Identification of High Death Risk Coronavirus Disease-19 Patients using Blood Tests.

Background: The coronavirus disease (COVID-19) pandemic has made a great impact on health-care services. The prognosis of the severity of the disease help reduces mortality by prioritizing the allocation of hospital resources. Early mortality prediction of this disease through paramount biomarkers is the main aim of this study. Materials and Methods: In this retrospective study, a total of 205 confirmed COVID-19 patients hospitalized from June 2020 to March 2021 were included. Demographic data, important blood biomarkers levels, and patient outcomes were investigated using the machine learning and statistical tools. Results: Random forests, as the best model of mortality prediction, (Matthews correlation coefficient = 0.514), were employed to find the most relevant dataset feature associated with mortality. Aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were identified as important death-related features. The decision tree method was identified the cutoff value of BUN >47 mg/dL and AST >44 U/L as decision boundaries of mortality (sensitivity = 0.4). Data mining results were compared with those obtained through the statistical tests. Statistical analyses were also determined these two factors as the most significant ones with P values of 4.4 × 10-7 and 1.6 × 10-6, respectively. The demographic trait of age and some hematological (thrombocytopenia, increased white blood cell count, neutrophils [%], RDW-CV and RDW-SD), and blood serum changes (increased creatinine, potassium, and alanine aminotransferase) were also specified as mortality-related features (P < 0.05). Conclusions: These results could be useful to physicians for the timely detection of COVID-19 patients with a higher risk of mortality and better management of hospital resources.

In silico identification and characterization of antineoplastic asparaginase enzyme from endophytic bacteria.

It is generally accepted that L-asparagine is an important amino acid required for the fast growth of cells. Cancerous cells receive this amino acid from extracellular sources. The depletion of L-asparagine from its surrounding environments by asparaginase enzyme can be used as a therapeutic strategy in cancer patients. This therapeutic enzyme is produced commercially mainly from bacteria such as Escherichia coli and Erwinia chrysanthemi. The side effects of such drugs have persuaded scientists to find new enzyme sources. In this study, in silico approach was applied to investigate L-asparaginase producing endophytic bacteria that produce more compatible enzymes within the body. Protein-protein basic local alignment search tool with E. coli and E. chrysanthemi asparaginase enzyme sequences against 262 endophytic bacteria were performed. The results with identity more than 35%, coverage more than 80%, and E-value less than 10-4 were selected. Then, some of bioinformatics tools were used to characterize them. A total of nine sequences consisting of seven known and two hypothetical proteins were identified in six bacterial species. The results showed that some of the asparaginase enzymes produced by endophytic bacteria possess more suitable immunological indices compared with asparaginase enzymes of E. coli and E. chrysanthemi. Herbaspirillum rubrisubalbicans was predicted to produce a nonallergen and nonantigen asparaginase enzyme. The number of antigenic determinants was predicted to be lower in asparaginase enzymes produced by Bacillus amyloliquefaciens, H. rubrisubalbicans, and H. seropedicae. Moreover, the number of high-scored B-cell epitopes was lower in enzyme sequences related to the mentioned bacteria and Paenibacillus polymyxa. The number of discontinuous epitopes and the number of T-cell epitopes were lower in B. amyloliquefaciens produced enzymes. Therefore, the therapeutic use of these enzymes is possible.

In Silico Identification of Probable Drug and Vaccine Candidates Against Antibiotic-Resistant Acinetobacter baumannii.

Acinetobacter baumannii is known as a Gram-negative bacterium that has become one of the most important health problems due to antibiotic resistance. Today, numerous efforts are being made to find new antibiotics against this nosocomial pathogen. As an alternative solution, finding bacterial target(s), necessary for survival and spread of most resistant strains, can be a benefit exploited in drug and vaccine design. In this study, a list of extensive drug-resistant and carbapenem-resistant (multidrug resistant) A. bumannii strains with complete sequencing of genome were prepared and common hypothetical proteins (HPs) composed of more than 200 amino acids were selected. Then, a number of bioinformatics tools were combined for functional assignments of HPs using their sequence. Overall, among 18 in silico investigated proteins, the results showed that 7 proteins implicated in transcriptional regulation, pilus assembly, protein catabolism, fatty acid biosynthesis, adhesion, urea catalysis, and hydrolysis of phosphate monoesters have theoretical potential of involvement in successful survival and pathogenesis of A. baumannii. In addition, immunological analyses with prediction softwares indicated 4 HPs to be probable vaccine candidates. The outcome of this work will be helpful to find novel vaccine design candidates and therapeutic targets for A. baumannii through experimental investigations.

Circular RNAs: epigenetic regulators in cancerous and noncancerous skin diseases.

