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Amitava Das

Bio: Amitava Das is an academic researcher from Indiana University. The author has contributed to research in topics: Wound healing & Inflammation. The author has an hindex of 33, co-authored 125 publications receiving 3465 citations. Previous affiliations of Amitava Das include Mayo Clinic & Baylor College of Medicine.


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Journal ArticleDOI
TL;DR: Given a central role in tissue repair and regeneration, the review focuses on the heterogeneity of monocytes and macrophages with current known mechanisms of differentiation and plasticity, including microenvironmental cues and molecular mediators, such as noncoding RNAs.
Abstract: Heterogeneity and high versatility are the characteristic features of the cells of monocyte-macrophage lineage. The mononuclear phagocyte system, derived from the bone marrow progenitor cells, is primarily composed of monocytes, macrophages, and dendritic cells. In regenerative tissues, a central role of monocyte-derived macrophages and paracrine factors secreted by these cells is indisputable. Macrophages are highly plastic cells. On the basis of environmental cues and molecular mediators, these cells differentiate to proinflammatory type I macrophage (M1) or anti-inflammatory or proreparative type II macrophage (M2) phenotypes and transdifferentiate into other cell types. Given a central role in tissue repair and regeneration, the review focuses on the heterogeneity of monocytes and macrophages with current known mechanisms of differentiation and plasticity, including microenvironmental cues and molecular mediators, such as noncoding RNAs.

507 citations

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TL;DR: Elevated macrophage miR-21 promotes efferocytosis and silences target genes PTEN and PDCD4, which in turn accounts for a net anti-inflammatory phenotype, which highlights the significance of miRs in the resolution of wound inflammation.
Abstract: At an injury site, efficient clearance of apoptotic cells by wound macrophages or efferocytosis is a prerequisite for the timely resolution of inflammation. Emerging evidence indicates that microRNA-21 (miR-21) may regulate the inflammatory response. In this work, we sought to elucidate the significance of miR-21 in the regulation of efferocytosis-mediated suppression of innate immune response, a key process implicated in resolving inflammation following injury. An increased expression of inducible miR-21 was noted in postefferocytotic peripheral blood monocyte-derived macrophages. Such induction of miR-21 was associated with silencing of its target genes PTEN and PDCD4. Successful efferocytosis of apoptotic cells by monocyte-derived macrophages resulted in the suppression of LPS-induced NF-κB activation and TNF-α expression. Interestingly, bolstering of miR-21 levels alone, using miR mimic, resulted in significant suppression of LPS-induced TNF-α expression and NF-κB activation. We report that efferocytosis-induced miR-21, by silencing PTEN and GSK3β, tempers the LPS-induced inflammatory response. Macrophage efferocytosis is known to trigger the release of anti-inflammatory cytokine IL-10. This study demonstrates that following successful efferocytosis, miR-21 induction in macrophages silences PDCD4, favoring c-Jun-AP-1 activity, which in turn results in elevated production of anti-inflammatory IL-10. In summary, this work provides direct evidence implicating miRNA in the process of turning on an anti-inflammatory phenotype in the postefferocytotic macrophage. Elevated macrophage miR-21 promotes efferocytosis and silences target genes PTEN and PDCD4, which in turn accounts for a net anti-inflammatory phenotype. Findings of this study highlight the significance of miRs in the resolution of wound inflammation.

249 citations

Journal ArticleDOI
TL;DR: In this article, Bacopa monniera and Ginkgo biloba extracts were used to evaluate the antidementic and anticholinesterase activities in adult male Swiss mice.
Abstract: Bacopa monniera and Ginkgo biloba are well-known cognitive enhancers in Indian and Chinese traditional medicine systems. Standardized extracts of B. monniera and G. biloba were used to evaluate the antidementic and anticholinesterase activities in adult male Swiss mice. Antidementic activity was tested against scopolamine (3 mg/kg ip)-induced deficits in passive avoidance test. Three different extracts of B. monniera (30 mg/kg) and extract of G. biloba (15, 30 and 60 mg/kg) were administered postoperatively, daily for 7 days and 60 min after the last dose, i.e., on Day 7, first trial was conducted. In passive avoidance test, increased transfer latency time (TLT) and no transfer response (NTR) were taken as criteria for learning. TLT and NTR were significantly increased and decreased in second trial, 24 h after the first trial in control group and scopolamine-dementia group, respectively. The B. monniera- and G. biloba-treated groups produced significant increase in TLT and NTR on second trial (40-80%) after scopolamine treatment, thus, attenuating its antidementic effect. Both the extracts showed a dose (10-1000 microg)-dependent inhibitory effect on acetylcholinesterase (AChE) activity (in vitro), performed spectrophotometrically. IC(50) of G. biloba was 268.33 microg, whereas none of the extracts of B. monniera showed more than 50% inhibition. At a dose concentration of 30 and 60 mg/kg, extracts of G. biloba showed a cognitive enhancing property and, at the same time, a significant decrease in AChE-specific activity in both per se and scopolamine-dementia groups. These extracts possess a significant anticholinesterase and antidementic properties, which may be useful in the treatment of dementia.

