Anti-inflammatory and anti-diabetic properties of indanone derivative isolated from Fernandoa adenophylla in vitro and in silico studies.

Fernandoa adenophylla, due to the presence of phytochemicals, has various beneficial properties and is used in folk medicine to treat many conditions. This study aimed to isolate indanone derivative from F. adenophylla root heartwood and assess in-vitro anti-inflammatory and anti-diabetic characteristics at varying concentrations. Heat-induced hemolysis and glucose uptake by yeast cells assays were conducted to evaluate these properties. Besides, docking analyses were performed on four molecular targets. These studies were combined with molecular dynamics simulations to elucidate the time-evolving inhibitory effect of selected inhibitors within the active pockets of the target proteins (COX-1 and COX-2). Indanone derivative (10-100 µM) inhibited the lysis of human red blood cells from 9.12 ± 0.75 to 72.82 ± 4.36% and, at 5-100 µM concentrations, it significantly increased the yeast cells' glucose uptake (5.16 ± 1.28% to 76.59 ± 1.62%). Concluding, the isolated indanone might act as an anti-diabetic agent by interacting with critical amino acid residues of 5' adenosine monophosphate-activated protein kinase (AMPK), and it showed a binding affinity with anti-inflammatory targets COX-1, COX-2, and TNF-α. Besides, the obtained results may help to consider the indanone derivative isolated from F. adenophylla as a promising candidate for drug delivery, subject to outcomes of further in vivo and clinical studies.

Synthesis of Iron Oxide Nanoparticles from Madhuca indica Plant Extract and Assessment of Their Cytotoxic, Antioxidant, Anti-Inflammatory, and Anti-Diabetic Properties via Different Nanoinformatics Approaches.

Recently, nanobiotechnology has attracted a lot of attention, as it is a rapidly emerging field that is still growing and developing efficient and advanced therapeutic protocols under the umbrella of nanomedicine. It can revolutionize solutions to biomedical problems by developing effective treatment protocols and therapeutics. However, focus and research are still required to make these therapeutics more effective and safer to use. In this study, iron oxide nanoparticles were synthesized from Madhuca indica extract using green synthesis protocols. The nanoparticles were further characterized based on their absorption spectrum, size, structural morphology, and other related parameters. Biological assays were also performed to evaluate biological applications for the synthesized nanoparticles. In silico analysis was performed to assess the druglike properties of synthesized nanoparticles. The results proved an optimized synthesis of the iron oxide nanoparticles with the size of 56 nm confirmed by SEM. The FTIR analysis predicted the presence of nitro and carbonyl groups in the synthesized nanoparticles. The 81% DPPH inhibition confirmed the antioxidant activity, and the 96.20% inhibition of egg albumin protein confirmed the anti-inflamatory activity. Additionally, the 73.26% inhibition of α-amylase, which was more than that of the control used, confirmed the antidiabetic activity. The ADMET analysis confirmed the synthesized nanoparticles as potential therapeutic candidates as well. However, further evaluation for safety concerns is still required to use these FeONPs as potential therapeutic agents. This study can be proved as a significant contribution to the scientific community and a gateway to the future scientists who are willing to work on nanomedicine and nanobiotechnology. ADMET analysis confirmed the synthesized nanoparticles as potential therapeutic candidates as well. However, further evaluation for safety concerns is still required to use these FeONPs and potential therapeutic agents.

Comparative genomics of food-derived probiotic Lactiplantibacillus plantarum K25 reveals its hidden potential, compactness, and efficiency.

This study aimed to investigate the intricate genetic makeup of the Lactiplantibacillus plantarum K25 strain by conducting a comprehensive analysis of comparative genomics. The results of our study demonstrate that the genome exhibits a high-level efficiency and compactness, comprising a total of 3,199 genes that encode proteins and a GC content of 43.38%. The present study elucidates the evolutionary lineage of Lactiplantibacillus plantarum strains through an analysis of the degree of gene order conservation and synteny across a range of strains, thereby underscoring their closely interrelated evolutionary trajectories. The identification of various genetic components in the K25 strain, such as bacteriocin gene clusters and prophage regions, highlights its potential utility in diverse domains, such as biotechnology and medicine. The distinctive genetic elements possess the potential to unveil innovative therapeutic and biotechnological remedies in future. This study provides a comprehensive analysis of the L. plantarum K25 strain, revealing its remarkable genomic potential and presenting novel prospects for utilizing its unique genetic features in diverse scientific fields. The present study contributes to the existing literature on Lactiplantibacillus plantarum and sets the stage for prospective investigations and practical implementations that leverage the exceptional genetic characteristics of this adap organism.

