Publications by authors named "Upadhyayula Suryanarayana Murty"

39 Publications

Nootkatone confers antifibrotic effect by regulating the TGF-β/Smad signaling pathway in mouse model of unilateral ureteral obstruction.

Eur J Pharmacol 2021 Sep 2;910:174479. Epub 2021 Sep 2.

Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, PIN-781101, Assam, India. Electronic address:

Chronic kidney disease (CKD) with underlying interstitial fibrosis is often associated with end-stage renal disease (ESRD). In the present study, we investigated the renoprotective and antifibrotic potential of nootkatone (NTK), a bioactive sesquiterpene, in an experimental model of renal fibrosis. Unilateral ureteral obstruction (UUO) model was performed to induce renal fibrosis in Balb/C mice. The animals were randomly assigned into 5 groups: sham, NTK control, UUO control, UUO and NTK 5 mg/kg, and UUO and NTK 10 mg/kg. Animals received NTK at a dose of 5 mg/kg and 10 mg/kg orally for the next 14 consecutive days. UUO induced histological alterations, accumulation of extracellular matrix (ECM) components including collagens, fibronectin, and alpha-smooth muscle actin (α-SMA), activation of the transforming growth factor-β (TGF-β)/Smad signaling and oxidative damage in the obstructed kidneys. Our study revealed that NTK (10 mg/kg) inhibits UUO mediated kidney fibrosis in vivo. Administration of NTK (10 mg/kg) prevented the activation of the TGF-β/Smad signaling, expression of ECM components, markedly attenuated the renal tubular injury and fibrosis area (% area: 6.66 ± 1.45% vs UUO: 26.33 ± 2.90%). Administration of NTK at 10 mg/kg significantly restored the endogenous antioxidants and prevented the reactive oxygen species generation (25.31 ± 1.65% vs UUO: 45.01 ± 4.85%) and reduced the level of tumor necrosis factor (TNF)-α (95.22 ± 12.39 vs UUO: 215.57 ± 60.45 pg/mg protein) in the kidneys. Altogether, our findings suggest that NTK might be a budding therapeutic candidate for renal fibrosis.
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http://dx.doi.org/10.1016/j.ejphar.2021.174479DOI Listing
September 2021

3D printing and enteric coating of a hollow capsular device with controlled drug release characteristics prepared using extruded Eudragit® filaments.

Pharm Dev Technol 2021 Nov 29;26(9):1010-1020. Epub 2021 Aug 29.

Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER)-Guwahati, Changsari, India.

This work focuses on the extrusion of a brittle, tacky, cationic copolymer i.e. Eudragit® E-100 to prepare filament and subsequent 3D printing of hollow capsular device using the extruded filament. An optimum amount of talc and triethyl citrate was used for the possible extrusion of the polymer. There was no thermal and chemical degradation of the polymer observed after extrusion confirmed by DSC and FTIR analysis. Microscopic analysis of the printed capsule showed the layer-by-layer manner of 3D printing. Capsule parts were printed according to the set dimensions (00 size) with minimal deviation. Printed capsule showed the soluble behaviour in gastric fluid pH 1.2 where within 15 min the encapsulated drug encounters with the dissolution medium and almost 70% drug was dissolved within 4 hr. In case of phosphate buffer pH 6.8, the printed capsule showed a longed swelling behaviour up to 12 hr and then gradually bursting of capsule occurred wherein more than 90% encapsulated drug was dissolved within 36 hr. Enteric coating of the printed capsule showed similar behaviour in alkaline medium that observed with non-enteric capsule. This indicates the potential application of this printed capsules for both gastric and intestinal specific delayed drug delivery by a single step enteric coating process.
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http://dx.doi.org/10.1080/10837450.2021.1970765DOI Listing
November 2021

Theoretical and experimental validation of praziquantel with different polymers for selection of an appropriate matrix for hot-melt extrusion.

Int J Pharm 2021 Sep 31;607:120964. Epub 2021 Jul 31.

Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER)-Guwahati, Changsari 781101, Assam, India; National Centre for Pharmacoengineering, NIPER-Guwahati, Changsari 781101, Assam, India. Electronic address:

The selection of an appropriate matrix for the preparation of amorphous extrudate in hot-melt extrusion (HME) deals with the study of various solid-state properties of drugs and polymers. Therefore, it is necessary to have an appropriate knowledge of drug-polymer miscibility, the interaction between the drug-polymer on mixing, and Gibb's free thermal energy of mixing to screen polymers through thermodynamic phase diagrams, to be suitable amorphous matrix system for HME. Here, we evaluated the possibility of three different polymers, namely, Eudragit®EPO, polyvinyl alcohol (PVA), Kollicoat®IR (KIR) with Praziquantel (PZQ), with proper validation of the Flory-Huggins theory and construction of the phase diagram using the melting point depression approach to determine a suitable matrix for HME. The solubility parameter theoretical calculation approach was used as a preliminary study to validate the miscibility of PZQ with three different polymers. Theoretical and experimental validation studies using the Flory-Huggins interaction parameter value using the melting point depression approach and the effect of PZQ loading on the interaction parameter were systematically validated to predict thermodynamic phase diagrams and Gibbs free energy of mixing for screening these polymers for the preparation of amorphous extrudate. Using the phase diagram, the thermal processing temperature for the HME was determined using a T-φ phase diagram to obtain an appropriate matrix. The obtained extrudates were further validated through physical appearance, microscopic structure, thermal and functional group characterizations, followed by the PZQ assay. Thus, considering the solid-state properties, the processing parameters of HME were selected to obtain stable extrudates and an appropriate matrix for PZQ loading.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120964DOI Listing
September 2021

Quercetin and piperine enriched nanostructured lipid carriers (NLCs) to improve apoptosis in oral squamous cellular carcinoma (FaDu cells) with improved biodistribution profile.

Eur J Pharmacol 2021 Oct 29;909:174400. Epub 2021 Jul 29.

