The Hemiscorpius lepturus scorpion is known as the most dangerous scorpion in the south and southwest regions of Iran. This scorpion can cause illness and even death in humans and animals. The purpose of this study was to investigate the metabolic and endocrine effects of different fractions of Hemiscorpius lepturus venom. For this purpose, scorpion venom was extracted by electric shock method and after separating the solution phase and activation of the venom by freeze drying method and with the help of column chromatography by Sephadex G-250 gel, 6 fractions were separated based on optical absorption at 280 nm. Then 72 male Wistar rats were divided into 8 equal groups including control (NS), crude venom (1000 µg/kg), fractions I (120 µg/kg), II (430 µg/kg), III (80µg/kg), IV (180 µg/kg), V (60 µg/kg) and VI (130 µg/kg) divided and according to the above amounts, respectively, with normal saline, crude venom and different fractions through intraperitoneal injection. After 1, 3, 24 and 72 hours, the concentration of glucose and the insulin, glucagon and cortisol were measured by elisa with specific rat kits. The results showed that the injection of crude venom and all fractions caused a significant increase in glucose compared to the control group. Also, a significant increase of cortisol and glucagon was observed after injection in crude venom and fractions II and VI. Also, the average insulin in the groups receiving crude venom and fractions II and VI showed a significant decrease. These findings showed that the injection of different fractions of Hemiscorpius lepturus scorpion venom can affect the metabolic process and cause changes in the metabolic processes by affecting the glucose regulating hormones. Identifying these effects, considering the wide effects of these hormones in metabolism, as well as the changes caused by the venom fractions, can help to identify the toxicity mechanisms as accurately as possible and also to adopt specific treatment methods in cases of scorpion stings. be helpful and useful.

Today, the attention of researchers is directed to natural sources to discover new anticancer drugs, so that more than 60% of existing anticancer drugs are of natural origin. Bioactive peptides from aquatic protein sources with multiple biological activities, including anticancer, are promising in this field. The present study was conducted with the aim of evaluating the cytotoxicity of hydrolyzed protein of Greater lizardfish on breast cancer cells. Greater lizardfish meat was hydrolyzed with enzymatic hydrolysis with alcalase and papain enzymes with ratios of 2 and 4% and during 90 and 180 minutes. Mouse breast cancer cell lines (4T1) were subjected to protein hydrolysate samples (1 mg/ml) and incubated for 48 and 72 hours, and then cytotoxicity was determined by MTT colorimetric test. The samples hydrolyzed with alcalase enzyme showed strong cytotoxicity in 48 hours (14.19 to 74.54%) and 72 hours (95.51 to 96.14%) incubation. The samples hydrolyzed with papain also showed moderate toxicity in 48-hour incubation (5.72 to 26.56%) and strong toxicity in 72-hour incubation (93.27 to 96.26%). The highest cytotoxicity in 48-hour incubation was observed by the sample hydrolyzed with alcalase at a concentration of 4% for 180 minutes (74.54%), but in 72-hour incubation, all samples showed cytotoxicity above 90%. The protein hydrolysate of Greater lizardfish inhibited the growth of breast cancer cells and probably with more research in the future, it can be used in cancer treatment.

2Background and purpose: Due to the absence of a conclusive cure for a severely painful mouth ulcer, the creation of a medication to regulate this ailment is greatly advantageous. Folinic acid is a derivative of 5-formyl tetrahydrofolic acid. Unlike folic acid (the synthetic form of folate), folinic acid is a form of folate found naturally in foods. Folinic acid can be converted to other active forms of folate in the body and has the activity of the complete vitamin folic acid. Since folinic acid has wound-healing effects, it may play an important role in accelerating the healing of aphthous wounds. By determining the optimal dose, folinic acid can be suggested as a recommended treatment option for people with oral ulcers such as aphthous wounds. The purpose of this study is to investigate the effect of folinic acid on the growth of gingival fibroblast cells as a treatment for mouth ulcers. Materials and methods: During this experimental study, human gingival fibroblast cell lines were cultured in sterile conditions in a DMEM culture medium of 10% bovine serum and 1% penicillin and tetracycline antibiotics at 37 degrees. These cells were exposed to different concentrations of folinic acid drug (5, 20, 25, 30, 40, 50, 80, 100 μM). The MTT method was used to evaluate cell viability and determine IC50 (inhibitory concentration). In this experiment, due to the uncertainty of its range of toxicity on cells, the relative toxicity was determined in a pilot phase and with few repetitions. Each concentration was repeated four times and incubated at different times (24, 48, and 72 hours). After the incubation time, the supernatant of each well was discarded and 100 μl of MTT solution was added to each well. After four hours of incubation, the supernatant was discarded and 100 μL of DMSO was added. Then, using an ELISA reader, the optical absorbance of each well was measured at a wavelength of 540-690 nm. Finally, IC50, which indicates the drug concentration necessary to inhibit 50% of cell growth, was calculated using the growth curve, and the results were analyzed using SPSS software version 19. Results: In this study, the effect of folinic acid cytotoxicity on human gingival fibroblast cell line (HGF1) in a cell culture medium was investigated three times in different concentrations. The results showed that 70% of the cells were still alive in 24 hours up to a concentration of 100 μM, which can indicate the effective use of this drug for the treatment of pest damage. In 48 hours, IC50= 1.78 μM was obtained, which indicates that in studies with a time limit of 48 hours, up to a dose of 80 μM of folinic acid can be used to use the therapeutic effects of this drug. In 72 hours, IC50 was calculated as 66.7 μM. Conclusion: These findings provide valuable information about the dose-response relationship and the impact of folic acid on HGF1 cells. It indicates that higher concentrations of folic acid are needed initially to achieve a significant reduction in cell growth, but with longer exposure, lower concentrations can be effective.