Molecular Characterization of spa, hld, fmhA, and lukD Genes and Computational Modeling the Multidrug Resistance of Staphylococcus Species through Callindra harrisii Silver Nanoparticles.

The problem of multidrug resistance in bacterial pathogens is significant and is related to the high morbidity and death rates of living things due to increased levels of beta-lactamases. Plant-derived nanoparticles have gained a great significance in the field of science and technology to combat bacterial diseases, especially multidrug-resistant bacteria. This study examines the multidrug resistance and virulent genes of identified pathogenic Staphylococcus species obtained from Molecular Biotechnology and Bioinformatics Laboratory (MBBL), culture collection. The polymerase chain reaction-based characterization of Staphylococcus aureus and Staphylococcus argenteus having ON875315.1 and ON876003.1 accession IDs revealed the presence of the spa, LukD, fmhA, and hld genes. The green synthesis of silver nanoparticles (AgNPs) was carried out by utilizing the leaf extract of Calliandra harrisii, of which metabolites act as capping and reducing agents for the precursor of nano-synthesis, i.e., AgNO3 of 0.25 M. The synthesized AgNPs were characterized via UV-vis spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray analysis which inferred the bead-like shape of our nanoparticles with the size of 2.21 nm with the existence of aromatic and hydroxyl functional groups at surface plasmon resonance of 477 nm. The antimicrobial activity by AgNPs showed 20 mm inhibition of Staphylococcus species as compared to the vancomycin and cefoxitin antibiotics along with crude plant extract, which showed a minimum zone of inhibition. The synthesized AgNPs were also analyzed for various biological activities like anti-inflammatory with 99.15% inhibition in protein denaturation, antioxidant with 99.8% inhibition in free radical scavenging, antidiabetic with 90.56% inhibition of alpha amylase assay, and anti-haemolytic with 89.9% inhibition in cell lysis which shows good bioavailability and biocompatibility of the nanoparticles with the biological system of the living being. The amplified genes (spa, LukD, fmhA, and hld) were also analyzed for their interaction with AgNPs computationally at the molecular level. The 3-D structure of AgNP and amplified genes was retrieved from ChemSpider (ID: 22394) and Phyre2 online server, respectively. The binding affinities of AgNP with spa, LukD, fmhA, and hld were -7.16, -6.5, -6.45, and -3.3 kJ/mol, respectively, which infers a good docking score except of hld which is -3.3 kJ/mol due to its small size. The salient features of biosynthesized AgNPs proved to be an effective approach in combating the multidrug-resistant Staphylococcus species in the future.

Identification of Bacterial Strains and Development of anmRNA-Based Vaccine to Combat Antibiotic Resistance in Staphylococcus aureus via In Vitro and In Silico Approaches.

The emergence of antibiotic-resistant microorganisms is a significant concern in global health. Antibiotic resistance is attributed to various virulent factors and genetic elements. This study investigated the virulence factors of Staphylococcus aureus to create an mRNA-based vaccine that could help prevent antibiotic resistance. Distinct strains of the bacteria were selected for molecular identification of virulence genes, such as spa, fmhA, lukD, and hla-D, which were performed utilizing PCR techniques. DNA extraction from samples of Staphylococcus aureus was conducted using the Cetyl Trimethyl Ammonium Bromide (CTAB) method, which was confirmed and visualized using a gel doc; 16S rRNA was utilized to identify the bacterial strains, and primers of spa, lukD, fmhA, and hla-D genes were employed to identify the specific genes. Sequencing was carried out at Applied Bioscience International (ABI) in Malaysia. Phylogenetic analysis and alignment of the strains were subsequently constructed. We also performed an in silico analysis of the spa, fmhA, lukD, and hla-D genes to generate an antigen-specific vaccine. The virulence genes were translated into proteins, and a chimera was created using various linkers. The mRNA vaccine candidate was produced utilizing 18 epitopes, linkers, and an adjuvant, known as RpfE, to target the immune system. Testing determined that this design covered 90% of the population conservancy. An in silico immunological vaccine simulation was conducted to verify the hypothesis, including validating and predicting secondary and tertiary structures and molecular dynamics simulations to evaluate the vaccine's long-term viability. This vaccine design may be further evaluated through in vivo and in vitro testing to assess its efficacy.

Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib.

