Shared early molecular mechanisms revealed in P301S and 5xFAD Alzheimer's disease mouse models.

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by early molecular events that influence disease progression. Still, the molecular mechanisms caused by different mutations of AD are not understood. We have performed a multidisciplinary study to investigate and compare the early stages of the pathology in two transgenic AD mouse models: P301S and 5xFAD.

Unleashing the future: The revolutionary role of machine learning and artificial intelligence in drug discovery.

Drug discovery is a complex and multifaceted process aimed at identifying new therapeutic compounds with the potential to treat various diseases. Traditional methods of drug discovery are often time-consuming, expensive, and characterized by low success rates. Because of this, there is an urgent need to improve the drug development process using new technologies.

Neurons Specialize in Presynaptic Autophagy: A Perspective to Ameliorate Neurodegeneration.

The efficient and prolonged neurotransmission is reliant on the coordinated action of numerous synaptic proteins in the presynaptic compartment that remodels synaptic vesicles for neurotransmitter packaging and facilitates their exocytosis. Once a cycle of neurotransmission is completed, membranes and associated proteins are endocytosed into the cytoplasm for recycling or degradation. Both exocytosis and endocytosis are closely regulated in a timely and spatially constrained manner.

Structure-Guided Identification of Novel Aromatase Inhibitors Targeting Breast Carcinoma.

Aromatase inhibitors play a critical therapeutic role in treating ER+ breast cancer, especially in postmenopausal women. However, their efficacy is often limited by resistance and severe side effects. Identifying new compounds that can disrupt aromatase enzyme function is essential.

Annual rhythm in immune functions of blood leucocytes in an ophidian, Natrix piscator.

Annual variations in animal's physiological functions are an essential strategy to deal with seasonal challenges which also vary according to the time of year. Information regarding annual adaptations in the immune-competence to cope with seasonal stressors in reptiles is scarce. The present research plan was designed to analyze the presence of circannual immune rhythms in defense responses of the leucocytes in an ophidian, Natrix piscator.

Clinical utility of i-gel and BlockBuster™ supraglottic devices for airway management in postburn injury contracture neck patients under general anesthesia: A randomized controlled trial.

Background: Post burn injury contracture (PBC) neck patients pose a unique challenge for the anesthesiologists. The use of supraglottic device (SGDs) for managing such patients is being increasingly used. We compared i-gel and LMA BlockBuster™ in PBC adult patients under general anesthesia (GA).

Renal Mitochondrial ATP Transporter Ablation Ameliorates Obesity-Induced CKD.

Significance Statement: This study sheds light on the central role of adenine nucleotide translocase 2 (ANT2) in the pathogenesis of obesity-induced CKD. Our data demonstrate that ANT2 depletion in renal proximal tubule cells (RPTCs) leads to a shift in their primary metabolic program from fatty acid oxidation to aerobic glycolysis, resulting in mitochondrial protection, cellular survival, and preservation of renal function. These findings provide new insights into the underlying mechanisms of obesity-induced CKD and have the potential to be translated toward the development of targeted therapeutic strategies for this debilitating condition.

Mutations associated with autism lead to similar synaptic and behavioral alterations in both sexes of male and female mouse brain.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder based on synaptic abnormalities. The estimated prevalence rate of male individuals diagnosed with ASD prevails over females is in a proportion of 4:1. Consequently, males remain the main focus in ASD studies in clinical and experimental settings.

Plasmepsin II inhibitory potential of phytochemicals isolated from African antimalarial plants: a computational approach.

Plamepsin II has been identified as a therapeutic target in the life cycle and may lead to a drastic reduction in deaths caused by malaria worldwide. Africa flora is rich in medicinal qualities and possesses both simple and complex bioactive phytochemicals. This study utilized computational approaches like molecular docking, molecular dynamics simulation, quantum chemical calculations and ADMET to evaluate the plasmepsin II inhibitory properties of phytochemicals isolated from African antimalarial plants.

Nitric Oxide Synthase Inhibition Prevents Cell Proliferation in Glioblastoma.

Glioblastoma multiforme (GBM) is a prevalent and aggressive primary brain tumor, presenting substantial treatment challenges and high relapse rates. GBM is characterized by alterations in molecular signaling and enzyme expression within malignant cells. This tumor exhibits elevated nitric oxide (NO) levels.

Effects of extended-release 7-nitroindazole gel formulation treatment on the behavior of Shank3 mouse model of autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral deficits such as abnormalities in communication, social interaction, anxiety, and repetitive behavior. We have recently shown that the Shank3 mutation in mice representing a model of ASD causes excessive nitric oxide (NO) levels and aberrant protein S-nitrosylation. Further, 10-day daily injections of 7-NI, a neuronal nitric oxide synthase inhibitor, into Shank3 and Cntnap2 mutant mice (models of ASD) at a dose of 80 mg/kg reversed the manifestations of ASD phenotype.

Seasonal Immune Rhythms of head kidney and spleen cells in the freshwater Teleost, .

Annual rhythms in immune function are the reflection of a crucial physiological strategy to deal with environmental stressors. The fish are pivotal animal models to study the annual rhythm and to understand the evolution of the vertebrate biological system. The current research was planned to assess the annual changes in the innate immune functions of immune cells in a teleost, .

The NO Answer for Autism Spectrum Disorder.

Autism spectrum disorders (ASDs) include a wide range of neurodevelopmental disorders. Several reports showed that mutations in different high-risk ASD genes lead to ASD. However, the underlying molecular mechanisms have not been deciphered.

Machine-learning technique, QSAR and molecular dynamics for hERG-drug interactions.

