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Marine species are known as rich sources of metabolites largely involved in the pharmaceutical industry. This study aimed to evaluate in silico the effect of natural compounds identified in algae on the SARS-CoV-2 Main protease, RNA-dependent-RNA polymerase activity (RdRp), endoribonuclease (NSP15) as well as on their interaction with viral spike protein. A total of 45 natural compounds were screened for their possible interaction on SARS-CoV-2 target proteins using Maestro interface for molecular docking, molecular dynamic (MD) simulation to estimate compounds binding affinities. Among the algal compounds screened in this study, three (Laminarin, Astaxanthin and 4'-chlorostypotriol triacetate) exhibited the lowest docking energy and best interaction with SARS-CoV-2 viral proteins (Main protease, RdRp, Nsp15, and spike protein). The complex of the main protease with laminarin shows the most stable RMSD during a 150 ns MD simulation time. Which indicates their possible inhibitory activity on SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

The coronavirus disease 2019 (COVID-19), which emerged in December 2019, continues to be a serious health concern worldwide. There is an urgent need to develop effective drugs and vaccines to control the spread of this disease. In the current study, the main phytochemical compounds of Nigella sativa were screened for their binding affinity for the active site of the RNA-dependent RNA polymerase (RdRp) enzyme of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The binding affinity was investigated using molecular docking methods, and the interaction of phytochemicals with the RdRp active site was analyzed and visualized using suitable software. Out of the nine phytochemicals of N. sativa screened in this study, a significant docking score was observed for four compounds, namely α-hederin, dithymoquinone, nigellicine, and nigellidine. Based on the findings of our study, we report that α-hederin, which was found to possess the lowest binding energy (-8.6 kcal/mol) and hence the best binding affinity, is the best inhibitor of RdRp of SARS-CoV-2, among all the compounds screened here. Our results prove that the top four potential phytochemical molecules of N. sativa, especially α-hederin, could be considered for ongoing drug development strategies against SARS-CoV-2. However, further in vitro and in vivo testing are required to confirm the findings of this study.

Chronic lymphocytic leukemia (CLL) is an incurable neoplasm of B-lymphocytes, which accounts for about one-third of all leukemias. Ocimum sanctum, an herbaceous perennial, is considered as one of the important sources of drugs for the treatment of various diseases, including cancers and autoimmune diseases. The present study was designed to screen various phytochemicals of O. sanctum for discovering their potential to inhibit Bruton’s tyrosine kinase (BTK), a well-known drug target of CLL. Various phytochemicals of O. sanctum were screened for their potential to inhibit BTK using several in silico protocols. First, the molecular docking approach was used to calculate the docking scores of the selected phytochemicals. Then, the selected top-ranked phytochemicals were screened for their physicochemical characteristics using ADME analysis. Finally, the stability of the selected compounds in their corresponding docking complexes with BTK was analysed using molecular dynamics simulations. Primarily, our observations revealed that, out of the 46 phytochemicals of O. sanctum, six compounds possessed significantly better docking scores (ranging from −9.2 kcal/mol to −10 kcal/mol). Their docking scores were comparable to those of the control inhibitors, acalabrutinib (−10.3 kcal/mol), and ibrutinib (−11.3 kcal/mol). However, after ADME analysis of these top-ranked six compounds, only three compounds (Molludistin, Rosmarinic acid, and Vitexin) possessed drug likeliness characteristics. During the MD analysis, the three compounds Molludistin, Rosmarinic acid, and Vitexin were found to remain stable in the binding pocket in their corresponding docking complexes with BTK. Therefore, among the 46 phytochemicals of O. sanctum tested in this study, the three compounds, Molludistin, Rosmarinic acid, and Vitexin are the best inhibitors of BTK. However, these findings need to be confirmed by biological experiments in the laboratory.

Candida albicans and Staphylococcus aureus, representing two different kingdoms, are the most frequently isolated pathogens from invasive infections. Their pathogenic attributes, combined with drug resistance, make them a major threat and a challenge to successful treatments, mainly when involved in polymicrobial biofilm-associated infections. In the present study, we investigated the antimicrobial potential of Lactobacillus metabolite extracts (LMEs) purified from cell-free supernatant of four Lactobacillus strains (KAU007, KAU0010, KAU0021, and Pro-65). Furthermore, LME obtained from the strain KAU0021 (LMEKAU0021), being the most effective, was analyzed for its anti-biofilm property against mono- and polymicrobial biofilms formed by C. albicans and S. aureus. The impact of LMEKAU0021 on membrane integrity in single and mixed culture conditions was also evaluated using propidium iodide. The MIC values recorded for LMEKAU0021 was 406 µg/mL, 203 µg/mL, and 406 µg/mL against planktonic cells of C. albicans SC5314, S. aureus and polymicrobial culture, respectively. The LMEKAU0021 at sub-MIC values potentially abrogates both biofilm formation as well as 24 h mature mono- and polymicrobial biofilms. These results were further validated using different microscopy and viability assays. For insight mechanism, LMEKAU0021 displayed a strong impact on cell membrane integrity of both pathogens in single and mixed conditions. A hemolytic assay using horse blood cells at different concentrations of LMEKAU0021 confirmed the safety of this extract. The results from this study correlate the antimicrobial and anti-biofilm properties of lactobacilli against bacterial and fungal pathogens in different conditions. Further in vitro and in vivo studies determining these effects will support the aim of discovering an alternative strategy for combating serious polymicrobial infections caused by C. albicans and S. aureus.