BCR-ABL1 is a fusion protein as a result of a unique chromosomal translocation (producing the so-called Philadelphia chromosome) that serves as a clinical biomarker primarily for chronic myeloid leukemia (CML); the Philadelphia chromosome also occurs, albeit rather rarely, in other types of leukemia. This fusion protein has proven itself to be a promising therapeutic target. Exploiting the natural vitamin E molecule gamma-tocotrienol as a BCR-ABL1 inhibitor with deep learning artificial intelligence (AI) drug design, this study aims to overcome the present toxicity that embodies the currently provided medications for (Ph+) leukemia, especially asciminib. Gamma-tocotrienol was employed in an AI server for drug design to construct three effective de novo drug compounds for the BCR-ABL1 fusion protein. The AIGT's (Artificial Intelligence Gamma-Tocotrienol) drug-likeliness analysis among the three led to its nomination as a target possibility. The toxicity assessment research comparing AIGT and asciminib demonstrates that AIGT, in addition to being more effective nonetheless, is also hepatoprotective. While almost all CML patients can achieve remission with tyrosine kinase inhibitors (such as asciminib), they are not cured in the strict sense. Hence it is important to develop new avenues to treat CML. We present in this study new formulations of AIGT. The docking of the AIGT with BCR-ABL1 exhibited a binding affinity of -7.486 kcal/mol, highlighting the AIGT's feasibility as a pharmaceutical option. Since current medical care only exclusively cures a small number of patients of CML with utter toxicity as a pressing consequence, a new possibility to tackle adverse instances is therefore presented in this study by new formulations of natural compounds of vitamin E, gamma-tocotrienol, thoroughly designed by AI. Even though AI-designed AIGT is effective and adequately safe as computed, in vivo testing is mandatory for the verification of the in vitro results.

Enzyme Inhibitory Activities of Extracts and Carpachromene from the Stem of Ficus benghalensis.

Ficus benghalensis is one of the potential medicinal plants which is used locally for the treatment of various ailments such as diabetes, antiasthmatic, and wound healing. To provide a scientific background to these folklores, the current study was designed to evaluate the extract and isolated compound against various enzymes such as ureases, tyrosinase, and phosphodiesterase. The methanolic extract and carpachromene demonstrated a significant urease inhibition effect with maximum percent inhibition of 72.09 and 92.87%, respectively. Regarding the tyrosinase inhibition, the percent antagonist effect of carpachromene and the methanolic extract was 84.80 and 70.98%, respectively. The phosphodiesterase was also significantly antagonized by crude extract and carpachromene with a maximum percent inhibition of 82.98% and 89.54%, respectively. The docking study demonstrated that the carpachromene fits well into the active site of all three enzymes with significant interactions. Carpachromene might possess the potential to inhibit all three enzymes and can effectively treat different diseases associated with the hyperactivity of these enzymes. In conclusion, the crude extract and carpachromene exhibit significant urease, tyrosinase, and phosphodiesterase inhibitory activity which might be used against various diseases. In conclusion, the crude extract and carpachromene exhibit significant urease, tyrosinase, and phosphodiesterase inhibitory activity which might be used against diabetes and bronchoconstriction. Further, the current study provides scientific backup to the folklore (antidiabetic and antiasthmatic) of Ficus benghalensis.

Pharmacological activities and gas chromatography-mass spectrometry analysis for the identification of bioactive compounds from Justicia adhatoda L.

The current study aimed to assess the pharmacological potential of Justicia adhatoda by evaluating the presence of biologically active compounds using the gas chromatography-mass spectrometry approach and to undertake biological activities for the effectiveness of the present compounds using standard tests. A total of 21 compounds were identified in the gas chromatography-mass spectrometry analysis of the ethyl acetate fraction in which 14 of the identified compounds are recognized for their pharmacological potential in the literature. In total, four fractions (ethyl acetate, chloroform, n-hexane, and aqueous) were evaluated for pharmacological activities. In carrageenan-induced inflammation, the chloroform fraction exhibited high anti-inflammatory activity (46.51%). Similarly, the analgesic potential of ethyl acetate fraction was the most effective (300 mg/kg) in the acetic acid-induced test. Similarly, in the formalin test, ethyl acetate fraction exhibited maximum inhibition in both early (74.35%) and late phases (88.38). Maximum inhibition of pyrexia (77.98%) was recorded for the ethyl acetate fraction (300 mg/kg). In DPPH assay, the ethyl acetate fraction revealed the highest scavenging potential among other fractions (50 µg/ml resulted in 50.40% and 100 µg/ml resulted in 66.74% scavenging).