Neurons sequester the cholesterol-inhibiting TFEB in oligodendrocyte cytoplasm to safeguard myelination and neural function.

Myelination is essential for normal brain function, yet the mechanisms governing neuron-oligodendrocyte interactions that ensure proper myelination levels remain poorly understood. Here, we identify transcription factor EB (TFEB) as a molecular link that connects extrinsic neuronal cues to intrinsic oligodendrocyte transcriptional programs, regulating central nervous system myelination. Using a TFEB epitope-tagged knock-in mouse model, we find that neurons sequester most of the TFEB protein in the cytoplasm of myelinating oligodendrocytes.

Quantum Dots in Neurotheranostics for the Treatment of Alzheimer's Disease.

Age-related neurodegeneration is one of the primary causes associated with the pathogenesis of Alzheimer's disease (AD). Currently, there are 5.8 million cases of AD worldwide.

Somatic loss-of-function mutations in CIDEB reduce hepatic steatosis by increasing lipolysis and fatty acid oxidation.

Background & Aims: Somatic and germline CIDEB mutations are associated with protection from chronic liver diseases. The mechanistic basis and whether CIDEB suppression would be an effective therapy against fatty liver disease remain unclear.

Methods: 21 CIDEB somatic mutations were introduced into cells to assess functionality.

Metformin and its Nanoformulations in Cancer Prevention and Therapy.

Currently, the resistance to antineoplastic drugs is an important critical challenge in managing several forms of cancers. An improved prognosis for cancer patients is often associated with increased cell death markers. The objective of the current review article was to discuss how metformin works at the molecular level to fight different types of cancer.

Synthesis and Anticancer Activity of Metformin-Phenolic Acid Conjugates.

The leading cause of death worldwide is cancer. Several studies suggest phenolic acids and metformin as potential cancer treatment options because of their biological and therapeutic properties. So, we synthesized some novel metformin-phenolic acid conjugates.

A Comparative, Multicenter, Prospective, Randomized Study to Evaluate the Efficacy, Safety, and Delay of Relapse of Ceramide-Based Post-biotic Moisturizer Versus Paraffin-Based Moisturizer in Mild to Moderate Atopic Dermatitis.

Background: Atopic dermatitis (AD) is a chronic relapsing inflammatory disease that impacts the quality of life of affected individuals as well as their families. Its pathogenesis involves impaired skin barrier function and immune dysregulation. Moisturizers are used in AD management as they help in repairing the skin barrier.

Enhanced Red Luminescence in Dy/Eu Co-doped Calcium Alumino Borosilicate Glasses for w-LED Applications.

Dy and Eu co-doped borosilicate glasses have been synthesised via melt quench technique. Amorphous behaviour of the sample has been verified by XRD study. FT-IR analysis confirmed the presence of various bonds in the host lattice.

Genetically Labeled Premyelinating Oligodendrocytes: Bridging Oligodendrogenesis and Neuronal Activity.

To myelinate axons, oligodendrocyte precursor cells (OPCs) must stop dividing and differentiate into premyelinating oligodendrocytes (preOLs). PreOLs are thought to survey and begin ensheathing nearby axons, and their maturation is often stalled at human demyelinating lesions. Lack of genetic tools to visualize and manipulate preOLs has left this critical differentiation stage woefully understudied.

Antilipase and antioxidant activities of topiramate-phenolic acid conjugates: Computational modelling, synthesis, and in-vitro investigations.

A series of ten topiramate-phenolic acid conjugates (T1-T10) were synthesized, and evaluated for their pancreatic lipase inhibitory and antioxidant potentials. The design of the compounds reflected the structural attributes extracted from robust QSAR models developed for predicting the pancreatic lipase inhibition potency. Conjugate T4 competitively inhibited pancreatic lipase with IC value of 8.

Aggressive Course of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): An Illustration of Two Cases and Review of Literature.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a central nervous system demyelinating disease that has become a major source of morbidity among children and adults. In the first case, we present an 18-year-old Hispanic female with a recently resolved upper respiratory infection who presented with fever, headache, progressive quadriparesis, urinary retention, and encephalopathy. The hospital course involved autonomic dysfunction and prolonged intubation requiring tracheostomy and gastrostomy.

Structure based exploration of mitochondrial alpha carbonic anhydrase inhibitors as potential leads for anti-obesity drug development.

