Data science-driven analyses of drugs inducing hypertension as an adverse effect.

The utilization of approved medication is a requisite to combat certain diseases for health; however, the undesirable adverse effects (AEs) due to medication are generally unavoidable. Hypertension is one of such AEs resulting from approved medication in which blood pressure in the arteries gets elevated and is a risk factor for several diseases including heart and kidney failure. HTs are the approved drugs that can cause hypertension as an AE. Here, the goal of the study is to investigate the structural and functional diversities of HTs. In our quest to unravel the structural parameters of the HTs, a systematic analysis of the HTs having a different number and type of ring systems was conducted. The cellular component, molecular function and biological processes adopted by the gene products were analyzed. Moreover, our systematically done analysis suggests that all the target families are active in a common pathway, that is, nerve transmission. A comparison of the selected structural and functional aspect of HTs with anti-hypertensives suggests that HTs follow certain structural and functional features in spite of many possibilities. Our study provides a promising methodology that considers the influence of structural diversity of AE causing agents on a functional perspective for precursory clinical decision making. This could be extended to explore the structural and functional trends that are adopted by agents causing certain diseases or AEs.

Ethylenediamine-assisted growth of multi-dimensional ZnS nanostructures and study of its charge transfer mechanism on supercapacitor electrode and photocatalytic performance.

In recent years, much interest has been raised by materials with multi-purpose characteristics as the performance of electrochemical energy devices such as supercapacitors and photocatalytic activities depend strongly on the properties of materials. This study delineates various parameters like morphology, energy band gap, charge transfer resistance, different defect states, diffusion coefficient and functional groups adsorbed on the surface of material to assess the performance of supercapacitor electrodes and photocatalytic degradation efficiency of synthesised multi-dimensional ZnS nanostructures. Ethylenediamine (EN)-mediated multi-dimensional ZnS nanostructures were grown by the solvothermal route. One-dimensional (1D), 2D and 3D morphologies were obtained by varying the ratio of de-ionised water and EN, taken as 1:3, 1:2 and 1:1, respectively. The EN molecules effectively capped most of the surfaces of the ZnS nanoparticles formed, preventing agglomeration of nanoparticles due to the decrement in surface energy. The oriented attachment of these clusters resulted in the formation of 1D, 2D and 3D morphologies. The plausible chemistry in the formation of 1D, 2D and 3D nanostructures has been elaborated. Charge transfer properties of prepared electrodes have been examined using the electrochemical impedance spectroscopy (EIS) technique because better charge transfer causes diminishing electron/hole recombination and hence better photodegradation efficiency. Among the synthesised materials, the 2D nanostructure degraded the eosin Y dye to maximum 90.71% efficiency with rate constant 34 × 10-3 min-1. 2D nanostructures possess better charge transfer and hence better photodegradation efficiency. Various studies using methods of UV-vis, Fourier-transform infrared, Brunauer-Emmett-Teller, x-ray photoelectron spectroscopy and photoluminescence spectra are in good agreement with the obtained photodegradation results. After analysing cyclic voltammetry curves and EIS, a higher diffusion coefficient is obtained for 1D nanostructure material, hence a higher specific capacitance and higher energy density of 159.12 F g-1 and 22.75 KWh kg-1 are found in this case. Only 9% loss of specific capacitance is found after 1000 cycles, showing a relatively high cycling stability in 3D nanostructures. The excellent supercapacitive property can be attributed to the porous structure and high specific surface area. Thus, the synthesised multi-dimensional ZnS nanostructures are proved to be a potential candidate for both photocatalytic and supercapacitor electrode performance.

Network-based approach highlighting interplay among anti-hypertensives: target coding-genes: diseases.

