In Silico Identification of Hub Genes as Observing Biomarkers for Gastric Cancer Metastasis.

Perception of hub genes engaged in metastatic gastric cancer (mGC) promotes novel ways to diagnose and treat the illness. The goal of this investigation is to recognize the hub genes and reveal its molecular mechanism. In order to explore the potential facts for gastric cancer, the expression profiles of two different datasets were used (GSE161533 and GSE54129). The genes were confirmed to be part of the PPI network for gastric cancer pathogenesis and prognosis. In Cytoscape, the CytoHubba module was used to discover the hub genes. Responsible hub genes were identified. Data from Kaplan-Meier plotter confirmed the predictive value of these distinct genes in various stages of gastric malignancy. Upregulated and downregulated genes were identified to utilize for further analysis. Positive regulation by a host of viral process, positive regulation of granulocyte differentiation, negative regulation of histone H3-K9 methylation were found in DEGs analysis. In addition, five KEGG pathways were identified as an essential enhancer that include nucleotide excision repair; base excision repair; DNA replication; homologous recombination; and complement and coagulation cascades. POLE, BUB1B, POLD4, C3, BLM, CCT7, PRPF31, APEX1, PSMA7, and CDC45 were chosen as hub genes after combining the PPI results. Our study recommends that BUB1B, CCT7, APEX1, PSMA7, and CDC45 might be potential biomarkers for gastric cancer. These biomarkers are upregulated genes. Therefore, suppression of these genes will increase the survival rate in gastric cancer patients.

Curcumin-Based Inhibitors of Thrombosis and Cancer Metastasis Promoting Factor CLEC 2 from Traditional Medicinal Species Curcuma longa.

The CLEC-2 receptor protein belongs to the C-type lectin superfamily of transmembrane receptors that have one or more C-type lectin-like domains. CLEC-2 is a physiological binding receptor of podoplanin (PDPN), which is expressed on specific tumour cell types and involved in tumour cell-induced platelet aggregation and tumour metastasis. CLEC-2 and podoplanin-expressing tumour cells interact to increase angiogenesis, tumour development, and metastasis. CLEC-2 is a hemi-immunoreceptor tyrosine-based activation motif (hemi-ITAM) receptor located on platelets and a subset of dendritic cells that are expressed constitutively. This molecule is secreted by activated platelets around tumours and has been shown to inhibit platelet aggregation and tumour metastasis in colon carcinoma by binding to the surface of tumour cells. Pharmacokinetic studies were carried using a DrugLiTo, and molecular docking was performed using AutoDock Tools 1.5.6 (ADT). Twenty-nine bioactive compounds were included in the study, and four of them, namely, piperine, dihydrocurcumin, bisdemethoxycurcumin, and demothoxycurcumin, showed potential antagonist properties against the target. The resultant best bioactive was compared with commercially available standard drugs. Further, validation of respective compounds with an intensive molecular dynamics simulation was performed using Schrödinger software. To the best of our knowledge, this is the first report on major bioactive found on clove as natural antagonists for CLEC-2 computationally. To further validate the bioactive and delimit the screening process of potential drugs against CLEC-2, in vitro and in vivo studies are needed to prove their efficacy.

Occupational health hazards on workers exposure to lead (Pb): A genotoxicity analysis.

BACKGROUND: The present investigation of genotoxicity of lead (Pb) among workers exposed to inorganic Pb environment, which appears to be first of its kind in South India, was undertaken to assess the seriousness, the ill effects of health contributed by this serious environmental pollutant. METHODS: A total of 144 samples comprising of exposed (n=72), and control (n=72) subjects were screened. Demographic data and their associated health levels were undertaken by means of a questionnaire. The blood samples collected were subjected to chromosomal analysis, micronuclei assessment and comet assay. RESULTS: A higher level of Pb was quantified in the blood samples of all exposed subjects. An overview of the genotoxic assessment helped us understand parameters such as age do not affect or bring about any difference in the genotoxic potential of the exposed and control subjects. The only signification feature that resulted in an enhanced genotoxic potential was the years of exposure to the Pb environment that accumulated the dosage of Pb over the years. CONCLUSION: The high positivity of genotoxic potential of Pb in a country like India highlights the need for labelling hazardous metals in paint containers as a means to assure strict regulations.

Optimizing the Management of Cadmium Bioremediation Capacity of Metal-Resistant Pseudomonas sp. Strain Al-Dhabi-126 Isolated from the Industrial City of Saudi Arabian Environment.

