Integrative study of chicken lung transcriptome to understand the host immune response during Newcastle disease virus challenge.

Introduction: Newcastle disease is one of the significant issues in the poultry industry, having catastrophic effects worldwide. The lung is one of the essential organs which harbours Bronchus-associated lymphoid tissue and plays a vital role in the immune response. Leghorn and Fayoumi breeds are known to have differences in resistance to Newcastle disease. Along with genes and long non-coding RNAs (lncRNAs) are also known to regulate various biological pathways through gene regulation. Methods: This study analysed the lung transcriptome data and identified the role of genes and long non-coding RNAs in differential immune resistance. The computational pipeline, FHSpipe, as used in our previous studies on analysis of harderian gland and trachea transcriptome was used to identify genes and lncRNAs. This was followed by differential expression analysis, functional annotation of genes and lncRNAs, identification of transcription factors, microRNAs and finally validation using qRT-PCR. Results and discussion: A total of 8219 novel lncRNAs were identified. Of them, 1263 lncRNAs and 281 genes were differentially expressed. About 66 genes were annotated with either an immune-related GO term or pathway, and 12 were annotated with both. In challenge and breed-based analysis, most of these genes were upregulated in Fayoumi compared to Leghorn, and in timepoint-based analysis, Leghorn challenge chicken showed downregulation between time points. A similar trend was observed in the expression of lncRNAs. Co-expression analysis has revealed several lncRNAs co-expressing with immune genes with a positive correlation. Several genes annotated with non-immune pathways, including metabolism, signal transduction, transport of small molecules, extracellular matrix organization, developmental biology and cellular processes, were also impacted. With this, we can understand that Fayoumi chicken showed upregulated immune genes and positive cis-lncRNAs during both the non-challenged and NDV-challenge conditions, even without viral transcripts in the tissue. This finding shows that these immune-annotated genes and coexpressing cis-lncRNAs play a significant role in Fayoumi being comparatively resistant to NDV compared to Leghorn. Our study affirms and expands upon the outcomes of previous studies and highlights the crucial role of lncRNAs during the immune response to NDV. Conclusion: This analysis clearly shows the differences in the gene expression patterns and lncRNA co-expression with the genes between Leghorn and Fayoumi, indicating that the lncRNAs and co-expressing genes might potentially have a role in differentiating these breeds. We hypothesise that these genes and lncRNAs play a vital role in the higher resistance of Fayoumi to NDV than Leghorn. This study can pave the way for future studies to unravel the biological mechanism behind the regulation of immune-related genes.

Stability Indicating UPLC Method Development and Validation for the Quantitative Estimation of Pazopanib in Pure form and Marketed Pharmaceutical Dosage form.

An analytical, accurate, precise, specific, efficient and simple Ultra-Performance Liquid Chromatography method has been developed and validated for the determination of Pazopanib in bulk and was applied on marketed Pharmaceutical Dosage form. The mobile phase used for the chromatographic runs consisted of 0.1% OPA Buffer and Acetonitrile in the ratio of 30:70% v/v. The separation was achieved on a BHEL UPLC column using isocratic mode. Pazopanib Drug peak were well separated and were detected by a PDA detector at 256 nm. The developed method was linear at the concentration range 6-14 µg/ml for Pazopanib. The method has been validated according to ICH guidelines with respect to system suitability, specificity, precision, accuracy and robustness. The LOD and LOQ for the Pazopanib were found to be 0.5853 µg/ml and 1.7738µg/ml respectively. The developed method is simple, precise, specific, accurate and rapid, making it suitable for estimation of Pazopanib in bulk and marketed pharmaceutical dosage form dosage form.

Method Development and Validation of Lorlatinib by RP-HPLC.

