evaluated by using the DPPH assay while the anti-proliferative activity was assessed by using the MTT assay. The morphological characteristics of apoptotic cells were examined by using the dual acridine orange/ethidium bromide staining. Flow cytometry was used to evaluate the induction of multi-caspase activity and changes in the cell cycle. Results: The acetone and water extracts exhibited antioxidant activity in a concentration dependent manner. The extracts inhibited the growth of the KB cell line with IC₅₀ values of 0.2 mg/mL and 1 mg/mL, respectively for acetone and water. Morphological changes such as cell shrinkage, rounding and formation of membrane blebs were observed in the treated cells. In acridine orange/ethidium bromide staining, the number of apoptotic cells increased as the concentration of the extracts increased. The activation of multi-caspase activity in KB cells treated with Tulbaghia violacea extracts was concentration dependent, leading to cell death by apoptosis and cell cycle arrest at the G₂/M phase. Conclusions: The acetone and water extracts of Tulbaghia violacea appear to have anti-cancer activity against human oral cancer cells and need to be investigated further.

Objective: To evaluate the structural and chemical composition of plant and the antioxidant and antimicrobial activities promoted by hexanic, ethanolic and ethyl acetate fractions obtained from leaves of Conocarpus erectus. Methods: Organic fractions were characterized through UPLC-MS and GC-MS. Antioxidant potential was performed through DPPH and molybdenum phosphate techniques. Antibacterial and antifungal assays were performed in accordance with Clinical and Laboratory Standards Institute protocols. Results: The obtained biomass of Conocarpus erectus leaves showed the high presence of glucose (0.45 g/L), cellulose (28.69%), Na (55.126 μg/L) and K (31.163 μg/L). We identified seven compounds in the hexanic and ethyl acetate fractions, and eight compounds in ethanolic fraction. Moreover, phenolic compounds are prevalent in all organic fractions with values of (10.04 ± 0.24), (221.26 ± 1.84), (340.53 ± 0.84) mg/g GAE to hexanic, ethyl acetate and ethanolic fraction, respectively. Antioxidant results showed a high potential in ethyl acetate fraction (71.82 ± 6.87)% and (10.89 ± 0.05)% in DPPH and molybdenum phosphate techniques, respectively. The ethanolic fraction showed moderate bacteriostatic and bactericidal activity against Staphylococcus aureus and presented a high fungistatic potential for all Candida species tested. Conclusions: Organic fractions obtained from leaves of Conocarpus erectus present antimicrobial and antioxidant properties, and these findings contribute to scientific information for the effectiveness on use of this plant in the development of a phytotherapic compound.