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The occurrence of viral co-infection is always a challenging issue in pediatrics which indicates underestimation of causal viral pathogens. A 6-year-old girl child from Patna had diagnosed a rare case of multi-viral co-infection in February 2020. She was manifested with oblivion along with high-grade fever, weakness, nasal bleed, headache, and body ache. She had altered sensorium with mildly dilated pupils. Her three classical meningeal sign i.e. Kernig's sign, Brudzinski's sign, and nuchal rigidity were found positive. She clinically investigated with a strong suspicion of viral infectivity. Awfully, she was diagnosed with multi-viral co-infection including Japanese Encephalitis, Dengue, Chikungunya, Cytomegalovirus, and Rubella where as HSV and VZV detected borderline. The IgM detection for JE using the CSF sample was found equivocal. The infection was also confirmed by CECT brain scanning. She got proper medication including antiemetic, antipyretic, antiepileptic drugs, antibiotics, anti-viral drugs, and 20% Mannitol for reducing the intra cranial pressure. After medication under proper clinical supervision, she improved completely with any seizures and viral infections. She advised for follow-up after a month. Such occurrences of multi-viral co-infections deserve proper attention and awareness among the healthcare experts about the severity of drugs.

In view of the significant role of Post kala-azar dermal Leishmaniasis (PKDL) patients in the transmission/recurrence of visceral leishmaniasis (VL) outbreaks, control of PKDL is among the priorities. As the Single Dose AmBisome 10 mg/kg (SDA) became the obvious choice for the treatment of VL, therefore, in this study, 896 patients were included to explore the probability of developing PKDL. Among the treated patients, 30 (3.35%) of them found confirmed as PKDL with clinical symptoms. Out of the 30 patients, 53.33% male and 46.67% female patients had macular lesions respectively, with a median time (Interquartile range [IQR]) to development of 13.5 (9–23.5) and 23 (9-17) months following treatment. No, significant associations were established concerning any patient's demographics and clinical characteristics. However, with the patients presenting with confirmed PKDL, females were significantly younger than males. This study suggests the rate of PKDL appearance is directly associated with 10 mg/kg of SDA and therefore there is a need for more concerns regarding doses during treatment.

A green synthesis of silver nanoparticles was synthesized by AgNO3 with arabinoxylan, isolated from green stem of Andrographis paniculata (Kalmegh). The synthesized Ag NPs-arabinoxylan conjugates were characterized by UV–vis spectroscopy, FE-SEM, TEM, XRD, TGA, EDX, and Zeta potential experiments. The Ag NPs formation was established by the surface plasmon resonance band ~410.25 nm. SEM image showed mostly spherical morphology of Ag NPs. The fcc crystalline nature was identified by XRD, SAED and the size were 24.5 and 25 nm from TEM and XRD analysis respectively. The prepared Ag NPs showed dose-dependent antimicrobial activity against Streptococcus pneumonia, Candida albicans and E. coli. The nanoparciles damage 4% hemolysis to human RBCs at 12.5 μg/mL. MTT assay of Ag NPs showed that half of the cell killed at 10 μg/mL and wound healing assay observed effective inhibition cell proliferation.

Dispersion of zirconia powder in aqueous suspension using suitable dispersant for coating application was studied. Zeta potential experiments were conducted in search of stable suspensions....

Background: From Gaya and adjoining regions, the trend in patients admitted with acute neurological illness was investigated. Illnesses were identified as sudden outbreaks of Japanese virus encephalitis (JE), Herpes simplex virus encephalitis (HSV-1&2), and other acute encephalitis syndrome (AES). Objective: In the current study, an investigation was carried out to assess potential infectious pathogens in patients aged 16 years or younger who were admitted to Anugrah Narayan Magadh Memorial Medical College Hospital, Gaya, with encephalitis-like symptoms. Methods: Cross-epidemiological, serological, and molecular biological studies were performed on samples collected from 71 patients below 16 years of age. Patients’ clinical histories, i.e. fever, socio-demographic characteristics, and other clinical data, were extracted from patient files. Results: The results showed confirmed AES cases, including 49.30% JE and 7.04% HSV positive patients. A higher case-fatality rate of 40% in JE and 40% HSV cases below 7 years of age were observed during treatment would become an unavoidable concern. The epidemical sex ratio was observed to be higher in girls than in boys (1.26:1). Conclusion: The results suggested that JE virus was found to be a main causative risk factor responsible for disease transmission in the outbreak area.

