Potential Epha2 Receptor Blockers Involved in Cerebral Malaria from Taraxacum officinale, Tinospora cordifolia, Rosmarinus officinalis and Ocimum basilicum: A Computational Approach.

Cerebral malaria (CM) is a severe manifestation of parasite infection caused by Plasmodium species. In 2018, there were approximately 228 million malaria cases worldwide, resulting in about 405,000 deaths. Survivors of CM may live with lifelong post-CM consequences apart from an increased risk of childhood neurodisability. EphA2 receptors have been linked to several neurological disorders and have a vital role in the CM-associated breakdown of the blood-brain barrier. Molecular docking (MD) studies of phytochemicals from Taraxacum officinale, Tinospora cordifolia, Rosmarinus officinalis, Ocimum basilicum, and the native ligand ephrin-A were conducted to identify the potential blockers of the EphA2 receptor. The software program Autodock Vina 1.1.2 in PyRx-Virtual Screening Tool and BIOVIA Discovery Studio visualizer was used for this MD study. The present work showed that blocking the EphA2 receptor by these phytochemicals prevents endothelial cell apoptosis by averting ephrin-A ligand-expressing CD8+ T cell bioadhesion. These phytochemicals showed excellent docking scores and binding affinity, demonstrating hydrogen bond, electrostatic, Pi-sigma, and pi alkyl hydrophobic binding interactions when compared with native ligands at the EphA2 receptor. The comparative MD study using two PDB IDs showed that isocolumbin, carnosol, luteolin, and taraxasterol have better binding affinities (viz. -9.3, -9.0, -9.5, and -9.2 kcal/mol, respectively). Ocimum basilicum phytochemicals showed a lower docking score but more binding interactions than native ligands at the EphA2 receptor for both PDB IDs. This suggests that these phytochemicals may serve as potential drug candidates in the management of CM. We consider that the present MD study provides leads in drug development by targeting the EphA2 receptor in managing CM. The approach is innovative because a role for EphA2 receptors in CM has never been highlighted.

A Novel Diabetes Healthcare Disease Prediction Framework Using Machine Learning Techniques.

Diabetes is a chronic disease that continues to be a significant and global concern since it affects the entire population's health. It is a metabolic disorder that leads to high blood sugar levels and many other problems such as stroke, kidney failure, and heart and nerve problems. Several researchers have attempted to construct an accurate diabetes prediction model over the years. However, this subject still faces significant open research issues due to a lack of appropriate data sets and prediction approaches, which pushes researchers to use big data analytics and machine learning (ML)-based methods. Applying four different machine learning methods, the research tries to overcome the problems and investigate healthcare predictive analytics. The study's primary goal was to see how big data analytics and machine learning-based techniques may be used in diabetes. The examination of the results shows that the suggested ML-based framework may achieve a score of 86. Health experts and other stakeholders are working to develop categorization models that will aid in the prediction of diabetes and the formulation of preventative initiatives. The authors perform a review of the literature on machine models and suggest an intelligent framework for diabetes prediction based on their findings. Machine learning models are critically examined, and an intelligent machine learning-based architecture for diabetes prediction is proposed and evaluated by the authors. In this study, the authors utilize our framework to develop and assess decision tree (DT)-based random forest (RF) and support vector machine (SVM) learning models for diabetes prediction, which are the most widely used techniques in the literature at the time of writing. It is proposed in this study that a unique intelligent diabetes mellitus prediction framework (IDMPF) is developed using machine learning. According to the framework, it was developed after conducting a rigorous review of existing prediction models in the literature and examining their applicability to diabetes. Using the framework, the authors describe the training procedures, model assessment strategies, and issues associated with diabetes prediction, as well as solutions they provide. The findings of this study may be utilized by health professionals, stakeholders, students, and researchers who are involved in diabetes prediction research and development. The proposed work gives 83% accuracy with the minimum error rate.