Background: Dengue virus is a potential source of propagating dengue hemorrhagic fever. This virus leads to dengue hemorrhagic fever/dengue shock syndrome, benign syndrome, and severe syndrome and due to its infection, there occurs alterations at multiple levels such as gene expression and pathway levels. So, it is critical to understand the pathogenesis of dengue infection in terms of gene expression and the associated functions. Methods: For this purpose, here, we have analyzed the temporal gene expression profiling for the dengue hemorrhagic fever dataset at 12, 24, and 48 hours. Results: The outcome appears that the dengue hemorrhagic fever evolves differently at different time periods or stages. Counclusions: The change in the gene expression pattern increases exponentially from 12 hours to 48 hours and the number of altered functions (pathways) also increases. Wnt, apoptosis, and transcription signaling are among the critical pathways which are dominantly altered. In the initial phase (first 12 hours), only two pathways are altered due to dengue infection, while in the next 12 hours, eight pathways are altered, and finally, in the next 24 hours, 11 pathways are altered and most of these 11 pathways are very critical in terms of biological pathways and functions.

A total of 20 Lactobacillus strains isolated from fermented dates were tested for their probiotic potential by comparing their pH stability, resistance to low pH, and ability to tolerate bile salts. Out of 20 strains, 3 strains named as Lactobacillus pentosus KAU001, Lactiplantibacillus pentosus KAU002, and Lactiplantibacillus plantarum KAU003 had a high tolerance of acids and bile salts and the capability to adhere to the intestinal wall. In addition, the three isolates were tested for their anti-oxidation, anti-glucosidase inhibition, cholesterol-lowering, and anti-inflammation properties. Among them, strain KAU001 and KAU002 inhibited α-glucosidase, lowered cholesterol level, inhibited nitric oxide production, and showed a higher anti-oxidative ability that was significantly better than strain KAU003. Both strains also significantly inhibited the release of inflammatory mediators such as TNF-α, IL-6 and IL-10 induced by LPS on RAW 264.7 macrophages (p < 0.001). The results indicated that KAU001 and KAU002 have the highest probiotic potential, potentially modulating metabolic health and reducing pro-inflammatory cytokines in response to allergic reactions.

Gastric cancer (GC) is a significant health concern worldwide, with a GLOBOCAN estimate of 1.08 million novel cases in 2020. It is the leading cause of disability-adjusted life years lost to cancer, with the fourth most common cancer in males and the fifth most common cancer in females. Strategies are pursued across the globe to prevent gastric cancer progression as a significant fraction of gastric cancers have been linked to various pathogenic (bacterial and viral) infections. Early diagnosis (in Asian countries), and non-invasive and surgical treatments have helped manage this disease with 5-year survival for stage IA and IB tumors ranging between 60% and 80%. However, the most prevalent aggressive stage III gastric tumors undergoing surgery have a lower 5-year survival rate between 18% and 50%. These figures point to a need for more efficient diagnostic and treatment strategies, for which the oncolytic viruses (OVs) appear to have some promise. OVs form a new therapeutic agent class that induces anti-tumor immune responses by selectively killing tumor cells and inducing systemic anti-tumor immunity. On the contrary, several oncogenic viruses have been shown to play significant roles in malignancy progression in the case of gastric cancer. Therefore, this review evaluates the current state of research and advances in understanding the dual role of viruses in gastric cancer.

BackgroundThe epidemic of 2019 novel coronavirus (SARS-CoV-2) is challenge to the world which was at first confirmed in the Wuhan city of China in December 2019. It was declared a pandemic by the World Health Organization (WHO) in March 2020. In the current work we evaluated effect of health policy of Saudi Arabia for the management of COVID-19 pandemic in early phase and compared to other four countries. MethodBased on the Ministry of Health, Kingdom of Saudi Arabia (KSA) data, the summary of daily report of COVID-19 was prepared from 02 March to 30 April 2020. Further, the daily report of enhancement in cases and recovery of the patients was also summarized. Moreover, the incidence, death and recoveries of COVID-19 cases in KSA were compared with major infected country including China, Italy, Spain and United State of America (USA). The important role of artificial intelligence was shown for the development of drug targets against to infectious diseases Results In KSA, the first case of COVID-19 was reported on 02 March 2020. Since then, it has affected 22,753 persons till the end of the April 2020. Also, the results showed that the infection rate of COVID-19 increased continuously during the current period of study in KSA. Nevertheless, the rate of death due to COVID-19 is much less with comparison to China, Italy, Spain, and USA due to good medical facilities along with quick action by the government of KSA after the emergence of first case. There is a dire need to develop new platforms and approaches to combat new and old diseases including COVID-19 at warp speed when compared to traditional approaches. DeepDrug’s approach to drug discovery and development showed brighter future towards the discovery of novel drugs against infectious diseases including COVID-19.ConclusionCurrently, there is higher probability of COVID-19 spread at any place. Therefore good health policy, precautionary measures and medical facility of whole nations should be excellent to combat against the COVID-19 pandemic until the reliable vaccine or antiviral drug developed for the proper treatment of virus. The artificial intelligence (AI) based available process might be very helpful for the drug discovery and development against of old and newly discovered diseases including COVID-19.

