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Background. Breast cancer is one of the most common types of cancer diagnosed and the second leading cause of death among women. Breast cancer susceptibility proteins of type 1 and 2 are human tumor suppressor genes. Genetic variations/mutations in these two genes lead to overexpression of human breast tumor suppressor genes (e.g., BRCA1, BRCA2), which triggers uncontrolled duplication of cells in humans. In addition, multidrug resistance protein 1 (MDR1), an important cell membrane protein that pumps many foreign substances from cells, is also responsible for developing resistance to cancer chemotherapy. Aim of the Study. The aim of this study was to analyze some natural compounds or their derivatives as part of the development of strong inhibitors for breast cancer. Methodology. Molecular docking studies were performed using compounds known in the literature to be effective against BRCA1 and BRCA2 and MDR1, with positive control being 5-fluorouracil, an antineoplastic drug as a positive control. Results. The binding affinity of the compounds was analyzed, and it was observed that they had a better binding affinity for the target proteins than the standard drug 5-fluorouracil. Among the compounds analyzed, α-hederin, andrographolide, apigenin, asiatic acid, auricular acid, sinularin, curcumin, citrinin, hispolon, nerol, phytol, retinol palmitate, and sclareol showed the best binding affinity energy to the BRCA1, BRCA2, and MDR1 proteins, respectively. Conclusions. α-Hederin, andrographolide, apigenin, asiatic acid, auricular acid, hispolon, sclareol, curcumin, citrinin, and sinularin or their derivatives can be a good source of anticancer agents in breast cancer.

The demand for medicinal plants and their derived substances is increasing day by day due to their relevance in the context of drug discovery and development. The goal of this investigation is to assess the pharmacological and phytochemical potentials of the grossly underexplored Antidesma montanum Blume (Family: Phyllanthaceae). The methanolic extract of the leave of this plant was fractionated and then followed by initial screening of phytochemical. The investigation of the pharmacological potential, which includes antioxidant, antidiarrheal, anti-inflammatory, analgesic, anti-pyretic, and anxiolytic evaluations, was accomplished using an in vitro free radical scavenging assay with 2,2-diphenyl-1-picrylhydrazyl (DPPH), castor oil-induced diarrheal test, egg albumin test, acetic acid-induced writhing model, brewer’s yeast induced fever test, swing test, open field, and light-dark test, respectively. The investigation o phytochemicals proposes that the methanol extract of A. montanum possesses flavonoids, tannins, terpenoids, saponins, amino acids, fixed oils, and sterols. Pharmacological evaluation suggests that A. montanum possesses significant antioxidant, anti-diarrheal, anti-inflammatory, and analgesic effects. The methanol and chloroform fractions exhibited better DPPH radical scavenging activities with an IC50: 103 ± 0.05 and 108.7 ± 0.05 µg/ml, respectively. The methanol and chloroform fractions also showed anti-inflammatory capacities in the egg albumin (IC50 values: 89.10 ± 0.07 and 92.85 ± 0.07 µg/ml, respectively) model. The plant also showed anti-pyretic and anxiolytic activities in a dose-dependent manner. One of the possible sources of phytotherapeutic lead compounds is A. montanum. To extract and analyze the key bioactive components of this essential therapeutic plant, more research is required.

Diterpenes and their derivatives have many biological activities, including anti-inflammatory and immunomodulatory effects. To date, several diterpenes, diterpenoids, and their laboratory-derived products have been demonstrated for antiarthritic activities. This study summarizes the literature about diterpenes and their derivatives acting against rheumatoid arthritis (RA) depending on the database reports until 31 August 2021. For this, we have conducted an extensive search in databases such as PubMed, Science Direct, Google Scholar, and Clinicaltrials.gov using specific relevant keywords. The search yielded 2708 published records, among which 48 have been included in this study. The findings offer several potential diterpenes and their derivatives as anti-RA in various test models. Among the diterpenes and their derivatives, andrographolide, triptolide, and tanshinone IIA have been found to exhibit anti-RA activity through diverse pathways. In addition, some important derivatives of triptolide and tanshinone IIA have also been shown to have anti-RA effects. Overall, findings suggest that these substances could reduce arthritis score, downregulate oxidative, proinflammatory, and inflammatory biomarkers, modulate various arthritis pathways, and improve joint destruction and clinical arthritic conditions, signs, symptoms, and physical functions in humans and numerous experimental animals, mainly through cytokine and chemokine as well as several physiological protein interaction pathways. Taken all together, diterpenes, diterpenoids, and their derivatives may be promising tools for RA management.

