The role of noncoding RNAs in metabolic reprogramming of cancer cells.

Metabolic reprogramming is a well-known feature of cancer that allows malignant cells to alter metabolic reactions and nutrient uptake, thereby promoting tumor growth and spread. It has been discovered that noncoding RNAs (ncRNAs), including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), have a role in a variety of biological functions, control physiologic and developmental processes, and even influence disease. They have been recognized in numerous cancer types as tumor suppressors and oncogenic agents. The role of ncRNAs in the metabolic reprogramming of cancer cells has recently been noticed. We examine this subject, with an emphasis on the metabolism of glucose, lipids, and amino acids, and highlight the therapeutic use of targeting ncRNAs in cancer treatment.

The impact of DAPK1 and mTORC1 signaling association on autophagy in cancer.

BACKGROUND: The autophagy pathway is used by eukaryotic cells to maintain metabolic homeostasis. Autophagy has two functions in cancerous cells which could inhibit tumorigenesis or lead to cancer progression by increasing cell survival and proliferation. METHODS AND RESULTS: In this review article, Web of Science, PubMed, Scopus,  and Google Scholar were searched and summarized published studies to explore the relationship between DAPK1 and mTORC1 signaling association on autophagy in cancer. Autophagy is managed through various proteins including the mTOR, which is two separated structural and functional complexes known as mTORC1 and mTORC2. MTORC1 is an important component of the regulatory pathway affecting numerous cellular functions including proliferation, migration, invasion, and survival. This protein plays a key role in human cancers. The activity level of mTORC1 is regulated by the death-associated protein kinases (DAPks) family, especially DAPK1. In many cancers, DAPK1 acts as a tumor suppressor which can be attributed to its ability to suppress cellular transformation and to inhibit metastasis. CONCLUSIONS: A deep investigation not only will reveal more about the function of DAPK1 but also might provide insights into novel therapies aimed to modulate the autophagy pathway in cancer and to achieve better cancer therapy.

SARS-CoV-2: phenotype, genotype, and characterization of different variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), a major international public health concern. Because of very similar amino acid sequences of the seven domain names, SARS-CoV-2 belongs to the Coronavirinae subfamily of the family Coronaviridae, order Nidovirales, and realm Riboviria, placed in exceptional clusters, but categorized as a SARS-like species. As the RNA virus family with the longest genome, the Coronaviridae genome consists of a single strand of positive RNA (25-32 kb in length). Four major structural proteins of this genome include the spike (S), membrane (M), envelope (E), and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. By engaging with its receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 infects host cells. According to the most recent epidemiological data, as the illness spread globally, several genetic variations of SARS-CoV-2 appeared quickly, with the World Health Organization (WHO) naming 11 of them. Among these, seven SARS-CoV-2 subtypes have received the most attention. Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.617.2) are now designated as variations of concern (VOC) (B.1.1.529). Lambda (C.37) and Mu are variations of interest (VOI) (B.1.621). The remaining six are either being monitored or are no longer considered a threat. On the basis of studies done so far, antiviral drugs, antibiotics, glucocorticoids, recombinant intravenous immunoglobulin, plasma therapy, and IFN-α2b have been used to treat patients. Moreover, full vaccination is associated with lower infection and helps prevent transmission, but the risk of infection cannot be eliminated completely in vaccinated people.

An Overview on the Common Laboratory Parameter Alterations and their Related Molecular Pathways in Screening for COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 mainly affects the tissues expressing angiotensinconverting enzyme 2 (ACE2). ACE2 is used as a receptor for the virus to enter the cells. Once SARS-CoV-2 enters the cells, it leads to further events through signaling pathways. This pathophysiological condition can appear as changes in laboratory tests. METHOD: However, the lack of studies in this area is strongly felt. The present study was conducted to review the most common abnormalities in laboratory tests caused by COVID-19 and their related molecular pathways and outcomes. RESULTS: It showed that the levels of IL-6, CRP, PCT, AST/ALT, bilirubin, ALP, GGT, LDH, ferritin, D-dimer, and neutrophils increased. Conversely, the levels of albumin and lymphocytes decreased. Since most of these parameters were related to hepatic function, their alterations indicated liver injury. CONCLUSIONS: Overall, the parameters CRP, D-dimer, and CBC are more important in diagnosis. Moreover, it seems that MAPK and NF-κB are the most frequent signaling pathways in which alterations may contribute to the pathogenesis of the virus. Altogether, our review encourages researchers to study signaling pathways as potential molecular targets to achieve effective treatment.

