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Khalid Bashir Dar,1 Ishfaq Shafi Khan,2 Shajrul Amin,1 Aijaz Hassan Ganie,3 Aashiq Hussain Bhat,4 Showkat Ahmad Dar,5 Bilal Ahmad Reshi,6 Showkat Ahmad Ganie1 1Department of Clinical Biochemistry/Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir, India; 2Centre of Research for Development, University of Kashmir, Srinagar, Jammu and Kashmir, India; 3Department of Botany, University of Kashmir, Srinagar, Jammu and Kashmir, India; 4Cancer Research and Diagnostic Centre, SKIMS, Srinagar, Jammu and Kashmir, India; 5Regional Research Institute of Unani Medicine, Srinagar, Jammu and Kashmir, India; 6Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir, IndiaCorrespondence: Showkat Ahmad GanieDepartment of Clinical Biochemistry/Biochemistry, University of Kashmir, Srinagar, Jammu and Kashmir 190006, IndiaTel +91 9419-972-678Email zubaidashowkat3@gmail.comIntroduction: Chronic inflammation is implicated in a multitude of diseases, including arthritis, neurodegeneration, autoimmune myositis, type 2 diabetes, rheumatic disorders, spondylitis, and cancer. Therefore, strategies to explore potent anti-inflammatory regimens are pivotal from a human-health perspective. Medicinal plants represent a vast unexplored treasure trove of therapeutically active constituents with diverse pharmacological activities, including anti-inflammatory properties. Herein, we evaluated Cousinia thomsonii, an edible medicinal herb, for its anti-inflammatory/immunomodulatory properties.Methods: Soxhlet extraction was used to obtain different solvent extracts (hexane, ethyl acetate, ethanol, methanol, and aqueous extract) in increasing order of polarity. In vitro anti-inflammatory assays were performed to investigate the effects of extracts on protein denaturation, proteinase activity, nitric oxide surge, and erythrocyte-membrane stabilization. The most effective extracts, ie, ethyl acetate (CTEA) and ethanol (CTE) extracts (150– 200 g) were selected for further in vivo analysis using albino Wistar rats. Wistar rats received varying concentrations of CTEA and CTE (25, 50, and 100 mg/kg) for 3 weeks, followed by a single subplantar injection of lipopolysaccharide. Dexamethasone served as positive control. Blood was obtained from the retro-orbital plexus and serum separated for estimation of proinflammatory cytokines (IL6, IL1β, IFNγ and TNFα). Western blotting was performed to study expression patterns of crucial proteins implicated in the NFκB pathway, ie, NFκB p65, NFκB1 p50, and NFκB2 p52. Histopathological examination was done and gas chromatography–mass spectrometry (GC-MS) carried out to reveal the identity of compounds responsible for ameliorating effects of C. thomsonii.Results: Among five tested extracts, CTEA and CTE showed marked inhibition of protein denaturation, proteinase activity, nitric oxide surge and erythrocyte-membrane hemolysis at 600 μg/mL (P< 0.001). Both these extracts showed no toxic effects up to a dose of 2,500 mg/kg. Extracts exhibited concentration-dependent reductions in expression of IL6, IL1β, IFNγ, TNFα, NFκB-p65, NFκB1, and NFκB2 (P< 0.05). Healing effects of extracts were evident from histopathological investigation. GC-MS analysis revealed the presence of important anti-inflammatory compounds, notably stigmast-5-en-3-ol, oleate, dotriacontane, ascorbic acid, n-hexadecanoic acid, and α-tocopherol, in C. thomsonii.Conclusion: C. thomsonii possesses significant anti-inflammatory/immunomodulatory potential by virtue of modifying levels of proinflammatory cytokines/markers and NFκB proteins.Keywords: chronic inflammation, interleukin, cytokine, immunoresponse, nitric oxide, compounds

Ethnopharmacological Relevance: Rheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood., Aim of the Study: This study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development., Materials and Methods: Four types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations., Results: Cell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 μg/ml., Histopathology: Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts., Conclusion: This study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study explores the synthesis and characterization of superabsorbent hydrogels derived from chemically modified gum Arabic, designed for controlled folic acid release. The synthesis involves a two-step process: carboxymethylation followed by grafting with 2-hydroxyethyl methacrylate via gamma irradiation. The resulting hydrogels exhibit enhanced mechanical strength and controlled diffusivity, essential for nutrient delivery systems. Key factors such as copolymer composition and irradiation dose are investigated, affecting the synthesis process. Systematic studies of swelling behaviors reveal that the hydrogel achieves a maximum swelling of 888.1% at 40 °C. The hydrogels are loaded with folic acid, and in vitro, sustained release profiles are examined under various pH conditions. The maximum release of 83.3% is observed after 24 h at pH 7.0, following a Korsmeyer-Peppas release mechanism. Different characterization techniques, confirm the successful synthesis and unique properties of the superabsorbent hydrogels. Rheological behavior analysis, scanning electron microscopy, and biocompatibility assessments provide a comprehensive understanding of the hydrogel structures. Gamma irradiation ensures a homogeneous network structure, crucial for optimal swelling behavior and mechanical properties. This research highlights the potential of eco-friendly biopolymer hydrogels in precise drug delivery applications, leveraging the safety and process control benefits of gamma irradiation., (© 2024 Wiley‐VCH GmbH.)

In the ever-evolving field of drug discovery, the integration of Artificial Intelligence (AI) and Machine Learning (ML) with cheminformatics has proven to be a powerful combination. Cheminformatics, which combines the principles of computer science and chemistry, is used to extract chemical information and search compound databases, while the application of AI and ML allows for the identification of potential hit compounds, optimization of synthesis routes, and prediction of drug efficacy and toxicity. This collaborative approach has led to the discovery, preclinical evaluations and approval of over 70 drugs in recent years. To aid researchers in the pursuit of new drugs, this article presents a comprehensive list of databases, datasets, predictive and generative models, scoring functions and web platforms that have been launched between 2021 and 2022. These resources provide a wealth of information and tools for computer-assisted drug development, and are a valuable asset for those working in the field of cheminformatics. Overall, the integration of AI, ML and cheminformatics has greatly advanced the drug discovery process and continues to hold great potential for the future. As new resources and technologies become available, we can expect to see even more groundbreaking discoveries and advancements in these fields.Communicated by Ramaswamy H. Sarma.

The present study aimed to investigate the morphological features, phytochemicals, phenolic content, and antioxidant activity in different parts of Lagotis cashmeriana . The morphological features depicted that the plant is 7.9 ± 1.699 cm tall with flowers arranged into an inflorescence. The length of inflorescence was 2.597 ± 0.796 cm. Basal leaves were measuring 2.99 ± 0.58 cm. Besides, the number of basal leaves and inflorescence ranged from 4-9 and 0-4 respectively. Methanolic extract of leaves displayed the highest phenolic content (169.5 µg/mL of GAE), followed by inflorescences (157 µg/mL of GAE). Among aqueous extracts, leaves displayed the highest phenolic content (88.38 µg/mL of GAE), followed by inflorescences (76.95 µg/mL of GAE). The results of antioxidant study revealed that the methanolic extracts of leaves possessed the highest antioxidant potential (180.76 µg/mL of AAE). Interestingly, for each extract, there was a positive correlation between the phenolic content and the antioxidant activity.

