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Article ; Online: Integrated in-silico and in-vitro assessments of HDAC6 inhibitor efficacy in mitigating amyloid beta pathology in Alzheimer's disease.

Choudhary, Gajendra / Prajapat, Manisha / Kaur, Gurjeet / Singh, Harvinder / Mahendiratta, Saniya / Prakash, Ajay / Medhi, Bikash

Journal of biomolecular structure & dynamics

2023 , Page(s) 1–11

Abstract: Alzheimer's disease, marked by memory loss and cognitive decline, is associated with amyloid-beta (Aβ) peptide accumulation in the brain. The enzyme neprilysin (NEP), crucial for Aβ degradation, decreases with age and in sporadic Alzheimer's disease, ... ...

Abstract	Alzheimer's disease, marked by memory loss and cognitive decline, is associated with amyloid-beta (Aβ) peptide accumulation in the brain. The enzyme neprilysin (NEP), crucial for Aβ degradation, decreases with age and in sporadic Alzheimer's disease, leading to increased Aβ build-up. This study hypothesized the targeting of enzyme HDAC6, believed to influence NEP activity. An in-silico study was conducted using an FDA-approved drug database, with the focus on their interaction with the HDAC6 structure. Among tested ligands, Panobinostat showed the most favourable interaction with HDAC6. In-vitro experiments on the SH-SY5Y neuronal cell line confirmed these findings, with Panobinostat inhibiting HDAC6, enhancing NEP levels, and reducing Aβ load. The study suggests Panobinostat as a potential Alzheimer's therapeutic agent, mitigating Aβ accumulation
Language	English
Publishing date	2023-10-25
Publishing country	England
Document type	Journal Article
ZDB-ID	49157-3
ISSN	1538-0254 ; 0739-1102
ISSN (online)	1538-0254
ISSN	0739-1102
DOI	10.1080/07391102.2023.2274518
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Article: A Novel Inhibitor of DKK1/LRP6 Interactions Against the Alzheimer Disease: An Insilco Approach.

Prajapat, Manisha / Singh, Harvinder / Chaudhary, Gajendra / Sarma, Phulen / Kaur, Gurjeet / Prakash Patel, Ajay / Medhi, Bikash

Bioinformatics and biology insights

2023 Volume 17, Page(s) 11779322231183762

Abstract: The activation of the Wnt signaling pathway is implicated in a neuroprotective mechanism against the Alzheimer disease. When this pathway is blocked, it activates GSK3 beta, leading to tau hyperphosphorylation and the apoptosis of neurons. Dickkopf- ... ...

Abstract	The activation of the Wnt signaling pathway is implicated in a neuroprotective mechanism against the Alzheimer disease. When this pathway is blocked, it activates GSK3 beta, leading to tau hyperphosphorylation and the apoptosis of neurons. Dickkopf-related protein 1 (DKK1) is a protein that competes with the Wnt ligand for the low-density lipoprotein receptor-related protein 6 (LRP6) receptor's binding, interrupting the Wnt-induced Fzd-Wnt-LRP6 complex. This counteracts Wnt's neuroprotective effect and contributes to the progression of the Alzheimer disease. The aim of this study was to use in silico approach to develop new agents that can combat the Alzheimer disease by targeting the interaction between DKK1 and LRP6. To achieve this, we conducted a virtual screening (Vsw) of the Asinex-CNS database library (n = 54 513) compounds against a generated grid in LRP6 protein. From this screening, we selected 6 compounds based on their docking score and performed molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations on the selected ligands. Next, we evaluated the Absorption, Distribution, Metabolism, and Excretion (ADME) results of the 6 screened compounds using the Quick prop module of Schrödinger. We then employed several computational techniques, including PCA (Principal Component Analysis), DCCM (Dynamic Cross-Correlation Map), molecular dynamics simulation, and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA)-based negative binding free energy (BFE) calculation, to further analyze the compounds. Our extensive computational analysis resulted in the identification of 3 potential hits, LAS 29757582, LAS 29984441, and LAS 29757942. These compounds were found to block the interaction of DKK1 with LRP6 (A and B interface) protein, and their potential as therapeutic agents was supported by negative BFE calculation. Therefore, these compounds show potential as possible therapeutic agents for treating the Alzheimer disease through targeting the interaction between DKK1 and LRP6.
Language	English
Publishing date	2023-06-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2423808-9
ISSN	1177-9322
ISSN	1177-9322
DOI	10.1177/11779322231183762
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Article ; Online: Role of intravenous aspirin versus oral aspirin in the treatment of acute coronary syndrome: Answering a clinical query by systematic review and meta-analysis of randomized controlled trials.

