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In the past two decades, the treatment of metastatic colorectal cancer (mCRC) has been revolutionized as multiple cytotoxic, biological, and targeted drugs are being approved. Unfortunately, tumors treated with single targeted agents or therapeutics usually develop resistance. According to pathway-oriented screens, mCRC cells evade EGFR inhibition by HER2 amplification and/or activating Kras-MEK downstream signaling. Therefore, treating mCRC patients with dual EGFR/HER2 inhibitors, MEK inhibitors, or the combination of the two drugs envisaged to prevent the resistance development which eventually improves the overall survival rate. In the present study, we aimed to screen potential phytochemical lead compounds that could multi-target EGFR, HER2, and MEK1 (Mitogen-activated protein kinase kinase) using a computer-aided drug design approach that includes molecular docking, endpoint binding free energy calculation using MM-GBSA, ADMET, and molecular dynamics (MD) simulations. Docking studies revealed that, unlike all other ligands, apigenin and kaempferol exhibit the highest docking score against all three targets. Details of ADMET analysis, MM/GBSA, and MD simulations helped us to conclusively determine apigenin and kaempferol as potentially an inhibitor of EGFR, HER2, and MEK1 apigenin and kaempferol against mCRC at a systemic level. Additionally, both apigenin and kaempferol elicited antiangiogenic properties in a dose-dependent manner. Collectively, these findings provide the rationale for drug development aimed at preventing CRC rather than intercepting resistance.

As per world health organization (WHO) report in 2020 about 2.3 million were diagnosed globally with breast cancer and around 6.85 lacs death occurs globally due to breast cancer. In such case usage of natural anticancer remedies can provide beneficial results, but unfortunately natural drugs are not being practically useful due to trifling bioavailability and unempirical data of effectiveness. In current study, liposomal gels were formulated by using liposomes entrapped with natural compound like seasamine, aloe-emodin, gallic acid, catechin, butein, 6-gingerol and curcumin as active drugs. Liposomal gels were formulated using carbopol (1.5 % w/w) with variable concentration of propylene glycol, in another formulation mixture 1 % w/w HPMC, 1 % w/w microcrystalline cellulose and 3 % w/w sodium alginate were also used. From characterization results of all of the above formulations, formulation with 1.5 % w/w carbopol and 5 % w/w propylene glycol has shown significant release of active drugs. In addition to this penetration effect of propylene glycol was also accessed for topical liposome gel formulation; the data reveals that propylene glycol has no significant penetration boosting impact with liposomal gel formulation.

Breast/mammary cancer is the most common cancer in women due to abandoned breast tissue growth. Many therapies and treatments are available for breast cancer treatment. However, each therapy or treatment has its side effect. The natural compound has uncovered a significant influence on the development of contemporary therapy with reduced side effects. But it lags behind in the race due to lesser bioavailability and indecorous delivered dosage form. In this research efforts made to develop a novel targeted dose delivery system for breast cancer. The breast cancer cell has shown higher expression of HIF-1α, TOP-II α, Proteine Kinase C, and MMP-2 receptors. By reviewing the literature followed by molecular modeling with these receptors, seven natural compounds were identified which have significant effect on above receptors: sesamin, aloe-emodin, gallic acid, catechin, Butein, 6-gingerol, and curcumin, respectively. Hence Liposomes were prepared with different formulations to entrap all the above active compounds. Then formulated liposomes were characterized, and their stabilities were also evaluated for 60 days at room temperature and 2-8 °C. Among all formulations, liposomes with GCDCA (1.8 mM), lecithin (62.12 mM), and cholesterol (25.88 mM) have proven to be the most stable, robust, and effective formulation using breast cancer MCF-7 cell line.

Lung cancer is a severe health problem that affects more men than women around the world. The goal of this study was to identify the biomarker hub genes for lung cancer in order to ascertain the biological pathway and protein- protein interaction networks. The microarray datasets GSE80796, GSE68571, GSE118370 and GSE43458 were retrieved from the GEO database and were analysed using GEO2R. STRING, Cytoscape, and cytoHubba were used to construct the PPI network and hub genes. GEPIA was used to obtain the overall survival and expression level in LUAD/LUSC and normal tissue. The MTT assay was used to examine antiproliferative activity. PI staining was used to determine the cell cycle arrest. qPCR was used to analyse gene expressions. The datasets revealed a total of 401 common DEGs, with 258 up-regulated genes and 143 down-regulated genes. Further

Understanding how MHC class II (MHC-II) binding peptides with differing lengths exhibit specific interaction at the core and extended sites within the large MHC-II pocket is a very important aspect of immunological research for designing peptides. Certain efforts were made to generate peptide conformations amenable for MHC-II binding and calculate the binding energy of such complex formation but not directed toward developing a relationship between the peptide conformation in MHC-II structures and the binding affinity (BA) (IC