Biobased materials are expanding dramatically in various industrial applications due to their unique intrinsic properties. In this study, various chemical functionalization procedures were used to synthesize guar gum, a naturally occurring polysaccharide-based polyurea, and its iodine complexes. Firstly, guar gum was subjected to tosylation reaction using p-toluene sulphonyl chloride to introduce tosyl moieties in the polymer chain with the degree of substitution (DS) ranging between 0.16 and 1.54. Sample having the highest degree of tosyl moiety was further reacted with tris(2-aminoethyl) amine to produce 6-deoxy-6-tris(2-aminoethyl) amine derivative via nucleophilic substitution reaction to impart amino functional groups. The degree of substitution in 6-deoxy-6-tris(2-aminoethyl) amine derivative was found to be 0.59. 6-deoxy-6-tris(2-aminoethyl) amine derivative was reacted with different diisocyanates (Toluene-2,4-diisocyanate (TDI), 1,6-diisocyanatohexane (HMDI)) to produce guar gum based polyurea. Iodine complexes of the resulting polyurea were prepared by reacting with different iodinating agents. Different chemical reactions, formation of polyurea and its iodine complexes were thoroughly analyzed by different analytical techniques such as FT-IR, NMR, elemental analysis, XRD, UV-Vis spectroscopy, and a reaction scheme has been proposed. Morphological and rheological characteristics were analyzed by SEM and viscosity measurement. Thermal analysis was carried out by TGA and DSC studies. Finally, by examining the complex's UV-Vis spectra, the iodine release characteristics from polyurea‑iodine complexes were investigated., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Plant responses to abiotic stresses are dynamic, following the unpredictable changes of physical environmental parameters such as temperature, water and nutrients. Physiological and phenotypical responses to stress are intercalated by periods of recovery. An earlier stress can be remembered as 'stress memory' to mount a response within a generation or transgenerationally. The 'stress priming' phenomenon allows plants to respond quickly and more robustly to stressors to increase survival, and therefore has significant implications for agriculture. Although evidence for stress memory in various plant species is accumulating, understanding of the mechanisms implicated, especially for crops of agricultural interest, is in its infancy. Rice is a major food crop which is susceptible to abiotic stresses causing constraints on its cultivation and yield globally. Advancing the understanding of the stress response network will thus have a significant impact on rice sustainable production and global food security in the face of climate change. Therefore, this review highlights the effects of priming on rice abiotic stress tolerance and focuses on specific aspects of stress memory, its perpetuation and its regulation at epigenetic, transcriptional, metabolic as well as physiological levels. The open questions and future directions in this exciting research field are also laid out., (© 2024 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

We developed a facile method for the fabrication of a biodegradable delivery system composed of two blocks: curdlan and curcumin. This was achieved by chemical functionalization of curdlan through tosylation, amination followed by complexation with curcumin. A comprehensive evaluation of structural characterization and component stability showed that cur-cum complex exhibited better anticancer properties with enhanced thermal properties. The cur-cum complex shows pH sensitive sustained release behaviour with higher release at acidic pH and kinetic data of drug release follows the Korsmeyer-Peppas model. The cur-cum complex has ability to block the proliferation of the MCF-7 cell line as revealed by MTT assay which showed increased toxicity of cur-cum complex against these cell lines. The results obtained from western blot analysis demonstrated that the co-administration of cur and cum effectively induced apoptosis in MCF-7 cells. This effect was observed by a considerable upregulation of the Bcl-2/Bax ratio, a decline in mRNA expression of LDHA, level of lactate and LDH activity. The results clearly depict the role of functionalized curdlan as efficient carrier for curcumin delivery with prolonged, sustained release and enhanced bioavailability, thereby improving the overall anticancer activity., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chemical modification represents a highly efficacious approach for enhancing the physicochemical characteristics and biological functionalities of natural polysaccharides. However, not all polysaccharides have considerable pharmacologic activity; so, appropriate chemical modification strategies can be selected in accordance with the distinct structural properties of polysaccharides to aid in improving and encouraging the presentation of their biological activities. Hence, there has been a growing interest in the chemical alteration of polysaccharides due to their various properties such as antioxidant, anticoagulant, antiviral, anticancer, biomedical, antibacterial, and immunomodulatory effects. This paper offers a comprehensive examination of recent scientific advancements produced over the past four years in the realm of unique chemical and functional modifications in curdlan and pullulan structures. This review aims to provide readers with an overview of the structural activity correlations observed in the backbone structures of curdlan and pullulan, as well as the diverse chemical modification processes employed for these polysaccharides. Additionally, the review aims to examine the effects of combining various bioactive molecules with chemically modified curdlan and pullulan and explore their potential applications in various important fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Small Alpine onion Allium humile (Alliaceae) is a common traditional Indian medicine used for blood purification, anti-inflammatory, anti-asthmatic, anti-diabetic and seasoning agents. It is also used for the treatment of asthma, jaundice, stomach problems, cardiovascular disorders and anti-cancer agent., Aim of the Study: In this study, various extracts from the A. humile were taken and their therapeutic activity against dyslipidemia was evaluated in wistar rat models., Materials and Methods: The extraction was done by Soxhlet extraction and the extracts (hexane, ethyl acetate, methanol, ethanol and aqueous) obtained were then tested for nitric oxide radical scavenging activity. The effective extracts i.e., methanol and ethyl acetate were then selected for in vivo studies in wistar rats. Dyslipidemia was induced in rats by feeding them high fat diet, and extracts of varying concentrations were administered to assess their potential for decreasing dyslipidemia. Statin was used as a positive control. After treatment, the blood was drawn and serum was separated for tests such as lipid profile, atherogenic index, lipid peroxidation and histopathological study. GC-MS analysis was carried out to identify the types of compounds present in A. humile extracts and FTIR analysis of extracts was done to determine the types of chemical bonds and functional groups., Results: The phytochemical screening of A. humile extracts revealed a high concentration of flavonoids, alkaloids, phenols, terpenoids, and saponins. Different extracts were evaluated to inhibit the nitric oxide at different concentrations. At the concentration of 700 μg/ml, methanol extract showed maximum inhibition of 78.26%, followed by ethyl acetate, ethanol, aqueous and hexane have shown 62.25%, 54.26%, 47.59% and 36.99% respectively. The GC-MS analysis of methanol and ethyl acetate extracts revealed many compounds. The FTIR analysis showed the presence of many functional groups pertaining to various compounds. The methanolic extract (100 mg/kg) was more active (P < 0.0001) than the ethyl acetate extract in lowering lipid levels, lipid peroxidation, and the decreasing development of the lipoidal layer in aortic wall and rupture of the intima and media confirmed by histopathological study., Conclusion: The results indicate that A. humile methanolic extract was more active than the ethyl acetate extract in lowering lipid levels, lipid peroxidation, inhibiting NOS production and the decreasing development of the lipoidal layer in aortic wall and thus could serve potential antihyperlipidemic agent to enhance cardiovascular health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Atherosclerosis is a global concern that worsens with age, and plants that are effective medicinal herbs can give a viable alternative. PKC is a key factor in cardiovascular and other disorders; targeting it can reduce the risk of these diseases. We evaluated Allium humile for PKC inhibition and therapeutic efficacy against atherosclerosis. Soxhlet extraction was done to obtain extracts (hexane, ethyl acetate, methanol, ethanol and aqueous) and then tested for DPPH radical scavenging and PKC inhibitory activity. The methanolic extract was more active than the other extracts, so it was subjected to column chromatography, and seventeen fractions were obtained. Only 11, 12, and 15 showed good activity against PKC. Wistar rats were divided into six groups and each group received high fat diet for 30 days. Then the three potent fractions (10 mg/kg) were administered for 15 days along with high fat diet. Fraction II had the highest effectiveness (P < 0.0001) in decreasing lipid levels, lipid peroxidation, reducing IL-6 and TNF-α expression, and raising nitric oxide. This also demonstrated a decrease in PKC activity, as well as a decrease in the formation of the lipoidal layer in the aorta wall and rupture of the intima and media as validated by histological analysis. The two compounds, phytol acetate and cyanidin 3-(6″-o-malonyllaminaribioside) were characterised in fraction II by NMR and HRMS and cyanidin 3-(6″-o-malonyllaminaribioside) inhibited PKC more efficiently. Thus, Allium humile has strong anti-atherogenic activity as well as the ability to inhibit PKC both in vitro and in vivo., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Showkat Ahmad Ganie reports financial support was provided by University of Kashmir. Showkat Ahmad Ganie reports a relationship with University of Kashmir that includes: employment. Showkat has patent pending to Nil. Nil., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Barley (Hordeum vulgare) is an important cereal crop, and its development, defence, and stress responses are modulated by different hormones including jasmonates (JAs) and the antagonistic gibberellins (GAs). Barley productivity is severely affected by the foliar biotrophic fungal pathogen Blumeria hordei. In this study, primary leaves were used to examine the molecular processes regulating responses to methyl-jasmonate (MeJA) and GA to B. hordei infection along the leaf axis. Flow cytometry, microscopy, and spatiotemporal expression patterns of genes associated with JA, GA, defence, and the cell cycle provided insights on cell cycle progression and on the gradient of susceptibility to B. hordei observed along the leaf. Notably, the combination of B. hordei with MeJA or GA pre-treatment had a different effect on the expression patterns of the analysed genes compared to individual treatments. MeJA reduced susceptibility to B. hordei in the proximal part of the leaf blade. Overall, distinctive spatiotemporal gene expression patterns correlated with different degrees of cell proliferation, growth capacity, responses to hormones, and B. hordei infection along the leaf. Our results highlight the need to further investigate differential spatial and temporal responses to pathogens at the organ, tissue, and cell levels in order to devise effective disease control strategies in crops., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Food industry is the biggest and rapidly growing industries all over the world. This sector consumes around 40 % of the total plastic produced worldwide as packaging material. The conventional packaging material is mainly petrochemical based. However, these petrochemical based materials impose serious concerns towards environment after its disposal as they are nondegradable. Thus, in search of an appropriate replacement for conventional plastics, biopolymers such as polysaccharides (starch, cellulose, chitosan, natural gums, etc.), proteins (gelatin, collagen, soy protein, etc.), and fatty acids find as an option but again limited by its inherent properties. Attention on the initiatives towards the development of more sustainable, useful, and biodegradable packaging materials, leading the way towards a new and revolutionary green era in the food sector. Eco-friendly packaging materials are now growing dramatically, at a pace of about 10-20 % annually. The recombination of biopolymers and nanomaterials through intercalation composite technology at the nanoscale demonstrated some mesmerizing characteristics pertaining to both biopolymer and nanomaterials such as rigidity, thermal stability, sensing and bioactive property inherent to nanomaterials as well as biopolymers properties such as flexibility, processability and biodegradability. The dramatic increase of scientific research in the last one decade in the area of bionanocomposites in food packaging had reflected its potential as a much-required and important alternative to conventional petroleum-based material. This review presents a comprehensive overview on the importance and recent advances in the field of bionanocomposite and its application in food packaging. Different methods for the fabrication of bionanocomposite are also discussed briefly. Finally, a clear perspective and future prospects of bionanocomposites in food packaging were presented., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Main Conclusion: Role of salinity responsive metabolites of rice and its wild species has been discussed. Salinity stress is one of the important environmental stresses that severely affects rice productivity. Although, several vital physio-biochemical and molecular responses have been activated in rice under salinity stress which were well described in literatures, the mechanistic role of salt stress and microbes-induced metabolites to overcome salt stress in rice are less studied. Nevertheless, over the years, metabolomic studies have allowed a comprehensive analyses of rice salt stress responses. Hence, we review the salt stress-triggered alterations of various metabolites in rice and discuss their significant roles toward salinity tolerance. Some of the metabolites such as serotonin, salicylic acid, ferulic acid and gentisic acid may act as signaling molecules to activate different downstream salt-tolerance mechanisms; whereas, the other compounds such as amino acids, sugars and organic acids directly act as protective agents to maintain osmotic balance and scavenger of reactive oxygen species during the salinity stress. The quantity, type, tissues specificity and time of accumulation of metabolites induced by salinity stress vary between salt-sensitive and tolerant rice genotypes and thus, contribute to their different degrees of salt tolerance. Moreover, few tolerance metabolites such as allantoin, serotonin and melatonin induce unique pathways for activation of defence mechanisms in salt-tolerant varieties of rice, suggesting their potential roles as the universal biomarkers for salt tolerance. Therefore, these metabolites can be applied exogenously to the sensitive genotypes of rice to enhance their performance under salt stress. Furthermore, the microbes of rhizosphere also participated in rice salt tolerance either directly or indirectly by regulating their metabolic pathways. Thus, this review for the first time offers valuable and comprehensive insights into salt-induced spatio-temporal and genotype-specific metabolites in different genotypes of rice which provide a reference point to analyze stress-gene-metabolite relationships for the biomarker designing in rice. Further, it can also help to decipher several metabolic systems associated with salt tolerance in rice which will be useful in developing salt-tolerance cultivars by conventional breeding/genetic engineering/exogenous application of metabolites., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

