Dimethyl fumarate is an inhibitor of pathological angiogenesis.

Vascular endothelial growth factor (VEGF), a pro-angiogenic molecule, supports blood vessel growth during wound healing but also drives pathological neovascularization in blinding eye diseases such as neovascular age-related macular degeneration (nAMD). Dimethyl fumarate (DMFu), an FDA-approved drug for multiple sclerosis, has previously shown promising anti-inflammatory properties in retinal pigment epithelium, a crucial structure disrupted by nAMD. Here, we extend the multi-phenotypic therapeutic potential of DMFu by discerning the anti-angiogenic capabilities of DMFu in choroidal and retinal endothelial cells.

The Mechanism of PMC (2,2,5,7,8-Pentamethyl-6-chromanol), a Sterically Hindered Phenol Antioxidant, in Rescuing Oxidized Low-Density-Lipoprotein-Induced Cytotoxicity in Human Retinal Pigment Epithelial Cells.

Geographic atrophy or late-stage dry age-related macular degeneration (AMD) is characterized by drusen deposition and progressive retinal pigment epithelium (RPE) degeneration, leading to irreversible vision loss. The formation of drusen leads to dyshomeostasis, oxidative stress, and irreversible damage to the RPE. In this study, we used an in vitro model of oxidized low-density lipoprotein (ox-LDL)-induced human RPE damage/death to investigate the mechanism through which a sterically hindered phenol antioxidant compound, PMC (2,2,5,7,8-pentamethyl-6-chromanol), protects the RPE against ox-LDL-induced damage.

Japanese Encephalitis Associated With Quadriplegia: The First Reported Case of Nepal.

Japanese encephalitis (JE), a viral infection transmitted by Culex mosquitoes, primarily affects children and adolescents in endemic regions, with severe cases leading to life-threatening neurological complications. We report the first documented case of JE-associated quadriplegia in Nepal, involving a 19-year-old male presenting with high-grade fever, altered sensorium, vomiting, and profound motor dysfunction. Neurological examination confirmed quadriplegia, while cerebrospinal fluid analysis revealed mildly elevated protein and glucose levels, and brain imaging was unremarkable.

Preoperative kidney tumor risk estimation with AI: From logistic regression to transformer.

We consider the problem of renal mass risk classification to support doctors in adjuvant treatment decisions following nephrectomy. Recommendation of adjuvant therapy based on the mass appearance poses two major challenges: first, morphologic patterns may sometimes overlap across subtypes of varying risks. Second, interobserver variability is large.

Iron sensing, signalling and acquisition by microbes and plants under environmental stress: Use of iron-solubilizing bacteria in crop biofortification for sustainable agriculture.

Iron is very crucial micronutrient prerequisite for growth of all cellular organisms including plants, microbes, animals and humans. Though iron (Fe) is present in abundance in earth's crust, but most of its forms present in soil are biologically unavailable, thus putting a constraint to utilize it. Plants and microorganisms maintain iron homeostasis to balance the supply of enough Fe for metabolism from their surrounding environments and to avoid excessive toxic levels.

Endomucin regulates the endothelial cytoskeleton independently of VEGF.

The endothelial glycocalyx, lining the apical surface of the endothelium, is involved in a host of vascular processes. The glycocalyx is comprised of a network of membrane-bound proteoglycans and glycoproteins along with associated plasma proteins. One such glycoprotein is endomucin (EMCN), which our lab has revealed is a modulator of VEGFR2 function.

Elderly Patients at Risk of Malnutrition Presenting to a Tertiary Hospital in Nepal: A Descriptive Cross-sectional Study.

Introduction: The nutritional status of elderly people is crucial for healthy aging, enabling them to maintain productive lives and reduce the progression of chronic diseases. Given that the quality of life tends to decline with age, it becomes particularly crucial for elderly individuals. Therefore, this study was aimed to find out the prevalence of elderly patients at risk of malnutrition in a tertiary hospital.

LPS-Induced Mitochondrial Dysfunction Reduces Oocyte Maturation and Developmental Competence of Buffalo Embryos via ROS Mediated TLR4 Signalling.

Problem: Lipopolysaccharide (LPS) from gram-negative bacteria has reportedly been associated with infectious diseases like metritis, which has a substantial adverse effect on animal reproductive performance and causes serious financial losses for the dairy sector. The current work aimed to establish the impact of LPS on in vitro oocyte maturation and subsequent in vitro developmental competence of oocytes, as well as to investigate the explanatory molecular mechanism underlying this effect.

