Micro-nanoemulsion and nanoparticle-assisted drug delivery against drug-resistant tuberculosis: recent developments.

Tuberculosis (TB) is a major global health problem and the second most prevalent infectious killer after COVID-19. It is caused by () and has become increasingly challenging to treat due to drug resistance. The World Health Organization declared TB a global health emergency in 1993.

The Implication of Mechanistic Approaches and the Role of the Microbiome in Polycystic Ovary Syndrome (PCOS): A Review.

As a complex endocrine and metabolic condition, polycystic ovarian syndrome (PCOS) affects women's reproductive health. These common symptoms include hirsutism, hyperandrogenism, ovulatory dysfunction, irregular menstruation, and infertility. No one knows what causes it or how to stop it yet.

Multispectroscopic, virtual and insights into the photoaging defense mediated by the natural food colorant bixin.

An upsurge in early onset of photoaging due to repeated skin exposure to environmental stressors such as UV radiation is a challenge for pharmaceutical and cosmeceutical divisions. Current reports indicate severe side effects because of chemical or synthetic inhibitors of matrix metalloproteases (MMPs) in anti-skin aging cosmeceuticals. We evaluated the adequacy of bixin, a well-known FDA certified food additive, as a scavenger of free radicals and its inhibitory mechanism of action on MMP1, collagenase, elastase, and hyaluronidase.

The influence of machine learning technologies in gut microbiome research and cancer studies - A review.

Gut microbial profiles induce cancer growth and impact treatment effectiveness, tolerance, and safety. There is still more to discover about the relationship between diseases and the microbiota and its clinical consequences. Even though much of the study is still in its early phases, the 'omics' technologies were widely used for microbiome analysis due to the increased size of datasets available in public databases.

Designing, Synthesis, and Anti-Breast Cancer Activity of a Series of New Quinazolin-4(1H)-one Derivatives.

The inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) protein could be a promising treatment for breast cancer. In this regard, docking studies were accomplished on various functionalized organic molecules. Among them, several derivatives of quinazolin-4(1H)-one exhibited anti-breast cancer activity and satisfied the drug likeliness properties.

Computational investigation to identify potent inhibitors of the GTPase-Kirsten RAt sarcoma virus (K-Ras) mutants G12C and G12D.

K-Ras mutations are frequent in various cancer types, and according to recent research, K-Ras possesses four-drug targeting sites. This increased our interest in finding potential small molecule inhibitors with anticancer activity to treat K-Ras-driven cancers. We utilized integrated bioinformatic strategies, such as XP docking, MM-GBSA, cell-line cytotoxicity prediction, ADMET, and molecular simulation, to discover potential inhibitors of G12C and G12D mutants compared to sotorasib, which is a recent FDA-approved inhibitor of G12C.

Effect of shape and anthocyanin capping on antibacterial activity of CuI particles.

The recent upsurge of antibiotic-resistant infections has posed to be a serious health concern worldwide. In the present paper, the effect of shape & capping agent on the antibacterial activity (on Skin and Urinary Tract Infection (UTI) causing bacteria) of copper iodide (CuI) particles was probed. CuI synthesized without a capping agent was leaf-like, and that with one was prismatic in shape.

Comparison of potential inhibitors and targeting fat mass and obesity-associated protein causing diabesity through docking and molecular dynamics strategies.

Genome-wide association studies (GWAS) have identified an association between polymorphisms in the FTO gene and obesity. The FTO: rs9939609, an intronic variant, is considered a risk allele for developing diabesity in homozygous and heterozygous forms. This study aimed to investigate the molecular structure of the available inhibitors specific to the FTO mutations along with the rs9939609 variant.

Residue interaction networks of K-Ras protein with water molecules identifies the potential role of switch II and P-loop.

The mutant K-Ras with aberrant signaling is the primary cause of several cancers. The proposed study investigated the influence of water molecules in K-Ras crystal structure, where they have a significant function by understanding their residue interaction networks (RINs). We analyzed the RINs of K-Ras with and without water molecules and determined their interaction properties.

Molecular dynamics simulations to decipher the structural and functional consequences of pathogenic missense mutations in the galactosylceramidase (GALC) protein causing Krabbe's disease.

Krabbe disease (KD), also known as globoid cell leukodystrophy disease, is an autosomal recessive lysosomal storage genetic disorder, which is caused by the deficiency of galactocerebrosidase (GALC) coding gene (). This study aimed to use extensive computational pipelines in understanding the missense mutations in GALC. We retrieved 176 mutations from the public databases and subjected them to pathogenicity, stability, and conservation analyses.

Structural analysis of missense mutations in galactokinase 1 (GALK1) leading to galactosemia type-2.