COVID-19 has infected millions and significantly affected the global economy and healthcare systems. Despite continuous lockdowns, symptomatic management with currently available medications, and numerous vaccination drives, it is still far more difficult to control. Against COVID-19 infection, the pressure to develop vaccines and drugs has led to using some currently available medications like remdesivir, azithromycin, hydroxychloroquine and ritonavir. Understanding the importance and potential of harmless molecules to tackle SARS-COV-2, we designed the present study to identify potential natural phytocompounds. In the present study, we docked natural compounds and standard drugs against SARS-COV-2 proteins: papain-like protease, main protease and helicase. ADME/T and ProTox-II analyses were used to determine the toxicity of phytocompounds and drugs. The docking analysis revealed that podophyllotoxin gave the highest binding affinity scores of -8.1, -7.1 and -7.4 kcal/mol against PLpro, Mpro and helicase, respectively. Among the control drugs, doxycycline hydrochloride showed the highest binding affinity of -10.5, -8.4 and -8.8 kcal/mol against PLpro, Mpro and helicase. The results of this study revealed that podophyllotoxin and doxycycline hydrochloride could be promising inhibitors against SARS-Cov-2. Molecular dynamic simulations were executed for the best docked (PLpro-podophyllotoxin) complex, and the results displayed stable conformation and convergence. Energy plot results predicted a global minima average energy of -95 kcal/mol and indicated podophyllotoxin's role in stabilizing protein and making it compact and complex. FarPPI server used MM/GBSA approach to determine free binding affinity, and helicase-gallic acid complex showed the highest affinity, respectively. Therefore, it can be concluded that there is still a need for in vitro and in vivo studies to support further and validate these findings and validate these findings.Communicated by Ramaswamy H. Sarma.

Cell division is driven by nucleic acid metabolism, and thymidylate synthase (TYMS) catalyzes a rate-limiting step in nucleotide synthesis. As a result, thymidylate synthase has emerged as a critical target in chemotherapy. 5-Fluorouracil (5-FU) is currently being used to treat a wide range of cancers, including breast, pancreatic, head and neck, colorectal, ovarian, and gastric cancers The objective of this study was to establish a new methodology for the low-cost, one-pot synthesis of uracil derivatives (UD-1 to UD-5) and to evaluate their therapeutic potential in BC cells. One-pot organic synthesis processes using a single solvent were used for the synthesis of drug analogues of Uracil. Integrated bioinformatics using GEPIA2, UALCAN, and KM plotter were utilized to study the expression pattern and prognostic significance of TYMS, the key target gene of 5-fluorouracil in breast cancer patients. Cell viability, cell proliferation, and colony formation assays were used as in vitro methods to validate the in silico lead obtained. BC patients showed high levels of thymidylate synthase, and high expression of thymidylate synthase was found associated with poor prognosis. In silico studies indicated that synthesized uracil derivatives have a high affinity for thymidylate synthase. Notably, the uracil derivatives dramatically inhibited the proliferation and colonization potential of BC cells in vitro. In conclusion, our study identified novel uracil derivatives as promising therapeutic options for breast cancer patients expressing the augmented levels of thymidylate synthase., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Delphinium roylei Munz is an indigenous medicinal plant to India where its activity against cancer has not been previously investigated, and its specific interactions of bioactive compounds with vulnerable breast cancer drug targets remain largely unknown. Therefore, in the current study, we aimed to evaluate the anti-breast cancer activity of different extracts of D. roylei against breast cancer and deciphering the molecular mechanism by Network Pharmacology combined with Molecular Docking and in vitro verification. The experimental plant was extracted with various organic solvents according to their polarity index. Phytocompounds were identified by High resolution-liquid chromatography-mass spectrometry (HR-LC/MS) technique, and SwissADME programme evaluated their physicochemical properties. Next, target(s) associated with the obtained bioactives or breast cancer-related targets were retrieved by public databases, and the Venn diagram selected the overlapping targets. The networks between overlapping targets and bioactive were visualized, constructed, and analyzed by STRING programme and Cytoscape software. Finally, we implemented a molecular docking test (MDT) using AutoDock Vina to explore key target(s) and compound(s). HR-LC/MS detected hundreds of phytocompounds, and few were accepted by Lipinski's rules after virtual screening and therefore classified as drug-like compounds (DLCs). A total of 464 potential target genes were attained for the nine quantitative phytocompounds and using Gene Cards, OMIM and DisGeNET platforms, 12063 disease targets linked to breast cancer were retrieved. With Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment, a total of 20 signalling pathways were manifested, and a hub signalling pathway (PI3K-Akt signalling pathway), a key target (Akt1), and a key compound (8-Hydroxycoumarin) were selected among the 20 signalling pathways via molecular docking studies. The molecular docking investigation revealed that among the nine phytoconstituents, 8-hydroxycoumarin showed the best binding energy (-9.2 kcal/mol) with the Akt1 breast cancer target. 8-hydroxycoumarin followed all the ADME property prediction using SwissADME, and 100 nanoseconds (ns) MD simulations of 8-hydroxycoumarin complexes with Akt1 were found to be stable. Furthermore, D. roylei extracts also showed significant antioxidant and anticancer activity through in vitro studies. Our findings indicated for the first time that D. roylei extracts could be used in the treatment of BC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mir, Bhat, Kumar, Dhiman, Alkhanani, Almilaibary, Dar, Ganie and Mir.)