Dengue is a mosquito-borne viral infection, with its prevention and control depending on effective vector control measures. At present, dengue virus (DENV) is an epidemic in more than 100 countries of Southeast Asia, Africa, Eastern Mediterranean, the Americas and the Western Pacific. Several alkaloids isolated from natural herbs can serve as a reservoir for antiDENV drug development. Traditionally, plant extracts rich in alkaloids are used for the treatment of fever and have also revealed antimicrobial activity against various pathogenic bacteria, fungi and virus. The present narrative review collates the literature-based scenario of alkaloids and derivatives acting on DENV. The mechanism of action of such alkaloids with antiDENV and vector activity is also discussed.

Objective To explore potential natural products against severe acute respiratory syndrome coronavirus (SARS-CoV-2) via the study of structural and non-structural proteins of human coronaviruses. Methods In this study, we performed an in-silico survey of 25 potential natural compounds acting against SARS-CoV-2. Molecular docking studies were carried out using compounds against 3-chymotrypsin-like protease (3CLPRO), papain-like protease (PLPRO), RNA-dependent RNA polymerase (RdRp), non-structural protein (nsp), human angiotensin converting enzyme 2 receptor (hACE2R), spike glycoprotein (S protein), abelson murine leukemia viral oncogene homolog 1 (ABL1), calcineurin-nuclear factor of activated T-cells (NFAT) and transmembrane protease serine 2. Results Among the screened compounds, amentoflavone showed the best binding affinity with the 3CLPRO, RdRp, nsp13, nsp15, hACE2R. ABL1 and calcineurin-NFAT; berbamine with hACE2R and ABL1; cepharanthine with nsp10, nsp14, nsp16, S protein and ABL1; glucogallin with nsp15; and papyriflavonol A with PLPRO protein. Other good interacting compounds were juglanin, betulinic acid, betulonic acid, broussooflavan A, tomentin A, B and E, 7-methoxycryptopleurine, aloe emodin, quercetin, tanshinone I, tylophorine and furruginol, which also showed excellent binding affinity towards a number of target proteins. Most of these compounds showed better binding affinities towards the target proteins than the standard drugs used in this study. Conclusion Natural products or their derivatives may be one of the potential targets to fight against SARS-CoV-2. Electronic Supplementary Material Supplementary materials (Appendixes 1–6) are available in the online version of this article at DOI: 10.1007/s11655-021-3504-5

Dengue remains one of the most serious and widespread mosquito-borne viral infections in human beings, with serious health problems or even death. About 50 to 100 million people are newly infected annually, with almost 2.5 billion people living at risk and resulting in 20,000 deaths. Dengue virus infection is especially transmitted through bites of Aedes mosquitos, hugely Hindawi BioMed Research International Volume 2021, Article ID 4224816, 23 pages https://doi.org/10.1155/2021/4224816 spread in tropical and subtropical environments, mostly found in urban and semiurban areas. Unfortunately, there is no particular therapeutic approach, but prevention, adequate consciousness, detection at earlier stage of viral infection, and appropriate medical care can lower the fatality rates. This review offers a comprehensive view of production, transmission, pathogenesis, and control measures of the dengue virus and its vectors.

Ascorbic acid (AA) has been reported for the management of diarrhea. The anti-diarrheal potential and modulatory activities of AA on some commonly used anti-diarrheal drugs were investigated. For this purpose, the activities of AA on castor oil-induced diarrhea in Swiss mice were examined. As standard anti-diarrheal agents, we used prazosin, propranolol, loperamide, and nifedipine with or without AA. The results revealed that AA at 25 mg/kg (i.p.) and all other standard drugs exhibited significant (p < 0.05) diarrheal attenuating activities in mice. However, the impact was more pronounced in the loperamide and propranolol groups. AA administrated with prazosin and propranolol had a higher rate of latent periods and a lower rate of diarrheic secretion during the study period (4 h) than that of the other single or mixed groups. Furthermore, a molecular docking study illustrated that AA displayed good binding affinities with (α1) (–5.2 Kcal/mol), α2b (–5.4 Kcal/mol), α2c (-5.6 Kcal/mol), β1(–5.3 Kcal/mol) and β2(–6.4 Kcal/mol) adrenoceptors. Of note, AA exerted a significant anti-diarrheal effect and it was seen to modulate the anti-diarrheal effects of α- and β-adrenergic receptor blocking agents in Swiss mice.

