Exploring the anti-cancer and antimetastatic effect of Silymarin against lung cancer.

Lung cancer metastasis remains a significant challenge in cancer therapy, necessitating the exploration of novel treatment modalities. Silymarin, a natural compound derived from milk thistle, has demonstrated promising anticancer properties. This work explored the inhibitory effects of silymarin on lung cancer metastasis and revealed the underlying processes, focusing on matrix metalloproteinase (MMP) 2 and MMP-9 activities. Using a combination of in vitro and molecular docking analyses, we found that silymarin effectively reducing the lung cancer cells' motility and invasion by modulation of expression of MMP-2 and MMP-9. Furthermore, MTT assays revealed a dose-dependent inhibition of cell proliferation upon silymarin treatment and found the IC50 value at 58 µM. We observe that apoptotic morphology characteristic in silymarin treated groups. Cell cycle analysis exhibit the cell cycle arrest at G1 phase, 25.8 % increased apoptosis in silymarin treated groups, as evidenced by Annexin V staining. Moreover, silymarin treatment shows the lipid peroxidation in elevated level and reduced in enzymatic antioxidant level, indicating its potential role in mitigating oxidative stress induce cell death. Gelatin zymography assay indicates the silymarin has ability to inhibit the MMP-2 and MMP-9 expression in lung cancer. Additionally, cell migration assays and colony formation assays demonstrated impaired migratory and colony-forming abilities of lung cancer cells when treated with silymarin. Molecular docking studies further supported the binding affinity of silymarin with MMP-2 and MMP-9, demonstrate the -10.26 and -6.69 kcal/mol of binding energy. Collectively, our findings highlight the multifaceted anticancer properties of silymarin against lung cancer metastasis, providing insights into its therapeutic potential as an adjuvant treatment strategy.

Green synthesis of cerium oxide nanoparticles usingTribulus terrestris: characterization and evaluation of antioxidant, anti-inflammatory and antibacterial efficacy against wound isolates.

Multi-drug resistance (MDR) infections are a significant global challenge, necessitating innovative and eco-friendly approaches for developing effective antimicrobial agents. This study focuses on the synthesis, characterization, and evaluation of cerium oxide nanoparticles (CeO2NPs) for their antioxidant, anti-inflammatory, and antibacterial properties. The CeO2NPs were synthesized using aTribulus terrestrisaqueous extract through an environmentally friendly process. Characterization techniques included UV-visible spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), x-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive x-ray (EDX) analysis. The UV-vis spectroscopy shows the presence of peak at 320 nm which confirms the formation of CeO2NPs. The FT-IR analysis of the CeO2NPs revealed several distinct functional groups, with peak values at 3287, 2920, 2340, 1640, 1538, 1066, 714, and 574 cm-1. These peaks correspond to specific functional groups, including C-H stretching in alkynes and alkanes, C=C=O, C=C, alkanes, C-O-C, C-Cl, and C-Br, indicating the presence of diverse chemical bonds within the CeO2NPs. XRD revealed that the nanoparticles were highly crystalline with a face-centered cubic structure, and SEM images showed irregularly shaped, agglomerated particles ranging from 100-150 nm. In terms of biological activity, the synthesized CeO2NPs demonstrated significant antioxidant and anti-inflammatory properties. The nanoparticles exhibited 82.54% antioxidant activity at 100 µg ml-1, closely matching the 83.1% activity of ascorbic acid. Additionally, the CeO2NPs showed 65.2% anti-inflammatory activity at the same concentration, compared to 70.1% for a standard drug. Antibacterial testing revealed that the CeO2NPs were particularly effective against multi-drug resistant strains, includingPseudomonas aeruginosa,Enterococcus faecalis, and MRSA, with moderate activity againstKlebsiella pneumoniae. These findings suggest that CeO2NPs synthesized viaT. terrestrishave strong potential as antimicrobial agents in addressing MDR infections.

Deep Learning Prediction of Inflammatory Inducing Protein Coding mRNA in P. gingivalis Released Outer Membrane Vesicles.