Introduction: Despite cancer treatment strides, mortality due to ovarian cancer remains high globally. While immunotherapy has proven effective in treating cancers with low cure rates, it has limitations. Growing evidence suggests that both tumoral and non-tumoral components of the tumor immune microenvironment (TIME) play a significant role in cancer growth. Therefore, developing novel and focused therapy for ovarian cancer is critical. Studies indicate that TIME is involved in developing ovarian cancer, particularly genome-, transcriptome-, and proteome-wide studies. As a result, TIME may present a prospective therapeutic target for ovarian cancer patients., Areas Covered: We examined several TIME-targeting medicines and the connection between TIME and ovarian cancer. The key protagonists and events in the TIME and therapeutic strategies that explicitly target these events in ovarian cancer are discussed., Expert Opinion: We highlighted various targeted therapies against TIME in ovarian cancer, including anti-angiogenesis therapies and immune checkpoint inhibitors. While these therapies are in their infancy, they have shown promise in controlling ovarian cancer progression. The use of 'omics' technology is helping in better understanding of TIME in ovarian cancer and potentially identifying new therapeutic targets. TIME-targeted strategies could account for an additional treatment strategy when treating ovarian cancer.

Subclinical mastitis (SCM) is a predominant form of mastitis wherein major visible signs of disease are absent. The present study aimed to determine acute phase proteins (APPs) like ferritin, C-reactive protein (CRP), and microalbumin (Malb) in 135 composite milk and serum samples of healthy ( n = 25) and SCM ( n = 110) cows. As bovine mastitis is an inflammatory disease, the present study also aimed at finding novel anti-inflammatory compounds from natural sources by repurposing approach using computational studies. The findings of the present study revealed substantial elevation ( p < 0.001) in milk SCC and an increase in ferritin, CRP, and Malb ( p < 0.001) in milk and sera of the SCM group as compared to healthy animals. Receiver operating characteristics of milk SCC, milk, and serum APPs unraveled statistically substantial alteration ( p < 0.001). Further, SCC was correlated with milk APPs ferritin (r = 0.26 **, p < 0.002), CRP (r = 0.19 *, p < 0.02), and Malb (r = 0.21 *, p < 0.01). Additionally, milk SCC was correlated with serum ferritin (r = 0.28 **, p < 0.001), CRP (r = 0.16, p > 0.05), and Malb (r = 0.16, p > 0.05). The findings of molecular docking revealed that Chaetoglobosin U was the most effective molecule that showed the highest binding affinity (kcal/mol) of -10.1 and -8.5 against ferritin and albumin. The present study concluded that the estimation of cow-side tests, SCC, and APPs in milk/serum is suitable to detect SCM and screening herd community. Furthermore, Chaetoglobosin U could be developed as a promising anti-inflammatory inhibitor; however, further studies are required to validate these findings.

Ethnopharmacological Relevance: Cousinia thomsonii is traditionally known for treating various diseases including joint pain, swelling, body ache, asthma, dermatitis, cough and arthritis., Aim of the Study: This study employs lipopolysaccharide induced inflammatory wistar-rat model to evaluate efficacy of Cousinia thomsonii active-extracts on the expression of crucial inflammatory markers viz. iNOS, PPAR-γ, Rel-A, COX-2 and serum analysis of CRP., Materials and Methods: Methanol and aqueous extracts were administered orally at 25, 50, 100 mg/kg doses for 21 days. Serum was collected on 22nd day and rats were sacrificed to extract paw tissues. Dexamethasone (0.5 mg/kg) served as positive control. Immunoblotting and qPCR was used for expression analysis of iNOS, PPAR-γ, Rel-A, COX-2 respectively. ELISA was employed for evaluating CRP levels. Discovery-studio and Auto-Dock-Vina were used to check docking interactions of various identified compounds., Results: Both extracts caused dose-dependent decline in iNOS, Rel-A, COX-2 and CRP levels, while there was a dose-dependent increase in PPAR-γ expression. Methanol extract dominated immunomodulatory potential as compared with the aqueous extract. The results of the GCMS revealed the presence of ten compounds. Some of these compounds include 1-Octacosanol, Ethyl Linoleate, 1-Heptacosanol, 1-Hexadecanol, 1-Dodecanol and Behenic alcohol having strong anti-inflammatory, antimicrobial, anti-acne and anti-viral activities. Molecular Docking scores were calculated between each target protein and selected compounds. The best affinity/interactions were observed between 1-Octacosanol towards iNOS, PPAR-γ, Rel-A, COX-2 and CRP with binding energy of -10.4, -11.1, -8.6, -9.9 and -7.9 (kcal/mol) respectively. These compounds may act as strong inhibitors for iNOS, Rel-A, COX-2 and CRP or as agonists for PPAR-γ; thereby inducing anti-inflammatory/immuno-modulatory activities., Conclusions: The results indicate that Cousinia thomsonii contains therapeutically active compounds and thus could serve as potential therapeutic regimen against diverse inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Bovine milk is an important food component in the human diet due to its nutrient-rich metabolites. However, bovine subclinical mastitis alters the composition and quality of milk. In present study, California mastitis testing, somatic cell count, pH, and electrical conductivity were used as confirmatory tests to detect subclinical mastitis. The primary goal was to study metabolome and identify major pathogens in cows with subclinical mastitis. In this study, 29 metabolites were detected in milk using gas chromatography−mass spectrometry. Volatile acidic compounds, such as hexanoic acid, hexadecanoic acid, lauric acid, octanoic acid, n-decanoic acid, tricosanoic acid, tetradecanoic acid, and hypogeic acid were found in milk samples, and these impart good flavor to the milk. Metaboanalyst tool was used for metabolic pathway analysis and principal component estimation. In this study, EC and pH values in milk were significantly increased (p < 0.0001), whereas fat (p < 0.04) and protein (p < 0.0002) significantly decreased in animals with subclinical mastitis in comparison to healthy animals. Staphylococcus aureus was the predominant pathogen found (n = 54), followed by Escherichia coli (n = 30). Furthermore, antibiotic sensitivity revealed that Staphylococcus aureus was more sensitive to gentamicin (79.6%), whereas Escherichia coli showed more sensitivity to doxycycline hydrochloride (80%)., Competing Interests: The authors declare no conflicts of interest.

Crop domestication is a co-evolutionary process that has rendered plants and animals significantly dependent on human interventions for survival and propagation. Grain legumes have played an important role in the development of Neolithic agriculture some 12,000 years ago. Despite being early companions of cereals in the origin and evolution of agriculture, the understanding of grain legume domestication has lagged behind that of cereals. Adapting plants for human use has resulted in distinct morpho-physiological changes between the wild ancestors and domesticates, and this distinction has been the focus of several studies aimed at understanding the domestication process and the genetic diversity bottlenecks created. Growing evidence from research on archeological remains, combined with genetic analysis and the geographical distribution of wild forms, has improved the resolution of the process of domestication, diversification and crop improvement. In this review, we summarize the significance of legume wild relatives as reservoirs of novel genetic variation for crop breeding programs. We describe key legume features, which evolved in response to anthropogenic activities. Here, we highlight how whole genome sequencing and incorporation of omics-level data have expanded our capacity to monitor the genetic changes accompanying these processes. Finally, we present our perspective on alternative routes centered on de novo domestication and re-domestication to impart significant agronomic advances of novel crops over existing commodities. A finely resolved domestication history of grain legumes will uncover future breeding targets to develop modern cultivars enriched with alleles that improve yield, quality and stress tolerance., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.)