Fish diversity indices and their correlation with seasonal fluctuation of physicochemical parameters of Hasadanga beel was aimed to be studied. A three-year study on the relationship between the seasonal fluctuation of water quality parameters and fish biodiversity indices was conducted in Hasadanga Beel, a floodplain lake of Nadia district, West Bengal to measure the ecological health of the lake. Samples of water and fish species were collected at pre-monsoon, monsoon and post-monsoon period from 2015-2017 to estimate physicochemical parameters of water and fish biodiversity indices i.e. Shannon-Weaver species diversity index, Margalef’s Species richness index, Pielou’s Species evenness index and Simpson’s index of dominance. Total of 34 different fish species belonging to 8 Orders were found during the study period which varies seasonally. Water temperature (20.0-31.4 °C), pH (7.70-8.75), dissolved oxygen (3.9-5.0 mg/l), Free CO2 (0.0-15.0 mg/l), total alkalinity (156-193 mg/l), hardness (113-145 mg/l), and BOD (1.03-1.94 mg/l) values varied significantly (p

Compared to healthy pregnant women, changes in erythrocytic membrane anionic charge (EAC) and urinary glycosaminoglycans (UGAGS) have been reported in African women with preeclampsia. A single prev...

The progression of biotechnology and genetic engineering to produce transgenic animals by familiarizing the foreign DNA into the germline of an animal has elevated the potential of biological research to an unprecedented level. This technology not only beneficial in human welfare, society, and the environment but also harmful. At present, many transgenic species (goats, chickens, pigs, cows, mice, rabbits, sheep, etc.) are considered for research applications as well as latent profitable pharmaceutical productively. Transgenic animals are applied as the different models for the experiment of different diseases including HIV/AIDS, Alzheimer’s, Cardiovascular, and Diabetes Mellitus, Angiogenesis, and Cancer disease. The main disadvantages of transgenic animals are mutagenesis and function disorders, ecological problems, antibiotic resistance, and population of clones.

Lasia spinosa (L.) is used ethnobotanically for the treatment of various diseases, including rheumatoid arthritis, inflammation of the lungs, bleeding cough, hemorrhoids, intestinal diseases, stomach pain, and uterine cancer. This review is aimed at summarizing phytochemistry and pharmacological data with their molecular mechanisms of action. A search was performed in databases such as PubMed, Science Direct, and Google Scholar using the keywords: “Lasia spinosa,” then combined with “ethnopharmacological use,” “phytochemistry,” and “pharmacological activity.” This updated review included studies with in vitro, ex vivo, and in vivo experiments with compounds of known concentration and highlighted pharmacological Hindawi Oxidative Medicine and Cellular Longevity Volume 2021, Article ID 1602437, 12 pages https://doi.org/10.1155/2021/1602437 mechanisms. The research results showed that L. spinosa contains many important nutritional and phytochemical components such as alkanes, aldehydes, alkaloids, carotenoids, flavonoids, fatty acids, ketones, lignans, phenolics, terpenoids, steroids, and volatile oil with excellent bioactivity. The importance of this review lies in the fact that scientific pharmacological evidence supports the fact that the plant has antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antidiarrheal, antihelminthic, antidiabetic, antihyperlipidemic, and antinociceptive effects, while protecting the gastrointestinal system and reproductive. Regarding future toxicological and safety data, more research is needed, including studies on human subjects. In light of these data, L. spinosa can be considered a medicinal plant with effective bioactives for the adjuvant treatment of various diseases in humans.

The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague-Dawley rats, along with the gas chromatography-mass spectrometry (GC-MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC-MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC-MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (-8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.

Ebselen (SPI-1005) is an active selenoorganic compound that can be found potential inhibitory activity against different types of viral infections such as zika virus, influenza A virus, HCV, and HIV-1; and also be found to exhibit promising antiviral activity against SARS-CoV-2 in cell-based assays but its particular target action against specific non-structural and structural proteins of SARS-CoV-2 is unclear to date. The purpose of this study is to evaluate the anti-SARS-CoV-2 efficacy of Ebselen along with the determination of the specific target among the 12 most common target proteins of SARS-CoV-2. AutoDock Vina in PyRx platform was used for docking analysis against the 12 selected SARS-CoV-2 encoded drug targets. ADME profiling was examined by using SwissADME online server. The stability of binding mode in the target active sites was evaluated using molecular dynamics (MD) simulation studies through NAMD and Desmond package software application. In this docking study, we recognized that Ebselen possesses the highest affinity to N protein (C domain) (PDB ID: 6YUN) and PLpro (PDB ID: 6WUU) among the selected SARS-CoV-2 targets showing -7.4 kcal/mol binding energy. The stability of Ebselen-6YUN and Ebselen-6WUU was determined by a 100 ns trajectory of all-atom molecular dynamics simulation. Structural conformation of these two complexes displayed stable root mean square deviation (RMSD), while root mean square fluctuations (RMSF) were also found to be consistent. This molecular docking study may propose the efficiency of Ebselen against SARS-CoV-2 to a significant extent which makes it a candidature of COVID-19 treatment.Communicated by Ramaswamy H. Sarma.