The arthropod-transmitted chikungunya virus has emerged as an epidemic menace that causes debilitating polyarthritis. With this life-threatening impact on humans, the possible treatment requires to cure the viral infectivity. But, devoid of any vaccine against the chikungunya virus (CHIKV), there is a need to develop a novel chemotherapeutic strategy to treat this noxious infection. CHIKV carries highly compact P23pro-zbd structure that possesses potential RNA-binding surface domains which extremely influences the use of RNA template during genome replication at the time of infection and pathogenesis. Therefore, computational approaches were used to explore the novel small molecule inhibitors targeting P23pro-zbd domain. The tertiary structure was modeled and optimized using in silico approaches. The results obtained from PROCHECK (93.1% residues in favored regions), ERRAT (87.480 overall model quality) and ProSA (Z-score: -11.72) revealed the reliability of the proposed model. Interestingly, a previously reported inhibitor, chloroquine possesses good binding affinities with the target domain. In-depth analysis revealed that chloroquine derivatives such as didesethyl chloroquine hydroxyacetamide, cletoquine, hydroxychloroquine exhibited a better binding affinity. Notably, MD simulation analysis exhibited that Thr1312, Ala1355, Ala1356, Asn1357, Asp1364, Val1366, Cys1367, Ala1401, Gly1403, Ser1443, Tyr1444, Gly1445, Asn1459, and Thr1463 residues are the key amino acid responsible for stable ligand-protein interaction. The results obtained from this study provide new insights and advances the understanding to develop a new approach to consider effective and novel drug against chikungunya. However, a detailed in vivo study is required to explore its drug likeliness against this life-threatening disease.

Influenza virus is a common human pathogenic agent that has caused serious respiratory illness and death over the past century and in recent year. Treatment options against pandemic influenza strain A/H1N1 are very limited and unsatisfactory. Therefore we have developed iron oxide nanoparticles (IO-NPs) with particle size in the range of 10–15 nm against pandemic influenza strain A/H1N1/Eastern India/66/PR8-H1N1. Cell viability and anti-influenza activity was measured by MTT assay, plaque inhibition and quantifying viral transcripts using quantitative real-time PCR with Iron oxide nanoparticles in a dose- and time-dependent manner. 50% cell viability (TD50) was observed at 4.25 pg ± .2 pg of Iron oxide nanoparticles. The percentage of plaque inhibition relative to the infection and the IC50 (50% virus reduction) of PR8-H1N1strain (0.5 moi) were measured in vitro by the plate forming unit (pfu) in MA104 cells. Finding were observed at 01 pg after 72 h. The Antiviral activity determined by change in viral RNA transcripts within 24 h of virus infection by RT-PCR, 08 fold reductions in virus found when treated with Iron oxide nanoparticles Thus; it opens a new avenue for use of IP-NPs against virus infections.

Membrane technology has emerged as an important tool in sustainable management of water and energy owing to its high efficiency and low footprint. Ceramic polymer composite membranes are an emerging category which tends to combine the merits of both pure ceramic and polymeric membranes. The present work elucidates the role of electron microscopy in preparation and characterization of novel ceramic-supported-polymeric asymmetric composite membrane developed by successive pore size reduction of commercial macroporous ceramic support. In each step of preparation process, formation of a layer (ceramic intermediate layers and polymeric functional layer) with conforming properties was evaluated and its morphology was studied in details with the help of Field Emission Scanning Electron Microscopy (FESEM) analysis. An amine-functionalized composite membrane was developed using polyethyleneimine as functional layer material over modified alumina-based ceramic substrate. The membrane was found to exhibit a water permeability of 3.9-3.1 L m-2 h-1 bar-1 and a low molecular weight cut-off (< 2000) suggesting its nanofiltration nature toward contaminant rejection. The membrane demonstrated a maximum removal of 93.5% of Crystal Violet dye from 25 mg/l aqueous solution at 4 bar pressure. The excellent stability of the membrane in high-pressure application suggests its potential use in other nanofiltration application.

In this study, a low pressure novel ultrafiltration membrane has been developed using synthesized hydroxyapatite nanoparticle over low cost clay-alumina based porous ceramic substrate with multichannel configuration. The nanoparticles and membrane were characterized by FESEM, EDX, XRD, BET, FTIR analyses. The FESEM and EDX images revealed a crack free uniform hydroxyapatite coating layer over porous support with maximum presence of Ca and P at top of the active layer compared to other ceramic elements. The nominal pore size of the membrane was measured as 2.8 nm (BET analysis). Bench scale membrane separation process was performed for the removal of toxic Pb(II) from spiked aqueous solution using 500 mm long synthesized hydroxyapatite ceramic membrane. The clean water permeability and the flux were 79.8 L m−2h−1 bar−1 and 28.4 L m−2h−1 (at 0.5 bar pressure), respectively. The developed membrane showed 99.6% rejections of Pb(II) from 5 mg L−1 solutions at 1 bar pressure. Furthermore, pH effect on rejection efficiency was also studied and it demonstrated maximum rejections at pH 7.4. The probable mechanism of high rejection was established by XPS analysis as complexation reaction. The membrane was regenerated and subsequently reused. However, this study highlights on designing, fabrication and performance evaluation of novel hydroxyapatite clay-alumina ceramic ultrafiltration membrane in bench scale via simple method that can be potentially applied for industrial purposes.