Orange red is a food and cosmetic coloring agent made by the amalgamation of two azo dyes carmoisine and sunset yellow. The current study demonstrates the effect of different concentrations of orange red on antioxidant status, inflammatory biomarkers (TNFα, IFNγ, IL1β, IL6, COX-2, iNOS, and NFκB/p65), biochemical enzymes, and liver histology. In totality, 25 male Wistar rats were procured and arbitrarily alienated into 5 different groups each with 5 animals. Group I was taken as the control. Groups II-V were designated as treatment groups. Groups II and III were administered with (5 and 25 mg/kg b.wt.) and groups IV and V with (150 and 300 mg/kg b.wt.) of orange red via oral gavage for 30 days. It was observed that both low and high concentrations of orange red (25, 150, and 300 mg/kg) remarkably augmented the levels of serum inflammatory cytokines (TNFα, IFNγ, IL1β, and IL6) and the protein and gene expression of COX-2, iNOS, and NFκB/p65. A significant decrease in glutathione reductase, glutathione peroxidase, glutathione- S -transferase, superoxidase dismutase, and catalase activity was observed with increasing concentration of orange red. Furthermore, an increase in the level of several vital biochemical parameters and damage severity to hepatic tissue was also found dose dependent.

High-throughput sequencing technologies (HSTs) have revolutionized crop breeding. The advent of these technologies has enabled the identification of beneficial quantitative trait loci (QTL), genes, and alleles for crop improvement. Climate change have made a significant effect on the global maize yield. To date, the well-known omic approaches such as genomics, transcriptomics, proteomics, and metabolomics are being incorporated in maize breeding studies. These approaches have identified novel biological markers that are being utilized for maize improvement against various abiotic stresses. This review discusses the current information on the morpho-physiological and molecular mechanism of abiotic stress tolerance in maize. The utilization of omics approaches to improve abiotic stress tolerance in maize is highlighted. As compared to single approach, the integration of multi-omics offers a great potential in addressing the challenges of abiotic stresses of maize productivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Farooqi, Nawaz, Wani, Choudhary, Rana, Sah, Afzal, Zahra, Ganie, Razzaq, Reyes, Mahmoud, Elansary, El-Abedin and Siddique.)

Identifying the genetic components underlying yield-related traits in soybean is crucial for improving its production and productivity. Here, 211 soybean genotypes were evaluated across six environments for four yield-related traits, including seed yield per plant (SYP), number of pods per plant number of seeds per plant and 100-seed weight (HSW). Genome-wide association study (GWAS) and genomic prediction (GP) analyses were performed using 12,617 single nucleotide polymorphism markers from NJAU 355K SoySNP Array. A total of 57 SNPs were significantly associated with four traits across six environments and a combined environment using five Genome-wide association study models. Out of these, six significant SNPs were consistently identified in more than three environments using multiple GWAS models. The genomic regions (±670 kb) flanking these six consistent SNPs were considered stable QTL regions. Gene annotation and in silico expression analysis revealed 15 putative genes underlying the stable QTLs that might regulate soybean yield. Haplotype analysis using six significant SNPs revealed various allelic combinations regulating diverse phenotypes for the studied traits. Furthermore, the GP analysis revealed that accurate breeding values for the studied soybean traits is attainable at an earlier generation. Our study paved the way for increasing soybean yield performance within a short breeding cycle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bhat, Adeboye, Ganie, Barmukh, Hu, Varshney and Yu.)

Key Message: Endophytes are crucial for the promotion of rice growth and stress tolerance and can be used to increase rice crop yield. Endophytes can thus be exploited in biotechnology and genetic engineering as eco-friendly and cost-effective means for the development of high-yielding and stress-tolerant rice plants. Rice (Oryza sativa) crop is continuously subjected to biotic and abiotic stresses, compromising growth and consequently yield. The situation is exacerbated by climate change impacting on ecosystems and biodiversity. Genetic engineering has been used to develop stress-tolerant rice, alongside physical and chemical methods to mitigate the effect of these stresses. However, the success of these strategies has been hindered by short-lived field success and public concern on adverse effects associated. The limited success in the field of stress-tolerant cultivars developed through breeding or transgenic approaches is due to the complex nature of stress tolerance as well as to the resistance breakdown caused by accelerated evolution of pathogens. It is therefore necessary to develop novel and acceptable strategies to enhance rice stress tolerance and durable resistance and consequently improve yield. In the last decade, plant growth promoting (PGP) microbes, especially endophytes, have drawn the attention of agricultural scientists worldwide, due to their ability to mitigate environmental stresses in crops, without causing adverse effects. Increasing evidence indicates that endophytes effectively confer fitness benefits also to rice under biotic and abiotic stress conditions. Endophyte-produced metabolites can control the expression of stress-responsive genes and improve the physiological performance and growth of rice plants. This review highlights the current evidence available for PGP microbe-promoted tolerance of rice to abiotic stresses such as salinity and drought and to biotic ones, with special emphasis on endophytes. Associated molecular mechanisms are illustrated, and prospects for sustainable rice production also in the light of the impending climate change, discussed., (© 2021. Crown.)

Key Message: Plant height of soybean is associated with a haplotype block on chromosome 19, which classified 211 soybean accessions into five distinct groups showing significant differences for the target trait. Genetic variation is pivotal for crop improvement. Natural populations are precious genetic resources. However, efficient strategies for the targeted utilization of these resources for quantitative traits, such as plant height (PH), are scarce. Being an important agronomic trait associated with soybean yield and quality, it is imperative to unravel the genetic mechanisms underlying PH in soybean. Here, a genome-wide association study (GWAS) was performed to identify single nucleotide polymorphisms (SNPs) significantly associated with PH in a natural population of 211 cultivated soybeans, which was genotyped with NJAU 355 K Soy SNP Array and evaluated across six environments. A total of 128 SNPs distributed across 17 chromosomes were found to be significantly associated with PH across six environments and a combined environment. Three significant SNPs were consistently identified in at least three environments on Chr.02 (AX-93958260), Chr.17 (AX-94154834), and Chr.19 (AX-93897200). Genomic regions of ~ 130 kb flanking these three consistent SNPs were considered as stable QTLs, which included 169 genes. Of these, 22 genes (including Dt1) were prioritized and defined as putative candidates controlling PH. The genomic region flanking 12 most significant SNPs was in strong linkage disequilibrium (LD). These SNPs formed a single haplotype block containing five haplotypes for PH, namely Hap-A, Hap-B, Hap-C, Hap-D, and Hap-E. Deployment of such superior haplotypes in breeding programs will enable development of improved soybean varieties with desirable plant height., (© 2022. The Author(s).)

Sodium benzoate is a widely used food and pharmaceutical preservative due to its antibacterial and antifungal activity. In the present study effect of different concentrations of sodium benzoate on hepatic antioxidants, inflammatory cytokines (TNF-α, IFN-γ, IL-1β and IL-6), biochemical markers and histopathology of liver was evaluated. Twenty five adult rats (aged 1-2 months) with 5 rats per group were randomly distributed into 5 groups. Group 1 rats were used as control and all groups (1-5) were provided with water and fed ad libitum . In addition to usual water and food, rats of group 2, 3, 4 and 5 were treated with 70, 200, 400 and 700 mg/kg b.wt of sodium benzoate once a day via oral gavage for 30 days. Our results showed that activity of glutathione peroxidase (GPx), catalase (CAT), glutathione-s-transferase (GST), glutathione reductase (GR) and superoxide dismutase (SOD) in rats decreased significantly when treated with 200, 400 and 700 mg/kg b.wt of sodium benzoate. Increase in the concentration of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, serum total protein, albumin, globulin, urea and creatinine was found to be dose dependent. Severe histopathological damage was observed in the hepatic tissue at higher concentrations of sodium benzoate. It was noticed that high concentrations of sodium benzoate (200, 400 and 700 mg/kg b.wt) produce significant increase in inflammatory cytokine markers (TNF-α, IFN-γ, IL-1β and IL-6) in comparison to control. Sodium benzoate at concentration of 70 mg/kg b.wt did not produce any significant changes in any of the above studied parameters.