Application of phytoremediation technology in decontamination of a fish culture pond fed with coal mine effluent using three aquatic macrophytes.

In the present study, three aquatic macrophytes, Eichhornia crassipes, Salvinia molesta, and Pistia stratiotes were used to assess their relative efficacies in decontamination of a fish culture pond, regularly fed with coal mine effluent (CME). The level of metals like Fe, Mn, Ni, Zn, Cu, Pb, Cr, and Cd were much higher in CME-fed pond water than their recommended limits in drinking water set by the Bureau of Indian standards and in effluents by the Environmental Protection Agency. The levels of metal were lowered substantially in CME-fed pond water after exposure of the above plants to such water, however, metal levels in the plants increased tremendously. The increased metal levels in plants severely damaged their physiological and biochemical processes. The contents of chlorophyll a, b and carotenoid were reduced by 63.2, 64.2, and 46.3%, respectively, in E. crassipes, 41, 57.4, and 57.8% in S. molesta, and 42, 62, and 61% in P. stratiotes. The accumulating metals also generated oxidative stress in plants, as evident from the increased superoxide dismutase and catalase activities and enhanced malondialdehyde content. The E. crassipes was the most potent in absorbing the metals from the CME-fed pond water, followed by S. molesta and P. stratiotes.

Coal mine effluent-led bioaccumulation of heavy metals and histopathological changes in some tissues of the catfish Clarias batrachus.

Coal mining generates huge quantity of toxic effluent which consistently pollutes the neighboring wetlands where the local inhabitants regularly cultivate edible fishes. In the present study the concentration of heavy metals Fe, Zn, Cu, Mn, Ni, Cd, Pb and Cr were analyzed in the water and various tissues of edible catfish Clarias batrachus reared in a pond receiving effluents from Rajrappa coal mine, Jharkhand, India. The metal concentrations in the pond water were dramatically higher (Fe 350%, Zn 423%, Cu 12%, Mn 7029%, Ni 713%, Cd 1700%, Pb 4333% and Cr 588%) than the safe limit of Environmental Pollution Agency (2003) as well as the control tap water. Excessive amounts of metals in effluent caused their substantial transfer to the different tissues of the catfish reared in such ponds. Results showed that accumulation of metals in fish tissues were in the following order: liver > kidney > air breathing organ (ABO) > gills > skin > brain > muscles. Among the various tissues the highest accumulation of most of the metals was recorded in the liver (2.05-271.28 mg/kg dry weight) and lowest in the muscles (1.39-30.27 mg/kg dry weight), while the concentration of metals in other tissues ranged in between. The accumulation of heavy metals in tissues appears to cause remarkable histopathological alterations in skin, gills, ABO, liver and kidney that might be leading to deleterious effect on fish physiology and consequently impact the consumers of such fishes.

Decontamination of coal mine effluent generated at the Rajrappa coal mine using phytoremediation technology.

Toxicity of the effluent generated at the Rajrappa coal mine complex under the Central Coalfields Limited (CCL, a subsidiary of Coal India Limited) in Jharkhand, India was investigated. The concentrations (mg L-1) of all the toxic metals (Fe, Mn, Ni, Zn, Cu, Pb, Cr, and Cd) in the coal mine effluent were above the safe limit suggested by the Environmental Protection Agency (EPA 2003). Among these, Fe showed the highest concentration (18.21 ± 3.865), while Cr had the lowest effluent concentration (0.15 ± 0.014). Efforts were also made to detoxify the effluent using two species of aquatic macrophytes namely "'Salvinia molesta and Pistia stratiotes." After 10 days of phytoremediation, S. molesta removed Pb (96.96%) > Ni (97.01%) > Cu (96.77%) > Zn (96.38%) > Mn (96.22%) > Fe (94.12%) > Cr (92.85%) > Cd (80.99%), and P. stratiotes removed Pb (96.21%) > Fe (94.34%) > Ni (92.53%) > Mn (85.24%) > Zn (79.51%) > Cr (78.57%) > Cu (74.19%) > Cd (72.72%). The impact of coal mine exposure on chlorophyll content showed a significant decrease of 42.49% and 24.54% from control values in S. molesta and P. stratiotes, respectively, perhaps due to the damage inflicted by the toxic metals, leading to the decay of plant tissues.

