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Article ; Online: Viral infection and host immune response in diabetes.

Joshi, Garima / Das, Anushka / Verma, Garima / Guchhait, Prasenjit

2023 Volume 76, Issue 5, Page(s) 242–266

Abstract: Diabetes, a chronic metabolic disorder disrupting blood sugar regulation, has emerged as a prominent silent pandemic. Uncontrolled diabetes predisposes an individual to develop fatal complications like cardiovascular disorders, kidney damage, and ... ...

Abstract	Diabetes, a chronic metabolic disorder disrupting blood sugar regulation, has emerged as a prominent silent pandemic. Uncontrolled diabetes predisposes an individual to develop fatal complications like cardiovascular disorders, kidney damage, and neuropathies and aggravates the severity of treatable infections. Escalating cases of Type 1 and Type 2 diabetes correlate with a global upswing in diabetes-linked mortality. As a growing global concern with limited preventive interventions, diabetes necessitates extensive research to mitigate its healthcare burden and assist ailing patients. An altered immune system exacerbated by chronic hyperinflammation heightens the susceptibility of diabetic individuals to microbial infections, including notable viruses like SARS-CoV-2, dengue, and influenza. Given such a scenario, we scrutinized the literature and compiled molecular pathways and signaling cascades related to immune compartments in diabetics that escalate the severity associated with the above-mentioned viral infections in them as compared to healthy individuals. The pathogenesis of these viral infections that trigger diabetes compromises both innate and adaptive immune functions and pre-existing diabetes also leads to heightened disease severity. Lastly, this review succinctly outlines available treatments for diabetics, which may hold promise as preventive or supportive measures to effectively combat these viral infections in the former.
MeSH term(s)	Humans ; COVID-19/immunology ; COVID-19/virology ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Virus Diseases/immunology ; Virus Diseases/virology ; Immunity, Innate ; Diabetes Mellitus/immunology ; Diabetes Mellitus/virology ; Dengue/immunology ; Dengue/virology ; Diabetes Mellitus, Type 2/immunology ; Diabetes Mellitus, Type 2/virology ; Influenza, Human/immunology ; Influenza, Human/virology ; Adaptive Immunity
Language	English
Publishing date	2023-12-08
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1492141-8
ISSN	1521-6551 ; 1521-6543
ISSN (online)	1521-6551
ISSN	1521-6543
DOI	10.1002/iub.2794
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Zs.A 1611: Show issues

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Article ; Online: CXCR3 antagonist rescues ER stress and reduces inflammation and JEV infection in mice brain.

Singh, Anamika / Ghosh, Riya / Guchhait, Prasenjit

Cytokine

2023 Volume 172, Page(s) 156380

Abstract: The endoplasmic reticulum (ER) is crucial for maintaining cellular homeostasis, and synthesis and folding of proteins and lipids. The ER is sensitive to stresses including viral infection that perturb the intracellular energy level and redox state, and ... ...

Abstract	The endoplasmic reticulum (ER) is crucial for maintaining cellular homeostasis, and synthesis and folding of proteins and lipids. The ER is sensitive to stresses including viral infection that perturb the intracellular energy level and redox state, and accumulating unfolded/misfolded proteins. Viruses including Japanese encephalitis virus (JEV) activates unfolded protein response (UPR) causing ER stress in host immune cells and promotes inflammation and apoptotic cell death. The chemokine receptor CXCR3 has been reported to play important role in the accumulation of inflammatory immune cells and neuronal cell death in several disease conditions. Recently we described the involvement of CXCR3 in regulating inflammation and JEV infection in mice brain. Supplementation with a CXCR3 antagonist AMG487 significantly reduced JEV infection in the mice brain in conjunction with the downregulation of UPR pathway via PERK:eIF2α:CHOP, and decreased mitochondrial ROS generation, inflammation and apoptotic cell death. Alongside, AMG487 treatment improved interferon (IFN)-α/β synthesis in JEV-infected mice brain. Thus, suggesting a potential therapeutic role of CXCR3 antagonist against JEV infection.
MeSH term(s)	Animals ; Mice ; Encephalitis Virus, Japanese ; Encephalitis, Japanese/metabolism ; Endoplasmic Reticulum Stress ; Inflammation/drug therapy ; Brain/metabolism
Chemical Substances	N-(1-(3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido(2,3-d)pyrimidin-2-yl)ethyl)-N-pyridin-3-ylmethyl-2-(4-trifluoromethoxyphenyl)acetamide
Language	English
Publishing date	2023-10-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2023.156380
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Zs.A 2840: Show issues

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Article ; Online: Alpha-ketoglutarate supplementation reduces inflammation and thrombosis in type 2 diabetes by suppressing leukocyte and platelet activation.