Method Of Study: Buffalo cumulus-oocyte complexes (COCs) were challenged with 0, 5, 10 and 20 µg/mL LPS during IVM followed by IVF and IVC.

Endomucin selectively regulates vascular endothelial growth factor receptor-2 endocytosis through its interaction with AP2.

The endothelial glycocalyx, located at the luminal surface of the endothelium, plays an important role in the regulation of leukocyte adhesion, vascular permeability, and vascular homeostasis. Endomucin (EMCN), a component of the endothelial glycocalyx, is a mucin-like transmembrane glycoprotein selectively expressed by venous and capillary endothelium. We have previously shown that knockdown of EMCN impairs retinal vascular development in vivo and vascular endothelial growth factor 165 isoform (VEGF165)-induced cell migration, proliferation, and tube formation by human retinal endothelial cells in vitro and that EMCN is essential for VEGF165-stimulated clathrin-mediated endocytosis and signaling of VEGF receptor 2 (VEGFR2).

Optimising Electroporation Condition for CRISPR/Cas-Mediated Knockout in Zona-Intact Buffalo Zygotes.

Somatic cell nuclear transfer or cytoplasm microinjection has widely been used to produce genome-edited farm animals; however, these methods have several drawbacks which reduce their efficiency. In the present study, we describe an easy adaptable approach for the introduction of mutations using CRISPR-Cas9 electroporation of zygote (CRISPR-EP) in buffalo. The goal of the study was to determine the optimal conditions for an experimental method in which the CRISPR/Cas9 system is introduced into in vitro-produced buffalo zygotes by electroporation.

Mito-Q supplementation of in vitro maturation or in vitro culture medium improves maturation of buffalo oocytes and developmental competence of cloned embryos by reducing ROS production.

Mito-Q is a well-known mitochondria-specific superoxide scavenger. To our knowledge, the effect of Mito-Q on buffalo oocyte maturation and developmental competency of cloned embryos has not been examined. To investigate the effects of Mito-Q on the in vitro maturation (IVM) of buffalo oocytes and the developmental competence of cloned embryos, different concentration of Mito-Q were supplemented with IVM (0, 0.

Mitochondria-targeted antioxidant MitoQ ameliorates ROS production and improves cell viability in cryopreserved buffalo fibroblasts.

Cryopreservation commonly decreases the cellular functionality and post-thaw viability of cells. Reactive oxygen species (ROS) generated during cryopreservation degrade mitochondrial activity and promote the release of cytochrome C which activates caspases required for apoptosis. Antioxidants have the potential to improve the recovery efficiency of cells by reducing ROS production and maintaining mitochondrial membrane potential (MMP).

Microbes-mediated sulphur cycling in soil: Impact on soil fertility, crop production and environmental sustainability.

Reduction in soil fertility and depletion of natural resources due to current intensive agricultural practices along with climate changes are the major constraints for crop productivity and global food security. Diverse microbial populations' inhabiting the soil and rhizosphere participate in biogeochemical cycling of nutrients and thereby, improve soil fertility and plant health, and reduce the adverse impact of synthetic fertilizers on the environment. Sulphur is 4th most common crucial macronutrient required by all organisms including plants, animals, humans and microorganisms.

Induced Pluripotent Stem Cells in the Era of Precise Genome Editing.

Genome editing has enhanced our ability to understand the role of genetics in a number of diseases by facilitating the development of more precise cellular and animal models to study pathophysiological processes. These advances have shown extraordinary promise in a multitude of areas, from basic research to applied bioengineering and biomedical research. Induced pluripotent stem cells (iPSCs) are known for their high replicative capacity and are excellent targets for genetic manipulation as they can be clonally expanded from a single cell without compromising their pluripotency.

Remediation plan of nano/microplastic toxicity in food.

Microplastic pollution is causing a stir globally due to its persistent and ubiquitous nature. The scientific collaboration is diligently working on improved, effective, sustainable, and cleaner measures to control the nano/microplastic load in the environment especially wrecking the aquatic habitat. This chapter discusses the challenges encountered in nano/microplastic control and improved technologies like density separation, continuous flow centrifugation, oil extraction protocol, electrostatic separation to extract and quantify the same.