Background and Objective Andrographis paniculata belonging to Acanthaceae family is well-known potential hepatoprotective herb. The role of diet on human health and diseases including Hepatocellular Carcinoma has been demonstrated by innumerable studies which have also testified that plant-derived micro-RNAs, transferred to animals via oral consumption wherein it alters host gene expression and this provides the evidence for inter-species gene regulation. Herein, we aim to explore the role of predicted miRNAs of A. paniculata on human health.Methods and ResultsIn the present study, A. paniculata miRNAs have been predicted and their impact on human transcriptome is uncovered by employing computational approach. By implementing miRNA prediction on A. paniculata genomic data and plant miRNA sequences present in miRBase repository, we have identified 20 miRNAs which are confined to 16 miR families. 197 human target genes were predicted for the identified miRNAs, which were further subjected to Gene Ontology analysis and network analysis revealing their significant role in various biological processes and signaling pathways. The identified hub proteins HGF, NRP2 and CCND1 show their significant involvement in cancerous pathways including STAT3, MAPK, TGF-β, mTOR and VEGFR pathways. Deregulation of these pathways has been reported as oncogenic response involved in Hepatocellular Carcinoma, cell proliferation and metastasis.ConclusionThe findings of our study suggest potentially beneficiary role of A. paniculata miRNAs in regulating cancer via cross-species genetic regulation. Conclusively, our study sustains the promising theory of inter-species gene regulation.

Thiram (tetramethylthiuramdisulfide) or thiram sulphide is a dithiocarbamate group of non-systemic group of fungicide which are applied for seed treatment, control of the crop pests, to repel animals, etc. Moreover, thiram has also been responsible to cause moderate skin sensitivity and eye irritation. Higher exposure to thiram might also lead to developmental damages to newborn and neurotoxic effects to non-target organisms. Advancing to prevent such toxic effects and prevention of soil fertility from thiram and thiram-like chemicals is indispensable. The analytical High-Performance Thin-Layer Chromatography (HPTLC) is a simple, quick and a reliable method was proposed and validated for the detection and quantification of various small molecules for many years. This manuscript represents the solution to use microbes to degrade the thiram present in the soil and for that, HPTLC based method to study thiram degradation by Pseudomonas has been designed. Herein, a HPTLC protocol formalised to reveal the detection and quantification of thiram within the range of 100 to 700 ng/spot on TLC plate. The same concentration was then used for calculating percent microbial degradation of thiram from the culture broth. To perform the microbial degradation of thiram, Pseudomonas otitidis strain TD-8 and Pseudomonas stutzeri strain TD-18 were taken as thiram degrader microbial strain. The efficacy of TD-8 to degrade thiram was identified to be 81 and 99% when grown in presence of thiram for 4 days and 8 days, respectively, while TD-18 strain's efficacy to degrade thiram was found to be 57% and 99% when grown in presence of thiram for 4 days and 8 days, respectively.

A library of 1,4-dihydropyridine-based 1,2,3-triazol derivatives has been designed, synthesized, and evaluated their cytotoxic potential on colorectal adenocarcinoma (Caco-2) cell lines. All compounds were characterized and identified based on their 1H and 13C NMR (Nuclear Magnetic Resonance) spectroscopic data. Furthermore, molecular docking of best anticancer hits with target proteins (protein kinase CK2α, tankyrase1, and tankyrase2) has been performed. Our results implicated that most of these compounds have significant antiproliferative activity with IC50 values between 0.63 ± 0.05 and 5.68 ± 0.14 µM. Moreover, the mechanism of action of most active compounds 13ab′ and 13ad′ suggested that they induce cell death through apoptosis in the late apoptotic phase as well as dead phase, and they could promote cell cycle arrest at the G2/M phase. Furthermore, the molecular docking study illustrated that 13ad′ possesses better binding interaction with the catalytic residues of target proteins involved in cell proliferation and antiapoptotic pathways. Based on our in vitro and in silico study, 13ad′ was found to be a highly effective anti-cancerous compound. The present data indicate that dihydropyridine-linked 1,2,3-triazole conjugates can be generated as potent anticancer agents.

Structure-based pharmacophore models are often developed by selecting a single protein-ligand complex with good resolution and better binding affinity data which prevents the analysis of other structures having a similar potential to act as better templates. PharmRF is a pharmacophore-based scoring function for selecting the best crystal structures with the potential to attain high enrichment rates in pharmacophore-based virtual screening prospectively. The PharmRF scoring function is trained and tested on the PDBbind v2018 protein-ligand complex dataset and employs a random forest regressor to correlate protein pocket descriptors and ligand pharmacophoric elements with binding affinity. PharmRF score represents the calculated binding affinity which identifies high-affinity ligands by thorough pruning of all the PDB entries available for a particular protein of interest with a high PharmRF score. Ligands with high PharmRF scores can provide a better basis for structure-based pharmacophore enumerations with a better enrichment rate. Evaluated on 10 protein-ligand systems of the DUD-E dataset, PharmRF achieved superior performance (average success rate: 77.61%, median success rate: 87.16%) than Vina docking score (75.47%, 79.39%). PharmRF was further evaluated using the CASF-2016 benchmark set yielding a moderate correlation of 0.591 with experimental binding affinity, similar in performance to 25 scoring functions tested on this dataset. Independent assessment of PharmRF on 8 protein-ligand systems of LIT-PCBA dataset exhibited average and median success rates of 57.55% and 74.72% with 4 targets attaining success rate 90%. The PharmRF scoring model, scripts, and related resources can be accessed at https://github.com/Prasanth-Kumar87/PharmRF.