Agarwal, Sakshi / Ghosh, Riya / Verma, Garima / Khadgawat, Rajesh / Guchhait, Prasenjit

Clinical and experimental immunology

2023 Volume 214, Issue 2, Page(s) 197–208

Abstract: The interplay between platelets and leukocytes contributes to the pathogenesis of inflammation, thrombosis, and cardiovascular diseases (CVDs) in type 2 diabetes (T2D). Our recent studies described alpha-ketoglutarate (αKG), a Krebs cycle intermediate ... ...

Abstract	The interplay between platelets and leukocytes contributes to the pathogenesis of inflammation, thrombosis, and cardiovascular diseases (CVDs) in type 2 diabetes (T2D). Our recent studies described alpha-ketoglutarate (αKG), a Krebs cycle intermediate metabolite as an inhibitor to platelets and leukocytes activation by suppressing phosphorylated-Akt (pAkt) through augmentation of prolyl hydroxylase-2 (PHD2). Dietary supplementation with a pharmacological concentration of αKG significantly inhibited lung inflammation in mice with either SARS-CoV-2 infection or exposed to hypoxia treatment. We therefore investigated if αKG supplementation could suppress hyperactivation of these blood cells and reduce thromboinflammatory complications in T2D. Our study describes that dietary supplementation with αKG (8 mg/100 g body wt. daily) for 7 days significantly reduced the activation of platelets and leukocytes (neutrophils and monocytes), and accumulation of IL1β, TNFα, and IL6 in peripheral blood of T2D mice. αKG also reduced the infiltration of platelets and leukocytes, and accumulation of inflammatory cytokines in lungs by suppressing pAkt and pP65 signaling. In a cross-sectional investigation, our study also described the elevated platelet-leukocyte aggregates and pro-inflammatory cytokines in circulation of T2D patients. T2D platelets and leukocytes showed an increased aggregation and thrombus formation in vitro. Interestingly, a pre-incubation of T2D blood samples with octyl αKG significantly suppressed the activation of these blood cells and ameliorated aggregate/thrombus formation in vitro. Thus, suggesting a potential therapeutic role of αKG against inflammation, thrombosis, and CVDs in T2D.
MeSH term(s)	Humans ; Mice ; Animals ; Ketoglutaric Acids/metabolism ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Platelet Activation ; Inflammation/metabolism ; Leukocytes/pathology ; Blood Platelets/pathology ; Thrombosis/drug therapy ; Thrombosis/etiology ; Cardiovascular Diseases/pathology ; Cytokines/metabolism ; Dietary Supplements
Chemical Substances	Ketoglutaric Acids ; Cytokines
Language	English
Publishing date	2023-06-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxad086
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Article ; Online: Role of Platelet Cytokines in Dengue Virus Infection.

Singh, Anamika / Bisht, Piyush / Bhattacharya, Sulagna / Guchhait, Prasenjit

Frontiers in cellular and infection microbiology

2020 Volume 10, Page(s) 561366

Abstract: Platelets are anucleated blood cells derived from bone marrow megakaryocytes and play a crucial role in hemostasis and thrombosis. Platelets contain specialized storage organelles, called alpha-granules, contents of which are rich in cytokines such as C- ... ...