In this study, 23 bacterial strains were isolated from a Cadmium (Cd) contaminated soil in the industrial city, Riyadh of Saudi Arabia. Among these isolates six strains were found to withstand cadmium contamination and grow well. From the six isolates Pseudomonas sp. strain Al-Dhabi-122-127 were found to resist cadmium toxicity to a higher level. The isolates were subjected to biochemical and 16S rDNA gene sequence characterization to confirm their identification. The bacterial strain Al-Dhabi-124 showed 1.5 times higher Cd-degrading activity than Al-Dhabi-122 and Al-Dhabi-123, and Al-Dhabi-126 exhibited 3.5 times higher Cd-degrading activity, higher than the other strains. An atomic absorption spectrophotometer study showed that the strain Al-Dhabi-126 absorbed Cd, and that the bacterial strain Al-Dhabi-126 was found to tolerate cadmium level up to 2100 µg/mL. The bacterial strain Al-Dhabi-126 showed a maximum Cd removal efficacy at pH between 6.0 and 8.0. The efficacy decreased sharply after an increase in pH (9.0). An optimum temperature of 50 °C and pH 6.0 were found to be effective for the Cd removal process by the isolate. The study indicated that the bacterial strain Al-Dhabi-126 can be used effectively for the bioremediation of heavy metals like cadmium, a major toxic pollutant in industrial effluents.

Bioactivity assessment of the Saudi Arabian Marine Streptomyces sp. Al-Dhabi-90, metabolic profiling and its in vitro inhibitory property against multidrug resistant and extended-spectrum beta-lactamase clinical bacterial pathogens.

BACKGROUND: Metabolites obtained from the marine microorganisms were known for their important role in microbial inhibition. Interestingly, bioprospecting of secondary metabolites from marine derived actinomycetes has huge demand especially in the treatment of multi drug resistant clinical pathogens. The present study subjected towards the identification of promising antimicrobial actinomycetes from the Arabian Gulf regions and metabolic profiling of the crude organic solvent extract by chromatographic techniques. METHODS: The strains were characterized by 16S rRNA sequencing. Extracellular metabolites were profiled by performing GC-MS analysis. MIC values of the compounds were detected using broth dilution technique. RESULTS: A Gram positive, spore forming filamentous Streptomyces sp. Al-Dhabi-90 possessed good antibacterial activities against the drug resistant pathogens were confirmed by 16S rRNA gene sequencing. Further, the gas chromatography coupled with mass spectrum analysis data revealed that the organic solvent extract of the fermented Streptomyces sp. Al-Dhabi-90 contained major components such as 3-methylpyridazine, n-hexadecanoic acid, indazol-4-one, octadecanoic acid and 3a-methyl-6-((4-methylphenyl) sul respectively. The Minimum Inhibitory Concentration (MIC) of the extract against Staphylococcus aureus and Klebsiella pneumoniae were 12.5 and 50µg/ml respectively. Against drug resistant ESBL pathogens such as Escherichia coli, Pseudomonsa aeroginosa and Proteus mirabilis were 12.5, and 25µg/ml respectively. Interestingly, the extract showed promising activity against the vancomycin resistant Enterococcus faecium at 50µg/ml. The increased level of cellular constituents after the extract treatment evidenced that the metabolites altered the membrane integrity of the pathogens. CONCLUSION: Conclusively, the marine Streptomyces sp. Al-Dhabi-90 is an ideal source for the treatment of multi drug resistant clinical pathogens.

Characterization of Silver Nanomaterials Derived from Marine Streptomyces sp. Al-Dhabi-87 and Its In Vitro Application against Multidrug Resistant and Extended-Spectrum Beta-Lactamase Clinical Pathogens.

A novel antagonistic marine Streptomyces sp. Al-Dhabi-87 that was recovered from the Gulf region of Saudi Arabia was used to synthesize silver nanoparticles (NP) from the culture free extract. The produced NP were confirmed by UV-visible spectroscopy (UV-Vis), high-resolution scanning electron microscope (HRSEM), transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), Energy Dispersive Spectroscopy (EDAX), and X-ray Powder Diffraction (XRD), and broth micro dilution techniques were employed for the determination of minimum inhibitory concentrations (MIC) values. The synthesized NP was authenticated by alterations in color and wavelength scanning. HRSEM and TEM analysis confirmed that the size of the NP ranged from 10 to 17 nm and that it was spherical in shape. In addition, the FTIR spectrum revealed a variation in the band values from 500 to 3300 cm−1 respectively. Rietveld refinement analysis of the XRD data confirmed the size of the NP, which coincided with the results of the TEM analysis. In addition, the Riveted refinement analysis supported the TEM data. The NP documented significant activity against the wound infection microbial strains, such as Enterococcus faecalis, Staphylococcus epidermidis, and Staphylococcus aureus. Gram negative bacteria, such as Pseudomonas aeruginosa, Klebsiella pneumonia, and Escherichia coli revealed MIC values of 0.039, 0.078, and 0.152 mg/mL, respectively. The promising activity of NP towards extended-spectrum beta-lactamases E.coli, drug resistant Acinetobacter baumannii, and multidrug resistant S. aureus (at 0.018, 0.039, and 0.039 mg/mL, respectively) was advantageous. Overall, NP that were obtained from the novel Streptomyces sp. Al-Dhabi-87, with its promising antimicrobial activity towards the drug resistant pathogens, would be useful for healing infectious diseases.