Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network.

The nuclear immunophilin FKBP25 interacts with chromatin-related proteins and transcription factors and is suggested to interact with nucleic acids. Currently the structural basis of nucleic acid binding by FKBP25 is unknown. Here we determined the nuclear magnetic resonance (NMR) solution structure of full-length human FKBP25 and studied its interaction with DNA. The FKBP25 structure revealed that the N-terminal helix-loop-helix (HLH) domain and C-terminal FK506-binding domain (FKBD) interact with each other and that both of the domains are involved in DNA binding. The HLH domain forms major-groove interactions and the basic FKBD loop cooperates to form interactions with an adjacent minor-groove of DNA. The FKBP25–DNA complex model, supported by NMR and mutational studies, provides structural and mechanistic insights into the nuclear immunophilin-mediated nucleic acid recognition.

The association of microorganisms with livestock as endosymbionts, opportunists, and pathogens has been a matter of debate for a long time. Several livestock-associated bacterial and other microbial species have been identified and characterized through traditional culture-dependent genomic approaches. However, it is imperative to understand the comprehensive microbial network of domestic animals for their wellness, disease management, and disease transmission control. Since it is strenuous to provide a niche replica to any microorganisms while culturing them, thus a substantial number of microbial communities remain obscure. Metagenomics has laid out a powerful lens for gaining insight into the hidden microbial diversity by allowing the direct sequencing of the DNA isolated from any livestock sample like the gastrointestinal tract, udder, or genital system. Through metatranscriptomics and metabolomics, understanding gene expression profiles of the microorganisms and their molecular phenotype has become unchallenging. With large data sets emerging out of the genomic, metagenomic, and other meta-omics methods, several computational tools have also been developed for curation, assembly, gene prediction, and taxonomic profiling of the microorganisms. This review provides a detailed account of the beneficial and pathogenic organisms that dwell within or on farm animals. Besides, it highlights the role of meta-omics and computational tools in a comprehensive analysis of livestock-associated microorganisms.

Heterotrimeric guanine nucleotide–binding proteins (G proteins) that function as molecular switches for cellular growth and metabolism are activated by GTP and inactivated by GTP hydrolysis. In uveal melanoma, a conserved glutamine residue critical for GTP hydrolysis in the G protein α subunit is often mutated in Gα _q or Gα ₁₁ to either leucine or proline. In contrast, other glutamine mutations or mutations in other Gα subtypes are rare. To uncover the mechanism of the genetic selection and the functional role of this glutamine residue, we analyzed all possible substitutions of this residue in multiple Gα isoforms. Through cell-based measurements of activity, we showed that some mutants were further activated and inactivated by G protein–coupled receptors. Through biochemical, molecular dynamics, and nuclear magnetic resonance–based structural studies, we showed that the Gα mutants were functionally distinct and conformationally diverse, despite their shared inability to hydrolyze GTP. Thus, the catalytic glutamine residue contributes to functions beyond GTP hydrolysis, and these functions include subtype-specific, allosteric modulation of receptor-mediated subunit dissociation. We conclude that G proteins do not function as simple on-off switches. Rather, signaling emerges from an ensemble of active states, a subset of which are favored in disease and may be uniquely responsive to receptor-directed ligands.