Mosquitoes are vectors for a variety of infectious illnesses, and chemical synthetic insecticides have made it possible to control them effectively. Mosquito repellents are a typical means of keeping mosquitos at bay. Because of its main effectiveness of skin permeability, N,N-Diethyl-meta-toluamide (DEET) is one of the most extensively used mosquito repellents but a dangerous synthetic chemical. DEET was identified about a decade ago to inhibit mosquito's Odorant Binding Protein 1 (OBP1), impairing the mosquito's ability to recognise the host body odour. OBP1 has been identified as a possible target for the development of new mosquito repellents since its discovery. Essential oils from different plants, on the other hand, have been used to repel mosquitos since antiquity. One essential oil from the Curcuma longa (Zingiberales: Zingiberaceae) rhizome display mosquito repellent properties, according to the literature. Furthermore, one of the phytochemicals found in abundance in C. longa essential oil, ar-turmerone, exhibits mosquito repellency as comparable to synthetic DEET. Till date studies on in-silico interaction of natural ar-turmerone with OBP1, which we depict in our current work are scarce. Further, there exist no published reports demonstrating the literary evidence on detailed insights of interaction of DEET with OBP1 along with Molecular Dynamics (MD) simulation studies. We further performed detailed molecular investigations using pharmacophore analysis of ar-turmerone and compared it with DEET, where our findings in the current manuscript unveils for the first time that ar-turmerone is a functional, structural and pharmacophoric analogue of DEET.

Coronaviruses (CoVs) belong to a group of RNA viruses that cause diseases in vertebrates including. Newer and deadlier than SARS CoV-2 are sought to appear in future for which the scientific community must be prepared with the strategies for their control. Spike protein (S-protein) of all the CoVs require angiotensin-converting enzyme2 (ACE2), while CoVs also require hemagglutinin-acetylesterase (HE) glycoprotein receptor to simultaneously interact with O-acetylated sialic acids on host cells, both these interactions enable viral particle to enter host cell leading to its infection. Target inhibition of viral S-protein and HE glycoprotein receptor can lead to a development of therapy against the SARS CoV-2. The proposition is to recognize molecules from the bundle of phytochemicals of medicinal plants known to possess antiviral potentials as a lead that could interact and mask the active site of, HE glycoprotein which would ideally bind to O-acetylated sialic acids on human host cells. Such molecules can be addressed as 'HE glycoprotein blockers'. A library of 110 phytochemicals from

Colorectal cancer (CRC) is the most common malignancy of digestive system with significant mortality rate. CRC patients with comparable clinical symptoms or at similar stages of the disease have different outcomes. This underlying clinical result is almost inevitably due to genetic heterogeneity. Therefore, the current study aimed to highlight gene signatures during CRC and unveil their potential mechanisms through bioinformatic analysis. The gene expression profiles (GSE28000, GSE33113, GSE44861, and GSE37182) were downloaded from the Gene Expression Omnibus database, and the differential expressed genes (DEGs) were identified in normal tissues and tumor tissue samples of CRC patients. In total, 8931 DEGs were identified in CRC, including 411 up-regulated genes and 166 down-regulated genes. Further, a protein-protein interaction network was constructed and the highly related genes were clustered using the Molecular Complex Detection algorithm (MCODE) to retrieve the core interaction in different genes' crosstalk. The screened hub genes were subjected to functional enrichment analysis. GO analysis results showed that up-regulated DEGs were significantly enriched in biological processes (BP), including cell division, cell cycle, and cell proliferation; the down-regulated DEGs were significantly enriched in BP, including cellular homeostasis, detoxification, defense response, intracellular signaling cascade. Additionally, KEGG pathway analysis displayed the up-regulated DEGs were enriched in the cell cycle, TNF signaling, chemokine signaling pathway, while the down-regulated DEGs were enriched in NF-kB signaling, mineral reabsorption. Furthermore, the overall survival and expression levels of hub genes were detected by the UALCAN database and were further validated using Human Protein Atlas database. Taken together the identified DEGs (MT2A, CCNB1, DLGAP5, CCNA2, CXCL2, and RACGAP1) enhance our understanding of the molecular pathways that underpin CRC pathogenesis and could be exploited as molecular targets and diagnostic biomarkers for CRC therapy.

Background: Addressing religious and spiritual needs are important components of holistic healthcare. Little is known about the general public’s perspectives about pharmacists providing spiritual care (SC). Objectives: To explore how community members perceive, experience, and desire pharmacist-provided SC. Method: IRB approval was obtained for this observational, cross-sectional study. Adults receiving COVID-19 vaccinations at an immunization clinic completed an investigator-designed 33-item online survey. The survey measured respondents’ perspectives about and experiences with pharmacist-provided SC, as well as demographic characteristics. Results: Of the respondents (n = 261), 57% were female and 46% were Hispanic/Latino. Most (59%) agreed that their religion/spirituality would be important to them if they were ill; 64% also agreed that it would be helpful for a pharmacist to know about patients’ religious/spiritual beliefs pertaining to their healthcare, and 60% agreed that pharmacists should provide SC to patients who request it. While 96% indicated that they had never talked to a pharmacist about a spiritual or religious matter related to their health or medication, 96% also indicated that no pharmacist had asked to pray with them. These results are contextualized perhaps by the finding that 76% reported having no professional relationship with a pharmacist. Conclusion: Respondents often reported an openness to receiving SC from pharmacists. Most respondents, however, had not received SC from a pharmacist. Future studies should be conducted to better understand patient preferences for pharmacist-provided SC.

