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Article ; Online: High molecular weight heparin-induced angiogenesis mainly mediated via basic fibroblast growth factor-2- an in-vivo (CAM) and in-silico analysis

Reji Manjunathan / Kartik Mitra / Rahul Vasvani / Mukesh Doble

Biochemistry and Biophysics Reports, Vol 37, Iss , Pp 101609- (2024)

1481

Abstract: Background: High-molecular weight heparin (HMWH), a molecule extensively used as an anticoagulant, shows concentration-dependent angiogenic and anti-angiogenic potential. So far, no studies have reported the interactive potential of HMWH with various pro- ...

Abstract	Background: High-molecular weight heparin (HMWH), a molecule extensively used as an anticoagulant, shows concentration-dependent angiogenic and anti-angiogenic potential. So far, no studies have reported the interactive potential of HMWH with various pro-angiogenic growth factors under physiological conditions. Haence, we aimed to find the impact of major pro-angiogenic growth factors under HMWH induced angiogenesis. Methods: Chicken Chorioallantoic Membranes (CAMs) are incubated with various concentrations of HMWH. Semiquantitative PCR method was implemented to measure the changes in the transcription level of pro-angiogenic growth factors. The scanning electron microscopic technique is applied to find the morphological changes in CAM. Molecular docking and molecular dynamics simulation studies using NAMD and CHARMM force field discerned the heparin-binding mode with the pro-angiogenic growth factors. Results: HMWH can enhance the transcription level of major pro-angiogenic growth factors, significantly impacting FGF2 under 100 μM concentration. The in-silico analysis reveals that HMWH shows the highest binding affinity with FGF2. Further, molecular dynamics and interaction studies using 1 kDa Heparin against FGF2 showed that the former binds stably with the latter due to a strong salt bridge formation between the sulfate groups and arginine residues (ARG 119 and ARG109). Conclusion: The combined experimental and in-silico analysis results reveal that HMWH can interact with pro-angiogenic growth factors under micromolar concentration while inducing angiogenesis. This observation further supports the therapeutic benefits of HMWH as an angiogenic factor under such low concentration. This technique is used to replenish the blood supply to chronic wounds to speed healing and prevent unnecessary amputations.
Keywords	High-molecular weight heparin ; HMWH ; Fibroblast growth factor ; FGF2 ; Matrix metalloproteinase 2- MMP2 ; Molecular docking ; Biology (General) ; QH301-705.5 ; Biochemistry ; QD415-436
Subject code	630
Language	English
Publishing date	2024-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: High molecular weight heparin-induced angiogenesis mainly mediated via basic fibroblast growth factor-2- an

Manjunathan, Reji / Mitra, Kartik / Vasvani, Rahul / Doble, Mukesh

Biochemistry and biophysics reports

2023 Volume 37, Page(s) 101609

Abstract	Background: High-molecular weight heparin (HMWH), a molecule extensively used as an anticoagulant, shows concentration-dependent angiogenic and anti-angiogenic potential. So far, no studies have reported the interactive potential of HMWH with various pro-angiogenic growth factors under physiological conditions. Haence, we aimed to find the impact of major pro-angiogenic growth factors under HMWH induced angiogenesis. Methods: Chicken Chorioallantoic Membranes (CAMs) are incubated with various concentrations of HMWH. Semiquantitative PCR method was implemented to measure the changes in the transcription level of pro-angiogenic growth factors. The scanning electron microscopic technique is applied to find the morphological changes in CAM. Molecular docking and molecular dynamics simulation studies using NAMD and CHARMM force field discerned the heparin-binding mode with the pro-angiogenic growth factors. Results: HMWH can enhance the transcription level of major pro-angiogenic growth factors, significantly impacting FGF2 under 100 μM concentration. The Conclusion: The combined experimental and
Language	English
Publishing date	2023-12-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2831046-9
ISSN	2405-5808 ; 2405-5808
ISSN (online)	2405-5808
ISSN	2405-5808
DOI	10.1016/j.bbrep.2023.101609
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Article ; Online: Self-Assembled Inhalable Immunomodulatory Silk Fibroin Nanocarriers for Enhanced Drug Loading and Intracellular Antibacterial Activity.

Mitra, Kartik / Chadha, Anju / Muthuvijayan, Vignesh / Doble, Mukesh

ACS biomaterials science & engineering

2022 Volume 8, Issue 2, Page(s) 708–721

Abstract: In this study, a pH-induced self-assembly-based method has been developed to form silk fibroin nanoparticles (SFN-2) with a higher drug loading capacity (21.0 ± 2.1%) and cellular uptake than that of silk fibroin particles produced by a conventional ... ...