Application of toxic materials for fabrication of membrane and its use for water treatment may create serious environmental threats. In this study, a new alternative approach was employed to synthesize copper oxide (CuO) nanoparticles (NPs) via green route using Catharanthus Roseus leaf extract and its efficacy as membrane material was also explored for chromium (VI) removal. Optimization by response surface methodology was adopted for uniform nanoparticle synthesis. The low cost clay-alumina ceramic support was coated with CuO slurry by dip coating method for the fabrication of membrane where the structural properties of CuO NPs in active layer were also studied. Adhesion of CuO NPs on membrane surface was established by FESEM analysis where the images demonstrated homogeneous and defect free coating over porous support. A detailed XPS analysis revealed the binding properties of the CuO NPs with clay-alumina membrane surface and the rejection mechanism of chromium (VI). BET analyses further confirmed the pore size reduction of the coated membrane towards ultrafiltration range (from 1-1.5 μm to 3.2 nm). The novel CuO clay-alumina ceramic membrane showed high clean water permeability, flux and toxic chromium (VI) ions rejection as 85.51 L m−2 h−1 bar−1, 253 L m−2 h−1 and 88.08%, respectively. This paper explores a new alleyway of environment friendly membrane preparation process that can be potentially elaborated for waste water treatment in large scale.

The crystallographic structure of the Leishmania donovani serine hydroxymethyltransferase ( Ld SHMT), an attractive target for the design of leishmanicidal agents, is still unknown. Serine hydroxymethyltranferase (SHMT) is a key enzyme in the purine biosynthesis pathway, which is essential for the synthesis of DNA in leishmania parasite. Aim of this study is to find out the novel drug candidate against this parasitic protozoan. The present study describes the development of a robust homology model of Ld SHMT to forecast interaction phenomenon with inhibitory molecules using structure-based drug designing strategy. Here we report a robust three-dimensional structure (98.4% of the residues were in the most favored region and additional allowed region) which consist of N terminal small domain (residues 1–46), N terminal large domain (residues 46–298) and C terminal domain (residues 299–457). The second N-terminal domain or the large domain (residues 46–298) binds PLP, has most of the active site residues and folds into α–β–α type sandwich containing eight α-helices wrapped around seven mixed β-sheets and third is the C-terminal domain (residues 299–457) folds into an α–β sandwich. Docking studies of diverse reported structures with modeled protein exhibited good binding affinities. Purvalanol, revealed a good binding affinity (− 29.78) and residues involved in interaction are ASP208, Arg243, His236 and Lys237 forming hydrogen bonds, which signifies the presence of strong interaction with the target protein. Methotrexate-alpha-arginine and fluoresceinated have also exhibited good binding affinity − 38.85 and − 37.27 respectively. Pemetrexed, which has been earlier implicated in treatment of lung cancer, also exhibited a good binding affinity (− 32.76).The residues which played a crucial role in the formation of strong H bonds are Ser102, Gly101, Arg243, Lys360, Asn361 and Lys 237. Apart from these molecules, several other molecules also showed strong interaction with Ld SHMT. Overall, the present study is believed to provide valuable information to design a new compound with improved activity for antileishmanial therapeutics development.

A novel clay-alumina ceramic composite membrane has been fabricated comprising of hydroxyethyl cellulose and CuO nanoparticles for separation of Cr (VI) and Pb (II) from contaminated water. It was prepared by slurry casting method over low cost clay-alumina ceramic substrate. The active layer formation of the prepared membrane was confirmed by FESEM, EDX and XPS analysis. The pore structure of macroporous ceramic substrate was improved from 0.5 to 1.5 μm to 3 nm by addition of CuO nanoparticles in combination with biopolymer which resulted in consequent improvement of heavy metal rejection rate. The permeability was determined as 34.99 L m −2 h −1 bar −1 . The membrane exhibited significant performances and stability on rejection of toxic Pb (II) and Cr (VI) ions from spiked solution and simulated wastewater. Although the operational pressure range was 0–5 bar, maximum percentage of rejection achieved was 97.14% for Pb (II) at 2 bar transmembrane pressure from spiked water. Similarly maximum percentage of rejection was obtained at 2 bar transmembrane pressure for Cr (VI) was 91.44%. The reusability of the membrane was also studied and obtained results suggested that the prepared membrane may be used for real application. It is believed that this CuO nanoparticles containing clay-alumina ceramic composite membrane will be an effective solution for removal of heavy metals from contaminated water.