A simple, Accurate, precise method was developed for the estimation of the Lorlatinib in API form and Marketed pharmaceutical dosage form by RP-HPLC. Chromatogram was run through Hypersil C18 (4.6mm×150mm, 5µm) Particle size Column and Mobile phase containing Methanol and Water taken in the ratio of 25: 75% v/v was pumped through column at a flow rate of 1.0 ml/min. Temperature was maintained at 38ºC. Optimized wavelength selected was 310 nm. Retention times of Lorlatinib were found to be 3.513 minutes respectively. The %RSD for the Repeatability and Intermediate Precision of the Lorlatinib were found to be within limits. %Recovery was obtained 98.96% and it was found to be within the limits for Lorlatinib respectively. The LOD, LOQ values obtained from regression equations of Lorlatinib were 0.332µg/ml and 1.0078 µg/ml respectively. Regression equation of Lorlatinib was found to be y = 39948x + 16821 respectively. The Retention times was decreased and run time was decreased, so the method developed was simple and economical that can be adopted in regular Quality control test in Industries.

Cutting-Edge Developments and Patent Trends in Microspheres Drug Delivery: A Comprehensive Overview.

Microspheres have emerged as innovative drug delivery platforms with significant potential to improve the therapeutic efficacy of drugs with limited aqueous solubility and prolong their release. This abstract provides an overview of recent developments in microsphere research, highlighting key trends and innovative approaches. Recent studies have focused on various aspects of microspheres, including formulation techniques, materials selection, and their applications in drug delivery. Recent breakthroughs in polymer science have paved the way for the creation of innovative biodegradable and biocompatible materials for microsphere fabrication, improving drug encapsulation effectiveness and release dynamics. Notably, the integration of nanomaterials and functionalized polymers has enabled precise control over drug release rates and enhanced targeting capabilities. The utilization of microspheres for administering a diverse array of therapeutic substances, including anticancer drugs, anti-inflammatory agents, and peptides, has gained significant attention. These microspheres have demonstrated the potential to enhance drug stability, minimize dosing frequency and enhance patient adherence.

In-vitro Studies of Extracts of Plumbago Zeylanica in Cancer Cell Lines.

Despite increased use of early detection methods and more aggressive treatment strategies, the worldwide incidence of colorectal cancer is still on the rise. Consequently, it remains urgent to identify novel agents with enhanced efficacy in prevention and/or therapeutic protocols. Our studies focused on the use of Plumbagin, a natural phytochemical that showed promising results against other tumor types, to determine its effectiveness in blocking the proliferation and survival of colon cancer cells in experimental protocols mimicking the environment in primary tumors (attached culture conditions) and in circulating tumor cells (unattached conditions). Under both experimental settings, exposure of HCT116 cells to Plumbagin concentrations in the low micromolar range resulted in cell cycle arrest at the G1 phase, apoptosis via the mitochondrial cell death pathway, and increased production of reactive oxygen species. The cell cycle effects were more noticeable in attached cells, whereas the induction of cell death was more evident in unattached cells. These effects were consistent with the nature and the magnitude of the alterations induced by Plumbagin on the expression levels of a set of proteins known to play key roles in the regulation of cell cycle dynamics, apoptosis mechanisms and cell proliferation. In light of its previously reported lack of toxicity on normal colon cells and the striking anti-survival effect on colon cancer cells observed in our study, Plumbagin should be considered a promising drug for the treatment of colon cancer.

In-silico analysis of cattle blood transcriptome to identify lncRNAs and their role during bovine tuberculosis.

Long noncoding RNAs (lncRNAs) are RNA molecules with a length greater than 200 nucleotides that do not code for functional proteins. Although, genes play a vital role in immune response against a disease, it is less known that lncRNAs also contribute through gene regulation. Bovine tuberculosis is a significant zoonotic disease caused by Mycobacterium bovis (M. bovis) in cattle. Here, we report the in-silico analysis of the publicly available transcriptomic data of calves infected with M. bovis. A total of 51,812 lncRNAs were extracted across all the samples. A total of 216 genes and 260 lncRNAs were found to be differentially expressed across all the 4 conditions-infected vs uninfected at 8- and 20-week post-infection (WPI), 8 vs 20-WPI of both infected and uninfected. Gene Ontology and Functional annotation showed that 8 DEGs were annotated with immune system GOs and 2 DEGs with REACTOME immune system pathways. Co-expression analysis of DElncRNAs with DEGs revealed the involvement of lncRNAs with the genes annotated with Immune related GOs and pathways. Overall, our study sheds light on the dynamic transcriptomic changes in response to M. bovis infection, particularly highlighting the involvement of lncRNAs with immune-related genes. The identified immune pathways and gene-lncRNA interactions offer valuable insights for further research in understanding host-pathogen interactions and potential avenues for genetic improvement strategies in cattle.