Abstract	Platelets are anucleated blood cells derived from bone marrow megakaryocytes and play a crucial role in hemostasis and thrombosis. Platelets contain specialized storage organelles, called alpha-granules, contents of which are rich in cytokines such as C-X-C Motif Chemokine Ligand (CXCL) 1/4/7, (C-C motif) ligand (CCL) 5/3, CXCL8 (also called as interleukin 8, IL-8), and transforming growth factor β (TGF-β). Activation of platelets lead to degranulation and release of contents into the plasma. Platelet activation is a common event in many viral infections including human immunodeficiency virus (HIV), H1N1 influenza, Hepatitis C virus (HCV), Ebola virus (EBV), and Dengue virus (DENV). The cytokines CXCL8, CCL5 (also known as Regulated on Activation, Normal T Expressed and Secreted, RANTES), tumor necrosis factor α (TNF-α), CXCL1/5 and CCL3 released, promote development of a pro-inflammatory state along with the recruitment of other immune cells to the site of infection. Platelets also interact with Monocytes and Neutrophils and facilitate their activation to release different cytokines which further enhances inflammation. Upon activation, platelets also secrete factors such as CXCL4 (also known as platelet factor, PF4), CCL5 and fibrinopeptides which are critical regulators of replication and propagation of several viruses in the host. Studies suggest that CXCL4 can both inhibit as well as enhance HIV1 infection. Data from our lab show that CXCL4 inhibits interferon (IFN) pathway and promotes DENV replication in monocytes
MeSH term(s)	Blood Platelets ; Cytokines ; Dengue ; Dengue Virus ; Humans ; Influenza A Virus, H1N1 Subtype
Chemical Substances	Cytokines
Keywords	covid19
Language	English
Publishing date	2020-09-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2020.561366
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Article ; Online: Interplay between hypoxia and inflammation contributes to the progression and severity of respiratory viral diseases.

Bhattacharya, Sulagna / Agarwal, Sakshi / Shrimali, Nishith M / Guchhait, Prasenjit

Molecular aspects of medicine

2021 Volume 81, Page(s) 101000

Abstract: History of pandemics is dominated by viral infections and specifically respiratory viral diseases like influenza and COVID-19. Lower respiratory tract infection is the fourth leading cause of death worldwide. Crosstalk between resultant inflammation and ... ...

Abstract	History of pandemics is dominated by viral infections and specifically respiratory viral diseases like influenza and COVID-19. Lower respiratory tract infection is the fourth leading cause of death worldwide. Crosstalk between resultant inflammation and hypoxic microenvironment may impair ventilatory response of lungs. This reduces arterial partial pressure of oxygen, termed as hypoxemia, which is observed in a section of patients with respiratory virus infections including SARS-CoV-2 (COVID-19). In this review, we describe the interplay between inflammation and hypoxic microenvironment in respiratory viral infection and its contribution to disease pathogenesis.
MeSH term(s)	COVID-19 ; Humans ; Hypoxia ; Inflammation ; Pandemics ; SARS-CoV-2
Language	English
Publishing date	2021-07-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	197640-0
ISSN	1872-9452 ; 0098-2997
ISSN (online)	1872-9452
ISSN	0098-2997
DOI	10.1016/j.mam.2021.101000
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Zs.A 1189: Show issues

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Article ; Online: Redox responsive poly(allylamine)/eudragit S-100 nanoparticles for dual drug delivery in colorectal cancer.

Gupta, Aastha / Sood, Ankur / Dhiman, Ankita / Shrimali, Nishith / Singhmar, Ritu / Guchhait, Prasenjit / Agrawal, Garima

Biomaterials advances

2022 Volume 143, Page(s) 213184

Abstract: Herein, we report redox responsive, colon cancer targeting poly(allylamine) (PA)/eudragit S-100 (EU) nanoparticles (PAEU NPs) (≈59 nm). These disulfide crosslinked PAEU NPs are developed via air oxidation of thiolated PA and thiolated EU, eliminating the ...

Abstract	Herein, we report redox responsive, colon cancer targeting poly(allylamine) (PA)/eudragit S-100 (EU) nanoparticles (PAEU NPs) (≈59 nm). These disulfide crosslinked PAEU NPs are developed via air oxidation of thiolated PA and thiolated EU, eliminating the need of any external crosslinking agent for dual drug delivery. PAEU NPs can effectively encapsulate both hydrophilic doxorubicin (DOX) and hydrophobic curcumin (Cur) drug with ≈85 % and ≈97 % encapsulation efficiency respectively. Here, the combination of drugs having different anticancer mechanism offers the possibility of developing nanosystem with enhanced anticancer efficacy. The developed PAEU NPs show good colloidal stability and low drug release under physiological conditions, while high DOX (≈98 %) and Cur (≈93 %) release is observed in reducing environment (10 mM GSH). Further, DOX and Cur loaded PAEU NPs exhibit higher cancer cell killing efficiency as compared to individual free drugs. In vivo biodistribution studies with Balb/C mice display the retention of PAEU NPs in the colon region up to 24 h presenting the developed approach as an efficient way for colorectal cancer therapy.
MeSH term(s)	Mice ; Animals ; Tissue Distribution ; Allylamine ; Nanoparticles ; Doxorubicin/therapeutic use ; Curcumin ; Oxidation-Reduction ; Colorectal Neoplasms/drug therapy
Chemical Substances	methylmethacrylate-methacrylic acid copolymer (25086-15-1) ; Allylamine (48G762T011) ; Doxorubicin (80168379AG) ; Curcumin (IT942ZTH98)
Language	English
Publishing date	2022-11-04
Publishing country	Netherlands
Document type	Journal Article
ISSN	2772-9508
ISSN (online)	2772-9508
DOI	10.1016/j.bioadv.2022.213184
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Article ; Online: Extracellular vesicles recovered from plasma of severe dengue patients induce CD4+ T cell suppression through PD-L1/PD-1 interaction.