Dairy cattle with a high milk yield are susceptible to many infectious diseases, such as mastitis. Subclinical mastitis (SCM) is the most prevalent form of mastitis that predominantly affects animal health, and causes adverse effects on the quality and quantity of milk. In dairy animals, subclinical mastitis often remains undetected, as no gross changes in udder characteristics are visible. In the present study, 135 Holstein Friesian dairy animals were selected and screened as healthy (n = 25) and mastitic (n = 110) based on diagnostic tests such as the California mastitis test, pH, electrical conductivity, and somatic cell count. In this study, the somatic cell count was used as a gold-standard test in differentiating subclinical mastitis animals from healthy ones. The present study was carried out to study polymorphisms in the bovine transferrin gene in cows (with subclinical mastitis and healthy). For the early detection of resistant/or susceptible animals, a useful marker could be provided by the detection of single-nucleotide polymorphisms (SNPs) in the transferrin gene, which are often associated with mammary innate immune response. The sequencing results revealed three nucleotide substitutions: two transversions (230 A > C, 231 C > A) and one transition (294 A > G) in susceptible cows as compared to disease-free subjects. The nucleotide variations at position 230 (GAC > GCA) and 231 (GAC > GCA) were nonsynonymous, and corresponded to an amino acid change from aspartic acid to alanine; whereas at position 294 (GAA > GAG), the mutation was synonymous. In the present study, many in silico tools were taken into consideration to determine the effect of SNPs on protein structure and function. The PROVEAN tool found the amino acid substitution to be neutral and deleterious. PolyPhen-2 revealed the amino acid variations at positions 320 and 321 to most likely be damaging; and at the 341 position, the variations were benign. The I-Mutant and MUpro tools found that the protein stability decreased for nonsynonymous variations. The SIFT tool revealed the protein function was likely to be affected in nonsynonymous variations, with no change in the case of synonymous ones. Phylogenetic analysis of the bovine transferrin gene revealed a close relation of the CA allele with the Bos taurus transferrin, while the G allele was closely related to a cross of Bos indicus × Bos taurus serotransferrins, followed by the Bison bison transferrin. The least relation was shown by both alleles to Capra hircus, Ovis aries, and Bubalus bubalis.

Climate change with altered pest-disease dynamics and rising abiotic stresses threatens resource-constrained agricultural production systems worldwide. Genomics-assisted breeding (GAB) approaches have greatly contributed to enhancing crop breeding efficiency and delivering better varieties. Fast-growing capacity and affordability of DNA sequencing has motivated large-scale germplasm sequencing projects, thus opening exciting avenues for mining haplotypes for breeding applications. This review article highlights ways to mine haplotypes and apply them for complex trait dissection and in GAB approaches including haplotype-GWAS, haplotype-based breeding, haplotype-assisted genomic selection. Improvement strategies that efficiently deploy superior haplotypes to hasten breeding progress will be key to safeguarding global food security., (© 2021. The Author(s).)

Guar gum is a neutral, non-ionic polysaccharide that has been extensively utilized in the food industry as a stabilizer, excipients, and emulsifier agent. An oxidized derivative of this edible guar gum was prepared and used as a complexing agent for iron to obtain a polysaccharide-bound iron (II) complex. The degree of oxidation varies between 30.12 and 60.63% with a corresponding aldehyde content (0.59-1.79 mmol/g) and carboxyl contents (0.49-1.62 mmol/g), which were determined by the titrimetry method. Sophisticated spectroscopic techniques characterized all the products. The natural polymer-based hydrophilic and hydrophobic formulations as coating were used for achieving the sustained or prolonged release from the complex tablets. Release studies of the tablets were carried out in different mediums of varying pH. The total iron available from the tablets was compared with that obtained from ferrous fumarate prepared under similar conditions, and the results were found to be comparable. Release results demonstrate the pH-sensitive behaviour of the guar gum-based delivery system towards the controlled release of iron. Antianemic effect of new functionalized guar gum iron complexes was investigated on male albino rats. The complexes may exhibit the potential to recover the hematological index of the albino rats with some positive effects on improving rat's growth with iron deficiency anaemia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Improvements in yield and quality of rice are crucial for global food security. However, global rice production is substantially hindered by various biotic and abiotic stresses. Making further improvements in rice yield is a major challenge to the rice research community, which can be accomplished through developing abiotic stress-resilient rice varieties and engineering durable agrochemical-independent pathogen resistance in high-yielding elite rice varieties. This, in turn, needs increased understanding of the mechanisms by which stresses affect rice growth and development. Alternative splicing (AS), a post-transcriptional gene regulatory mechanism, allows rapid changes in the transcriptome and can generate novel regulatory mechanisms to confer plasticity to plant growth and development. Mounting evidence indicates that AS has a prominent role in regulating rice growth and development under stress conditions. Several regulatory and structural genes and splicing factors of rice undergo different types of stress-induced AS events, and the functional significance of some of them in stress tolerance has been defined. Both rice and its pathogens use this complex regulatory mechanism to devise strategies against each other. This review covers the current understanding and evidence for the involvement of AS in biotic and abiotic stress-responsive genes, and its relevance to rice growth and development. Furthermore, we discuss implications of AS for the virulence of different rice pathogens and highlight the areas of further research and potential future avenues to develop climate-smart and disease-resistant rice varieties.

Rice is a premier staple food that constitutes the bulk of the daily diet of the majority of people in Asia. Agricultural productivity must be boosted to support this huge demand for rice. However, production is jeopardized by soil salinity. Advances in whole-genome sequencing, marker-assisted breeding strategies, and targeted mutagenesis have substantially improved the toolbox of today's breeders. Given that salinity has a major influence on rice at both the seedling and reproductive stages, understanding and manipulating this trait will have an enormous impact on sustainable production. This article summarizes recent developments in the understanding of the mechanisms of salt tolerance and how state-of-the-art tools such as RNA guided CRISPR endonuclease technology including targeted mutagenesis or base and prime editing can help in gene discovery and functional analysis as well as in transferring favorable alleles into elite breeding material to speed the breeding of salt-tolerant rice cultivars., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Key Message: Cell wall plasticity plays a very crucial role in vegetative and reproductive development of rice under drought and is a highly potential trait for improving rice yield under drought. Drought is a major constraint in rice (Oryza sativa L.) cultivation severely affecting all developmental stages, with the reproductive stage being the most sensitive. Rice plants employ multiple strategies to cope with drought, in which modification in cell wall dynamics plays a crucial role. Over the years, significant progress has been made in discovering the cell wall-specific genomic resources related to drought tolerance at vegetative and reproductive stages of rice. However, questions remain about how the drought-induced changes in cell wall made by these genomic resources potentially influence the vegetative and reproductive development of rice. The possibly major candidate genes underlying the function of quantitative trait loci directly or indirectly associated with the cell wall plasticization-mediated drought tolerance of rice might have a huge promise in dissecting the putative genomic regions associated with cell wall plasticity under drought. Furthermore, engineering the drought tolerance of rice using cell wall-related genes from resurrection plants may have huge prospects for rice yield improvement. Here, we review the comprehensive multidisciplinary analyses to unravel different components and mechanisms involved in drought-induced cell wall plasticity at vegetative and reproductive stages that could be targeted for improving rice yield under drought.

