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Article: Phosphorylated derivatives that activate or inhibit mammalian adenosine kinase provide insights into the role of pentavalent ions in AK catalysis.

Park, Jae / Singh, Bhag / Maj, Mary C / Gupta, Radhey S

2004 Volume 23, Issue 2, Page(s) 167–177

Abstract: The enzyme adenosine kinase (AK) exhibits a nearly complete dependency on the presence ... of a large number of phosphorylated compounds on AK activity was examined. Several compounds ... pyrophosphate, were found to substitute for PVI in stimulating AK activity. Similar to PVI, these compounds ...

Abstract	The enzyme adenosine kinase (AK) exhibits a nearly complete dependency on the presence of pentavalent ions (PVI) such as phosphate, arsenate, and vanadate. To understand its basis, the effect of a large number of phosphorylated compounds on AK activity was examined. Several compounds, such as phosphoribosyl pyrophosphate, phosphoenol pyruvate, creatine phosphate, phosphorous acid, phosphonoformic acid, and inorganic pyrophosphate, were found to substitute for PVI in stimulating AK activity. Similar to PVI, these compounds lowered the Km of AK for adenosine. In contrast, many other structurally related compounds (i.e., phosphonoacetic acid, 2-carboxyethyl phosphonic acid, N-phosphonomethyl glycine, N-phosphonomethyl iminodiacetic acid) inhibited AK activity. These compounds seemed to compete with the activators for binding to AK. Structural comparisons of different compounds indicate that all activating compounds contain a net positive charge on the pentavalent atom (e.g., phosphorous), which should enable it to act as an acceptor for a nucleophilic group. We suggest that a phosphate (or other activator) bound near the active site participates in AK catalysis by forming a transient pentavalent intermediate with a nonbridging oxygen of the beta-phosphate in ATP. This interaction likely facilitates the transfer of gamma-phosphate from ATP to adenosine, thus accounting for the stimulating role of PVI in AK catalysis. The insight provided by these studies concerning the structural features of activators and inhibitors should also prove helpful in the design of more potent inhibitors of AK.
MeSH term(s)	Adenosine Kinase/antagonists & inhibitors ; Adenosine Kinase/chemistry ; Adenosine Kinase/metabolism ; Animals ; Anions ; Arsenates/metabolism ; Binding Sites ; CHO Cells/enzymology ; Catalysis ; Cations ; Cricetinae ; Kinetics ; Models, Chemical ; Molecular Structure ; Phosphates/metabolism ; Phosphorylation ; Structure-Activity Relationship ; Substrate Specificity ; Vanadates/metabolism
Chemical Substances	Anions ; Arsenates ; Cations ; Phosphates ; Vanadates (3WHH0066W5) ; Adenosine Kinase (EC 2.7.1.20)
Language	English
Publishing date	2004-04-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2143071-8
ISSN	1875-8355 ; 1573-4943 ; 1572-3887
ISSN (online)	1875-8355 ; 1573-4943
ISSN	1572-3887
DOI	10.1023/b:jopc.0000020083.81718.55
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Article ; Online: Genomic organization and linkage via a bidirectional promoter of the AP-3 (adaptor protein-3) mu3A and AK (adenosine kinase) genes: deletion mutants of AK in Chinese hamster cells extend into the AP-3 mu3A gene.

Singh, Bhag / Gupta, Radhey S

The Biochemical journal

2004 Volume 378, Issue Pt 2, Page(s) 519–528

Abstract: ... in these species are linked in a head-to-head fashion with the gene for the purine salvage pathway enzyme AK ... elements affecting transcription of these genes. In comparison with the AP-3 mu3A gene (27 kb), the AK ... respectively. The ratio of non-coding to coding sequence in the human AK gene is >550, which is the highest ...