Role of Oxidative Stress in Ocular Diseases: A Balancing Act.

Redox homeostasis is a delicate balancing act of maintaining appropriate levels of antioxidant defense mechanisms and reactive oxidizing oxygen and nitrogen species. Any disruption of this balance leads to oxidative stress, which is a key pathogenic factor in several ocular diseases. In this review, we present the current evidence for oxidative stress and mitochondrial dysfunction in conditions affecting both the anterior segment (e.

Characterization of sulfur-oxidizing bacteria isolated from mustard (Brassica juncea L.) rhizosphere having the capability of improving sulfur and nitrogen uptake.

Aims: The present investigation was carried out to isolate, screen and characterize potential sulfur-oxidizing bacteria (SOB) isolated from mustard field's soil.

Methods And Results: A total of 130 bacteria were isolated and after screening five maximum sulfate-producing isolates were optimized for culture conditions. The incubation time of 48 h was found optimum for all bacterial isolates and 30°C was the best temperature for the growth of SSD11, SSR1 and SSG8 whereas 35°C for SSF17.

MS-ResNet: disease-specific survival prediction using longitudinal CT images and clinical data.

Purpose: Medical imaging data of lung cancer in different stages contain a large amount of time information related to its evolution (emergence, development, or extinction). We try to explore the evolution process of lung images in time dimension to improve the prediction of lung cancer survival by using longitudinal CT images and clinical data jointly.

Methods: In this paper, we propose an innovative multi-branch spatiotemporal residual network (MS-ResNet) for disease-specific survival (DSS) prediction by integrating the longitudinal computed tomography (CT) images at different times and clinical data.

A multitask dual-stream attention network for the identification of KRAS mutation in colorectal cancer.

Purpose: It is of great significance to accurately identify the KRAS gene mutation status for patients in tumor prognosis and personalized treatment. Although the computer-aided diagnosis system based on deep learning has gotten all-round development, its performance still cannot meet the current clinical application requirements due to the inherent limitations of small-scale medical image data set and inaccurate lesion feature extraction. Therefore, our aim is to propose a deep learning model based on T2 MRI of colorectal cancer (CRC) patients to identify whether KRAS gene is mutated.

It Is Time for an Oil Change: Polyunsaturated Fatty Acids and Human Health.

Polyunsaturated fatty acids (PUFAs) such as docosahexaneoic acid (DHA) and eicosapentaneoic acid (EPA), play a critical role in a variety of neuronal functions, including facilitating neuronal growth and differentiation, increasing the density of the neuritic network, modulating cell membrane fluidity, regulating intracellular signaling and gene expression, and exhibiting antioxidant characteristics. Dietary DHA is selectively enriched and actively retained in the central nervous system, mainly in synaptic membranes, dendrites, and photoreceptors. In this review, we highlight the myriad roles of PUFAs in brain function and human health.

β-Cleavage of the prion protein in the human eye: Implications for the spread of infectious prions and human ocular disorders.

Recently, we reported β-cleavage of the prion protein (PrP) in human ocular tissues. Here, we explored whether this is unique to the human eye, and its functional implications. A comparison of the cleavage pattern of PrP in human ocular tissues with common nocturnal and diurnal animals revealed mainly β-cleavage in humans, and mostly full-length PrP in animal retinas.

Release of Iron-Loaded Ferritin in Sodium Iodate-Induced Model of Age Related Macular Degeneration: An In-Vitro and In-Vivo Study.

To evaluate the role of iron in sodium iodate (NaIO)-induced model of age-related macular degeneration (AMD) in ARPE-19 cells in-vitro and in mouse models in-vivo. ARPE-19 cells, a human retinal pigment epithelial cell line, was exposed to 10 mM NaIO for 24 h, and the expression and localization of major iron modulating proteins was evaluated by Western blotting (WB) and immunostaining. Synthesis and maturation of cathepsin-D (cat-D), a lysosomal enzyme, was evaluated by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) and WB, respectively.

Upregulation of brain hepcidin in prion diseases.

Accumulation of redox-active iron in human sporadic Creutzfeldt-Jakob disease (sCJD) brain tissue and scrapie-infected mouse brains has been demonstrated previously. Here, we explored whether upregulation of local hepcidin secreted within the brain is the underlying cause of iron accumulation and associated toxicity. Using scrapie-infected mouse brains, we demonstrate transcriptional upregulation of hepcidin relative to controls.