Jamil Zargan

The two types of bladder cancer, muscle invasive and non-muscle invasive (NMIBC), are among the most prevalent cancers worldwide. Despite this, even though muscle-invasive bladder cancer is more deadly, NMIBC requires more therapy due to a greater recurrence rate and more extended and expensive care. Immunotherapy, intravesical chemotherapy, cystoscopy, and transurethral resection (TUR) are among the treatments available. Crude scorpion venomand purified proteins and peptides, can suppress cancer metastasis in an in vitro or in vivo context, suppress cancer growth, halt the cell cycle, and cause cell apoptosis, according to an increasing number of experimental and preclinical studies. In this research, three novels discovered peptides (P2, P3 and P4. ProteomeXchange: PXD036231) from Buthotus saulcyi and, Odontobuthus doriae scorpions were used along with a peptide called pantinin (as a control). The phylogenetic tree showed that the peptides belong to Chaperonin HSP60, Chrysophsin2 and Pheromone-binding protein2, respectively. These peptides were docked with four known antigens, BAGE, BLCAP, PRAME and ROR1 related to bladder cancer and three bacterial antigens FliC, FliD and FimH to investigate their antimicrobial and anticancer properties. The results showed that peptides 2 and 3 have the best binding rate. The MD simulation results also confirmed the binding of peptides 2 and 3 to antigens. The penetration power of peptides 2 and 3 in the membrane of cancer cells and bacterial cells was also simulated, and the results of RMSD and PD confirmed it. QSAR suggests that peptides 2 and 3 can act as anti-cancer and anti-microbial peptides. Communicated by Ramaswamy H. Sarma

Background and Objectives In recent years the isolation of effective molecules from snake venom as drugto treatment of some incurable diseases is considered by many biological research centers. The aim ofthis investigation was to determine electrophorotic and chromatographic patterns of Pseudocerastespersicus venom and in-vitro study of bactericidal and anti-cancer properties of its fractions in humanhepatocellular liver carcinoma cell line (HepG2).Subjects and Methods The fractions of venom were isolated and collected using preparative RP-HPLC.The Bactericidal activity of fractions in 20μg/ml of protein concentration was investigated toward Gramnegativeand Gram-positive bacteria using MTT and MIC assays. Then, the cytotoxic effects of fractionswith higher antibacterial properties were measured by MTT reduction, neutral uptake and comet assaysfollowing exposure of HepG2 cancer cells to 20 and 40 μg/ml of protein concentration.Results SDS-PAGE pattern of the crude venom revealed 10 major bands with molecular weight rangingfrom 13.2 to 99.25 kDa and the separation of fractions from the venom by HPLC resulted in collectionof 11 different fractions. The results of this study showed that two fractions (4 & 8) have a significantantibacterial activity against Gram-positive as compared to Gram- negative bacteria. The study of theanti-cancer effect of these two fractions also showed that fraction 8 was more toxic in HepG2 cells.Conclusion We for the first time reported bactericidal and anti cancer effects of isolated fractions ofPersian horned viper venom. These properties make components of these fractions a favorable sourcefor isolation of molecule (s) with antibacterial and anti tumor activities.

We describe a new species of the genus Eryx Daudin, 1803 from southern Iran that is morphologically closely related to the Indian sand boa, E. johnii. The new species, Eryx sistanensis sp. nov. has a distribution range from Zabol in the Sistan Region to the southern parts of Sistan & Baluchistan, as well as Hormozgan Province of Iran. Morphologically, E. sistanensis sp. nov. differs from E. johnii by having fewer dorsal scale rows at midbody and the tail tip is not as blunt as E. johnii. The genetic distance (p-distance) between the new species and the Indian sand boa is considerable (9.1% for cytb and 11.8% for COI).

Scorpion venoms contain potentially useful pharmacological agents. Several studies demonstrate that the venoms of some scorpions induce apoptosis and inhibit the growth of cancer cells; therefore, they have been investigated for isolating anticancer components. In this study, antitumor effects of Hottentotta schach crude venom on MCF-7 (breast cancer cell line) as test group and Vero (African green monkey kidney normal cell line) as control group were analyzed. Cell toxicity was analyzed using MTT and neutral red (NR) uptake assays and apoptosis induction was analyzed using comet assay and caspase-3 activity. Oxidative stress following Hottentotta schach crude venom treatment was analyzed using nitrite oxide (NO) determination assay, reduced glutathione (GSH) and catalase enzyme activity assays. Results showed that crude venom (25-200 mu g/mL) induced apoptosis and inhibited the growth of MCF-7 and to a lesser extent in Vero cell lines. Nitrite oxide concentration increased while glutathione concentration and catalase enzyme activity were decreased in MCF-7 cells; however, results in Vero cells were reversed completely. It can be concluded that Hottentotta schach crude venom disturbs the oxidation and reduction potential in cancer cells and ultimately induce apoptosis. So this venom can be used as a good source for isolation and designing new anticancer drugs.