Aim: The Insilco study uses deep learning algorithms to predict the protein-coding pg m RNA sequences. Material and methods: The NCBI GEO DATA SET GSE218606's GEO R tool discovered P.G's outer membrane vesicles' most differentially expressed mRNA. Genemania analyzed differentially expressed gene networks. Transcriptomics data were collected and labeled on P. gingivalis protein-coding mRNA sequence and pseudogene, lincRNA, and bidirectional promoter lincRNA. Orange, a machine learning tool, analyzed and predicted data after preprocessing. Naïve Bayes, neural networks, and gradient descent partition data into training and testing sets, yielding accurate results. Cross-validation, model accuracy, and ROC curve were evaluated after model validation. Results: Three models, Neural Networks, Naive Bayes, and Gradient Boosting, were evaluated using metrics like Area Under the Curve (AUC), Classification Accuracy (CA), F1 Score, Precision, Recall, and Specificity. Gradient Boosting achieved a balanced performance (AUC: 0.72, CA: 0.41, F1: 0.32) compared to Neural Networks (AUC: 0.721, CA: 0.391, F1: 0.314) and Naive Bayes (AUC: 0.701, CA: 0.172, F1: 0.114). While statistical tests revealed no significant differences between the models, Gradient Boosting exhibited a more balanced precision-recall relationship. Conclusion: In silico analysis using machine learning techniques successfully predicted protein-coding mRNA sequences within Porphyromonas gingivalis OMVs. Gradient Boosting outperformed other models (Neural Networks, Naive Bayes) by achieving a balanced performance across metrics like AUC, classification accuracy, and precision-recall, suggests its potential as a reliable tool for protein-coding mRNA prediction in P. gingivalis OMVs.

Prevalence, antimicrobial susceptibility patterns and associated factors of Streptococcus pyogenes among apparently healthy school children in Mekelle city primary schools, Northern Ethiopia.

Background: Streptococcus pyogenes is one of the major public health concerns causing human infections ranging from skin and throat infections to acute rheumatic fever and post streptococcal glomerulonephritis. Moreover, nowadays drug-resistant strains of S. pyogenes are emerging and can be transmitted through apparently healthy carriers to susceptible individuals. Objective: To assess the prevalence, antimicrobial susceptibility pattern and associated factors S. pyogenes among apparently healthy school children in Mekelle city primary schools, Northern Ethiopia. Methods: A cross-sectional study was conducted among 504 apparently healthy school children from February to May 2018. We used structured questionnaire to collect socio-demographic data. Throat specimens were collected using sterile cotton Swab and transported for culture, antimicrobial susceptibility and identification of S. pyogenes according to standard operating procedures. Data were analyzed using Stata 13 for descriptive statistics, bivariate and multivariate logistic regression. P-value <0.05 was declared statistically significance. Results: The mean age of the study participants was 11.5 years of which 55 % of them were females. The overall prevalence of S. pyogenes was 8.3 %. Being female, having low monthly income, weak personal hygiene, poor hand washing habit and crowded living style were significantly associated with the occurrence of S. pyogenes. The isolates of S. pyogenes showed resistance to Penicillin (69.1 %), Amoxicillin-Clavulanic acid (62 %), Ampicillin (54.6 %), Ceftriaxone (47.6 %), Tetracycline (14.4 %), Cefoxitin (7.2 %). About 57.15 % isolates were multidrug-resistant. Conclusions: This study revealed that some isolates of S. pyogenes among the apparently healthy school children were resistant to commonly prescribed antibiotic agents and associated with hygienic conditions and living style. Therefore, it is recommended to practice antimicrobial susceptibility test to maintain rational antibiotic use and improve hygienic and hand washing practices to decrease the likelihood of carriage rate.

One-Pot Synthesis of Silver/Zirconium Nanoparticles Using Sargassum tenerrimum for the Evaluation of Their Antibacterial and Antioxidant Activities.

INTRODUCTION: The global health threat posed by worldwide antimicrobial resistance necessitated immediate multisectoral action by the scientific community to achieve sustainable development goals. Silver and zirconium nanoparticles (Ag/ZrO-NPs), known for their antimicrobial properties, have the potential to combat pathogens effectively, making them versatile for various applications across different fields. OBJECTIVE:  This study aims to synthesize and characterize Sargassum tenerimum-mediated Ag/ZrO-NPs and evaluate their antioxidant and antibacterial efficacy against multidrug resistant (MDR) pathogens. METHODOLOGY: The synthesis of Ag/ZrO-NPs using the one-pot green synthesis method was conducted and followed by using characterization techniques, namely, UV-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), X-ray diffraction analysis (XRD), and energy-dispersive X-ray analysis (EDX). The antibacterial activity was assessed using the agar well diffusion method, and antioxidant activity was determined using the DPPH(2,2-diphenyl-1-picrylhydrazyl) method. Statistical analysis was analyzed using the IBM SPSS Statistics for Windows, version 21.0 (released 2012, IBM Corp., Armonk, NY). RESULTS: The green-synthesized Ag/ZrO-NPs exhibited a color change from dark brown to creamy white, indicating the successful reduction of the nanoparticles. UV-analysis peaks were observed at 310-330 nm, while the FT-IR analysis showed the peaks at various wavelengths, such as 648.9 cm-1 (alkyne C-H bond), 1041.14 cm-1 (aliphatic fluoro compounds, C-F stretch), 1382.54 cm-1 (dimethyl -CH3), 1589.6 cm-1 (primary amine, N-H bond), and 3353.8 cm-1 (aliphatic secondary amine, N-H stretch). The crystallinity of the nanoparticles was determined to be 59.5%, while the remaining 40.5% exhibited an amorphous structure. The SEM image revealed the spherically agglomerated structure of the nano-ranged size Ag/ZrO-NPs. The EDX analysis indicated the presence of elemental compositions Zr (16.2%), Ag (18.8%), and C (28.7%) in the green-synthesized Ag/ZrO-NPs. These nanoparticles demonstrated significant antibacterial activity against Pseudomonas aeruginosa, Enterococcus faecalis, and Methicillin-resistant Staphylococcus aureus (MRSA). The moderate antibacterial activity against E. coli showed thesignificant antioxidant activity in a dose-dependent manner. CONCLUSION: The green-synthesized Ag/ZrO-NPs showed notable antibacterial and antioxidant activity. In future aspects, it may be used as a potential drug after completion of in-vivo and in-vitro studies.

