rahat ali - Academia.edu (original) (raw)

Papers by rahat ali

Research paper thumbnail of Role of seed priming to enhance growth and development of crop plants against biotic and abiotic stresses

Abiotic and biotic stresses severely affect the crop’s growth and development at every stage of g... more Abiotic and biotic stresses severely affect the crop’s growth and development at every stage of growth cycle. Seed priming is helpful technique to enhance seed germination and growth in stress environment. Seed priming is a control procedure followed by re-drying which will allow the seed to imbibe water stimulate the internal biological process essential for germination but this process will not permit the seed to be truly germinate. Currently many seed priming method have been used like hydro-priming, osmo-priming, halo-priming, thermo-priming, bio-priming and solid matrix priming. Various studies confirmed that seed priming has several advantages including, early emergence high water use efficiency, stand establishment, deeper roots germination in broad range of temperature and resistance against disease and environmental stresses.

Research paper thumbnail of Hesperidin Targets Leishmania donovani Sterol C-24 Reductase to Fight against Leishmaniasis

ACS Omega, 2021

Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found ... more Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found effective against an array of pathogens including fungi, bacteria, viruses, and protozoa. Here, we evaluated its antileishmanial activity and possible mechanism of action through different in vitro and in silico experiments. It inhibited the growth and proliferation of the parasites significantly with a IC50 value of 1.019 ± 0.116 mM in vitro. It also reduced the growth of intramacrophagic amastigotes with a IC50 value of 0.2858 ± 0.01398 mM. It induced the reactive oxygen species (ROS) in parasites in a dosedependent manner. Through 2,7-dichloro dihydro fluorescein diacetate (H 2 DCFDA) staining, it was observed that around 96.9% parasites were ROS positive at 2.0 mM concentration of hesperidin. The ROS generated led to the apoptosis of parasites in a dose-dependent manner as observed by annexin/PI staining. Molecular docking with one of the very important and unique drug-targets of Leishmania donovani sterol C-24 reductase resulted in its significant inhibition. Here, we for the first time showed that hesperidin induced the antileishmanial response through the induction of apoptosis and inhibition of sterol C-24 reductase. Our study will be helpful in the development of a cost-effective antileishmanial lead with higher efficacy.

Research paper thumbnail of GC–MS analysis of phytoconstituents of Acacia nilotica and its molecular docking with drug-targets of Leishmania donovani to combat leishmanaisis

Acacia nilotica is an important medicinal plant, found in Africa, Middle East, and Indian subcont... more Acacia nilotica is an important medicinal plant, found in Africa, Middle East, and Indian subcontinent. Every part of the plant possesses a wide array of biologically-active and therapeutically important compounds and have been used in traditional-system of medicine. We reported the antileishmanial activity of Acacia nilotica (A. nilotica) bark methanolic extract through in vitro assays and dissected the mechanism of its action through in silico studies. Bark methanolic extract exhibited anti-promastigote and anti-amastigote potency with IC50 value of 19.6 + 0.9037 µg/ml and 77.52 + 5.167 µg/ml respectively in time and dose dependent manner. It showed very low cytotoxicity having CC50 value of 432.7 + 7.71 µg/ml on human-macrophage cell line, THP-1. The major constituents identified by GC-MS analysis are 13-docosenoic acid (34.06%), lupeol(20.15 %), 9,12-octadecadienoic acid (9.92 %) and 6-octadecanoic acid (8.43 %) bind effectively with the potential drug-targets of Leishmania donovani (L. donovani) including sterol 24-c-methytransferase (SMT), trypanothione reductase (TR), pteridine reductase (PTR1) and adenine phosphorybosyl transferase (APRT); suggest the possible mechanism of its antileishmanial action. The highest affinity with all these targets was shown by lupeol. The pharmacokinetic studies, predicted bioactivity scores and acute toxicity studies of major extract constituents support safe antileishmanial drug candidate. This study proved the antileishmanial potential of bark-methanolic extract A. nilotica and its mechanism of action through the inhibition of potential drug targets of L. donovani.

Research paper thumbnail of Pregnancy in a Secondary Infertile Woman with Polycystic Ovarian Syndrome (PCOS) –A Case Report

Case Report Polycystic ovarian syndrome, also called Stein-Leventhal syndrome, is a disorder invo... more Case Report Polycystic ovarian syndrome, also called Stein-Leventhal syndrome, is a disorder involving multiple endocrine systems resulting in abnormal levels of gonadotropins, androgens, and glucose in the blood. Several other manifestations arise in association with PCOS like a blockage in the fallopian tube, endometrial polyps, cervical cancer, ovarian cancer, etc. We hereby delineate a case of a 34-year-old married female in whom PCOS was diagnosed at the age of 22. After her marriage, she presented with the complaint of infertility. Investigations revealed that she had a polyp in her right fallopian tube after which a polypectomy was performed. She was able to conceive six months after the surgery was done. Currently, after seven years, she presented with the same complaint of infertility. After undergoing relevant procedures, her secondary infertility was ascertained as a result of PCOS. Following regular medications, she was able to get pregnant with triplets. This pregnancy ...