Ergosterol is the key sterol component in the cell membrane of fungi including moulds and yeasts. Any decrease in the levels of ergosterol in the cell membrane of fungi render them venerable to cell membrane damage and even its death. Majority of antifungal drug targets the key enzymes involved in ergosterol biosynthesis pathway. The biochemical pathway for the synthesis of Ergosterol is a complex one, though the reactions carried by Squalene Epoxidase (SE) and 14α-demethylase (CYP51- a member of Cytochrome P450 family) serves to the key rate limiting reactions that can impact the overall production of Ergosterol. Allylamines class of antifungal drug target SE while Azoles target the CYP51. Currently advancement in the drug development is focused to introduce newer drugs that can simultaneously inhibit both this rate limiting enzymes. However, natural compounds established to possess antifungal activity but the major loophole about their understanding lies in the fact that their mode of action are severely unstudied. One such well-established antifungal natural phytochemical is Eugenol, and in current manuscript we investigated its efficacy to interact with both, SE and CYP51 of Candida albicans using molecular Docking, Free energy change calculations and Molecular Dynamics (MD) simulation, showing promising outcomes. For experimental studies, terbinafine, clotrimazole and eugenol showed 4 μg/ml, 2 μg/ml, and 512 μg/ml MIC

A single gene mutation can cause a number of human diseases that affect the quality of life. Until the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) systems, it was challenging to correct a gene mutation to avoid a disease by reverting phenotypes. The advent of CRISPR technology has changed the field of gene editing, given its simplicity and intrinsic programmability, surpassing the limitations of both zinc-finger nuclease and transcription activator-like effector nuclease and becoming the method of choice for therapeutic gene editing by overcoming the bottlenecks of conventional gene-editing techniques. Currently, there is no commercially available medicinal cure to correct a gene mutation that corrects and reverses the abnormality of a gene's function. Devising reprogramming strategies for faithful recapitulation of normal phenotypes is a crucial aspect for directing the reprogrammed cells toward clinical trials. The CRISPR-Cas9 system has been promising as a tool for correcting gene mutations in maladies including blood disorders and muscular degeneration as well as neurological, cardiovascular, renal, genetic, stem cell, and optical diseases. In this review, we highlight recent developments and utilization of the CRISPR-Cas9 system in correcting or generating gene mutations to create model organisms to develop deeper insights into diseases, rescue normal gene functionality, and curb the progression of a disease. Delivery of CRISPR-components being a pivotal aspect in proving its effectiveness, various proven delivery systems have also been briefly discussed.

Cervical cancer (CC) is the world's fourth most prevalent cancer among women. The mortality rate of cervical cancer increases each year due to a lack of early diagnosis. Our study aims to find potential genes linked to cervical cancer and validate the findings using docking analysis. The microarray datasets (GSE6791, GSE7803, GSE9750, GSE39001, GSE52903, GSE63514, and GSE75132) were downloaded from the GEO (Gene Expression Omnibus) database. A total of 1160 Differentially Expressed Genes (DEGs) were discovered using the R statistical language, including 825 up-regulated and 335 down-regulated genes. STRING, which predicts the potential interaction between genes at the protein level, was used to build the PPI network of these DEGs. Moreover, hub gene expression analysis was carried out by CytoHubba plugin Cytoscape. CDK1 was considered for subsequent molecular docking because of its frequent appearance throughout the analysis. CDK1 was docked with the 399 phytochemicals of Indian kitchen spices. The top three compounds namely, Vicenin 2, 2-O,3-O,4-O,6-O-Tetragalloyl-d-glucopyranose and Pentagalloylglucose, were chosen based on their docking scores and their interactions with the key amino acids present in the ATP binding pocket, like the positive control Dinaciclib. In conclusion, the findings of this study may lead to new insights on CC diagnosis, aetiology, and treatment options. In the future, it may be possible to develop particular diagnostics and therapies for CC by identifying hub genes and studying overexpressed proteins as therapeutic targets.

Breast cancer (BC) is a malignancy that affects a large number of women around the world. The purpose of the current study was to use bioinformatics analysis to uncover gene signatures during BC and their potential mechanisms. The gene expression profiles (GSE29431, GSE10810, and GSE42568) were retrieved from the Gene Expression Omnibus database, and the differential expressed genes (DEGs) were identified in normal tissues and tumour tissue samples from BC patients. In total, 296 DEGs were identified in BC, including 46 upregulated genes and 250 downregulated genes. GO and KEGG pathway analysis were performed. A PPI network of the DEGs was also constructed. GO analysis results showed that upregulated DEGs were significantly enriched in biological processes (BP), including cell division, mitotic cell cycle, chromosome separation, and cell division. MF analysis showed that upregulated DEGs controlled the microtubule cytoskeleton, the microtubule organising center, the cytoskeleton, and the chromosome-centric region. KEGG analysis revealed the upregulated DEGs mainly regulated p53 signaling, while the downregulated DEGs were enriched in the AMPK signalling pathway and PPAR signalling pathway. Moreover, five hub genes with a high degree of stability were identified, including NUSAP1, MELK, CENPF, TOP2A, and PPARG. Experimental validation showed that all five hub genes had the same expression trend as predicted. The overall survival and expression levels of hub genes were detected by Kaplan-Meier-plotter and the UALCAN database and were further validated using the Human Protein Atlas database. Taken together, the identified key genes enhance our understanding of the molecular pathways that underpin BC pathogenesis. As a result, our novel findings could be used as molecular targets and diagnostic biomarkers in the treatment of BC. This study is based on empirical evidence, making it an appealing read for the global scientific community.

