Multifaceted targets of cannabidiol in epilepsy: Modulating glutamate signaling and beyond.

Cannabidiol has been reported to interact with broad-spectrum biological targets with pleiotropic pharmacology including epilepsy although a cohesive mechanism is yet to be determined. Even though some studies propose that cannabidiol may manipulate glutamatergic signals, there is insufficient evidence to support cannabidiol direct effect on glutamate signaling, which is important in intervening epilepsy. Therefore, the present study aimed to analyze the epilepsy-related targets for cannabidiol, assess the differentially expressed genes with its treatment, and identify the possible glutamatergic signaling target. In this study, the epileptic protein targets of cannabidiol were identified using the Tanimoto coefficient and similarity index-based targets fishing which were later overlapped with the altered expression, epileptic biomarkers, and genetically altered proteins in epilepsy. The common proteins were then screened for possible glutamatergic signaling targets with differentially expressed genes. Later, molecular docking and simulation were performed using AutoDock Vina and GROMACS to evaluate binding affinity, ligand-protein stability, hydrophilic interaction, protein compactness, etc. Cannabidiol identified 30 different epilepsy-related targets of multiple protein classes including G-protein coupled receptors, enzymes, ion channels, etc. Glutamate receptor 2 was identified to be genetically varied in epilepsy which was targeted by cannabidiol and its expression was increased with its treatment. More importantly, cannabidiol showed a direct binding affinity with Glutamate receptor 2 forming a stable hydrophilic interaction and comparatively lower root mean squared deviation and residual fluctuations, increasing protein compactness with broad conformational changes. Based on the cheminformatic target fishing, evaluation of differentially expressed genes, molecular docking, and simulations, it can be hypothesized that cannabidiol may possess glutamate receptor 2-mediated anti-epileptic activities.

Field application of Ca-doped ZnO nanoparticles to maize and wheat plants.

Nanoparticles play a vital role in modern agriculture to provide the nutrients required by plants. Herein, we report the preparation of calcium-doped zinc oxide nanoparticles (CZO NPs) via a simple and cost-effective co-precipitation method, with the aim of realizing increased fertilizer response. The synthesized nanoparticles were analyzed to study their physicochemical properties using various characterization techniques. The X-ray diffraction pattern showed a small shift in peak position towards higher values of 2θ and reduced crystal size after the zinc oxide (ZnO) matrix had been doped with Ca. Field-emission scanning electron microscopy images clearly revealed a grain-like surface morphology. The X-ray photoelectron spectroscopy study produced evidence of Zn2+ substitution by Ca2+ and enhanced Zn-O bond strengths in the CZO samples. Two major crops, maize (Zea mays L.) and wheat (Triticum aestivum L.) were selected to study the impact of the CZO NP-based nanofertilizer on plant growth. During the study, the effect of the CZO-based fertilizer on growth parameters such as seed germination, root and shoot length, plant height, root and stem width, number of leaves, and leaf size was studied based on comparisons with control plants. We observed significantly increased plant growth parameters after the application of the CZO NP-based fertilizers.

The marijuana-schizophrenia multifaceted nexus: Connections and conundrums towards neurophysiology.

Delta-9-tetrahydrocannabinol, a component of marijuana, interacts with cannabinoid receptors in brain involved in memory, cognition, and emotional control. However, marijuana use and schizophrenia development is a complicated and contentious topic. As a result, more investigation is needed to understand this relationship. Through the functional enrichment analysis, we report the delta-9-tetrahydrocannabinol to manipulate the homeostatic biological process and molecular function of different macromolecules. Additionally, using molecular docking and subsequent processing for molecular simulations, we assessed the binding ability of delta-9-tetrahydrocannabinol with the estrogen-related protein, dopamine receptor 5, and hyaluronidase. It was found that delta-9-tetrahydrocannabinol may have an impact on the brain's endocannabinoid system and may trigger the schizophrenia progression in vulnerable people. Delta-9-tetrahydrocannabinol may interfere with the biological function of 18 proteins linked to schizophrenia and disrupt the synaptic transmission (dopamine, glutamine, and gamma-aminobutyric acid). It was discovered that it may affect lipid homeostasis, which is closely related to membrane integrity and synaptic plasticity. The negative control of cellular and metabolic processes, fatty acids binding /activity, and the manipulated endocannabinoid system (targeting cannabinoid receptors) were also concerned with delta-9-tetrahydrocannabinol. Hence, this may alter neurotransmitter signaling involved in memory, cognition, and emotional control, showing its direct impact on brain physiological processes. This may be one of the risk factors for schizophrenia development which is also closely tied to some other variables such as frequency, genetic vulnerability, dosage, and individual susceptibility.