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, Kamrup, Assam, India. Electronic address:

Oral squamous cellular carcinoma (OSCC) is considered a life-threatening disease with detection in late stages, which forces us to opt for dangerous treatment with a combination of chemotherapy and radiotherapy. Herbal components such as piperine and quercetin are derived from edible sources, proving their anticancer potential against oral cancer cells in vitro. Encapsulation into lipid matrix-mediated nanostructured lipid carriers (NLCs) can make both drugs bio-accessible. NLCs were synthesised using the high shear homogenisation method and characterised for their physicochemical properties, followed by in vitro cellular evaluation in FaDu oral cancer cells. NLCs showed negatively charged particles smaller than 180 nm with a polydispersity index (PDI) of <0.3. Both drugs were found to encapsulate sufficiently, with >85% entrapment efficiency and an improved drug release profile compared to their pristine counterparts. Differential scanning calorimetry (DSC) thermograms showed conversion into an amorphous matrix in lyophilized NLCs, which was supported by X-ray diffraction (XRD) analysis. The cytotoxicity assay showed the IC concentration for dual drug-loaded NLCs, which was more effective than the pure drug solution. NLCs were found to be internalised in cells in a short time with an almost 95% co-localization rate. Dual drug-loaded NLCs showed maximum depolarisation of the mitochondrial membrane along with more apoptotic changes. Improved apoptosis was confirmed in NLCs using flow cytometry. The in vivo biodistribution of Coumarin-6 labelled NLCs in rats confirmed their efficient distribution in various parts of the oral cavity through oral administration. Optimised dual drug-loaded NLCs provide a better option for delivering both drugs through a single lipid matrix against oral cancer.
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http://dx.doi.org/10.1016/j.ejphar.2021.174400DOI Listing
October 2021

3D printed hollow microneedles array using stereolithography for efficient transdermal delivery of rifampicin.

Int J Pharm 2021 Aug 19;605:120815. Epub 2021 Jun 19.

Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER)-Guwahati, Changsari, Assam, India; National Centre for Pharmacoengineering, NIPER-Guwahati, Changsari, Assam, India. Electronic address:

A 3D printed assembly of hollow microneedles (HMNs) array, conjoined with a reservoir void, was designed and additively manufactured using stereolithography (SLA) technology utilizing a proprietary class-I resin. The HMNs array was utilized for transdermal delivery of high molecular weight antibiotics, i.e., rifampicin (M 822.94 g/mol), which suffers from gastric chemical instability, low bioavailability, and severe hepatotoxicity. HMNs morphology was designed with sub-apical holes present in a quarter of the needle tip to improve its mechanical strength and integrity of the HMNs array. The HMNs array was characterized by optical microscopy and electron microscopy to ascertain the print quality and uniformity across the array. The system was also subjected to mechanical characterization for failure and penetration analyses. The ex vivo permeation and consequent transport of rifampicin across porcine skin were systematically evaluated. Finally, in vivo examinations of rifampicin administration through the microneedle reservoir system in SD rats revealed efficient penetration and desired bioavailability.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120815DOI Listing
August 2021

Transporter-mediated drug-drug interactions: advancement in models, analytical tools, and regulatory perspective.

Drug Metab Rev 2021 Jun 2:1-36. Epub 2021 Jun 2.

Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, India.

Drug-drug interactions mediated by transporters are a serious clinical concern hence a tremendous amount of work has been done on the characterization of the transporter-mediated proteins in humans and animals. The underlying mechanism for the transporter-mediated drug-drug interaction is the induction or inhibition of the transporter which is involved in the cellular uptake and efflux of drugs. Transporter of the brain, liver, kidney, and intestine are major determinants that alter the absorption, distribution, metabolism, excretion profile of drugs, and considerably influence the pharmacokinetic profile of drugs. As a consequence, transporter proteins may affect the therapeutic activity and safety of drugs. However, mounting evidence suggests that many drugs change the activity and/or expression of the transporter protein. Accordingly, evaluation of drug interaction during the drug development process is an integral part of risk assessment and regulatory requirements. Therefore, this review will highlight the clinical significance of the transporter, their role in disease, possible cause underlying the drug-drug interactions using analytical tools, and update on the regulatory requirement. The recent approaches which emphasize the advancement in the discovery of drug-drug interactions are also highlighted in this review. Besides, we discuss several endogenous biomarkers that have shown to act as substrates for many transporters, which could be potent determinants to find the drug-drug interactions mediated by transporters. Transporter-mediated drug-drug interactions are taken into consideration in the drug approval process therefore we also provided the extrapolated decision trees from to , which may trigger the follow-up to clinical studies.
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http://dx.doi.org/10.1080/03602532.2021.1928687DOI Listing
June 2021

A review on herbal Nrf2 activators with preclinical evidence in cardiovascular diseases.

Phytother Res 2021 Sep 24;35(9):5068-5102. Epub 2021 Apr 24.

Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, India.

Cardiovascular diseases (CVDs) are an ever-growing problem and are the most common cause of death worldwide. The uncontrolled production of reactive oxygen species (ROS) and the activation of ROS associated with various cell signaling pathways with oxidative cellular damage are the most common pathological conditions connected with CVDs including endothelial dysfunction, hypercontractility of vascular smooth muscle, cardiac hypertrophy and heart failure. The nuclear factor E2-related factor 2 (Nrf2) is a basic leucine zipper redox transcription factor, together with its negative regulator, kelch-like ECH-associated protein 1 (Keap1), which serves as a key regulator of cellular defense mechanisms to combat oxidative stress and associated diseases. Multiple lines of evidence described here support the cardiac protective property of Nrf2 in various experimental models of cardiac related disease conditions. In this review, we emphasized the molecular mechanisms of Nrf2 and described the detailed outline of current findings on the therapeutic possibilities of the Nrf2 activators specifically from herbal origin in various CVDs. Based on evidence from various preclinical experimental models, we have highlighted the activation of Nrf2 pathway as a budding therapeutic option for the prevention and treatment of CVDs, which needs further investigation and validation in the clinical settings.
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http://dx.doi.org/10.1002/ptr.7137DOI Listing
September 2021

Toll-like receptor 4: An attractive therapeutic target for acute kidney injury.

Life Sci 2021 Apr 3;271:119155. Epub 2021 Feb 3.

Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari PIN-781101, Assam, India. Electronic address:

Acute kidney injury (AKI) is a progressive renal complication which significantly affects the patient's life with huge economic burden. Untreated acute kidney injury eventually progresses to a chronic form and end-stage renal disease. Although significant breakthroughs have been made in recent years, there are still no effective pharmacological therapies for the treatment of acute kidney injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response plays a pivotal role in the pathogenesis of acute kidney injury. The expression of TLR4 has been seen in resident renal cells, including podocytes, mesangial cells, tubular epithelial cells and endothelial cells. Activation of TLR4 signaling regulates the transcription of numerous pro-inflammatory cytokines and chemokines, resulting in renal inflammation. Therefore, targeting TLR4 and its downstream effectors could serve as an effective therapeutic intervention to prevent renal inflammation and subsequent kidney damage. For the first time, this review summarizes the literature on acute kidney injury from the perspective of TLR4 from year 2010 to 2020. In the current review, the role of TLR4 signaling pathway in AKI with preclinical evidence is discussed. Furthermore, we have highlighted several compounds of natural and synthetic origin, which have the potential to avert the renal TLR4 signaling in preclinical AKI models and have shown protection against AKI. This scientific review provides new ideas for targeting TLR4 in the treatment of AKI and provides strategies for the drug development against AKI.
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http://dx.doi.org/10.1016/j.lfs.2021.119155DOI Listing
April 2021

3D printing of immediate-release tablets containing olanzapine by filaments extrusion.