Abstract	The cDNA and genomic DNA for the mu3A subunit of the AP-3 (adaptor protein-3) complex were cloned from Chinese hamster cells. The AP-3 mu3A genes in Chinese hamster, human and mouse each comprise nine exons and eight introns, with all introns located in identical positions in the species studied. The AP-3 mu3A genes in these species are linked in a head-to-head fashion with the gene for the purine salvage pathway enzyme AK (adenosine kinase). These genes share the first exon, and a 512 bp fragment covering the intervening untranslated sequence has the characteristic of a CpG island promoter, and it effectively carried out transcription in both directions. Deletion studies indicate that this region contains both positive and negative regulatory elements affecting transcription of these genes. In comparison with the AP-3 mu3A gene (27 kb), the AK gene in human is very large (558 kb), with average exon and intron lengths of approx. 100 bp and 55.7 kb respectively. The ratio of non-coding to coding sequence in the human AK gene is >550, which is the highest reported for any gene. We also present evidence that a number of AK- mutants of Chinese hamster ovary cells contain large deletions that affect both of these genes. In addition to lacking part of the AK gene, two of these mutants also lacked all of the exons and introns corresponding to the AP-3 mu3A gene. These mutants should prove useful in elucidating the role of AP-3 mu3A in vesicle-mediated protein sorting--a process that is altered in Hermansky-Pudlak syndrome. Detailed phylogenetic analysis of the micro family of proteins presented here also provides insight into how different AP complexes are related and may have evolved.
MeSH term(s)	Adaptor Protein Complex 3/classification ; Adaptor Protein Complex 3/genetics ; Adaptor Protein Complex mu Subunits/classification ; Adaptor Protein Complex mu Subunits/genetics ; Adenosine Kinase/genetics ; Animals ; Base Sequence ; CHO Cells ; Cell Line ; Cloning, Molecular ; Cricetinae ; Cricetulus/genetics ; Exons ; Gene Deletion ; Gene Order ; Genetic Linkage ; Genome ; Humans ; Introns ; Mice ; Molecular Sequence Data ; Phylogeny ; Promoter Regions, Genetic ; Sequence Homology, Amino Acid ; Transcriptional Activation
Chemical Substances	Adaptor Protein Complex 3 ; Adaptor Protein Complex mu Subunits ; Adenosine Kinase (EC 2.7.1.20)
Language	English
Publishing date	2004-03-01
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BJ20031219
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Article: Studies on AK-5 tumor: further characterization of rat histiocytoma.

Khar, A / Gupta, P D / Krishnamurthi, D

Indian journal of experimental biology

1990 Volume 28, Issue 12, Page(s) 1101–1106

Abstract: ... been described. The AK-5 grows as ascites as well as solid subcutaneous tumor. The ascites from one ...

Abstract	Properties of a transplantable rat histiocytoma which behaves like a macrophage-like cell, have been described. The AK-5 grows as ascites as well as solid subcutaneous tumor. The ascites from one animal can give between 10(8) and 10(9) cells whereas the subcutaneous tumor grows between 20 and 40 cm3 size. These cells possess various degradative enzymes, macrophage markers and glucocorticoid receptors. Beside histopathology the surface topography and ultrastructure of these cells are described.
MeSH term(s)	Animals ; Cell Division ; Female ; Histiocytoma, Benign Fibrous/ultrastructure ; Macrophages/ultrastructure ; Male ; Rats ; Rats, Inbred Strains ; Tumor Cells, Cultured/ultrastructure
Language	English
Publishing date	1990-12
Publishing country	India
Document type	Journal Article
ZDB-ID	416061-7
ISSN	0975-1009 ; 0019-5189
ISSN (online)	0975-1009
ISSN	0019-5189
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Article ; Online: Competition for resources in an exclusion model with biased lane-changing mechanism.

Gupta, Ankita / Gupta, Arvind Kumar

Physical review. E

2024 Volume 109, Issue 3-1, Page(s) 34132

Abstract: The motivation for the proposed work is drawn from the attachment-detachment observed in biological and physical transport processes that entail finite resources. We investigate the influence of limited particle availability on particle dynamics within ... ...