Evaluating Pb-based and Pb-free Halide Perovskites for Solar-Cell Applications: A Simulation Study.

Metal halide Pb-based and Pb-free perovskite crystal structures are an essential class of optoelectronic materials due to their significant optoelectronic properties, optical absorption and tuneable emission spectrum properties. However, the most efficient optoelectronic devices were based on the Pb as a monovalent cation, but its toxicity is a significant hurdle for commercial device applications. Thus, replacing the toxic Pb with Pb-free alternatives (such as tin (Sn)) for diverse photovoltaic and optoelectronic applications is essential. Moreover, replacing the volatile methylammonium (MA) with cesium (Cs) leads to the development of an efficient perovskite absorber layer with improved optical & thermal stability and stabilized photoconversion efficiency. This paper discusses the correlation between the experimental and theoretical work for the Pb-based and Pb-free perovskites synthesised using the hot-injection method at different temperatures. Here, simulation is also carried out using the help of SCAPS-1D software to study the effect of various parameters of CsSnI3 and CsPbI3 layers on solar cell performance. This experimental and theoretical comparative study of the Hot-injection method synthesised CsPbI3 and CsSnI3 perovskites is rarely investigated for optoelectronic applications.

Novel Dual COX-2/5-LOX Inhibitory Activity by Chalcone Derivatives: A Safe and Efficacious Anti-Inflammatory Agent.

BACKGROUND: Non-communicable diseases are chronic systemic inflammation in humans that occurs because of enhanced inflammatory mediators of the arachidonic acid cas-cade. We aimed to explore whether the lead chalcone compounds could exhibit anti-inflam-matory activity via dual blockage of COX-2/5-LOX enzymes and their regulatory mechanism. METHODS: RAW 264.7 macrophages were collected from NCC, Pune, for in-vitro experiments. The IC50 values of chalcone compounds C45 and C64 were calculated. RAW 264.7 macro-phages were treated with C45 and C64 (10%, 5%, 2.5%, 0.125%, and 0.0625% concentration). The cell viability was carried out with an MTT assay. The COX-1, COX-2, 5-LOX, PGE2, and LTB4 levels were detected by ELISA-based kits. The in-vivo evaluation was carried out in Male Wistar rats (250-300 g, 7-8 weeks old) with acute and chronic anti-inflammatory models and histopathological studies on the stomach, liver, and kidney. RESULTS: The present study described the in-vitro and in-vivo biological evaluation of dual COX-2/5-LOX inhibitors in chalcone derivatives (C45 and C64) compounds showed the most effective COX-2 and 5-LOX inhibition with IC50 values 0.092 and 0.136µM respectively. Simultaneously, compound C64 showed comparable selectivity towards COX-2 with a Selec-tivity Index (SI) of 68.43 compared to etoricoxib, with an SI of 89.32. In-vivo carrageenan-induced rat paw oedema activity, the compound C64 showed a significant reduction in oedema with 78.28% compared to indomethacin with 88.07% inhibition. Furthermore, cotton pellet-induced granuloma activity revealed that compound C64 significantly reduced 32.85% com-pared with standard 40.13% granuloma inhibition. CONCLUSION: The chalcone compound C64, (E)-1-(4-Amino-2-hydroxyphenyl)-3-(3,4,5-tri-methoxyphenyl)-prop-2-en-1-one was proved to be a potent and novel Dual COX-2/5-LOX inhibitor with improved gastric safety profiling.

Breed and timepoint-based analysis of chicken harderian gland transcriptome during Newcastle disease virus challenge.