Drug Dev Ind Pharm 2021 Feb 1:1-10. Epub 2021 Feb 1.

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, Assam, India.

In this work, hot-melt extrusion (HME) is coupled with fused deposition modeling (FDM) mediated 3D printing to demonstrate additive manufacturing to fabricate immediate release (IR) prototypes of olanzapine with the aim of enhanced solubility using a fast disintegrating polymer (Kollicoat IR). Drug-polymer solubility and interaction parameters were estimated by Hansen solubility parameters and Hildebrand-Scott equation. The obtained values signified drug-polymer miscibility. The detailed physicochemical evaluations of the developed filament through HME and its derived 3D printed tablet by FDM technique were assessed thoroughly by several analytical means such as light microscopy, DSC, XRD, FT-IR, SEM, etc. The average disintegration time of this developed 3D printed IR tablet was found to be 63.33 (±3.6) sec complying with the USP limit. Additionally, dissolution study data revealed almost close correlations and both showed 100% of drug release within 15 min, thus complying with the definition of IR tablet. Thus, this study demonstrates the feasibility of directly using olanzapine-Kollicoat IR through the HME process without the addition of any plasticizers, organic solvents, etc. and coupling of HME with 3D printing technology allowing prototypes of IR tablet of olanzapine.
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http://dx.doi.org/10.1080/03639045.2021.1879833DOI Listing
February 2021

Nanostructured lipid carriers as a strategy for encapsulation of active plant constituents: Formulation and in vitro physicochemical characterizations.

Chem Phys Lipids 2021 03 2;235:105037. Epub 2021 Jan 2.

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Kamrup, Assam, India. Electronic address:

Active plant constituents obtained from edible sources have manifested their pharmacological potential as a therapy against several diseases. But the lack of their desired physicochemical properties such as solubility, permeability ultimately leads to poor bioavailability. Two potent active plant constituents namely, quercetin and piperine having a problem with either solubility or permeability or both, and hence require an advanced lipid-mediated separate formulation system to improve their aforementioned concerns. Concerning advancement in nanoformulations, lipid-based nano-carriers systems have created their mark as a novel drug delivery system. Therefore, an advanced formulation like nanostructured lipid carriers (NLCs) has been formulated individually for both the active plant constituents/drugs through the solvent evaporation technique using high shear homogenization method followed by sonication. Compritol® 888 ATO, a solid lipid, and squalene as liquid lipid was used in their optimized ratios to formulate individual NLCs. Blank and individual drugs loaded NLCs were further characterized for their in vitro physicochemical properties. NLCs showed a negative surface charge with an average particle size below 200 nm. Electron microscopy images showed an anomalous structure of both the formulated NLCs with higher % drug encapsulation efficiency (DEE) with the desired in vitro drug release profile. In the case of quercetin-NLCs, 93.18 ± 5.5 % DEE was observed followed by drug release up to 45.0 ± 1.3 % within 12 h, while piperine-NLCs showed 91.80 ± 2.51 % DEE and drug release up to 38 ± 5.2 % at the same time. XRD and DSC plots showed the conversion of both the drugs into an amorphous structure encapsulated in a lyophilized NLCs matrix. Finally, the safety profile for formulated NLCs was confirmed by haemolysis assay. Hence, the developed active plant constituents enriched NLCs can further be delivered separately and/or in combination, and also may further be evaluated both in vitro and in vivo means.
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http://dx.doi.org/10.1016/j.chemphyslip.2020.105037DOI Listing
March 2021

In-line treatments and clinical initiatives to fight against COVID-19 outbreak.

Respir Med 2020 Oct 17:106192. Epub 2020 Oct 17.

National Institute of Pharmaceutical Education and Research (NIPER-Guwahati), Department of Pharmaceuticals, Ministry of Chemicals & Fertilizers, Govt. of India, Sila Katamur (Halugurisuk), Changsari, Kamrup, 781101, Guwahati, Assam, India. Electronic address:

In December 2019, when the whole world is waiting for Christmas and New Year, the physicians of Wuhan, China, are astounded by clusters of patients suffering from pneumonia from unknown causes. The pathogen isolated from the respiratory epithelium of the patients is similar to previously known coronaviruses with some distinct features. The disease was initially called nCoV-2019 or SARS-nCoV-2 and later termed as COVID-19 by WHO. The infection is rapidly propagating from the day of emergence, spread throughout the globe and now became a pandemic which challenged the competencies of developed nations in terms of health care management. As per WHO report, 216 countries are affected with SARS-CoV-19 by August 5, 2020 with 18, 142, 718 confirmed cases and 691,013 deaths reports. Such huge mortality and morbidity rates are truly threatening and calls for some aggressive and effective measures to slow down the disease transmission. The scientists are constantly engaged in finding a potential solution to diagnose and treat the pandemic. Various FDA approved drugs with the previous history of antiviral potency are repurposed for COVID-19 treatment. Different drugs and vaccines are under clinical trials and some rapid and effective diagnostic tools are also under development. In this review, we have highlighted the current epidemiology through infographics, disease transmission and progression, clinical features and diagnosis and possible therapeutic approaches for COVID-19. The article mainly focused on the development and possible application of various FDA approved drugs, including chloroquine, remdesivir, favipiravir, nefamostate mesylate, penciclovir, nitazoxanide, ribavirin etc., vaccines under development and various registered clinical trials exploring different therapeutic measures for the treatment of COVID-19. This information will definitely help the researchers to understand the in-line scientific progress by various clinical agencies and regulatory bodies against COVID-19.
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http://dx.doi.org/10.1016/j.rmed.2020.106192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567661PMC
October 2020

Histone Lysine Demethylase JMJD2D/KDM4D and Family Members Mediate Effects of Chronic Social Defeat Stress on Mouse Hippocampal Neurogenesis and Mood Disorders.

Brain Sci 2020 Nov 9;10(11). Epub 2020 Nov 9.

Epigenetics & Neuropsychiatric Disorders Laboratory, CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Habsiguda, Hyderabad, Telangana 500007, India.

