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1.
J Biomol Struct Dyn ; : 1-13, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34854365

RESUMO

A computational investigation was carried out to find out potential phytochemicals that could inhibit the binding of human angiotensin-converting enzyme-2 (ACE2) receptors to spike protein of SARS-CoV-2 which is an essential step to gain entry inside human cells and onset of viral infection known as Coronavirus disease (COVID-19). A library of phytochemicals was screened by virtual screening against ACE2 receptors resulting in twenty phytochemicals out of 686 which had binding energy (-11.8 to -6.9 kcal/mol). Drug-likeness gave five hits, but ADMET analysis yielded 4 nontoxic hit phytochemicals. Molecular dynamics simulation of four-hit compounds resulted in acceptable stability and good dynamics behavior. These phytochemicals are Hinokinin, Gmelanone, Isocolumbin, and Tinocordioside, from Vitis vinifera, Gmelina arborea, and Tinospora cordifolia. The above-mentioned phytochemicals may be promising ACE2 inhibitors and can prevent infection of SARS-CoV-2 by inhibiting the entry of the virus into host cells.Communicated by Ramaswamy H. Sarma.

2.
Sci Rep ; 11(1): 22853, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819529

RESUMO

Breeding for higher yield and wider adaptability are major objectives of soybean crop improvement. In the present study, 68 advanced breeding lines along with seven best checks were evaluated for yield and attributing traits by following group balanced block design. Three blocks were constituted based on the maturity duration of the breeding lines. High genetic variability for the twelve quantitative traits was found within and across the three blocks. Several genotypes were found to outperform check varieties for yield and attributing traits. During the same crop season, one of the promising entries, NRC 128,was evaluated across seven locations for its wider adaptability and it has shown stable performance in Northern plain Zone with > 20% higher yield superiority over best check PS 1347. However, it produced 9.8% yield superiority over best check in Eastern Zone. Screening for waterlogging tolerance under artificial conditions revealed that NRC 128 was on par with the tolerant variety JS 97-52. Based on the yield superiority, wider adaptability and waterlogging tolerance, NRC 128 was released and notified by Central Varietal Release Committee (CVRC) of India, for its cultivation across Eastern and Northern Plain Zones of India.

3.
Toxics ; 9(11)2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34822704

RESUMO

Sulfamethoxazole (SMX) is a frequently used antibiotic for the treatment of urinary tract, respiratory, and intestinal infections and as a supplement in livestock or fishery farming to boost production. The release of SMX into the environment can lead to the development of antibiotic resistance among the microbial community, which can lead to frequent clinical infections. SMX removal from water is usually done through advanced treatment processes, such as adsorption, photocatalytic oxidation, and biodegradation. Among them, the advanced oxidation process using TiO2 and its composites is being widely used. TiO2 is a widely used photocatalyst; however, it has certain limitations, such as low visible light response and quick recombination of e-/h+ pairs. Integrating the biochar with TiO2 nanoparticles can overcome such limitations. The biochar-supported TiO2 composites showed a significant increase in the photocatalytic activities in the UV-visible range, which resulted in a substantial increase in the degradation of SMX in water. The present review has critically reviewed the methods of biochar TiO2 composite synthesis, the effect of biochar integration with the TiO2 on its physicochemical properties, and the chemical pathways through which the biochar/TiO2 composite degrades the SMX in water or aqueous solution. The degradation of SMX using photocatalysis can be considered a useful model, and the research studies presented in this review will allow extending this area of research on other types of similar pharmaceuticals or pollutants in general in the future.