Life cycle assessment of greenhouse gas emission from the dairy production system - review.

Climate change is altering ecological systems and poses a serious threat to human life. Climate change also seriously influences on livestock production by interfering with growth, reproduction, and production. Livestock, on the other hand, is blamed for being a significant contributor to climate change, emitting 8.1 gigatonnes of CO2-eq per year and accounting for two-thirds of global ammonia emissions. Methane (CH4), nitrous oxide (N2O), and carbon dioxide (CO2) are three major greenhouse gases (GHG) that are primarily produced by enteric fermentation, feed production, diet management, and total product output. Ruminants account for three-quarters of total CO2-equivalent (CO2-eq) emissions from the livestock sector. The global dairy sector alone emits 4.0% of global anthropogenic GHG emissions. Hence, dairy farming needs to engage in environmental impact assessment. Public concern for a sustainable and environmentally friendly farming system is growing, resulting in the significant importance of food-based life cycle assessment (LCA). Over the last decade, LCA has been used in agriculture to assess total GHG emissions associated with products such as milk and manure. It includes the production of farm inputs, farm emissions, milk processing, transportation, consumer use, and waste. LCA studies on milk production would assist us in identifying the specific production processes/areas that contribute to excessive greenhouse gas emissions when producing milk and recommending appropriate mitigation strategies to be implemented for a clean, green, and resilient environment.

A comprehensive analysis of Trehalose-6-phosphate synthase (TPS) gene for salinity tolerance in chickpea (Cicer arietinum L.).

Soil salinity affects various crop cultivation but legumes are the most sensitive to salinity. Osmotic stress is the first stage of salinity stress caused by excess salts in the soil on plants which adversely affects the growth instantly. The Trehalose-6-phosphate synthase (TPS) genes play a key role in the regulation of abiotic stresses resistance from the high expression of different isoform. Selected genotypes were evaluated to estimate for salt tolerance as well as genetic variability at morphological and molecular level. Allelic variations were identified in some of the selected genotypes for the TPS gene. A comprehensive analysis of the TPS gene from selected genotypes was conducted. Presence of significant genetic variability among the genotypes was found for salinity tolerance. This is the first report of allelic variation of TPS gene from chickpea and results indicates that the SNPs present in these conserved regions may contribute largely to functional distinction. The nucleotide sequence analysis suggests that the TPS gene sequences were found to be conserved among the genotypes. Some selected genotypes were evaluated to estimate for salt tolerance as well as for comparative analysis of physiological, molecular and allelic variability for salt responsive gene Trehalose-6-Phosphate Synthase through sequence similarity. Allelic variations were identified in some selected genotypes for the TPS gene. It is found that Pusa362, Pusa1103, and IG5856 are the most salt-tolerant lines and the results indicates that the identified genotypes can be used as a reliable donor for the chickpea improvement programs for salinity tolerance.

Development of High Yielding Fusarium Wilt Resistant Cultivar by Pyramiding of "Genes" Through Marker-Assisted Backcrossing in Chickpea (Cicer arietinum L.).