This rare case with multi-viral co-infection had been diagnosed in Au-gust 2018 in Patna, India. The depicted case was observed in seven-year-old girl child who manifested with unconsciousness along with fever, headache, weakness, body ache and irregular pupil movement. She had experienced intermittent abnormal body movement with star-ing look for every 3 hours. These symptoms were akin to epileptic sei-zures. Clinical investigations were advised with a strong suspicion of viral infection. Awfully, she was diagnosed with multi-viral co-infection including Japanese Encephalitis, Dengue, Chikungunya, Herpes Sim-plex Virus (HSV), Cytomegalovirus (CMV) and Rubella from both blood and Cerebrospinal fluid (CSF) samples. The infections were further confirmed by using reverse transcriptase polymerase chain reaction (RT-PCR). She got proper medication with antibiotic and antiviral cov-erage. She improved with complete cessation of seizures and was ad-vised to follow up after one month. Such incidences of multi-viral co-infections warrant focus on healthcare providers awareness in order to prevent its occurrence and severity of illness. [J Med Allied Sci 2019; 9(2.000): 100-102]

The concept of rational treatment, target to therapy, is an old and interesting process in drug discovery that includes the entire step from target identification to successful treatments of disease and is based on new drug delivery approach. In this current review, we have tried to compile maximum data which are published in a recent journal and books from 2005 to 2017 in all areas related with treatment of leishmaniasis. During last decade (2005–2015), there are a number of preclinical drug(s) undergone into clinical phase (Ph-III) and our institute (RMRIMS, Patna) is dedicated to the basic and clinical research of leishmaniasis. Today, there are number of drugs of choice for the treatment of leishamaisis (AmBisome and miltefosine) and more are in a clinical trial (Phase IV), which have > 94% efficacy and success rates. Moreover, there are 98 candidates (drugs) in preclinical development stages and most of them are antleishmanial agents. The nine (9) antleishmanial agents are in Phase III (efficacy) trials (combination with first line drugs). The success rate of combination therapy are having > 98%. The chemical classification of all drugs which have under preclinical trial is classified as chalcones (18), azoles (15), and quinolines (9) compounds. The drug target is based on classifications of drugs or drug candidates that revealed that topoisomerase have higher success rate (42%) followed by cysteine protease (13%). This study suggest that the drug target against this site such as topoisomerase and cysteine proteases will have > 50% success rate. In this review, number of diagrams have been elucidated to understand overall and clear picture, and its structural group which is responsible for development of drug(s) against leishmaniasis.

Acid-sensing ion channels are ligand/proton-gated ion channels belonging to the family of the degenerin/epithelial Na+ channel (DEG/ENaC). They function as a sodium-selective pore for Ca2+ entry into neuronal cells during pathological conditions. The blocking of this channel has therapeutic importance, because at basal physiological pH (7.2), it is in a closed state and under a more acidic condition, and the ASIC1a ion channel is activated. To investigate the different states of the hASIC1a channel based on mutational analysis, structure-based virtual screening and molecular dynamics simulation studies. The system showed stability after 30 ns (after 1500 frame), and it was stabilized to an average value around 2.2Å. During the simulation, the ion channel residues in persistent contact with toxin PcTx1 were D237, E238, D347, D351, E219 and E355. These residues are important physiologically for the activation of the channel. From in silico alanine scanning, the significant hotspots obtained in hASIC1 are E344, P347, F352, D351, E355 and E219. From the sitemap analysis, it was evident that the sitemap found one of the active sites at the PcTx1 binding site with a site score of 1.086 and a D-score of 1.035 for hASIC1. We obtained a few promising hits and final potential hits from the virtual screening in hASIC1 that made interactions with the residues in the acidic pocket (E344, P347, F352, D351, E355 and E219). Based on these studies, the hits and scaffolds of potential therapeutic interest against various pathological conditions are associated with hASIC1a for future studies.

The development of new membranes with improved separation properties, high mechanical and thermal stability using inexpensive and naturally abundant materials is of utmost importance for sustainable development and environmental applications. Ceramic materials due to their high chemical, mechanical and thermal stability in combination to their facile surface functionalization have inspired material scientists to design innovative low-cost ceramic-based membrane supports. This study focuses on the preparation and characterization of novel asymmetric ultrafiltration ceramic membrane coated with single separation layer made of TiO2 nanoparticles, and its application to removal of alizarin dye from aqueous solutions. The membrane was prepared by a simple and one-step deposition of micrometer-thick titania layer on the internal surface of the tubular-shape porous clay-alumina membrane support from an aqueous colloidal suspension of titanium oxide (TiO2) nanoparticles with size of 10 nm. The colloidal suspension was prepared in the presence of 0.2 wt.% of Dolapix, and 30 g of an aqueous solution of polyvinyl alcohol at 12 wt.% and 66 mL of H2O. Microfiltration tubular supports of 10 mm/7 mm (outer/inner diameter) were prepared through an extrusion method followed by a sintering process using China Clay Rajmahal grade and alumina, as mineral precursors. The composition of 25% of clay and 75% of alumina was selected in this work as it showed a lower sintering temperature (Tf = 1350 °C) which could ensure low cost elaboration process, an average water flux of 850 L h−1 m−2 bar−1 as well as enhanced mechanical performance (≈37 MPa) and large porosity (48%) with an average pore diameter of 0.75 µm. SEM characterization showed that at the sintering temperature of 800 °C, the TiO2 nanoparticles coated densely and homogeneously the ceramic support forming a thin layer of about 4.2 µm in thickness and leading to a clear reduction of the mean pore size (50 nm approximatively) while providing a water permeability of 117 L h−1 m−2 bar−1. The so-designed ultrafiltration (UF) tubular ceramic membrane has proved efficient for alizarin red dye removal with a retention rate of 99% and a permeate flux of 70 L h−1 m−2 at pH 9 and a transmembrane pressure of 5 bar.