4.
J Assoc Physicians India ; 69(10): 11-12, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34781659

RESUMO

Ticagrelor is a potent, oral P2Y12 inhibitor used as a part of dual antiplatelet therapy (DAPT) in acute coronary syndromes (ACS). New evidence has emerged for its use in ACS, which may be crucial for the Indian context. This brought together nearly 150 experts in ACS management across the country who reviewed the current evidence and discussed the same through a series of 10 meetings on an online platform. With all experts' agreement, the key expert opinions for the P2Y12 inhibitors use in ACS management were finalized. These include the following. In ACS patients aged <75 years, with diabetes, a history of stroke/transient ischemic attack, and chronic kidney disease, ticagrelor may be preferred over other P2Y12 inhibitors. It may also be preferred in the elderly above 75 years with clopidogrel is a suitable alternative in patients at high-risk of bleeding. Rates of stent thrombosis are lower with ticagrelor than clopidogrel. In patients managed with fibrinolysis, use ticagrelor after 48 hours if streptokinase was the fibrinolytic agent or it can be used after 12 to 24 hours if fibrin-specific fibrinolytic was used. Rates of major bleeding in patients treated with fibrinolysis are similar to clopidogrel. Prehospital administration may be preferred over in-hospital administration with expected bleeding rates similar to clopidogrel. Switching among P2Y12 inhibitors should be done with due consideration of their pharmacodynamics. At present, DAPT should be continued for 12 months with discontinuation after three to six months in patients with high bleeding risk. The use of low dose ticagrelor may be considered in cases with high-bleeding risk. DAPT or ticagrelor continuation beyond one year should be individualized considering ischemic and bleeding risks. Dyspnea is a common, mild, and transient and does not necessitate ticagrelor discontinuation. Severe dyspnea should be investigated thoroughly. In conclusion, ticagrelor (180 mg, 90 mg, and 60 mg doses), a potent antiplatelet is expected to reshape the antiplatelet use in the management of ACS.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Prova Pericial , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Resultado do Tratamento
5.
Oxid Med Cell Longev ; 2021: 1987588, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594472

RESUMO

Luteolin is a naturally occurring secondary metabolite belonging to the class of flavones. As many other natural flavonoids, it is often found in combination with glycosides in many fruits, vegetables, and plants, contributing to their biological and pharmacological value. Many preclinical studies report that luteolin present excellent antioxidant, anticancer, antimicrobial, neuroprotective, cardioprotective, antiviral, and anti-inflammatory effects, and as a consequence, various clinical trials have been designed to investigate the therapeutic potential of luteolin in humans. However, luteolin has a very limited bioavailability, which consequently affects its biological properties and efficacy. Several drug delivery strategies have been developed to raise its bioavailability, with nanoformulations and lipid carriers, such as liposomes, being the most intensively explored. Pharmacological potential of luteolin in various disorders has also been underlined, but to some of them, the exact mechanism is still poorly understood. Given the great potential of this natural antioxidant in health, this review is aimed at providing an extensive overview on the in vivo pharmacological action of luteolin and at stressing the main features related to its bioavailability, absorption, and metabolism, while essential steps determine its absolute health benefits and safety profiles. In addition, despite the scarcity of studies on luteolin bioavailability, the different drug delivery formulations developed to increase its bioavailability are also listed here.

6.
J Biomol Struct Dyn ; : 1-12, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637693

RESUMO

The RNA-dependent RNA polymerase (RdRp) is one of the crucial enzymes in severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) catalysing the replication of RNA, therefore acts as a potential target for antiviral drug design. The fixation of a ligand in the active site of RdRp may alter the SARS-CoV-2 life cycle. Present work aimed at identifying novel inhibitors of the SARS-CoV-2 RdRp enzyme by performing pharmacophore-based virtual screening, molecular docking and molecular dynamics simulation (MDS). Initially, the pharmacophore model of SARS-CoV-2 RdRp was constructed and the resulting model was used to screen compounds from ChEMBL, ZINC and PubChem databases. During the investigation, 180 compounds were screened using the above model and subjected to molecular docking with RdRp. Two compounds viz. ChEMBL1276156 and PubChem135548348 showed a strong binding affinity with RdRp than its standard inhibitor, Remdesivir. Toxicity prediction of these two compounds reveals their non-toxic nature. These compounds were further subjected to MDS for 100 ns to check their stability after binding with RdRp. The MDS of RdRp-ChEMBL1276156 and RdRp-PubChem135548348 complexes show enhanced stability in comparison to the RdRp-Remdesivir complex. The average interaction energy calculated after 100 ns of MDS was -146.56 and -172.68 KJ mol-1 for RdRp-CHEMBL1276156 complex and RdRp-PubChem135548348 complex, respectively, while -59.90 KJ mol-1 for RdRp-Remdesivir complex. The current investigation reveals that these two compounds are potent inhibitors of SARS-CoV-2 RdRp and they could be tested in the experimental condition to evaluate their efficacy against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