Kaur, Hardeep / Sarma, Phulen / Bhattacharyya, Anusuya / Rohit, Manojkumar / Prajapat, Manisha / Kumar, Subodh / Prakash, Ajay / Medhi, Bikash

Indian journal of pharmacology

2023 Volume 55, Issue 2, Page(s) 133–137

Abstract: Background: Aspirin is indicated in the emergency management of acute coronary syndrome. However, oral aspirin has erratic bioavailability compared to i.v. formulation.: Objective: The objective of this study was to evaluate the comparative efficacy ... ...

Abstract	Background: Aspirin is indicated in the emergency management of acute coronary syndrome. However, oral aspirin has erratic bioavailability compared to i.v. formulation. Objective: The objective of this study was to evaluate the comparative efficacy and safety of intravenous (IV) and oral aspirin in acute coronary syndrome. Study design: This was a systematic review and meta-analysis. Results: Two randomized controlled trials were included. Compared to oral aspirin, lower platelet aggregability was seen with IV aspirin at 5 min and 20 min. Lower thromboxane B2 and lower platelet CD-62p levels were noted in the IV group; however, no significant difference was observed in terms of "composite cardiovascular death, stroke, and myocardial infarction (MI) at 4-6 weeks," "any cause mortality," "cardiovascular mortality," "occurrence of stroke," and "occurrence of MI/reinfarction." However, no difference was noted in terms of the occurrence of serious adverse events. Conclusion: IV aspirin showed some advantages in terms of platelet aggregability biomarkers at 20 min and 1 week with comparable safety to oral aspirin. No difference was seen in terms of clinical outcomes (at 24 h, 7, and 30 days) and the occurrence of serious adverse events.
MeSH term(s)	Humans ; Acute Coronary Syndrome/drug therapy ; Aspirin/therapeutic use ; Randomized Controlled Trials as Topic ; Administration, Intravenous ; Stroke/drug therapy ; Stroke/prevention & control
Chemical Substances	Aspirin (R16CO5Y76E)
Language	English
Publishing date	2023-06-13
Publishing country	India
Document type	Meta-Analysis ; Systematic Review ; Journal Article
ZDB-ID	605829-2
ISSN	1998-3751 ; 0253-7613
ISSN (online)	1998-3751
ISSN	0253-7613
DOI	10.4103/ijp.ijp_1147_20
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Article: Retrospective Observational Study to Assess Safety and Tolerability of Nebulized Colistin for the Treatment of Patients With Pneumonia in Real-World Settings in Respiratory ICU.

Talwar, Deepak / Prajapat, Deepak / Talwar, Surbhi / Talwar, Dhruv

Cureus

2024 Volume 16, Issue 2, Page(s) e54652

Abstract: ... of nebulized colistin therapy.: Results: All enrolled patients (N=30, males: 22, females: 8; average age: 71 ...

Abstract	Introduction: Colistin is used to treat hospital-acquired pneumonia and ventilator-associated pneumonia. However, direct drug deposition at the site of infection may improve its efficacy and reduce systemic exposure. The aim of this study was to assess the safety and tolerability of nebulized colistin among Indian patients diagnosed with pneumonia caused by multidrug-resistant gram-negative bacilli in real-world settings. Methodology: We retrospectively reviewed the medical records of patients treated with nebulized colistin for pneumonia. We assessed the adverse events and relevant abnormal laboratory findings of nebulized colistin therapy. Results: All enrolled patients (N=30, males: 22, females: 8; average age: 71.06 years) were treated for 13.36 days. Almost 80% of patients had a history of shortness of breath, which was a major symptom when they were admitted to the hospital. The patients were administered nebulized colistin for an average of six days (8 hours per day). The most common dosing schedule was 1 million international units (MIU)/8 hours. No serious adverse event was observed, and only one patient died while on the treatment but the death was not related to colistin treatment. The average sequential organ failure assessment score for all patients was 6.5. Conclusion: Our study demonstrated the efficient clinical utility and well-tolerated safety profile of nebulized colistin in the treatment of patients with pneumonia. Neurotoxicity and nephrotoxicity were not reported. Since a significant percentage of patients were with chronic respiratory diseases, our study further indicates the safety and effectiveness of nebulized colistin in chronic obstructive pulmonary disease (COPD) patients too.
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.54652
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Article: A systematic review for the development of Alzheimer's disease in

Prajapat, Manisha / Kaur, Gurjeet / Choudhary, Gajendra / Pahwa, Paras / Bansal, Seema / Joshi, Rupa / Batra, Gitika / Mishra, Abhishek / Singla, Rubal / Kaur, Harminder / Prabha, Praisy K / Patel, Ajay Prakash / Medhi, Bikash

Frontiers in aging neuroscience

2023 Volume 15, Page(s) 1296919

Abstract: Alzheimer's disease (AD) is the most common progressive neurodegenerative disease and is associated with dementia. Presently, various chemical and environmental agents are used to ... ...