Guanylate kinase (GK; EC 2.7.4.8) is an important enzyme which catalyzed the ATP-dependent phosphorylation of GMP (guanosine monophosphate) into GDP (guanosine diphosphate) for survival of parasites; this suggests that it is a good target for design inhibitor(s). Knowledge of 3D structure of GKLdv is essential for elucidating interaction studies with the inhibitors and compared with substrate binding pattern in both the built model and template structures. The final reliable model of GKLdv has revealed α/β type protein with a G-X2-G-X-G-K that has a catalytic conserved domain in both template and model structure. The core domain consists of a central five-stranded parallel β-sheet (β5, β6, β3 and β4) whereas model has both α1-α10 and β1-β9 and active sites consist of flexible loop (FL1 to FL3). The superimposition structure of main-chain atoms of the GK model with closely homologue of GK (1EX7, chain A), has revealed better alignment and its root mean square deviation (RMSD) (43% similarity) is 0.602 Ǻ. The virtual screening result has suggested that the binding pocket interacts with 5GP (5′-guanylic acid) with exhibited higher score in both GOLD and LigandFit scores and involve in amino acid interaction (H-bonding) are Arg40, Try80, Tyr52, Ser36, Glu71, and Asp102. The reported antileishmanial diospyrin (IC₅₀-7.2 μM) has also exhibited higher binding activities (Dock score - 49.314 and Fitness score - 52.69) with frequently involved amino acids are Arg45, Glu102, Tyr35, Tyr54, Ser38, Tyr82, Ile103, Asp104, Lys106, Lys18, Pro13 and Ser14. The sigma pi interaction between Ile103 with diospyrin ring has revealed greater stable complex after molecular dynamic simulation studies. The best scoring compounds need for further validation in-vitro test.

Although, the precise host defence mechanism(s) is not completely understood, T cell-mediated immune responses is believed to play a pivotal role in controlling parasite infection. Here we target the stage dependent over expressed gene. Here, the consensus based computational approach was adopted for the screening of potential major histocompatibility complex class I restricted epitopes. Based on the computational analysis and previously published report, a set 19 antigenic proteins derived from Leishmania donovani were screened for further characterization as vaccine candidates. A total of 49 epitopes were predicted, which revealed a comprehensive binding affinity to the 40 different MHC class I supertypes. Based on the population coverage and HLA cross presentation, nine highly promiscuous epitopes such as LTYDDVWTV (P1), FLFPQRTAL(P2), FLFSNGAVV (P3), YIYNFGIRV (P4), YMTAAFAAL (P5), KLLRPFAPL (P6), FMLGWIVTI (P7), SLFERNKRV (P8), and SVWNRIFTL (P9) which have either a high or an intermediate TAP binding affinity were selected for further analysis. Theoretical population coverage analysis of polytope vaccine (P1-P9) revealed more than 92% population. Stimulation with the cocktail of peptide revealed a proliferative CD8+ T cell response and increased IFN-γ production. An upregulated NF-κB activity is thought to be play a pivotal role in T cell proliferation against the selected peptide. The Th1-type cytokine profile (presence of IFN-γ and absence of IL-10) suggests the potentiality of the cocktail of epitope as a subunit vaccine against leishmaniasis. However, the efficiency of these epitopes to trigger other Th1 cytokines and chemokines in a humanized mice model could explore its plausibility as a vaccine candidate. J. Cell. Biochem. 119: 378-391, 2018. © 2017 Wiley Periodicals, Inc.

Visceral leishmaniasis, a protozoan disease transmitted by phlebotomine sandflies which affect mostly in Indian sub-continent. The treatment for visceral leishmaniasis (VL) caused by Leishmania donovani are limited and unsatisfactory. Currently available drug against such as miltefosine and polymer based drugs amBisome has high efficacy against VL but found serious side effects and poor absorbance. To overcome this, we developed peptide (glycine) coated iron oxide (Fe3O4) nanoparticles (GINPs) encapsulated amphoterecin B (AmB) drug against visceral leishmaniasis. Synthesis of GINPs was carried out and different characterization technique used to confirm the synthesis and size of GINPs GINPs-AmB showed that particle size in the range of 10–15 nm and closed to spherical in shaped. GINPs-AmB showed release rate of AmB is higher at lower pH. Significantly two fold higher efficacies of GINP encapsulated AmB during in vitro study. There was a substantial reduction in the total parasite burden in spleen in treated groups (GINPs encapsulate AmB), compare to AmB alone. The results obtained from this study revealed that AmB loaded GINPs is twofold effective than AmB and therefore, it opens a new avenue for use of AmB loaded GINPs against VL.