7.
J Mol Graph Model ; 109: 108028, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34649146

RESUMO

Owing to the shortage of specific medicines, the global pandemic of COVID-19 caused by SARS-CoV-2 has been the greatest challenge for the science community. Researchers from all over the world developed some drugs which failed to completely suppress the contiguous disease. SARS-CoV-2 main protease (Mpro), an important component in viral pathogenesis, is considered as a prospective drug target to stop SARS-CoV-2 infection. Since identification of phytochemicals with anti-Mpro activity has been carried out to develop the potential drugs against SARS-CoV-2. Therefore, the present study was conducted to screen phytochemicals of Berberis asiatica for anti-SARS-CoV-2 activity. Through text mining, thirty phytochemicals were reported from B. asiatica, of which, three phytochemicals (Berbamine, Oxyacanthine, and Rutin) show high affinity with the SARS-CoV-2 Mpro and exhibited favorable intermolecular interactions with the catalytic residues (His41 and Cys145) and other essential residues. The molecular dynamics simulation showed that Mpro-phytochemical complexes are more stable, less fluctuating, more compact, and moderately extended than the Mpro-X77 (Reference) complex. The number of H-bonds and MMPBSA results also demonstrates that Berbamine, Oxyacanthine, and Rutin are potent Mpro inhibitors having free energy of -20.79, -33.35, and -31.12 kcal mol-1 respectively. The toxicity risk prediction supports all phytochemicals for drug-like and non-toxic nature. From the result, we propose that binding of these phytochemicals could hamper the function of Mpro. This work suggests that selected phytochemicals could be used as novel anti-COVID-19 drug candidates, and might act as novel compounds for in vitro and in vivo study.


Assuntos
Berberis , COVID-19 , Benzilisoquinolinas , Humanos , Isoquinolinas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases , Rutina , SARS-CoV-2
8.
Mol Divers ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637068

RESUMO

Blocking the main replicating enzyme, 3 Chymotrypsin-like protease (3CLpro) is the most promising drug development strategy against the SARS-CoV-2 virus, responsible for the current COVID-19 pandemic. In the present work, 9101 drugs obtained from the drug bank database were screened against SARS-CoV-2 3CLpro prosing deep learning, molecular docking, and molecular dynamics simulation techniques. In the initial stage, 500 drug-screened by deep learning regression model and subjected to molecular docking that resulted in 10 screened compounds with strong binding affinity. Further, five compounds were checked for their binding potential by analyzing molecular dynamics simulation for 100 ns at 300 K. In the final stage, two compounds {4-[(2s,4e)-2-(1,3-Benzothiazol-2-Yl)-2-(1h-1,2,3-Benzotriazol-1-Yl)-5-Phenylpent-4-Enyl]Phenyl}(Difluoro)Methylphosphonic Acid and 1-(3-(2,4-dimethylthiazol-5-yl)-4-oxo-2,4-dihydroindeno[1,2-c]pyrazol-5-yl)-3-(4-methylpiperazin-1-yl)urea were screened as potential hits by analyzing several parameters like RMSD, Rg, RMSF, MMPBSA, and SASA. Thus, our study suggests two potential drugs that can be tested in the experimental conditions to evaluate the efficacy against SARS-CoV-2. Further, such drugs could be modified to develop more potent drugs against COVID-19.