Pusa 391, a mega desi chickpea variety with medium maturity duration is extensively cultivated in the Central Zone of India. Of late, this variety has become susceptible to Fusarium wilt (FW), which has drastic impact on its yield. Presence of variability in the wilt causing pathogen, Fusarium oxysporum f.sp. ciceri (foc) across geographical locations necessitates the role of pyramiding for FW resistance for different races (foc 1,2,3,4 and 5). Subsequently, the introgression lines developed in Pusa 391 genetic background were subjected to foreground selection using three SSR markers (GA16, TA 27 and TA 96) while 48 SSR markers uniformly distributed on all chromosomes, were used for background selection to observe the recovery of recurrent parent genome (RPG). BC1F1 lines with 75-85% RPG recovery were used to generate BC2F1. The plants that showed more than 90% RPG recovery in BC2F1 were used for generating BC3F1. The plants that showed more than 96% RPG recovery were selected and selfed to generate BC3F3. Multi-location evaluation of advanced introgression lines (BC2F3) in six locations for grain yield (kg/ha), days to fifty percent flowering, days to maturity, 100 seed weight and disease incidence was done. In case of disease incidence, the genotype IL1 (BGM 20211) was highly resistant to FW in Junagarh, Indore, New Delhi, Badnapur and moderately resistant at Sehore and Nandyal. GGE biplot analysis revealed that IL1(BGM20211) was the most stable genotype at Junagadh, Sehore and Nandyal. GGE biplot analysis revealed that IL1(BGM 20211) and IL4(BGM 20212) were the top performers in yield and highly stable across six environments and were nominated for Advanced Varietal Trials (AVT) of AICRP (All India Coordinated Research Project on Chickpea) in 2018-19. BGM20211 and BGM 20212 recorded 29 and 28.5% average yield gain over the recurrent parent Pusa 391, in the AVT-1 and AVT-2 over five environments. Thus, BGM20211 was identified for release and notified as Pusa Manav/Pusa Chickpea 20211 for Madhya Pradesh, Gujarat and Maharashtra, Southern Rajasthan, Bundhelkhand region of Uttar Pradesh states by the Central Sub-Committees on Crop Standards, Notification and Release of Varieties of Agricultural Crops, Ministry of Agriculture and Farmers Welfare, Government of India, for commercial cultivation in India (Gazette notification number S.O.500 (E) dt. 29-1-2021).Such pyramided lines give resilience to multiple races of fusarium wilt with added yield advantage.

Computational investigation of benzalacetophenone derivatives against SARS-CoV-2 as potential multi-target bioactive compounds.

Benzalacetophenones, precursors of flavonoids are aromatic ketones and enones and possess the immunostimulant as well as antiviral activities. Thus, benzalacetophenones were screened against the COVID-19 that could be lethal in patients with compromised immunity. We considered ChEBI recorded benzalacetophenone derivative(s) and evaluated their activity against 3C-like protease (3CLpro), papain-like protease (PLpro), and spike protein of SARS-Cov-2 to elucidate their possible role as antiviral agents. The probable targets for each compound were retrieved from DIGEP-Pred at 0.5 pharmacological activity and all the modulated proteins were enriched to identify the probably regulated pathways, biological processes, cellular components, and molecular functions. In addition, molecular docking was performed using AutoDock 4 and the best-identified hits were subjected to all-atom molecular dynamics simulation and binding energy calculations using molecular mechanics Poisson-Boltzmann surface area (MMPBSA). The compound 4-hydroxycordoin showed the highest druglikeness score and regulated nine proteins of which five were down-regulated and four were upregulated. Similarly, enrichment analysis identified the modulation of multiple pathways concerned with the immune system as well as pathways related to infectious and non-infectious diseases. Likewise, 3'-(3-methyl-2-butenyl)-4'-O-ß-d-glucopyranosyl-4,2'-dihydroxychalcone with 3CLpro, 4-hydroxycordoin with PLpro and mallotophilippen D with spike protein receptor-binding domain showed highest binding affinity, revealed stable interactions during the simulation, and scored binding free energy of -26.09 kcal/mol, -16.28 kcal/mol, and -39.2 kcal/mol, respectively. Predicted anti-SARS-CoV-2 activities of the benzalacetophenones reflected the requirement of wet lab studies to develop novel antiviral candidates.

Ficus benghalensis promotes the glucose uptake- Evidence with in silico and in vitro.