Research paper thumbnail of Assessment of the Antileishmanial Potential of Cassia fistula Leaf Extract

ACS Omega, 2021

Cassia fistula has a wide array of biologically active and therapeutically important class of com... more Cassia fistula has a wide array of biologically active and therapeutically important class of compounds. Leishmania donovani important drug targets, sterol 24-c methyltransferase (LdSMT), trypanothione reductase (LdTR), pteridine reductase (LdPTR1), and nucleoside hydrolase (LdNH), were modelled, and molecular docking was performed against the abundant phytochemicals of its leaf extract. Molecular docking results provided the significant prima facie evidence of the leaf extract to have antileishmanial potential. To confirm this, we performed in vitro antileishmanial and cytotoxicity assays. Methanolic extract of C. fistula leaves showed growth inhibition and proliferation of L. donovani promastigote with an IC 50 value of 43.31 ± 4.202 μg/mL. It also inhibited the growth of intra-macrophagic amastigotes with an IC 50 value of 80.76 ± 3.626 μg/mL. C. fistula extract was found cytotoxic at a very high concentration on human macrophages (CC 50 = 626 ± 39 μg/mL). Annexin V/propidium iodide (PI) staining assay suggested partial apoptosis induction in parasites by C. fistula to exert its antileishmanial activity. Here, for the first time, we have shown the antileishmanial potential of C. fistula leaves. Overall, our results could open new insight for an affordable and natural antileishmanial with high efficacy and less toxicity.

Research paper thumbnail of Leishmania donovani infection differentially regulates small G-proteins

Journal of cellular biochemistry, Jan 26, 2018

Leishmania is a protozoan parasite that resides and replicates in macrophages and causes leishman... more Leishmania is a protozoan parasite that resides and replicates in macrophages and causes leishmaniasis. The parasite alters the signaling cascade in host macrophages and evades the host machinery. Small G-proteins are GTPases, grouped in 5 different families that play a crucial role in the regulation of cell proliferation, cell survival, apoptosis, intracellular trafficking, and transport. In particular, the Ras family of small G-proteins has been identified to play a significant role in the cellular functions mentioned before. Here, we studied the differential expression of the most important small G-proteins during Leishmania infection. We found major changes in the expression of different isoforms of Ras, mainly in N-Ras. We observed that Leishmania donovani infection led to enhanced N-Ras expression, whereas it inhibited K-Ras and H-Ras expression. Furthermore, an active N-Ras pull-down assay showed enhanced N-Ras activity. L donovani infection also increased extracellular signa...

Research paper thumbnail of Sphingosine-1-phosphate signaling in Leishmania donovani infection in macrophages

PLoS neglected tropical diseases, Aug 1, 2018

Sphingosine-1-phosphate (S1P) is a crucial regulator of a wide array of cellular processes, such ... more Sphingosine-1-phosphate (S1P) is a crucial regulator of a wide array of cellular processes, such as apoptosis, cell proliferation, migration, and differentiation, but its role in Leishmania donovani infection is unknown. In the present study, we observed that L. donovani infection in THP-1 derived macrophages (TDM) leads to decrease in the expression of S1pr2 and S1pr3 at mRNA level. We further observed that Leishmania infection inhibits the phosphorylation of sphingosine kinase 1 (sphK1) in a time-dependent manner. Exogenous S1P supplementation decreases L. donovani induced ERK1/2 phosphorylation and increases p38 phosphorylation in TDM, resulting in a decrease in the intracellular parasite burden in a dose-dependent manner. On the other hand, sphK inhibition by DMS increases ERK1/2 phosphorylation leading to increased IL-10 and parasite load. To gain further insight, cytokines expression were checked in S1P supplemented TDM and we observed increase in IL-12, while decrease IL-10 e...

Research paper thumbnail of Restorative management of the cleft patient: CLP series part 10

Orthodontic Update, 2014

This article describes the role of the restorative dentist in the multidisciplinary management of... more This article describes the role of the restorative dentist in the multidisciplinary management of cleft lip and palate patients. The various clinical presentations and restorative challenges are outlined. The restorative treatment of cleft patients requires the use of a wide range of different clinical skills and techniques to achieve oral rehabilitation. The various treatment modalities are described and range from minimally invasive adhesive techniques to conventional fixed and removable prosthodontics, obturators and the use of dental implants. The eventual restorative outcomes are related to the initial severity of the defect and the degree of success of the previous surgical and orthodontic interventions. Clinical Relevance: This article will be of interest to clinicians, technicians, dental care professionals and other members of the team who are involved in the oral rehabilitation of cleft patients.

Research paper thumbnail of Implication of sphingosine-1-phosphate signaling in diseases: molecular mechanism and therapeutic strategies

Journal of Receptors and Signal Transduction, 2017

Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular processes that ... more Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular processes that is initiated by the intracellular production of bioactive lipid molecule, sphingosine-1-phosphate. Binding of sphingosine-1-phosphate to its extracellular receptors activates diverse downstream signaling that play a critical role in governing physiological processes. Increasing evidence suggests that this signaling pathway often gets impaired during pathophysiological and diseased conditions and hence manipulation of this signaling pathway may be beneficial in providing treatment. In this review, we summarized the recent findings of S1P signaling pathway and the versatile role of the participating candidates in context with several disease conditions. Finally, we discussed its possible role as a novel drug target in different diseases.

Research paper thumbnail of Robust controller design for attitude control of control moment gyroscope

2015 12th International Bhurban Conference on Applied Sciences and Technology (IBCAST), 2015

Robust controller design in presence of disturbance and system parameter uncertainties has been a... more Robust controller design in presence of disturbance and system parameter uncertainties has been a challenging task. In this paper attitude control of ECP 750 Gyroscope in presence of uncertainties is solved using LMI based multi objective state feedback H2 /H∞ controller. The attitude control problem addressed here resembles the formulation of polytopic model of MIMO gyroscope model to cater the parameter uncertainty and subsequent robust controller design using LMI framework is novelty of this work. MATLAB simulation results show better robust attitude control and disturbance rejection.