In the present study, transcriptomic analysis of 10-days old baby kernels of two contrasting maize genotypes, namely VQL-2 (high kernel Zn accumulator) and CM-145 (low kernel Zn accumulator), under low- and optimum- soil Zn conditions generated 1948 differentially expressed transcripts. Among these, 666 and 437 transcripts were up-regulated and down-regulated respectively in VQL-2; whereas, 437 and 408 transcripts were up-regulated and down-regulated respectively in CM-145. Remarkably, 135 transcription factors and 77 known Zn transporters expressed differentially. By comparing the transcripts differentially expressed between the optimum-Zn and low-Zn libraries of the contrasting genotypes, we identified 21,986 and 26,871 SNPs, respectively. Similarly, 6810 and 8192 InDels were found between optimum- and low-Zn growing conditions, respectively. Further, 21 differentially expressed genes were co-localized with already known QTLs associated with Zn uptake, such as qZn10, CQZnK9-1 and YNZnK6. These findings will be useful to develop high Zn-accumulator maize through marker-assisted breeding in future., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Folic acid a synthetic form of folate, is the oxidized form of folate which acts as a coenzyme in one carbon transfer reactions required in the biosynthesis of DNA and RNA and its deficiency could be related to diseases such as neural tube defects, Alzheimer's disease, pregnancy complications and cancer. Inulin is a polydisperse polysaccharide comprising mostly of fructosyl fructose units. An oxidized derivative of this inulin was prepared and used as a complexing agent for folic acid to obtain a polysaccharide bound folic acid conjugate. The aldehyde content and degree of oxidation of the oxidized inulin were determined by acid-base titrations. All the products were characterized by sophisticated spectroscopic and thermal methods of analysis. Release studies of folic acid from conjugates were carried out in different pH media and the results demonstrate the pH-sensitive behavior of the inulin-based delivery system towards the controlled release of folic acid., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Dipsacus inermis Wall. is an edible Himalayan herb which is extensively used in traditional Ayurvedic system of medicine against various inflammation related disorders., Aim of the Study: This study was designed to evaluate the anti-inflammatory effects of Dipsacus inermis Wall. methanol extract (DIME) by using in vitro and in vivo models and to elucidate the underlying mechanism of action., Materials and Methods: The in vitro anti-inflammatory potential of DIME was determined in LPS stimulated J774A.1 cells. The inhibitory effect of DIME on COX-2, PGE2 and inflammatory cytokines was determined by ELISA and RT-PCR. The suppression of ROS in response to DIME was determined by flow cytometry. Phosphorylation of NF-κBp65 and IκB degradation was determined by western blotting., Results: Significant inhibition of NO, COX-2, PGE2 and pro-inflammatory cytokines including IL-1β, TNF-α and IL-6 was found in response to DIME in LPS stimulated J774A.1 cells. The extract was found to down regulate the LPS induced expression of TNF-α, IL-6, iNOS and COX-2 along with inhibition of intracellular ROS. The in vivo studies carried on Wistar rats showed significant preventive effect of DIME against acetic acid induced increase in vascular permeability and carrageenan induced paw edema along with stabilization of histopathological alterations., Conclusion: The study demonstrated that DIME has significant in vitro and in vivo anti-inflammatory effect which is mediated by inhibiting the activation of NF-κB pathway. Our data opened a promising new pharmacological approach of designing anti-inflammatory drugs by studying individual fractions of the plant extract., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Neurodegeneration entails progressive loss of neuronal structure as well as function leading to cognitive failure, apathy, anxiety, irregular body movements, mood swing and ageing. Proteomic dysregulation is considered the key factor for neurodegeneration. Mechanisms involving deregulated processing of proteins such as amyloid beta (Aβ) oligomerization; tau hyperphosphorylation, prion misfolding; α-synuclein accumulation/lewy body formation, chaperone deregulation, acetylcholine depletion, adenosine 2A (A2A) receptor hyperactivation, secretase deregulation, leucine-rich repeat kinase 2 (LRRK2) mutation and mitochondrial proteinopathies have deeper implications in neurodegenerative disorders. Better understanding of such pathological mechanisms is pivotal for exploring crucial drug targets. Herein, we provide a comprehensive outlook about the diverse proteomic irregularities in Alzheimer's, Parkinson's and Creutzfeldt Jakob disease (CJD). We explicate the role of key neuroproteomic drug targets notably Aβ, tau, alpha synuclein, prions, secretases, acetylcholinesterase (AchE), LRRK2, molecular chaperones, A2A receptors, muscarinic acetylcholine receptors (mAchR), N-methyl-D-aspartate receptor (NMDAR), glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) and mitochondrial/oxidative stress-related proteins for combating neurodegeneration and associated cognitive and motor impairment. Cross talk between amyloidopathy, synucleinopathy, tauopathy and several other proteinopathies pinpoints the need to develop safe therapeutics with ability to strike multiple targets in the aetiology of the neurodegenerative disorders. Therapeutics like microtubule stabilisers, chaperones, kinase inhibitors, anti-aggregation agents and antibodies could serve promising regimens for treating neurodegeneration. However, drugs should be target specific, safe and able to penetrate blood-brain barrier.

Food dyes are important component of food in this fast life. Metanil yellow and carmoisine are two azo dyes which are being used at an alarming rate for increasing visual appearance and consumer validity of food. There is a lot of controversy regarding the genotoxicity of these two dyes. In the present study genotoxicity of two food dyes metanil yellow and carmoisine was evaluated using Allium cepa as indicator. The effect of these two azo dyes was determined at concentration of 0.25 %, 0.50 %, 0.75 % and 1.0 % for 24 h and 48 h of exposure period using root meristematic cells of Allium cepa . Some genotoxicity parameters like mitotic indices and chromosomal aberrations were studied. It was found that both metanil yellow and carmoisine caused a significant reduction in mitotic index and also produce different kinds of chromosomal aberrations mostly at higher concentration and longer exposure period. The different kinds of aberrations that were observed in meristematic cells after treatment with both metanil yellow and carmoisine are disorientation at metaphase, metaphase stickiness, anaphase stickiness, anaphase bridge, c-mitosis and chromosome breaks. The genotoxicity of carmoisine was found very high as compared to metanil yellow at all concentrations and exposure periods. Thus it was concluded from the present study that carmoisine and metanil yellow have genotoxic activities and should be taken in very control and limited doses., Competing Interests: None., (© 2020 Published by Elsevier B.V.)

MicroRNAs (miRNAs) are tiny (20-24 nt bp) regulatory non-protein-coding RNA molecules that have been extensively characterized and found important for many physiological and developmental processes. The miss-expression of miRNAs leads to various defects in plants. MicroRNAs repress gene expression by directing mRNA degradation or translational arrest. Several proteins such as PP43A, HYL1, DCL, HST are indispensable role players in promoting miRNA biogenesis in plants. During miRNA biogenesis, lariat RNAs are produced as by-products of pre-mRNA splicing which have a negative role in regulation of miRNA homeostasis. By acting as a decoy and by sequestering to the dicing complex, lariat RNA can prevent the processing of miRNAs. A number of bioinformatic tools with different methodologies are available to identify and validate miRNAs and their targets. Many miRNAs have been reported in different crops for different traits; however, no reports are available on their use in plant breeding. Recently, researchers have developed trait specific miRNA-based molecular markers (miRNA-SSRs/SNP) for many quantitative traits in different plant species. In the future, these molecular markers can be used for plant breeding programs. In this review, a comprehensive up-to-date information is provided on the bioinformatic tools used for analysis of plant miRNAs and their targets, the number of miRNAs, their biogenesis, gene silencing mechanism and miRNA-based molecular markers., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© King Abdulaziz City for Science and Technology 2019.)

Ageratum conyzoides L. (Asteraceae) is an invasive aromatic herb with immense therapeutic importance. The herb is distributed in tropical and subtropical regions. A. conyzoides has imparted numerous ethnomedicinal uses because it has been used to cure various ailments that include leprosy, skin disorders, sleeping sickness, rheumatism, headaches, dyspnea, toothache, pneumonia and many more. A number of phytoconstituents have been scrutinized such as alkaloids, flavonoids, terpenes, chromenes, and sterols from almost every part of this plant. These phytoconstituents have shown diverse pharmacological properties including antimicrobial, anti-inflammatory, analgesic, antioxidant, anticancer, antiprotozoal, antidiabetic, spasmolytic, allelopathy, and many more. The plant A. conyzoides has provided a platform for doing pharmaceutical and toxicological research in order to isolate some promising active compounds and authenticate their safety in clinical uses. A. conyzoides provides principal information for advanced studies in the field of pharmaceutical industries and agriculture. Present review article describes the cytogenetics, ethnobotany, phytochemistry, pharmacology, and toxicological aspects of A. conyzoides., (© 2019 John Wiley & Sons, Ltd.)