Introduction: Newcastle disease is a highly infectious disease caused by the Newcastle Disease Virus (NDV) and has a devastating financial impact on the global chicken industry. It was previously established that Leghorn and Fayoumi breeds of chicken exhibit variable resistance against NDV infection. The harderian gland is the less studied tissue of the chicken, known to play an essential role in the immune response. Methods: Our previous study, we reported differential gene expression and long noncoding RNAs (lncRNAs) between challenged and non-challenged chickens in the Harderian gland transcriptomic data. Now, we report the analysis of the same data studying the differential expression patterns between Leghorn and Fayoumi and between different timepoints during disease. First, the pipeline FHSpipe was used for identification of lncRNAs, followed by differential expression analysis by edgeR (GLM), functional annotation by OmicsBox, co-expression analysis using WGCNA and finally validation of selected lncRNAs and co-expressing genes using qRT-PCR. Results: Here, we observed that Leghorn showed a higher number of upregulated immune-related genes than Fayoumi in timepoint-based analysis, especially during the initial stages. Surprisingly, Fayoumi, being comparatively resistant, showed little difference between challenged and non-challenged conditions and different time points of the challenge. The breed-based analysis, which compared Leghorn with Fayoumi in both challenged and non-challenged conditions separately, identified several immune-related genes and positive co-expressing cis lncRNAs to be upregulated in Fayoumi when compared to Leghorn in both challenged and non-challenged conditions. Discussion: The current study shows that Leghorn, being comparatively more susceptible to NDV than Fayoumi, showed several immune-related genes and positive co-expressing cis lncRNAs upregulated in challenged Leghorn when compared to non-challenged Leghorn and also in different timepoints during challenge. While, breed-based analysis showed that there were more upregulated immune genes and positive cis-lncRNAs in Fayoumi than Leghorn. This result clearly shows that the differences in the expression of genes annotated with immune-related GO terms and pathways, i.e., immune-related genes and the co-expressing cis-lncRNAs between Leghorn and Fayoumi, and their role in the presence of differences in the resistance of Leghorn and Fayoumi chicken against NDV. Conclusion: These immune-genes and cis-lncRNAs could play a role in Fayoumi being comparatively more resistant to NDV than Leghorn. Our study elucidated the importance of lncRNAs during the host defense against NDV infection, paving the way for future research on the mechanisms governing the genetic improvement of chicken breeds.

Experimental and Theoretical Investigations of MAPbX3 -Based Perovskites (X=Cl, Br, I) for Photovoltaic Applications.

This work mainly focuses on synthesizing and evaluating the efficiency of methylammonium lead halide-based perovskite (MAPbX3 ; X=Cl, Br, I) solar cells. We used the colloidal Hot-injection method (HIM) to synthesize MAPbX3 (X=Cl, Br, I) perovskites using the specific precursors and organic solvents under ambient conditions. We studied the structural, morphological and optical properties of MAPbX3 perovskites using XRD, FESEM, TEM, UV-Vis, PL and TRPL (time-resolved photoluminescence) characterization techniques. The particle size and morphology of these perovskites vary with respect to the halide variation. The MAPbI3 perovskite possesses a low band gap and low carrier lifetime but delivers the highest PCE among other halide perovskite samples, making it a promising candidate for solar cell technology. To further enrich the investigations, the conversion efficiency of the MAPbX3 perovskites has been evaluated through extensive device simulations. Here, the optical constants, band gap energy and carrier lifetime of MAPbX3 were used for simulating three different perovskite solar cells, namely I, Cl or Br halide-based perovskite solar cells. MAPbI3 , MAPbBr3 and MAPbCl3 absorber layer-based devices showed ~13.7 %, 6.9 % and 5.0 % conversion efficiency. The correlation between the experimental and SCAPS simulation data for HIM-synthesized MAPBX3 -based perovskites has been reported for the first time.

Experimental analysis of methylammonium and Formamidinium-based halide perovskite properties for optoelectronic applications.