Abstract	In this study, a pH-induced self-assembly-based method has been developed to form silk fibroin nanoparticles (SFN-2) with a higher drug loading capacity (21.0 ± 2.1%) and cellular uptake than that of silk fibroin particles produced by a conventional desolvation method (SFN-1). Using the self-assembly method, rifampicin-encapsulated silk fibroin nanoparticles (R-SFN-2) were prepared with a size of 165 ± 38 nm at an optimum pH of 3.8.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Drug Delivery Systems/methods ; Drug Liberation ; Fibroins/chemistry ; Fibroins/pharmacology ; Pharmaceutical Preparations
Chemical Substances	Anti-Bacterial Agents ; Pharmaceutical Preparations ; Fibroins (9007-76-5)
Language	English
Publishing date	2022-01-21
Publishing country	United States
Document type	Journal Article
ISSN	2373-9878
ISSN (online)	2373-9878
DOI	10.1021/acsbiomaterials.1c01357
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Book ; Online: Common Information Belief based Dynamic Programs for Stochastic Zero-sum Games with Competing Teams

Kartik, Dhruva / Nayyar, Ashutosh / Mitra, Urbashi

2021

Abstract: Decentralized team problems where players have asymmetric information about the state of the underlying stochastic system have been actively studied, but \emph{games} between such teams are less understood. We consider a general model of zero-sum ... ...

Abstract	Decentralized team problems where players have asymmetric information about the state of the underlying stochastic system have been actively studied, but \emph{games} between such teams are less understood. We consider a general model of zero-sum stochastic games between two competing teams. This model subsumes many previously considered team and zero-sum game models. For this general model, we provide bounds on the upper (min-max) and lower (max-min) values of the game. Furthermore, if the upper and lower values of the game are identical (i.e., if the game has a \emph{value}), our bounds coincide with the value of the game. Our bounds are obtained using two dynamic programs based on a sufficient statistic known as the common information belief (CIB). We also identify certain information structures in which only the minimizing team controls the evolution of the CIB. In these cases, we show that one of our CIB based dynamic programs can be used to find the min-max strategy (in addition to the min-max value). We propose an approximate dynamic programming approach for computing the values (and the strategy when applicable) and illustrate our results with the help of an example. Comment: arXiv admin note: text overlap with arXiv:1909.01445
Keywords	Computer Science - Multiagent Systems ; Electrical Engineering and Systems Science - Systems and Control
Subject code	005
Publishing date	2021-02-10
Publishing country	us
Document type	Book ; Online
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Book ; Online: Testing for Anomalies

Kartik, Dhruva / Nayyar, Ashutosh / Mitra, Urbashi

Active Strategies and Non-asymptotic Analysis

2020

Abstract: The problem of verifying whether a multi-component system has anomalies or not is addressed. Each component can be probed over time in a data-driven manner to obtain noisy observations that indicate whether the selected component is anomalous or not. The ...

Abstract	The problem of verifying whether a multi-component system has anomalies or not is addressed. Each component can be probed over time in a data-driven manner to obtain noisy observations that indicate whether the selected component is anomalous or not. The aim is to minimize the probability of incorrectly declaring the system to be free of anomalies while ensuring that the probability of correctly declaring it to be safe is sufficiently large. This problem is modeled as an active hypothesis testing problem in the Neyman-Pearson setting. Component-selection and inference strategies are designed and analyzed in the non-asymptotic regime. For a specific class of homogeneous problems, stronger (with respect to prior work) non-asymptotic converse and achievability bounds are provided. Comment: arXiv admin note: text overlap with arXiv:1911.06912
Keywords	Computer Science - Information Theory
Publishing date	2020-05-14
Publishing country	us
Document type	Book ; Online
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Book ; Online: Adaptive Sampling for Estimating Distributions

Kartik, Dhruva / Sood, Neeraj / Mitra, Urbashi / Javidi, Tara

A Bayesian Upper Confidence Bound Approach

2020

Abstract: The problem of adaptive sampling for estimating probability mass functions (pmf) uniformly well is considered. Performance of the sampling strategy is measured in terms of the worst-case mean squared error. A Bayesian variant of the existing upper ... ...