2Background and purpose: Among the different categories of antifungal drugs, azole antifungals have received more attention due to their broad spectrum, high potency, and acting on specific target enzyme. Fluconazole is one of these drugs that as a bis-triazole, was the first triazole drug to enter the market. New-generation antifungal drugs such as albaconazole and voriconazole have been designed by replacing one of the triazole rings of fluconazole with other heterocycles. Based on this strategy, in this research, a new derivative of fluconazole in which a triazole residue of fluconazole is replaced by 4-benzylpiperazine dithiocarbamate was synthesized and its effects were evaluated in vitro. Materials and methods: The desired final compound (6) was obtained from the reaction of two key intermediates, oxirane, and N-benzylpiperazine, in the presence of carbon disulfide and triethylamine in ethanol. To prepare the oxirane derivative, the reaction of a ketonic compound namely 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl) ethan-1-one with trimethylsulfoxonium iodide was used. On the other hand, for the synthesis of N-benzyl piperazine, benzyl chloride was refluxed with the excess of piperazine. It should be noted that the purification of the compounds was done with common methods of extraction and recrystallization and there is no need for chromatography. The structure of the final synthesized compound was confirmed by infrared (IR) nuclear magnetic resonance (NMR) and mass spectrometry (MS). The antifungal activity of the synthesized compound was investigated in comparison with fluconazole against several species of pathogenic fungi sensitive to fluconazole, including Candida albicans, Candida glabrata, Candida parapsilosis, Candida krusei, and Candida tropicalis, as well as fluconazole-resistant isolates, and the minimum inhibitory concentration (MIC) was determined in vitro by broth micro-dilution method. In addition, the hemolytic effect on red blood cells and cytotoxicity on HepG2 cells were investigated for this compound. The docking mode of the target compound with lanosterol 14α-demethylase (CYP51) enzyme was also studied. Results: Preliminary investigation of antifungal effects on ten fungi strains sensitive to fluconazole showed that the target compound with MIC values between 0.063 and 1 μg/ml has strong antifungal effects on C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis. In general, its antifungal activity was 4-64 times more than that of fluconazole. Also, the compound showed a good anti-Candida profile against fluconazole-resistant species. While the MIC values of fluconazole against C. albicans and C. krusei isolates were equal to or greater than 64 μg/ml, compound 6 effectively inhibited the growth of C. albicans and C. krusei resistant to fluconazole at concentrations of 8 or 16 μg/ml. The MIC value of this compound against C. parapsilosis was equal to 0.5 μg/ml. The results of in vitro hemolysis and cytotoxicity tests also showed that this compound is as safe for human cells as fluconazole. The docking study showed that the designed compound can interact more tightly with the lanosterol 14α-demethylase enzyme due to the presence of a benzylpiperazine dithiocarbamate scaffold in its structure. Conclusion: According to the obtained results, the compound synthesized in this study is a suitable candidate for conducting in vivo tests and other preclinical and pharmacokinetic tests to discover a new antifungal drug.

2Background and Objective: Heavy metals are regarded as serious contaminants due to their toxicity, persistence in natural conditions, and ability to enter and accumulate (bioaccumulation and biomagnification) in food chains. The aim of this study was to investigate the concentrations of the heavy metals Pb, Cd, Cu, Zn, Cr, Fe and Ni in surface agricultural soils of the Miandoab landfill area. Materials and Methods: In this study, 57 soil samples were collected from a depth of 0-20 cm. After preparing and digesting in the laboratory, the samples were analyzed using a inductively coupled plasma spectrometer (ICP-OES). The Ecological Risk Potential Index (EPRI), Earth Accumulation Index (Igeo), Principal Components Test (PCA) Pearson's Correlation, Cluster Analysis, and One-T-test were utilized. Statistical processing was conducted using SPSS software. Results: According to the results of the single T-test, the average concentrations of Pb, Cd, Cu, Zn, Cr, Ni did not significantly differ from their background concentration in the soil (p≥0. 05). A significant difference was pbserved only for Fe (p<0. 05), indicating a geological origin for this element. The EPRI was within the low-risk range, with an average value of 46. 95. PCA revealed that the first factor was positively associated with Cr, Pb and Fe,the second factor with Zn and Cu,and the third factor with Cd. Cluster analysis showed that Fe was predominantly influenced by natural resources. According to the land accumulation index, all metals, except Cu, were classified non-polluted or slightly polluted at stations 2 and 4. Conclusion: The origin of elements is related to both natural and human factors. Specifically, Cr, Pb and Cd are more likely to originate from man-made sources, while Fe primarily comes from natural sources. The decrease in the concentration of metals can be attributed to continuous and annual ploughing, inactivity of the landfill, biological absorption by crops, soil leaching and transporting to lower depths