Evaluation of Antibacterial Efficacy of Centella asiatica-Mediated Selenium Oxide Nanoparticles Against Multidrug-Resistant Upper Respiratory Isolates.

Background The evolution of new respiratory diseases, especially upper respiratory tract infections and resistance of pathogens to various antibiotic treatments, needs an alternative way of medication. Chronic respiratory infections in both adults and infants are the major cause of morbidity and mortality, particularly in developing countries. The widespread application of nanomaterials in the field of medicine and the incorporation of nanoparticles in drugs are taken into account. These nanomaterials are involved along with the biosynthesis of plant extract. In this study, selenium oxide nanoparticles (SeO-NPs), known as a significant trace element for human health, were synthesized in an eco-friendly manner. Methodology Green synthesis of Centella asiatica-mediated SeO-NPs was proceeded by titration method and nanoparticles were synthesized. The color intensity, morphological characters, functional properties, and involvement of phytochemical compounds were studied by using UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX) analysis. Results The synthesized extract showed a color change from brown to ruby red. Results obtained by characterization and biological assays depicted that the Centella asiatica-mediated SeO-NPs showed absorbance at the peak level 320 nm by UV-Vis spectroscopy, several phytochemical compounds, and O-H functional groups by FT-IR which may be involved in the reduction of the selenium oxide nanoparticles. The XRD showed 57.1% crystalline and 42.6% amorphous nature. The SEM images showed that agglomerated spherical shapes were involved in biological activities. The EDX analysis showed the presence of Se, C, and O compounds. Further, the antibacterial activity of the synthesized nanoparticles showed significant activity in the multidrug-resistant respiratory pathogens. Conclusions Based on the characterization studies and biomedical assays, it can be concluded that the incorporation of SeO-NPs along with the plant extract serves as the best remedy and organic treatment for upper respiratory tract infections. We plan to conduct further in-vivo, toxicity-level studies, and clinical trials.

Phytosynthesis of Nickel Oxide Nanoparticles and Their Antioxidant and Antibacterial Efficacy Studies.

INTRODUCTION:  Multidrug-resistant (MDR) bacteria are widely acknowledged as a significant and pressing public health concern. Tribulus terrestris has been used as a health tonic in traditional medicine since ancient Vedic times. It was also utilized to synthesize small, well-dispersed metal nanoparticles (NPs). The biosynthesized nickel oxide nanoparticles (NiO-NPs) have a broad spectrum of biomedical uses. OBJECTIVE:  The objective of the research was to utilize a green synthesis method to synthesize NiO-NPs using Tribulus terrestris, subsequently characterize, and this study aimed to assess the antioxidant and antibacterial effectiveness of these NPs against wound isolates that are resistant to multiple drugs. MATERIALS AND METHODS:  The synthesis of NiO-NPs was achieved through the titration method, which is a green synthesis approach, and it was characterized by using techniques such as ultraviolet-visible spectroscopy (UV), Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, and energy dispersive X-ray (EDX). The antioxidant activity of the NPs was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and antibacterial activity was done using the agar well diffusion method. IBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States) is used for statistical analysis. RESULTS:  The biosynthesized NiO-NPs exhibited a color change from dark brown to dark green, indicating the successful reduction of the NPs. UV analysis peaks were observed at 310-350 nm, while FT-IR analysis showed the peaks at various wavelengths such as 629.31cm-1 (halo compound; C-Br stretching), 957.80cm-1(aromatic phosphates; P-O-C stretch), 1004.65cm-1 (aliphatic phosphates; P-O-C stretch), 1094.93cm-1 (organic siloxane or silicone; Si-O-Si), 1328.38cm-1 (dialkyl/aryl sulfones), 1604.88cm-1 (open-chain azo-N=N-), 2928.68cm-1 (methylene C-H asym/sym stretch), 3268.65cm-1 (normal polymeric "OH" stretch). The crystallinity of the NPs was determined to be 24.7%, while the remaining 75.6% exhibited an amorphous structure. The SEM image revealed a spherically agglomerated structure of the nano-ranged size NiO-NPs. The EDX analysis indicated the presence of elemental compositions Ni (7.4%), O (39.4%), and C (53.3%) in the biosynthesized NiO-NPs. These NPs demonstrated significant antibacterial activity against Pseudomonas aeruginosa and Klebsiella pneumoniae, moderate antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), and the lowest antibacterial activity against Enterococcus faecalis. CONCLUSION:  Our in vitro results demonstrate that the biosynthesized NiO-NPs exhibit significant antioxidant and antibacterial activity. These NPs can be used as a future antimicrobial medication, particularly against MDR clinical wound isolates of K. pneumoniae, P. aeruginosa, and MRSA.

