PBMC MicroRNAs: Promising Biomarkers for the Differential Diagnosis of COVID-19 Patients with Abnormal Coagulation Indices.

MicroRNAs, or miRNAs, may involve in coagulation and inflammation pathways caused by severe Coronavirus disease (COVID-19). Accordingly, this attempt was made to explore the behavior of peripheral blood mononuclear cells (PBMCs) miRNAs as effective biomarkers to diagnose COVID-19 patients with normal and abnormal coagulation indices. We selected the targeted miRNAs (miR-19a-3p, miR-223-3p, miR-143-5p, miR-494-3p and miR-301a-5p) according to previous reports, whose PBMC levels were then determined by real-time PCR. Receiver operating characteristic (ROC) curve was obtained to clarify the diagnostic potency of studied miRNAs. The differentially expressed miRNA profiles and corresponding biological activities were predicted in accordance with bioinformatics data. Targeted miRNAs' expression profiles displayed a significant difference between COVID-19 subjects with normal and abnormal coagulation indices. Moreover, the average miR-223-3p level expressed in COVID-19 cases with normal coagulation indices was significantly lower than that in healthy controls. Based on data from ROC analysis, miR-223-3p and miR-494-3p are promising biomarkers to distinguish the COVID-19 cases with normal or abnormal coagulation indices. Bioinformatics data highlighted the prominent role of selected miRNAs in the inflammation and TGF-beta signaling pathway. The differences existed in the expression profiles of selected miRNAs between the groups introduced miR-494-3p and miR-223-3p as potent biomarkers to prognosis the incidence of COVID-19.

Investigation of the combined effects of cadmium chloride, silver nitrate, lead nitrate, methyl jasmonate, and salicylic acid on morphometric and biochemical characteristics of St. John's wort.

Hypericum perforatum L., is a sprawling, leafy herb that grows in open, disturbed areas, known as St. John's wort, has a variety of secondary metabolites that can be used for medicinal and therapeutic purposes. Heavy metals have become the most dangerous pollutants in the environment. The effect of cadmium chloride, lead nitrate, silver nitrate, methyl jasmonate, and salicylic acid was studied on several morphometric and biochemical features of St. John's wort simultaneously using the Taguchi statistical method. The results showed cadmium chloride and lead nitrate reduced the morphometric and biochemical properties of St. John's wort while salicylic acid compensated for the adverse effects of heavy metals. Simultaneously, use of salicylic acid and silver nitrate with cadmium chloride and lead nitrate reduced the toxic effects of these metals on morphometric properties. Methyl jasmonate improved growth characteristics at low levels and inhibited at higher levels. Also, according to the results, salicylic acid could reduce the effects of heavy metals on the biochemical properties, while silver nitrate acts like heavy metals, especially at higher levels. Salicylic acid reduced the harmful effects of these heavy metals and at all levels was able to create a better induction effect on St. John's wort. These elicitors mainly changed the adverse effects of heavy metals by strengthening the pathways of the antioxidant system in St. John's wort. The research assumptions were validated, which suggests that the Taguchi method could be considered in an optimum culture of medicinal plants under different treatments such as heavy metals and elicitors.

TEMPRANILLO homologs in apple regulate flowering time in the woodland strawberry Fragaria vesca.

The long juvenile period of fruit trees makes their breeding costly and time-consuming. Therefore, flowering time engineering and shortening the juvenile phase have become a breeding priority for the genetic improvement of fruit tree crops. Many economically valuable fruit trees belong to the Rosaceae family including apples and strawberries. TEMPRANILLO (TEM) acts as a key player in flowering time control through inhibiting FT function. Two genes with high sequence similarity with the Arabidopsis TEM genes were isolated from apple (Malus domestica). Due to the complexity of carrying out functional studies in apple, we characterized their function in woodland strawberry as well as their expression in apple. The expression of MdTEM genes in apple tissues from juvenile plants was dramatically higher than that in the tissues from adult trees. In woodland strawberry, the overexpression of MdTEM genes down-regulated FvFT1, FvGA3OX1, and FvGA3OX2 genes in strawberry. The MdTEM-overexpressing lines exhibited delayed flowering, in terms of days to flowering and the number of leaves at flowering. While, RNAi-mediated silencing of TEM resulted in five days earlier flowering, with a lower number of leaves, a higher trichome density, and in some cases, caused in vitro flowering. According to these results and in silico analyses, it can be concluded that MdTEM1 and MdTEM2 can be considered as orthologs of FvTEM and probably AtTEM genes, which play an important role in regulating the juvenile phase and flowering time through regulating FT and GA biosynthetic pathway.