Abstract	The problem of adaptive sampling for estimating probability mass functions (pmf) uniformly well is considered. Performance of the sampling strategy is measured in terms of the worst-case mean squared error. A Bayesian variant of the existing upper confidence bound (UCB) based approaches is proposed. It is shown analytically that the performance of this Bayesian variant is no worse than the existing approaches. The posterior distribution on the pmfs in the Bayesian setting allows for a tighter computation of upper confidence bounds which leads to significant performance gains in practice. Using this approach, adaptive sampling protocols are proposed for estimating SARS-CoV-2 seroprevalence in various groups such as location and ethnicity. The effectiveness of this strategy is discussed using data obtained from a seroprevalence survey in Los Angeles county.
Keywords	Statistics - Methodology ; Computer Science - Machine Learning
Subject code	310
Publishing date	2020-12-07
Publishing country	us
Document type	Book ; Online
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Article ; Online: Preparation of Curdlan sulphate - Chitosan nanoparticles as a drug carrier to target Mycobacterium smegmatis infected macrophages.

Ravindran, Radhika / Mitra, Kartik / Arumugam, Senthil Kumar / Doble, Mukesh

Carbohydrate polymers

2021 Volume 258, Page(s) 117686

Abstract: In this study, curdlan sulphate - chitosan nanoparticles were prepared through polyelectrolyte complexing at a mass ratio of 2:1 respectively. The curdlan was produced by fermentation with Agrobacterium sp. ATCC 31750, which was then sulphated to form ... ...

Abstract	In this study, curdlan sulphate - chitosan nanoparticles were prepared through polyelectrolyte complexing at a mass ratio of 2:1 respectively. The curdlan was produced by fermentation with Agrobacterium sp. ATCC 31750, which was then sulphated to form the polyanionic polymer. A first-line tuberculosis drug, Rifampicin and a phytochemical, DdPinitol, were encapsulated into Curdlan Sulphate (CS) - Chitosan Nanoparticles (C) (CSC NPs) of size 205.41 ± 7.24 nm. The drug release kinetics followed a Weibull model with initial burst release (48 % Rifampicin and 27 % d-Pinitol within 6 h), followed by a sustained release. The prepared CSC: d-PIN + RIF NPs was cytocompatible and entered the M.smegmatis infected macrophages through multiple endocytic pathways including clathrin, caveolae and macropinocytosis. They showed superior bactericidal activity (2.4-2.7 fold) within 4 h when compared to free drug Rifampicin (1.6 fold). The drug encapsulated CSC: RIF suppressed the pro-inflammatory gene (TNF-α by 3.66 ± 0.19 fold) and CSC: d-PIN + RIF increased expression of the anti-inflammatory gene (IL-10 by 13.09 ± 0.47 fold). Expression of TGF- β1 gene also increased when treated with CSC: d-PIN + RIF (13.00 ± 0.19 fold) which provided the immunomodulatory activity of the encapsulated CSC NPs. Thus, curdlan sulphate - chitosan polyelectrolyte complex can be a potential nanocarrier matrix for intracellular delivery of multiple drugs.
MeSH term(s)	Animals ; Cell Survival ; Chitosan/chemistry ; Drug Carriers/chemistry ; Drug Delivery Systems ; Drug Liberation ; Endocytosis ; Hydrogen-Ion Concentration ; Inflammation ; Kinetics ; Macrophages/drug effects ; Macrophages/metabolism ; Macrophages/microbiology ; Mice ; Mycobacterium Infections, Nontuberculous/drug therapy ; Mycobacterium smegmatis/drug effects ; Nanoparticles/chemistry ; Polyelectrolytes/chemistry ; Polymers/chemistry ; RAW 264.7 Cells ; Rifampin/pharmacology ; beta-Glucans/chemistry
Chemical Substances	Drug Carriers ; Polyelectrolytes ; Polymers ; beta-Glucans ; chitosan sulfate ; polyanions ; curdlan (6930DL209R) ; Chitosan (9012-76-4) ; curdlan sulfate (I1BSR8FDW9) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2021-01-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1501516-6
ISSN	1879-1344 ; 0144-8617
ISSN (online)	1879-1344
ISSN	0144-8617
DOI	10.1016/j.carbpol.2021.117686
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Article ; Online: Atypical presentations of hydatid cyst in children and their management.

Mandal, Kartik Chandra / Halder, Pankaj / Mondal, Gobinda / Debnath, Bidyut / Mitra, Dipanwita / Mukhopadhyay, Biswanath

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology

2022 Volume 41, Issue 6, Page(s) 643–648

Abstract: Hydatid cyst (HC) is uncommon in children and usually involves a single organ, the lung being the most common site followed by the liver. A series of 18 children who presented with HC at different organs of the body managed at our institute over a period ...