Research paper thumbnail of Microbial Hydroxylation of Hydroxyprogesterones and α-Glucosidase Inhibition Activity of Their Metabolites

Zeitschrift für Naturforschung B, 2007

Microbial transformation of 11α-hydroxyprogesterone (1) with Cunninghamella elegans, Gibberella f... more Microbial transformation of 11α-hydroxyprogesterone (1) with Cunninghamella elegans, Gibberella fujikuroi, Fusarium lini, and Candida albicans yielded 11α,15α,16α-trihydroxypregn-4- ene-3,20-dione (3), 11α-hydroxy-5α-pregnane-3,20-dione (4), 6β ,11α-dihydroxypregn-4-ene-3,20- dione (5), 11α-hydroxypregna-1,4-diene-3,20-dione (6), 11α,17β -dihydroxyandrost-4-en-3-one (7), and 11α,15α-dihydroxypregn-4-ene-3,20-dione (8). On the other hand, microbial transformation of 17α-hydroxyprogesterone (2) with Cunninghamella elegans and Fusarium lini yielded 11α,17α- dihydroxypregn-4-ene-3,20-dione (9), and 17α-hydroxypregna-1,4-diene-3,20-dione (10). The structures of the metabolites 3 - 10 were deduced on the basis of spectroscopic methods. Compound 3 was identified as a new metabolite, which exhibited a promising inhibitory activity against the α-glucosidase enzyme.

Research paper thumbnail of Effect of Low Level Feeding of Tylosin and Zinc Bacitracin on the Weight Gain and Immunity of Broiler Chicks Vaccinated Against Newcastle Disease Virus

Journal of Biological Sciences, 2003

Research paper thumbnail of Linear quadratic tracking for noisy signal with state space recursive least squares noise rejection

2013 XXIV International Conference on Information, Communication and Automation Technologies (ICAT), 2013

In many real life problems, related to closed loop control systems the reference signal is corrup... more In many real life problems, related to closed loop control systems the reference signal is corrupted by additive noise. The noisy reference signal leads to inferior tracking by the plant. However tracking performance can further improved if noise is removed from the reference signal prior applying to the control system. In this paper, we present a linear quadratic regulator (LQR) based control scheme that incorporates state space recursive least squares (SSRLS) method for cleaning the noisy reference signal. The proposed closed loop structure provides an optimal tracking of a reference signal while minimizing the effect of external disturbance acting on the plant. The prior knowledge about the external disturbance is utilized by the control scheme. Functioning of the proposed algorithm is demonstrated with the help of computer simulations with a practical application of third order system of grid tie converters. The result shows significant improvement in tracking performance as compared to the tracking of a noisy reference signal applied directly to the control system.

Research paper thumbnail of Self tuned SSRLS filter for online tracking and removal of power Line Interference from Electrocardiogram

ABSTRACT Power-Line Interference (PLI) may seriously distort the ECG (Electrocardiogram) signal r... more ABSTRACT Power-Line Interference (PLI) may seriously distort the ECG (Electrocardiogram) signal rendering the ECG analysis inaccurate. Various types of Notch filtering and adaptive cancellation schemes have been used to eliminate PLI interference from ECG. In this paper we propose an enhanced adaptive noise canceller (ANC) based on State Space Recursive Least Square (SSRLS) for elimination of PLI. SSRLS algorithm is a state space model-dependent recursive algorithm characterized by fast rate of convergence and hence exhibits excellent tracking performance. State-space formulation of noise model enables SSRLS filter to be implemented in an instinctive manner in comparison to other approaches. The proposed method is very effective for online tracking of PLI without requiring a reference noise source. The proposed method can also be employed to filter out the PLI even when corrupted ECG signal has low signal-to-noise ratio (SNR).

Research paper thumbnail of A New Anticholinergic Steroidal Alkaloid from Fritillaria imperialis of Turkish Origin

Research paper thumbnail of Ammonium versus Nitrate Nutrition of Plants Stimulates Microbial Activity in the Rhizosphere

Plant and Soil, 2005

Using an alkaline calcareous soil, pot experiments were conducted to elucidate the effects of NH ... more Using an alkaline calcareous soil, pot experiments were conducted to elucidate the effects of NH 4 + vs. NO 3) nutrition (50 or 100 mg kg)1 soil) of wheat and maize on microbial activity in the rhizosphere and bulk soils. Dicyandiamide was used as nitrification inhibitor to maintain NH 4 + as the predominant N source for plants grown in NH 4 +-treated soil. While maize grew equally well on both N sources, root and shoot growth of wheat was higher under NH 4 + than under NO 3) nutrition. Bacterial population density on roots, but not in the rhizosphere soil, was higher under NH 4 + than under NO 3 supplied at 150 mg N kg)1 soil; whereas at both N levels applied, NH 4 + compared to NO 3) nutrition of wheat and maize significantly increased microbial biomass in the rhizosphere soil. Under both plant species, NH 4 + vs. NO 3) nutrition also increased aerobic and anaerobic respiration, and dehydrogenase activity in the rhizosphere. As microbial activity in the planted bulk and unplanted soils was hardly affected by the N-source, we hypothesize that the stimulation by NH 4 + of the rhizosphere microbial activity was probably due to higher availability of root exudates under NH 4 + than under NO 3) nutrition.

Research paper thumbnail of Cynaroside inhibits Leishmania donovani UDP-galactopyranose mutase and induces reactive oxygen species to exert antileishmanial response

Bioscience Reports, 2021

Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activiti... more Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time- and dose-dependent manner with 50% of inhibitory concentration (IC50) value of 49.49 ± 3.515 µM in vitro. It inhibited the growth of parasite significantly at only 20 µM concentration when used in combination with miltefosine, a standard drug which has very high toxicity. It also inhibited the intra-macrophagic parasite significantly at low doses when used in combination with miltefosine. It showed less toxicity than the existing antileishmanial drug, miltefosine at similar doses. Propidium iodide staining showed that cynaroside inhibited the parasites in G0/G1 phase of cell cycle. 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining showed cynaroside induced antileishmanial activity through reac...