Green Synthesis of Molybdenum Nanoparticles From Solanum xanthocarpum and Evaluation of Their Antimicrobial and Antioxidant Activity Against Multidrug-Resistant Wound Isolates.

INTRODUCTION: In recent years, antimicrobial drug resistance has emerged as a serious global public health concern, according to the World Health Organization data. The emergence of pathogens resistant to multiple drugs has been linked to an increase in morbidity and mortality from microbial infections. The study's main goal is to explore the efficacy of using Solanum xanthocarpum in the green synthesis of molybdenum nanoparticles (Mo NPs) for antibacterial and antioxidant properties. METHODS: An eco-friendly method of synthesizing Mo NPs was accomplished using an aqueous extract of Solanum xanthocarpum. Characterization of the synthesized nanoparticles was done by UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX). After that, antibacterial and antioxidant activity was further evaluated. RESULTS: The UV-visible spectrophotometer analysis confirmed the presence of synthesized Mo NPs showing a peak around 320 nm. The presence of functional compounds like C-CI, C-H, C=C, and O=C=O was confirmed by FT-IR spectrum analysis. The positions of diffraction peaks in Mo NP patterns were identified using XRD analysis; they were more crystalline (82.7%) and less amorphous (17.3%). The presence of the elements molybdenum (Mo), carbon (C), and oxygen (O) was confirmed by the EDX spectrum and irregular shapes shown in the SEM images. Further, the antimicrobial study results showed the formation of an inhibition zone against 27 mm for Klebsiella pneumoniae, 24 mm for Pseudomonas aeruginosa, 22 mm for Staphylococcus aureus, and 24 mm for Enterococcus faecalis, respectively, at a high concentration 80 µg/ml of Mo NPs. The maximum antioxidant activity at 100 µg/ml was 73.49%, compared to the standard ascorbic acid (74.25%). Additionally, the moderate activity at 60 µg/ml was 53.21%, compared to the standard (56.5%), and the minimal activity at 20 µg/ml was 30.21%, compared to the standard (36.89%). CONCLUSION: The environmentally friendly synthesized Mo NPs from Solanum xanthocarpum exhibited antioxidant activity. Furthermore, the findings show that Mo NPs mediated by Solanum xanthocarpum can inhibit antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis. In order to understand further how nanoparticles work against bacteria that are resistant to many drugs, additional research and clinical studies would be needed.

Prediction of deleterious non-synonymous SNPs of TMPRSS2 protein combined with Molecular Dynamics Simulations and free energy analysis to identify the potential peptide substrates against SARS-CoV-2.

Globally the SARS-CoV-2 viral infection demands for the new drugs, the TMPRSS2 target plays a vital role in facilitating the virus entry. The aim of the present study is to identify the potential peptide substrate from the Anti-viral database against TMPRSS2 of SARS-CoV-2. The compound screening and variation analysis were performed using molecular docking analysis and online tools such as PROVEAN and SNAP2 server, respectively. The re-docked crystal structure peptide substrate exhibits -128.151 kcal/mol whereas the RRKK peptide substrate shows -134.158 kcal/mol. Further, the selected compounds were proceeded with Molecular Dynamics Simulation, it explores the stability of the complex by revealing the hotspot residues (His296 and Ser441) were active for nucleophilic attack against TMPRSS2. The average Binding Free Energy values computed through MM/GBSA for RRKK, Camostat, and Crystal Structure were shown -69.9278 kcal/mol, -64.5983 kcal/mol, and -63.9755 kcal/mol, respectively against TMPRSS2. The 'rate of acylation' emerges as an indicator for RRKK's efficacy, it maintains the distance of 3.2 Å with Ser441 resembles, whilst its -NH backbone stabilizes at 2.5 Å 'Michaelis Complex' which leads to prevent the entry of SARS-CoV-2 to human cells. The sequence variation analysis explores that the V160 and G6 substitutions are essential to emphasize the uncover possibilities for the ongoing drug discovery research. Therefore, the identified peptide substrate found to be potent against SARS-CoV-2 and these results will be valuable for ongoing drug discovery research.Communicated by Ramaswamy H. Sarma.