242 citations

Journal ArticleDOI
TL;DR: A role for NRP-1 is revealed as a modulator of multiple growth factor targets that regulate liver fibrosis and the vascular changes that accompany it and may have broad implications for liver cirrhosis and myofibroblast biology in a variety of other organ systems and disease conditions.
Abstract: PDGF-dependent hepatic stellate cell (HSC) recruitment is an essential step in liver fibrosis and the sinusoidal vascular changes that accompany this process. However, the mechanisms that regulate PDGF signaling remain incompletely defined. Here, we found that in two rat models of liver fibrosis, the axonal guidance molecule neuropilin-1 (NRP-1) was upregulated in activated HSCs, which exhibit the highly motile myofibroblast phenotype. Additionally, NRP-1 colocalized with PDGF-receptor beta (PDGFRbeta) in HSCs both in the injury models and in human and rat HSC cell lines. In human HSCs, siRNA-mediated knockdown of NRP-1 attenuated PDGF-induced chemotaxis, while NRP-1 overexpression increased cell motility and TGF-beta-dependent collagen production. Similarly, mouse HSCs genetically modified to lack NRP-1 displayed reduced motility in response to PDGF treatment. Immunoprecipitation and biochemical binding studies revealed that NRP-1 increased PDGF binding affinity for PDGFRbeta-expressing cells and promoted downstream signaling. An NRP-1 neutralizing Ab ameliorated recruitment of HSCs, blocked liver fibrosis in a rat model of liver injury, and also attenuated VEGF responses in cultured liver endothelial cells. In addition, NRP-1 overexpression was observed in human specimens of liver cirrhosis caused by both hepatitis C and steatohepatitis. These studies reveal a role for NRP-1 as a modulator of multiple growth factor targets that regulate liver fibrosis and the vascular changes that accompany it and may have broad implications for liver cirrhosis and myofibroblast biology in a variety of other organ systems and disease conditions.

146 citations

Journal ArticleDOI
TL;DR: It is shown that PDGF promotes a phenotype of HSC evidenced by enhanced H SC-driven vascular tube formation in vitro and enhanced HSC coverage of sinusoids in vivo, and a key role for ephrin-B2 is identified as a downstream effector of PDGF signaling.

135 citations


Cited by
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Journal ArticleDOI
TL;DR: This critical review discusses the origins of MOF luminosity, which include the linker, the coordinated metal ions, antenna effects, excimer and exciplex formation, and guest molecules.
Abstract: Metal–organic frameworks (MOFs) display a wide range of luminescent behaviors resulting from the multifaceted nature of their structure. In this critical review we discuss the origins of MOF luminosity, which include the linker, the coordinated metal ions, antenna effects, excimer and exciplex formation, and guest molecules. The literature describing these effects is comprehensively surveyed, including a categorization of each report according to the type of luminescence observed. Finally, we discuss potential applications of luminescent MOFs. This review will be of interest to researchers and synthetic chemists attempting to design luminescent MOFs, and those engaged in the extension of MOFs to applications such as chemical, biological, and radiation detection, medical imaging, and electro-optical devices (141 references).

4,407 citations

Journal ArticleDOI
15 Mar 2016-Immunity
TL;DR: This review discusses the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing,pro-fibrotic, anti- inflammatory, anti -fib rotic, Pro-resolving, and tissue-regenerating phenotypes after injury, and highlights how some of these mechanisms and macrophage activation states could be exploited therapeutically.

2,284 citations

Journal ArticleDOI
TL;DR: The protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti‐microbial defense, anti-tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity are discussed.
Abstract: Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF, and produce pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-12, IL-23, and TNF-α; and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-β. M1 and M2 macrophages have different functions and transcriptional profiles. They have unique abilities by destroying pathogens or repair the inflammation-associated injury. It is known that M1/M2 macrophage balance polarization governs the fate of an organ in inflammation or injury. When the infection or inflammation is severe enough to affect an organ, macrophages first exhibit the M1 phenotype to release TNF-α, IL-1β, IL-12, and IL-23 against the stimulus. But, if M1 phase continues, it can cause tissue damage. Therefore, M2 macrophages secrete high amounts of IL-10 and TGF-β to suppress the inflammation, contribute to tissue repair, remodeling, vasculogenesis, and retain homeostasis. In this review, we first discuss the basic biology of macrophages including origin, differentiation and activation, tissue distribution, plasticity and polarization, migration, antigen presentation capacity, cytokine and chemokine production, metabolism, and involvement of microRNAs in macrophage polarization and function. Secondly, we discuss the protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti-microbial defense, anti-tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity.

2,176 citations

01 Feb 1995
TL;DR: In this paper, the unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio using DFT, MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set.
Abstract: : The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

1,652 citations