Background: Obesity has emerged as a major health challenge globally in the last two decades. Dysregulated fatty acid metabolism and de novo lipogenesis are prime causes for obesity development which ultimately trigger other co-morbid pathological conditions thereby risking life longevity. Fatty acid metabolism and de novo lipogenesis involve several biochemical steps both in cytosol and mitochondria.

Conditional spatial biased intuitionistic clustering technique for brain MRI image segmentation.

In clinical research, it is crucial to segment the magnetic resonance (MR) brain image for studying the internal tissues of the brain. To address this challenge in a sustainable manner, a novel approach has been proposed leveraging the power of unsupervised clustering while integrating conditional spatial properties of the image into intuitionistic clustering technique for segmenting MRI images of brain scans. In the proposed technique, an Intuitionistic-based clustering approach incorporates a nuanced understanding of uncertainty inherent in the image data.

Pkd1l1-deficiency drives biliary atresia through ciliary dysfunction in biliary epithelial cells.

Background & Aims: Syndromic biliary atresia is a cholangiopathy characterized by fibro-obliterative changes in the extrahepatic bile duct (EHBD) and congenital malformations including laterality defects. The etiology remains elusive and faithful animal models are lacking. Genetic syndromes provide important clues regarding the pathogenic mechanisms underlying the disease.

Androgens at the skin surface regulate pathogenesis through the activation of quorum sensing.

Unlabelled: the most frequent cause of skin infections, is more common in men than women and selectively colonizes the skin during inflammation. Yet, the specific cues that drive infection in these settings remain unclear. Here we show that the host androgens testosterone and dihydrotestosterone promote pathogenesis and skin infection.

Cerebral vasospasm due to Fusarium solani meningitis: A complication from medical tourism. Case report and literature review.

Objectives: Medical tourism is expanding globally, with patients seeking cosmetic procedures abroad. To date, little information is known regarding the risks and outcomes of cosmetic tourism, especially potential stroke complications. Here, we present a case of fungal meningitis in the setting of medical tourism leading to ischemic strokes and vasospasm.

Drug repurposing a compelling cancer strategy with bottomless opportunities: Recent advancements in computational methods and molecular mechanisms.

Drug discovery has customarily focused on a de novo design approach, which is extremely expensive and takes several years to evolve before reaching the market. Discovering novel therapeutic benefits for the current drugs could contribute to new treatment alternatives for individuals with complex medical demands that are safe, inexpensive, and timely. In this consequence, when pharmaceutically yield and oncology drug efficacy appear to have hit a stalemate, drug repurposing is a fascinating method for improving cancer treatment.

IGFBP2 expressing midlobular hepatocytes preferentially contribute to liver homeostasis and regeneration.

Although midlobular hepatocytes in zone 2 are a recently identified cellular source for liver homeostasis and regeneration, these cells have not been exclusively fate mapped. We generated an Igfbp2-CreER knockin strain that specifically labels midlobular hepatocytes. During homeostasis over 1 year, zone 2 hepatocytes increased in abundance from occupying 21%-41% of the lobular area.

Modeling of chitosan modified PLGA atorvastatin-curcumin conjugate (AT-CU) nanoparticles, overcoming the barriers associated with PLGA: An approach for better management of atherosclerosis.

Conjugate drugs are evolving into potent techniques in the drug development process for enhancing the biopharmaceutical, physicochemical, and pharmacokinetic properties. Atorvastatin (AT) is the first line of treatment for coronary atherosclerosis; however its therapeutic efficacy is limited because of its poor solubility and fast pass metabolism. Curcumin (CU) is evidenced in several crucial signaling pathways linked to lipid regulation and inflammation.

Positive selection of somatically mutated clones identifies adaptive pathways in metabolic liver disease.

Somatic mutations in nonmalignant tissues accumulate with age and injury, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate genes in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to nonalcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7, a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance.

In vivo screening identifies SPP2, a secreted factor that negatively regulates liver regeneration.

Background And Aims: The liver is remarkably regenerative and can completely recover even when 80% of its mass is surgically removed. Identification of secreted factors that regulate liver growth would help us understand how organ size and regeneration are controlled but also provide candidate targets to promote regeneration or impair cancer growth.

Approach And Results: To enrich for secreted factors that regulate growth control, we induced massive liver overgrowth with either YAP or MYC .

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.