Little is known about student pharmacists' perspectives of spirituality and spiritual care (SC) in pharmacy education and practice. The purpose of this study was to examine student pharmacists' perspectives about spirituality and incorporating SC in pharmacy education and practice.Student pharmacists were recruited from two private pharmacy schools in California, one religiously-affiliated and one non-religiously affiliated. A faculty member at each school invited student pharmacists via email or through Zoom (Zoom Video Communications) chat to complete the 37-item online survey through an embedded link. The investigator-designed survey was comprised of 22 items inquiring about spirituality and SC as well as several items assessing demographic and religious characteristics.Participants included 470 student pharmacists (87.2% response rate) who were 28.9 ± 5.7 years old on average. Half of the respondents (50.5%) attended the non-religiously affiliated university. Most of the respondents were female (67%), Christian (67.8%), spiritual (79.2%), and religious (75.2%). They "agreed" or "strongly agreed" that: "understanding patients' spiritual beliefs is an important part of pharmacy practice" (83%), "I would pray with my patients as a pharmacist" (54.8%), "it is appropriate for a pharmacist to have spiritual or religious conversations with patients" (52.9%), and "it is appropriate for a pharmacist to pray with and for patients who request it" (66.9%). These beliefs were positively correlated with self-reported religiosity and spirituality.Most students considered themselves spiritual and religious and felt that spirituality and learning about SC were important. The respondents' SC perspectives were associated with their religiosity and spirituality.

Background Patients’ religious and spiritual beliefs affect their health behaviors, health outcomes, and interactions with health care providers. Incorporating spiritual support in clinical care contributes positively to patient health outcomes. No known studies have explored spiritual care (SC) within the context of pharmacy practice. Objective To examine pharmacist perspectives about SC, the frequency with which SC is incorporated in pharmacy practice, and the ways that pharmacists provide SC. Methods Data were collected using a cross-sectional statewide survey. The 57-item questionnaire was mailed to 1000 randomly selected registered pharmacists in California in 2019. Descriptive statistics, Pearson correlation, independent samples t test, and chi-square tests were used to analyze the data. Results Most of the 215 respondents were female (57.5%); the average length of work experience was 23.3 years (SD = 14.4). Just over half practiced in an urban setting (51.1%); similarly, half worked with terminally ill patients (50.2%). Most of the respondents were “somewhat” to “very spiritual” (77.8%) and “somewhat” to “very religious” (64.3%). Most pharmacists agreed that pharmacists should know about patients’ spiritual concerns that may relate to their health (60.5%), that they should practice in a spiritually sensitive manner (73.4%), and that addressing patients’ spiritual concerns improved their mental and physical health (76.7%). Respondents “rarely” to “very often or always” prayed privately for a patient (63.8%) and talked to patients about a spiritual and/or religious topic (51.2%), encouraged a patient to pray (49.3%), referred patients to their clergy or religious leader (39.5%), and prayed with a patient (33.5%). The frequency of spiritual services provided by pharmacists differed by their own spirituality, religiosity, and perception of institutional support (P Conclusion Most of the respondents were spiritual and religious and believed that spirituality is important for their patients. Thus, some provided SC to their patients. Future research is warranted to examine ethically appropriate strategies for pharmacists to provide SC.

Objective Pharmacists are encouraged to provide whole-person care. Because holistic care is conceptualized as including spiritual care (SC), this study investigated the experiences and perspectives of pharmacists regarding SC in pharmacy practice. Methods Data for this cross-sectional, qualitative study were collected from a survey mailed to 1000 randomly selected registered pharmacists in California in 2019. The data reported here are the responses to open-ended questions eliciting information about the last time the pharmacists provided SC to a patient, indicators that a patient needs spiritual assistance, and religious beliefs thought to be harmful. The data were content-analyzed by 2 investigators. Results Although 215 pharmacists responded to the survey, only 141 responded to the open-ended questions. Most of the respondents were women (58%), Christian (70%), religious (73%), attended religious services (78%), and practiced in an urban setting (56%). The themes observed indicated that these pharmacists prayed with, and for, patients; talked to patients about God and religion; referred patients to spiritual services; were sensitive to patients’ spiritual or religious beliefs; and listened to patients’ expressions of spirituality. Some respondents, however, avoided religious conversations and requests; some also reported unwillingness to provide SC to patients. The pharmacists had limited education, knowledge, and awareness about SC. Conclusions The pharmacists in this sample reported diverse perspectives about SC that ranged from acceptance to rejection of SC in patient care. Pharmacists are not fully engaged in providing SC because of several challenges, including limited education and training on SC. Scholarly inquiry is needed to examine how pharmacists can best provide SC in pharmacy practice.