Nowadays, the toxicity of lead in metal-halide perovskites is the most precarious obstruction in the commercialization of perovskite-based optoelectronic devices. However, Pb-free metal halide perovskites as environment-friendly materials because of their exceptional properties, such as band-gap tunability, narrow emission spectra, low toxicity and easy solution-processability, are potential candidates for optoelectronic applications. Recently, literature reported the poor structural stability and low-emission intensity of Bi-based perovskite NCs. Still, this paper focuses on the fabrication of Formamidinium (FA)-based Bi mixed halide and Methylammonium(MA)-based Bi-pure halide perovskites using Ligand-Assisted Reprecipitation Technique (LARP) technique. XRD diffraction patterns of FA-based perovskites were slightly broad, signifying the nanocrystalline form and limited size of perovskite nanocrystals. While the XRD diffraction patterns of MA3Bi2X9 (X = Cl/Br/I) perovskites were narrow, signifying the amorphous nature and larger size of perovskite nanocrystals. The peak positions were varied in MA-based bismuth halide perovskites with respect to the halide variation from Br to Cl to I ions. The optical study shows the variation in band gap and average lifetime with respect to halide variation leading to enhanced optical properties for device applications. The band-gap of FA3Bi2BrxCl1-x & FA3Bi2IxCl1-x perovskites was calculated to be around 3.7 & 3.8 eV, respectively, while in MA-halide perovskites the band-gap was calculated to be 2.8 eV, 3.1 eV & 3.4 eV with respect to halide variation from I to Cl to Br in perovskite samples using Tauc's plot respectively. Moreover, simulation is carried out using the SCAPS-1D software to study the various parameters in MA & FA-based Bi-pure or mixed halide perovskites. Here, we discussed the variation in efficiency with respect to the thickness variation from 100 to 500 nm for MA3Bi2I9 halide perovskites. These MA3Bi2I9 halide perovskites show minimum efficiency of 4.65 % at 100 nm thickness, while the perovskite sample exhibits maximum efficiency of 10.32 % at 500 nm thickness. Thus, the results stated that the thickness of absorber layers directly affects the device characteristics for optoelectronic applications.

Integrated analysis of genes and long non-coding RNAs in trachea transcriptome to decipher the host response during Newcastle disease challenge in different breeds of chicken.

Newcastle disease is a highly infectious economically devastating disease caused by Newcastle disease Virus in Chicken (Gallus gallus). Leghorn and Fayoumi are two breeds which show differential resistance patterns towards NDV. This study aims to identify the differentially expressed genes and lncRNAs during NDV challenge which could play a potential role in this differential resistance pattern. A total of 552 genes and 1580 lncRNAs were found to be differentially expressing. Of them, 52 genes were annotated with both Immune related pathways and Gene ontologies. We found that most of these genes were upregulated in Leghorn between normal and challenged chicken but several were down regulated between different timepoints after NDV challenge, while Fayoumi showed no such downregulation. We also observed that higher number of positively correlating lncRNAs was found to be downregulated along with these genes. This shows that although Leghorn is showing higher number of differentially expressed genes in challenged than in non-challenged, most of them were downregulated during the disease between different timepoints. With this we hypothesize that the downregulation of immune related genes and co-expressing lncRNAs could play a significant role behind the Leghorn being comparatively susceptible breed than Fayoumi. The computational pipeline is available at https://github.com/Venky2804/FHSpipe.

Symbiotic Antimicrobial Effects of Cellulose-Based Bio-Nanocomposite for Disease Management of Agricultural Crops.

In the present work, a bionanocomposite for plant crop protection was prepared by non-toxic biocompatible & biodegradable nanomaterials (Cellulose & TiO2 ) to utilize its synergistic effects against antimicrobial pathogens. The commercially available microcrystalline cellulose has been reduced to a nanometric scale regime using acid hydrolysis, while the standard TiO2 nano-powder of particle size ~20 nm has been used to prepare their nanocomposite (NC). The antibacterial studies via agar well diffusion method demonstrated that after 72 h of incubation, parent nanomaterials Ncell and TiO2 were not showing any activity against phytopathogens X. campestris pv. campestris, and Clavibacter while the nanocomposite's NC's were still effective depicting both bacteriostatic and bactericidal actions. However, the bacterial growth of biocontrol P. fluorescence was not affected by Ncell, TiO2 NPs and NC after 72 h of incubation. The antifungal testing results via poison food agar assay method suggest that the nanocomposite, along with Ncell and TiO2 NPs, exhibited strong inhibition of fungal growth of Phytophthora Spp at 0.125 mg/ml concentration while for F. graminearum, similar effect was observed at 0.25 mg/ml concentration. The nanocomposite has proved its potential by exhibiting longer & stronger synergistic effects against plant pathogens as a good antimicrobial agent for protection of agricultural crops.