Circular RNAs: Novel Biomarkers in Spermatogenesis Defects and Male Infertility.

Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs involved in several cellular and biological processes, including gene expression regulation, microRNA function, transcription regulation, and translation modification. Therefore, these non-coding RNAs have important roles in the pathogenesis of various diseases. Male infertility is mainly due to abnormal sperm parameters such as motility, morphology, and concentration. Recent studies have confirmed the role of circRNAs in spermatogenesis, and the expression of several circRNAs is confirmed in seminal plasma, spermatozoa, and testicular tissue. It is suggested that deregulation of circRNAs is involved in different types of male infertility, including azoospermia, oligozoospermia, and asthenozoospermia. In the present review, we aimed to discuss the potential roles of circRNAs in spermatogenesis failure, sperm defects, and male infertility. Due to their conserved and special structure and tissue-specific expression pattern, circRNAs can be applied as reliable noninvasive molecular biomarkers, therapeutic and pharmaceutical targets in male infertility.

Protective role of ellagic acid and taurine against fluoxetine induced hepatotoxic effects on biochemical and oxidative stress parameters, histopathological changes, and gene expressions of IL-1ß, NF-κB, and TNF-α in male Wistar rats.

PURPOSES: Hepatic bioactivation of fluoxetine (FXN) could increase free radicals' generation provoking hepatotoxicity. Therefore, the protective effects of ellagic acid (EA) and taurine (TAU) treatments against fluoxetine-induced liver damage in rats were examined. MATERIALS AND METHODS: Sixty four male Wistar rats were randomly assigned to 8 groups (n = 8). Group (1) Control, group (2) FXN, group (3) FXN + EA, group (4) FXN + TAU, group (5) FXN + EA + TAU, group (6) EA, group (7) TAU, and group (8) EA + TAU. Then, the serum and tissue parameters of the oxidative stress were examined. KEY FINDINGS: FXN significantly raised serum MDA, protein carbonyl, lipid profile, ALT, AST, ALP, total bilirubin, serum IL-1ß; and gene expressions of IL-1ß, NF-κB, and TNF-α. Moreover, it significantly decreased HDL-C, ferric reducing antioxidant power (FRAP), catalase activity, vitamin C, and SOD activity in the liver compared to group 1. When compared to group 2, EA and TAU treatment dramatically increased antioxidant capacity and lowered hepatotoxic biochemical markers and cellular inflammation. Results also showed a protective effect of treatment against oxidative damage caused by hepatocytes' cytoarchitecture. SIGNIFICANCE: Our study concluded the beneficial effects of EA and TAU on FXN-induced hepatotoxicity. These effects were derived from free radical scavenging properties and the anti-inflammatory effects related to IL-1ß, NF-κB, and TNF-α gene expression inhibition.

Quercetin Synergistically Enhances the Anticancer Efficacy of Docetaxel through Induction of Apoptosis and Modulation of PI3K/AKT, MAPK/ERK, and JAK/STAT3 Signaling Pathways in MDA-MB-231 Breast Cancer Cell Line.

Docetaxel is widely used in the treatment of metastatic breast cancer. However, its effectiveness is limited due to chemoresistance and its undesirable side effects. The combination of chemotherapeutic agents and natural compounds is an effective strategy to overcome drug resistance and the ensuing inevitable toxicities. Quercetin is a natural flavonoid with strong antioxidant and anticancer activities. This study aimed to evaluate the cytotoxic and modulatory effects of combined docetaxel and quercetin on the MDA-MB-231 human breast cancer cell line. The cell viability was assessed by MTT assay. The induction of apoptosis was examined using flow cytometry. The role of p53 in the apoptotic process was evaluated via qRT-PCR. The levels of BAX, BCL2, ERK1/2, AKT, and STAT3 proteins were measured by Western blot analysis. The results showed that the single-agent treatment with docetaxel or quercetin leads to a decrease in the viability of the MDA-MB-231 cells at 48 h. Furthermore, the combination of docetaxel (7 nM) and quercetin (95 µM) displayed the greatest synergistic effects with a combination index value of 0.76 accompanied by the up regulation of p53 and a significant increase in BAX level, as well as decrease in the levels of BCL2, pERK1/2, AKT, and STAT3 proteins (P < 0.05). The concomitant use of docetaxel and quercetin leads to the cell growth inhibition associated with the induction of apoptosis and inhibition of cell survival. Therefore, this study provides a promising therapeutic approach to enhance the efficacy of docetaxel in a less-toxic manner.