Research paper thumbnail of Evaluation of the Genotoxicity of Chlorpyrifos in Common Indus Valley Toad, <i>Bufo stomaticus</i> Using Alkaline Single-Cell Gel Electrophoresis (Comet) Assay

Agricultural Sciences, 2014

Chlorpyrifos is a commonly used pesticide of organophosphate group, which causes toxicological ef... more Chlorpyrifos is a commonly used pesticide of organophosphate group, which causes toxicological effects in non-target organisms especially fish and frogs. In the present study, the genotoxicity of sublethal concentrations of chlorpyrifos was observed in the erythrocytes of common Indus valley toad, Bufo stomaticus, using the Alkaline Single-Cell Gel Electrophoresis (Comet) assay. In the first step, acute toxicity of chlorpyrifos was evaluated by exposing the tadpoles to high concentrations of the pesticide. The acute LC 50 value of chlorpyrifos, calculated by Trimmed Spearman-Karber (TSK) in static bioassay, was found to be 930.0 µg/L. On the basis of acute LC 50 value, the tadpoles were exposed to three sublethal concentrations (155, 233 and 465 µg/L) of chlorpyrifos for 96 h. Blood cells were collected at every 24 h interval and were subjected to the Alkaline Single-Cell Gel Electrophoresis assay. The observed DNA damage was concentration and time-dependent, and those levels of DNA damage in between the tested concentrations and times were significantly different (p < 0.05). The tadpoles exposed to different concentrations of chlorpyrifos also showed different morphological abnormalities. It was concluded that chlorpyrifos is a genotoxic pesticide causing DNA damage in Bufo stomaticus.

Research paper thumbnail of Comparative analysis of micronuclei and DNA damage induced by Ochratoxin A in two mammalian cell lines

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2011

The fungal toxin, Ochratoxin A (OTA), is a common contaminant in human food and animal feed. The ... more The fungal toxin, Ochratoxin A (OTA), is a common contaminant in human food and animal feed. The present study evaluated micronucleus (MN) induction by OTA in comparison with its ability to induce cytotoxicity and DNA damage in two mammalian cell lines, CHO-K1-BH 4 Chinese hamster ovary cells and TK6 human lymphoblastoid cells. Micronuclei were evaluated by flow cytometry, cytotoxicity was estimated by relative population doubling (RPD), while direct DNA damage and oxidative DNA damage were measured with the Comet assay, performed without and with digestion by formamidopyrimidine-DNA glycosylase (fpg). For the MN and cytotoxicity measurements, the cell lines were treated for 24 h (CHO cells) or 27 h (TK6 cells) with 5-25 M OTA in the absence of exogenous metabolic activation. The OTA treatments resulted in concentration-responsive increases in cytotoxicity, with higher concentrations of the agent being more cytotoxic in CHO cells than TK6 cells. 15 M OTA produced positive responses for MN induction and hypodiploid events (a measure of aneugenicity) in both cell lines; this concentration of OTA also produced cytotoxicity near to the recommended limit for the assay (45 ± 5% RPD). A time course assay with TK6 cells indicated that at least 4 h of OTA treatment were required to produce a positive MN response. For the Comet assay DNA damage assessments, the cell lines were treated with 5-50 M OTA for 4 h. Direct DNA damage was detected in TK6 cells, but not CHO cells, while concentration-related increases in fpg-sensitive sites were detected for both cell lines. The consistent association of oxidative DNA damage with OTA exposure suggests its involvement in producing OTA-induced clastogenicity and aneugenicity; however, based on its detection in TK6 cells direct DNA damage could be involved in any human risk posed by OTA exposure.

Research paper thumbnail of Mutant frequency in comparison to oxidative DNA damage induced by ochratoxin A in L5178Y tk +/− (3.7.2C) mouse lymphoma cells

Drug and Chemical Toxicology, 2013

Ochratoxin A (OTA) is a naturally occurring mycotoxin that contaminates animal feed and human foo... more Ochratoxin A (OTA) is a naturally occurring mycotoxin that contaminates animal feed and human food. OTA is nephrotoxic, hepatotoxic, immunosuppressive and a potent renal carcinogen in rodents. In the present study, we evaluated the genotoxicity of OTA in L5178Y tk(+/-) (3.7.2C) mouse lymphoma cells using the microwell version of the mouse lymphoma gene mutation assay (MLA) and the comet assay modified to detect oxidative DNA damage. Cells were treated for 4 hours with 0, 5, 10, 25, 50 or 100 µM of OTA in the presence and absence of exogenous metabolic activation (S9). Benzo[a]pyrene (1 µg/mL) and 4-nitroquinoline-1-oxide (0.1 µg/mL) were used as positive control with and without S9, respectively. OTA treatment produced dose-dependent increases in cytotoxicity and tk mutant frequency, with significant increases in mutant frequency detected at concentrations ≥25 µM with and without S9. Similarly treated cells were used for the comet assay conducted with and without formamidopyrimidine-DNA glycosylase for the determination of oxidative DNA damage. OTA exposure resulted in a significant increase in both direct and oxidative DNA damage, with induction of oxidative damage being greater. The results indicate that OTA is mutagenic in mouse lymphoma assay; and that OTA-generated oxidative DNA damage is, at least partially, responsible for its mutagenicity in the assay.

