Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU.

PURPOSE: Co-administration of microRNAs and chemotherapy drugs effectively treats several cancers. The current study sought to investigate the function of matrix metalloproteinase 16 (MMP16) and miR-193a-5p in the pathogenesis of gastric cancer (GC). MATERIALS/METHODS: Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients. RESULTS: The current study found that while MMP16 expression increased in GC patients (P â€‹< â€‹0.0001), miR-193a-5p expression significantly decreased (P â€‹< â€‹0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P â€‹< â€‹0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p. CONCLUSIONS: These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth.

Identification of potential biomarkers for melanoma cancer (black tumor) using bioinformatics strategy: a study based on GEO and SRA datasets.

Melanoma, a highly invasive type of skin cancer that penetrates the entire dermis layer, is associated with increased mortality rates. Excessive exposure of the skin to sunlight, specifically ultraviolet radiation, is the underlying cause of this malignant condition. The appearance of unique skin moles represents a visible clue, referred to as the "ugly duckling" sign, indicating the presence of melanoma and its association with cellular DNA damage. This research aims to explore potential biomarkers derived from microarray data, employing bioinformatics techniques and methodologies, for a thorough investigation of melanoma skin cancer. The microarray dataset for melanoma skin cancer was obtained from the GEO database, and thorough data analysis and quality control measures were performed to identify differentially expressed genes (DEGs). The top 14 highly expressed DEGs were identified, and their gene information and protein sequences were retrieved from the NCBI gene and protein database. These proteins were further analyzed for domain identification and network analysis. Gene expression analysis was conducted to visualize the upregulated and downregulated genes. Additionally, gene metabolite network analysis was carried out to understand the interactions between highly interconnected genes and regulatory transcripts. Molecular docking was employed to investigate the ligand-binding sites and visualize the three-dimensional structure of proteins. Our research unveiled a collection of genes with varying expression levels, some elevated and others reduced, which could function as promising biomarkers closely linked to the development and advancement of melanoma skin cancer. Through molecular docking analysis of the GINS2 protein, we identified two natural compounds (PubChem-156021169 and PubChem-60700) with potential as inhibitors against melanoma. This research has implications for early detection, treatment, and understanding the molecular basis of melanoma.

Evolutionary analysis of buffalo sterol regulatory element-binding factor (SREBF) family genes and their affection on milk traits.

The sterol regulatory element-binding factor (SREBF) genes are a vital group of proteins binding to the sterol regulatory element 1 (SRE-1) regulating the synthesis of fatty acid. Two potential candidate genes (SREBF1 and SREBF2) have been identified as affecting milk traits. This study aims to identify the SREBF family of genes and find candidate markers or SREBF genes influencing lactation production in buffalo. A genome-wide study was performed and identified seven SREBF genes randomly distributed on 7 chromosomes and 24 protein isoforms in buffalos. The SREBF family of genes were also characterized in cattle, goat, sheep and horse, and using these all-protein sequences, a phylogenetic tree was built. The SREBF family genes were homologous between each other in the five livestock. Eight single nucleotide polymorphisms (SNPs) within or near the SREBF genes in the buffalo genome were identified and at least one milk production trait was associated with three of the SNP. The expression of SREBF genes at different lactation stages in buffalo and cattle from published data were compared and the SREBF genes retained a high expression throughout lactation with the trend being the same for buffalo and cattle. These results provide valuable information for clarifying the evolutionary relationship of the SREBF family genes and determining the role of SREBF genes in the regulation of milk production in buffalo.

In-Silico Screening and Molecular Dynamics Simulation of Drug Bank Experimental Compounds against SARS-CoV-2.