9.
Endosc Int Open ; 9(10): E1530-E1535, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34540546

RESUMO

Background and study aims Ulcers with high-risk stigmata have significant rebleeding rates despite standard endoscopic therapy. Data on over-the-scope clip (OTSC) for recurrent bleeding is promising but data on first line therapy is lacking. We report comparative outcomes of OTSC as first-line therapy versus standard endoscopic therapy in ulcers with high-risk stigmata. Patients and methods Consecutive adults who underwent endoscopic therapy for ulcers with high-risk stigmata between July 2019 to September 2020 were included. Patients were grouped into OTSC or standard therapy based on first-line therapy used on index endoscopy. Outcomes measured included: 1) intra-procedural hemostasis based on endoscopic documentation of adequate hemostasis; 2) 7-day rebleeding (> 2 g/dL drop in hemoglobin, hematochezia or hemorrhagic shock); 3) cost of endoscopic interventions; and 4) procedure duration measured as endoscope insertion to removal time. Cost of tools used during the index endoscopy was included. Results Sixty-eight patients were included, 47 were in standard therapy and 21 in the OTSC group. Hemostasis was achieved in 95.2 % in the OTSC group compared to 83.0 % in the standard therapy group ( P  = 0.256, number needed to treat [NNT]: 9). Procedure time was shorter in the OTSC group (23 vs. 16 minutes, P  = 0.002). Cost of endoscopic interventions were comparable, P  = 0.203. Early rebleeding was less often in OTSC group, two (9.5 %) compared to 10 (21.3 %) in standard therapy group, NNT 9. Conclusions Use of OTSCs as first-line treatment for ulcers bleed probably improves hemostasis and decreases early rebleeding. Use of OTSC as first-line therapy shortened procedure duration without increasing the cost of endoscopic interventions.

10.
Int J Clin Pediatr Dent ; 14(2): 331-334, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413617

RESUMO

Aim: Skeletal class III malocclusion are the most challenging orthodontic problem to treat. Diagnosis and treatment in early stage was important to boost self-esteem of patient. Our aim was to correct skeletal relationship and anterior crossbite to enhance the growth of maxilla. Background: Class III malocclusion can be due to retrognathic maxilla, prognathic mandible or combination. Complexity of class III malocclusion depends upon abnormal growth pattern of maxilla and mandible. Maxilla growth ceases around 8-10 years and mandible continue till 16 years. Early intervention boosts self-esteem of the patient. Case description: This case presents with clinical feature of retrognathic maxilla at the age of six years. The patient had concave profile with incompetent lips. The mentolabial sulcus was normal and obtuse nasolabial angle with high clinical Frankfurt mandibular angle (FMA). There was reverse overjet of 1 mm. Cephalometric analysis showed a class III skeletal pattern with retrognathic maxilla and orthognathic mandible with increase in lower facial height and increases in gonial angle. The rapid maxillary expansion (RME) with reverse pull face mask was planned. The expansion screw was activated to loosen the circumaxillary suture. Conclusion: After active treatment anterior crossbite was corrected. The patient sagittal discrepancy was improved. Early mixed dentition period is the best time to begin class III treatment. Clinical significance: Early treatment with maxillary protraction and palatal expansion can correct most anterior-posterior skeletal discrepancy. How to cite this article: Jha AK, Chandra S. Early Management of Class III Malocclusion in Mixed Dentition. Int J Clin Pediatr Dent 2021;14(2):331-334.