Galactosemia type 2 is an autosomal recessive disorder characterized by the deficiency of galactokinase (GALK) enzyme due to missense mutations in GALK1 gene, which is associated with various manifestations such as hyper galactosemia and formation of cataracts. GALK enzyme catalyzes the adenosine triphosphate (ATP)-dependent phosphorylation of α-d-galactose to galactose-1-phosphate. We searched 4 different literature databases (Google Scholar, PubMed, PubMed Central, and Science Direct) and 3 gene-variant databases (Online Mendelian Inheritance in Man, Human Gene Mutation Database, and UniProt) to collect all the reported missense mutations associated with GALK deficiency.

Glandular hair constituents of Mallotus philippinensis Muell. fruit act as tyrosinase inhibitors: Insights from enzyme kinetics and simulation study.

The glandular hair extracts from the fruit rind of Mallotus philippinensis Muell. is employed to treat various skin infections, however the anti-tyrosinase activity remains unknown. Hence the present study inspected on the anti-melanogenic activity of M.

Genotype-phenotype correlation in patients with isovaleric acidaemia: comparative structural modelling and computational analysis of novel variants.

Isovaleric acidaemia (IVA) is an autosomal recessive inborn error of leucine metabolism. It is caused by a deficiency in the mitochondrial isovaleryl-CoA dehydrogenase (IVD) enzyme. In this study, we investigated eight patients with IVA.

Deciphering the impact of somatic mutations in exon 20 and exon 9 of PIK3CA gene in breast tumors among Indian women through molecular dynamics approach.

We examined 25 breast tumor samples for somatic mutations in exon 20 and exon 9 of PIK3CA gene in South Indian population. Genomic DNA was isolated and amplified for PIK3CA gene, followed by direct sequencing of purified polymerase chain reaction products. We identified PI3K3CA mutations in 5 of 25 (20%), including four of the mutations in p.

Next generation delivery system for proteins and genes of therapeutic purpose: why and how?

Proteins and genes of therapeutic interests in conjunction with different delivery systems are growing towards new heights. "Next generation delivery systems" may provide more efficient platform for delivery of proteins and genes. In the present review, snapshots about the benefits of proteins or gene therapy, general procedures for therapeutic protein or gene delivery system, and different next generation delivery system such as liposome, PEGylation, HESylation, and nanoparticle based delivery have been depicted with their detailed explanation.

BSA nanoparticle loaded atorvastatin calcium--a new facet for an old drug.

Background: Currently, the discovery of effective chemotherapeutic agents poses a major challenge to the field of cancer biology. The present study focuses on enhancing the therapeutic and anti cancer properties of atorvastatin calcium loaded BSA (ATV-BSA) nanoparticles in vitro.

Methodology/results: BSA-ATV nanoparticles were prepared using desolvation technique.

Molecular docking and molecular dynamics study on the effect of ERCC1 deleterious polymorphisms in ERCC1-XPF heterodimer.

Excision repair cross complementation group 1 (ERCC1) is an important protein in the nucleotide excision repair (NER) pathway, which is responsible for removing DNA adducts induced by platinum based compounds. The heterodimer ERCC1-XPF is one of two endonucleases required for NER. Genetic variations or polymorphisms in ERCC1 gene alter DNA repair capacity.

Exploration of structural stability in deleterious nsSNPs of the XPA gene: A molecular dynamics approach.

Background: Distinguishing the deleterious from the massive number of non-functional nsSNPs that occur within a single genome is a considerable challenge in mutation research. In this approach, we have used the existing in silico methods to explore the mutation-structure-function relationship in the XPAgene.

Materials And Methods: We used the Sorting Intolerant From Tolerant (SIFT), Polymorphism Phenotyping (PolyPhen), I-Mutant 2.

In silico analysis of structural and functional consequences in p16INK4A by deleterious nsSNPs associated CDKN2A gene in malignant melanoma.

In this study, we identified the most deleterious nsSNP in CDKN2A gene through structural and functional properties of its protein (p16INK4A) and investigated its binding affinity with cdk6. Out of 118 SNPs, 14 are nsSNPs in the coding region and 17 SNPs were found in the untranslated region (UTR). FastSNP suggested that 7 SNPs in the 5' UTR might change the protein expression levels.

Investigations on the interactions of scorpion neurotoxins with the predicted structure of D1 dopamine receptor by protein-protein docking method. A bioinformatics approach.

Dopamine receptors play a critical role in the cell signalling process responsible for information transfer in neurons functioning in the nervous system. Development of improved therapeutics for disorders like Parkinson's disease and schizophrenia would be significantly enhanced with the availability of the 3D structure for the dopamine receptors. Scorpion neurotoxins are unique source of structural templates from which new therapeutic agents might be developed.