Background: Ficus benghalensis L. is traditionally used to manage diabetes; also used in various herbal formulations, and is indicated as an insulin sensitizer. Hence, present work attempted in identifying the probable lead hits to promote glucose uptake via computational approach followed by experimental evaluation of hydroalcoholic extract of Ficus benghalensis L. bark in yeast cells. Methods: The in vitro assay for glucose uptake was performed in the baker yeast whereas in-silico study involved retrieving the phytoconstituents from open sources, and predicting for probable targets of diabetes followed by drug-likeness score, probable side effects, and ADMET profile. Homology modeling was performed to construct the target protein glucose transporter-2. In addition, the binding affinity of each ligand with glucose transporter was predicted using AutoDock 4.2. Results: A total of 17 phytoconstituents from F. benghalensis were identified to possess the anti-diabetic effects. Among them, 4-methoxybenzoic acid scored the highest drug-likeness score and lupeol acetate had the maximum binding affinity of -8.02 kcal/mol with 9 pi-interactions via Tyr324, Phe323, Ile319, Ile200, Ile28, Phe24, and Ala451. Similarly, the extract showed the highest glucose uptake efficacy in yeast cells at 500 µg/mL. Conclusion: Herein the present study reflected the probable activity of the phytoconstituents from F. benghalensis in promoting the glucose uptake via the in silico and in vitro approaches.

GLUT-2 mediated glucose uptake analysis of Duranta repens: In-silico and In-vitro approach.

Background: Type-2 diabetes mellitus is a common metabolic disorder characterized by insulin resistance, a relative impairment in insulin secretion, and a certain degree of genetic predisposition. The rapid rise in the prevalence of diabetes mellitus around the world has assisted in the development of new pharmacologically active compounds. The current study was aimed to investigate and validate the anti-diabetic activity of wild-grown plant Duranta repens L. Material and methods: In-silico molecular docking via AutoDock tools 4.2 and in-vitro glucose uptake assay using yeast cells was performed to investigate the anti-diabetic property of plant Duranta repens. Further, mRNA-based gene ontology enrichment analysis was performed to predict the imitated ontology by the bio-actives from Duranta repens. Results: The in-silico study results reveal that among the 9 active phytoconstituents docked against GLUT-2 protein, α-onocerin possessed the highest binding affinity of -10.23 kcal/mol with no predicted adverse effects and also complies with Lipinski's rule of five. Also, in-vitro studies reflected in a 5 mM glucose solution, hydro-alcoholic extract of Duranta repens at different concentrations enhanced glucose uptake in yeast cells. Conclusion: Duranta repens extract enhanced the glucose uptake in yeast cells which may be due to the presence of α-onocerin; possessed the better interaction. Also, no adverse effects were predicted for α-onocerin. Thus, it can be speculated  that Duranta repens may possess anti-diabetic activity which may be due to α-onocerin and other related bioactives; needs to be further confirmed vi a  experimental studies.

Assessing immuno-expression of p53 protein and TP 53 gene amplification in histologically negative surgical margins of oral squamous cell carcinoma patients and normal oral mucosa.

OBJECTIVE: To assess and compare the immuno-expression of p53 and TP 53 gene amplification and correlate local recurrence and survival in histologically negative surgical margins of oral squamous cell carcinoma (OSCC) with normal oral mucosa. METHODS: Forty formalin-fixed paraffin-embedded tissue blocks of HNMs of OSCC and 40 normal oral mucosa samples were analyzed for p53 immunostaining and TP 53 gene amplification by PCR. RESULTS: Significantly, higher positivity was noted with p53 immuno-expression, TP53 gene amplification, and combined p53 and TP53 expression in the study group compared to the control group (C0.05). Most cases that were positive for p53 immuno-expression, TP 53 gene amplification, and combined p53 and TP53 expression showed local recurrence and poor survival. Kaplan-Meier survival analysis showed that subjects with TP53 and combined p53 and TP53 positivity had decreased survival rate than their negative counterparts. CONCLUSION: Detection of p53 in HNMs of OSCC can be used as a biomarker to identify patients at a higher risk of developing local recurrence and to predict survival. CLINICAL RELEVANCE: Combined p53 and TP 53 assessment may be more reliable for predicting LR to help clinicians and surgeons in treatment planning.