Streptococcus pyogenes is one of the most common bacteria causing sinusitis in children and adult patients. Probiotics are known to cause antagonistic effects on S. pyogenes growth and biofilm formation. In the present study, we demonstrated the anti-biofilm and anti-virulence properties of Lactiplantibacillus plantarum KAU007 against S. pyogenes ATCC 8668. The antibacterial potential of L. plantarum KAU007 metabolite extract (LME) purified from the cell-free supernatant of L. plantarum KAU007 was evaluated in terms of minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). LME was further analyzed for its anti-biofilm potential using crystal violet assay and microscopic examination. Furthermore, the effect of LME was tested on the important virulence attributes of S. pyogenes, such as secreted protease production, hemolysis, extracellular polymeric substance production, and cell surface hydrophobicity. Additionally, the impact of LME on the expression of genes associated with biofilm formation and virulence attributes was analyzed using qPCR. The results revealed that LME significantly inhibited the growth and survival of S. pyogenes at a low concentration (MIC, 9.76 µg/mL; MBC, 39.06 µg/mL). Furthermore, LME inhibited biofilm formation and mitigated the production of extracellular polymeric substance at a concentration of 4.88 μg/mL in S. pyogenes. The results obtained from qPCR and biochemical assays advocated that LME suppresses the expression of various critical virulence-associated genes, which correspondingly affect various pathogenicity markers and were responsible for the impairment of virulence and biofilm formation in S. pyogenes. The non-hemolytic nature of LME and its anti-biofilm and anti-virulence properties against S. pyogenes invoke further investigation to study the role of LME as an antibacterial agent to combat streptococcal infections.

Simple Summary Herein, we examined the facile synthesis of ZnONPs using aqueous extract of Salvia officinalis without any additional stabilizing/capping agents. When compared to chemically synthesized nanoparticles, green chemistry-based synthesis using medicinal plants has less harmful effects. The photocatalytic degradation of methyl orange under UV light irradiation was performed with 92.47% degradation efficiency, and the reaction rate constant (kapp) was found to be 0.02134 min−1. In addition, the antifungal activity of biofabricated ZnONPs was determined against Candida albicans isolates by standard protocols of broth microdilution and disc diffusion assay. Phytofabricated ZnONPs using S. officinalis were found to be more effective against drug-resistant Candida albicans isolates and have efficient photocatalytic properties. Abstract The facile bio-fabrication of zinc oxide (ZnO) nanoparticles (NPs) is described in this study using an aqueous leaf extract of Salvia officinalis L. as an efficient stabilizing/capping agent. Biosynthesis of nanomaterials using phytochemicals present in the plants has received great attention and is gaining significant importance as a possible alternative to the conventional chemical methods. The properties of the bio-fabricated ZnONPs were examined by different techniques, such as UV-visible spectroscopy, X-ray diffraction spectroscopy (XRD), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and thermogravimetric/differential scanning calorimetry analysis (TGA/DTG). The photocatalytic activity of ZnONPs was investigated against methyl orange (MO) under UV light irradiation. Under optimum experimental conditions, ZnONPs exhibited 92.47% degradation of MO. Furthermore, the antifungal activity of bio-fabricated ZnONPs was determined against different clinical Candida albicans isolates following standard protocols of broth microdilution and disc diffusion assay. The susceptibility assay revealed that ZnONPs inhibit the growth of all the tested fungal isolates at varying levels with MIC values ranging from 7.81 to 1.95 µg/mL. Insight mechanisms of antifungal action appeared to be originated via inhibition of ergosterol biosynthesis and the disruption of membrane integrity. Thus, it was postulated that bio-fabricated ZnONPs have sustainable applications in developing novel antifungal agents with multiple drug targets. In addition, ZnONPs show efficient photocatalytic efficiency without any significant catalytic loss after the catalyst was recycled and reused multiple times.

Cadmium (Cd) is a toxic heavy metal and an abiotic stressor to plants; however, inoculation of endophytic bacteria can raise resistance in plants against Cd, as well as improve plant growth. In the present study, two endophytic bacterial strains were isolated from Solanum nigrum, identified as Serratia sp. IU01 and Enterobacter sp. IU02 by 16S DNA sequencing. Both IU01 and IU02 were tolerant up to 9.0 mM of Cd in culture broth and successive increase in Cd concentration from 0 mM to 9.0 mM, led to an increase in the SOD enzyme activity of the isolates. Both strains were capable of indole-3-acetic acid (IAA) synthesis and phosphate solubilization, detected through gas spectrometry-mass chromatography (GC-MS) and Pikovskaya agar medium respectively. Brassica juncea plants stressed with 0–25 mg/kg Cd showed retardation in all growth attributes, however, inoculation of strain IU01 and IU02 significantly promoted the plant growth attributes as compared to control. Moreover, antioxidant enzymes and metabolites against reactive oxygen species (ROS) including polyphenol oxidase (PPO), peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), alcohol dehydrogenase (ADH), reduced glutathione (GSH), malondialdehyde (MDA), flavonoid and polyphenolic contents were also significantly relieved by inoculation of IU01 and IU02 in plant exposed to different concentration of Cd stress as compared to control plants. Phytohormone production, phosphate solubilization, and/or antioxidative support of IU01 and IU02 might be responsible for growth promotion and Cd resistance in the plant.

