👤 Sudipta Chakrabarti

We have extracted and characterized Phasa fish (Setipinna phasa) oil for the first time to evaluate the anti-obesity and related anti-inflammatory effects on obese mice. Inbred male albino BALB/c mice were segregated into three categories: control (C), Obese control group (OC), and Phasa fish oil treated group (TX). To establish the potentiality of Setipinna phasa oil for its anti-obesity and anti-inflammatory properties, it was extracted and characterized using GC-MS method. To evaluate the anti-obesity effect, different parameters were considered, such as body weight, lipid composition, obesity, and obesity associated inflammation. The physicochemical characteristics of Phasa fish oil revealed that the oil quality was good because acid value, peroxide value, p-anisidine value, Totox value, refractive index, and saponification value were within the standard value range. The GC-MS study explored the presence of fatty acids beneficial to health such as Hexadec-9-enoic acid; Octadec-11-enoic acid; EPA, DHA, Methyl Linolenate, etc. The application of Setipinna phasa oil on the treated mice group acutely lowered body weight and serum lipid profile compared to the obese group. In connection with this, leptin, FAS, and pro-inflammatory cytokines TNF-α genes expression were downregulated in the treated group compared to the obese group. The Phasa oil treated group had an elevated expression of PPAR-α, adiponectin, LPL gene, and anti-inflammatory markers IL-10 and IL-1Ra compared to the obese group. This study suggests that Phasa fish oil, enriched with essential fatty acid, might be used as an anti-obesity and anti-inflammatory supplement. Show less

Evolutionarily conserved genes often play critical roles in organismal physiology. Here, we describe multiple roles of a previously uncharacterized Class III metallophosphodiesterase in Drosophila, an ortholog of the MPPED1 and MPPED2 proteins expressed in the mammalian brain. dMpped, the product of CG16717, hydrolyzed phosphodiester substrates including cAMP and cGMP in a metal-dependent manner. dMpped is expressed during development and in the adult fly. RNA-seq analysis of dMppedKO flies revealed misregulation of innate immune pathways. dMppedKO flies showed a reduced lifespan, which could be restored in Dredd hypomorphs, indicating that excessive production of antimicrobial peptides contributed to reduced longevity. Elevated levels of cAMP and cGMP in the brain of dMppedKO flies was restored on neuronal expression of dMpped, with a concomitant reduction in levels of antimicrobial peptides and restoration of normal life span. We observed that dMpped is expressed in the antennal lobe in the fly brain. dMppedKO flies showed defective specific attractant perception and desiccation sensitivity, correlated with the overexpression of Obp28 and Obp59 in knock-out flies. Importantly, neuronal expression of mammalian MPPED2 restored lifespan in dMppedKO flies. This is the first description of the pleiotropic roles of an evolutionarily conserved metallophosphodiesterase that may moonlight in diverse signaling pathways in an organism. Show less

Retinopathy of prematurity (ROP) is a neurovascular complication in preterm babies, leading to severe visual impairment, but the underlying mechanisms are yet unclear. The present study aimed at unraveling the molecular mechanisms underlying the pathogenesis of ROP. A comprehensive screening of candidate genes in preterms with ROP ( Show less

Upregulation of endothelin 1 (ET-1) causing blood flow alteration and increased extracellular matrix production are characteristic features of diabetic angiopathy. Several glucose-induced signaling mechanisms cause ET-1 upregulation in diabetic angiopathy. Extracellular signal-regulated kinase 5 (ERK5) is a member of the MAPK family, which plays a key role in cardiovascular development. ERK kinase (MEK) 5 is the specific MEK for ERK5 activation. In this study we examined the role of glucose-induced ERK5 signaling in mediating ET-1 expression in diabetic angiopathy. We investigated retinas from 1-month STZ-induced diabetic rats and human macro- and microvascular endothelial cells to study ERK5-dependent ET-1 alterations. Glucose (25 mmol/L) caused significant upregulation of ET-1 mRNA and downregulation of ERK5 and Kruppel-like factor 2 (KLF2) after 24 h treatment in the endothelial cells. Simultaneously, phospho-ERK5 proteins were reduced. Activation of ERK5 by constitutively active MEK5 (caMEK5) upregulated KLF2 and suppressed ET-1 expression in both cell lines, whereas ERK5 siRNA transfection resulted in decreased ERK5 and KLF2 and increased ET-1 mRNA expression. In addition, caMEK5 prevented glucose-induced upregulation of ET-1. Furthermore, 1 month of diabetes caused a significant increase in retinal ET-1 mRNA and decrease in ERK5 mRNA expression. These data indicate that ERK5 signaling regulates glucose-induced ET-1 expression in diabetes. The ERK5/ET-1 pathway may provide a potential novel target for the treatment of diabetic angiopathy. Show less

Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln3(-/-)) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3(-/-) mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis. Show less