The roles of lncRNAs and miRNAs in pancreatic cancer: a focus on cancer development and progression and their roles as potential biomarkers.

Pancreatic ductal adenocarcinoma (PDAC) is among the most penetrative malignancies affecting humans, with mounting incidence prevalence worldwide. This cancer is usually not diagnosed in the early stages. There is also no effective therapy against PDAC, and most patients have chemo-resistance. The combination of these factors causes PDAC to have a poor prognosis, and often patients do not live longer than six months. Because of the failure of conventional therapies, the identification of key biomarkers is crucial in the early diagnosis, treatment, and prognosis of pancreatic cancer. 65% of the human genome encodes ncRNAs. There are different types of ncRNAs that are classified based on their sequence lengths and functions. They play a vital role in replication, transcription, translation, and epigenetic regulation. They also participate in some cellular processes, such as proliferation, differentiation, metabolism, and apoptosis. The roles of ncRNAs as tumor suppressors or oncogenes in the growth of tumors in a variety of tissues, including the pancreas, have been demonstrated in several studies. This study discusses the key roles of some lncRNAs and miRNAs in the growth and advancement of pancreatic carcinoma. Because they are involved not only in the premature identification, chemo-resistance and prognostication, also their roles as potential biomarkers for better management of PDAC patients.

Screening and identification of potential biomarkers for pancreatic cancer: An integrated bioinformatics analysis.

Pancreatic cancer is one of the highly invasive and the seventh most common cause of death among cancers worldwide. To identify essential genes and the involved mechanisms in pancreatic cancer, we used bioinformatics analysis to identify potential biomarkers for pancreatic cancer management. Gene expression profiles of pancreatic cancer patients and normal tissues were screened and downloaded from The Cancer Genome Atlas (TCGA) bioinformatics database. The Differentially expressed genes (DEGs) were identified among gene expression signatures of normal and pancreatic cancer, using R software. Then, enrichment analysis of the DEGs, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, was performed by an interactive and collaborative HTML5 gene list enrichment analysis tool (enrichr) and ToppGene. The protein-protein interaction (PPI) network was also constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and ToppGenet web based tool followed by identifying hub genes of the top 100 DEGs in pancreatic cancer using Cytoscape software. Over 2000 DEGs with variable log2 fold (LFC) were identified among 34,706 genes. Principal component analysis showed that the top 20 DEGs, including H1-4, H1-5, H4C3, H4C2, RN7SL2, RN7SL3, RN7SL4P, RN7SKP80, SCARNA12, SCARNA10, SCARNA5, SCARNA7, SCARNA6, SCARNA21, SCARNA9, SCARNA13, SNORA73B, SNORA53, SNORA54 might distinguish pancreatic cancer from normal tissue. GO analysis showed that the top DEGs have more enriched in the negative regulation of gene silencing, negative regulation of chromatin organization, negative regulation of chromatin silencing, nucleosome positioning, regulation of chromatin silencing, and nucleosomal DNA binding. KEGG analysis identified an association between pancreatic cancer and systemic lupus erythematosus, alcoholism, neutrophil extracellular trap formation, and viral carcinogenesis. In PPI network analysis, we found that the different types of histone-encoding genes are involved as hub genes in the carcinogenesis of pancreatic cancer. In conclusion, our bioinformatics analysis identified genes that were significantly related to the prognosis of pancreatic cancer patients. These genes and pathways could serve as new potential prognostic markers and be used to develop treatments for pancreatic cancer patients.

Immunomodulatory actions of vitamin D in various immune-related disorders: a comprehensive review.

For many years, vitamin D has been acknowledged for its role in maintaining calcium and phosphate balance. However, in recent years, research has assessed its immunomodulatory role and come up with conflicting conclusions. Because the vitamin D receptor is expressed in a variety of immune cell types, study into the precise role of this molecule in diseases, notably autoimmune disorders, has been made possible. The physiologically activated version of vitamin D also promotes a tolerogenic immunological condition in addition to modulating innate and acquired immune cell responses. According to a number of recent studies, this important micronutrient plays a complex role in numerous biochemical pathways in the immune system and disorders that are associated with them. Research in this field is still relatively new, and some studies claim that patients with severe autoimmune illnesses frequently have vitamin D deficiencies or insufficiencies. This review seeks to clarify the most recent research on vitamin D's immune system-related roles, including the pathophysiology of major disorders.