Cancer is among the highly complex disease and renal cell carcinoma is the sixth-leading cause of cancer death. In order to understand complex diseases such as cancer, diabetes and kidney diseases, high-throughput data are generated at large scale and it has helped in the research and diagnostic advancement. However, to unravel the meaningful information from such large datasets for comprehensive and minute understanding of cell phenotypes and disease pathophysiology remains a trivial challenge and also the molecular events leading to disease onset and progression are not well understood. With this goal, we have collected gene expression datasets from publicly available dataset which are for two different stages (I and II) for renal cell carcinoma and furthermore, the TCGA and cBioPortal database have been utilized for clinical relevance understanding. In this work, we have applied computational approach to unravel the differentially expressed genes, their networks for the enriched pathways. Based on our results, we conclude that among the most dominantly altered pathways for renal cell carcinoma, are PI3K-Akt, Foxo, endocytosis, MAPK, Tight junction, cytokine-cytokine receptor interaction pathways and the major source of alteration for these pathways are MAP3K13, CHAF1A, FDX1, ARHGAP26, ITGBL1, C10orf118, MTO1, LAMP2, STAMBP, DLC1, NSMAF, YY1, TPGS2, SCARB2, PRSS23, SYNJ1, CNPPD1, PPP2R5E. In terms of clinical significance, there are large number of differentially expressed genes which appears to be playing critical roles in survival.

The coronavirus disease 2019 (COVID-19), which emerged in December 2019, continues to be a serious health concern worldwide. There is an urgent need to develop effective drugs and vaccines to control the spread of this disease. In the current study, the main phytochemical compounds of Nigella sativa were screened for their binding affinity for the active site of the RNA-dependent RNA polymerase (RdRp) enzyme of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The binding affinity was investigated using molecular docking methods, and the interaction of phytochemicals with the RdRp active site was analyzed and visualized using suitable software. Out of the nine phytochemicals of N. sativa screened in this study, a significant docking score was observed for four compounds, namely α-hederin, dithymoquinone, nigellicine, and nigellidine. Based on the findings of our study, we report that α-hederin, which was found to possess the lowest binding energy (–8.6 kcal/mol) and hence the best binding affinity, is the best inhibitor of RdRp of SARS-CoV-2, among all the compounds screened here. Our results prove that the top four potential phytochemical molecules of N. sativa, especially α-hederin, could be considered for ongoing drug development strategies against SARS-CoV-2. However, further in vitro and in vivo testing are required to confirm the findings of this study.

Marine species are known as rich sources of metabolites involved mainly in the pharmaceutical industry. This study aimed to evaluate the effect of biologically active compounds in the marine sponge on the SARS-CoV-2 RNA-dependent-RNA polymerase protein (RdRp) using the in-silico method. A total of 51 marine compounds were checked for their possible interaction with SARS-CoV-2 RdRp using Maestro interface for molecular docking, molecular dynamic (MD) simulation, and MM/GBSA method to estimate compounds binding affinities. Among the 51 compounds screened in this study, two (mycalamide A, and nakinadine B) exhibited the lowest docking energy and best interaction. Among these compounds, mycalamide A was identified as a potent inhibitor of SARS-CoV-2 RdRp that showed the best and stable interaction during molecular dynamic simulation, with residues (Asp760 and Asp761) found in the catalytic domain of RdRp. The analysis through MM/GBSA for molecular dynamic simulation results revealed binding energy −59.7 ± 7.18 for Mycalamide A and −56 ± 10.55 for Nakinadine B. These results elucidate the possible use of mycalamide A for treating coronavirus disease. Communicated by Ramaswamy H. Sarma

The dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a novel, promising and emerging biological target for therapeutic intervention in neurodegenerative diseases, especially in Alzheimer’s disease (AD). The molMall database, comprising rare, diverse and unique compounds, was explored for molecular docking-based virtual screening against the DYRK1A protein, in order to find out potential inhibitors. Ligands exhibiting hydrogen bond interactions with key amino acid residues such as Ile165, Lys188 (catalytic), Glu239 (gk+1), Leu241 (gk+3), Ser242, Asn244, and Asp307, of the target protein, were considered potential ligands. Hydrogen bond interactions with Leu241 (gk+3) were considered key determinants for the selection. High scoring structures were also docked by Glide XP docking in the active sites of twelve DYRK1A related protein kinases, viz. DYRK1B, DYRK2, CDK5/p25, CK1, CLK1, CLK3, GSK3β, MAPK2, MAPK10, PIM1, PKA, and PKCα, in order to find selective DYRK1A inhibitors. MM/GBSA binding free energies of selected ligand–protein complexes were also calculated in order to remove false positive hits. Physicochemical and pharmacokinetic properties of the selected six hit ligands were also computed and related with the proposed limits for orally active CNS drugs. The computational toxicity webserver ProTox-II was used to predict the toxicity profile of selected six hits (molmall IDs 9539, 11352, 15938, 19037, 21830 and 21878). The selected six docked ligand–protein systems were exposed to 100 ns molecular dynamics (MD) simulations to validate their mechanism of interactions and stability in the ATP pocket of human DYRK1A kinase. All six ligands were found to be stable in the ATP binding pocket of DYRK1A kinase.

