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Objective: Endoplasmic reticulum-metallopeptidase 1 (ERMP1) is involved in cellular response to oxidative stress. However, its functional role in proliferation and progression of cancer cells remains unknown. The focus of this study was to investigate the molecular-mechanisms in which ERMP1 modulates the proliferation and progression of colorectal cancer (CRC) cells under normal and environment stress conditions. Materials and Methods: In this experimental study, ERMP1 expression was evaluated using reverse transcriptionquantitative polymerase chain reaction (RT-qPCR) in CRC cells. ERMP1 was knocked down using lentiviral transduction of ERMP1-specific shRNA into HCT116 cells. ERMP1 was also upregulated using lipofectamine transfection of ERMP1-overexpressing vector into SW48 cells. To evaluate the role of ERMP1 in the cellular and environmental stress conditions, ERMP1-downregulated cells were exposed to stressful conditions including starvation, serum free medium, and treatment with redox or chemotherapy agents for 72 hours. The expression of AKT, p-AKT, phospho-mammalian target of rapamycin (p-mTOR), β-catenin, p-β-catenin, E-cadherin, and Glucose-regulating protein 78 (GRP78) proteins was evaluated by western blotting. The expression of ERMP1, CYCLIN D, and c-MYC was evaluated by RT-qPCR. The cell surface localization of GRP78, cell cycle distribution, and apoptosis were determined by Flow cytometry. Results: ERMP1 knock-down reduced the cellular proliferation, inactivated the PI3K/AKT pathway, prompted the G1 arrest, and attenuated the free β-catenin and CYCLIN D expression. Opposite results were obtained in ERMP1- overexpressed cells. Knock-down of ERMP1 also reduced the GRP78 localization at the cell surface. Various environmental stress conditions differently affected the ERMP1-downregulated cells. Conclusion: ERMP1 functioned as an oncogene in CRC cells by promoting malignant characteristics. The phosphoinositide 3-kinases (PI3K)/AKT/β-catenin pathway and localization of GRP78 were closely related to the effects of ERMP1. Consequently, ERMP1 might be regarded as a promising target in therapeutic strategies related to CRC. [ABSTRACT FROM AUTHOR]

The occurrence of viral infections and approaches to handling them are very challenging and require prompt diagnosis and timely treatment. Recently, genomic medicine approaches have come up with the discovery of the competing endogenous RNA (ceRNA) network, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) on the basis of gene silencing. CircRNAs, as a group of non-encoded RNAs, make a loop-like structure by back-splicing through 3' and 5' ends. They are stable, abundant, specific, and highly conserved and can be quickly generated at large scales in vitro . CircRNAs have the potential to contribute in several cellular processes in a way that some serve as microRNA sponges, cellular transporters, protein-binding RNAs, transcriptional regulators, and immune system modulators. CircRNAs can even play an important role in modulating antiviral immune responses. In the present review, circRNAs' biogenesis, function, and biomarker and therapeutic potential as well as their prospective applications as vaccines against viral infections such as SARS-CoV-2 are explained. By considering their unique properties, their potential to be used as novel vaccines, biomarkers, and a therapeutic approach appears possible., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Sarcoidosis is a worldwide inflammatory disorder of unknown etiology that is characterized by the formation of non-caseating immune granulomas in involved organs,most commonly in the lungs and eyes. Although clinical manifestations of sarcoidosis depend on the organs involved, the most common symptoms include fatigue, fever, weight loss, eye pain, dyspnea, and chest pain. Sarcoidosis usually undergoes spontaneous regression, yet its chronic form progressively threatens the involved organs through the induction of fibrotic damage. Despite decades of medical research, the etiology of sarcoidosis still remains unclear. Nevertheless, a combination of contributors, including genetic factors, environmental exposures, and microbial agents, is believed to trigger the inflammatory state observed in this disease. Furthermore, a highly polarized Th1 and Th17 response with diminished immunomodulatory mechanisms constitute the most significant immunological event associated with this disorder. Indeed, sarcoid granulomas, which consist of highly activated antigen-presenting cells (APCs) and lymphocytes, maintain a robust specialized niche to facilitate antigen presentation and exaggerated immune responses. Both the unknown etiology and multisystem nature of the disease have hampered the development of specific therapeutics and definitive diagnostic assays for sarcoidosis. Consequently, its diagnosis and treatment still represent a challenging task for clinicians. In this article, we aim to summarize contemporary findings of sarcoidosis and its etiology, pathogenesis, and treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Competing Interests: The authors declare no conflict of interest.