11.
J Pharm Bioallied Sci ; 13(Suppl 1): S696-S698, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34447184

RESUMO

Background: Student psychological health has been an increasing concern. The COVID-19 pandemic situation has brought this vulnerable population into renewed focus. Objective: Our study aims to conduct a timely assessment of the effects of the COVID-19 pandemic on the mental health of college graduates and postgraduates. Methodology: We conducted online survey with 550 students to understand the effects of the pandemic on their psychology and well-being. The data were analyzed through quantitative and qualitative methods. Results: Of the 550 students, 138 (71%) indicated increased stress and anxiety due to the COVID-19 outbreak. When asked about how the lockdown in COVID-19 situation affecting them, 97% said that it is severely affecting them. When asked about what the problems do you faced during online class, 5% said the Internet, 83.8% said noninteractive, and 11.2% said lack of explanatory mediums. When asked about number of hours spent on the Internet, 100% said more than 10 h. When asked about the activities to keep yourself busy during lockdown in COVID-19 situation, 37% said social media followed by 23% who mentioned cooking. Conclusion: Due to the long-lasting pandemic situation and onerous measures such as lockdown and stay-at-home orders, the COVID-19 pandemic brings negative impacts on education. The findings of our study highlight the urgent need to develop interventions and preventive strategies to address the psychological health of college students.

12.
J Biomol Struct Dyn ; : 1-11, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34459700

RESUMO

Dyes are being increasingly utilized across the globe, but there is no appropriate method of bioremediation for their full mineralization from the environment. Laccases are key enzymes that help microbes to degrade dyes as well as their intermediate metabolites. Various dyes have been reported to be degraded by bacteria, but it is still unclear how these enzymes function during dye degradation. To effectively eradicate toxic dyes from the system, it is essential to understand the molecular function of enzymes. As a result, the interaction of laccase with different toxic dyes was investigated using molecular docking. Based on the highest binding energy we have screened ten dyes with positive interaction with laccase. Evaluating the MD simulation results, three out of ten dyes were more stable as potential targets for degradation by laccase of Bacillus subtilis. As a result, subsequent research focused solely on the results of three substrates: pigment red, fuchsin base, and Sudan IV. Analysis of MD simulation revealed that pigments red 23, fuchsin base, and Sudan IV form hydrogen and hydrophobic bond as well as Vander Waals interactions with the active site of laccase to keep it stable in aqueous solution. The conformation of laccase is greatly altered by the inclusion of all three substrates in the active site. The MD simulation findings show that laccase complexes remain stable throughout the catalytic reaction. Therefore, this research provides a molecular understanding of laccase expression and its role in the bioremediation of the pigments red 23, fuchsin base, and Sudan IV.Communicated by Ramaswamy H. Sarma.

13.
Sci Total Environ ; 794: 148723, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34217075

RESUMO

Providing a valuable application to the under-utilized solid residue of co-pyrolysis of biomass and plastics could substantially improve economic and environmental sustainability of the process, thereby fostering circular economy. This study focuses on the variation of thermal and physiochemical characteristics of solid char, produced from the co-pyrolysis of waste low-density polyethylene (WLDPE) and Eucalyptus wood with varying pyrolysis temperatures from 300 to 550 °C, residence times of 90-150 min, and relative percentage of 33% and 25% (w/w) WLDPE in the feedstock. The highest values of yield (37%), energy density (1.25) and high heat value (31 MJ/Kg) were observed with the char produced at 300 °C. The physical inhibition caused by the overlaying plastic coating on the surface of the char below 450 °C resulted in the same. However, with the increase in temperature, increase in fuel ratio by 78-79% and fixed carbon content by 68-69% were observed. The highest concentrations of fixed carbon (39%), fuel ratio (0.81) along with the lowest O/C and H/C ratios (0.07 and 0.13) were observed with the chars produced above 450 °C depicting their high degree of carbonization. The fuel value indices of all the chars were > 500 GJ/m3 indicating their suitability as high-quality fuels. Significant influences of residence time and feedstock ratio were also observed on properties of the char. The analysis of variance and principal component analysis also depicted significant variations in the properties of the char produced below and above the temperatures of 450 °C due to the inhibitory and synergetic effects. While the chars produced at 300-350 °C could be used for combustion/co-combustion in coal-fired boilers, chars produced above 450 °C can be opted as household fuel due to their low losses of energy, water vapour, and smoke during combustion.