Highly efficient micellar extraction of toxic picric acid into novel ionic liquid: Effect of parameters, solubilization isotherm, evaluation of thermodynamics and design parameters.

A simple and new approach in cloud point extraction (CPE) method was developed for removal of picric acid (PA) by the addition of N,N,N,N',N',N'-hexaethyl-ethane-1,2-diammonium dibromide ionic liquid (IL) in non-ionic surfactant Triton X-114 (TX-114). A significant increase in extraction efficiency was found upon the addition of dicationic ionic liquid (DIL) at both nearly neutral and high acidic pH. The effects of different operating parameters such as pH, temperature, time, concentration of surfactant, PA and DIL on extraction of PA were investigated and optimum conditions were established. The extraction mechanism was also proposed. A developed Langmuir isotherm was used to compute the feed surfactant concentration required for the removal of PA up to an extraction efficiency of 90%. The effects of temperature and concentration of surfactant on various thermodynamic parameters were examined. It was found that the values of ΔG° increased with temperature and decreased with surfactant concentration. The values of ΔH° and ΔS° increased with surfactant concentration. The developed approach for DIL mediated CPE has proved to be an efficient and green route for extraction of PA from water sample.

Combination of carvacrol with methotrexate suppresses Complete Freund's Adjuvant induced synovial inflammation with reduced hepatotoxicity in rats.

The present study evaluated the therapeutic benefit of the combination of carvacrol, an isoprenoid having potential anti-inflammatory action, with methotrexate in suppressing Complete Freund's Adjuvant induced arthritis and attenuating methotrexate induced hepatic damage. Arthritis was induced in rats with Complete Freund's Adjuvant. Animals received methotrexate (2mg/kg) intraperitonealy once a week for 5 weeks alone and along with carvacrol orally (50 and 100mg/kg) respectively from the 10th to the 42nd day. Control and carvacrol alone group were also studied. Paw volume, hypernociception, and erythrocyte sedimentation rate were evaluated as arthritic markers. Hepatic marker enzymes in serum; myeloperoxidase, protein oxidation, and oxidative measures were determined in the liver homogenate. Liver histological assessments were also carried out. Methotrexate significantly controlled arthritis; however, liver damage was evident due to oxidative stress and rise in myeloperoxidase levels. Carvacrol suppressed the hyperalgesic response, significantly alleviated arthritis and reduced damage to the hepatocytes owing to a decline in the levels of myeloperoxidase and oxidative markers. High dose of the combination reduced the levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase by 24.74%, 30.2% and 28.14% compared with methotrexate treatment. Histological assessment also revealed that carvacrol minimizes methotrexate induced liver toxicity. In combination, carvacrol promoted the anti-arthritic action of methotrexate, reduced neutrophils infiltration and peroxidative damage to the liver. Therefore, carvacrol can serve as a useful adjuvant and promote the safe use of methotrexate in the management of arthritis.

Insecticidal and oviposition deterrent properties of some spices against coleopteran beetle, Sitophilus oryzae.