Depression, anxiety and related mood disorders are major psychiatric illnesses worldwide, and chronic stress appears to be one of the primary underlying causes. Therapeutics to treat these debilitating disorders without a relapse are limited due to the incomplete molecular understanding of their etiopathology. In addition to the well-studied genetic component, research in the past two decades has implicated diverse epigenetic mechanisms in mediating the negative effects of chronic stressful events on neural circuits. This includes the cognitive circuitry, where the dynamic hippocampal dentate gyrus (DG) neurogenesis gets affected in depression and related affective disorders. Most of these epigenetic studies have focused on the impact of acetylation/deacetylation and methylation of several histone lysine residues on neural gene expression. However, there is a dearth of investigation into the role of demethylation of these lysine residues in chronic stress-induced changes in neurogenesis that results in altered behaviour. Here, using the chronic social defeat stress (CSDS) paradigm to induce depression and anxiety in C57BL/6 mice and DG neural stem/progenitor cell (NSCs/NPCs) culture we show the role of the members of the JMJD2/KDM4 family of histone lysine demethylases (KDMs) in mediating stress-induced changes in DG neurogenesis and mood disorders. The study suggests a critical role of JMJD2D in DG neurogenesis. Altered enrichment of JMJD2D on the promoters of (inhibitor of differentiation 2) and (SRY-Box Transcription Factor 2) was observed during proliferation and differentiation of NSCs/NPCs obtained from the DG. This would affect the demethylation of repressive epigenetic mark H3K9, thus activating or repressing these and possibly other genes involved in regulating proliferation and differentiation of DG NSCs/NPCs. Treatment of the NSCs/NPCs culture with Dimethyloxallyl Glycine (DMOG), an inhibitor of JMJDs, led to attenuation in their proliferation capacity. Additionally, systemic administration of DMOG in mice for 10 days induced depression-like and anxiety-like phenotype without any stress exposure.
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http://dx.doi.org/10.3390/brainsci10110833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695311PMC
November 2020

Extruded filaments derived 3D printed medicated skin patch to mitigate destructive pulmonary tuberculosis: design to delivery.

Expert Opin Drug Deliv 2021 02 15;18(2):301-313. Epub 2020 Nov 15.

Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (Niper)-guwahati, Changsari, India.

: Quercetin in combination with polyvinylpyrrolidone (PVP) was found to limit the spreading of necrosis to unaffected tissues in tuberculosis-infected mice. Therefore, we hypothesized that 3D printed medicated skin patch incorporated with a quercetin-PVP combination would provide an appropriate therapeutic drug concentration with desired sustained release profile.: We fabricated quercetin-PVP 40 extruded-filaments by hot-melt extrusion (HME) technique along with Eudragit® RSPO and tri-ethyl citrate and further printed it to make medicated skin patches using fused deposition modeling (FDM) based 3D Printing technology. Various characterizations were performed to optimize the 3D-printed patch formulation.: Patch formulation has been optimized for several characterization parameters and was further assessed using SEM, DSC, and XRD studies to confirm the conversion of crystalline quercetin into an amorphous form. Finally, the pharmacokinetic profile of an optimized patch was studied in rats showing prolonged T, lowered C, and reduced fluctuations in plasma concentrations till 18 days with single skin application of 3D-printed medicated patch.: Overall data confirmed the feasibility of developing 3D printed medicated skin patches to provide plasma levels for continued 18 days in rats after a single application.
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http://dx.doi.org/10.1080/17425247.2021.1845648DOI Listing
February 2021

Targeting NLRP3 inflammasome as a promising approach for treatment of diabetic nephropathy: Preclinical evidences with therapeutic approaches.

Eur J Pharmacol 2020 Oct 26;885:173503. Epub 2020 Aug 26.

Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, PIN-781101, Assam, India. Electronic address:

Diabetes mellitus is an increasingly prevalent disease around the globe. The epidemic of diabetes mellitus and its complications pretenses the foremost health threat globally. Diabetic nephropathy is the notable complication in diabetes, leading to end-stage renal disease (ESRD) and premature death. Abundant experimental evidence indicates that oxidative stress and inflammation are the important mediators in diabetic kidney diseases and interlinked with various signal transduction molecular mechanisms. Inflammasomes are the critical components of innate immunity and are recognized as a critical mediator of inflammation and autoimmune disorders. NOD-like receptor protein 3 (NLRP3) inflammasome is the well-characterized protein and it exhibits the sterile inflammation through the regulation of pro-inflammatory cytokines interleukin (IL)-1β and IL-18 production in tissues. In recent years, the role of NLRP3 inflammasome in the pathophysiology of diabetic kidney diseases in both clinical and experimental studies has generated great interest. In the current review, we focused on and discussed the role of NLRP3 inflammasome in diabetic nephropathy. A literature review was performed using online databases namely, PubMed, Scopus, Google Scholar and Web of science to explore the possible pharmacological interventions that blunt the NLRP3 inflammasome-caspase-1-IL-1β/IL-18 axis and shown to have a beneficial effect in diabetic kidney diseases. This review describes the inhibition of NLRP3 inflammasome activation as a promising therapeutic target for drug discovery in future.
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http://dx.doi.org/10.1016/j.ejphar.2020.173503DOI Listing
October 2020

Stimuli-responsive In situ gelling system for nose-to-brain drug delivery.

J Control Release 2020 11 31;327:235-265. Epub 2020 Jul 31.

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER-Guwahati), Department of Pharmaceuticals, Ministry of Chemicals & Fertilizers, Govt. of India, Sila Katamur (Halugurisuk), Changsari, Kamrup-781101, Guwahati, Assam, India. Electronic address:

The diagnosis and treatment of neurological ailments always remain an utmost challenge for research fraternity due to the presence of BBB. The intranasal route appeared as an attractive and alternative route for brain targeting of therapeutics without the intrusion of BBB and GI exposure. This route directly and effectively delivers the therapeutics to different regions of the brain via olfactory and trigeminal nerve pathways. However, shorter drug retention time and mucociliary clearance curtail the efficiency of the intranasal route. The in situ mucoadhesive gel overthrow the limitations of direct nose-to-brain delivery by not only enhancing nasal residence time but also minimizing the mucociliary clearance and enzymatic degradation. This delivery system further improves the nasal absorption as well as bioavailability of drugs in the brain. The in situ mucoadhesive gel is a controlled and sustained release system that facilitates the absorption of various proteins, peptides and other larger lipophilic and hydrophilic moieties. Owing to multiple benefits, in situ gelling system has been widely explored to target the brain via nasal route. However, very few review works are reported which explains the application of in situ nasal gel for brain delivery of CNS acting moieties. Hence, in this piece of work, we have initially discussed the global statistics of neurological disorders reported by WHO and other reputed organizations, nasal anatomy, mechanism and challenges of nose-to-brain drug delivery. The work mainly focused on the use of different stimuli-responsive polymers, specifically thermoresponsive, pH-responsive, and ion triggered systems for the development of an effective and controlled dosage form, i.e., in situ nasal gel for brain targeting of bioactives. We have also highlighted the origin, structure, nature and phase transition behavior of the smart polymers found suitable for nasal administration, including poloxamer, chitosan, EHEC, xyloglucan, Carbopol, gellan gum and DGG along with their application in the treatment of neurological disorders. The article is aimed to gather all the information of the past 10 years related to the development and application of stimuli-responsive in situ nasal gel for brain drug delivery.
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http://dx.doi.org/10.1016/j.jconrel.2020.07.044DOI Listing
November 2020

Analytical method development and validation of reverse-phase high-performance liquid chromatography (RP-HPLC) method for simultaneous quantifications of quercetin and piperine in dual-drug loaded nanostructured lipid carriers.

J Pharm Biomed Anal 2020 Jul 29;186:113325. Epub 2020 Apr 29.

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, 781101, Assam, India. Electronic address:

Quercetin and piperine are often used as an add-on therapy for various diseases, however both drug exhibits poor aqueous solubility and photosensitivity issue. Therefore, the aim of the present study is to improve the pharmaceutical challenges by incorporating both the drugs in nanostructured lipid carriers (NLCs) and to develop a sensitive, selective, accurate and precise reverse-phase high performance liquid chromatography (RP-HPLC) method for the simultaneous analysis of both drugs in NLCs. Effective chromatographic separation of quercetin and piperine was achieved on Hypersil gold C-18 column and mobile phase consisting of a mixture of acetonitrile and HPLC grade water (pH 2.6, adjusted with 2%v/v glacial acetic acid) in an isocratic elution mode. The flow rate of the mobile phase was 1 mL/min, column temperature at 35 ± 0.2 °C and the injection volume was 20 μL. The retention time for quercetin and piperine were found to be at 2.80 min and 10.36 min, respectively and detected at an isobestic wavelength of 346 nm using a photodiode array (PDA) detector. The method was found to be specific for the simultaneous analysis of quercetin and piperine in presence of NLCs matrix, accurate (>90%) and precise (%RSD < 2%). The validated RP-HPLC method effectively utilised to determine the percentage drug entrapment efficiency cum percentage drug loading of quercetin and piperine in NLCs enriched formulations along with the secondary estimation of in vitro cumulative percentage drug release study. The results were found to be reliable, hence the validated RP-HPLC method could be further used for the simultaneous detection and quantification of both these drugs in other lipid-based nano-formulations such as solid-lipid nanoparticles, polymer-lipid hybrid nanoparticles, lipid drug conjugates, etc. in in vitro and in vivo.
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http://dx.doi.org/10.1016/j.jpba.2020.113325DOI Listing
July 2020

Recent strategies and advances in the fabrication of nano lipid carriers and their application towards brain targeting.

J Control Release 2020 05 12;321:372-415. Epub 2020 Feb 12.

National Institute of Pharmaceutical Education and Research (NIPER-Guwahati), Department of Pharmaceuticals, Ministry of Chemicals & Fertilizers, Govt. of India, NH 37, NITS Mirza, Kamrup, 781125 Guwahati, Assam, India. Electronic address:

In last two decades, the lipid nanocarriers have been extensively investigated for their drug targeting efficiency towards the critical areas of the human body like CNS, cardiac region, tumor cells, etc. Owing to the flexibility and biocompatibility, the lipid-based nanocarriers, including nanoemulsion, liposomes, SLN, NLC etc. have gained much attention among various other nanocarrier systems for brain targeting of bioactives. Across different lipid nanocarriers, NLC remains to be the safest, stable, biocompatible and cost-effective drug carrier system with high encapsulation efficiency. Drug delivery to the brain always remains a challenging issue for scientists due to the complex structure and various barrier mechanisms surrounding the brain. The application of a suitable nanocarrier system and the use of any alternative route of drug administration like nose-to-brain drug delivery could overcome the hurdle and improves the therapeutic efficiency of CNS acting drugs thereof. NLC, a second-generation lipid nanocarrier, upsurges the drug permeation across the BBB due to its unique structural properties. The biocompatible lipid matrix and nano-size make it an ideal drug carrier for brain targeting. It offers many advantages over other drug carrier systems, including ease of manufacturing and scale-up to industrial level, higher drug targeting, high drug loading, control drug release, compatibility with a wide range of drug substances, non-toxic and non-irritant behavior. This review highlights recent progresses towards the development of NLC for brain targeting of bioactives with particular reference to its surface modifications, formulations aspects, pharmacokinetic behavior and efficacy towards the treatment of various neurological disorders like AD, PD, schizophrenia, epilepsy, brain cancer, CNS infection (viral and fungal), multiple sclerosis, cerebral ischemia, and cerebral malaria. This work describes in detail the role and application of NLC, along with its different fabrication techniques and associated limitations. Specific emphasis is given to compile a summary and graphical data on the area explored by scientists and researchers worldwide towards the treatment of neurological disorders with or without NLC. The article also highlights a brief insight into two prime approaches for brain targeting, including drug delivery across BBB and direct nose-to-brain drug delivery along with the current global status of specific neurological disorders.
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http://dx.doi.org/10.1016/j.jconrel.2020.02.020DOI Listing
May 2020

Insulin receptor knockdown blocks filarial parasite development and alters egg production in the southern house mosquito, Culex quinquefasciatus.

PLoS Negl Trop Dis 2018 04 12;12(4):e0006413. Epub 2018 Apr 12.

Department of Biochemistry and Molecular Biology, University of Nevada, Reno, Nevada, United States of America.