Assuntos
Eucalyptus , Pirólise , Biomassa , Polietileno , Madeira
14.
J Biomol Struct Dyn ; : 1-18, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34225570

RESUMO

The leaves and fruits of Aegle marmelos (L.) have antidiabetic activity. However, the mode of action and molecules having antidiabetic activity are not known. Hence, we conducted molecular docking of phytochemicals with various molecular antidiabetic targets to find the same. Docking prioritized Dipeptidyl peptidase-4 (DPP-4) as the main target for phytochemicals of Aegle marmelos. DPP-4 inactivates intestinal peptides, glucagon-like peptide-1 (GLP-1), and Gastric inhibitory polypeptide (GIP). GLP-1 and GIP stimulate a decline in blood glucose levels, but DPP-4 inhibits their functions resulting high level of glucose. Hence inhibiting the activity of DPP-4 is a well-known strategy to treat Type 2 diabetes. Therefore, to find a mechanism that may be involved to act as a natural inhibitor of DPP-4, we screened five phytochemicals out of seventy-three based on Virtual Screening, ADMET Drug-likeness analysis, and PAINS filtering. Further, all five phytochemicals, i.e. Aegeline, Citral, Marmesinin, Auraptene, ß-Bisabolene, and reference compound subjected MDS for analyzing the stability of docked complexes to assess the fluctuation and conformational changes during protein-ligand interaction. The values of RMSD, RG, RMSF, SASA, and Gibbs energy revealed the good stability of these phytochemicals in the active site pocket of DPP-4 in comparison to reference. Additionally, we have done the pharmacophore analysis, which revealed many common pharmacophore features between screened phytochemicals of A. marmelos and reference molecule. Our results show that these phytochemicals are potential antidiabetic candidates and can be further modified and evaluated to develop more effective antidiabetic drugs against DPP-4 to treat Type 2 Diabetes. Communicated by Ramaswamy H. Sarma.

15.
PLoS One ; 16(6): e0252759, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34125862

RESUMO

Bacterial Leaf Blight (BLB) disease is an extremely ruinous disease in rice, caused by Xanthomonas oryzae pv. oryzae (Xoo). Although various chemicals are available to manage BLB, they are toxic to the environment as well as humans. Hence there is a need to develop new pesticides as alternatives to hazardous chemicals. Therefore, a study was carried out to discover new potent natural pesticides against Xoo from different solvent extracts of Vernonia cinerea. Among all the fractions, the methanolic extract showed the highest inhibition zone. Further, to gain mechanistic insight of inhibitory action, 40 molecules of methanolic extracts were subjected for in silico study against two enzymes D-alanine-D-alanine ligase (Ddl) and Peptide deformylase (PDF). In silico study showed Rutin and Methanone, [1,4-dimethyl-7-(1- methylethyl)-2- azulenyl]phenyl have a good binding affinity with Ddl while Phenol, 2,4-bis(1-phenylethyl)- and 1,2-Benzenedicarboxylic acid, diisooctyl ester showed an excellent binding affinity to PDF. Finally, the system biology approach was applied to understand the agrochemical's effect in the cell system of bacteria against both the enzymes. Conclusively, these four-hit compounds may have strong potential against Xoo and can be used as biopesticides in the future.