System biology-based investigation of Silymarin to trace hepatoprotective effect.

Silymarin is used as a hepatoprotective agent since ancient times which could be via its potent anti-oxidant effect. However, the mode of silymarin for the hepatoprotective effect has not been established with the targets involved in hepatic cirrhosis. The present study investigated the multiple interactions of the flavonolignans from Silybum marianum with targets involved in hepatic cirrhosis using a series of system biology approaches. Chemo-informative tools and databases i.e. DIGEP-Pred and DisGeNET were used to predict the targets of flavonolignans and proteins involved in liver cirrhosis respectively. Further, STRING was used to enrich the protein-protein interaction for the flavonolignans-modulated targets. Similarly, molecular docking was performed using AutoDock Vina. Additionally, molecular dynamics simulation and MM-PBSA calculations were carried out for the lead-hit complexes by GROMACS. Thirteen flavonolignans were identified from S. marianum, in which silymonin exhibited the highest drug-likeness score i.e. 1.09. Similarly, CTNNB1 was found to be regulated by the 12 different flavonolignans and was majorly expressed within the compound(s)-protein(s)-pathway(s) network. Further, silymonin had the highest binding affinity; binding energy -9.2 kcal/mol with the CTNNB1 and formed very stable hydrogen bond interactions with Arg332, Ser336, Lys371, and Arg475 throughout 100 ns molecular dynamic production run. The binding free energy of CTNNB1-silymonin complex was found to be -15.83 ± 2.71 kcal/mol. The hepatoprotective property of S. marianum may be due to the presence of silymonin and silychristin; this could majorly modulate CTNNB1, HMOX1, and CASP8 in combination with other flavonolignans. Our findings further suggest designing the in-vitro and in-vivo studies to validate the interaction of flavonolignans with identified targets to strengthen present findings of S. marianum as a hepatoprotective..

Network pharmacology of AYUSH recommended immune-boosting medicinal plants against COVID-19.

The Ministry of AYUSH recommended the use of a decoction of the mixture of Ocimum tenuiflorum, Cinnamomum verum, Piper nigrum, Zingiber officinale, and Vitis vinifera as a preventive measure by boosting the immunity against the severity of infection caused by a novel coronavirus (COVID-19). The present study aimed to identify the probable modulated pathways by the combined action of AYUSH recommended herbal tea and golden milk formulation as an immune booster against COVID-19. Reported phytoconstituents of all the medicinal plants were retrieved from the ChEBI database, and their targets were predicted using DIGEP-Pred. STRING database and Cytoscape were used to predict the protein-protein interaction and construct the network, respectively. Likewise, MolSoft and admet SAR2.0 were used to predict the druglikeness score and ADMET profile of phytoconstituents. The study identified the modulation of HIF-1, p53, PI3K-Akt, MAPK, cAMP, Ras, Wnt, NF-kappa B, IL-17, TNF, and cGMP-PKG signaling pathways to boost the immune system. Further, multiple pathways were also identified which are involved in the regulation of pathogenesis of the multiple infections and non-infectious diseases due to the lower immune system. Results indicated that the recommended herbal formulation not only modulated the pathways involved in boosting the immunity but also modulated the multiple pathways that are contributing to the progression of multiple disease pathogenesis which would add the beneficial effect in the co-morbid patients of hypertension and diabetes. The study provides the scientific documentation of the role of the Ayurvedic formulation to combat COVID-19.

Withanolides from Withania somnifera as an immunity booster and their therapeutic options against COVID-19.