Eighteen spices were screened for their insecticidal potential and antiovipositional properties against the rice weevil- Sitophilus oryzae-a serious insect pest of stored food grains. The bioefficacy of the powders and hexane extracts of selected spices were determined by assessing the toxicity, effect on F1 progeny, contact toxicity, persistence and seed viability. Responses varied with the spices, dosage and exposure time. Powders of mace and pepper, at 1% level were highly effective resulting in total mortality of S. oryzae by one week followed by nutmeg and clove with 100% mortality and cinnamon and star anise with 90% mortality at 5% concentration. These spices also completely inhibited F1 progeny. The hexane extracts of these spices at 1,000 ppm showed insecticidal activity, with pepper extract recording 100% mortality by 5 days. S. oryzae was susceptible to clove oil resulting in 92% mortality. Mortality was 51.63% in nutmeg, 66.6% in cinnamon, and 79.8% in case of mace and star anise. Hexane extracts of star anise, cinnamon and clove at 0.59 µl/cm(2) on filter paper discs induced 100% mortality by 72 h. These spices offered protection to wheat up to 9 months without affecting seed germination thereby showing promise as grain protectants.

Comparative effects of curcumin and its synthetic analogue on tissue lipid peroxidation and antioxidant status during nicotine-induced toxicity.

INTRODUCTION: Tobacco consumption is one of the leading preventable causes of death and disease worldwide. Nicotine, a major toxic component of tobacco, has been identified as an important risk factor for lung-related diseases. Increasing evidence demonstrates that oxidative stress plays a crucial aetiological role in the development of lung-related diseases. The present study aims at evaluating the protective role of curcumin and a synthetic analogue of curcumin (BDMC-A) on nicotine-induced oxidative stress. METHODS: Male albino rats of Wistar strain were used for the experimental study. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg body weight (five days a week, for 22 weeks) and curcuminoids were given simultaneously by intragastric intubation for 22 weeks. Measurement of lipid peroxidation indices, thiobarbituric acid reactive substances and hydroperoxides, nitric oxide and antioxidants, such as superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, vitamin E and vitamin C, were used as biomarkers for testing the antioxidant potential of the drugs. RESULTS: Oxidative stress, as evidenced by lipid peroxidation indices, was significantly increased in nicotine-treated groups. Administration of curcumin and BDMC-A abrogated this effect. The antioxidant status which was decreased in nicotine was effectively modulated by both curcumin and BDMC-A treatment. However, the reduction in oxidative stress was more pronounced in BDMC-A treatment groups compared to those treated with curcumin. CONCLUSION: The present study suggests that BDMC-A exerts its protective effect by modulating the extent of lipid peroxidation and augmenting the antioxidant defence system.

Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in Wistar rats.

Nicotine, a major toxic component of cigarette smoke, plays a key role in the development of cardiovascular disease and lung cancer. In the present study, we have synthesized an analog of curcumin and biomonitored its influence over biochemical marker enzymes and lipid profiles on nicotine-induced toxicity in Wistar rats. The effects were compared with that of curcumin, a well-known antioxidant and anti-hyperlipidemic agent. Toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week, for 22 weeks), and curcumin (80 mg/kg) was given simultaneously along with nicotine by intragastric intubation for 22 weeks. Measurements of activities of the biochemical marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase and of plasma lipid profiles were used to monitor the anti-hyperlipidemic effects of curcuminoids. In nicotine-treated rats, enhanced plasma marker enzymes and lipid profiles were observed. Administration of curcumin or curcumin analog to nicotine-treated rats significantly reduced the activity of marker enzymes and plasma lipid levels. Thus, our findings suggest that curcumin and its analog exert an anti-hyperlipidemic effect against nicotine-induced lung toxicity and may be a promising agent for treatment of hyperlipidemia and atherosclerosis.

Modulatory effects of curcumin on lipid peroxidation and antioxidant status during nicotine-induced toxicity.

Nicotine, a pharmacologically active substance in tobacco, has been identified as a major risk factor for lung diseases. In the present study, we evaluated the protective effects of curcumin on tissue lipid peroxidation and antioxidants in nicotine-treated Wistar rats. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg (5 days a week, for 22 weeks). Curcumin (80 mg/kg) was given simultaneously by intragastric intubation for 22 weeks. The enhanced level of tissue lipid peroxides in nicotine-treated rats was accompanied by a significant decrease in the levels of ascorbic acid, vitamin E, reduced glutathione, glutathione peroxidase, superoxide dismutase and catalase. Administration of curcumin significantly lowered the level of lipid peroxidation and enhanced the antioxidant status. The results of the present study suggest that curcumin exerts its protective effect against nicotine-induced lung toxicity by modulating the extent of lipid peroxidation and augmenting antioxidant defense system.