Elucidating the relation between the medicines: targets, targets: diseases and diseases: diseases are of fundamental significance as-is for societal benefit. Hypertension is one of the dangerous health conditions prevalent in society, is a risk factor for several other diseases if left untreated and anti-hypertensives (AHs) are the approved drugs to treat it. The goal of the study is to decipher the connection between hypertension with other health conditions, however, is challenging due to the large interactome. To fulfill the aim, the strategy involves prior clustering of the AHs into groups as per our previous method, followed by the analyzing functional association of the target coding-genes (tc-genes) and health conditions for each group. Following our recently published work where the AHs are clustered into six groups such that molecules having similar patterns come together, here, the distribution of molecular functions and the cellular components adopted by the tc-genes of each group are analyzed. The analyses indicate that kidney, heart, brain or lung related ailments are commonly associated with the tc-genes. The association of selective tc-genes to health conditions suggests a preference for certain health conditions despite many possibilities. Analyses of experimentally validated drug-drug combinations indicate the trend in successful AHs combinations. Clinically validated combinations bind different targets. Our study provides a promising methodology in a network-based approach that considers the influence of structural diversity of AHs to the functional perspective of tc-genes concerning the health conditions. The method could be extended to explore disease-disease relationships.

Elucidating the preference of dimeric over monomeric form for thermal stability of Thermus thermophilus isopropylmalate dehydrogenase: A molecular dynamics perspective.

An oligomer usually refers to a macromolecular complex formed by non-covalent interactions of monomers. Several thermophilic proteins are oligomers. The significance of oligomerization of individual proteins for stability at higher temperature is of prime importance for understanding evolution and increasing industrial productivity. The functional form of Thermus thermophilius isopropylmalate dehydrogenase (IPMDH), a widely studied protein to understand the factors affecting the thermal stability of a protein is a dimer, a simplest oligomer. To decipher the relationship between the effects of oligomerization on thermal stability of a protein, we have applied all-atom molecular mechanics approach by analyzing how temperature effects dynamics of a subunit in the presence and absence of another subunit in dimeric (SS) and monomeric forms (SA), respectively, before its denaturation begins. Comparing the difference in overall dynamic structural aspects at two different temperatures, 300 K and 337 K. Analysis of root mean square deviation (RMSD), root mean square fluctuations (RMSF) and Cα-Cα distance with an increase in temperature from 300 K to 337 K for a total of 0.2 µs reveals higher thermal stability of the dimer as compared to monomer. In contrast to dimeric form, the monomer is relatively stable at 300 K but cannot withstand the structural stability at 337 K leading to loosening of intramolecular interactions with maximum fluctuation at B23-B24 within a subunit. Energetic and structural properties indicate that B24-B24' is the major contributor to maintaining subunit-subunit interaction at 337 K. Correlation between the favorable interaction energy (IE) with the minimal perturbance in Cα atoms of domain 2 in a subunit in the presence of another subunit enhances the rigidity of the domain with subunit-subunit interaction. Overall, the study indicates that the dimeric over monomeric form enhances the protein's thermal stability and not all major subunit interacting regions contribute equally in maintaining the former.

An Exploration of Electrocatalytic Analysis and Antibacterial Efficacy of Electrically Conductive Poly (D-Glucosamine)/Graphene Oxide Bionanohybrid.

The diversification of environment congenial and conservative nanocomposites is prestigious because of increasing contamination in biota. Poly (D-glucosamine), a natural biopolymer is contemplated as a promising biodegradable polysaccharide for various applications mainly in food packaging, bone substitutes, and water filtration. The drawback of poly (D-glucosamine) is nadir mechanical strength and high hydrophilicity which could be amended by the introduction of graphene oxide (GO) nanoparticles (shows excellent load transfer). Homogeneous distribution and well dispersion of GO nanoparticles in poly (D-glucosamine) matrix have been concluded by SEM investigation. Inclusions of 1% GO into the biopolymer matrix results in enhancement of 83.21 MPa of tensile strength in contrary to pristine poly (D-glucosamine). It can be elucidated that increment in properties is due to the crosslinking reaction takes place between the amine and epoxide moieties that exist within poly (D-glucosamine) matrix and GO respectively. The thermal stability of nanocomposites has been increased on addition of nanofiller confirmed by TGA analysis. The resultant nanocomposites were examined for antimicrobial screening against various contagious bacterial strains for packaging applications. Electrochemical characteristics and capacitive investigation of the composites were also studied using cyclic voltammetry and impedance (EIS) respectively. EIS elucidated that the nanocomposite modified electrode exhibited good capacitance behaviour with the Bode phase angle (-45°) which proves the candidates have good capacitive properties. The electrocatalytic properties are found to be diffusion controlled in alkaline medium with good electrical conductivity with low resistance. It is envisioned that the resultant bionanocomposite has potential applications in packaging industry.