For the last few years, the world has been going through a difficult time, and the reason behind this is severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), one of the significant members of the Coronaviridae family. The major research groups have shifted their focus towards finding a vaccine and drugs against SARS-CoV-2 to reduce the infection rate and save the life of human beings. Even the WHO has permitted using certain vaccines for an emergency attempt to cut the infection curve down. However, the virus has a great sense of mutation, and the vaccine's effectiveness remains questionable. No natural medicine is available at the community level to cure the patients for now. In this study, we have screened the vast library of experimental drugs of Drug Bank with Schrodinger's maestro by using three algorithms: high-throughput virtual screening (HTVS), standard precision, and extra precise docking followed by Molecular Mechanics/Generalized Born Surface Area (MMGBSA). We have identified 3-(7-diaminomethyl-naphthalen-2-YL)-propionic acid ethyl ester and Thymidine-5'-thiophosphate as potent inhibitors against the SARS-CoV-2, and both drugs performed impeccably and showed stability during the 100 ns molecular dynamics simulation. Both of the drugs are among the category of small molecules and have an acceptable range of ADME properties. They can be used after their validation in in-vitro and in-vivo conditions.

The Impact of Paulownia Leaves Extract on Performance, Blood Biochemical, Antioxidant, Immunological Indices, and Related Gene Expression of Broilers.

The current research sought to assess the effects of paulownia leaves extract (PLE) on performance, blood hematological, antioxidant activity, and immunological response of broiler chicken. In total, two hundred 1-day-old male Cobb 500 chicks were allocated randomly into four equal treatments with 5 replicates. The first treatment served as a control (CNT) and was fed the basal diet only, while the other treated treatments were fed on the basal diet supplemented with 0.1, 0.3, and 0.5 g/kg diet of PLE, respectively. The performance results showed significant increments (P < 0.05) in live body weight (LBW), weight gain (WG), and European production efficiency factors (EPEIs) (linearly; p < 0.001) in cooperated with increasing PLE levels in broiler diets. At the same time, feed conversion ratio (FCR) and livability percentages were numerically enhanced under the effects of PLE supplementation. Moreover, a notable increase (P < 0.05 or 0.01) in oxidative remarks activity (GSH, glutathione; SOD, super oxide-dismutase and CAT, catalase) and elevated levels of immunoglobulin (IgM, immunoglobulin M and IgG, immunoglobulin G) were noted (P < 0.05) for treatments fed with PLE in a dose-dependent manner. Also, a dramatic linear increase was observed in mRNA expression of IGF-1, GHR, IL-1ß, and IL-10 genes of broiler chickens. This study concluded that enriched broiler feeds with 0.5 g/kg PLE might be a beneficial strategy to promote broiler health and production.

Dietary Parsley Seed Mitigates Methomyl-Induced Impaired Growth Performance, Hemato-Immune Suppression, Oxidative Stress, Hepato-Renal Damage, and Pseudomonas aeruginosa Susceptibility in Oreochromis niloticus.

The present experiment investigated the potential protective role of parsley (Petroselinum crispum) seed meal (PSM) in alleviating methomyl (MET)-adverse impacts on growth, whole-body composition, hematological indicators, hepatorenal function, immune response, oxidative status, and disease resistance to Pseudomonas aeruginosa. For this purpose, 225 healthy Nile tilapia (Oreochromis niloticus) were allotted into five groups (45 fish/group in triplicate). One group was reared in clean water and fed a non-supplemented basal diet, while the other groups were exposed to 20.39 µg L-1 MET and fed a non-fortified basal diet or basal diets supplemented with 0.5, 1.0, or 2.0% of PSM for 60 days. The obtained data revealed significantly lower weight gain, feed intake, and specific growth rate, but higher feed conversion ratio and decreases in crude protein, lipid, and ash contents in the MET-exposed fish. Anemia, leukopenia, lymphocytopenia, and esonipenia were also obvious. Furthermore, MET-exposed fish had significantly higher serum levels of hepatic enzymes and renal damage products. Nevertheless, there was a significant depletion of enzymatic and non-enzymatic antioxidants and increased malondialdehyde, myeloperoxidase, and tumor necrosis factor-α levels in MET-exposed fish. The MET exposure significantly depressed lysozyme activity, nitric oxide, complement3, acetylcholinesterase activity, total proteins, globulin, and albumin levels in O. niloticus serum. Furthermore, pathological alterations in the liver and kidney were noted. The relative percentage of survival rate in MET-exposed fish was dramatically reduced on day 14 post-challenge with P. aeruginosa. The inclusion of PSM, on the other hand, greatly alleviated most of the MET-related negative effects. Taken together, the dietary intervention with PSM has a promising role in alleviating MET-deleterious impacts, rendering parsley seeds a viable aqua feed additive for O. niloticus.