Abstract	Hydatid cyst (HC) is uncommon in children and usually involves a single organ, the lung being the most common site followed by the liver. A series of 18 children who presented with HC at different organs of the body managed at our institute over a period of 5 years is presented here. The clinico-radiological evaluation was done in all patients followed by pharmacotherapy/surgery and was followed up for 2 years. Demographic data, organs of involvement, clinical presentations and investigations, response to oral albendazole therapy, surgical procedures, operative findings, perioperative clinical courses, and surgical outcomes were recorded. The mean age of presentation was 7.7 years with a male:female ratio of 11:7. All patients were symptomatic at presentation and four (22.22%) had atypical symptoms (obstructive jaundice, bladder outlet obstruction, and acute abdominal pain). Liver HC was more common than lung HC. Three patients (16.6%) had synchronous involvement of the lung and liver/spleen. All the patients underwent surgical excision of the cyst as none of them responded to preoperative pharmacotherapy. Open surgery was done in 15 patients and laparoscopic excision was carried out in three (16.6%). Two patients had abnormal communications (cysto-biliary/cysto-bronchial), which were managed successfully. Neither any major perioperative morbidity nor mortality was nor any recurrence was seen in a 2-year clinical follow-up, no significant perioperative morbidity or mortality occurred, and no recurrence was noted. In conclusion, single organ HC is more common in children, with more prevalence of hepatic than pulmonary HC. Early surgical excision of the cyst should be considered (preferably laparoscopic whenever possible) instead of pharmacotherapy.
MeSH term(s)	Humans ; Male ; Child ; Female ; Echinococcosis/diagnosis ; Echinococcosis/therapy ; Echinococcosis, Hepatic ; Albendazole/therapeutic use ; Cysts/drug therapy
Chemical Substances	Albendazole (F4216019LN)
Language	English
Publishing date	2022-12-09
Publishing country	India
Document type	Case Reports ; Journal Article
ZDB-ID	632595-6
ISSN	0975-0711 ; 0254-8860
ISSN (online)	0975-0711
ISSN	0254-8860
DOI	10.1007/s12664-022-01283-y
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Article ; Online: Inhibitory activity of traditional plants against Mycobacterium smegmatis and their action on Filamenting temperature sensitive mutant Z (FtsZ)-A cell division protein.

Ravindran, Radhika / Chakrapani, Gayathri / Mitra, Kartik / Doble, Mukesh

PloS one

2020 Volume 15, Issue 5, Page(s) e0232482

Abstract: The study was designed to assess whether plant extracts / phytochemical (D-Pinitol) synergistically combine with antituberculosis drugs and act on Mycobacterium smegmatis (M. smegmatis) as well as assess their mode of action on Mycobacterium tuberculosis ...

Abstract	The study was designed to assess whether plant extracts / phytochemical (D-Pinitol) synergistically combine with antituberculosis drugs and act on Mycobacterium smegmatis (M. smegmatis) as well as assess their mode of action on Mycobacterium tuberculosis (M.tb) Filamenting temperature sensitive mutant Z (FtsZ) protein. Resazurin microtitre plate assay (Checker board) was performed to analyze the activity of plant extracts against M. smegmatis. Synergistic behaviour of plant extracts / D-Pinitol with Isoniazid (INH) and Rifampicin (RIF) were determined by time-kill and checker board assays. Elongation of M. smegmatis cells due to this treatment was determined by light microscopy. The effect of Hexane methanol extract (HXM) plant extracts on cell viability was determined using PI/SYTO9 dual dye reporter Live/Dead assay. Action of HXM plant extracts / D-Pinitol on inhibition of FtsZ protein was done using Guanosine triphosphatase (GTPase) light scattering assay and quantitative Polymerase Chain Reaction (qPCR). The Hexane-methanolic plant extract of Acacia nilotica, Aegle marmelos and Glycyrrhiza glabra showed antimycobacterial activity at 1.56 ± 0.03, 1.32 ± 0.02 and 1.25 ± 0.03 mg/mL respectively and that of INH and RIF were 4.00 ± 0.06 μg/mL and 2.00 ± 0.04 μg/mL respectively. These plant extracts and major phytochemical exudate D-Pinitol was found to act synergistically with antimycobacterial drugs INH and RIF with an FIC index ~ 0.20. Time-Kill kinetics studies indicate that, these plant extracts were bacteriostatic in nature. D-Pinitol in conjunction with INH and RIF exhibited a 2 Log reduction in the growth of viable cells compared to untreated. Attempt to elucidate their mode of action through phenotypic analysis indicated that these plant extracts and D-Pinitol was found to interfere in cell division there by leading to an abnormal elongated cellular morphology. HXM extracts and D-Pinitol synergistically combined with the first line tuberculosis drugs, INH and RIF, to act on M. smegmatis. The increase in the length of M. smegmatis cells on treatment with D-Pinitol and HXM extract of the plants indicated that they hinder the cell division mechanism thereby leading to a filamentous phenotype, and finally leading to cell death. In addition, the integrity of the bacterial cell membrane is also altered causing cell death. Further gene expression analysis showed that these plant extracts and D-Pinitol hampers with function of FtsZ protein which was confirmed through in vitro inhibition of FtsZ-GTPase enzymatic activity.
MeSH term(s)	Antitubercular Agents/administration & dosage ; Bacterial Proteins/antagonists & inhibitors ; Bacterial Proteins/genetics ; Cell Division/drug effects ; Cytoskeletal Proteins/antagonists & inhibitors ; Cytoskeletal Proteins/genetics ; Drug Synergism ; Gene Expression Regulation, Bacterial/drug effects ; Genes, Bacterial/drug effects ; Humans ; In Vitro Techniques ; Inositol/administration & dosage ; Inositol/analogs & derivatives ; Isoniazid/administration & dosage ; Microbial Sensitivity Tests ; Mutation ; Mycobacterium smegmatis/cytology ; Mycobacterium smegmatis/drug effects ; Mycobacterium smegmatis/genetics ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Plant Extracts/administration & dosage ; Plants, Medicinal ; Rifampin/administration & dosage ; Temperature
Chemical Substances	Antitubercular Agents ; Bacterial Proteins ; Cytoskeletal Proteins ; FtsZ protein, Bacteria ; Plant Extracts ; pinitol (484-68-4) ; Inositol (4L6452S749) ; Isoniazid (V83O1VOZ8L) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2020-05-01
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0232482
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Article ; Online: Inhibitory activity of traditional plants against Mycobacterium smegmatis and their action on Filamenting temperature sensitive mutant Z (FtsZ)-A cell division protein.