Research paper thumbnail of Role of seed priming to enhance growth and development of crop plants against biotic and abiotic stresses

Abiotic and biotic stresses severely affect the crop’s growth and development at every stage of g... more Abiotic and biotic stresses severely affect the crop’s growth and development at every stage of growth cycle. Seed priming is helpful technique to enhance seed germination and growth in stress environment. Seed priming is a control procedure followed by re-drying which will allow the seed to imbibe water stimulate the internal biological process essential for germination but this process will not permit the seed to be truly germinate. Currently many seed priming method have been used like hydro-priming, osmo-priming, halo-priming, thermo-priming, bio-priming and solid matrix priming. Various studies confirmed that seed priming has several advantages including, early emergence high water use efficiency, stand establishment, deeper roots germination in broad range of temperature and resistance against disease and environmental stresses.

Research paper thumbnail of Hesperidin Targets Leishmania donovani Sterol C-24 Reductase to Fight against Leishmaniasis

ACS Omega, 2021

Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found ... more Hesperidin, a naturally occurring flavanoid, is present in citrus family of fruits. It was found effective against an array of pathogens including fungi, bacteria, viruses, and protozoa. Here, we evaluated its antileishmanial activity and possible mechanism of action through different in vitro and in silico experiments. It inhibited the growth and proliferation of the parasites significantly with a IC50 value of 1.019 ± 0.116 mM in vitro. It also reduced the growth of intramacrophagic amastigotes with a IC50 value of 0.2858 ± 0.01398 mM. It induced the reactive oxygen species (ROS) in parasites in a dosedependent manner. Through 2,7-dichloro dihydro fluorescein diacetate (H 2 DCFDA) staining, it was observed that around 96.9% parasites were ROS positive at 2.0 mM concentration of hesperidin. The ROS generated led to the apoptosis of parasites in a dose-dependent manner as observed by annexin/PI staining. Molecular docking with one of the very important and unique drug-targets of Leishmania donovani sterol C-24 reductase resulted in its significant inhibition. Here, we for the first time showed that hesperidin induced the antileishmanial response through the induction of apoptosis and inhibition of sterol C-24 reductase. Our study will be helpful in the development of a cost-effective antileishmanial lead with higher efficacy.

Research paper thumbnail of GC–MS analysis of phytoconstituents of Acacia nilotica and its molecular docking with drug-targets of Leishmania donovani to combat leishmanaisis

Acacia nilotica is an important medicinal plant, found in Africa, Middle East, and Indian subcont... more Acacia nilotica is an important medicinal plant, found in Africa, Middle East, and Indian subcontinent. Every part of the plant possesses a wide array of biologically-active and therapeutically important compounds and have been used in traditional-system of medicine. We reported the antileishmanial activity of Acacia nilotica (A. nilotica) bark methanolic extract through in vitro assays and dissected the mechanism of its action through in silico studies. Bark methanolic extract exhibited anti-promastigote and anti-amastigote potency with IC50 value of 19.6 + 0.9037 µg/ml and 77.52 + 5.167 µg/ml respectively in time and dose dependent manner. It showed very low cytotoxicity having CC50 value of 432.7 + 7.71 µg/ml on human-macrophage cell line, THP-1. The major constituents identified by GC-MS analysis are 13-docosenoic acid (34.06%), lupeol(20.15 %), 9,12-octadecadienoic acid (9.92 %) and 6-octadecanoic acid (8.43 %) bind effectively with the potential drug-targets of Leishmania donovani (L. donovani) including sterol 24-c-methytransferase (SMT), trypanothione reductase (TR), pteridine reductase (PTR1) and adenine phosphorybosyl transferase (APRT); suggest the possible mechanism of its antileishmanial action. The highest affinity with all these targets was shown by lupeol. The pharmacokinetic studies, predicted bioactivity scores and acute toxicity studies of major extract constituents support safe antileishmanial drug candidate. This study proved the antileishmanial potential of bark-methanolic extract A. nilotica and its mechanism of action through the inhibition of potential drug targets of L. donovani.

Research paper thumbnail of Pregnancy in a Secondary Infertile Woman with Polycystic Ovarian Syndrome (PCOS) –A Case Report

Case Report Polycystic ovarian syndrome, also called Stein-Leventhal syndrome, is a disorder invo... more Case Report Polycystic ovarian syndrome, also called Stein-Leventhal syndrome, is a disorder involving multiple endocrine systems resulting in abnormal levels of gonadotropins, androgens, and glucose in the blood. Several other manifestations arise in association with PCOS like a blockage in the fallopian tube, endometrial polyps, cervical cancer, ovarian cancer, etc. We hereby delineate a case of a 34-year-old married female in whom PCOS was diagnosed at the age of 22. After her marriage, she presented with the complaint of infertility. Investigations revealed that she had a polyp in her right fallopian tube after which a polypectomy was performed. She was able to conceive six months after the surgery was done. Currently, after seven years, she presented with the same complaint of infertility. After undergoing relevant procedures, her secondary infertility was ascertained as a result of PCOS. Following regular medications, she was able to get pregnant with triplets. This pregnancy ...