Inhibition of nicotine-induced toxicity by curcumin and curcumin analog: a comparative study.

The present study was undertaken to evaluate the effects of curcumin and curcumin analog on blood oxidant-antioxidant status during nicotine-induced toxicity in male Wistar rats. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week, for 22 weeks). The enhanced circulatory lipid peroxides in nicotine-treated rats was accompanied by a significant decrease in the levels of ascorbic acid, vitamin E, reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase. There was a reduction in the levels of zinc with an elevation of copper and ferritin in nicotine-treated rats. Administration of curcumin and curcumin analog significantly lowered the lipid peroxidation and enhanced the antioxidant status with modulation in the levels of zinc, copper, and ferritin. However, the effect was more significant in curcumin analog-treated rats than in curcumin-treated rats. The results of the present study suggest that curcumin and curcumin analog exert their protective effects by modulating the extent of lipid peroxidation and enhancing the antioxidant status.

Protective effect of curcumin on circulatory lipid peroxidation and antioxidant status during nicotine-induced toxicity.

Nicotine, an active substance present in tobacco has been identified as a major risk factor for lung related diseases. In the present study, we have evaluated the protective effect of curcumin on circulatory lipid peroxidation and antioxidants in nicotine administered Wistar rats. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg body weight (5 days a week, for 22 weeks) and curcumin (80 mg/kg body weight) was given simultaneously along with nicotine by intragastric intubation for 22 weeks. Enhanced lipid peroxidation (41.68%) in the circulation of nicotine treated animals was accompanied by a significant decrease in the levels of ascorbic acid, vitamin E, reduced glutathione, glutathione peroxidase, superoxide dismutase and catalase. Further, reduction in the levels of zinc and elevation of copper and ferritin were observed in circulation of nicotine treated rats. Administration of curcumin significantly lowered the concentrations of lipid peroxides (36%) and enhanced the antioxidant status with modulation in the levels of zinc, copper and ferritin. Our data suggest that curcumin exerts its preventive effects by modulating the degree of lipid peroxidation, antioxidant status and trace element levels.

Detection of Bacteroides infection by counter immunoelectrophoresis test.

The counterimmunoelectrophoresis (CIE) test using sonicated antigens of Bacteroides fragilis NCTC 2553 and a B. asaccharolyticus strain, standardised in the laboratory yielded a negative result in the 50 normal sera tested, while it was positive in 24 of 34 (71%) patients with infection due to black pigmented bacteroides and in 10 of 15 (67%) with B. fragilis infection. The microagglutination test (MAT) done in parallel showed a positivity of only 44 and 40 per cent respectively. The CIE test done with B. asaccharolyticus antigen was negative in 87 per cent of patients with infection due to B. fragilis whereas MAT showed cross reactivity to a greater extent.

Rapid identification of clinically important bacteroides by coagglutination method.

A coagglutination technique using indigenous reagents was applied for the rapid identification of Bacteroides fragilis and the black pigmented bacteroides group, using colony suspensions. All the 58 strains of B. fragilis and 42 strains of black pigmented bacteroides tested could be correctly identified by this method. The specificity of the coagglutination reagent was confirmed by the absence of cross reactivity with the related species of bacteroides, viz., B. distasonis, B. ovatus, B. vulgatus and B. thetaiotaomicron as well as other anaerobic and aerobic bacteria. A panel of four antisera against B. fragilis was required for correct identification of the strains tested, indicating the presence of multiple serotypes. On the other hand, all 42 strains of black pigmented bacteroides tested could be identified, using a single reagent as these strains appeared to have no antigenic type variants.