Kumari, Sharda / Bandyopadhyay, Bhaswati / Singh, Anamika / Aggarwal, Suruchi / Yadav, Amit Kumar / Vikram, Naval Kishore / Guchhait, Prasenjit / Banerjee, Arup

mBio

2023 , Page(s) e0182323

Abstract: Importance: Severe dengue manifestations caused by the dengue virus are a global health problem. Studies suggest that severe dengue disease depends on uncontrolled immune cell activation, and excessive inflammation adds to the pathogenesis of severe ... ...

Abstract	Importance: Severe dengue manifestations caused by the dengue virus are a global health problem. Studies suggest that severe dengue disease depends on uncontrolled immune cell activation, and excessive inflammation adds to the pathogenesis of severe dengue disease. Therefore, it is important to understand the process that triggers the uncontrolled activation of the immune cells. The change in immune response in mild to severe dengue may be due to direct virus-to-cell interaction or it could be a contact-independent process through the extracellular vesicles (EVs) released from infected cells. The importance of circulating EVs in the context of dengue virus infection and pathogenesis remains unexplored. Therefore, understanding the possible biological function of circulating EVs may help to delineate the role of EVs in the progression of disease. Our present study highlights that EVs from plasma of severe dengue patients can have immunosuppressive properties on CD4+ T cells which may contribute to T cell suppression and may contribute to dengue disease progression.
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.01823-23
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Article ; Online: Elevated glycosylation of CD36 in platelets is a risk factor for oxLDL-mediated platelet activation in type 2 diabetes.

Agarwal, Sakshi / Saha, Sandhini / Ghosh, Riya / Sarmadhikari, Debapriyo / Asthana, Shailendra / Maiti, Tushar K / Khadgawat, Rajesh / Guchhait, Prasenjit

The FEBS journal

2023 Volume 291, Issue 2, Page(s) 376–391

Abstract: Platelet activation and related cardiovascular complications are the hallmarks of type 2 diabetes (T2D). We investigated the mechanism of platelet activation in T2D using MS-based identification of differentially expressed platelet proteins with a focus ... ...

Abstract	Platelet activation and related cardiovascular complications are the hallmarks of type 2 diabetes (T2D). We investigated the mechanism of platelet activation in T2D using MS-based identification of differentially expressed platelet proteins with a focus on glycosylated forms. Glycosylation is considered one of the common post-translational modifications in T2D, and N/O-linked glycosylation of glycoproteins (GPs)/integrins is known to play crucial roles in platelet activation. Our platelet proteome data revealed elevated levels of GPs GPIbα, GPIIbIIIa, GPIV (CD36), GPV and integrins in T2D patients. T2D platelets had elevated N-linked glycosylation of CD36 at asparagine (Asn)
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/genetics ; Glycosylation ; Molecular Docking Simulation ; Platelet Activation/physiology ; Lipoproteins, LDL/pharmacology ; Risk Factors ; Integrins/metabolism
Chemical Substances	oxidized low density lipoprotein ; Lipoproteins, LDL ; Integrins
Language	English
Publishing date	2023-10-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.16976
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Article: High-mobility group box 1 protein promotes dengue virus replication by interacting with untranslated regions of viral genome

Chaudhary, Nidhi / Srivastava, Shikha / Dave, Upma / Ojha, Amrita / Guchhait, Prasenjit / Chandele, Anmol / Patel, Ashok Kumar

Virus research. 2022 Feb., v. 309

2022

Abstract: Dengue virus (DENV) is most prevalent arthropod-borne human pathogen belongs to Flaviviridae family causes thousands of deaths annually. HMGB1 is highly conserved, ubiquitously expressed, non-histone nuclear protein which plays important role in diseases ...