Recent Progress in Selective COX-2 Inhibitor Formulations and Therapeutic Applications - A Patent Review (2012-2022).

INTRODUCTION: Cyclooxygenase (COX), in literature, known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for the formation of prostanoids, including thromboxane and prostaglandins from arachidonic acid. COX-1 does housekeeping activity, whereas COX- 2 induces inflammation. Continuous rise in COX-2 gives birth to chronic pain-associated disorders, i.e., arthritis, cardiovascular complications, macular degeneration, cancer, and neurodegenerative disorders. Despite their potent anti-inflammatory effects, the detrimental effects of COX-2 inhibitors coexist in healthy tissues. Non-preferential NSAIDs cause gastrointestinal discomfort, whereas selective COX-2 inhibitors exert higher cardiovascular risk and renal impairment on chronic use. METHODS: This review paper covers key patents published between 2012-2022 on NSAIDs and coxibs, highlighting their importance, mechanism of action, and patents related to formulation and drug combination. So far, several drug combinations with NSAIDS have been used in clinical trials to treat chronic pain besides combating the side effects. CONCLUSION: Emphasis has been given on the formulation, drug combination, administration routesmodification, and alternative routes, i.e., parenteral, topical, and ocular DEPOT, improving its riskbenefit ratio of NSAIDs to improvise their therapeutic availability and minimize the adverse effects. Considering the wide area of research on COX-2 and ongoing studies, and future scope of view for the better use of the NSAIDs in treating debilitating disease-associated algesia.

Surface engineering of colloidal quaternary chalcogenide Cu2ZnSnS4 nanocrystals: a potential low-cost photocatalyst for water remediation.

Colloidal route synthesis of quaternary compound CZTS (Cu2ZnSnS4) has been anticipated with an inimitable combination of coordinating ligands and solvents using the hot injection technique. CZTS is recognized as one of the worthiest materials for photo-voltaic/catalytic applications due to its exclusive properties (viz., non-toxic, economical, direct bandgap, high absorbance coefficient, etc.). This paper demonstrates the formation of crystalline, single-phased, monodispersed, and electrically passivated CZTS nanoparticles using a distinctive combination of ligands viz. oleic acid (OA)-trioctylphosphine (TOP) and butylamine (BA)-trioctylphosphine (TOP). Detailed optical, structural, and electrochemical studies were done for all CZTS nanoparticles, and the most efficient composition was found using ligands butylamine and TOP. CZTS nanocrystals were rendered hydrophilic via surface-ligand engineering, which was used for photocatalysis studies of organic pollutants. Malachite green (MG) and rhodamine 6G (Rh) for water remediation have great commercial prospects. The unique selling proposition of this work is the rapid synthesis time (~ 45 min) of colloidal CZTS nanocrystals, cost-effective ligand-exchange process, and negligible material wastage (~ 200 µl per 10 ml of pollutant) during photocatalytic experiments.

Visible-light driven noble metal (Au, Ag) permeated multicomponent Cu2ZnSnS4 nanocrystals: A potential low-cost photocatalyst for textile effluents and heavy metal removal.