Wilson’s disease is a disease of abnormal copper metabolism in which free serum copper level is raised. The objective of the study was to determine, whether in Wilson disease, l-cysteine/l-cystine influx into RBC was decreased or not and the specific amino acid transporter affected by copper in normal human RBC. For l-cysteine/l-cystine influx, ten untreated cases, ten treated cases and ten age and sex matched healthy controls were recruited. To study the effect of copper on l-cysteine/l-cystine influx in RBC, 15 healthy subjects were selected. RBC GSH and l-cysteine/l-cystine influx were estimated by Beautler’s and Yildiz’s method respectively. In untreated cases, l-cysteine/l-cystine influx and erythrocyte GSH level were decreased showing that elevated level of free copper in serum or media decreased l-cysteine/l-cystine influx in human RBC. Copper treatment inhibited L amino acid transporter in normal RBC specifically.

In this study, the authors show that online multiplayer gaming via local Wi-Fi can be used as a “social lubricant” to increase social connections between co-located strangers at a cafe. In a field experiment in real world cafes, they recruited people who were sitting alone at the same cafe to play an online game together using iPads, from wherever each happened to be sitting. Some pairs could see each other; some were facing in opposite directions, some were in separate rooms. Visibility influenced how and how much players communicated outside of the game, but had no impact on enjoyment or self-reported experience of social connection. The authors measured “friendship drive” and found that social yearners were more interested in gaming with a stranger and more likely to hope to see their gaming partner again than were socially satiated players. Friendship drive did not impact communication between players or feeling social connection. DOI: 10.4018/jgcms.2012040101 2 International Journal of Gaming and Computer-Mediated Simulations, 4(2), 1-18, April-June 2012 Copyright © 2012, IGI Global. Copying or distributing in print or electronic forms without written permission of IGI Global is prohibited. more “bonding social capital” (small, strong networks with strong emotional support) than

A comparative study has been carried out on the microstructural evolution and hardness of the Al-4.5Cu alloy and in-situ Al-4.5Cu-5TiB2 composite, either water quenched from, or subjected to, rolling at mushy zone temperatures. The cast alloy shows coarse α-Al dendrites, while the composite contains rosette-type grains with TiB2 particles located at the grain boundaries. The plate-shaped specimens, in cast or pre-hot-rolled conditions, have been rolled at temperatures corresponding to 10, 20, or 30 vol pct liquid to thickness reductions in the range of 2.5 to 10 pct. While the alloy could be rolled defect free, the cast composites undergo alligatoring, except when thickness reduction is 5 pct or lower at 30 vol pct liquid. Alligatoring is caused by strain localization and shear failure, and is prevented partially on prior hot rolling, causing homogenization and equiaxed grain formation. Mushy state rolling leads to nearly equiaxed grains having bimodal size distributions. The surfaces with a larger volume fraction of finer grains exhibit higher microhardness than the center. Exposure to mushy zone causes grain growth in the alloy but not in the composite, due to Zener pinning by TiB2 particles. On rolling at low liquid content to a large thickness reduction, the unmelted grains deform and work-harden significantly, causing an increase in hardness.

In thermoforming technique thermoplastic sheets are heated up well above their glass transition temperature and formed to the required shape by using an appropriate mold. Characterization of thermoplastic materials for thermoforming can be accomplished by employing polymer bubble inflation and rheology tests instead of undertaking expensive biaxial tensile testing. Polymer bubble inflation technique is very sensitive to process condition variations, so a robust experimental methodology is essential. Design and development of one such experimental system was undertaken by carrying out a variety of preliminary tests. This paper presents the experimental methodology developed for polymer bubble inflation. The developed experimental system demonstrates highly repeatable polymer bubble inflations. Bubble inflations were conducted at different temperatures and different diameter circular clamping using acrylonitrile butadiene styrene (ABS) thermoplastic. Polymer sheet initial sag due to heating and its influenc...

This paper examines how young adults process information related to privacy, and how that affects their attitude towards behavioral targeted advertising. Differences between computer novices and experts were examined based on the Elaboration Likelihood Model (Petty & Cacioppo, 1984), which argues that people who have the ability to process information do so differently than those who do not have the ability. Consistent with the theory, we found that computer novices were relying on peripheral cues to process information related to security due to their lack of knowledge. We also identified an “uncanny valley” effect where people liked customization of targeted advertisements, but then became uncomfortable if the advertisements seemed to know too much of their past behavior until the suggestions were perfectly aligned with their interests.

This study explores social ranks, participations and knowledge dissemination within an online game design community. We describe how social ranks have evolved and supported the overall participation over time. We argue that higher social rank members drive the community in terms of forming effective idea and knowledge sharing. A multi-method analysis technique using content analysis, qualitative interview, and server level quantitative data of users in Sploder.com supports our claim.