Abstract	The motivation for the proposed work is drawn from the attachment-detachment observed in biological and physical transport processes that entail finite resources. We investigate the influence of limited particle availability on particle dynamics within two parallel totally asymmetric simple exclusion lanes, with one lane incorporating only particle detachment and the other considering particle attachment. We establish a theoretical framework by employing vertical mean-field theory in conjunction with singular perturbation technique. The analytical findings are supported by numerical and stochastic validation using a finite-difference scheme and the Gillespie algorithm. By utilizing these approaches, we scrutinize various stationary properties, including particle densities, phase boundaries, and particle currents for both lanes. Our analysis reveals that the complexity of the phase diagram exhibits a nonmonotonic trend in the number of stationary phases as the particle count increases. Each phase diagram is constructed with respect to the intrinsic boundary parameters, illustrating both bulk and surface transitions occurring within the lanes. The interplay between finite resources and coupling mechanisms gives rise to two phases involving upward shock in one of the lanes, while two phases exhibit synchronized downward shock in both lanes. Finally, we delve into shock dynamics to comprehend critical phase transitions occurring in the system.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.109.034132
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Article ; Online: Neuroprotective Effects of Isolated Mangiferin from Swertia chirayita Leaves Regulating Oxidative Pathway on Streptozotocin-Induced Diabetic Neuropathy in Experimental Rats.

Shivam / Gupta, Asheesh Kumar

Central nervous system agents in medicinal chemistry

2024

Abstract: Background: Oxidative stress has an important role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complication of diabetes mellitus. Swertia chirayita is a rich source of phenolic ... ...

Abstract	Background: Oxidative stress has an important role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complication of diabetes mellitus. Swertia chirayita is a rich source of phenolic constituents and has hypoglycemic, anti-inflammatory, and antioxidant properties. Aims: This study was performed to evaluate the neuroprotective effect in diabetes by enhancing antioxidant defense against oxidative stress, which exhibits a neuroprotective effect in streptozotocin- induced diabetic rats. Objectives: The objective of this study was to elucidate the therapeutic potential of bioactive compounds of Swertia chirayita for diabetic complications. Methods: The present work focused on isolating the bioactive from the leaves of Swertia absinthe for acute toxicity studies, assessing its protective effects against diabetes and diabetic neuropathy as well as its mode of action in STZ-induced Wistar rats. The local area of Moradabad is the place from where the leaves of Swertia chirayita were gathered. Mangiferin was isolated and identified using spectroscopic techniques, such as UV, HPLC, 1H NMR, C13 NMR, MAS, and FTIR. Mangiferin was administered in doses of 15 and 30 mg/kg to test its effect on experimentally induced diabetes. The sciatic nerves of all groups were examined histopathologically. The protective effect of the drug against diabetes and diabetic neuropathy was demonstrated by measures, such as blood glucose level, body weight, food intake, thermal hyperalgesia, grip strength, spontaneous locomotor test, and lipid profile analysis. Sciatic nerve cells of the treated groups showed less inflammation, degeneration, and necrosis. Results: The results of this study confirmed that mangiferin alleviated diabetic neuropathic pain, possibly by reducing inflammatory cytokines (TNF-α, TGF-β1, IL-1β, and IL-6), strong antioxidant activity, and NGF in sciatic nerves. It may be a therapeutic agent. Conclusion: Our results suggested that active phytochemicals of Swertia chirayita showed preventive and curative effects against STZ-induced diabetic neuropathy in rats, which might be due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.
Language	English
Publishing date	2024-01-16
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2227560-5
ISSN	1875-6166 ; 1871-5249
ISSN (online)	1875-6166
ISSN	1871-5249
DOI	10.2174/0118715249255977231213053039
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Article: Study of Clinical Profile and Risk Factors for Ischemic Stroke in Young Adults.

Ak, Chethan / Gupta, Ritu / Warkade, Vinay

The Journal of the Association of Physicians of India

2022 Volume 70, Issue 4, Page(s) 11–12

Abstract: Stroke in young adults has become a rising concern in developing countries as it leads to large economic impact by causing disability in the most economically productive years.Although stroke is uncommon in young age group, we are facing patients with ... ...