Clinical evaluation of Trivrta powder (Operculina turpethum Linn.) and Aragvadha Patra Lepa (paste of leaves of Cassia fistula Linn.) in the management of Vicharchika (eczema).

BACKGROUND: In Ayurveda, majority of skin diseases have been mentioned under the umbrella of Kushtha and in other words, it can be listed as "Ayurvedic dermatology." Among them, Vicharchika (eczema) included under Kshudra Kushtha, has been mentioned as curable disease, but due to relapsing nature of the disease and hazardous side effects of the modern drugs, it is difficult to manage. Ayurveda classics described a number of formulations to combat Kushtha (skin diseases) which offers effective remedy for eczema. Therefore, the attempt was done to assess the effect of Nitya Virechana (regular purgation) along with local application in its management. AIM AND OBJECTIVE: The aim of this study is to compare the efficacy of Trivritta powder along with Aragvadha Patra Lepa (paste) and Aragvadha Patra Lepa (paste) alone as local application in the management of Vicharchika (eczema). MATERIALS AND METHODS: A total of 63 patients of Vicharchika (eczema) were selected and allocated in 2 groups, out of which 60 patients (30 patients each) completed the trial treatment. Group A received Trivritta powder (Operculina turpethum Linn.) along with local application of paste of leaves of Aragvadha (Cassia fistula Linn.) and group B received local application of Aragvadha Patra Lepa (paste) for the duration of 4 weeks. RESULTS: All calculations were calculated through 'Graph Pad In Stat 3' software. Nitya Virechana (regular purgation) by Trivritta along with Aragvadha Patra Lepa (group A) proved more effective to control itching, discharge, burning sensation, eruption, discoloration, pain and edema of cases of Vicharchika. CONCLUSION: Treatment with Trivritta (Operculina turpethum Linn.) along with local application of paste of Aragvadha Patra Lepa is effective in reducing the symptoms of Vicharchika Kushtha (eczema).

Community level workers: awareness generation for improving children's health.

BACKGROUND: Routine immunisation and Vitamin A supplementation are two of many services offered by Government of India to reduce child mortality and morbidity. The three groups of community level workers (CLWs) i.e. Auxiliary Nurse Midwives from health department, Anganwadi Workers from women and child development department and Accredited Social Health Activists (ASHAs) are responsible for raising awareness and demand for these services. OBJECTIVES: The paper assesses the knowledge and participation of CLWs in generating awareness about the two services namely immunisation and Vitamin A supplementation among eligible mothers; and mother's knowledge on these two services. METHODS: The study was conducted in 16 villages of two administrative blocks of Udaipur district in Rajasthan. Multistage purposive sampling was used for study area selection. Data collection was done using mixed methods-1) observations of 16 Maternal and Child Health and Nutrition days; 2) questionnaire based survey of 46 CLWs; and 3) questionnaire based survey of 321 programme beneficiaries i.e. infant's mothers. RESULTS: Limited knowledge of CLWs and their participation in awareness generation activities for the two services was noticed, which was also reflected in the poor knowledge among mothers on the two services. CONCLUSION: The study results may partially explain the poor child immunization in Rajasthan. Initiatives to increase CLWs' knowledge of child immunization and Vitamin A supplementation; and increasing their participation in awareness generation activities need serious consideration by the healthcare system to improve immunization coverage.

Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase.

Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 µs were carried out on wild type and mutant's functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies.

In vitro thrombolytic activity of Dhamasa (Fagonia arabica Linn.), Kushta (Saussurea lappa Decne.), and Guduchi (Tinospora cordifolia Thunb.).

INTRODUCTION: Thrombotic disorders are among the major fatal conditions affecting the society. Treatment modalities used for such disorders are either surgical interventions or use of drugs such as urokinase, streptokinase (SK), or tissue plasminogen activators to dissolve the blood clots. These modalities have their own limitations and side effects apart from being expensive. There is a need for safer and cost effective antithrombolytic agents. AIM: To evaluate in vitro thrombolytic property of Dhamasa (Fagonia arabica Linn.), Kushta (Saussurea lappa Decne.), and Guduchi (Tinospora cordifolia Thunb.) plant extract. MATERIALS AND METHODS: Venous blood drawn from 20 healthy volunteers was allowed to form clots which was weighed and treated with the extract of test plant materials to disrupt the clots. Weight of clot after and before treatment provided a percentage of clot lysis. SK was used as a positive and water as a negative control. STATISTICAL ANALYSIS USED: The significance between % clot lysis of five groups by means of weight difference was tested by the one-way ANOVA. RESULTS: Clot lysis observed were 68.06%, 14.85%, 25.01%, 92.54%, and 3.00% for Dhamasa, Kushta, Guduchi, SK, and distilled water, respectively. CONCLUSION: Herbal extracts possess thrombolytic properties and lyse blood clots in vitro.

Factors affecting the performance of community health workers in India: a multi-stakeholder perspective.

BACKGROUND: Community health workers (CHWs) form a vital link between the community and the health department in several countries. In India, since 2005 this role is largely being played by Accredited Social Health Activists (ASHAs), who are village-level female workers. Though ASHAs primarily work for the health department, in a model being tested in Rajasthan they support two government departments. Focusing on the ASHA in this new role as a link worker between two departments, this paper examines factors associated with her work performance from a multi-stakeholder perspective. DESIGN: The study was done in 16 villages from two administrative blocks of Udaipur district in Rajasthan. The findings are based on 63 in-depth interviews with ASHAs, their co-workers and representatives from the two departments. The interviews were conducted using interview guides. An inductive approach with open coding was used for manual data analysis. RESULTS: This study shows that an ASHA's motivation and performance are affected by a variety of factors that emerge from the complex context in which she works. These include various personal (e.g. education), professional (e.g. training, job security), and organisational (e.g. infrastructure) factors along with others that emerge from external work environment. The participants suggested various ways to address these challenges. CONCLUSION: In order to improve the performance of ASHAs, apart from taking corrective actions at the professional and organisational front on a priority basis, it is equally essential to promote cordial work relationships amongst ASHAs and other community-level workers from the two departments. This will also have a positive impact on community health.

Validation of drug-like inhibitors against Mycobacterium tuberculosis L-aspartate α-decarboxylase using nuclear magnetic resonance (1H NMR).

The catalytic activity of L-aspartate α-decarboxylase (ADC) is essential for the growth of several micro-organisms, including Mycobacterium tuberculosis (Mtb), and has triggered efforts for the development of pharmaceutically active compounds against tuberculosis. The present study is a continuation of our recent chemoinformatics-based design approach for identifying potential drug-like inhibitors against MtbADC. We report an NMR-based protocol that allows label-free and direct monitoring of enzymatic conversion, which we have combined with a systematic testing of reported and newly identified potential inhibitors against MtbADC. Quantification of enzymatic conversion in the absence and presence of inhibitors allowed for a relative measure of the inhibitory effect (k(rel)). Among the newly identified compounds, D-tartrate, L-tartrate, and 2,4-dihydroxypyrimidine-5-carboxylate were found to inhibit the enzyme with k(rel) values of 0.36, 0.38, and 0.54, respectively. In addition to the identification of potential building blocks for the development of therapeutic agents, the current study highlights the importance of electrostatic interactions governing enzyme-inhibitor binding.