The efficiency of organic biomass towards heavy metal remediation can be enhanced by inclusion of inorganic nanomaterials. In this study, nanocomposite was synthesized by dead yeast biomass and titania nanoparticles through immobilization method. The nanocomposite was further applied into spiked water and real effluent of tannery for effective sorption of Cr (VI). The nanocomposite was characterized using FESEM, TEM, BET, XRD, FTIR, and XRF analysis. Excellent potential of Cr (VI) removal efficiency (99.92%) was observed at varied operational conditions by using the nanocomposite. The quadratic model resulted from optimization predicted the response from the input limits. The equilibrium data obtained from sorption process was fitted both in Langmuir and Freundlich isotherm model. Langmuir adsorption isotherm showed significantly high monolayer sorption capacity (162.07 mg g −1 ) of the nanocomposite. The kinetics of the process was described by Pseudo-second-order model and the thermodynamic study showed an exothermic and spontaneous Cr (VI) sorption process. Desorption and reuse of the nanocomposite material had insignificant effect on Cr (VI) rejection efficiency.

The diagnosis of visceral leishmaniasis (VL) is one of the foremost barriers in the control of this disease, as demonstration of the parasite by splenic/bone marrow aspiration is relatively difficult and requires expertise and laboratory support. The aim of the present study was to find a noninvasive diagnostic approach using the existing recombinant kinesine-39 (rK-39) immunochromatographic nitrocellulose strips test (ICT) with a human sweat specimen for the diagnosis of VL. The investigation was carried out on specimens (blood, sweat, and urine) collected from 58 confirmed VL, 50 confirmed post kala-azar dermal leishmaniasis (PKDL), 36 healthy control, and 35 patients from other diseases. The data obtained from this study reveal that 96.6% clinically confirmed active VL participants were found to be positive when tested against a sweat specimen. Interestingly, the scenario was similar when tested against a blood specimen (96.6% positive by rK-39). Moreover, a test of both sweats and blood specimens from 50 PKDL participants resulted in 100% positivity, whereas no healthy control participants were found to be rK-39 positive. The sensitivity of the rK-39 ICT in sweat specimen was 94.7%, whereas the specificity was 100% in healthy controls from endemic, nonendemic, and other infectious diseases, respectively. No difference was observed in sweat specimen of VL and PKDL cases which signifies its reliability. However, further evaluation of this method on a larger scale could enhance the reliability of the proposed model so that it could be used efficiently in VL management and eradication.

Novel amine functionalized composite membranes were prepared over tubular ceramic substrate using facile dip-coating and cross-flow filtration approach. The two fabricated membranes, P-60S and P-60S-EDTA with polyethyleneimine (PEI) and EDTA-modified PEI as functional layers respectively, were characterized in terms of EDX, FTIR, XPS, FESEM, AFM and contact angle analyses which confirmed their stable physical and chemical structure for use in high pressure application. Clean water permeability and MWCO study revealed the superior permeability and rejection efficiency of the P-60S-EDTA compared to the P-60S membrane. Incorporation of bulky EDTA molecules in the membrane functional layer simultaneously decreased pore size and increased membrane hydrophilicity. The removal of As(V), Cr(VI) and Cu(II) heavy metals by both membranes were found to be highly pH dependent and overall rejection improved in case of P-60S-EDTA membrane [99.82% for Cu(II), 96.75% for As(V) and 97.22% for Cr(VI)]. Interestingly, rejection of As(V) and Cr(VI) was significantly improved in presence of Cu(II) due to volume resistance provided by EDTA-Cu(II) complex towards the passage of other heavy metal ions. Excellent stability of P-60S-EDTA membrane in continuous operation of 36 h in both ideal and practical water environment suggests its promising application in real field heavy metal contaminated waste water treatment.