The novel SARS-CoV-2 is the etiological agent causing the Coronavirus disease 2019 (COVID-19), which continues to become an inevitable pandemic outbreak. Over a short span of time, the structures of therapeutic target proteins for SARS-CoV-2 were identified based on the homology modelled structure of similar virus, SARS-CoV that transmitted rapidly in 2003. Since the outset of the disease, the research community has been looking for a potential drug lead. Out of all the known resolved structures related to SARS-CoV-2; 3-chymotrypsin (3 C) like protease (3CL

The novel SARS-CoV-2 is the etiological agent causing the Coronavirus disease 2019 (COVID-19), which continues to become an inevitable pandemic outbreak. Over a short span of time, the structures of therapeutic target proteins for SARS-CoV-2 were identified based on the homology modelled structure of similar SARS-CoV transmission of 2003. Since the onset of the disease, the research community has been looking for a potential drug lead. Out of all the known resolved structures related to SARS-CoV, Main protease (Mpro) is considered an attractive anti-viral drug target on the grounds of its role in viral replication and probable non-interactive competency to bind to any viral host protein. To the best of our knowledge, till date only one compound has been identified and tested in-vivo as a potent inhibitor of Mpro protein, addressed as N3 (PubChem Compound CID: 6323191) and is known to bind irreversibly to Mpro suppressing its activity. Using computational approach, we intend to identify a probable natural fungal metabolite to interact and inhibit Mpro. After screening various small molecules for molecular docking and dynamics simulation, we propose Pyranonigrin A, a secondary fungal metabolite to possess potent inhibitory potential against the Main protease (Mpro) expressed in SARS-CoV-2 virus., Graphical abstract Unlabelled Image, Highlights • Searching inhibitor for Main Protease (Mpro) of SARS-CoV2 • Purpose to block viral replication and packaging in host • Mpro interaction with fungal metabolite- Pyranonigrin A • Studies involving docking and molecular dynamics

The pandemic outbreak of COVID-19 virus (SARS-CoV-2) has become critical global health issue. The biophysical and structural evidence shows that SARS-CoV-2 spike protein possesses higher binding affinity towards angiotensin-converting enzyme 2 (ACE2) and hemagglutinin-acetylesterase (HE) glycoprotein receptor. Hence, it was selected as a target to generate the potential candidates for the inhibition of HE glycoprotein. The present study focuses on extensive computational approaches which contains molecular docking, ADMET prediction followed by molecular dynamics simulations and free energy calculations. Furthermore, virtual screening of NPACT compounds identified 3,4,5-Trihydroxy-1,8-bis[(2R,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]benzo[7]annulen-6-one, Silymarin, Withanolide D, Spirosolane and Oridonin were interact with high affinity. The ADMET prediction revealed pharmacokinetics and drug-likeness properties of top-ranked compounds. Molecular dynamics simulations and binding free energy calculations affirmed that these five NPACT compounds were robust HE inhibitor.

Since its origin, the emergence of vector-borne infections has taken a toll on incalculable human lives. The use of chemical insecticides is one of the early known methods of vector control and although their use is still a prevalent way to combat insect population sadly the perils of insects related transmission still persists. Most commonly, the existing insecticides face the wrath of getting resisted repeatedly, paying way to develop resilient, efficient, and cost-effective natural insecticides. In this study, computational screening was performed using homology modelling, E-pharmacophore feature mapping, molecular docking, Density Function Theory (DFT) assessment, Molecular mechanics generalized Born surface area (MM-GBSA) based binding free energy calculations and Molecular Dynamics (MD) simulation to identify a potential lead phytochemical out of a manually curated library from published literature. The protein target used under this study is insect Butyrylcholine esterase (BChE). Additionally, in vitro insect (Aedes aegypti) BChE inhibition assay was also performed with the top phytochemical identified from in silico assessments. Our research highlights that curcumin leads to inhibition of enzyme BChE of Ae. aegypti. The identified mode of action of curcumin as an insect BChE inhibitor indicates the possibility of its use as an environment friendly and natural futuristic insecticide.

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Background High confidence in vaccination programmes is crucial for maintaining high coverage rates. Across the European Union (EU), however, vaccine delays and refusals are contributing to declining immunisation rates in a number of countries and are leading to increases in disease outbreaks. Methods We assessed the overall state of confidence in vaccines among the public in all 28 EU member states and among general practitioners (GP) in ten EU member states, conducting the largest ever study on attitudes to vaccines and vaccination in the EU, eliciting the views of approximately 28,000 respondents across the 28 EU member states. Results We found that a number of member states (including France, Greece, Italy, and Slovenia) have become more confident in the safety of vaccines since 2015, but that the Czech Republic, Finland, Poland, and Sweden have become less confident. While GPs generally hold higher levels of vaccine confidence than the public, the survey found that 36% of GPs surveyed in Czech Republic and 25% in Slovakia do not agree that the MMR vaccine is safe and 29% and 19% respectively do not believe it is important. Countries whose GPs hold higher confidence in vaccines tend to have a larger proportion of the public expressing positive vaccination beliefs. Conclusions Even countries with well-established vaccination programmes and high levels of confidence are not immune to rising vaccine hesitancy. There is a need for continuous monitoring, preparedness and response plans to maintain and increase confidence in the importance, effectiveness and safety of vaccines, among both the public and health professionals.

