Computational screening of phytocompounds from identifies potential inhibitors of influenza A (H3N2) virus by targeting hemagglutinin.

The H3N2 subtype of the influenza A virus continues to be a notable public health issue due to its association with seasonal epidemics and severe human morbidity. The constrained effectiveness of current antiviral medications, combined with the inevitable emergence of drug-resistant variants, mandates the exploration of innovative therapeutic approaches. This study focuses on the identification of phytocompounds from with the potential to target hemagglutinin, viral protein involved in viral entry by binding to sialyl glycoconjugates receptors on the surface of host cells.

Serotype-specific clinical features and spatial distribution of dengue in northern Kerala, India.

Background: Collection and compilation of spatial, meteorological, entomological, and virological data are critical in mitigating climate-sensitive emerging infections like dengue. This study was a holistic attempt to understand the dengue situation in the Kasaragod district of Kerala, India.

Methods: This cross-sectional study was conducted in 13 health institutions from June to July 2021.

Development of PEGylated Cu nanoclusters: A nontoxic, multifunctional colloidal system for bioimaging and peroxide sensing.

This study introduces the development of blue-emitting colloidal Cu NCs through a novel and easy PEGylation method using different functional groups, including -SH and -COOH. The surface functionalization controls the size, cellular toxicity, and emission properties of Cu NCs. The combination of PEG, thiol, and carboxylic groups protects the particle surface from aggregation and oxidation.

Sensitization of cancer cells towards Cisplatin and Carboplatin by protein kinase D inhibitors through modulation of ATP7A/B (copper transport ATPases).

Drug resistance of cancer cells is a significant impediment to effective chemotherapy. One primary reason for this is copper exporters - ATPase copper transporting alpha (ATP7A) and ATPase copper transporting beta (ATP7B). These molecular pumps belong to P-type ATPases and dispose off the Platinum (Pt) based anticancer drugs from cancer cells, causing resistance in them.

Development of a paper printed colorimetric sensor based on Cu-Curcumin nanoparticles for evolving point-of-care clinical diagnosis of sodium.

The homeostatic control of Sodium (Na) ion in the human body assumes paramount relevance owing to its physiological importance. Any deviation from the normal level causes serious health problems like hypernatremia, hyponatremia, stroke, kidney problems etc. Therefore, quantification of Na levels in body fluids has significant diagnostic and prognostic importance.

Green Synthesis of Engineered CdS Nanoparticles with Reduced Cytotoxicity for Enhanced Bioimaging Application.

The modern epoch of semiconductor nanotechnology focuses on its application in biology, especially in medical sciences, to fetch direct benefits to human life. Fabrication of devices for biosensing and bioimaging is a vibrant research topic nowadays. Luminescent quantum dots are the best option to move with, but most of them are toxic to living organisms and hence cannot be utilized for biological applications.

Evaluation of diagnostic accuracy of developed rapid SARS-COV-2 IgG antibody test kit using novel diluent system.

Immunochromatographic assay kits are used in primary diagnostics which is based on the principle of antigen and antibody interaction. These kits play pivotal role in rapid surveillance of infectious diseases at early stages as well as for the surveillance of the contagious diseases. The immunochromatographic test kits lacks sensitivity and specificity with certain diseases.

A slow, efficient and safe nanoplatform of tailored ZnS QD-mycophenolic acid conjugates for drug delivery against dengue virus 2 genome replication.

Dengue is a major health concern causing significant mortality, morbidity and economic loss. The development of anti-dengue viral drugs is challenging due to high toxicity, as well as off-target/side effects. We engineered size tuned ZnS QDs as a platform for the efficient delivery of mycophenolic acid (MPA) against dengue virus serotype 2 (DENV2) to evaluate the drug efficacy and toxicity using the DENV2 sub-genomic replicon system in BHK21 cells.

Label Free, Nontoxic Cu-GSH NCs as a Nanoplatform for Cancer Cell Imaging and Subcellular pH Monitoring Modulated by a Specific Inhibitor: Bafilomycin A1.

Metal nanoparticles-based sensors invoked much research attention in the biomedical field, especially in applications involving live cell imaging and monitoring. Here, a simple cost-effective method is adopted to synthesize glutathione coated copper nanoclusters (Cu-GSH NCs) with strong bright red fluorescence (625 nm). The clusters were found to be containing five Cu(0) atoms complexed with one molecule of glutathione (GSH) as evidenced by MALDI-TOF MS analysis.