Lymphatic filariasis, commonly known as elephantiasis, is a painful and profoundly disfiguring disease. Wuchreria bancrofti (Wb) is responsible for >90% of infections and the remainder are caused by Brugia spp. Mosquitoes of the genera Culex (in urban and semi-urban areas), Anopheles (in rural areas of Africa and elsewhere), and Aedes (in Pacific islands) are the major vectors of W. bancrofti. A preventive chemotherapy called mass drug administration (MDA), including albendazole with ivermectin or diethylcarbamazine citrate (DEC) is used in endemic areas. Vector control strategies such as residual insecticide spraying and long-lasting insecticidal nets are supplemental to the core strategy of MDA to enhance elimination efforts. However, increasing insecticide resistance in mosquitoes and drug resistance in parasite limit the effectiveness of existing interventions, and new measures are needed for mosquito population control and disruption of mosquito-parasite interactions to reduce transmission. Mosquito insulin signaling regulates nutrient metabolism and has been implicated in reduced prevalence and intensity of malaria parasite, Plasmodium falciparum, infection in mosquitoes. Currently no data are available to assess how insulin signaling in mosquitoes affects the development of multi-cellular parasites, such as filarial nematodes. Here, we show that insulin receptor knockdown in blood fed C. quinquefasciatus, the major vector of Wb in India, completely blocks the development of filarial nematode parasite to the infective L3 stage, and results in decreased ecdysteroid production and trypsin activity leading to fewer mosquito eggs. These data indicate that a functional mosquito insulin receptor (IR) is necessary for filarial parasite development and mosquito reproduction. Therefore, insulin signaling may represent a new target for the development of vector control or parasite blocking strategies.
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http://dx.doi.org/10.1371/journal.pntd.0006413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918164PMC
April 2018

Aspergillus Secondary Metabolite Database, a resource to understand the Secondary metabolome of Aspergillus genus.

Sci Rep 2017 08 4;7(1):7325. Epub 2017 Aug 4.

Division of Pharmacology & Toxicology, CSIR-IICT (Indian Institute of Chemical Technology), Ministry of Science & Technology (GOI), Uppal Road, Tarnaka, Hyderabad, Telangana, 500017, India.

Aspergillus is a genus of ubiquitous fungi that are pathologically & therapeutically important. Aspergillus Secondary Metabolites Database (A2MDB) is a curated compendium of information on Aspergillus & its secondary metabolome. A2MDB catalogs 807 unique non-redundantsecondary metabolites derived from 675 Aspergillus species. A2MDB has a compilation of 100 cellular targets of secondary metabolites, 44 secondary metabolic pathways, 150 electron and light microscopy images of various Aspergillus species. A phylogenetic representation of over 2500 strains has been provided. A2MDB presents a detailed chemical information of secondary metabolites and their mycotoxins. Molecular docking models of metabolite-target protein interactions have been put together. A2MDB also has epidemiological data representing Aspergillosis and global occurrence of Aspergillus species. Furthermore a novel classification of Aspergillosis along with 370 case reports with images, were made available. For each metabolite catalogued, external links to related databases have been provided. All this data is available on A2MDB, launched through Indian Institute of Chemical Technology, Hyderabad, India, as an open resource http://www.iictindia.org/A2MDB . We believe A2MDB is of practical relevance to the scientific community that is in pursuit of novel therapeutics.
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http://dx.doi.org/10.1038/s41598-017-07436-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544713PMC
August 2017

Isolation and characterization of phthalates from Brevibacterium mcbrellneri that cause cytotoxicity and cell cycle arrest.

EXCLI J 2017 24;16:375-387. Epub 2017 Mar 24.

Biology Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad -500 007, India.

Bacteria belonging to the family Brevibacterieae are ubiquitous Gram positive organisms that are responsible for the feet odour and cheese aroma. is a relatively new member belonging to Brevibacterieae. In the current manuscript we discuss isolation of biologically active metabolites from . Two aromatic esters were isolated from by "Bioassay guided fractionation strategy" and identified as di-(2-ethylhexyl) phthalate and dibutyl phthalate by chemical characterization using biophysical techniques. The phthalate compounds show broad spectrum antibacterial activity and mosquito larvicidal activity. Mosquito larvicidal activity has been attributed to inhibition of acetylcholinesterase enzyme activity. These compounds were found to be cytotoxic in multiple cell lines causing cell cycle arrest in G1 phase.
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http://dx.doi.org/10.17179/excli2017-145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427467PMC
March 2017

Acetylcholinesterase inhibitory activity of stigmasterol & hexacosanol is responsible for larvicidal and repellent properties of Chromolaena odorata.

Biochim Biophys Acta Gen Subj 2017 Mar 1;1861(3):541-550. Epub 2016 Dec 1.

Biology Division, Council for Scientific and Industrial Research - Indian Institute of Chemical Technology (Ministry of Science and Technology), Uppal Road, Tarnaka, Hyderabad 500607, India; NIPER Guwahati, Institute of Pharmacy, Guwahati Medical College & Hospital, 1st Floor, Guwahati 781 032, Assam, India.

Background: Chromolaena odorata, has been traditionally known for its insect repellent property. Aim of this study was to determine larvicidal tendency of C. odorata on Culex quinquefasciatus and isolate compounds responsible for this activity and to determine the mechanism of action of these compounds.

Methods: C. odorata plant extract was screened for mosquito larvicidal activity. The extract was fractionated using chromatography and the bioactive fraction showing larvicidal activity was identified. The chemical nature of the compounds in the bioactive fraction was determined using NMR and Mass spectrometry.

Results: We identified phytosterols and alkanols to be the compounds regulating larvicidal activity in the bioactive fraction of the plant extract. Stigmasterol and 1-hexacosanol were identified to be the chief orchestrators of larvicidal activity and their mode of action has been observed to be neurotoxicity. At a molecular level both stigmasterol and 1-hexacosanol were found to be inhibiting acetylcholinesterase activity in C. quinquefasciatus & A. aegypti. The acetylcholinesterase inhibitory effect was validated in vitro using recombinant acetylcholinesterase and ex vivo in larval homogenates of Culex and Aedes. Electrophysiological studies using electroantennography have shown enhanced neural response to these compounds.

Conclusions: Neurotoxic effect of C. odorata derived stigmasterol and 1-hexacosanol, exerted through acetylcholinesterase inhibition was responsible for the mortality of C. quinquefasciatus, A. aegypti &Chironomus riparius. EAG studies pointed out hyper-excitability of the olfactory system by these compounds.

General Significance: These compounds are natural agents for mosquito control that can be used in vector control as larvicidal compounds, pending further investigations.
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http://dx.doi.org/10.1016/j.bbagen.2016.11.044DOI Listing
March 2017

Spatial distribution and cluster analysis of dengue using self organizing maps in Andhra Pradesh, India, 2011-2013.

Parasite Epidemiol Control 2018 Feb 4;3(1):52-61. Epub 2016 Nov 4.

Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India.