Licorice Extract Supplementation Affects Antioxidant Activity, Growth-Related Genes, Lipid Metabolism, and Immune Markers in Broiler Chickens.

The objective of this study was to evaluate the Glycyrrhiza glabra effect on growth performance, blood parameters, antioxidant and lysosomal activity, histology and immunohistochemistry of liver and intestine, and the gene expression profile of broiler chickens. A total of 180 Cobb500 broiler chicks (one-week-old) were used in this study. Chicks were distributed randomly into three treatment groups; the first group received drinking water without any supplementation (control group). In contrast, birds in groups 2 and 3 received licorice supplementation in drinking water with 0.4 and 0.8 g licorice/liter, respectively. Results revealed that licorice at a 0.4 g/L of water level improved body weight, weight gain, feed intake, and FCR. Licorice also exhibits a broad range of biological activities such as hypolipidemic, hypoglycemic, hepatoprotective, immunostimulant, and antioxidant effects. The morphometric analysis of different parameters of the intestine revealed a significant increase in the intestinal villi length, width, and villi length/crypt depth in the group supplemented with licorice 0.4 gm/L compared to other groups. The number of CD3 positive in both duodenum and ileum was increased in the licorice 0.4 gm/L group compared to other groups. The expression of growth-related genes was significantly increased with licorice supplementation and modulation of the lipid metabolism genes in the liver and upregulated to the mRNA expression of both superoxide dismutase (SOD1) and Catalase (CAT). Our results revealed that licorice supplementation increased the growth performance of broiler chickens and impacted the birds' antioxidant activity through modulation of the growth-related genes, lipid metabolic markers, and antioxidant-related pathways.

Molecular docking analysis of mefluhybenamine with lung cancer targets.

Lung cancer is the most prevalent type of cancer worldwide, with 2.21 million cases and 1.80 million fatalities in 2020. The main factor influencing lung cancer is smoking, and the most common form of lung cancer, non-small cell lung cancer (NSCLC), accounts for around 80% of instances compared to small cell carcinoma, and about 75% of patients are already in an advanced stage when they are detected. Despite significant early detection and therapy improvements, the five-year survival rate for NSCLC is not encouraging. Therefore, it is essential to look into the molecular origins of non-small cell lung cancer to develop more effective therapeutic strategies-the binding affinities and energy landscape with the proteins. Cyclin Dependent kinase 2 (CDK2) and Insulin-like Growth Factor 1 Receptor (IGF1) were more substantial and sustained in lung cancer that was chosen as the two primary target proteins in this. We screened the entire Drug Bank-prepared library of 1,55,888 compounds and found (2R,3R)-7-(Methylsulfonyl)-3-(2,4,5-trifluorophenyl) -1,2,3,4-tetrahydropyrido[1,2-a] benzimidazol-2-aminium (Mefluhybenamine) to be a significant inhibitor. Mefluhybenamine showed strong hydrogen bonding and other bonding topologies, such as van der Waals force, in its high docking scores of -6.168 Kcal/mol and -5.26 Kcal/mol, and ADMET results showed excellent bioavailability, remarkable solubility, no side effects, and toxicity. The molecular dynamicsimulation confirmed the compound's stability and interaction pattern for 100 ns in an SPC water medium with the slightest deviation and fluctuation. Data shows that Mefluhybenamine is a potential candidate. However, validation of the compound is essential.