Cloning and functional attributes of a serine protease gene from haloalkaliphilic bacteria are described. The protease gene of ∼1,600 bp amplified from the genomic DNA was cloned into TA vector followed by the sub-cloning into pUC19 for expression. Growth of the organism and gene expression was studied at 30 and 37 °C in the presence of 0.5–2.0 mM IPTG. Sequencing of the gene and homology search of the sequence revealed that the gene encoded an extracellular alkaline serine protease belonging to superfamily subtilisin-like hydrolases. The amino acid sequence alignment resulted from the BLAST search of the subtilisin exhibited high sequence homology with the Bacillus subtilis ssp. subtilis strain 168 and subtilisins of other Bacillus sp., B. subtilis and B. mojavensis. The deduced amino acid sequence exhibited a mature protease of a 419 amino acid, single-chained monomeric peptide with the large number of the positively charged amino acids suggesting its hydrophilic nature.

A new series of benzoyl chloride-substituted 2,4-thiazolidinedione derivatives have been synthesized by the condensation of 2-amino-4-aryl-thiazole and 4′-chlorosulfonyl benzylidine-2,4-thiazolidinedione. New compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. Furthermore, new products were tested for in vitro antituberculosis activity against Mycobacterium tuberculosis using isoniazid and rifampicin as control drugs. The results of bioassay demonstrated that some of the newly synthesized 2,4-thiazolidinedione derivatives emerged as lead molecules with excellent MIC (mg/mL) values against mentioned organisms compared to standard drugs. The structure of the final analogs has been confirmed on the basis of IR, 1H NMR, mass spectral, and elemental analysis.

Ancient health science, such as Ayurveda of India, depends on natural products. Ayurveda is still an active and important system of medicine in India. Many Ayurvedic herbal preparations have found their way in the pharmacopeias of different countries. With the advent of chemotherapy, several of these preparations are supplemented by more effective or less toxic synthetic drugs. It is now generally felt that the bulk of the drugs in use are human made. Continuous use of such synthetic xenobiotic and therapeutic agents may affect the metabolic and excretory functions leading to secondary physiological changes in liver. Hepatocellular carcinoma (HCC) is one of the primary malignancies associated with physiological Relevance. The present investigation relates to the influence of andrographolide, an active compound of Andrographis paniculata Nees. It reverses an experimental liver carcinogenic condition of mice to normal and might be a potential therapeutic/preventive agent for human liver cancer. Objective. A. paniculata (Kalmegh) is extensively used in the Indian traditional system of medicine as a hepatoprotective and hepatostimulative agent and has been reported to have protective effect against different hepatotoxins. Materials and methods. Histomorphological, ultrastructural, and biochemical studies were performed for the effect of the andrographolide on control mice, mice treated with hexachlorocyclohexane (BHC) only and BHC + andrographolide. Enzymes for liver function tests were analyzed by spectrophotometric method. Results. The BHC experimental model forms an irreversible liver tumor in male mice. The histological and ultrastructural changes observed in andrographolide supplementation emphasize the recovery of the damaged liver. This recovery was also reflected in the neoplastic nodule formation. The activity of phosphorylase and glucose-6-phosphatase in the liver of the andrographolidesupplemented group suggests improved glycogenolysis in liver. Serum glutamate pyruvate transaminase, serum glutamate oxalate transaminase, alkaline phosphatase, acid phosphatase, and γ-glutamyl transpeptidase showed a significant decrease in andrographolide-supplemented animals as compared with BHC-treated animals, suggesting regenerative effects elicited by andrographolide. Conclusion. The study indicates that the regenerative capability elicited by andrographolide is possibly due to its ability to reactivate liver function enzymes that catalyze the reaction of several biochemical and synthetic processes and that it may be useful for severe liver damage conditions.

Purpose To determine the inter- and intrarater reliability of the clock-face grading system as used by 3 fellowship-trained sports medicine surgeons. Methods Arthroscopic video was taken of the femoral tunnel placement during 20 consecutive anterior cruciate ligament (ACL) reconstructions performed by 2 surgeons. All femoral tunnels were created using a medial portal technique. The video was taken using a 30° arthroscope placed in the lateral portal and showed the femoral tunnel as well as the remainder of the femoral notch, the posterior cruciate ligament, and the menisci for orientation. Three fellowship-trained sports medicine surgeons were asked to review the videos and assign an o'clock position to the femoral tunnel from the 9 to the 3 o'clock positions in "half-hour" increments. They were also asked to review the videos again 6 months later to determine intrarater reliability. Inter-rater reliability was evaluated using the intraclass correlation coefficient (ICC) 2-way mixed effect model with absolute agreement. The Spearman rank-order correlation coefficient ( r ) was applied to evaluate intrarater reliability. Results The inter-rater reliability as measured by the ICC revealed poor agreement between the 3 surgeons (ICC = 0.204, 95% confidence interval = −0.015 to 0.491, F = 2.8, P = .004). The intrarater reliability at a 6-month interval was found to be moderate ( r 's = .43, P = .004). Conclusions The inter-rater reliability of the clock-face femoral tunnel grading system was found to be poor among fellowship-trained sports medicine surgeons whereas the intrarater reliability was found to be moderate. The utility of the femoral tunnel clock-face grading system may be compromised by suboptimal inter- and intrarater reliability, making it less useful as a tool of communication between surgeons. Level of Evidence Level IV, case series with poor reference standard.