Background: Due to the possible biomedical potential of nanoparticles, titanium dioxide nanoparticles (TiO2 NPs) have received great attention in cancer research. Although selectivity of cytotoxicity with TiO2 NPs in various cells is clinically significant comparisons of cancer and non-cancer cells have been limited. Therefore, we here studied exposure to TiO2 NPs in colorectal cancer cells (CRCs) and human umbilical vein endothelial cells (HUVECs). Methods: After characterization of TiO2 NPs, culture and treatment of cells (HCT116, HT29 and HUVEC), viability was assessed by MTT assay and in terms of morphological features. Acridine orange (AO) and propidium iodide (PI) assays were carried out to estimate the incidence of apoptosis. The RT-PCR method was also employed to evaluate the expression of P53, Bax, Bcl-2 and Caspase 3. Results: Exposure to increasing concentrations of TiO2 NPs enhanced overall cell survival of HCT116 cells and reduced the Bcl-2 and Caspase 3 expression while the ratio of Bax/Bcl-2 was down-regulated. TiO2 NPs at 400 and 50 μg/ml concentrations suppressed cell proliferation and induced apoptosis of HT29 cells and also up-regulated P53 and Bax at the mRNA level, enhanced the Bax/Bcl-2 ratio and eventually up-regulated Caspase 3 mRNA. Although, inhibition of cell proliferation in HUVECs was seen at 200 and 400 μg/ml TiO2 NPs, it was not marked. Conclusion: TiO2 NPs have selective bio-effects on exposed cells with dose- and cell-dependent influence on viability. Cell proliferation in HCT116 as a metastatic colorectal cancer cell line appeared to be stimulated via multiple signaling pathways, with promotion of apoptosis in less metastatic cells at 50 and 400 μg/ml concentrations. This was associated with elevated P53, Bax and Caspase 3 mRNA and reduced Bcl-2 expression. However, TiO2 NPs did not exert any apparent significant effects on HUVECs as hyperproliferative angiogenic cells., (Creative Commons Attribution License)

Background: Immunotherapy is one promising therapeutic strategy against glioma, an aggressive form of brain cancer. Previous studies have demonstrated that multiple tumor antigens exist and can be used to induce tumor specific T cell responses. Furthermore, recently it was shown that TLR4-primed mesenchymal stem cells (MSCs), also known as MSC1, mostly elaborate pro-inflammatory mediators. Compared to MSCs, MSC-derived microvesicles (MVs) have advantageous properties that present them as stable, long lasting effectors with no risk of immune rejection. Therefore, peripheral blood monocyte derived dendritic cells (MoDCs) have been used to load tumor antigens and stimulate T cell mediated responses in the presence of MSC1-derived MVs in vitro. Methods: The B92 tumor cell line was heated to 43°C for 90 min prior to preparation of tumor cell lysates. MVs were purified by differential ultracentrifugation after isolation, stimulation of proliferation and treatment of MSCs. Autologous T cells isolated from non-adherent cells were harvested during the procedure to generate MoDCs and then incubated with heat stressed tumor cell lysate pulsed DCs in the presence of MSC1-derived MVs. T cells were then co-cultured with tumor cells in 96-well plates at a final volume of 200 μl CM at an effector: target ratio of 100:1 to determine their specific cytotoxic activity. Results: Flow cytometric analysis, T cell mediated cytotoxicity showed that heat stressed tumor antigen pulsed MoDCs and MSC1-derived MVs primed T cells elicited non-significantly enhanced cytotoxic activity toward B92 tumor cells (P≥0.05). Conclusion: These findings may offer new insights into tumor antigen presenting technology involving dendritic cells and MSC1-derived MVs. Further exploration of the potential of such nanoscale particles in immunotherapy and in novel cancer vaccine settings appears warranted., (Creative Commons Attribution License)