Abstract	Alzheimer's disease (AD) is the most common progressive neurodegenerative disease and is associated with dementia. Presently, various chemical and environmental agents are used to induce
Language	English
Publishing date	2023-12-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2023.1296919
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Article ; Online: Connectomics: A pharmacologic viewpoint.

Harikrishnareddy, Dibbanti / Prajapat, Manisha / Kumar, Subodh / Prakash, Ajay / Medhi, Bikash

Indian journal of pharmacology

2019 Volume 50, Issue 6, Page(s) 299–301

MeSH term(s)	Animals ; Biomedical Research ; Brain/drug effects ; Brain/ultrastructure ; Caenorhabditis elegans/ultrastructure ; Connectome/methods ; Drug Discovery ; Humans ; Neural Networks, Computer
Language	English
Publishing date	2019-02-19
Publishing country	India
Document type	Editorial
ZDB-ID	605829-2
ISSN	1998-3751 ; 0253-7613
ISSN (online)	1998-3751
ISSN	0253-7613
DOI	10.4103/ijp.IJP_2_19
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Zs.A 1983: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 311: Show issues

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Article ; Online: A Novel Inhibitor of DKK1/LRP6 Interactions Against the Alzheimer Disease

Manisha Prajapat / Harvinder Singh / Gajendra Chaudhary / Phulen Sarma / Gurjeet Kaur / Ajay Prakash Patel / Bikash Medhi

Bioinformatics and Biology Insights, Vol

An Insilco Approach

2023 Volume 17

Abstract	The activation of the Wnt signaling pathway is implicated in a neuroprotective mechanism against the Alzheimer disease. When this pathway is blocked, it activates GSK3 beta, leading to tau hyperphosphorylation and the apoptosis of neurons. Dickkopf-related protein 1 (DKK1) is a protein that competes with the Wnt ligand for the low-density lipoprotein receptor–related protein 6 (LRP6) receptor’s binding, interrupting the Wnt-induced Fzd-Wnt-LRP6 complex. This counteracts Wnt’s neuroprotective effect and contributes to the progression of the Alzheimer disease. The aim of this study was to use in silico approach to develop new agents that can combat the Alzheimer disease by targeting the interaction between DKK1 and LRP6. To achieve this, we conducted a virtual screening (Vsw) of the Asinex-CNS database library (n = 54 513) compounds against a generated grid in LRP6 protein. From this screening, we selected 6 compounds based on their docking score and performed molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations on the selected ligands. Next, we evaluated the Absorption, Distribution, Metabolism, and Excretion (ADME) results of the 6 screened compounds using the Quick prop module of Schrödinger. We then employed several computational techniques, including PCA (Principal Component Analysis), DCCM (Dynamic Cross-Correlation Map), molecular dynamics simulation, and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA)–based negative binding free energy (BFE) calculation, to further analyze the compounds. Our extensive computational analysis resulted in the identification of 3 potential hits, LAS 29757582, LAS 29984441, and LAS 29757942. These compounds were found to block the interaction of DKK1 with LRP6 (A and B interface) protein, and their potential as therapeutic agents was supported by negative BFE calculation. Therefore, these compounds show potential as possible therapeutic agents for treating the Alzheimer disease through targeting the interaction between DKK1 and ...
Keywords	Biology (General) ; QH301-705.5
Subject code	540
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Extragingival pyogenic granuloma of the lower lip masquerading as a vascular lesion.

Prajapat, Jyoti / Prajapat, Rajesh / Khanagar, Sanjeev B / Siddeeqh, Salman

Journal of oral and maxillofacial pathology : JOMFP

2022 Volume 26, Issue Suppl 1, Page(s) S119–S123

Abstract: ... of the lower lip simulating as a vascular lesion in young male of 30 years old diagnosed by ultrasound followed ...