Quercetin and Methotrexate in Combination have Anticancer Activity in Osteosarcoma Cells and Repress Oncogenic MicroRNA-223.

INTRODUCTION: Osteosarcoma (OS) is one of the most common bone neoplasms in adolescents. Notable short- and long-term toxic effects of OS chemotherapy regimens have been reported. Hence, new chemotherapeutic agents with the ability to potentiate OS chemotherapy drugs and protect non-tumorous tissues are required. METHODS: Saos-2 cells were treated with Methotrexate (MTX) and Quercetin (Que) (a polyphenolic flavonoid with anti-tumor effects) alone and in combination. MTT assay was performed to investigate the cytotoxicity of the drugs. Moreover, apoptosis-involved genes, including miR-223, p53, BCL-2, CBX7, and CYLD expression were analyzed via qRT-PCR. Annexin V-FITC/PI kit was employed to assess the apoptosis rate. RESULTS: The MTT results showed that Que increases MTX cytotoxicity on OS cells. The measured IC50s are 142.3 µM for QUE and 13.7 ng/ml for MTX. A decline in MTX IC50 value was observed from 13.7 ng/ml to 8.45 ng/ml in the presence of Que. Moreover, the mRNA expression outcomes indicated that the combination therapy significantly up-regulates the tumor suppressor genes, such as p53, CBX7, and CYLD, and declines anti-apoptotic genes BCL-2 and miR-223, which can lead to proliferation inhibition and apoptosis inducement. Furthermore, the apoptosis rate increased significantly from 6.03% in the control group to 38.35% in Saos-2 cells that were treated with the combination of MTX and Que. CONCLUSION: Que, with the potential to boost the anticancer activity of MTX on Saos-2 cancer cells through proliferation inhibition and apoptosis induction, is a good candidate for combination therapy.

Proteomic, biochemical, and anatomical influences of nanographene oxide on soybean (Glycine max).

Nano-graphene oxide (NGO) is an engineered nanostructure that is used in various fields including biology, chemistry, medicine, and environmental protection. This kind of highly used nanomaterial (NM) is being released and accumulated gradually in nature and can have some adverse influences on living organisms including plants. Soybean as a cultivated plant with a high importance in food industry, but sensitive to stresses, was chosen in the present study to be examined in terms of proteomic, biochemical, and anatomical properties under the NGO stress. Accordingly, a 2-dimensional gel electrophoresis (2-DE) approach was adopted for proteomic analysis of the NGO treated soybean roots, where significant changes were observed in the abundance of 48 proteins. MALDI TOF/TOF analysis revealed the upregulation of the proteins involved in the redox regulation in plants. Furthermore, anatomical examination of soybean roots under light microscopy showed that the NGO could enter into the root epidermis through the apoplastic pathway and accumulated in some parts of the root. With increasing NGO concentration, the diameter of the vascular apertures increased and then decreased at higher concentrations. To evaluate the toxicity of NGO, some of the growth parameters including fresh and dry weight, and height of the shoots, as well as some stress-related biochemical properties such as H2O2 production, antioxidant enzymes activity, and phenolics and flavonoids contents were measured. The results indicated that NGO could cause an oxidative stress, which can be considered a toxic effect evoking antioxidative and detoxification mechanisms in soybean.

Prognostic Value of LncRNA KRT18P55 in Patients with Intestinal Type of Gastric Cancer.