A multi-epitope vaccine designed against blood-stage of malaria: an immunoinformatic and structural approach.

Malaria is a complex disease caused by parasites of the genus Plasmodium and is the leading cause of morbidity and mortality worldwide. The most severe form of malaria disease is caused by Plasmodium falciparum. Thus, a combination of different approaches is needed to control malaria. Resistance to first-line drugs and insecticides, on the other hand, makes the need for an effective vaccination more urgent than ever. Because erythrocyte parasites cause the most clinical symptoms, developing a vaccination for this stage of infection might be highly beneficial. In this research, we employed various bioinformatics methods to create an efficient multi-epitope vaccine that induces antibodies against the blood stage of malaria infection. For this purpose, we selected the malaria PfGARP protein as the target here. The B, HTL epitopes, and epitope conservation were predicted. The predicted epitopes (including 5 B and 5 HTL epitopes) were connected using suitable linkers, and the flagellin molecule was used as an adjuvant to improve its immunogenicity. The final construct vaccine with 414 amino acids long was designed. The vaccine's allergenicity, antigenicity, solubility, physicochemical characteristics, 2D and 3D structure modeling, molecular docking, molecular dynamics simulation, in silico cloning, and immunological simulation were tested. In silico immune simulation results showed significantly elevated IgG1 and IgM and T helper cells, INF γ, IL 2, and B-cell populations after the injection of the designed vaccine. These significant computational analyses indicated that our proposed vaccine candidate might activate suitable immune responses against malaria. However, in vitro and in vivo studies are essential for further validation.

Evaluation of anti-tumor effect of the exopolysaccharide from new cold-adapted yeast, Rhodotorula mucilaginosa sp. GUMS16 on chronic myeloid leukemia K562 cell line.

Recently, the development and application of fungal exopolysaccharides (EPS) as natural biopolymers are on the rise. The present study is based on the investigation of possible antiproliferative and antioxidant activities of EPS from the Rhodotorula mucilaginosa sp. GUMS16 on BCR-ABL positive cells (K562). The cytotoxicity, colony formation assays lactate and dehydrogenase (LDH) activity were performed to assess the possible cancer cell death. To elucidate the underlying antiproliferative mechanism of the EPS, cell cycle analysis following real-time PCR (gene expression assessment) were evaluated. The results indicated that, the EPS with an IC50 dose of 1500 µg/ml, reduced the viability of K562 cells without having toxic effects on normal cells as well as decrease in size and number of colonies in EPS-treated group (p < 0.0001). The increase of LDH was 2.75 times more than the control (p < 0.0001). Gene expression revealed up- and down-regulation of apoptotic and anti-apoptotic genes in EPS group compared with the control. Moreover, the DPPH scavenging activity of the EPS in treated cells was significantly higher than the control group (p < 0.0001). Taken together, we concluded that the EPS from GUMS16 strain is able to inhibit the growth of K562 cells besides having antioxidant activities.

NK cell upraise in the dark world of cancer stem cells.

One of the obstacles in treating different cancers, especially solid tumors, is cancer stem cells (CSCs) with their ability in resistance to chemo/radio therapy. The efforts for finding advanced treatments to overcome these cells have led to the emergence of advanced immune cell-based therapy (AICBT). Today, NK cells have become the center of attention since they have been proved to show an appropriate cytotoxicity against different cancer types as well as the capability of detecting and killing CSCs. Attempts for reaching an off-the-shelf source of NK cells have been made and resulted in the emergence of chimeric antigen receptor natural killer cells (CAR-NK cells). The CAR technology has then been used for generating more cytotoxic and efficient NK cells, which has increased the hope for cancer treatment. Since utilizing this advanced technology to target CSCs have been published in few studies, the present study has focused on discussing the characteristics of CSCs, which are detected and targeted by NK cells, the advantages and restrictions of using CAR-NK cells in CSCs treatment and the probable challenges in this process.