Tobacco is the major etiological factor for oral cancer development through the generation of oxidative stress. Therefore, markers of oxidative stress such as total antioxidant status, lipid peroxidation, and total thiol levels might be useful to monitor oxidative stress and predict overall survival in oral cancer patients. The study included 140 oral cancer patients and 50 healthy controls, who were classified as with the habit of tobacco and no habit of tobacco. Adjacent normal and malignant tissue samples were collected from oral cancer patients. Plasma and tissue levels of lipid peroxidation, thiol, and total antioxidant status were assayed by spectrophotometric methods. Thiol levels were significantly lower in controls with the habit of tobacco ( P = .033), oral cancer patients ( P = .0001), and malignant tissues ( P = .015) as compared to controls with no habit of tobacco, controls with the habit of tobacco, and adjacent normal tissues, respectively. Tobacco exposure was higher in oral cancer patients than controls with the habit of tobacco. Controls with the habit of tobacco who had lower thiol (odds ratio [OR] = 10.58, P = .008) and high tobacco exposure (OR = 0.251, P = .05) showed an elevated risk of oral cancer development. Patients showing a lipid peroxidation level above the cutoff level as compared to patients below the cutoff level showed poor overall survival, whereas those with thiol and total antioxidant status levels below the cutoff level as compared to their respective counterparts showed poor overall survival. In conclusion, lipid peroxidation and thiol could be useful for predicting the risk of oral carcinogenesis in healthy tobacco consumers and predicting overall survival of oral cancer patients.

Many plant products are known to exert antioxidative effects by quenching various free radicals and singlet molecular oxygen. Andrographis paniculata (Kalmegh) is used extensively in the Indian traditional system of medicine as a hepatoprotective and hepatostimulative agent and has been reported to have antioxidant effects against different hepatotoxins. The present study aims to analyze antioxidant properties of an active component, andrographolide (ANDLE), extracted from A paniculata. This study investigates the effect of andrographolide on the hepatocellular antioxidant defense system and lipid peroxidation of control mice, mice treated with hexachlorocyclohexane (BHC) only, and andrographolide + BHC. Glutathione (GSH), glutathione-s-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GSH-Px), γ-glutamyl transpeptidase (γ-GTP), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO) are studied by spectrophotometric methods. The BHC experimental model forms an irreversible liver tumor in male mice. The activities of GSH, GR, GSH-Px, SOD, and CAT show significant ( P ≤ .05) increases, while γ-GTP and GST show significant decreases ( P ≤ .05) in andrographolide-supplemented mice as compared with BHC-treated mice. This study indicates that the antioxidant effect of andrographolide could be due to its ability to activate antioxidant enzymes that catalyze the reaction of oxidants and are effective in severe liver damage.

Spontaneous level of chromosomal aberrations (CA) is considered to be indicative of inherent cancer predisposition, which plays a major role in total cancer incidence. We have studied spontaneous CA levels in in vitro cultured peripheral blood lymphocytes of pediatric cancer patients ( n = 77). Results were compared with those of control subjects ( n = 72), including: age-matched controls; elder controls (minimum age 60 years); and healthy first-degree relatives (FDR) of pediatric cancer patients. Pediatric cancer patients showed the highest mean CA/cell value, which was statistically significant as compared to their age-matched counterparts, elder controls, and the FDRs. As compared to 7% of all the three control groups collectively, 32.4% of pediatric cancer patients showed > 0.1 mean CA/cell value. One of the FDRs with a very high frequency of CA developed cancer within three years. The results suggest that spontaneous levels of chromosomal aberrations may be used as one of the biomarkers for cancer predisposition study.

Mitomycin-C (MMC) induced Chromosomal aberration (CA) frequencies were studied in 48 h peripheral blood lymphocyte (PBL) cultures of untreated cancer patients of young age (maximum age 12 years, n=77). Control population (n=71) consisted of age-matched group (maximum age 12 years, n=21); elder controls (minimum age 60 years, n=19) and healthy first degree relatives, i.e., parents or siblings of the pediatric cancer patients (mean age 24.3 years, n=31) as they share their genome and environment. Induced CA levels were found to be significantly higher among pediatric cancer patients as compared to control groups. The age-matched and elder control groups showed comparable CA levels. The first degree relatives controls showed higher induced CA levels as compared to pediatric and elder control groups. The present results indicate that there are different degrees of mutagen sensitivity prevailing in normal population. This may be responsible for differential cancer proneness. High degree of mutagen sensitivity in cancer patients may also be playing a major role in cancer onset at an early age.

Pseudomonas aeruginosa strain PK6, a potential petroleum hydrocarbon-degrading soil bacterium, was isolated from a site contaminated by a petroleum hydrocarbon spill from an automobile service station in Junagadh, Gujarat, India. Here, we provide the 6.04-Mb draft genome sequence of strain PK6, which has genes encoding enzymes for potential and related metabolic pathways of the strain.

Here, we report the draft genome sequence of Pseudomonas aeruginosa strain PFK10, isolated from the common effluent treatment plant (CETP) of the Ankleshwar industrial area of Gujarat, India. The 6.04-Mb draft genome sequence of strain PFK10 provides information about the genes encoding enzymes that enable the strain to decolorize and degrade textile azo dye.

Alkalibacillus haloalkaliphilus C-5 is a haloalkaliphilic bacterium that was isolated from a soil sample from the salty Sambhar Lake, Rajasthan, India. The organism is capable of alkaline protease production under conditions of pH 10 and 10% (wt/vol) salt. We sequenced and have reported the whole genome of Alkalibacillus haloalkaliphilus C-5, of Indian origin, for the first time.