Chemoinformatic identification of novel inhibitors against Mycobacterium tuberculosis L-aspartate α-decarboxylase.

L-aspartate α-decarboxylase (ADC) belongs to a class of pyruvoyl dependent enzymes and catalyzes the conversion of aspartate to ß-alanine in the pantothenate pathway, which is critical for the growth of several micro-organisms, including Mycobacterium tuberculosis (Mtb). Its presence only in micro-organisms, fungi and plants and its absence in animals, particularly human, make it a promising drug target. We have followed a chemoinformatics-based approach to identify potential drug-like inhibitors against Mycobacterium tuberculosis L-aspartate α-decarboxylase (MtbADC). The structure-based high throughput virtual screening (HTVS) mode of the Glide program was used to screen 333,761 molecules of the Maybridge, National Cancer Institute (NCI) and Food and Drug Administration (FDA) approved drugs databases. Ligands were rejected if they cross-reacted with S-adenosylmethionine (SAM) decarboxylase, a human pyruvoyl dependent enzyme. The lead molecules were further analyzed for physicochemical and pharmacokinetic parameters, based on Lipinski's rule of five, and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties. This analysis resulted in eight small potential drug-like inhibitors that are in agreement with the binding poses of the crystallographic ADC:fumarate and ADC:isoasparagine complex structures and whose backbone scaffolds seem to be suitable for further experimental studies in therapeutic development against tuberculosis.

A study on the method of Taila Bindu Pariksha (oil drop test).

Taila Bindu Pariksha, an ancient method of urine examination for ascertaining the prognosis of diseases, was very popular in the medieval period, the use of which became obsolete after 17(th) Century AD. Technique of this test is very crude and there are chances of variations in the observations. To revive this technique, it is necessary that the methodology of this test should be standardized so that the observations could be reproducible. To standardize the technique, apparently healthy volunteers were selected and various parameters were standardized for doing this test, i.e., shape and size of Patra (testing containers), volume of the urine, size of the oil drop, height of the oil drop from the surface of urine, variety of sesame oil, etc., Based on the literature, the parameters were changed one by one and observations were noted down. The whole method was recorded in the form of video clips for proper evaluation. The parameters standardized on the basis of observations can be considered as standard to be referred in future studies.

SIN-inhibitory phosphatase complex promotes Cdc11p dephosphorylation and propagates SIN asymmetry in fission yeast.

BACKGROUND: Cytokinesis in many eukaryotes involves the function of an actomyosin-based contractile ring. In fission yeast, actomyosin ring maturation and stability require a conserved signaling pathway termed the SIN (septation initiation network). The SIN consists of a GTPase (Spg1p) and three protein kinases, all of which localize to the mitotic spindle pole bodies (SPBs). Two of the SIN kinases, Cdc7p and Sid1p, localize asymmetrically to the newly duplicated SPB in late anaphase. How this asymmetry is achieved is not understood, although it is known that their symmetric localization impairs cytokinesis. RESULTS: Here we characterize a new Forkhead-domain-associated protein, Csc1p, and identify SIN-inhibitory PP2A complex (SIP), which is crucial for the establishment of SIN asymmetry. Csc1p localizes to both SPBs early in mitosis, is lost from the SPB that accumulates Cdc7p, and instead accumulates at the SPB lacking Cdc7p. Csc1p is required for the dephosphorylation of the SIN scaffolding protein Cdc11p and is thereby required for the recruitment of Byr4p, a component of the GTPase-activating subunit for Spg1p, to the SPB. CONCLUSIONS: Because Cdc7p does not bind to GDP-Spg1p, we propose that the SIP-mediated Cdc11p dephosphorylation and the resulting recruitment of Byr4p are among the earliest steps in the establishment of SIN asymmetry.