The most frequent kind of malignancy in the universe is skin cancer, which has been categorized into non-melanoma and melanoma skin cancer. There are no complete information of the skin carcinogenesis process. A variety of external and internal agents contribute to the non-melanoma and melanoma skin cancer pathogenesis. These factors are epigenetic changes, X-rays, genetic, arsenic compounds, UV rays, and additional chemical products. It was found that there could be a relationship between the appearing novel and more suitable therapies for participants in this class of diseases and detection of basic molecular paths. A covalently closed loop structure bond connecting the 5' and 3' ends characterizes a new group of extensively expressed endogenous regulatory RNAs, which are called circular RNAs (circRNAs). Mammals commonly express circRNAs. They are of high importance in tumorigenesis. Multiple lines evidence indicated that a variety of circular RNAs are associated with initiation and development of skin-related diseases such as skin cancers. Given that different circular RNAs (hsa_circ_0025039, hsa_circRNA006612, circRNA005537, and circANRIL) via targeting various cellular and molecular targets (e.g., CDK4, DAB2IP, ZEB1, miR-889, and let-7c-3p) exert their effects on skin cancers progression. Herein, for first time, we summarized different circular RNAs in skin cancers and noncancerous diseases. Moreover, we highlighted crosstalk between circular RNAs and ceRNAs in cancerous conditions.

Moonlight human ribosomal protein L13a downregulation is associated with p53 and HER2/neu expression in breast cancer.

Breast cancer is the most common malignancy among females worldwide. Recent studies have shown extra-ribosomal roles of the moonlight ribosomal proteins in the development of human cancers. Accurate quantification of the gene expression level is based on the selection of the reference genes whose expression is independent of cancer properties and patient's characteristics. The aim of this study was the evaluation of the expression level of a previously proposed ribosomal protein as moonlight, L13a (RPL13A), in breast cancer samples and their adjacent tissues. Its association with genes of known roles in developing cancers was also investigated. Traditionally used housekeeping genes were selected and their expression was analyzed in 80 surgically excised breast tissue specimens (40 tumors and 40 tumor-adjacent tissues) by applying three software tools including GeNorm, NormFinder, and BestKeeper to select the most stable reference genes. Then, mRNA expression levels of RPL13A and p53 were evaluated. Additionally, protein expression levels of RPL13A were measured. It was demonstrated that PUM1 and ACTB are the most reliable reference genes and RPL13A is the least stable gene. There was a positive correlation between RPL13A and p53 mRNA expression levels in all the tumor samples. Moreover, significant downregulation of RPL13A expression levels was revealed in HER2+ tumor samples compared to HER2- ones. There was also a marked decrease in p53 mRNA expression levels in HER2+ tumor subtypes. Our results suggest that there is a probable relationship between RPL13A decreased expression with p53 and HER2/neu expression in the breast cancer.

Leukemia-derived exosomes: Bringing oncogenic signals to blood cells.

Leukemia is a cancer, which is derived from leukocytes and precursors of leukocytes in the bone marrow. A large number of pivotal biological processes are linked to leukemia pathogenesis. More insights into these mechanisms can provide a better developing pharmacological platform for patients with leukemia. Among the different players in leukemia pathogenesis, exosomes have appeared as a new biological vehicle, which can transfer oncogenic signals to blood cells. Exosomes are nano-carriers, which enable transferring numerous cargos such as DNA fragments, RNAs, messenger RNAs, microRNAs, long noncoding RNA, and proteins. Targeting the contents of exosomes leads to the alteration of host cell behavior. Increasing evidence has indicated that leukemia-derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. In this regard, the importance of exosomes in terms of initiation and progression of leukemia was underlined in this study.

The roles of moonlight ribosomal proteins in the development of human cancers.

"Moonlighting protein" is a term used to define a single protein with multiple functions and different activities that are not derived from gene fusions, multiple RNA splicing, or the proteolytic activity of promiscuous enzymes. Different proteinous constituents of ribosomes have been shown to have important moonlighting extra-ribosomal functions. In this review, we introduce the impact of key moonlight ribosomal proteins and dependent signal transduction in the initiation and progression of various cancers. As a future perspective, the potential role of these moonlight ribosomal proteins in the diagnosis, prognosis, and development of novel strategies to improve the efficacy of therapies for human cancers has been suggested.

Bioactivity of malva sylvestris L., a medicinal plant from iran.

OBJECTIVES: Malva sylvestris L. (Malvaceae), an annual plant, has been already commonly used as a medicinal plant in Iran. In the present work, we evaluate some bioactivities of the plant extracts. MATERIALS AND METHODS: The aired-dried plant flowers and leaves were extracted by soxhlet apparatus with n-hexane, dichloromethane and methanol. The antimicrobial, cytotoxic, and phytotoxic of the plant extracts were evaluated using disk diffusion method, MTT, and Lettuce assays, respectively. RESULTS: Both flowers and leaves of M. sylvestris methanol extracts exhibited strong antibacterial effects against Erwinia carotovora, a plant pathogen, with MIC value of 128 and 256 µg/ml, respectively. The flowers extract also showed high antibacterial effects against some human pathogen bacteria strains such as Staphylococcus aureus, Streptococcus agalactiae, Entrococcus faecalis, with MIC value of 192, 200 and 256 µg/ml, respectively. The plant methanol extracts had relatively high cytotoxic activity against MacCoy cell line. CONCLUSION: We concluded that Malva sylvestris can be candidated as an antiseptic, a chemopreventive or a chemotherapeutic agent.