Semi-quantification of antibody-dependent enhancement (ADE) in the uptake of Adenovirus serotype 5 into THP-1 cells.

Replication defective recombinant Ad5 vectors (rAdV5) are extensively explored for its applications in gene therapy and vaccine delivery. Ad5 enter into monocytes and macrophages through CAR independent route as an immune complex termed as antibody-dependent enhancement (ADE). We developed an effective method for estimating the ADE of rAdV5 encoding GFP (rAdV5-GFP) into THP-1 cells, using fluorimetric semi-quantification of GFP.

Human skin fibrosis: up-regulation of collagen type III gene transcription in the fibrotic skin nodules of lower limb lymphoedema.

Objectives: To investigate the cellular and molecular pathophysiology involved in the development of fibrotic skin of grade-3 lymphoedema patients with a focus on collagen types.

Methods: Fibrotic and normal skin biopsy samples obtained from grade-3 lymphoedema patients and normal individuals, respectively, were analysed by histopathology, quantitative real-time PCR and immunohistochemistry to examine collagen gene expression.

Results: Histopathologic analysis revealed epidermal changes such as orthokeratosis, hypergranulosis and irregular acanthosis in the skin biopsies.

Mycophenolic acid (MPA) modulates host cellular autophagy progression in sub genomic dengue virus-2 replicon cells.

Cellular autophagy (Macrophagy) is a self-degradative process, executed through the network of autophagy associated genes (ATGs) encoded proteins. Both in vitro and in vivo studies suggest that dengue virus (DENV) induces autophagy and supports the viral genome replication and translation. Therefore, the cellular autophagy induced by dengue virus can be a good target for antiviral drug development.

Cytotoxicity of nanoparticles - Are the size and shape only matters? or the media parameters too?: a study on band engineered ZnS nanoparticles and calculations based on equivolume stress model.

Size dependent cytotoxicity of ZnS nanoparticles (NPs) was investigated in Human embryonic kidney (HEK-293) cell lines by MTT assay. The cells were incubated with varying concentration of ZnS NPs of sizes 4 nm, 10 nm and 25 nm for 48 h under different (cell culture) media viscosity conditions. The results showed that the toxicity is decreased with the particle size while it is negatively correlated with the viscosity of the media.

Inhibition of dengue virus by curcuminoids.

The dengue virus is considered to be a globally important human pathogen prevalent in tropical and subtropical regions of the world. According to a recent estimate, the disease burden due to DENV infections is ∼390 million infections per year globally in ∼100 countries including the southern US, Puerto Rico and Hawaii, resulting in nearly ∼25,000 deaths mostly among children. Despite the significant morbidity and mortality that results from DENV infections, there is currently no effective chemotherapeutic treatment for DENV infections.

Green Synthesis of High Temperature Stable Anatase Titanium Dioxide Nanoparticles Using Gum Kondagogu: Characterization and Solar Driven Photocatalytic Degradation of Organic Dye.

The present study reports a green and sustainable method for the synthesis of titanium dioxide (TiO₂) nanoparticles (NPs) from titanium oxysulfate solution using Kondagogu gum (), a carbohydrate polymer, as the NPs formation agent. The synthesized TiO₂ NPs were categorized by techniques such as X-Ray Diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy analysis, Raman spectroscopy, scanning electron microscope- Energy-dispersive X-ray spectroscopy (SEM-EDX), Transmission electron microscopy (TEM), High-resolution transmission electron microscopy (HR-TEM), UV-visible spectroscopy, Brunauer-Emmett-Teller (BET) surface area and particle size analysis. Additionally, the photocatalytic actions of TiO₂ NPs were assessed with regard to their ability to degrade an organic dye (methylene blue) from aqueous solution in the presence of solar light.

Proteomic analysis reveals the enhancement of human serum apolipoprotein A-1(APO A-1) in individuals infected with multiple dengue virus serotypes.

Objectives: Human serum protein profiling of the individual infected with multiple dengue virus serotypes for identifying the potential biomarkers and to investigate the cause for the severity of dengue virus infection.

Methods: Dengue virus NS1-positive serum samples were pooled into two groups (S2 and S3) based on the molecular serotyping and number of heterotypic infections. The pooled serum samples were subjected to two-dimensional gel electrophoresis (2DGE) to identify the differentially expressed proteins.

Occurrence of concurrent infections with multiple serotypes of dengue viruses during 2013-2015 in northern Kerala, India.

