Evaluation of Tridax procumbens Secondary Metabolites Anti-Tuberculosis Activity by In Vitro and In Silico Methods.

Mycobacterium tuberculosis is a human pathogen that causes Tuberculosis (TB) disease. Researchers have reported the activity of traditional medicinal plants against human pathogens. However, antimycobacterial studies of medicinal plants against M.

Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR.

Nuclear receptors are ligand-activated transcription factors that can often be useful drug targets. Unfortunately, ligand promiscuity leads to two-thirds of receptors remaining clinically untargeted. PXR is a nuclear receptor that can be activated by diverse compounds to elevate metabolism, negatively impacting drug efficacy and safety.

Crystal structure of human Cep57 C-terminal domain reveals the presence of leucine zipper and the potential microtubule binding region.

Cep57, a vital centrosome-associated protein, recruits essential regulatory enzymes for centriole duplication. Its dysfunction leads to anomalies, including reduced centrioles and mosaic-variegated aneuploidy syndrome. Despite functional investigations, understanding structural aspects and their correlation with functions is partial till date.

Haemostatic potency of sodium alginate/aloe vera/sericin composite scaffolds - preparation, characterisation, and evaluation.

Fabrication of haemostatic materials with excellent antimicrobial, biocompatible and biodegradable properties remains as a major challenge in the field of medicine. Haemostatic agents play vital role in protecting patients and military individuals during emergency situations. Natural polymers serve as promising materials for fabricating haemostatic compounds due to their efficacy in promoting hemostasis and wound healing.

A bromodomain-independent mechanism of gene regulation by the BET inhibitor JQ1: direct activation of nuclear receptor PXR.

Bromodomain and extraterminal (BET) proteins are extensively studied in multiple pathologies, including cancer. BET proteins modulate transcription of various genes, including those synonymous with cancer, such as MYC. Thus, BET inhibitors are a major area of drug development efforts.

Visceral Fat Indices: Do They Help Differentiate Crohn's Disease and Intestinal Tuberculosis in Children?

Background And Aims: Crohn's disease [CD] and intestinal tuberculosis [ITB] are often difficult to differentiate. Mesenteric fat hypertrophy is a feature of CD. We evaluated the utility of fat indices (visceral fat [VF] and subcutaneous fat [SF]) in differentiating CD and ITB in children.

Structure-guided approach to modulate small molecule binding to a promiscuous ligand-activated protein.

Ligand-binding promiscuity in detoxification systems protects the body from toxicological harm but is a roadblock to drug development due to the difficulty in optimizing small molecules to both retain target potency and avoid metabolic events. Immense effort is invested in evaluating metabolism of molecules to develop safer, more effective treatments, but engineering specificity into or out of promiscuous proteins and their ligands is a challenging task. To better understand the promiscuous nature of detoxification networks, we have used X-ray crystallography to characterize a structural feature of pregnane X receptor (PXR), a nuclear receptor that is activated by diverse molecules (with different structures and sizes) to up-regulate transcription of drug metabolism genes.

Crystal Structure of Rho1 Reveals Its Evolutionary Relationship with Other Rho GTPases.

The Rho protein, a homolog of Ras, is a member of the Ras superfamily of small GTPases. Rho family proteins are involved in cytoskeletal organization, cell mobility, and polarity, and are implicated in cancer morphogenesis. Although Rho homologs from higher-order mammalian organisms are well studied, there are few studies examining Rho proteins in lower-level single-celled organisms.

Water Networks Repopulate Protein-Ligand Interfaces with Temperature.

High-resolution crystal structures highlight the importance of water networks in protein-ligand interactions. However, as these are typically determined at cryogenic temperature, resulting insights may be structurally precise but not biologically accurate. By collecting 10 matched room-temperature and cryogenic datasets of the biomedical target Hsp90α, we identified changes in water networks that impact protein conformations at the ligand binding interface.

Molecular basis of crosstalk in nuclear receptors: heterodimerization between PXR and CAR and the implication in gene regulation.

The 48 human nuclear receptors (NRs) form a superfamily of transcription factors that regulate major physiological and pathological processes. Emerging evidence suggests that NR crosstalk can fundamentally change our understanding of NR biology, but detailed molecular mechanisms of crosstalk are lacking. Here, we report the molecular basis of crosstalk between the pregnane X receptor (PXR) and constitutive androstane receptor (CAR), where they form a novel heterodimer, resulting in their mutual inhibition.

Structural basis of BAK activation in mitochondrial apoptosis initiation.

BCL-2 proteins regulate mitochondrial poration in apoptosis initiation. How the pore-forming BCL-2 Effector BAK is activated remains incompletely understood mechanistically. Here we investigate autoactivation and direct activation by BH3-only proteins, which cooperate to lower BAK threshold in membrane poration and apoptosis initiation.

Efficacy of amitriptyline in pediatric functional abdominal pain disorders: A randomized placebo-controlled trial.

Background And Aim: Amitriptyline improves symptoms in functional abdominal pain disorders (FAPD) in adults with variable results in pediatric studies. The study aims to evaluate the efficacy of amitriptyline in pediatric FAPD.

Methods: In this open-label trial, children (≤ 18 years) diagnosed as FAPD based on ROME IV criteria were randomized to amitriptyline or placebo for 12 weeks.

Chelation therapy in liver diseases of childhood: Current status and response.

Chelation is the mainstay of therapy in certain pediatric liver diseases. Copper and iron related disorders require chelation. Wilson's disease (WD), one of the common causes of cirrhosis in children is treated primarily with copper chelating agents like D-penicillamine and trientine.