Colchicum luteum L. is an economically important and endangered medicinal plant of the Kashmir Himalaya. The corm extract is used for the treatment of rheumatism, gout, Behcet’s syndrome, and Alzheimer disease. It is also used extensively in plant breeding programs for the doubling of chromosomes. The present study was carried out for two years (2017–2019) to study the genetic diversity of C. luteum, an economically important and endangered medicinal plant of Kashmir Himalaya. The mapping of genetic diversity of C. luteum was estimated using Mahalanobis D2 analysis in the Aharbal (Kulgam), Dhara (Theed), and Baera Baal Hills (Harwan) of Kashmir Valley. The results showed the presence of 5 clusters for 30 populations. There were 17 populations in cluster-1, 1 in cluster-2, 2 in cluster-3, 3 in cluster-4, and 7 in cluster-5. The majority of the population was a group in cluster-1 followed by cluster-5. The maximum intracluster distance (D2 values) was observed in cluster-5 (46.55588) followed by cluster-3 (41.61871), and the maximum inter-cluster distance (D2 values) was observed in cluster-3 (46.55588) followed by cluster-5 (41.61871). Our study revealed that plant species possessed sufficient genetic diversity among the populations. Cluster-5 showed superiority in plant−1 respect of the maximum mean plant height (28.46 cm), leaf area (47.0 cm2), number of seeds plant−1 (26.85), corm length (5.15 cm), corm width (3.17 cm), fresh weight of corm plant (6.87 g), and dry weight of corm plant (4.81 g) as compared to other clusters. Out of five clusters, cluster-5 is a promising one for better yield and yield attributing traits. The present study revealed that plant species possessed sufficient genetic diversity among the populations as 30 populations were arranged into 5 clusters. Therefore, cluster-5, consisting of seven populations from the undisturbed area of Harwan, and consequently the populations from the same cluster can be multiplied for initiating a conservation and breeding program and can serve as a tool for the scientific community to evolve better contemporary varieties of C. luteum with profitable characters such as more yield of corms, etc. This will assist farmers, particularly the marginal farmers, to alleviate their income.

The facile bio-fabrication of zinc oxide (ZnO) nanoparticles (NPs) is described in this study using an aqueous leaf extract of Salvia officinalis&nbsp, L. as an efficient stabilizing/capping agent. Biosynthesis of nanomaterials using phytochemicals present in the plants has received great attention and is gaining significant importance as a possible alternative to the conventional chemical methods. The properties of the bio-fabricated ZnONPs were examined by different techniques, such as UV-visible spectroscopy, X-ray diffraction spectroscopy (XRD), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and thermogravimetric/differential scanning calorimetry analysis (TGA/DTG). The photocatalytic activity of ZnONPs was investigated against methyl orange (MO) under UV light irradiation. Under optimum experimental conditions, ZnONPs exhibited 92.47% degradation of MO. Furthermore, the antifungal activity of bio-fabricated ZnONPs was determined against different clinical Candida albicans isolates following standard protocols of broth microdilution and disc diffusion assay. The susceptibility assay revealed that ZnONPs inhibit the growth of all the tested fungal isolates at varying levels with MIC values ranging from 7.81 to 1.95 µg/mL. Insight mechanisms of antifungal action appeared to be originated via inhibition of ergosterol biosynthesis and the disruption of membrane integrity. Thus, it was postulated that bio-fabricated ZnONPs have sustainable applications in developing novel antifungal agents with multiple drug targets. In addition, ZnONPs show efficient photocatalytic efficiency without any significant catalytic loss after the catalyst was recycled and reused multiple times.

In many real-life situations, it is often observed that the degree of indeterminacy (neutrality) plays an important role along with the satisfaction and dissatisfaction levels of the decision maker(s) (DM(s)) in any decision making process. Due to some doubt or hesitation, it may necessary for DM(s) to take opinions from experts which leads towards a set of conflicting values regarding satisfaction, indeterminacy and dis-satisfaction level of DM(s). In order to highlight the above-mentioned insight, we have developed an effective framework which reflects the reality involved in any decision-making process. In this study, a multiobjective nonlinear programming problem (MO-NLPP) has been formulated in the manufacturing system. A new algorithm, neutrosophic hesitant fuzzy programming approach (NHFPA), based on single-valued neutrosophic hesitant fuzzy decision set has been proposed which contains the concept of indeterminacy hesitant degree along with truth and falsity hesitant degrees of different objectives. In order to show the validity and applicability of the proposed approach, a numerical example has been presented. The superiority of the proposed approach has been shown by comparing with other existing approaches. Based on the present work, conclusions and future scope have been presented.