Background: Dengue is a global human public health threat, causing severe morbidity and mortality. The occurrence of sequential infection by more than one serotype of dengue virus (DENV) is a major contributing factor for the induction of Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS), two major medical conditions caused by DENV infection. However, there is no specific drug or vaccine available against dengue infection.

High-throughput screening for the identification of small-molecule inhibitors of the flaviviral protease.

The mosquito-borne dengue virus serotypes 1-4 (DENV1-4) and West Nile virus (WNV) cause serious illnesses worldwide associated with considerable morbidity and mortality. According to the World Health Organization (WHO) estimates, there are about 390 million infections every year leading to ∼500,000 dengue haemorrhagic fever (DHF) cases and ∼25,000 deaths, mostly among children. Antiviral therapies could reduce the morbidity and mortality associated with flaviviral infections, but currently there are no drugs available for treatment.

RNA Interference in the Age of CRISPR: Will CRISPR Interfere with RNAi?

The recent emergence of multiple technologies for modifying gene structure has revolutionized mammalian biomedical research and enhanced the promises of gene therapy. Over the past decade, RNA interference (RNAi) based technologies widely dominated various research applications involving experimental modulation of gene expression at the post-transcriptional level. Recently, a new gene editing technology, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and the CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) system, has received unprecedented acceptance in the scientific community for a variety of genetic applications.

The bioactive lipid 4-hydroxyphenyl retinamide inhibits flavivirus replication.

Dengue virus (DENV), a member of the Flaviviridae family, is a mosquito-borne pathogen and the cause of dengue fever. The increasing prevalence of DENV worldwide heightens the need for an effective vaccine and specific antivirals. Due to the dependence of DENV upon the lipid biosynthetic machinery of the host cell, lipid signaling and metabolism present unique opportunities for inhibiting viral replication.

Biochemical characterization of P-type copper ATPases.

Copper ATPases, in analogy with other members of the P-ATPase superfamily, contain a catalytic headpiece including an aspartate residue reacting with ATP to form a phosphoenzyme intermediate, and transmembrane helices containing cation-binding sites [TMBS (transmembrane metal-binding sites)] for catalytic activation and cation translocation. Following phosphoenzyme formation by utilization of ATP, bound copper undergoes displacement from the TMBS to the lumenal membrane surface, with no H+ exchange. Although PII-type ATPases sustain active transport of alkali/alkali-earth ions (i.

Extremely low frequency magnetic fields induce oxidative stress in rat brain.

The present investigation was conducted to understand the influence of long-term exposure of rats to extremely low frequency magnetic fields (ELF-MF), focusing on oxidative stress (OS) on different regions of rat's brain. Male Wistar rats (21-day-old) were exposed to ELF-MF (50 Hz; 50 and 100 µT) for 90 days continuously; hippocampal, cerebellar and cortical regions from rats were analyzed for (i) reactive oxygen species (ROS), (ii) metabolites indicative of OS and (iii) antioxidant enzymes. In comparison to control group rats, the rats that were continuously exposed to ELF-MF caused OS and altered glutathione (GSH/GSSG) levels in dose-dependent manner in all the regions of the brain.

Distinctive features of catalytic and transport mechanisms in mammalian sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) and Cu+ (ATP7A/B) ATPases.

Ca(2+) (sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA)) and Cu(+) (ATP7A/B) ATPases utilize ATP through formation of a phosphoenzyme intermediate (E-P) whereby phosphorylation potential affects affinity and orientation of bound cation. SERCA E-P formation is rate-limited by enzyme activation by Ca(2+), demonstrated by the addition of ATP and Ca(2+) to SERCA deprived of Ca(2+) (E2) as compared with ATP to Ca(2+)-activated enzyme (E1·2Ca(2+)). Activation by Ca(2+) is slower at low pH (2H(+)·E2 to E1·2Ca(2+)) and little sensitive to temperature-dependent activation energy.

Involvement of protein kinase D in expression and trafficking of ATP7B (copper ATPase).

ATP7B is a P-type ATPase involved in copper transport and homeostasis. In experiments with microsomes isolated from COS-1 cells or HepG2 hepatocytes sustaining ATP7B heterologous expression, we found that ATP7B utilization of ATP includes autophosphorylation of an aspartyl residue serving as ATPase catalytic intermediate as well as phosphorylation of serine residues by protein kinase D (PKD). The latter was abolished by specific PKD inhibition with CID755673.