PURPOSE: Gastric cancer (GC) is a heterogeneous disease, and this heterogeneity significantly affects survival and treatment outcomes. Identification of molecular biomarkers specific for early-stage GC can help clinicians to choose more precise and effective treatment approaches. Long non-coding RNAs (lncRNAs) have the potential to be used as biomarkers because of their tissue specificity, stability, and availability in body fluids. In this study, we aimed to investigate changes in the expression levels of lncRNA KRT18P55 and to assess its biomarker potentials in patients with GC. METHODS: Tumor and non-tumor marginal tissues were collected from 102 patients at Noor-Nejat Hospital (Tabriz, Iran). RNA was isolated, and quantitative reverse transcriptase PCR (qRT-PCR) was performed to assess KRT18P55 expression levels in tumor and non-tumor tissue samples. The receiver operating characteristic (ROC) curve analysis was performed to evaluate potentials of KRT18P55 as a prognostic biomarker in GC. SPSS and GraphPad Prism software were used for data analysis. RESULTS: We found that KRT18P55 is significantly overexpressed in tumor as compared to non-tumor tissues (p < 0.0001). We found a significant association between KRT18P55 overexpression and intestinal GC subtype (p < 0.0001), lymph node metastasis (p = 0.013), and Helicobacter pylori infection (p = 0.033). Based on the ROC analysis, KRT18P55 showed a sensitivity and specificity of 53.92% and 77.45%, respectively. CONCLUSION: Overexpression of KRT18P55 in gastric tumors is suggestive of its oncogenic role in GC. In addition, KRT18P55 may be used as a potential prognosis biomarker and therapeutic target in intestinal GC subtype.

The molecular mechanism of nuclear signaling for degradation of cytoplasmic DNA: Importance in DNA damage response and cancer.

This review summarizes and addresses non-coding RNAs (rRNA, tRNA, Vault and Y RNA, snRNA, and miRNA) cytoplasmic decay pathways, the molecules, enzymes, and modifications such as uridylation, which play vital roles in the degradation processes in various eukaryotic organisms. Plus, SIRT1's role in fundamental cellular processes, including autophagy, DNA repair, DNA damage response (DDR), and the molecular mechanisms, is explored. Further, the HuR (an RNA-binding protein) impact on the expression of genes following DNA damage, and the pathways that regulate HuR function, which is through phosphorylation by Chk1/Cdk1 and Chk2, are specified. Finally, the role of DIF1/ Rnr2-Rnr4 in DDR has been discussed.

Modulation of telomerase expression and function by miRNAs: Anti-cancer potential.

Telomerase is a nucleoprotein reverse transcriptase that maintains the telomere, a protective structure at the ends of the chromosome, and is active in cancer cells, stem cells, and fetal cells. Telomerase immortalizes cancer cells and induces unlimited cell division by preventing telomere shortening. Immortalized cancer cells have unlimited proliferative potential due to telomerase activity that causes tumorigenesis and malignancy. Therefore, telomerase can be a lucrative anti-cancer target. The regulation of catalytic subunit of telomerase (TERT) determines the extent of telomerase activity. miRNAs, as an endogenous regulator of gene expression, can control telomerase activity by targeting TERT mRNA. miRNAs that have a decreasing effect on TERT translation mediate modulation of telomerase activity in cancer cells by binding to TERT mRNA and regulating TERT translation. In this review, we provide an update on miRNAs that influence telomerase activity by regulation of TERT translation.

Senescence is delayed by selenium in oilseed rape plants.

Leaf senescence is a genetically programmed process that can also be induced by nitrogen (N) deficiency. Although selenium (Se) delays leaf senescence, the underlying mechanisms are still unknown. To explore the mechanisms of Se-mediated delay of leaf senescence, we studied the biochemical and molecular events that occur during developmental and N deficiency-induced senescence. Oilseed rape (Brassica napus L.) plants were grown under adequate N (AN, 16 mM) or low N (LN, 4 mM) conditions during the rosette growth stage and treated with Se (15 µg plant-1 as Na2SeO4) either through roots or leaves for four weeks. Shoot dry matter production was not influenced, while the photosynthetic parameters were improved by Se application in both young and old leaves under both AN and LN conditions. The Se treatment rarely influenced the concentrations of reactive oxygen species (ROS), while it increased the nitric oxide (NO) levels in young and old leaves under both AN and LN conditions. The positive correlation between the NO level and leaf photosynthetic parameters in old leaves of LN plants suggested a role for NO boosting, mediated by Se, in the protection of aging leaves from LN-induced accelerated senescence. This implication was further supported by the clear down-regulation of SAG12-1 and up-regulation of Cab, particularly by root application of Se in old leaves of LN plants. Our results provide the first evidence that Se influences the expression of senescence-associated genes and delays senescence through NO signalling but is independent of the ROS defence system.