Abstract	Dengue virus (DENV) is most prevalent arthropod-borne human pathogen belongs to Flaviviridae family causes thousands of deaths annually. HMGB1 is highly conserved, ubiquitously expressed, non-histone nuclear protein which plays important role in diseases like metabolic disorders, cancer, and viral infections. However, the importance of HMGB1 in DENV infection is understudied. In this study, we observed that DENV-2 induces cytoplasmic translocation and secretion of HMGB1. Interestingly, inhibition of HMGB1 secretion by ethyl pyruvate (EP) enhanced viral propagation while silencing of HMGB1 resulted in abrogated viral replication in DENV-2 infected A549 cells. RNA-Electrophoretic mobility shift assay and immunoprecipitation showed that HMGB1 interacts with 5′-3′ UTRs of DENV-2 genome. This interaction further stimulates production of proinflammatory cytokines like TNF-α, IL-6 and IL-1β which have been implicated in pathogenesis of severe DENV disease. Together, our finding suggests that DENV-2 modulates HMGB1 translocation and HMGB1-DENV-2 UTRs RNA interaction further induces proinflammatory cytokines production in A549 cells. This study discloses HMGB1 as an important host factor contributing to disease pathogenesis and hence can be targeted as an alternative approach for antiviral development against DENV virus infection.
Keywords	Dengue virus ; RNA ; animal pathogens ; interleukin-6 ; nucleoproteins ; pathogenesis ; precipitin tests ; pyruvic acid ; research ; secretion ; viral genome ; virus replication ; viruses
Language	English
Dates of publication	2022-02
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2021.198668
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Zs.A 1965: Show issues

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Article ; Online: Elevated surface-bound complement FH alters the function of platelets and monocytes in FHR1/3 null healthy individuals.

Bhasym, Angika / Bhakuni, Teena / Guchhait, Prasenjit

Blood cells, molecules & diseases

2019 Volume 79, Page(s) 102349

Abstract: Complement factor H (FH) and FH-related proteins (FHRs), structurally similar proteins are involved in the regulation of complement activation. Homozygous deletion of FHR 1 and 3 proteins (FHR1/3-/-) is known as a risk factor for disorders such as aHUS ... ...

Abstract	Complement factor H (FH) and FH-related proteins (FHRs), structurally similar proteins are involved in the regulation of complement activation. Homozygous deletion of FHR 1 and 3 proteins (FHR1/3-/-) is known as a risk factor for disorders such as aHUS and SLE, characterised by thrombo-inflammatory complications. Interestingly, FHR1/3-/- genotype also exists as polymorphism in healthy population of various ethnicities around the world including 8-10% Indians. In an effort to understand the functional role of this polymorphism, we describe in this study an elevated surface-bound FH on platelets and monocytes, but not other blood cells in FHR1/3 -/- healthy individuals. The FHR1/3-/- platelets displayed diminish ability to form aggregates in response to agonists in vitro. The FHR1/3-/- monocytes displayed elevated secretion of TNFα, IL1β, IL6 and IL10 in response to TLR ligands. However, exogenous FH limits platelet aggregates formation as well as cytokine secretion in monocytes. Therefore, observations together suggest a differential regulation of platelets and monocytes by FH-FHR1/3 axis in healthy individuals. While these findings will need more detailed investigation, it is clear that the connection between FH-FHR axis and thrombo-inflammatory complications is likely to be complex in diseases including aHUS and SLE, and provide interesting new directions for future study.
MeSH term(s)	Blood Platelets/physiology ; Blood Proteins/deficiency ; Blood Proteins/metabolism ; Complement C3b Inactivator Proteins/metabolism ; Complement Factor H/pharmacology ; Cytokines/metabolism ; Healthy Volunteers ; Humans ; Monocytes/physiology ; Platelet Aggregation
Chemical Substances	Blood Proteins ; CFH protein, human ; CFHR2 protein, human ; Complement C3b Inactivator Proteins ; Cytokines ; factor H-related protein 1 ; Complement Factor H (80295-65-4)
Language	English
Publishing date	2019-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1237083-6
ISSN	1096-0961 ; 1079-9796
ISSN (online)	1096-0961
ISSN	1079-9796
DOI	10.1016/j.bcmd.2019.102349
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