Background And Objectives: Dengue is an emerging and re-emerging infectious disease, transmitted by mosquitoes. It is mostly prevalent in tropical and sub-tropical regions of the world, particularly, in Asia-Pacific region. To understand the epidemiology and spatial distribution of dengue, a retrospective surveillance study was conducted in the state of Andhra Pradesh, India during 2011-2013.

Material And Methods: District-wise disease endemicity levels were mapped through geographical information system (GIS) tools. Spatial statistical analysis such as Getis-Ord Gi* was performed to identify hot spots and cold spots of dengue disease. Similarly self organizing maps (SOM), a datamining tool was also applied to understand the endemicity patterns in study areas.

Results: The analysis shows that districts of Warangal, Karimnagar, Khammam and Vizianagaram are reported as hot spot regions whereas Adilabad and Nizamabad reported as cold spots for dengue. The SOM classify 23 districts in 03 major (07 sub) clusters. These SOM clusters were projected in the geographical space and based on the disease/cases intensity the districts were characterized into low, medium and high endemic areas.

Conclusion: This visualization approach, SOM-GIS helps the public health officials to identify the disease endemic zones and take real time decisions for disease management.
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http://dx.doi.org/10.1016/j.parepi.2016.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952657PMC
February 2018

Mutational analysis of the FIGLA gene in women with idiopathic premature ovarian failure.

Menopause 2015 May;22(5):520-6

From the 1Biology Division, CSIR Indian Institute of Chemical Technology, Hyderabad, India; 2Department of Genetics, Osmania University, Hyderabad, India; and 3Infertility Institute and Research Center, Secunderabad, India.

Objective: The aim of our study was to identify the association of FIGLA (factor in the germ line α) gene variants with premature ovarian failure (POF) in the Indian population.

Methods: Two hundred nineteen women with idiopathic POF and 230 healthy controls were recruited for this study. All exons, intron-exon boundaries, and untranslated regions of the FIGLA gene were analyzed by polymerase chain reaction and sequencing. All FIGLA variants were analyzed in silico, using PolyPhen, SIFT, MutationTaster, PMUT, I-Mutant, Mupro, Align-GVGD, PROVEAN, and HOPE software, to predict pathogenicity and changes in protein stability.

Results: Seven different FIGLA variants were detected among women with POF. Two exon 3 variants, c.427G → C and c.557C → T, showed strong association between cases and controls (P = 0.02 and P = 0.02, respectively). Significant differences in both of these variants were observed between cases and controls in genotype and dominant models. No significant difference between controls and women with POF was found on haplotype analysis. A nonsynonymous variant, p.(Arg83Cys), was found only in POF cases. Variant p.(Arg83Cys) lies in the functional domain of the FIGLA gene (basic helix-loop-helix), and protein alignments reveal that it is highly conserved among mammals. In silico analysis suggests the functional involvement of p.(Arg83Cys) and p.(Ser141Thr) variants in POF pathogenesis.

Conclusions: We have established a strong association between FIGLA gene variants and POF in Indian women, which may be a potential genetic risk factor in the development of idiopathic POF. However, further independent genetic and functional studies are necessary to confirm our findings.
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http://dx.doi.org/10.1097/GME.0000000000000340DOI Listing
May 2015

Towards seasonal forecasting of malaria in India.

Malar J 2014 Aug 10;13:310. Epub 2014 Aug 10.

Department of Earth, Atmospheric and Planetary Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Background: Malaria presents public health challenge despite extensive intervention campaigns. A 30-year hindcast of the climatic suitability for malaria transmission in India is presented, using meteorological variables from a state of the art seasonal forecast model to drive a process-based, dynamic disease model.

Methods: The spatial distribution and seasonal cycles of temperature and precipitation from the forecast model are compared to three observationally-based meteorological datasets. These time series are then used to drive the disease model, producing a simulated forecast of malaria and three synthetic malaria time series that are qualitatively compared to contemporary and pre-intervention malaria estimates. The area under the Relative Operator Characteristic (ROC) curve is calculated as a quantitative metric of forecast skill, comparing the forecast to the meteorologically-driven synthetic malaria time series.

Results And Discussion: The forecast shows probabilistic skill in predicting the spatial distribution of Plasmodium falciparum incidence when compared to the simulated meteorologically-driven malaria time series, particularly where modelled incidence shows high seasonal and interannual variability such as in Orissa, West Bengal, and Jharkhand (North-east India), and Gujarat, Rajastan, Madhya Pradesh and Maharashtra (North-west India). Focusing on these two regions, the malaria forecast is able to distinguish between years of "high", "above average" and "low" malaria incidence in the peak malaria transmission seasons, with more than 70% sensitivity and a statistically significant area under the ROC curve. These results are encouraging given that the three month forecast lead time used is well in excess of the target for early warning systems adopted by the World Health Organization. This approach could form the basis of an operational system to identify the probability of regional malaria epidemics, allowing advanced and targeted allocation of resources for combatting malaria in India.
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http://dx.doi.org/10.1186/1475-2875-13-310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251696PMC
August 2014

Design, synthesis and anti-mycobacterial activity of 1,2,3,5-tetrasubstituted pyrrolyl-N-acetic acid derivatives.

Eur J Med Chem 2014 Sep 1;84:118-26. Epub 2014 Jul 1.

Crop Protection Chemicals, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India. Electronic address:

A novel synthesis of highly substituted pyrrole-N-acetic derivatives is described through the coupling of 1,4-diketones with amino acids following Paal-Knorr's approach. These pyrrole-N-acetic acid derivatives are found to exhibit potent anti-mycobacterial activity against Mycobacterium smegmatis and Mycobacterium tuberculosis strain H37Rv. In particular, 5n, 5q &5r are found to display excellent anti-mycobacterial activity against M. tuberculosis strain H37Rv with MIC values in the range of 2.97 μM. Conversely, these compounds showed low cytotoxicity (selectivity index: >16.83) against HEK-293T cell line.
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http://dx.doi.org/10.1016/j.ejmech.2014.06.075DOI Listing
September 2014

Assessment of genotoxic effects of lead in occupationally exposed workers.

Environ Sci Pollut Res Int 2014 Oct 8;21(19):11469-80. Epub 2014 Jun 8.

Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad, Andhra Pradesh, 500007, India.