IntroductionPlasmodium falciparum synthesizes phosphatidylcholine for the membrane development through serine decarboxylase-phosphoethanolamine methyltransferase pathway for growth in human host. Phosphoethanolamine-methyltransferase (PfPMT) is a crucial enzyme for the synthesis of phosphocholine which is a precursor for phosphatidylcholine synthesis and is considered as a pivotal drug target as it is absent in the host. The inhibition of PfPMT may kill malaria parasite and hence is being considered as potential target for rational antimalarial drug designing.MethodsIn this study, we have used computer aided drug designing (CADD) approaches to establish potential PfPMT inhibitors from Asinex compound library virtually screened for ADMET and the docking affinity. The selected compounds were tested for in-vitro schizonticidal, gametocidal and cytotoxicity activity. Nontoxic compounds were further studied for PfPMT enzyme specificity and antimalarial efficacy for P. berghei in albino mice model.ResultsOur results have identified two nontoxic PfPMT competitive inhibitors ASN.1 and ASN.3 with better schizonticidal and gametocidal activity which were found to inhibit PfPMT at IC50 1.49μM and 2.31μM respectively. The promising reduction in parasitaemia was found both in orally (50 & 10 mg/kg) and intravenous (IV) (5& 1 mg/kg) however, the better growth inhibition was found in intravenous groups.ConclusionWe report that the compounds containing Pyridinyl-Pyrimidine and Phenyl-Furan scaffolds as the potential inhibitors of PfPMT and thus may act as promising antimalarial inhibitor candidates which can be further optimized and used as leads for template based antimalarial drug development.

The increased multidrug resistance among antimalarial drugs produces the urgency of potent anti malarial to combat resistant malaria and the malaria burden worldwide. The protein which may prevent the growth or transmission of malaria parasite may be the great target for rational drug designing. Plasmodium falciparum phosphoethanolamine methyltransferase (Pfpmt) absent in human catalyzes triple methylation of ethanolamine into phosphocholine for phosphatidylcholine biosynthesis from serine decarboxylation phosphoethanolamine methyltransferase pathway for the membrane development at asexual as well as sexual stages of parasite. The Plasmodium requires production of membrane rapidly for growth and multiplication. Hence, the phosphoethanolamine methyltransferase of Plasmodium falciparum was selected as drug target for rational drug designing. Using Discovery studio 3.5 software the library of zinc compounds was screened against target and analyzed. The compounds with better druglike properties and docking affinity and binding interaction for target protein were procured for in vitro analysis against Plasmodium falciparum culture (IC50). Compounds ZINC02103914 and ZINC12882412 were found to have good druglike properties and affinity for Pfpmt also inhibited P. falciparum growth at very low µM IC50 concentration 3.0 µM and 2.1 µM respectively also found nontoxic in vitro against HEK-293 cells. Simulation study of best inhibitor revealed the specificity for the target protein. Hence, the compounds possessed the immense probability of being inhibitors of Pfpmt and may be optimized as antimalarial agent for combinational therapy to overcome the multidrug resistance and may also be used as template for optimization and rational drug designing.

Glucose-1-Phosphate Thymidylyltransferase (RmlA) is one of the enzymes in rhamnose biosynthesis pathway, where rhamnose acts as linker of peptidoglycan and arabinogalacton in the cell wall, therefore RmlA is a potential enzyme for the survival of Mycobacterium tuberculosis (Mtb). To go into the depth of the structure for exploring binding regions, homology model of RmlA was built in Prime, Schrodinger v9.2. The model with lowest Discrete Optimized Potential Energy (DOPE) score of -35524.17 kcal/mol and RMSD of 0.1 Å with the template (1H5R_B) was subjected to Molecular Dynamics Simulation (MDS) for 5 ns to achieve its stable folding state. The tertiary structure of the proposed model is composed of α/β/α sandwich type protein with quasi-Rossmann type folding pattern. The substrate, deoxy Thymidine tri phosphate (dTTP) comprises of triphosphate (R1) and methyl (R2) side chains where, R1 is highly essential for the survival of Mtb. Therefore, nineteen side chain analogues of dTTP were designed by substituting R1 and R2 chain of dTTP using Combi Glide, Schrodinger v9.2 and docked with the target RmlA protein. Out of which two analogues such as, 6-[(2R,3S,5R)-5-[5-(2- aminoethyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl]-3-hydroxyoxolan-2 yl] hexanoic acid (COMP- 11) and 4-(2-{1-[(1S,3S,4S)-3-(5-carboxypentyl)-4-hydroxy-2-methylidenecyclopentyl]-2,4-dioxo- 1,2,3,4-tetrahydropyrimidin-5-yl}ethyl)morpholin-4-ium (COMP-12) showed the highest GLIDE score (-12.55 Kcal/mol and -11.58 Kcal/mol respectively) than that of substrate (-9.725 Kcal/mol). During simulations, hydrogen bonding profile between the two top hits and protein ranges up to 5 strong polar contacts which were much stronger than that of substrate. Similarly, the computational binding free energy of both the analogues was found to be less than -70 Kcal/mol which is much lower than that of substrate (-52.84 Kcal/mol). All these results suggest that these two compounds have more stable interaction than that of substrate inside the solvent condition and can be used as competitive inhibitors.