Portal Vein Thrombosis Might Develop by COVID-19 Infection or Vaccination: A Systematic Review of Case-Report Studies.

Background and Objective: Infection by the novel coronavirus disease 2019 (COVID-19) has been associated with different types of thrombotic complications same as portal vein thrombosis (PVT). However, by emerging vaccines of COVID, the thrombosis did not seem to be concerning anymore. Until new findings showed that, the vaccine of COVID itself can cause PVT. Method: We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the possibility of occurring PVT due to infection and vaccination of COVID-19. The results were reported in a narrative method and categorized into tables. Result: Overall, 40 cases of PVT from 34 studies were reviewed in this article. The prevalence of PVT following COVID-19 was more remarkable in males. However, it was more common in females after vaccinations of COVID-19 in the reviewed cases. Regardless of etiology, 20 of PVT cases reviewed in this article had at least one comorbidity. The most common clinical presentation was abdominal pain (AP). After anticoagulant therapies, most of the patients improved or discharged. Conclusion: As long as the laboratory findings are not appropriate enough to predict PVT, the diagnosis of this complication with whatever underlying reason is challengeable, while rapid diagnosis and treatment of that are vital. Therefore, by providing available data in an organized way, we aimed to prepare the information of infected patients for better and easier future diagnosis of PVT in new cases.

The Association of Major Depressive Disorder with Activation of NLRP3 Inflammasome, Lipid Peroxidation, and Total Antioxidant Capacity.

Increasing number of studies indicates that chronic inflammation and oxidative stress play an essential role in pathophysiology and some symptoms of major depressive disorder (MDD). In the present study, the inflammasome activity and oxidative stress status in untreated and antidepressant-treated MDD patients were compared to the healthy group. Blood samples were taken from 20 MDD patients receiving treatment, 20 first-episode MDD patients not receiving treatment, and 20 healthy controls. The expression level of NLRP3 and caspase-1 was measured by real-time PCR and the serum TAC and MDA were examined in the patients and the control groups. The results showed that the mRNA level of NLRP3 and caspase-1 genes was significantly elevated in MDD groups compared with that in the healthy volunteers (P < 0.005). The expression level of NLRP3 and caspase-1 has slightly decreased in the treated group compared with that in the untreated one, but it was not a meaningful decrease. Moreover, the serum MDA was significantly higher and TAC statistically was lower in untreated MDD patients compared with those in the healthy control group (P = 0.001, P = 0.001). It can be concluded that NLRP3 inflammasome is upregulated in MDD patients. Statistically significant reduction in the level of TAC along with increased lipid peroxidation was detectable in MDD patient's plasma. In contrast, there was no significant difference between the treated and non-treated groups in terms of oxidative stress (P = 0.6, P = 0.1). Our results suggested that inflammasome signaling pathway is a therapeutic potential for MDD.

Association between vitamin D receptor gene FokI and TaqI variants with autism spectrum disorder predisposition in Iranian population.

BACKGROUND AND AIM: Autism spectrum disorder (ASD) is one of the neurodevelopmental and cognitive conditions that involves 1 in 160 children around the world. Several studies showed that there is a relationship between vitamin D receptor (VDR) gene polymorphisms with the neurodevelopmental behavioral disorders. In the current study, we aimed to highlight the association of VDR gene polymorphisms (FokI and TaqI) with the risk of autism in Birjand population. MATERIAL AND METHODS: In this case-control study eighty-one patients recognized with ASD and one hundred-eight healthy controls were recruited to the study from 2017 to 2018. Genotyping was carried out by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technique for all subjects. RESULTS: Calculated odds ratio and P-value for the alleles of VDR gene FokI and TaqI variants between autistic patients and controls did not show a significant difference (P > 0.05). However, calculated homozygous recessive (tt) for TaqI polymorphism was statistically significant (P = 0.015) in control group and there was also statistically meaningful difference in both case and control groups in ft haplotype (P = 0.04). CONCLUSION: These results provide preliminary evidence that genetic variants of the VDR gene (FokI and TaqI) might have a possible reduced risk of ASD occurrence in children. The additional examination is needed to acquire more decisive and precise results in this area.