Viper venom contains antibacterial and cytotoxic components. The aim of this study was to identify and evaluate the antimicrobial and cytotoxic properties of the crude venom of Vipera latifii ( V. latifii ). Lyophilized venom of V. latifii was quantified by Bradford method and its antibacterial activity (6.25–400 μg/ml) was assessed using the MTT, MIC, Disc diffusion, and Well diffusion assays. Also, its cytotoxic activity was investigated using MTT reduction, Neutral uptake, and Comet assay on human liver cancer (HepG2) cell line. Crude venom showed antibacterial effects against Bacillus subtilis and Staphylococcus aureus , but was not effective on Escherichia coli . Also, the crude venom showed apoptotic and necrotic effects on human liver cancer cells. The venom of V. latifii can inhibit the growth of bacteria and cancer cells. These findings suggest that this may be a potential source of molecules with antibacterial and anticancer characteristics.

Transcriptional master regulators like Sox2 and Oct4, which are expressed in various human tumors, have been shown to cause tumor growth promotion as well as epithelial dysplasia by means of interfering with progenitor cell differentiation. In order to investigate the potential of Sox2‐Oct4 transcription factor decoy (TFD) strategy for differentiation therapy, mouse embryonic stem cells (mESCs) were used in this study as a model of cancer stem cells (CSCs). Sox2‐Oct4 complex decoy ODNs (cd‐ODNs) were designed according to their elements in the promoter region of Sox2 gene. DNA–protein interactions between decoy ODNs and their corresponding proteins were examined by electrophoretic mobility shift assay (EMSA). Then, decoy and scrambled ODNs were transfected into mESCs with lipofectamine under 2 inhibitors (2i) conditions. Fluorescence and confocal microscopy, cell viability, cell cycle and apoptosis analysis, alkaline phosphatase, embryoid body formation assay, and real‐time PCR were used to conduct further investigations. EMSA data showed that Sox2‐Oct4 decoy ODNs bound specifically to their recombinant proteins. The results revealed that the synthesized complex decoy can concomitantly target Sox2 and Oct4, which subsequently represses the stemness properties of mESCs compared to controls through decreasing cell viability, arresting cell cycle in G₀/G₁ phases, inducing apoptosis, and modulating differentiation in mESCs despite the presence of 2i/LIF in cell culture. While cd‐ODN strategy seems to offer great promise for cancer therapy, further studies are still required to put this powerful investigative tool in practice for a wide range of human cancers.

Introduction: Amid the plethora of methods to repair critical bone defects, there is no one perfect approach. In this study, we sought to evaluate a potent 3-dimensional (3D) bioactive SiO2-CaO-P2O5 glasses (bioglass)/gelatin (gel) scaffold for its biocompatibility by seeding cells as well as for its regenerative properties by animal implantation. Methods: Osteoblast cells were seeded onto nanocomposite scaffolds to investigate the process of critical-size calvarial defect via new bone formation. Scanning electron microscopy (SEM) was used to validate topography of the scaffolds, its homogeneity and ideal cellular attachment. Proliferation assay and confocal microscopy were used to evaluate its biocompatibility. To validate osteogenesis of the bioactive nanocomposite scaffolds, they were first implanted into rats and later removed and analyzed at different time points post mortem using histological, immunohistochemical and histomorphometric methods. Results: Based on in vitro results, we showed that our nanocomposite is highly cell-compatible material and allows for osteoblasts to adhere, spread and proliferate. In vivo results indicate that our nanocomposite provides a significant contribution to bone regeneration and is highly biodegradable and biocompatible. So, seeded scaffolds with osteoblasts enhanced repair of critical bone defects via osteogenesis. Conclusions: We demonstrate the feasibility of engineering a nanocomposite scaffold with an architecture resembling the human bone, and provide proof-of-concept validation for our scaffold using a rat animal model.