Traditionally, Withania somnifera is widely used as an immune booster, anti-viral, and for multiple medicinal purposes. The present study investigated the withanolides as an immune booster and anti-viral agents against the coronavirus-19. Withanolides from Withania somnifera were retrieved from the open-source database, their targets were predicted using DIGEP-Pred, and the protein-protein interaction was evaluated. The drug-likeness score and intestinal absorptivity of each compound were also predicted. The network of compounds, proteins, and modulated pathways was constructed using Cytoscape, and docking was performed using autodock4.0, and selected protein-ligand complexes were subjected to 100 ns Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-GBSA method. Withanolide_Q was predicted to modulate the highest number of proteins, showed human intestinal absorption, and was predicted for the highest drug-likeness score. Similarly, combined network interaction identified Withanolide_Q to target the highest number of proteins; RAC1 was majorly targeted, and fluid shear stress and atherosclerosis associated pathway were chiefly regulated. Similarly, Withanolide_D and Withanolide_G were predicted to have a better binding affinity with PLpro, Withanolide_M with 3CLpro, and Withanolide_M with spike protein based on binding energy and number of hydrogen bond interactions. MD studies suggested Withanoside_I with the highest binding free energy (ΔGbind-31.56 kcal/mol) as the most promising inhibitor. Among multiple withanolides from W. somnifera, Withanolide_D, Withanolide_G, Withanolide_M, and Withanolide_Q were predicted as the lead hits based on drug-likeness score, modulated proteins, and docking score to boost the immune system and inhibit the COVID-19 infection, which could primarily act against COVID-19. HighlightsWithanolides are immunity boosters.Withanolides are a group of bio-actives with potential anti-viral properties.Withanolide_G, Withanolide_I, and Withanolide_M from Withania somnifera showed the highest binding affinity with PLpro, 3CLpro, and spike protein, respectively.Withanolides from Withania somnifera holds promising anti-viral efficacy against COVID-19.Communicated by Vsevolod Makeev.

Reversal of insulin resistance by Ficus benghalensis bark in fructose-induced insulin-resistant rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Bark of Ficus benghalensis L. (family: Moraceae), commonly known as Banyan is recorded as Nyagrodha in Ayurvedic Pharmacopeia of India to manage burning sensation, obesity, diabetes, bleeding disorders, thirst, skin diseases, wounds, and dysmenorrhoea. However, the effect of F. benghalensis bark over glycolysis, gluconeogenesis, and appetite regulation in insulin-resistant pathogenesis has not been reported yet. AIM OF THE STUDY: The present study aimed to investigate the effect of hydroalcoholic extract of F. benghalensis bark in gluconeogenesis, glycolysis, and appetite regulation in fructose-induced insulin resistance in experimental rats. MATERIALS AND METHODS: Male Wister rats were supplemented with fructose in drinking water (10% w/v for 42 days and 20% w/v for next 12 days; a total of 54 days); insulin resistance was confirmed via the elevated area under the curve of the glucose during oral glucose tolerance test after 54 days and was subjected with extract treatment for next 30 days. After 30 days of treatment, animals were fasted to perform oral glucose and insulin tolerance test to estimate glucose and insulin levels. The blood sample was collected for biochemical estimation and the liver homogenate was prepared to estimate hepatic enzymes and enzymatic and non-enzymatic anti-oxidant biomarkers followed by histopathological evaluation. Also, glycogen content was quantified in gastrocnemius muscle and liver homogenates. Further, reported bioactives from the F. benghalensis were retrieved from the ChEBI database and docked against hexokinase, phosphofructokinase, glucose-6-phosphatase, lactate dehydrogenase, and fructose-1,6-biphosphatase to identify the probable lead hits against the enzymes involved in gluconeogenesis. RESULTS: Treatment with the F. benghalensis bark extract significantly increased the body weight and food intake and significantly decreased fructose supplemented water intake. Further, treatment with extract significantly increased the exogenous glucose clearance and well responded to the exogenous insulin. Further, extract treatment improved lipid metabolism, ameliorated plasma leptin, and multiple enzymatic and non-enzymatic antioxidant biomarkers. Likewise, it also improved gluconeogenesis mediated pathogenesis of non-alcoholic fatty liver injury. Additionally, molecular docking also identified mucusisoflavone A and B as lead hits in downregulating gluconeogenesis. CONCLUSION: Hydroalcoholic extract of F. benghalensis bark may prevent insulin resistance by downregulating gluconeogenesis and improving the appetite in fructose-induced insulin-resistant rats.