An exemplary vision to understand the fundamental role of metal-doped multi-components system such as Au/Ag doped CZTS (Cu2ZnSnS4) nanocrystals encourages the non-vacuum approach for the best performing photocatalyst. Hydrophilic nanoparticles (Au/Ag and CZTS) are allowed to amalgamate under NTP atmosphere, eradicating the prerequisite for high-end equipment. The potential of Au and Ag-doped CZTS nanoparticles was speculated using various optical and structural characterizations. The absorption range of CZTS nanoparticles lies in the visible range, while Au/Ag doping slightly red-shifts the absorption range, considered the desirable state for photocatalysis. The synthesized nanoparticles are highly monodispersed with ∼15-35 nm particle size for Ag, Au, and CZTS. Photocatalysis is a discernible scheme for treating wastewater containing dyes, textile effluents, chemicals, and heavy metals. Here, we strive to use these ex-situ synthesized nanomaterials as photocatalysts, where the real textile waste (collected from industrial outlets), dyes, and heavy metal (chromium (VI)) have been photo-reduced after scrutinizing the finest combination of Ag or Au doped CZTS. Au-CZTS shows superior catalytic activity with an efficiency of 99.7% with a rate constant of 0.2 min-1 (while Ag-CZTS shows 90% efficiency with a rate constant of 0.07 min-1); hence, used for real textile waste and heavy metal (Chromium VI) photo-reduction. The maximum efficiency achieved for textile-1, textile-2, and Cr (VI) reductions is 80%, 70%, and 97%, respectively. The nanocrystals are highly stable and recyclable, tested for 15 repeated cycles. These studies pave the way for developing cost-effective, environmentally-friendly, durable, and selective semiconductor-metal (Au/Ag) hybrid heterostructures as visible-light-driven photocatalysts for wastewater remediation.

Phytochemistry and Polypharmacological Potential of Colebrookea oppositifolia Smith.

BACKGROUND: Colebrookea oppositifolia Smith. is a valuable traditional therapeutic plant belonging to the family Lamiaceae. It is a dense and wool-like shrub that is mostly found in subtropical regions of some countries of Asia, such as China and India. It has been widely used for the mitigation of nervous system disorders like epilepsy. The active constituents of the plant have exhibited antioxidant, anti-microbial, and antifungal properties, which are considered due to the presence of polyphenols and flavonoids as chief chemical constituents. Flavonoids like quercetin, landenein, chrysin, and 5, 6, 7-trimethoxy flavones cause protein denaturation of the microbial cell wall. OBJECTIVES: To comprehend and assemble the fragmented pieces of evidence presented on the traditional uses, botany, phytochemistry, and pharmacology of the plant to reconnoiter its therapeutic perspective and forthcoming research opportunities. METHODS: The available information on Colebrookea oppositifolia has been established by electronically searching peer-reviewed literature from PubMed, Google Scholar, Springer, Scopus, Web of Science, and Science Direct over the earlier few years. RESULTS: The plant has been greatly used for the preparation of many herbal medicines which are used for treating traumatic injuries, fever, rheumatoid arthritis, headache, and gastric problems. From the aerial parts of the plant, a phenylethanoid glycoside named acteoside has been isolated and evaluated for its therapeutic potential viz. immunomodulatory, neuroprotective, hepatoprotective, analgesic, anti-tumour, antispasmodic, antioxidant, antibacterial, free radical scavenger, and improving sexual function. Acteoside showed neuroprotective activities against Aß-peptide, which is neurotoxic and causes apoptosis. The petroleum ether extract of the plant leaves offers many active compounds like sitosterol, n-triacontane, hydroxydotriacontyl ferulate, acetyl alcohol, and 3,7,4,2-tetramethoxyflavones which have shown hepatoprotective potential. CONCLUSION: The plant should be evaluated further for the estimation of some other health benefits. The consequences of restricted pharmacological screening and reported phytomolecules of Colebrookea oppositifolia Smith. advocate that there is still an exigent requisite for in-depth pharmacological studies of the plant.

Identification and differential expression of long non-coding RNAs and their association with XIST gene during early embryonic developmental stages of Bos taurus.