Radhika Ravindran / Gayathri Chakrapani / Kartik Mitra / Mukesh Doble

PLoS ONE, Vol 15, Iss 5, p e

2020 Volume 0232482

Abstract	The study was designed to assess whether plant extracts / phytochemical (D-Pinitol) synergistically combine with antituberculosis drugs and act on Mycobacterium smegmatis (M. smegmatis) as well as assess their mode of action on Mycobacterium tuberculosis (M.tb) Filamenting temperature sensitive mutant Z (FtsZ) protein. Resazurin microtitre plate assay (Checker board) was performed to analyze the activity of plant extracts against M. smegmatis. Synergistic behaviour of plant extracts / D-Pinitol with Isoniazid (INH) and Rifampicin (RIF) were determined by time-kill and checker board assays. Elongation of M. smegmatis cells due to this treatment was determined by light microscopy. The effect of Hexane methanol extract (HXM) plant extracts on cell viability was determined using PI/SYTO9 dual dye reporter Live/Dead assay. Action of HXM plant extracts / D-Pinitol on inhibition of FtsZ protein was done using Guanosine triphosphatase (GTPase) light scattering assay and quantitative Polymerase Chain Reaction (qPCR). The Hexane-methanolic plant extract of Acacia nilotica, Aegle marmelos and Glycyrrhiza glabra showed antimycobacterial activity at 1.56 ± 0.03, 1.32 ± 0.02 and 1.25 ± 0.03 mg/mL respectively and that of INH and RIF were 4.00 ± 0.06 μg/mL and 2.00 ± 0.04 μg/mL respectively. These plant extracts and major phytochemical exudate D-Pinitol was found to act synergistically with antimycobacterial drugs INH and RIF with an FIC index ~ 0.20. Time-Kill kinetics studies indicate that, these plant extracts were bacteriostatic in nature. D-Pinitol in conjunction with INH and RIF exhibited a 2 Log reduction in the growth of viable cells compared to untreated. Attempt to elucidate their mode of action through phenotypic analysis indicated that these plant extracts and D-Pinitol was found to interfere in cell division there by leading to an abnormal elongated cellular morphology. HXM extracts and D-Pinitol synergistically combined with the first line tuberculosis drugs, INH and RIF, to act on M. smegmatis. The increase in the length of M. smegmatis cells on treatment with D-Pinitol and HXM extract of the plants indicated that they hinder the cell division mechanism thereby leading to a filamentous phenotype, and finally leading to cell death. In addition, the integrity of the bacterial cell membrane is also altered causing cell death. Further gene expression analysis showed that these plant extracts and D-Pinitol hampers with function of FtsZ protein which was confirmed through in vitro inhibition of FtsZ-GTPase enzymatic activity.
Keywords	Medicine ; R ; Science ; Q
Subject code	580 ; 571
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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