Cyperus rotundus L. reverses the olanzapine-induced weight gain and metabolic changes-outcomes from network and experimental pharmacology.

Cyperus rotundus L. is used to treat multiple clinical conditions like inflammation, diarrhea, pyrosis, and metabolic disorders including diabetes and obesity. The present study aimed to predict the interaction of reported bioactives from Cyperus rotundus against obesity via network pharmacology and to evaluate the efficacy of hydroalcoholic extract of Cyperus rotundus against the olanzapine-induced weight gain and metabolic disturbances in experimental animals. Reported phytochemicals of Cyperus rotundus were retrieved from the open-source database(s) and published literature and their targets were predicted using SwissTargetPrediction, enriched in STRING, and bioactives-proteins-pathways network was constructed using Cytoscape. Further, the hydroalcoholic extract of Cyperus rotundus (100, 200, and 400 mg/kg/day, p.o.) was co-administered with olanzapine (2 mg/kg, i.p.) for 21 days in Sprague Dawley rats. During treatment, body weight and food intake were recorded; after the successful completion of 21 days of treatment, animals were fasted to perform oral glucose and insulin tolerance tests. Further, the animals were euthanized; blood and abdominal fat were collected for lipid profiling and histopathological examination respectively. Herein, network pharmacology predicted neuroactive ligand-receptor interaction as a primarily modulated pathway and protein tyrosine phosphatase 1b as a majorly triggered protein via the combined action of bioactives. Further, Cyperus rotundus significantly reversed weight gain, cumulative food intake, ameliorated the lipid and glucose metabolism, and promoted energy expenditure.

Systems and in vitro pharmacology profiling of diosgenin against breast cancer.

Aim: The purpose of this study was to establish a mode of action for diosgenin against breast cancer employing a range of system biology tools and to corroborate its results with experimental facts. Methodology: The diosgenin-regulated domains implicated in breast cancer were enriched in the Kyoto Encyclopedia of Genes and Genomes database to establish diosgenin-protein(s)-pathway(s) associations. Later, molecular docking and the lead complexes were considered for molecular dynamics simulations, MMPBSA, principal component, and dynamics cross-correlation matrix analysis using GROMACS v2021. Furthermore, survival analysis was carried out for the diosgenin-regulated proteins that were anticipated to be involved in breast cancer. For gene expression analyses, the top three targets with the highest binding affinity for diosgenin and tumor expression were examined. Furthermore, the effect of diosgenin on cell proliferation, cytotoxicity, and the partial Warburg effect was tested to validate the computational findings using functional outputs of the lead targets. Results: The protein-protein interaction had 57 edges, an average node degree of 5.43, and a p-value of 3.83e-14. Furthermore, enrichment analysis showed 36 KEGG pathways, 12 cellular components, 27 molecular functions, and 307 biological processes. In network analysis, three hub proteins were notably modulated: IGF1R, MDM2, and SRC, diosgenin with the highest binding affinity with IGF1R (binding energy -8.6 kcal/mol). Furthermore, during the 150 ns molecular dynamics (MD) projection run, diosgenin exhibited robust intermolecular interactions and had the least free binding energy with IGF1R (-35.143 kcal/mol) compared to MDM2 (-34.619 kcal/mol), and SRC (-17.944 kcal/mol). Diosgenin exhibited the highest cytotoxicity against MCF7 cell lines (IC50 12.05 ± 1.33) µg/ml. Furthermore, in H2O2-induced oxidative stress, the inhibitory constant (IC50 7.68 ± 0.51) µg/ml of diosgenin was lowest in MCF7 cell lines. However, the reversal of the Warburg effect by diosgenin seemed to be maximum in non-cancer Vero cell lines (EC50 15.27 ± 0.95) µg/ml compared to the rest. Furthermore, diosgenin inhibited cell proliferation in SKBR3 cell lines more though. Conclusion: The current study demonstrated that diosgenin impacts a series of signaling pathways, involved in the advancement of breast cancer, including FoxO, PI3K-Akt, p53, Ras, and MAPK signaling. Additionally, diosgenin established a persistent diosgenin-protein complex and had a significant binding affinity towards IGF1R, MDM2, and SRC. It is possible that this slowed down cell growth, countered the Warburg phenomenon, and showed the cytotoxicity towards breast cancer cells.