Glycogenes regulate a large number of biological processes such as cancer and development. In this work, we created an interaction network of 923 glycogenes to detect potential hubs from different mouse tissues using RNA-Seq data. DAVID functional cluster analysis revealed enrichment of immune response, glycoprotein and cholesterol metabolic processes. We also explored nsSNPs that may modify the expression and function of identified hubs using computational methods. We observe that the number of nsSNPs predicted by any two methods to affect protein function is 4, 7 and 2 for FLT1, NID2 and TNFRSF1B. Residues in the native and mutant proteins were analyzed for solvent accessibility and secondary structure change. Analysis of hubs can help in determining their degree of conservation and understanding their functions in biological processes. The nsSNPs proposed in this work may be further targeted through experimental methods for understanding structural and functional relationships of hub mutants.

Ovarian cancer is a leading cause of death due to the fact that most of the patients are diagnosed at an advanced stage(s) of disease progression because it cannot be detected at the early stage. An immunogenic tumor and immunotherapy is strongly pursued through targeting the immune checkpoints. In previous study, the immune signaling pathways and their components have been shown as a key factor for cancer initiation, progression, and finally a scope for diagnosis. Thus, in ovarian cancer the immune-based prognostic signature remains a potential that can be explored further. We have used gene expression GEO dataset with the focus to understand how the signaling pathways and their components altered are relevant to the immune system related functions. Finally, we have explored the possible herbal drug targets (Apigenin, Quercetin, and Resveratrol) based on gene expression profiling. The herbal drug structures have been retrieved from PubChem database and the 3D protein structures for the top-ranked genes have been obtained by using SwissModel tool and in the next step SwissDock tool has been applied for performing docking studies of the herbal drugs against the top ranked differentially expressed genes. We concluded that for ovarian cancer, immune systems associated pathways are TCR, UPS, Foxo, neuroactive ligand-receptor interaction, adrenergic, NK cell, TGF, TNF, NF-kB, BCR, and APC and docking profiling reveals that the most likely targets for quercetin are GNAI3, FGFR1, and LGALS3 while apigenin and resveratrol follow the similar trends in terms of delta G. Network-based study of the docked proteins reveals that FGFR1, GNAI3, RAC1, and RHEB control a large number of DEGs of immune system and the cluster of these genes also connect each other.

Rising levels of arsenic in ground water posing threats to millions of people residing in Indus plains whereas the magnitude of the risk is alarming need to control arsenic from leaching down into ground water becomes essential. The study was designed to assess the potential of three native tree seedlings to reclaim the arsenic affected soils in Pakistan. The study aimed at determining the impact of arsenic application on growth parameters of tree seedlings and accumulation of arsenic in plant parts. The laboratory experiment conducted at the Botanical Garden, University of the Punjab, Lahore revealed that E. camaldulensis, T. arjuna and S. tetrasperma have demonstrated varying adaptability to survive under the arsenic stress environment, establishing them as strong candidates to be exploited for arsenic remediation process. Arsenic treated plants showed reduced growth in terms of stem height, stem diameter, number of branches, number of leaves, root length, total plant length and biomass production as compared to plants grown without arsenic treatment. Arsenic accumulated in all vegetative parts of the plants, however, maximum arsenic accumulation was recorded in roots of E. camaldulensis (37.25 µg kg-1) followed by S. tetrasperma (35.76 µg kg-1) and T. arjuna (24.13 µg kg-1) when arsenic was applied @ 4.0 mg L-1. The study has shown that these trees can be grown on arsenic contaminated fields to reclaim the soil from arsenic content resulting in its substantial reduction leaching in groundwater., Journal of Applied Botany and Food Quality, Vol 91 (2018): Journal of Applied Botany and Food Quality

The West Nile virus (WNV) infections are generally asymptomatic and are considered as immediate concerns of biodefense due to the lack of any therapeutic remedies. In this work, we created an interaction network of 1159 differentially expressed genes to detect potential hub genes from WNV infected primary human macrophages. We go on to explore the genetic variations that can alter the expression and function of identified hub genes (HCLS1, SLC15A3, HCK, and LY96) using the PROVEAN Protein Batch tool and PolyPhen-2. Community analysis of the network revealed that these clusters were enriched in GO terms such as inflammatory response and regulation of proliferation. Analysis of hub genes can aid in determining their degree of conservation and may help us in understanding their functional roles in biological systems. The nsSNPs proposed in this work may be further targeted through experimental methods for improving treatment towards the infection of WNV.

Asian Pacific Journal of Cancer Prevention, 17, 8

Understanding of the three-dimensional structures of proteins that interact with carbohydrates covalently (glycoproteins) as well as noncovalently (protein-carbohydrate complexes) is essential to many biological processes and plays a significant role in normal and disease-associated functions. It is important to have a central repository of knowledge available about these protein-carbohydrate complexes as well as preprocessed data of predicted structures. This can be significantly enhanced by toolsde novowhich can predict carbohydrate-binding sites for proteins in the absence of structure of experimentally known binding site. PROCARB is an open-access database comprising three independently working components, namely, (i)Core PROCARB module, consisting of three-dimensional structures of protein-carbohydrate complexes taken from Protein Data Bank (PDB), (ii)Homology Models module, consisting of manually developed three-dimensional models of N-linked and O-linked glycoproteins of unknown three-dimensional structure, and (iii)CBS-Pred prediction module, consisting of web servers to predict carbohydrate-binding sites using single sequence or server-generated PSSM. Several precomputed structural and functional properties of complexes are also included in the database for quick analysis. In particular, information about function, secondary structure, solvent accessibility, hydrogen bonds and literature reference, and so forth, is included. In addition, each protein in the database is mapped to Uniprot, Pfam, PDB, and so forth.