Research paper thumbnail of Assessment of the Antileishmanial Potential of Cassia fistula Leaf Extract

ACS Omega, 2021

Cassia fistula has a wide array of biologically active and therapeutically important class of com... more Cassia fistula has a wide array of biologically active and therapeutically important class of compounds. Leishmania donovani important drug targets, sterol 24-c methyltransferase (LdSMT), trypanothione reductase (LdTR), pteridine reductase (LdPTR1), and nucleoside hydrolase (LdNH), were modelled, and molecular docking was performed against the abundant phytochemicals of its leaf extract. Molecular docking results provided the significant prima facie evidence of the leaf extract to have antileishmanial potential. To confirm this, we performed in vitro antileishmanial and cytotoxicity assays. Methanolic extract of C. fistula leaves showed growth inhibition and proliferation of L. donovani promastigote with an IC 50 value of 43.31 ± 4.202 μg/mL. It also inhibited the growth of intra-macrophagic amastigotes with an IC 50 value of 80.76 ± 3.626 μg/mL. C. fistula extract was found cytotoxic at a very high concentration on human macrophages (CC 50 = 626 ± 39 μg/mL). Annexin V/propidium iodide (PI) staining assay suggested partial apoptosis induction in parasites by C. fistula to exert its antileishmanial activity. Here, for the first time, we have shown the antileishmanial potential of C. fistula leaves. Overall, our results could open new insight for an affordable and natural antileishmanial with high efficacy and less toxicity.

Research paper thumbnail of Leishmania donovani infection differentially regulates small G-proteins

Journal of cellular biochemistry, Jan 26, 2018

Leishmania is a protozoan parasite that resides and replicates in macrophages and causes leishman... more Leishmania is a protozoan parasite that resides and replicates in macrophages and causes leishmaniasis. The parasite alters the signaling cascade in host macrophages and evades the host machinery. Small G-proteins are GTPases, grouped in 5 different families that play a crucial role in the regulation of cell proliferation, cell survival, apoptosis, intracellular trafficking, and transport. In particular, the Ras family of small G-proteins has been identified to play a significant role in the cellular functions mentioned before. Here, we studied the differential expression of the most important small G-proteins during Leishmania infection. We found major changes in the expression of different isoforms of Ras, mainly in N-Ras. We observed that Leishmania donovani infection led to enhanced N-Ras expression, whereas it inhibited K-Ras and H-Ras expression. Furthermore, an active N-Ras pull-down assay showed enhanced N-Ras activity. L donovani infection also increased extracellular signa...

Research paper thumbnail of Sphingosine-1-phosphate signaling in Leishmania donovani infection in macrophages

PLoS neglected tropical diseases, Aug 1, 2018

Sphingosine-1-phosphate (S1P) is a crucial regulator of a wide array of cellular processes, such ... more Sphingosine-1-phosphate (S1P) is a crucial regulator of a wide array of cellular processes, such as apoptosis, cell proliferation, migration, and differentiation, but its role in Leishmania donovani infection is unknown. In the present study, we observed that L. donovani infection in THP-1 derived macrophages (TDM) leads to decrease in the expression of S1pr2 and S1pr3 at mRNA level. We further observed that Leishmania infection inhibits the phosphorylation of sphingosine kinase 1 (sphK1) in a time-dependent manner. Exogenous S1P supplementation decreases L. donovani induced ERK1/2 phosphorylation and increases p38 phosphorylation in TDM, resulting in a decrease in the intracellular parasite burden in a dose-dependent manner. On the other hand, sphK inhibition by DMS increases ERK1/2 phosphorylation leading to increased IL-10 and parasite load. To gain further insight, cytokines expression were checked in S1P supplemented TDM and we observed increase in IL-12, while decrease IL-10 e...

Research paper thumbnail of Restorative management of the cleft patient: CLP series part 10

Orthodontic Update, 2014

This article describes the role of the restorative dentist in the multidisciplinary management of... more This article describes the role of the restorative dentist in the multidisciplinary management of cleft lip and palate patients. The various clinical presentations and restorative challenges are outlined. The restorative treatment of cleft patients requires the use of a wide range of different clinical skills and techniques to achieve oral rehabilitation. The various treatment modalities are described and range from minimally invasive adhesive techniques to conventional fixed and removable prosthodontics, obturators and the use of dental implants. The eventual restorative outcomes are related to the initial severity of the defect and the degree of success of the previous surgical and orthodontic interventions. Clinical Relevance: This article will be of interest to clinicians, technicians, dental care professionals and other members of the team who are involved in the oral rehabilitation of cleft patients.

Research paper thumbnail of Implication of sphingosine-1-phosphate signaling in diseases: molecular mechanism and therapeutic strategies

Journal of Receptors and Signal Transduction, 2017

Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular processes that ... more Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular processes that is initiated by the intracellular production of bioactive lipid molecule, sphingosine-1-phosphate. Binding of sphingosine-1-phosphate to its extracellular receptors activates diverse downstream signaling that play a critical role in governing physiological processes. Increasing evidence suggests that this signaling pathway often gets impaired during pathophysiological and diseased conditions and hence manipulation of this signaling pathway may be beneficial in providing treatment. In this review, we summarized the recent findings of S1P signaling pathway and the versatile role of the participating candidates in context with several disease conditions. Finally, we discussed its possible role as a novel drug target in different diseases.

Research paper thumbnail of Robust controller design for attitude control of control moment gyroscope

2015 12th International Bhurban Conference on Applied Sciences and Technology (IBCAST), 2015

Robust controller design in presence of disturbance and system parameter uncertainties has been a... more Robust controller design in presence of disturbance and system parameter uncertainties has been a challenging task. In this paper attitude control of ECP 750 Gyroscope in presence of uncertainties is solved using LMI based multi objective state feedback H2 /H∞ controller. The attitude control problem addressed here resembles the formulation of polytopic model of MIMO gyroscope model to cater the parameter uncertainty and subsequent robust controller design using LMI framework is novelty of this work. MATLAB simulation results show better robust attitude control and disturbance rejection.

