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Cancer is one of the deadliest diseases in many developed and developing countries. Continuous efforts are required for designing better therapeutic agents for the treatment of cancer with more efficacy, selectivity, and less toxicity. The fused heterocyclic ring system has been identified by several researchers as a privileged structure that can be used as a basis for drug discovery in medicinal chemistry. The hetero-aromatic bicyclic ring system acts as a pharmacophore in a wide range of drugs with therapeutic potential. According to studies in the literature, variously substituted benzimidazoles have distinct pharmacological profiles with multi-targeting ability, making them an important anchor for the production of novel therapeutic agents against complex cancers including breast cancer, skin cancer, and blood cancer. In this presented article we are discussed various synthetic methods for the synthesis of anticancer benzimidazoles and their derivatives in different solvent conditions, substrates, and various catalysts mainly those which are eco-friendly, and economical, which shows the anticancer activity. We also focused on various derivatives are under clinical trials containing Benzimidazole moiety.
Ferroptosis is caused by the iron-mediated accumulation of lipid peroxidation, which is distinct from apoptosis and necroptosis. Necrostatin-1 inhibits receptor-interacting ser-ine/threonine-protein kinase 1 (RIPK1) to initiate necroptosis; it also inhibits indoleamine 2,3-dioxygenase (IDO) to regulate tumor immunity. However, few studies have examined the off-target effect of necrostatin-1 on the ferroptosis pathway. The present study examined wheth-er necrostatin-1 could interrupt ferroptosis induced by system xc- inhibitors (sulfasalazine and erastin) and a glutathione peroxidase 4 inhibitor (RSL3) in Huh7 and SK-HEP-1 cells. Necrostatin-1 completely prevented decreases in cell viability induced by sulfasalazine and erastin; it partially blunted decreases in cell viability induced by RSL3. Necrostatin-1, ferrostatin-1, and deferoxamine repressed sulfasalazine-provoked membrane permeabilization, as detected by 7-aminoactinomycin D staining and lipid peroxidation measured using a C11-BODIPY probe. However, other RIPK1 inhibitors (necrostatin-1s and GSK2982772) and an IDO inhibitor (1-methyl-D-tryptophan) did not recover the decrease in cell viability induced by sulfasalazine. Necrostatin-1 potentiated sulfasalazine-induced expression of xCT, a catalytic subunit of system xc- in these cells. These results demonstrated that necrostatin-1 blocked fer-roptosis through a mechanism independent from RIPK1 and IDO inhibition in Huh7 and SK-HEP-1 cells, indicating that its antioxidant activity should be considered when using necrostatin-1 as a RIPK1 inhibitor.
Citation Format: Md Abdullah, Hanna Yuk, Do Hyung Kim, Haeseung Lee, Seung Jin Lee. Necrostatin-1 Protects Ferroptosis by xCT Induction in a RIPK1- and IDO-independent manner [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA034.
Fire hazards caused by leakages in gas circulation lines are dangerous and pose a threat that results in a significant loss of wealth, lives, and the environment. By adopting significant precautions, the risks of fire hazards can be reduced effectively through the use of new technologies and preventive measurements of the system. In addition, the effects of fire hazards due to leakage in gas circulation lines in the buildings as well as in the other systems can be assessed to create the context of preventive measures for a fire protection system in a way to overcome the fire hazards in gas circulation lines. The paper aims to review the effects of fire hazards due to leakage in gas circulation lines in Bangladesh. It is noted that in Bangladesh during 2018-2019, the total gas distribution line in the Titas gas system was measured as 13,138 km where the pressure-reducing system or gas riser was found as 1.2 million and the number of customers was found as 2.866 million. In the system, the number of fire accidents that occurred was 208 in the circulation system. Because of connecting the illegal gas lines and poor maintenance of the system, Bangladesh faces significant fire hazards every year. To avoid this kind of problem, proper maintenance along with the varieties of new technologies incorporating sensors and microcontrollers can be utilized.
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