The genotoxicological effects in 200 lead acid storage battery recycling and manufacturing industry workers in Hyderabad along with matched 200 controls were studied. The genetic damage was determined by comet, micronucleus (MN), and chromosomal aberration (CA) test in peripheral blood lymphocytes (PBL). The MN test was also carried out in buccal epithelial cells (BECs). Pb in ambient air, blood Pb (B-Pb) concentrations, and hematological parameters were measured. The superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), and malondialdehyde (MDA) formed were also studied. The results of the present study showed that there was a statistically significant (P < 0.01) increase in mean percent tail DNA, frequency of CA, and MN in PBL as well as in BEC as compared to controls. Pb in ambient air and B-Pb concentrations were found to be significantly higher (P < 0.01). The hematocrit, hemoglobin, and red blood cell values were significantly lowered in Pb-exposed workers in comparison to controls. SOD, GPx, and CAT levels were significantly decreased while GSH and MDA levels increased in exposed group when compared to control group. The present study suggests that environmental health standards should be enforced to control Pb contamination from battery industries to reduce human health risk.
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http://dx.doi.org/10.1007/s11356-014-3128-9DOI Listing
October 2014

Immune peptides modelling of Culex pipiens sp by in silico methods.

J Vector Borne Dis 2012 Mar;49(1):19-22

Bioinformatics Group, Biology Division, Indian Institute of Chemical Technology (CSIR), Hyderabad, India.

Background: In the past 60 years, antibiotics have been critical in the fight against infectious diseases caused by bacteria and other microbes. Development of resistance to the antibiotics is emerging as a major public health issue which has resulted in the search for new antibiotics in order to maintain a pool of effective drugs at all times. Currently, there is a great interest in cationic peptides as antibiotics. These are reported to destroy the host cell membrane rather interacting with the other cell components, which may not face emergence of resistance. In mosquitoes, peptides like cecropin, defensin and gambicin reported to have inhibitory effect on bacteria, fungi and parasites. These peptides are well-characterized at both the biochemical and molecular level from Anopheles and Culex species, yet their 3D structures were not reported.

Methods: Defensin, cecropin and gambicin immune peptides of Culex pipiens was characterised to have antiparasitic, antibacterial and antifungal activities. Since the crystal structure of defensin, cecropin and gambicin are not yet available their 3D structures were determined using homology modeling and Rosetta fragment insertion methods and were validated.

Results: Stereo chemical evaluation indicated that defensin and gambicin showed that 100% residues of constructed model lie in the most favoured and allowed regions. Cecropin iso-forms A and B showed 100% while C showed 97.6% residues that lie in most favoured and allowed regions, which indicated quality models.

Conclusion: Predicted model provide insight into their structure and aid in the development of novel antibiotic peptides.
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March 2012

Impact of weather variables on mosquitoes infected with Japanese encephalitis virus in Kurnool district, Andhra Pradesh.

Asian Pac J Trop Med 2012 May;5(5):337-41

Bioinformatics Group, Biology Division, Indian Institute of Chemical Technology (CSIR), Hyderabad, Andhra Pradesh, India.

Objective: To assess the virus infection in mosquitoes during different seasons and correlated with various climatic factors.

Methods: The field collected vectors were screened for Japanese encephalitis (JE) virus after dessication using ELISA method. Most of the positive pools were recorded from Culex tritaeniorhynchus (Cx. tritaeniorhynchus) and Culex. gelidus (Cx. gelidus) during JE transmission season (winter) and some positive pools were also reported during non JE transmission periods (i.e. summer and rainy seasons).

Results: The minimum infection rates (MIR) of 1.75 from Cx. tritaeniorhynchus and 0.17 from Cx. gelidus has been reported in the year 2002 at the beginning of the study and the values were found nil at the end of the study (2006) from the study areas of Kurnool district.

Conclusions: From this study it is noted that MIR of Cx. gelidus and Cx. tritaeniorhynchus were modulated by various meteorological parameters. The mosquito vector abundance increases after the monsoon period (winter) and lowest in dry season (summer). Similarly, MIR fluctuated between seasons with higher MIR recorded after monsoon period and lower in the rest of season. Impact of these metrological parameters in JE virus infected mosquitoes is discussed in this paper.
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http://dx.doi.org/10.1016/S1995-7645(12)60054-6DOI Listing
May 2012

Assessing the relationship among physicochemical properties of proteins with respect to hydrophobicity: a case study on AGC kinase superfamily.

Indian J Biochem Biophys 2010 Dec;47(6):370-7

Bioinformatics Group, Biology Division, Indian Institute of Chemical Technology (C.S.I.R), Hyderabad 500 007, Andhra Pradesh, India.

Understanding the protein structures is crucial, as it is involved in every cellular activity. Several experimental techniques, such as X-Ray crystallography, nuclear magnetic resonance and electron microscopy are available to gain insight about the structure and function of a protein molecule. Gigantic data on protein structural and sequential information is deposited in various repositories regularly which provide us the scope for more theoretical studies. Hydrophobicity always plays a vital role in tertiary structure formation and behavior of a protein molecule. This study focuses on elucidating influence of several physicochemical properties on hydrophobicity of AGC kinase proteins. AGC kinase superfamily is selected due to its tremendous structural and functional variability and sequence data availability. A combined data mining and stochastic approach confirmed that out of 47 parameters, transmembrane tendency influences the target variable most, followed by percent buried residues, GRAVY (Grand Average Hydropathicity) and aliphatic index. Calculating the influence of different physicochemical parameters and their interrelation will aid tremendously in the future of protein science.
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December 2010

Classification and clustering analysis of pyruvate dehydrogenase enzyme based on their physicochemical properties.

Bioinformation 2010 Apr 30;4(10):456-62. Epub 2010 Apr 30.

Bioinformatics Group, Biology Division, Indian Institute of Chemical Technology, Hyderabad-500607, A.P, India.

Biological systems are highly organized and enormously coordinated maintaining greater complexity. The increment of secondary data generation and progress of modern mining techniques provided us an opportunity to discover hidden intra and inter relations among these non linear dataset. This will help in understanding the complex biological phenomenon with greater efficiency. In this paper we report comparative classification of Pyruvate Dehydrogenase protein sequences from bacterial sources based on 28 different physicochemical parameters (such as bulkiness, hydrophobicity, total positively and negatively charged residues, α helices, β strand etc.) and 20 type amino acid compositions. Logistic, MLP (Multi Layer Perceptron), SMO (Sequential Minimal Optimization), RBFN (Radial Basis Function Network) and SL (simple logistic) methods were compared in this study. MLP was found to be the best method with maximum average accuracy of 88.20%. Same dataset was subjected for clustering using 2*2 grid of a two dimensional SOM (Self Organizing Maps). Clustering analysis revealed the proximity of the unannotated sequences with the Mycobacterium and Synechococcus genus.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951700PMC
http://dx.doi.org/10.6026/97320630004456DOI Listing
April 2010
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