This study evaluates the ameliorative potential of Rheum spiciformis methanolic (RS-MeOH) extract in reducing oxidative stress and hyperglycemia in albino rats along with characterization of possible therapeutic compound(s). Groups treated with 50 and 100 mg/kg bw plant extract (RS-MeOH ) decrease blood glucose levels from 359.9±8.2 to 209.5±8.5 mg/dl (50 mg/kg bw) and 354.7±13.3 to 162.5±7.4 mg/dl (100 mg/kg bw) on the 0 th and 14 th day (P<0.001) respectively. This reduction in blood glucose was significant as compared to glibenclamide (20 mg/dl) which reduced glucose levels from 297.7±11.39 to 132.9±8.74 mg/dl on 0 th and 14 th day respectively. Biochemical parameters triglycerdies, cholesterol, low density lipoprotein (LDL) and creatinine were also reduced in a dose dependent manner. Liver marker enzymes were positively modulated by administration of RS-MeOH (P<0.001). Antioxidant enzyme profile showed an enhanced/better pattern after the administration of RS-MeOH extracts for reduced glutathione, reduced glutathione (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and superoxide dismutase (SOD) in both liver and pancreas. Moreover pancreatic histopathology reports revealed β-cell restorative effects with RS-MeOH, thereby potentiating its role in improving blood glucose levels. RS-MeOH purification and isolation studies involving GC-MS and NMR techniques revealed presence of emodin type compounds in RS-MeOH. Overall Rheum spiciformis showed ameliorative action on oxidative stress and hyperglycemia, however further studies to explore the mechanism of action of possible therapeutic compound in invivo clinical trials will prove beneficial for the advancement of new oral antidiabetic drug., Competing Interests: There is none to declare., (© Georg Thieme Verlag KG Stuttgart · New York.)

Key Message: This review presents a comprehensive overview of the recent research on rice salt tolerance in the areas of genomics, proteomics, metabolomics and chemical genomics. Salinity is one of the major constraints in rice cultivation globally. Traditionally, rice is a glycophyte except for a few genotypes that have been widely used in salinity tolerance breeding of rice. Both seedling and reproductive stages of rice are considered to be the salt-susceptible stages; however, research efforts have been biased towards improving the understanding of seedling-stage salt tolerance. An extensive literature survey indicated that there have been very few attempts to develop reproductive stage-specific salt tolerance in rice probably due to the lack of salt-tolerant phenotypes at the reproductive stage. Recently, the role of DNA methylation, genome duplication and codon usage bias in salinity tolerance of rice have been studied. Furthermore, the study of exogenous salt stress alleviants in rice has opened up another potential avenue for understanding and improving its salt tolerance. There is a need to not only generate additional genomic resources in the form of salt-responsive QTLs and molecular markers and to characterize the genes and their upstream regulatory regions, but also to use them to gain deep insights into the mechanisms useful for developing tolerant varieties. We analysed the genomic locations of diverse salt-responsive genomic resources and found that rice chromosomes 1-6 possess the majority of these salinity-responsive genomic resources. The review presents a comprehensive overview of the recent research on rice salt tolerance in the areas of genomics, proteomics, metabolomics and chemical genomics, which should help in understanding the molecular basis of salinity tolerance and its more effective improvement in rice.

Toxic metals have disturbed the quality of freshwater ecosystems worldwide. The concentration of heavy metals was investigated in liver, gills and muscle tissues of Schizothorax niger and Cyprinus carpio captured from river Jhelum of Kashmir Himalaya. The heavy metals displayed a wide range of disparity in studied tissues, seasons, sites and species. Cu 2+ exhibited the highest concentration (279.6 μg/kg) in the liver tissues of S. niger in autumn at site 2 and the lowest (53.1 μg/kg) in the gill tissues in winter at site 1. In C. carpio, the Cu 2+ was recorded highest (309.4 μg/kg) in the liver tissues in autumn at site 2. The concentration of Zn 2+ was found highest (575.7 μg/kg) in the liver tissues at site 2 and the lowest (65.8 μg/kg) was recorded in the muscle tissues in autumn at site 1. Zn 2+ was recorded highest (416.6 μg/kg) in the liver tissues in autumn at site 3 and lowest (51.5 μg/kg) in the gills of C. carpio during winter at site 1 (control). The concentration of Pb 2+ (14.42 μg/kg) and Fe 2+ (323.9 μg/kg) was observed in the liver tissue and gills of S. niger at site 3. Similar levels of Pb 2+ and Fe 2+ were recorded in the tissues of C. carpio at different sites. Four-way ANOVA (four way) indicated a statistically significant variation (p ≤ 0.05) in heavy metals with the sites, seasons, species and organs. The study emphasises the utmost need to monitor the level of heavy metals in S. niger on a regular basis as this native fish species is showing a continuous decline in the freshwater ecosystems of Kashmir Valley.

Protein-Protein Interactions (PPIs) drive major signalling cascades and play critical role in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple malignancies and represent the critical targets for treating cancer. Herein, we discuss the key protein-protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM and PH. These domains are present in numerous enzymes/kinases, growth factors, transcription factors, adaptor proteins, receptors and scaffolding proteins and thus represent essential sites for targeting cancer. This review explores the candidature of various proteins involved in cellular trafficking (small GTPases, molecular motors, matrix-degrading enzymes, integrin), transcription (p53, cMyc), signalling (membrane receptor proteins), angiogenesis (VEGFs) and apoptosis (BCL-2family), which could possibly serve as targets for developing effective anti-cancer regimen. Interactions between Ras/Raf; X-linked inhibitor of apoptosis protein (XIAP)/second mitochondria-derived activator of caspases (Smac/DIABLO); Frizzled (FRZ)/Dishevelled (DVL) protein; beta-catenin/T Cell Factor (TCF) have also been studied as prospective anticancer targets. Efficacy of diverse molecules/ drugs targeting such PPIs although evaluated in various animal models/cell lines, there is an essential need for human-based clinical trials. Therapeutic strategies like the use of biologicals, high throughput screening (HTS) and fragment-based technology could play an imperative role in designing cancer therapeutics. Moreover, bioinformatic/computational strategies based on genome sequence, protein sequence/structure and domain data could serve as competent tools for predicting PPIs. Exploring hot spots in proteomic networks represents another approach for developing targetspecific therapeutics. Overall, this review lays emphasis on a productive amalgamation of proteomics, genomics, biochemistry, and molecular dynamics for successful treatment of cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of the present study was to evaluate the hepatoprotective activity of methanolic extract of Elsholtzia densa against experimentally induced acute (CCl 4 ) and chronic (paracetamol) liver injury in albino wistar rats. Activity was measured by monitoring the serum levels of ALT, ALP AST and LDH, total protein levels, bilirubin and albumin. The results of the CCl 4 and paracetamol-induced liver toxicity experiments showed that the rats treated with the methanolic extract of Elsholtzia densa exhibited a significant decrease in biochemical parameters as well as the proteins, which were all elevated in the CCl 4 and paracetamol group. The extract at a concentration of 300 mg/kg body wt. showed a significant decline (P≤0.05) in the levels of AST, ALT, ALP and LDH to 69.50±2.23IU/L, 60.01±2.25IU/L,46.20±2.24 IU/L and 150.21±5.68IU/L in CCl 4 injected animals and 51.12±2.20 IU/L,49.15±3.25 IU/L, 44.12±2.56 IU/L and 125.15±4.45 IU/L in paracetamol-treated animals when compared to the control group. The activities of tissue antioxidants GSH, GPx, GR, GST and CAT was significantly (P≤0.05) restored in dose dependent manner in animals treated with extracts as with acute and chronic hepatotoxic models. The current study confirmed the hepatoprotective effect of methanolic extract of Elsholtzia densa against the model hepatotoxicant CCl 4 and paracetamol., Competing Interests: The authors do not have any conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Gum arabic, a plant polysaccharide was oxidized with periodate to produce aldehyde groups by the cleavage of diols present in the sugar units. The oxidized gum was then iodinated with iodine monochloride (ICl) and the interaction between electrophilic iodine, I + and reactive carbonyl groups of the modified gum was studied.Results of titrimetric estimation performed to determine the extent of oxidation and aldehyde content in the oxidized gum showed that degree of oxidation ranged between 19.68-50.19% which was observed to increase with periodate concentration; the corresponding aldehyde content was calculated to be 5.15-40.42%. Different strengths of ICl were used to iodinate the oxidized gum and the iodine content of the complexes varied from 6.11-11.72% as determined by iodometric titration. Structure elucidation of the iodine complexes conclusively established the attachment of ICl molecules to CHO groups. A reaction scheme has been proposed suggesting an electrophilic addition of the reagent to the aldehyde groups, a mechanism that was also supported by iodide ion release studies., (Copyright © 2017 Elsevier Ltd. All rights reserved.)