Assuntos
Antibacterianos/farmacologia , Extratos Vegetais/farmacologia , Veronica/química , Xanthomonas/efeitos dos fármacos , Amidoidrolases/química , Amidoidrolases/metabolismo , Antibacterianos/química , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Ligantes , Metanol/química , Simulação de Acoplamento Molecular , Peptídeo Sintases/química , Peptídeo Sintases/metabolismo , Ácidos Ftálicos/análise , Ácidos Ftálicos/química , Ácidos Ftálicos/farmacologia , Extratos Vegetais/química , Ligação Proteica , Rutina/análise , Rutina/química , Rutina/farmacologia
16.
J Biomol Struct Dyn ; : 1-12, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34151733

RESUMO

COVID-19 caused by SARS-CoV-2 is responsible for the deaths of millions of people worldwide. It is having devastating effects on the people of all countries. In this regard, the phytochemicals of medicinal plants could be explored to prevent this disease. M. oleifera is a miracle plant with antibacterial, antiviral, and antioxidant properties because of its high content of flavonoids, glucosides and glucosinolates. Therefore, we constructed a library of 294 phytochemicals of M. oleifera and filtered it through the FAF-Drugs4. Further, molecular docking studies of filtered phytochemicals were performed with Mpro enzyme to investigate the binding interactions. Drug likeness properties, ADMET prediction were analyzed to determine the therapeutic aspect of these compounds. Based on the binding energy score of the top 4 compounds, the results indicate that Vicenin-2 has the highest binding affinity (-8.6 kcal mol-1) as compared to the reference molecule (-8.4 kcal mol-1). ADMET result reveals that all top four compounds have minimal toxic effects and good absorption. Further, 500 ns molecular dynamics simulation of the top four compounds showed that Kaempferol-3-O-rutinoside and Vitexin have good stability with Mpro. These two compounds were then subjected for MMPBSA (last 50 ns) calculation to analyze the protein-ligand stability and dynamic behavior. Kaempferol-3-O-rutinoside and Vitexin showed very good binding free energy i.e. -40.136 kJ mol-1 and -26.784 kJ mol-1, respectively. Promising outcomes from MD simulations evidence the worth of these compounds for future drug development to combat coronavirus disease.Communicated by Ramaswamy H. Sarma.

17.
Opt Express ; 29(10): 15031-15052, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33985212

RESUMO

Hybrid 3D Finite difference time domain-Monte Carlo ray tracing (FDTD-MCRT) algorithm has been developed to model and optimise small and large scale plasmonically-enhanced luminescent solar concentrator (pLSC) devices for photovoltaic (PV) applications. The configuration parameters (for example, dimensions, shape, and optical properties of metal nanoparticles, luminescent species, and host material) were used to characterise the probability of optical energy transfer and loss processes, as well as reflection, refraction, absorption, emission enhancement, and total internal reflection (TIR) in the pLSC. The algorithm was validated through modelling of various doping concentrations of CdSe/ZnS quantum dots (QD) and gold nano spheres (Au NS) where ∼50% enhancement in optical conversion efficiency (OCE) was observed for a plasmonic composite of 2 ppm Au NS and 0.008 wt. % QD.

18.
Comput Biol Med ; 134: 104483, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34020129

RESUMO

The search for effective treatment against novel coronavirus (COVID-19) remains a global challenge due to controversies on available vaccines. In this study, data of SARS coronavirus 3C-like protease (3CLpro) inhibitors; a key drug target in the coronavirus genome was retrieved from CHEMBL database. Quantitative Structure-Activity Relationship (QSAR) studies, Molecular docking, Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) and molecular dynamics simulation (MDS) were carried out using these 3CLpro inhibitors. QSAR model constructed using the data had correlation coefficient R2 value of 0.907; cross-validated correlation coefficient Q2 value of 0.866 and test set predicted correlation coefficient R2pred value of 0.517. Variance inflation factor (VIF) values for descriptors contained in the model ranged from 1.352 to 1.68, hence, these descriptors were orthogonal to one another. Therefore, the model was statistically significant and can be used to screen and design new molecules for their inhibitory activity against 3CLpro. Molecular docking showed that seven of the compounds (inhibitors) used in the study had a remarkable binding affinity (-9.2 to -10.3 kcal/mol) for 3CLpro. ADMET study revealed that five (CHEMBL Accession IDs 19438, 196635, 377150, 208763, and 210097) of the seven compounds with good binding ability obeyed Lipinski's rule of five. Hence, they were compounds with drug-like properties. MDS analysis revealed that 3CLpro-compound 21, 3CLpro-compound 22, 3CLpro-compound 40 complexes are very stable as compared to the reference 3CLpro-X77 complex. Therefore, this study identified three potent inhibitors of 3CLpro viz. CHEMBL194398, CHEMBL196635, and CHEMBL210097 that can be further explored for the treatment of COVID-19.