X-chromosomes inactivation (XCI) is a phenomenon that aims to equalize the dosage of X-linked gene products between XY males and XX females in mammals. XIST gene is the master regulator of X chromosome inactivation during early embryonic developmental stages of Bos taurus. Biological molecule such as lncRNA plays significant role in the control of XCI, by RNA-based regulatory mechanisms and are non-coding regions of the genome. In our study, using in-silico transcriptome data analysis approach, we analysed RNA-seq data of E35, E39 and E43 samples from bovine genital ridges of early embryonic stages, and identified lncRNA transcripts. More than 7 lakh lncRNA transcripts were identified. Further, our study identified DE-lncRNAs and genes between male and female and studied their co-expression. More than four thousand differentially expressed lncRNAs identified. The co-expression and RT-PCR study in the result showed that there exists an association between the XIST and DE-lncRNAs in early embryonic gonads of bovine at E35. In this study, the association between DE-lncRNAs and XIST gene indicates, the potentially important role of DE-lncRNAs during embryo development in bovine. In conclusion, this study shows there exist an interplay between genes and lncRNAs at transcriptome level of bovine during early embryonic days.

In silico prediction of the animal susceptibility and virtual screening of natural compounds against SARS-CoV-2: Molecular dynamics simulation based analysis.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. It has six open reading frames (orf1ab, orf3a, orf6, orf7a, orf8, and orf10), a spike protein, a membrane protein, an envelope small membrane protein, and a nucleocapsid protein, out of which, orf1ab is the largest ORF coding different important non-structural proteins. In this study, an effort was made to evaluate the susceptibility of different animals against SARS-CoV-2 by analyzing the interactions of Spike and ACE2 proteins of the animals and propose a list of potential natural compounds binding to orf1ab of SARS-CoV-2. Here, we analyzed structural interactions between spike proteins of SARS-CoV-2 and the ACE2 receptor of 16 different hosts. A simulation for 50 ns was performed on these complexes. Based on post-simulation analysis, Chelonia mydas was found to have a more stable complex, while Bubalus bubalis, Aquila chrysaetos chrysaetos, Crocodylus porosus, and Loxodonta africana were found to have the least stable complexes with more fluctuations than all other organisms. Apart from that, we performed domain assignment of orf1ab of SARS-CoV-2 and identified 14 distinct domains. Out of these, Domain 3 (DNA/RNA polymerases) was selected as a target, as it showed no similarities with host proteomes and was validated in silico. Then, the top 10 molecules were selected from the virtual screening of ∼1.8 lakh molecules from the ZINC database, based on binding energy, and validated for ADME and toxicological properties. Three molecules were selected and analyzed further. The structural analysis showed that these molecules were residing within the pocket of the receptor. Finally, a simulation for 200 ns was performed on complexes with three selected molecules. Based on post-simulation analysis (RMSD, RMSF, Rg, SASA, and energies), the molecule ZINC000103666966 was found as the most suitable inhibitory compound against Domain 3. As this is an in silico prediction, further experimental studies could unravel the potential of the proposed molecule against SARS-CoV-2.

Development, Characterization and In Vitro Antimicrobial Evaluation of Novel Flavonoids Entrapped Micellar Topical Formulations of Neomycin Sulfate.

Flavonoids are the secondary metabolites widely used in pharmaceutical industries due to their several health benefits. Quercetin and rutin, well known flavonoids possesses various pharmacological properties but the constraints of poor aqueous solubility and impermeability across cell membranes restricts their use in formulation development. Moreover, the rising problem of antimicrobial resistance has also caused a serious threat to human life, thus demanding the urgent need of developing more effective antimicrobial formulations. In view of this, the present research work is focused on utilizing the most feasible flavonoid-surfactant concentrations obtained from the already reported physico-chemical analysis in developing an improved neomycin topical formulation through drug combinatorial approach. The formulations were subjected for assessment of physical parameters such as determination of pH, viscosity and spreadability. The drug release profile of the formulations was studied through different mathematical models. After evaluation of all the parameters, two best formulations (NQ-T2 [HE] and NR-T1 [HE]) were selected for antimicrobial evaluation studies against different bacterial and fungal clinical isolates. Among the two formulations, NQ-T2 [HE] showed excellent antibacterial activity against the bacterial strains while NR-T1 [HE] also exhibited promising results when compared with the standard formulations. Overall, this study represents a possible solution to enhance the antimicrobial efficacy of neomycin formulations by combining them with flavonoids through micelles assisted drug combination approach.