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Epilepsy is a neurological disorder that is major cause of disability in the world. This is most severe medical condition related with different ion channel genes, inflammatory molecules depression and stress. For this purpose, precise diagnostic techniques are available. Genetic polymorphisms are major factors behind the occurrence of many disorders therefore they can be valid for diagnostic purpose. This study emphasis the finding of such markers in Lahore population. Epilepsy-causing gene GABRG2 was selected, and the gene was then examined to detect the presence of polymorphic markers with the help of molecular (PCR) and computational analysis. 50 blood samples of epilepsy patients were collected from Children hospital Lahore, out of which 2 samples were shown positive response for GABRG2 gene, indicating that this gene is becoming the cause of seizures in epilepsy patients. These samples underwent mutational screening, which revealed 6 new mutations in exon 3 region of these samples as a result of disease occurrence. There are no proper treatments of epilepsy offered despite the development of anti-leptic and anti-seizure drugs. To solve this issue, researchers are working to create innovative methods of treating epilepsy, that incorporate the use of herbal remedies. 31 plant compounds have been used in this study but only one compound cyanidin was selected on the base of best binding affinity. Moreover, SwissAdme, QSAR analysis and molecular simulations demonstrated that cyanidin is a best natural drug model which have best responses as compared to other epileptic drugs and can be tested for future application in laboratories. [ABSTRACT FROM AUTHOR]

Lactic acid bacteria has been extensively used in food industry because of widespread properties and Pediococcus is among one of them. This study aims to conduct a comprehensive genomic analysis of Pediococcus acidilactici strain BCB1H to elucidate its genetic composition, functional elements, and potential biotechnological applications. The objectives include identifying key genomic features such as coding sequences, tRNA and rRNA genes, antibiotic resistance genes, and secondary metabolite biosynthetic gene clusters, which will highlight the adaptability and potential of P. acidilactici strain BCB1H for use in a variety of industrial and therapeutic applications. P. acidilactici strain BCB1H was analyzed using whole-genome sequencing, which used advanced sequencing technologies to obtain comprehensive genomic data. Key genomic features, such as coding sequences, tRNA and rRNA genes, antibiotic resistance genes, and secondary metabolite biosynthetic gene clusters, were identified through bioinformatics analyses. The genomic analysis of P. acidilactici strain BCB1H revealed a genome size of approximately 1.92 million base pairs with a GC content of 42.4%. The annotation identified 1,895 genes across 192 subsystems, highlighting the metabolic pathways and functional categories. Notably, specialty genes associated with carbohydrate metabolism, stress response, pathogenicity, and amino acid synthesis were identified, underscoring the versatility and potential applications in food technology and medicine. These findings shed light on the genetic makeup and functional potential of P. acidilactici strain BCB1H, highlighting its flexibility and industrial importance. The genetic traits discovered suggest its prospective use in probiotics, food preservation, and biotechnological advancements. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a notorious pathogen associated with life-threatening infections, with its outer membrane protein A (OmpA) being a key contributor to its pathogenicity by targeting epithelial cell apoptosis. The study presents an in silico analysis of chalcone derivatives as potential therapeutic agents against the outer membrane protein A (OmpA) of Acinetobacter baumannii. We performed molecular docking to evaluate the binding interactions, revealing that isobavachalcone exhibited the highest binding affinity. Further fragment optimization (FOI) of isobavachalcone improved its binding energy. Additionally, ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis was conducted to assess the pharmacokinetic properties of the compounds. Antigenicity and allergenicity of the protein show that this protein is virulent and antigenic. Moreover, molecular docking was performed and the result shows that isobavachalcone showed the highest binding energy at -6.7 kcal/mol. Furthermore, for a more potent compound, fragment optimization was performed and led to a new lead compound fragment optimized isobavachalcone (FOI) which shows increased binding energy −6 kcal/mol. ADMET and toxicity analysis was performed of both the compounds isobavachalcone and FOI which revealed favorable pharmacokinetic profiles for both compounds, but toxicity analysis showed discrepancies, with the isobavachalcone exhibiting toxicity but FOI compound showing no detectable toxicity. This underscores the importance of structure optimization in drug development. Overall, chalcone derivatives show promise as antibacterial agents against A. baumannii, with computational analyses aiding in compound selection and optimization. While both isobavachalcone and its FOI showed favorable pharmacokinetics, in vivo and in vitro validation is needed to confirm their therapeutic potential. [ABSTRACT FROM AUTHOR]