Abstract	Pyogenic granuloma (PG) is a benign nonneoplastic mucocutaneous lesion. It occurs as a result of chronic irritation or due to hormonal changes. The most favorable site for this fairly common lesion is gingiva, but rarely, it can occur outside the oral cavity, later often difficult to diagnose, as a diverse group of the pathologic process can produce such lesions outside the oral cavity. The diagnosis is also challenging as the lesions appear as smooth or lobulated red nodules with easy bleeding, occasionally ulcerated mimicking malignancies. The purpose of this article is to report a rare case of extragingival PG of the lower lip simulating as a vascular lesion in young male of 30 years old diagnosed by ultrasound followed by histopathological examination.
Language	English
Publishing date	2022-02-28
Publishing country	India
Document type	Case Reports
ZDB-ID	2390999-7
ISSN	1998-393X ; 0973-029X
ISSN (online)	1998-393X
ISSN	0973-029X
DOI	10.4103/jomfp.jomfp_108_21
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Article ; Online: Update on omicron variant: What we know so far.

Choudhary, Gajendra / Prajapat, Manisha / Kumaravel, J / Prabha, Praisy K / Sarma, Phulen / Handa, Vrishbhanu / Kaur, Harminder / Patel, Ajay Prakash / Medhi, Bikash

Indian journal of pharmacology

2022 Volume 54, Issue 1, Page(s) 41–45

Abstract: The new omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in South Africa in November 2021 has been declared as a Variant of Concern by the World Health Organization. This variant has been found to carry ... ...

Abstract	The new omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in South Africa in November 2021 has been declared as a Variant of Concern by the World Health Organization. This variant has been found to carry multifold mutations that have not been observed in any of the variants detected so far. The majority of these mutations are present in spike protein, contributing to its ability to escape the currently available neutralizing antibodies and vaccines, as well as increasing the chances of reinfection. This brief communication provides an insight into mutations detected in the omicron variant and their impact on currently available interventions against SARS-CoV-2 and the need for a booster dose. We also discuss the severity status of infection due to this variant. Additionally, we highlight the hypothesis supporting the association of high HIV prevalence and the appearance of the omicron variant of SARS-CoV-2 in immune-compromised individuals.
MeSH term(s)	Antibodies, Viral ; COVID-19 ; Humans ; SARS-CoV-2/genetics ; Viral Envelope Proteins/genetics
Chemical Substances	Antibodies, Viral ; Viral Envelope Proteins
Language	English
Publishing date	2022-03-28
Publishing country	India
Document type	Journal Article
ZDB-ID	605829-2
ISSN	1998-3751 ; 0253-7613
ISSN (online)	1998-3751
ISSN	0253-7613
DOI	10.4103/ijp.ijp_955_21
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Article ; Online: Folic acid as placebo in controlled clinical trials of hydroxychloroquine prophylaxis in COVID-19: Is it scientifically justifiable?

Kaur, Hardeep / Sarma, Phulen / Bhattacharyya, Anusuya / Prajapat, Manisha / Kumar, Subodh / Prakash, Ajay / Medhi, Bikash

Medical hypotheses

2021 Volume 149, Page(s) 110539

Abstract: Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In ... ...

Abstract	Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In clinical studies, FA level was lowest among severe patients compared to mild and moderate disease. A single controlled study reported the benefit of combination of folic acid with Pyridoxine & cyanocobalamin in terms of clinical and laboratory cure parameters. One hypothesis associates the differences in geographical variation of disease severity with prevalence of methyl tertahydrofolic acid reductase (MTHFR) C677T polymorphism. Other possible domains, where FA is hypothesized to be beneficial are COVID-19 associated pulmonary hypertension and hyper-homocystinemia. So, scientific justification of using folic acid as placebo in COVID-19 trials seems scientifically not credible and this may be one of the major factors for failure of many agents. We need to be more careful in choosing our placebo especially when conducting a placebo controlled trial.
MeSH term(s)	Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/complications ; COVID-19/drug therapy ; COVID-19/prevention & control ; Folic Acid/therapeutic use ; Humans ; Hydroxychloroquine/therapeutic use ; Hyperhomocysteinemia/complications ; Hyperhomocysteinemia/drug therapy ; Hypertension, Pulmonary/complications ; Hypertension, Pulmonary/drug therapy ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Models, Theoretical ; Nitric Oxide Synthase Type III/metabolism ; Placebos ; Protein Binding ; Randomized Controlled Trials as Topic ; Research Design
Chemical Substances	Placebos ; Hydroxychloroquine (4QWG6N8QKH) ; Folic Acid (935E97BOY8) ; NOS3 protein, human (EC 1.14.13.39) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; MTHFR protein, human (EC 1.5.1.20) ; Methylenetetrahydrofolate Reductase (NADPH2) (EC 1.5.1.20) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-02-20
Publishing country	United States
Document type	Letter
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2021.110539
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