Ink-jet printing and drop-casting deposition of 2H-phase SnSe2and WSe2nanoflake assemblies for thermoelectric applications.

The development of simple, scalable, and cost-effective methods to prepare Van der Waals materials for thermoelectric applications is a timely research field, whose potential and possibilities are still largely unexplored. In this work, we present a systematic study of ink-jet printing and drop-casting deposition of 2H phase SnSe2and WSe2nanoflake assemblies, obtained by liquid phase exfoliation, and their characterization in terms of electronic and thermoelectric properties. The choice of optimal annealing temperature and time is crucial for preserving phase purity and stoichiometry and for removing dry residues of ink solvents at inter-flake boundaries, while maximizing the sintering of nanoflakes. An additional pressing is beneficial to improve nanoflake orientation and packing, thus enhancing electric conductivity. In nanoflake assemblies deposited by drop casting and pressed at 1 GPa, we obtained thermoelectric power factors at room temperature up to 2.2 × 10-4mW m-1K-2for SnSe2and up to 3.0 × 10-4mW m-1K-2for WSe2.

Identification of α-amylase inhibitors from flavonoid fraction of Feronia elephantum and its integration with in-silico studies.

Postprandial hyperglycemia is associated with an increase in blood glucose levels after a meal, which is further associated with various risk factors like cardiovascular diseases. α-amylase is a digestive enzyme and secreted by the salivary glands and pancreas, which helps to catalyze the hydrolysis of the internal α-1,4-glycosidic linkages in starch breaking them into smaller units. Hence, the present study is aimed to identify flavonoids from the fruit pulp of Feronia elephantum as α-amylase inhibitors via in-silico and in-vitro protocols. In-silico tools like ADVERPred, PubChem, MolSoft, Discovery studio 2019, and Autodock 4.0 were used to predict the information related to phytoconstituents, drug-likeness character, and probable side effects. In-vitro α-amylase inhibitory activity was performed with five different concentrations of flavonoid fraction of hydroalcoholic extract of the fruit pulp of Feronia elephantum using 1% starch solution and DNS reagent. Four flavonoids were identified from 25 bio-actives present in the fruit pulp of Feronia elephantum. Three bio-actives were predicted to possess a positive drug-likeness score, from which 5,4-dihydroxy3-3(3-methyl-but2-enyl)3,5,6-trimethoxy-flavone-7-O-ß-d-Glucopyranoside was predicted to possess the highest drug-likeness score of 0.70. Vitexin and 5,4-dihydroxy3-3(3-methyl-but2-enyl)3,5,6-trimethoxy-flavone-7-O-ß-d-Glucopyranoside were predicted to possess nephrotoxicity as an adverse effect. The percent inhibition of α-amylase by a flavonoid-rich fraction at 100 µg/ml was found to be 45.95% as compared to standard acarbose with 74.79% inhibition at 100 µg/ml. Further, docking studies predicted that vitexin possessed the highest binding affinity (binding energy - 7.98 kcal/mol) as compared to standard acarbose with binding energy - 5.24 kcal/mol. There were no significant side effects predicted, in-vitro α-amylase inhibitory activity of the flavonoid-rich fraction may be due to the presence of vitexin, predicted via in-silico molecular docking; further, which needs to be further validated via in-vivo protocols.

Caution with carotids: A necessary cognizance.

Most aberrations in the cervical course of the internal carotid artery are generally encountered as incidental findings due to their asymptomatic nature. However these morphological variations if not identified intra operatively or pre operatively may lead to vascular accidents. It is essential to be aware of the existence of tortuosity, kinking, and coiling of these great vessels while considering patients for surgeries of head and neck cancer, pharyngeal resections, traumatic injury repair, etc. Our paper presents a case series of four patients in whom carotid dolichoarteriopathies were observed during the course of neck dissection. It aims to highlight the precautions required to avoid morbidity in such patients.