Research paper thumbnail of Microbial Hydroxylation of Hydroxyprogesterones and α-Glucosidase Inhibition Activity of Their Metabolites

Zeitschrift für Naturforschung B, 2007

Microbial transformation of 11α-hydroxyprogesterone (1) with Cunninghamella elegans, Gibberella f... more Microbial transformation of 11α-hydroxyprogesterone (1) with Cunninghamella elegans, Gibberella fujikuroi, Fusarium lini, and Candida albicans yielded 11α,15α,16α-trihydroxypregn-4- ene-3,20-dione (3), 11α-hydroxy-5α-pregnane-3,20-dione (4), 6β ,11α-dihydroxypregn-4-ene-3,20- dione (5), 11α-hydroxypregna-1,4-diene-3,20-dione (6), 11α,17β -dihydroxyandrost-4-en-3-one (7), and 11α,15α-dihydroxypregn-4-ene-3,20-dione (8). On the other hand, microbial transformation of 17α-hydroxyprogesterone (2) with Cunninghamella elegans and Fusarium lini yielded 11α,17α- dihydroxypregn-4-ene-3,20-dione (9), and 17α-hydroxypregna-1,4-diene-3,20-dione (10). The structures of the metabolites 3 - 10 were deduced on the basis of spectroscopic methods. Compound 3 was identified as a new metabolite, which exhibited a promising inhibitory activity against the α-glucosidase enzyme.

Research paper thumbnail of Effect of Low Level Feeding of Tylosin and Zinc Bacitracin on the Weight Gain and Immunity of Broiler Chicks Vaccinated Against Newcastle Disease Virus

Journal of Biological Sciences, 2003

Research paper thumbnail of Linear quadratic tracking for noisy signal with state space recursive least squares noise rejection

2013 XXIV International Conference on Information, Communication and Automation Technologies (ICAT), 2013

In many real life problems, related to closed loop control systems the reference signal is corrup... more In many real life problems, related to closed loop control systems the reference signal is corrupted by additive noise. The noisy reference signal leads to inferior tracking by the plant. However tracking performance can further improved if noise is removed from the reference signal prior applying to the control system. In this paper, we present a linear quadratic regulator (LQR) based control scheme that incorporates state space recursive least squares (SSRLS) method for cleaning the noisy reference signal. The proposed closed loop structure provides an optimal tracking of a reference signal while minimizing the effect of external disturbance acting on the plant. The prior knowledge about the external disturbance is utilized by the control scheme. Functioning of the proposed algorithm is demonstrated with the help of computer simulations with a practical application of third order system of grid tie converters. The result shows significant improvement in tracking performance as compared to the tracking of a noisy reference signal applied directly to the control system.

Research paper thumbnail of Self tuned SSRLS filter for online tracking and removal of power Line Interference from Electrocardiogram

ABSTRACT Power-Line Interference (PLI) may seriously distort the ECG (Electrocardiogram) signal r... more ABSTRACT Power-Line Interference (PLI) may seriously distort the ECG (Electrocardiogram) signal rendering the ECG analysis inaccurate. Various types of Notch filtering and adaptive cancellation schemes have been used to eliminate PLI interference from ECG. In this paper we propose an enhanced adaptive noise canceller (ANC) based on State Space Recursive Least Square (SSRLS) for elimination of PLI. SSRLS algorithm is a state space model-dependent recursive algorithm characterized by fast rate of convergence and hence exhibits excellent tracking performance. State-space formulation of noise model enables SSRLS filter to be implemented in an instinctive manner in comparison to other approaches. The proposed method is very effective for online tracking of PLI without requiring a reference noise source. The proposed method can also be employed to filter out the PLI even when corrupted ECG signal has low signal-to-noise ratio (SNR).

Research paper thumbnail of A New Anticholinergic Steroidal Alkaloid from Fritillaria imperialis of Turkish Origin

Research paper thumbnail of Ammonium versus Nitrate Nutrition of Plants Stimulates Microbial Activity in the Rhizosphere

Plant and Soil, 2005

Using an alkaline calcareous soil, pot experiments were conducted to elucidate the effects of NH ... more Using an alkaline calcareous soil, pot experiments were conducted to elucidate the effects of NH 4 + vs. NO 3) nutrition (50 or 100 mg kg)1 soil) of wheat and maize on microbial activity in the rhizosphere and bulk soils. Dicyandiamide was used as nitrification inhibitor to maintain NH 4 + as the predominant N source for plants grown in NH 4 +-treated soil. While maize grew equally well on both N sources, root and shoot growth of wheat was higher under NH 4 + than under NO 3) nutrition. Bacterial population density on roots, but not in the rhizosphere soil, was higher under NH 4 + than under NO 3 supplied at 150 mg N kg)1 soil; whereas at both N levels applied, NH 4 + compared to NO 3) nutrition of wheat and maize significantly increased microbial biomass in the rhizosphere soil. Under both plant species, NH 4 + vs. NO 3) nutrition also increased aerobic and anaerobic respiration, and dehydrogenase activity in the rhizosphere. As microbial activity in the planted bulk and unplanted soils was hardly affected by the N-source, we hypothesize that the stimulation by NH 4 + of the rhizosphere microbial activity was probably due to higher availability of root exudates under NH 4 + than under NO 3) nutrition.

Research paper thumbnail of Cynaroside inhibits Leishmania donovani UDP-galactopyranose mutase and induces reactive oxygen species to exert antileishmanial response

Bioscience Reports, 2021

Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activiti... more Cynaroside, a flavonoid, has been shown to have antibacterial, antifungal and anticancer activities. Here, we evaluated its antileishmanial properties and its mechanism of action through different in silico and in vitro assays. Cynaroside exhibited antileishmanial activity in time- and dose-dependent manner with 50% of inhibitory concentration (IC50) value of 49.49 ± 3.515 µM in vitro. It inhibited the growth of parasite significantly at only 20 µM concentration when used in combination with miltefosine, a standard drug which has very high toxicity. It also inhibited the intra-macrophagic parasite significantly at low doses when used in combination with miltefosine. It showed less toxicity than the existing antileishmanial drug, miltefosine at similar doses. Propidium iodide staining showed that cynaroside inhibited the parasites in G0/G1 phase of cell cycle. 2,7-dichloro dihydro fluorescein diacetate (H2DCFDA) staining showed cynaroside induced antileishmanial activity through reac...