One of the most well-known anti-targets defining medication cardiotoxicity is the voltage-dependent hERG K + channel, which is well-known for its crucial involvement in cardiac action potential repolarization. Torsades de Pointes, QT prolongation, and sudden death are all caused by hERG (the human Ether-à-go-go-Related Gene) inhibition. There is great interest in creating predictive computational () tools to identify and weed out potential hERG blockers early in the drug discovery process because testing for hERG liability and the traditional experimental screening are complicated, expensive and time-consuming.

Nature and Strength of Sulfur-Centered Hydrogen Bond in Methanethiol Aqueous Solutions.

Methanethiol (M) and water (W) clusters like dimers (MW, M, and W), trimers (MW, MW, M, and W), and tetramers (MW, MW, MW, M, and W) were studied to assess the strength of sulfur-centered hydrogen bonding using different levels of theories, viz, HF, MP2, MP3, MP4, B3LYP, B3LYP-D3, CCSD, CCSD(T)-F12, and CCSD(T) along with aug-cc-pVNZ (where N = D, T, and Q) basis sets. Interaction energies were found to be in the range of -3.3 to -5.

Genomic and structural mechanistic insight to reveal the differential infectivity of omicron and other variants of concern.

Background: The genome of SARS-CoV-2, is mutating rapidly and continuously challenging the management and preventive measures adopted and recommended by healthcare agencies. The spike protein is the main antigenic site that binds to the host receptor hACE-2 and is recognised by antibodies. Hence, the mutations in this site were analysed to assess their role in differential infectivity of lineages having these mutations, rendering the characterisation of these lineages as variants of concern (VOC) and variants of interest (VOI).

Identification of natural small molecule modulators of MurB from Salmonella enterica serovar Typhi Ty2 strain using computational and biophysical approaches.

The increase of antibiotic-resistant bacterial pathogens has created challenges in treatment and warranted the design of antibiotics against comparatively less exploited targets. The peptidoglycan (PG) biosynthesis delineates unique pathways for the design and development of a novel class of drugs. Mur ligases are an essential component of bacterial cell wall synthesis that play a pivotal role in PG biosynthesis to maintain internal osmotic pressure and cell shape.

Evaluation of the sex steroids mediated modulation of leucocyte immune responses in an ophidian .

The immune-suppressive role of sex steroids in mammals is well documented, but information on other vertebrates is limited. The present study was planned to analyze the effect of testosterone and progesterone in the modulation of immune functions of leucocytes in a reptile, . Reptiles are unique organisms and this study is novel in that it provides an insight into immune-reproductive cross-talk in a reptile.

Novel 5,6-diphenyl-1,2,4-triazine-3-thiol derivatives as dual COX-2/5-LOX inhibitors devoid of cardiotoxicity.

A novel series of 5,6-diphenyl-1,2,4-triazine-3-thiol derivatives were designed, synthesized, and screened for their inhibitory potential against COX-2 and 5-LOX enzymes. The compounds from the series have shown moderate to excellent inhibitory potential against both targets. Compound 6k showed the inhibitions against COX-2 (IC = 0.

Seasonal immune rhythm of leukocytes in the freshwater snakehead fish, Channa punctatus.

Annual rhythms are observed in many physiological processes and are an important approach to cope with seasonal stressors. The use of lower vertebrates as an experimental model is crucial to understand the evolution of this biological clock. This study aims to characterize the seasonal variability in the leukocyte immune responses in Channa punctatus.

Identification of a promising inhibitor from (star anise) against the main protease of SARS-CoV-2: insights from the computational study.

SARS-CoV-2, the causing agent of coronavirus disease (COVID-19), first broke out in Wuhan and rapidly spread worldwide, resulting in a global health emergency. The lack of specific drugs against the coronavirus has made its spread challenging to control. The main protease (M) is a key enzyme of SARS-CoV-2 used as a key target in drug discovery against the coronavirus.

A cross-talk between nitric oxide and the glutamatergic system in a Shank3 mouse model of autism.

Nitric oxide (NO) is a multifunctional signaling molecule that plays a crucial role in synaptic transmission and neuronal function. Pioneering studies show that nitric oxide (NO) and S-nitrosylation (SNO, the NO-mediated posttranslational modification) can engender nitrosative stress in the brain, contributing to neurodegenerative diseases. Little is known, however, about the aberrant NO signaling in neurodevelopmental disorders including autism spectrum disorder (ASD).

Conformational stability and structural analysis of methanethiol clusters: a revisit.

B3LYP/cc-pV(D/T/Q)Z and CCSD/cc-pVDZ levels of theory predict three minima for both dimers and trimers of methanethiol. Predictions at B3LYP/cc-pVDZ corroborates exceedingly well with the earlier reported experimental value but significantly differ from the previous computational predictions. Interaction energy between the molecules decreases with an increase in the size of the basis set for both the dimer and trimer.

Conformational and structural stability of and 2-propylthiols: a revisit.

The conformational and structural stability of -propanethiol (nP) is revisited owing to the prevailing ambiguity in the literature reported hitherto, and the rationale for 2-propanethiol's (2P) most stable conformers is analyzed. Based on the rotation around the C-C and C-S bonds, four conformers for nP and two conformers for 2-propanethiol (2P) were found to have the lowest energies at the CCSD/cc-pVDZ level of theory. The two conformers of 2P are anti (T), and gauche (G), and those of nP are T-G, G-G, T-T, and G-T.

Arsenic alters nitric oxide signaling similar to autism spectrum disorder and Alzheimer's disease-associated mutations.

Epidemiological studies have proven that exposure to Arsenic (AS) leads to the development of many neurological disorders. However, few studies have investigated its molecular mechanisms in the brain. Our previous work has revealed nitric oxide (NO)-mediated apoptosis and SNO reprogramming in the cortex following arsenic treatment, yet the role of NO and S-nitrosylation (SNO) in AS-mediated neurotoxicity has not been investigated.