Plasmodium falciparum, the deadly protozoan parasite, causes malaria. Malaria remains one of the deadliest infectious diseases in the world. The RNA-Seq data sets were downloaded from NCBI Short Read Archive under accession number SRP009370 for our analysis. Differentially expressed genes (DEGs) between Ring (R) and early trophozoite (ET), late trophozoite (LT), schizont (Sc), gametocyte stages (GII), gametocyte stages (GV), ookinete (Oo) stages are 2442, 2796, 2935, 2807, 2180, 2895 respectively. There are total 4594 unique DEGs in the samples. DAVID was used to categorize enriched biological themes in the list of DEGs. It can be seen that main functions related to GO term ‘Biological Process’ are antigenic variation, pathogenesis, single organismal cell-cell adhesion, GO term ‘Cellular Component’ are host cell plasma membrane, infected host cell surface knob and GO term ‘Molecular Function’ are cell adhesion molecule binding, ATP-dependent RNA helicase activity. We found that PF3D7_1000400, PF3D7_1000600, PF3D7_0900500, PF3D7_0901500, PF3D7_0937400 were most up regulated and PF3D7_0632800, PF3D7_0711700, PF3D7_0712400, PF3D7_0712600, PF3D7_0712900, PF3D7_0808600 and PF3D7_0808700 were most down regulated genes involved in antigenic variation. Also PF3D7_0930300 was most up-regulated in Sc, LT and Oo stages and PF3D7_0936500 was most up-regulated in GV stage and PF3D7_0632800, PF3D7_0711700, PF3D7_0712400, PF3D7_0712600, PF3D7_0712900, PF3D7_0808600, PF3D7_0808700 were most down regulated genes involved in pathogenesis. A total of 300 pathways were predicted using KAAS server. Majority of the DEGs were found to be associated with important biological pathways such as metabolic pathways, biosynthesis of secondary metabolites, ribosome, spliceosome, biosynthesis of antibiotics, purine metabolism.

The information necessary for proteins to correctly fold into biologically active three dimensional (3D) structures is present in the amino acid sequence. The ways by which proteins fold still remain one of the unexplained mysteries in the field of protein biochemistry. Investigating the impact and consequences of protein misfolding can help decipher the molecular causes behind the complex amyloid diseases such as Alzheimer’s disease (AD) and Parkinson’s disease. Various participating molecular entities like amyloid beta (Aβ), tau protein, and non-beta sheets are facilitating the pathogenesis of Alzheimer’s disease. Understanding their structure as well as their mechanism of action is useful to decode the therapeutic treatment for these complex diseases.

Monoacylglycerol lipase (MAGL) is one of the key enzymes of the endocannabinoid system (ECS). It hydrolyzes one of the major endocannabinoid, 2-arachidonoylglycerol (2-AG), an endogenous full agonist at G protein coupled cannabinoid receptors CB1 and CB2. Numerous studies showed that MGL inhibitors are potentially useful for the treatment of pain, inflammation, cancer and CNS disorders. These provocative findings suggested that pharmacological inhibition of MAGL function may confer significant therapeutic benefits. In this study, we presented hybrid ligand and structure-based approaches to obtain a novel set of virtual leads as MAGL inhibitors. The constraints used in this study, were Glide score, binding free energy estimates and ADME properties to screen the ZINC database, containing approximately 21 million compounds. A total of seven virtual hits were obtained, which showed significant binding affinity towards MAGL protein. Ligand, ZINC24092691 was employed in complex form with the protein MAGL, for molecular dynamics simulation study, because of its excellent glide score, binding free energy and ADME properties. The RMSD of ZINC24092691 was observed to stay at 0.1 nm (1 A) in most of the trajectories, which further confirmed its ability to inhibit the protein MAGL. The hits were then evaluated for their ability to inhibit human MAGL. The compound ZINC24092691 displayed the noteworthy inhibitory activity reducing MAGL activity to 21.15% at 100 nM concentration, with an IC50 value of 10 nM.

Glycogenes regulate a wide array of biological processes in the development of organisms as well as different diseases such as cancer, primary open-angle glaucoma, and renal dysfunction. The objective of this study was to explore the role of differentially expressed glycogenes (DEGGs) in three major tissues such as brain, muscle, and liver using mouse RNA-seq data, and we identified 579, 501, and 442 DEGGs for brain versus liver (BvL579), brain versus muscle (BvM501), and liver versus muscle (LvM442) groups. DAVID functional analysis suggested inflammatory response, glycosaminoglycan metabolic process, and protein maturation as the enriched biological processes in BvL579, BvM501, and LvM442, respectively. These DEGGs were then used to construct three interaction networks by using GeneMANIA, from which we detected potential hub genes such asPEMTandHPXN(BvL579),IGF2andNID2(BvM501), andSTAT6andFLT1(LvM442), having the highest degree. Additionally, our community analysis results suggest that the significance of immune system related processes in liver, glycosphingolipid metabolic processes in the development of brain, and the processes such as cell proliferation, adhesion, and growth are important for muscle development. Further studies are required to confirm the role of predicted hub genes as well as the significance of biological processes.