Assuntos
COVID-19 , Vírus da SARS , Antivirais , Humanos , Simulação de Acoplamento Molecular , Inibidores de Proteases/farmacologia , Relação Quantitativa Estrutura-Atividade , SARS-CoV-2
19.
Lab Invest ; 101(7): 952-965, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33875792

RESUMO

In the current study, a breast tumor xenograft was established in athymic nude mice by subcutaneous injection of the MCF-7 cell line and assessed the tumor progression by photoacoustic spectroscopy combined with machine learning tools. The advancement of breast tumors in nude mice was validated by tumor volume kinetics and histopathology and corresponding image analysis by TissueQuant software compared to controls. The ex vivo tumors in progressive conditions belonging to time points, day 5th, 10th, 15th & 20th, were excited with 281 nm pulsed laser light and recorded the corresponding photoacoustic spectra in time domain. The spectra were then pre-processed, augmented for a 10-fold increase in the data strength, and subjected to wavelet packet transformation for feature extraction and selection using MATLAB software. In the present study, the top 10 features from all the time point groups under study were selected based on their prediction ranking values using the mRMR algorithm. The chosen features of all the time-point groups were then subjected to multi-class Support Vector Machine (SVM) algorithms for learning and classifying into respective time point groups under study. The analysis demonstrated accuracy values of 95.2%, 99.5%, and 80.3% with SVM- Radial Basis Function (SVM-RBF), SVM-Polynomial & SVM-Linear, respectively. The serum metabolomic levels during tumor progression complemented photoacoustic patterns of tumor progression, depicting breast cancer pathophysiology.


Assuntos
Neoplasias da Mama , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Metabolômica/métodos , Técnicas Fotoacústicas/métodos , Algoritmos , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/patologia , Camundongos Nus , Análise Espectral/métodos
20.
Intern Emerg Med ; 16(7): 1905-1911, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33797028

RESUMO

The recovery of gastrointestinal functions is an important determinant of course of acute pancreatitis and the timing of hospital discharge. Here, we evaluated association between fluid resuscitation volume and opioid use with clinically significant ileus development in patients with acute pancreatitis. Consecutive adults admitted with acute pancreatitis between January 2014 and December 2019 to our academic and two community hospital were included. The Bedside Index for Severe Acute Pancreatitis (BISAP) and systemic inflammatory response syndrome (SIRS) were used to predict severity of pancreatitis based on their readily availability. Severity of pancreatitis was determined based on the Revised Atlanta classification. Fluid resuscitation volume and opioid use were collected as administered on day 1 and day 2.Clinically significant ileus was determined based on treating physician's assessment. Forty-nine (11%) of 441 unique patients included in the study developed clinically significant ileus. Demographics of patients with or without ileus were similar between the two groups. On univariate analysis, the presence of SIRS syndrome (< 0.001), a > 3 BISAP score (p < 0.001), and severity of pancreatitis (p < 0.001) were associated with ileus, mean fluid resuscitation volume (5.6L vs 5.5L, p = 0.888) and cumulative median morphine-equivalent units (12 vs 12, p = 0.232) on day 1 and day 2 were not. However, ileus development was associated with increased hospital length of stay and admission to intensive care unit. On observations, clinically significant ileus development is associated with severity of acute pancreatitis, not with fluid resuscitation volume or opioid analgesia dose used in current standard of care.


Assuntos
Analgésicos Opioides/administração & dosagem , Hidratação , Pancreatite/fisiopatologia , Ressuscitação/métodos , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Íleus , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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