Research paper thumbnail of Evaluation of the Genotoxicity of Chlorpyrifos in Common Indus Valley Toad, <i>Bufo stomaticus</i> Using Alkaline Single-Cell Gel Electrophoresis (Comet) Assay

Agricultural Sciences, 2014

Chlorpyrifos is a commonly used pesticide of organophosphate group, which causes toxicological ef... more Chlorpyrifos is a commonly used pesticide of organophosphate group, which causes toxicological effects in non-target organisms especially fish and frogs. In the present study, the genotoxicity of sublethal concentrations of chlorpyrifos was observed in the erythrocytes of common Indus valley toad, Bufo stomaticus, using the Alkaline Single-Cell Gel Electrophoresis (Comet) assay. In the first step, acute toxicity of chlorpyrifos was evaluated by exposing the tadpoles to high concentrations of the pesticide. The acute LC 50 value of chlorpyrifos, calculated by Trimmed Spearman-Karber (TSK) in static bioassay, was found to be 930.0 µg/L. On the basis of acute LC 50 value, the tadpoles were exposed to three sublethal concentrations (155, 233 and 465 µg/L) of chlorpyrifos for 96 h. Blood cells were collected at every 24 h interval and were subjected to the Alkaline Single-Cell Gel Electrophoresis assay. The observed DNA damage was concentration and time-dependent, and those levels of DNA damage in between the tested concentrations and times were significantly different (p < 0.05). The tadpoles exposed to different concentrations of chlorpyrifos also showed different morphological abnormalities. It was concluded that chlorpyrifos is a genotoxic pesticide causing DNA damage in Bufo stomaticus.

Research paper thumbnail of Comparative analysis of micronuclei and DNA damage induced by Ochratoxin A in two mammalian cell lines

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2011

The fungal toxin, Ochratoxin A (OTA), is a common contaminant in human food and animal feed. The ... more The fungal toxin, Ochratoxin A (OTA), is a common contaminant in human food and animal feed. The present study evaluated micronucleus (MN) induction by OTA in comparison with its ability to induce cytotoxicity and DNA damage in two mammalian cell lines, CHO-K1-BH 4 Chinese hamster ovary cells and TK6 human lymphoblastoid cells. Micronuclei were evaluated by flow cytometry, cytotoxicity was estimated by relative population doubling (RPD), while direct DNA damage and oxidative DNA damage were measured with the Comet assay, performed without and with digestion by formamidopyrimidine-DNA glycosylase (fpg). For the MN and cytotoxicity measurements, the cell lines were treated for 24 h (CHO cells) or 27 h (TK6 cells) with 5-25 M OTA in the absence of exogenous metabolic activation. The OTA treatments resulted in concentration-responsive increases in cytotoxicity, with higher concentrations of the agent being more cytotoxic in CHO cells than TK6 cells. 15 M OTA produced positive responses for MN induction and hypodiploid events (a measure of aneugenicity) in both cell lines; this concentration of OTA also produced cytotoxicity near to the recommended limit for the assay (45 ± 5% RPD). A time course assay with TK6 cells indicated that at least 4 h of OTA treatment were required to produce a positive MN response. For the Comet assay DNA damage assessments, the cell lines were treated with 5-50 M OTA for 4 h. Direct DNA damage was detected in TK6 cells, but not CHO cells, while concentration-related increases in fpg-sensitive sites were detected for both cell lines. The consistent association of oxidative DNA damage with OTA exposure suggests its involvement in producing OTA-induced clastogenicity and aneugenicity; however, based on its detection in TK6 cells direct DNA damage could be involved in any human risk posed by OTA exposure.

Research paper thumbnail of Mutant frequency in comparison to oxidative DNA damage induced by ochratoxin A in L5178Y tk +/− (3.7.2C) mouse lymphoma cells

Drug and Chemical Toxicology, 2013

Ochratoxin A (OTA) is a naturally occurring mycotoxin that contaminates animal feed and human foo... more Ochratoxin A (OTA) is a naturally occurring mycotoxin that contaminates animal feed and human food. OTA is nephrotoxic, hepatotoxic, immunosuppressive and a potent renal carcinogen in rodents. In the present study, we evaluated the genotoxicity of OTA in L5178Y tk(+/-) (3.7.2C) mouse lymphoma cells using the microwell version of the mouse lymphoma gene mutation assay (MLA) and the comet assay modified to detect oxidative DNA damage. Cells were treated for 4 hours with 0, 5, 10, 25, 50 or 100 µM of OTA in the presence and absence of exogenous metabolic activation (S9). Benzo[a]pyrene (1 µg/mL) and 4-nitroquinoline-1-oxide (0.1 µg/mL) were used as positive control with and without S9, respectively. OTA treatment produced dose-dependent increases in cytotoxicity and tk mutant frequency, with significant increases in mutant frequency detected at concentrations ≥25 µM with and without S9. Similarly treated cells were used for the comet assay conducted with and without formamidopyrimidine-DNA glycosylase for the determination of oxidative DNA damage. OTA exposure resulted in a significant increase in both direct and oxidative DNA damage, with induction of oxidative damage being greater. The results indicate that OTA is mutagenic in mouse lymphoma assay; and that OTA-generated oxidative DNA damage is, at least partially, responsible for its mutagenicity in the assay.