Central Drug Research Institute

About: Central Drug Research Institute is a facility organization based out in Lucknow, Uttar Pradesh, India. It is known for research contribution in the topics: Leishmania donovani & Brugia malayi. The organization has 4357 authors who have published 7257 publications receiving 143871 citations. The organization is also known as: Central Drug Research Institute, Lucknow & CDRI.

Current drug targets for helminthic diseases

Abstract: More than 2 billion people are infected with helminth parasites across the globe. The burgeoning drug resistance against current anthelmintics in parasitic worms of humans and livestock requires urgent attention to tackle these recalcitrant worms. This review focuses on the advancements made in the area of helminth drug target discovery especially from the last few couple of decades. It highlights various approaches made in this field and enlists the potential drug targets currently being pursued to target economically important helminth species both from human as well as livestock to combat disease pathology of schistosomiasis, onchocerciasis, lymphatic filariasis, and other important macroparasitic diseases. Research in the helminths study is trending to identify potential and druggable targets through genomic, proteomic, biochemical, biophysical, in vitro experiments, and in vivo experiments in animal models. The availability of major helminths genome sequences and the subsequent availability of genome-scale functional datasets through in silico search and prioritization are expected to guide the experimental work necessary for target-based drug discovery. Organized and documented list of drug targets from various helminths of economic importance have been systematically covered in this review for further exploring their use and applications, which can give physicians and veterinarians effective drugs in hand to enable them control worm infections.

Purification, characterization and thermostability improvement of xylanase from Bacillus amyloliquefaciens and its application in pre-bleaching of kraft pulp

Abstract: Xylanases have important industrial applications but are most extensively utilized in the pulp and paper industry as a pre-bleaching agent. We characterized a xylanase from Bacillus amyloliquefaciens strain SK-3 and studied it for kraft pulp bleaching. The purified enzyme had a molecular weight of ~50 kDa with optimal activity at pH 9.0 and 50 °C. The enzyme showed good activity retention (85%) after 2 h incubation at 50 °C and pH 9.0. This enzyme obeyed Michaelis–Menten kinetics with regard to beechwood xylan with K m and V max values of 5.6 mg/ml, 433 μM/min/mg proteins, respectively. The enzyme activity was stimulated by Mn2+, Ca2+ and Fe2+ metal ions. Further, it also showed good tolerance to phenolics (2 mM) in the presence of syringic acid (no loss), cinnamic acid (97%), benzoic acid (94%) and phenol (97%) activity retention. The thermostability of xylanase was increased by 6.5-fold in presence of sorbitol (0.75 M). Further, pulp treated with 20U/g of xylanase (20IU/g) alone and with sorbitol (0.75M) reduced kappa number by 18.3 and 23.8%, respectively after 3 h reaction. In summary, presence of xylanase shows good pulp-bleaching activity, good tolerance to phenolics, lignin and metal ions and is amenable to thermostability improvement by addition of polyols. The SEM image showed significant changes on the surface of xylanase-treated pulp fiber as a result of xylan hydrolysis.

Genome-wide differential methylation analyses identifies methylation signatures of male infertility.

Abstract: Study question Do methylation changes in sperm DNA correlate with infertility? Study answer Loss of spermatogenesis and fertility was correlated with 1680 differentially-methylated CpGs (DMCs) across 1052 genes. What is known already Methylation changes in a number of genes have been correlated with reduced sperm count and motility. Study design, size, duration This case-control study used spermatozoal DNA from 38 oligo-/oligoastheno-zoospermic infertile patients and 26 normozoospermic fertile men. Participants/materials, settings, methods Genome-wide methylation analysis was undertaken using 450 K BeadChip on spermatozoal DNA from six infertile and six fertile men to identify DMCs. This was followed by deep sequencing of spermatozoal DNA from 32 infertile patients and 20 fertile controls. Main results and the role of chance A total of 1680 DMCs were identified, out of which 1436 were hypermethylated and 244 were hypomethylated. Classification of DMCs according to the genes identified BCAN, CTNNA3, DLGAP2, GATA3, MAGI2 and TP73 among imprinted genes, SPATA5, SPATA7, SPATA16 and SPATA22 among spermatogenesis-associated genes, KDM4C and JMJD1C, EZH2 and HDAC4 among genes which regulate methylation and gene expression, HLA-C, HLA-DRB6 and HLA-DQA1 among complementation and immune response genes, and CRISPLD1, LPHN3 and CPEB2 among other genes. Genes showing significant differential methylation in deep sequencing, i.e. HOXB1, GATA3, EBF3, BCAN and TCERG1L, are strong candidates for further investigations. The role of chance was ruled out by deep sequencing of select genes. Large-scale data N/A. Limitations, reason for caution Genome-wide analyses are fairly accurate, but may not be exactly validated in replication studies across all DMCs. We used the 't' test in the genome-wide methylation analysis, whereas other tests could provide a more robust and powerful analysis. Wider implications of the findings DMCs can serve as markers for inclusion in infertility screening panels, particularly those in the genes showing differential methylation consistent with previous studies. The genes validated by deep sequencing are strong candidates for investigations of their roles in spermatogenesis. Study funding/competing interest(s) The study was funded by the Council of Scientific and Industrial Research (CSIR), Govt. of India with grant number BSC0101 awarded to Rajender Singh. None of the authors has any competing interest to declare.