Apatite material obtained from natural sources of Tunisian mineral has been used for the development of membrane over clay–alumina-based microporous supports. For this purpose, supports of single-channel and 19-channel circular configurations were used. The apatite powder used for membrane preparation had average pore diameter of 4.02 μm. Coating formulation has been optimized to obtain stable suspension. Powder loading of 4 wt.% was found as optimum for obtaining a proper microfiltration membrane with 0.2 μm pore diameter. Single-channel membrane was used for characterization. The application to color removal from synthetic reactive dye solution was performed using membrane with 19-channel configuration. An average water flux of 200 and 80 l/m2 h was obtained for 19-channel support and membrane, respectively, in laboratory scale setup. Reactive red dye removal from synthetic dyeing solution was achieved up to 99%. Resulting saturated membrane was successfully regenerated using H2O2 at various con...

Targeted drug delivery systems are ideal technology to increase the maximum mechanism of action with smaller dose, we have developed miltefosine encapsulated PLGA–PEG nanoparticles (PPEM) to target macrophage of infected tissues against Leishmania donovani. The structural characterization of PLGA–PEG by transmission electron microscopy (TEM) has shown a size range of 10 to 15 nm. Synthesis and drug encapsulation confirmed by dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR) and confirmed NP encapsulation. The dose of nano encapsulated miltefosine decreased by fifty percent as compared to that of a conventional miltefosine and Amphoterecin B. The inhibition of amastigotes in the splenic tissue with nano encapsulated miltefosine (23.21 ± 23) was significantly more than the conventional miltefosine (89.22 ± 52.7) and Amphoterecin B (94.12 ± 55.1). This study signifies that there is an increased contact surface area of the nano encapsulated drug and significant reduction in size, improved the efficacy in both in vitro and in vivo study than that of the conventional miltefosine, Amphoterecin B.

Leishmania is a unicellular protozoan parasite which causes leishmaniasis, a neglected tropical disease. It possess a unique thiol metabolism comprising of several proteins among which, tryparedoxin (cTXN) and tryparedoxin peroxidase (cTXNPx), function in concert as oxidoreductases, utilizing trypanothione as a source of electrons to reduce the hydroperoxides produced by macrophages during infection. This detoxification pathway is unique and essential for the survival of Leishmania. Herein, we report the functional characterization of Leishmania donovani cTXN and its interaction with cTXNPx. The full length recombinant cTXN and cTXNPx proteins were purified in the native state and biochemical analysis showed that the cTXN-cTXNPx coupled system efficiently degraded hydrogen peroxide and tert-butyl hydroperoxide by transferring reducing equivalents from trypanothione. In silico investigation of the potential interaction between cTXN and cTXNPx proteins showed strong interaction of model structures with amino acids Ile109, Thr132, Glu107, Trp70, Trp39, Cys40 and His129 of Ld-cTXN and Thr54, Lys93, Arg128 and Asn152 of Ld-cTXNPx predicted to be involved in interaction. Moreover, co-purification, pull down assay and immunoprecipitation studies confirmed the interaction between Ld-cTXN and Ld-cTXNPx proteins. In addition, for the first time, we demonstrated at the translational level that Ld-cTXN protein is upregulated in Amp B resistant isolates accompanied by enhanced peroxidase activity, as compared to sensitive strains. Thus, our results show that Ld-cTXN and Ld-cTXNPx proteins acts in concert by physical interaction to form a strong peroxide stress detoxification system in Leishmania and their upregulation in Amp B resistant isolates imparts better stress tolerance, and hence fitter pathogens, as compared to sensitive strains.

To explore new protective measure against visceral leishmaniasis, reverse vaccinology approach was employed to identify key immunogenic regions which can mediate long-term immunity. In-depth computational analysis revealed nine promiscuous epitopes which can possibly be presented by 46 human leukocyte antigen, thereby broadening the worldwide population up to 94.16%. This is of reasonable significance that most of the epitopes shared 100% sequence homology with other Leishmania species and could evoke a common pattern of protective immune response. Transporter associated with antigen processing binding affinity, molecular docking approach followed by dynamics simulation and human leukocyte antigen stabilization assay suggested that the best five optimal set of epitopes bind in between α1 and α2 binding groove with sufficient affinity and stability which allows the translocation of intact epitope to the cell surface. Fascinatingly, the human leukocyte antigen stabilization assay exhibited a modest correlation with the positive immunogenicity score predicted by class I pMHC immunogenicity predictor. A support for this notion came from ELISA and FACS analysis where the epitopes as a cocktail induced CD8+ IFN-γ and Granzyme B levels significantly in treated visceral leishmaniasis subject which suggests the immunogenic ability of the selected epitopes.

The arthropod-transmitted chikungunya virus has emerged as an epidemic menace that causes debilitating polyarthritis. With this life-threatening impact on humans, the possible treatment requires to cure the viral infectivity. But, devoid of any vaccine against the chikungunya virus (CHIKV), there is a need to develop a novel chemotherapeutic strategy to treat this noxious infection. CHIKV carries highly compact P23