Abstract	Stroke in young adults has become a rising concern in developing countries as it leads to large economic impact by causing disability in the most economically productive years.Although stroke is uncommon in young age group, we are facing patients with ischemic stroke in young adults in daily practice. Material: It is a prospective observational study in which patients with ischemic stroke fulfilling the inclusion criteria were evaluated for risk factors and clinical profile was assessed.Chi-square test was used to compare data and p value<0.05 was considered to be significant. Observation: In this study 73 patients with ischemic stroke between 15-49 years were evaluated. Most of the patients were male (63%).The most common risk factors were dyslipidemia (67.1%), metabolic syndrome (64.3%), hyperhomocysteinemia (58.9%), smoking (52%) and hypertension (44.2%). Patients were further divided into two age groups (16-32 years and 33-49 years) for comparison. Metabolic syndrome and hypertension were significantly more frequent in age group of 33-49 years with p value of <0.05 but we could not find difference between two age groups for rest of the risk factors. Conclusion: Most of these are traditional risk factors which were previously seen in older age group, but now we are encountering these risk factors in younger age group also. As most of them are modifiable risk factors health education regarding lifestyle modification, health programs for screening and treating these risk factors should be started to reduce the mortality and morbidity of stroke among socioeconomically active age group.
MeSH term(s)	Adolescent ; Adult ; Aged ; Brain Ischemia/epidemiology ; Brain Ischemia/etiology ; Female ; Humans ; Hypertension/complications ; Hypertension/epidemiology ; Ischemic Stroke ; Male ; Metabolic Syndrome/complications ; Metabolic Syndrome/epidemiology ; Middle Aged ; Risk Factors ; Stroke/diagnosis ; Stroke/epidemiology ; Stroke/etiology ; Young Adult
Language	English
Publishing date	2022-04-20
Publishing country	India
Document type	Journal Article ; Observational Study
ZDB-ID	800766-4
ISSN	0004-5772
ISSN	0004-5772
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Article ; Online: Role of Neuromonitoring in the Spinal Separation of Pyopagus Twins

Mehak Sehgal / Minu Bajpai / AK Jaryal / Uditi Gupta

National Board of Examinations Journal of Medical Sciences, Vol 1, Iss 2, Pp 92-

2023 Volume 98

Abstract: Introduction and Aim: Separating the spinal cord while separating spine sharing conjoined twins may have long-lasting implications for the survivors. We aim to study the role of neurophysiological monitoring in delineating the spinal anatomy as an ... ...

Abstract	Introduction and Aim: Separating the spinal cord while separating spine sharing conjoined twins may have long-lasting implications for the survivors. We aim to study the role of neurophysiological monitoring in delineating the spinal anatomy as an important component to pre-operative planning and twin separation, thereby improving neurological outcome. Case Report: Study involves two pairs of pyopagus conjoined twins with a shared spine. The twins were subjected to neurophysiological monitoring under general anesthesia to identify the neuronal supply and cross-innervation of various organs including lower limbs and anal sphincters with respective brain. Pre-operatively, the spinal cord was seen to be joined terminally with varying degree in both set of twins. Neurophysiological monitoring done preoperatively on the first set of twins revealed cross innervation from twin B to twin A, although twin A had its independent complete innervation. The sphincter was predominantly controlled by twin A. In the second set of twins, there was no cross innervation, both twins had equal control of sphincter hence the sphincter allocation was done using other general and anatomical factors. Neurophysiological monitoring was also utilized intraoperatively to divide the cord in its functional midline instead of anatomical midline thereby preserving neural outflow and function. Post-operatively, both set of twins retained motor and sensory supply to lower limbs and mobilize both limbs well, aided with physiotherapy. Conclusion: Better functional outcomes are possible with the use of neurophysiological monitoring during the workup and management of spine-sharing conjoined twins.
Keywords	neurophysiological monitoring ; pyopagus ; conjoined ; twins ; Medicine ; R
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	National Board of Examinations
Document type	Article ; Online
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Article ; Online: Toxicological Assessment and Anti-diabetic Effects of Combined Extract of Chirata, Fenugreek and Sesame on Regulating TNF-α, TGF-β and Oxidative Stress in Streptozotocin Induced Diabetic Rats.

Shivam / Gupta, Asheesh Kumar

Current drug discovery technologies

2023

Abstract: Background: Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum are used as traditional medicines to treat diabetes mellitus. A collection of metabolic illnesses known as diabetes mellitus (DM) involves chronic hyperglycemia caused by flaws ... ...