Pediatric non-cirrhotic portal hypertension: Endoscopic outcome and perspectives from developing nations.

Non-cirrhotic portal hypertension (NCPH) forms an important subset of portal hypertension in children. Variceal bleed and splenomegaly are their predominant presentation. Laboratory features show cytopenias (hypersplenism) and preserved hepatic synthetic functions.

Unraveling the Structural Basis of Selective Inhibition of Human Cytochrome P450 3A5.

The human cytochrome P450 (CYP) CYP3A4 and CYP3A5 enzymes metabolize more than one-half of marketed drugs. They share high structural and substrate similarity and are often studied together as CYP3A4/5. However, CYP3A5 preferentially metabolizes several clinically prescribed drugs, such as tacrolimus.

Gastrointestinal bleeding due to pseudoaneurysms in children.

Radiological embolization is the treatment of choice in adults with visceral artery pseudoaneurysm (PSA) and gastrointestinal bleeding, but pediatric data is scanty. We analyzed the etiology, clinical presentation, and outcome of radiological intervention in children with PSA of celiac (CA) or superior mesenteric artery (SMA) branches. Electronic records of children with PSA of CA or SMA branches were reviewed and data on clinical and laboratory profile, radiological intervention, and outcome was recorded.

The genome of a Bacteroidetes inhabitant of the human gut encodes a structurally distinct enoyl-acyl carrier protein reductase (FabI).

Enoyl-acyl carrier protein reductase (FabI) catalyzes a rate-controlling step in bacterial fatty-acid synthesis and is a target for antibacterial drug development. A phylogenetic analysis shows that FabIs fall into four divergent clades. Members of clades 1-3 have been structurally and biochemically characterized, but the fourth clade, found in members of phylum Bacteroidetes, is uncharacterized.

Molecular docking, quantum chemical computational and vibrational studies on bicyclic heterocycle "6-nitro-2,3-dihydro-1,4-benzodioxine": Anti-cancer agent.

The heterocyclic aromatic compounds are primarily used to make pharmaceutical and agrochemicals. In addition, these compounds can be chosen as antioxidants, corrosion inhibitors, electro and opto-electronic devices, polymer material, dye stuff, developers, etc. On the account of this, the heterocyclic aromatic 6-nitro-2,3-dihydro-1,4-benzodioxine (6N3DB) was chosen and the structure is optimized to predict the important properties of it.

Peritoneal Lymphomatosis Masquerading as Pyoperitoneum in a Teenage Boy.

A 16-year-old boy presented with 1 month of fever, abdominal pain, and distension. The ascitic tap drained pus-like fluid, and ultrasonography showed diffuse thickening of the omentum and mesentery with echogenic ascites. A diagnosis of pyoperitoneum due to peritoneal tuberculosis with secondary infection was suspected, and antitubercular therapy was started elsewhere, but there was no improvement.

Structural basis for the pathogenesis of Campylobacter jejuni Hcp1, a structural and effector protein of the Type VI Secretion System.

The Type VI Secretion System (T6SS) provides enhanced virulence to Campylobacter jejuni and has been associated with a high incidence of bloody diarrhea. The hemolysin-coregulated protein (Hcp)-the hallmark of the T6SS-can act as a structural and effector protein. Unlike other T6SS-harboring bacteria, which possess multiple Hcp proteins each performing different functions, C.

Structure and Mechanisms of NT5C2 Mutations Driving Thiopurine Resistance in Relapsed Lymphoblastic Leukemia.

Activating mutations in the cytosolic 5'-nucleotidase II gene NT5C2 drive resistance to 6-mercaptopurine in acute lymphoblastic leukemia. Here we demonstrate that constitutively active NT5C2 mutations K359Q and L375F reconfigure the catalytic center for substrate access and catalysis in the absence of allosteric activator. In contrast, most relapse-associated mutations, which involve the arm segment and residues along the surface of the inter-monomeric cavity, disrupt a built-in switch-off mechanism responsible for turning off NT5C2.

Expression system for structural and functional studies of human glycosylation enzymes.

Vertebrate glycoproteins and glycolipids are synthesized in complex biosynthetic pathways localized predominantly within membrane compartments of the secretory pathway. The enzymes that catalyze these reactions are exquisitely specific, yet few have been extensively characterized because of challenges associated with their recombinant expression as functional products. We used a modular approach to create an expression vector library encoding all known human glycosyltransferases, glycoside hydrolases, and sulfotransferases, as well as other glycan-modifying enzymes.

Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase.

Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) play a central role in tryptophan metabolism and are involved in many cellular and disease processes. Here we report the crystal structure of human TDO (hTDO) in a ternary complex with the substrates L-Trp and O and in a binary complex with the product N-formylkynurenine (NFK), defining for the first time the binding modes of both substrates and the product of this enzyme. The structure indicates that the dioxygenation reaction is initiated by a direct attack of O on the C atom of the L-Trp indole ring.

Structure of AcrH-AopB Chaperone-Translocator Complex Reveals a Role for Membrane Hairpins in Type III Secretion System Translocon Assembly.

Type III secretion systems (T3SSs) are adopted by pathogenic bacteria for the transport of effector proteins into host cells through the translocon pore composed of major and minor translocator proteins. Both translocators require a dedicated chaperone for solubility. Despite tremendous efforts in the past, structural information regarding the chaperone-translocator complex and the topology of the translocon pore have remained elusive.