Micronutrient therapy and effective immune response: a promising approach for management of COVID-19.

The escalating prevalence of coronavirus disease 2019 (COVID-19) worldwide, with an increased rate of morbidity and mortality, highlights an urgent need to develop more effective therapeutic interventions. Despite the authorized treatment against COVID-19 by the European Union (EU), the safety and effectiveness of this therapeutic strategy for a wide variety of patients have remained a significant challenge. In this respect, micronutrients such as vitamins and minerals, as essential factors, can be considered for improving the function of the immune system and accelerating the treatment procedure. Dietary supplements can attenuate vascular and inflammatory manifestations related to infectious diseases in large part due to their anti-inflammatory and antioxidant properties. Recently, it has been revealed that poor nutritional status may be one of the notable risk factors in severe COVID-19 infections. In the current review, we focus on the micronutrient therapy of COVID-19 patients and provide a comprehensive insight into the essential vitamins/minerals and their role in controlling the severity of the COVID-19 infection. We also discuss the recent advancements, challenges, negative and positive outcomes in relevance to this approach.

Interplay between MAPK/ERK signaling pathway and MicroRNAs: A crucial mechanism regulating cancer cell metabolism and tumor progression.

Mitogen-activated protein kinase (MAPK) signal transduction, as a highly conserved signaling pathway, is reported to be involved in various biological events, including metabolic reprogramming, cell proliferation, survival, and differentiation. Mutations in key molecules involved in MAPK/ERK signaling and dysregulation of this pathway are very common events in various human malignancies, which make the MAPK signaling a crucial signaling pathway participating in the regulation of glucose uptake by malignant cells and tumorigenesis. MicroRNAs (miRNAs), as small non-coding RNAs, are critical regulators of gene expression that play key roles in cancer initiation and progression. On the other hand, these small RNAs mutually regulate the MAPK signaling which is often overexpressed in the case of cancer progression; suggesting that crosstalk between miRNAs and this signaling pathway plays a pivotal role in the development of human cancers. Some miRNAs such as miR-20b, miR-34c-3p, miR-152, miR-181a, and miR-302b through inhibiting MAPK signaling, and miR-193a-3p, miR-330-3p, and miR-592 by activating this signaling pathway, play imperative roles in tumorigenesis. Therefore, in this review, we aimed to focus on the interplay between miRNAs and MAPK signaling in the various steps of tumorigenesis, including metabolic regulation, cell proliferation, apoptosis, metastasis, angiogenesis, and drug resistance.

Crosstalk between miRNAs and signaling pathways involved in pancreatic cancer and pancreatic ductal adenocarcinoma.

Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide with 5-year survival rates below 8%. Most patients with PC and pancreatic ductal adenocarcinoma (PDAC) die after relapse and cancer progression as well as resistance to treatment. Pancreatic tumors contain a high desmoplastic stroma that forms a rigid mass and has a potential role in tumor growth and metastasis. PC initiates from intraepithelial neoplasia lesions leading to invasive cancer through various pathways. These lesions harbor particular changes in signaling pathways involved in the tumorigenesis process. These events affect both the epithelial cells, including the tumor and the surrounding stroma, and eventually lead to the formation of complex signaling networks. Genetic studies of PC have revealed common molecular features such as the presence of mutations in KRAS gene in more than 90% of patients, as well as the inactivation or deletion mutations of some tumor suppressor genes including TP53, CDKN2A, and SMAD4. In recent years, studies have also identified different roles of microRNAs in PC pathogenesis as well as their importance in PC diagnosis and treatment, and their involvement in various signaling pathways. In this study, we discussed the most common pathways involved in PC and PDAC as well as their role in tumorigenesis and progression. Furthermore, the miRNAs participating in the regulation of these signaling pathways in PC progression are summarized in this study. Therefore, understanding more about pathways involved in PC can help with the development of new and effective therapies in the future.

Envisioning the immune system to determine its role in pancreatic ductal adenocarcinoma: Culprit or victim?

Pancreatic ductal adenocarcinoma has a poor 5-year survival rate that makes it one of the most fatal human malignancies. Unfortunately, despite the serious improvement in the survival of most cancers, there has been a minor advance in pancreatic cancer (PC). Major advances in PC treatment have been assessed over the bygone twenty-year time span, yet some complications make the survival of the patients shorter. Getting to know the PC tumor microenvironment (TME) and the immunosuppression that happens during the pathogenesis of this malignancy could be a great help to understand the nature of the immune system and find better treatment modalities based on it. Although many immune cells are present in PC, immunosuppression of the TME leads to severe immune dysfunction in the patients, therefore immune effectors fail to do their functions. Lately, immunotherapy has been presented as one of the promising treatment strategies for different malignancies including hepatocellular carcinoma, melanoma, non-small cell lung cancer, and kidney cancer. In PC, there has been shown promising results centered around the TME, immune checkpoint inhibitors, cancer vaccines, and other approaches especially when used as combinational therapy. Here we dig a little deeper into the role of the immune system and possible therapeutic options in the treatment of PC.

Simultaneous microRNA-612 restoration and 5-FU treatment inhibit the growth and migration of human PANC-1 pancreatic cancer cells.

Despite the recent advances in the treatment of other cancers, the 5-year survival rate of pancreatic cancer remains under 9 %. Chemotherapy and surgical resection are the most common therapy methods. The regulatory role of microRNAs in different types of cancer has given them therapeutic importance. miR-612 has been downregulated in colorectal, bladder, liver, and some other types of cancer and could be considered a tumor-suppressor miRNA. 5-FU is one of the most common chemotherapeutic agents used in pancreatic cancer treatment, which is used in multiple drug regimens and combinatorial therapy methods. The aim of this study is the evaluation of miR-612 restoration in the PANC-1 cell line and using the tumor-suppressive effect of it in combination with 5-FU on cell growth and migration. MiR-612 mimic was transfected to PANC-1 cells through electroporation. Following the transfection, expression levels of miR-612 and BAX, BCL-2, Caspase-3, MMP9, and PD-L1 genes were measured by qRT-PCR. MTT assay was used to determine the cytotoxicity of miR-612 and 5-FU on PANC-1 cell viability. To confirm MTT results and to evaluate the quantitative effect of apoptosis induction flow cytometry test was used and in order to confirm apoptosis test results and cell cycle arrest evaluation DAPI staining and cell, cycle tests were conducted, respectively. Finally, to assess the inhibitory effect of miR-612 in combination with 5-FU on migration and growth wound healing and colony formation assays were used, respectively. Results demonstrated that miR-612 alongside 5-FU has an important role in the inhibition of migration and growth and also apoptosis induction in PANC-1 cells and could be considered as a supporting agent of chemotherapy and a novel therapeutic modality in pancreatic cancer treatment.