UNLABELLED To investigate the functional sites on a protein and the prediction of binding sites (residues)in proteins, it is often required to identify the binding site residues at different distance threshold from protein three dimensional (3D)structures. For the study of a particular protein chain and its interaction with the ligand in complex form, researchers have to parse the output of different available tools or databases for finding binding-site residues. Here we have developed a tool for calculating amino acid contact distances in proteins at different distance threshold from the 3D-structure of the protein. For an input of protein 3D-structure, ContPro can quickly find all binding-site residues in the protein by calculating distances and also allows researchers to select the different distance threshold, protein chain and ligand of interest. Additionally, it can also parse the protein model (in case of multi model protein coordinate file)and the sequence of selected protein chain in Fasta format from the input 3D-structure. The developed tool will be useful for the identification and analysis of binding sites of proteins from 3D-structure at different distance thresholds. AVAILABILITY IT CAN BE ACCESSED AT: http://procarb.org/contpro/

Background Adenine and guanine phosphates are involved in a number of biological processes such as cell signaling, metabolism and enzymatic cofactor functions. Binding sites in proteins for these ligands are often detected by looking for a previously known motif by alignment based search. This is likely to miss those where a similar binding site has not been previously characterized and when the binding sites do not follow the rule described by predefined motif. Also, it is intriguing how proteins select between adenine and guanine derivative with high specificity. Results Residue preferences for AMP, GMP, ADP, GDP, ATP and GTP have been investigated in details with additional comparison with cyclic variants cAMP and cGMP. We also attempt to predict residues interacting with these nucleotides using information derived from local sequence and evolutionary profiles. Results indicate that subtle differences exist between single residue preferences for specific nucleotides and taking neighbor environment and evolutionary context into account, successful models of their binding site prediction can be developed. Conclusion In this work, we explore how single amino acid propensities for these nucleotides play a role in the affinity and specificity of this set of nucleotides. This is expected to be helpful in identifying novel binding sites for adenine and guanine phosphates, especially when a known binding motif is not detectable.

Rubber trees infected with a host-specific cassiicolin toxin often experience considerable leaf fall, which in turn results in loss of crop productivity. It was recently revealed that cassiicolin-specific single-chain variable fragments (scFv) can successfully reduce the toxic effects of cassiicolin. However, the detailed mechanism of antibody action remains poorly understood. The primary sequence of the newly sequenced cassiicolin-specific scFv was highly homologous to several members of single-chain antibodies in the 14B7 family. In this study, with the aid of homology modeling, the three-dimensional structure of cassiicolin-specific scFv was elucidated, and was found to exhibit a characteristic immunoglobulin fold that mainly consists of β sheets. Additionally, molecular docking between the modeled scFv antibody and the available three-dimensional crystal structure of cassiicolin toxin was also performed. The predicted structural complex and the change in accessible surface area between the toxin and the scFv antibody upon complexation reveal the potential role of certain complementarity determining region (CDR) amino acid residues in the formation of the complex. These computational results suggest that mutagenesis experiments that are aimed at validating the model and improving the binding affinity of cassiicolin-specific scFv antibodies for the toxin should be performed.

In the present study, we have evaluated prophylactic role of various immunomodulators viz. lipopolysachharide, protein A and tuftsin to impart protection against experimental candidiasis in leukopenic mice. Both free as well as liposomised form of nystatin was not effective enough in offering complete cure against less susceptible isolate of Candida albicans (JNMCR) infection in immunodebilitant mice. Interestingly, the pretreatment of leukopenic mice with immunomodulators before challenging them with C. albicans increased therapeutic efficacy of the nystatin against systemic candidiasis. Efficacy of the treatment was evaluated on the basis of survival of the animals as well as fungal load in systemic circulation and various organs viz. liver, kidney, spleen and lungs of the treated animals.

In order to develop a prospective chemotherapeutic agent against opportunistic infections, it is important to know that host factors such as degree of immunological debility as well as recovery of immune functions to normality may contribute significantly to a successful elimination of the pathogens. We demonstrated previously that concomitant delivery of antimicrobial agents and immunomodulators to the pathogen harbouring-host contributes to the complete elimination of the deep-seated fungal infections (aspergillosis and candidiasis) in animals with normal immune status. Considering that neutropenic hosts are the main targets of such infections, it can be argued about the potential of the immunomodulator-based therapy in subjects with non-functional immune system. To resolve the hypothesis, we studied the role of immunomodulator tuftsin against experimental murine candidiasis in temporarily neutropenic Balb/c mice. The neutropenic mice were challenged with an isolate of Candida albicans that was showing less susceptibility to both free and liposomised-amphotericin B. The co-administration of tuftsin increased the efficiency of liposomised-polyene antibiotics (nystatin and amphotericin B) against experimental murine candidiasis in immunocompromised Balb/c mice. Pretreatment with liposomised tuftsin prior to C. albicans infection clearly enhanced protection against candidiasis, suggesting a prophylactic role of tuftsin in normal and temporarily neutropenic animals.