Quantitative structure-property relationship (QSPR) modeling has emerged as a pivotal tool in the field of medicinal chemistry and drug design, offering a predictive framework for understanding the correlation between chemical structure and physicochemical properties. Topological indices are mathematical descriptors derived from the molecular graphs that capture structural features and connectivity, playing a crucial role in QSPR analysis by quantitatively relating chemical structures to their physicochemical properties and biological activities. Lung cancer is characterized by its aggressive nature and late-stage diagnosis, often limiting treatment options and significantly impacting patient survival rates. This study focuses on the selection of drugs used to treat lung cancer, including dacomitinib, selpercatinib, tepotinib, trametinib, sotorasib, etoposide, alectinib, paclitaxel, dabrafenib, entrectinib, crizotinib, ceritinib, lorlatinib, afatinib, pralsetinib, brigatinib, erlotinib, adagrasib, gefitinib, vinorelbine, gemcitabine, docetaxel, and pemetrexed. Using molecular structural measures such as degree, neighborhood degree sum, and modified reverse degree, we have developed QSPR models to predict physicochemical properties through the topological indices derived from these structural measures. We then conducted a comparative analysis, incorporating correlation analysis, to identify the model with the highest predictive accuracy. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic compounds (PACs) are pervasive environmental contaminants derived from diverse sources including pyrogenic (e.g., combustion processes), petrogenic (e.g., crude oil), and biological origins. They are commonly found in gasoline, coal, and crude oil, reflecting their prevalence and varied origins in natural and anthropogenic activities. The aim of this study is to use Bacillus tropicus which is a spore-forming, gram-positive and facultative anaerobic bacteria, containing a gene for PACs degradtion. In this study bacterial sample was collected from women's vaginal discharge through streaking and spreading techniques. The DNA was extracted from bacterial culture and then the bacterium was identified through 16S rRNA which appeared to be B.tropicus. Then the computational analysis was conducted where the sequence similarity and functional analysis of alcohol dehydrogenase EutG protein from B.tropicus was analyzed through PSI-BLAT and SMART tool, respectively. The PSI-BLAST showed 100% query coverage score and 9 domains of alcohol dehydrogenase EutG protein were predicted through SMART tool. The quality of the protein was also assessed through ProQ server with a predicted LQ score of 8.091, a Maxsub score of − 0.350 and a z score of − 10.76. Then the phylogentic analysis was conducted to know the evolutionary relationship and closely related taxa. The 3D structure of the protein was predicted through SWISS MODEL and its quality was predicted through ERRAT with overall qauality factor of 98.708. The Ramachandran plot also predicted its quality and showed that 93.8% residues were in the most favored region. After this, 3D stucture of PACs were obtained from PubChem and molecular docking of the protein was performed with each of the compound. The lowest energy of − 10.3 was obtained with Indeno[1,2,3-cd] pyrene and the best docked complex was visulaized through discover studio to analyze its binding residues. Lastly, in-silico site-directed mutagenesis studies were performed which showed that the EutG gene (codes for alcoholic dehydrogenase) obtained from B. tropicus, will not get altered or have any decreasing effect on the enzyme's stability if it goes through any mutations. This suggests that B. tropicus can act as an efficient, non-virulent, and reliable candidate for the eco-friendly and cost-effective bioremediation of PACs. [ABSTRACT FROM AUTHOR]

Buruli ulcer (BU) a neglected disease induced by the bacterium Mycobacterium ulcerans, predominantly impacts tropical and subtropical areas with its pathophysiology ascribed to the Mycolactone protein. Current antibiotics frequently prove insufficient to manage advanced or chronic ulcers and the rise of drug resistance presents a considerable challenge. This work aims to address these challenges by employing computational methods to identify therapeutic candidates from organic compounds, which may be developed into more effective therapies for Buruli ulcer. The Gas-Chromatography Mass Spectrometry (GCMS) analysis of the Thymus Vulgaris identified the 29 bioactive compounds as potential drug candidates having different medicinal properties. Out of the 29 compounds against the mycolactone protein, 14 compounds demonstrated a binding affinity higher than − 6 kcal/mol predicted through PyRx. Among all compounds, gamma sitosterol and borneol showed the highest binding affinity − 7.7 kcal/mol. The ADMET analysis predicted that the compound borneol crosses the PGP + through the Blood Brain Barrier and gastrointestinal tract without violating Lipinski's rule of 5 having high water solubility, and log p-value of 2.29. The molecular dynamic simulation was performed and showed the Eigenvalue of 1.332692e-04. The leads identified in the study have demonstrated encouraging outcomes with regard to their efficacy, toxicity, pharmacokinetics, and safety. Further experimental investigations can be conducted to evaluate their anti-bacterial activity, and their molecular frameworks could be utilized as a valuable foundation for designing new drugs for the treatment of Buruli ulcer. [ABSTRACT FROM AUTHOR]

L. edodes (L. edodes) is the most consumed mushroom in the world and has been well known for its therapeutic potential as an edible and medicinal candidate, it contains dietary fibers, vitamins, proteins, minerals, and carbohydrates. In the current study butanolic extract of mushroom was used to form semisolid butanol extract. The current study aimed to explore biometabolites that might have biological activities in n-butanol extract of L. edodes using FT-IR and GC-MS and LC-MS. The synergistic properties of bioactive compounds were futher assessed by performing different biological assays such as antioxidant, anti-inflammatory and antidiabetic. FTIR spectra showed different functional groups including amide N-H group, Alkane (C-H stretching), and (C = C stretching) groups at different spectrum peaks in the range of 500 cm -1 to 5000 cm -1 respectively. GC-MS profiling of n-butanol extract depicted 34 potent biomolecules among those dimethyl; Morphine, 2TMS derivative; Benzoic acid, methyl ester 1-(2-methoxy-1-methylethoxy)-2-propanol were spotted at highest range. Results indicate that L. edodes n-butanol extract showed a maximum anti-inflammatory potential 91.4% at 300 mg/mL. Antioxidant activity was observed by measuring free radical scavenging activity which is 64.6% at optimized concentration along with good antidiabetic activity. In-silico study executed the biopotential of active ingredient morphine which proved the best docking score (- 7.0 kJ/mol) against aldose reductase. The in-silico drug design analysis was performed on biometabolites detected through GC-MS that might be a potential target for sulfatase-2 to treat ruminated arthritis. Morphine binds more strongly (- 7.9 kJ/mol) than other bioactive constituents indicated. QSAR and ADMET analysis shown that morphine is a good candidates against ruminated arthritis. The current study showed that L. edodes might be used as potent drug molecules to cure multiple ailments. As mushrooms have high bioactivity, they can be used against different diseases and to develop antibacterial drugs based on the current situation in the world in which drug resistance is going to increase due to misuse of antibiotics so new and noval biological active compounds are needed to overcome the situation., (© 2024. The Author(s).)