The Serum Level of Midkine in Patients With Multiple Sclerosis and Neuromyelitis Optica.

INTRODUCTION: Midkine (MK), a heparin-binding growth factor, is involved in neurological diseases by mediating the inflammatory responses through enhancing the leukocyte migration. The present study assesses the serum concentration of this growth factor among newly developed Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO) patients. METHODS: The present research, as a cross-sectional study, was performed at Isfahan University of Medical Sciences, Isfahan City, Iran. All samples were selected from patients who visited Kashani and Alzahra hospitals for two years (2014 to 2016). The MK level was assessed in 80 new MS cases, 80 NMO patients, and 80 healthy subjects. After collecting blood sera samples, MK serum level was measured using the ELISA. The obtained data were analyzed in SPSS. RESULTS: The Mean±SD MK level was 1038.58±44.73 pg/mL in the MS group, which was significantly higher than the Mean±SD MK level in the NMO (872.62±55.42 pg/mL) and control groups (605.02±9.42 pg/mL). CONCLUSION: Overall, these results demonstrated that MK plays a prominent role in inflammatory reactions and neuroautoimmune diseases, especially in MS. So, the MK level may be used for earlier diagnosis and also prevention of disease progression by using a special inhibitor.

Data-Worth Assessment for a Three-Dimensional Optimal Design in Nonlinear Groundwater Systems.

Groundwater model predictions are often uncertain due to inherent uncertainties in model input data. Monitored field data are commonly used to assess the performance of a model and reduce its prediction uncertainty. Given the high cost of data collection, it is imperative to identify the minimum number of required observation wells and to define the optimal locations of sampling points in space and depth. This study proposes a design methodology to optimize the number and location of additional observation wells that will effectively measure multiple hydrogeological parameters at different depths. For this purpose, we incorporated Bayesian model averaging and genetic algorithms into a linear data-worth analysis in order to conduct a three-dimensional location search for new sampling locations. We evaluated the methodology by applying it along a heterogeneous coastal aquifer with limited hydrogeological data that is experiencing salt water intrusion (SWI). The aim of the model was to identify the best locations for sampling head and salinity data, while reducing uncertainty when predicting multiple variables of SWI. The resulting optimal locations for new observation wells varied with the defined design constraints. The optimal design (OD) depended on the ratio of the start-up cost of the monitoring program and the installation cost of the first observation well. The proposed methodology can contribute toward reducing the uncertainties associated with predicting multiple variables in a groundwater system.

Evaluation of glucose-6-phosphate dehydrogenase serum level in patients with multiple sclerosis and neuromyelitis optica.

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) are both demyelinating disorders and oxidative stress is suggested to have a role in their pathogenesis. Glucose-6-phosphate dehydrogenase (G6PD) produces nicotinamide adenine dinucleotide phosphate (NADPH) via the pentose phosphate pathway. NADPH is not only involved in the synthesis of fatty acids necessary for myelination, but also it is involved in the defense against oxidative stress. Prescribing supplementary vitamin D as a part of the MS treatment plan can increase G6PD gene expression. The aim of this study was to determine the serum level of G6PD in patients with MS and NMO and its relationship with vitamin D, since it is yet to be explored thoroughly. Methods: In this case-control study, subjects were divided into three experimental and control groups. The experimental groups comprised 50 patients with relapsing-remitting MS (RRMS) who had a history of vitamin D consumption, 50 newly-diagnosed MS patients, and 50 patients with NMO. Control group included 65 healthy individuals. Serum level of G6PD was measured and compared among these groups. Results: No significant difference was seen between the G6PD level in patients with MS and NMO, but it should be noted that this level was significantly lower than the healthy group. G6PD serum level was significantly higher in patients with MS who had previously consumed supplementary vitamin D compared to those who had not. Conclusion: G6PD deficiency is observed in patients with MS and NMO. Also, supplementary vitamin D may induce favorable results on the G6PD level.