Abstract	Background: Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum are used as traditional medicines to treat diabetes mellitus. A collection of metabolic illnesses known as diabetes mellitus (DM) involves chronic hyperglycemia caused by flaws in insulin secretion, function, or both. Innate immunity and inflammation both play important roles in the etiology of diabetes-related microvascular problems. Objective: This study aims to examine the anti-diabetic effects and the acute toxicity of combined extract (1:1:1) of Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum. To address the demand for higher effectiveness and safety, the current effort aims to construct anti-diabetic preparations containing methanolic extract from herbal medications. Methods: The OECD 423 method was used to investigate acute toxicity in rats. Rats were used as test subjects, and rats were given a 35 mg/kg BW injection of streptozotocin to develop diabetes. The diabetic control group was given Glibenclamide 25 mg/kg BW, while the experimental group's diabetic rats received 125 mg/kg BW and 250 mg/kg BW of a combined methanolic extract of all plants. Among the measurements looked at were acute oral toxicity, behavioral changes, body weight, serum glucose levels, lipid profiles, oxidative stress, renal function tests, and inflammatory mediators. All the rat groups' histopathologies of the kidney, liver, and stomach were compared. The data were evaluated using analysis of variance, and a post hoc test was then carried out. Results: The combined extracts' medium lethal doses (LD50) were higher than 2000 mg/kg, indicating that they are not poisonous under the conditions that can be observed. Streptozotocin-induced diabetic rats' elevated blood glucose was found to be considerably lower (p 0.01) in the treated group of rats. In the treated group of rats, it was discovered that the damage and disarray in the cells typical of Streptozotocin-induced DM had been repaired. The treated group of rats returned to normal levels of the lipid profile, hyperglycemia, decreased serum protein and liver glycogen, increased liver function, and kidney function markers seen in the rats of the DM control group. Conclusion: The evaluated combined methanolic extract can be considered safe for use in rats. Combining methanolic extract from all selected medicinal plants (Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum) has a potential anti-diabetic effect and can be safely developed as an alternative medicine.
Language	English
Publishing date	2023-10-20
Publishing country	United Arab Emirates
Document type	Journal Article
ISSN	1875-6220
ISSN (online)	1875-6220
DOI	10.2174/0115701638252203230919092315
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Article ; Online: Mesenteric Panniculitis: An Enigma.

Gupta, Amit Kumar / Shrivastava, Niraj

Iranian journal of medical sciences

2024 Volume 49, Issue 3, Page(s) 201–203

MeSH term(s)	Humans ; Panniculitis, Peritoneal/diagnosis ; Tomography, X-Ray Computed
Language	English
Publishing date	2024-03-01
Publishing country	Iran
Document type	Journal Article
ZDB-ID	603872-4
ISSN	1735-3688 ; 0253-0716
ISSN (online)	1735-3688
ISSN	0253-0716
DOI	10.30476/IJMS.2023.98397.3074
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Article ; Online: Totally asymmetric simple exclusion process with local resetting in a resource-constrained environment.

Bhatia, Nikhil / Gupta, Arvind Kumar

Physical review. E

2024 Volume 109, Issue 2-1, Page(s) 24109

Abstract: Inspired by the process of mRNA translation, in which the stochastic degradation of mRNA-ribosome machinery is modeled by the resetting dynamics, we study an open totally asymmetric simple exclusion process with local resetting at the entry site in a ... ...

Abstract	Inspired by the process of mRNA translation, in which the stochastic degradation of mRNA-ribosome machinery is modeled by the resetting dynamics, we study an open totally asymmetric simple exclusion process with local resetting at the entry site in a resource-constrained environment. The effect of constrained resources on the stationary properties of the system has been comprehended in the form of the filling factor. The mean-field approximations are utilized to obtain stationary state features, such as density profiles and phase diagrams. The phase diagram possesses pure phases as well as coexisting phases, including a low-density-high-density phase separation, which did not manifest under periodic boundary conditions despite the system being closed there as well. The role of the resetting rate has been investigated on the stationary properties of the system, depending on how the filling factor scales with the system size. In contrast to the resetting model for infinite resources, two distinct phase transitions are observed for the smaller values of the filling factor leading to a change in the topology of the phase diagram. The impact of the resetting rate along with the finite-size effect has also been examined on the shock dynamics. All the mean-field results are found in remarkable agreement with the Monte Carlo simulations.
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.109.024109
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