👤 Pulin Bihari Dhar

Renal fibrosis is a prominent pathophysiologic change seen with the progression of chronic kidney disease. Angiotensin II (Ang II), the central peptide of the renin-angiotensin aldosterone system (RAAS), is known to cause fibrosis under various disease conditions. Fibroblast growth factor receptor-1 (FGFR1) plays a critical role in epithelial to mesenchymal transition and tubulointerstitial fibrosis, but its role in Ang II-induced fibrosis in renal epithelial cells (RECs) and renal fibroblasts (RFbs) remains poorly understood. Our study aimed to investigate the role of FGFR1 in Ang II-induced fibrosis in both REC, RFbs and explore the potential of chimeric peptide (CP) in attenuating it. We developed a time-dependent in vitro fibrosis model using REC exposed to Ang II and analyzed the expression of FGFR1 and fibrotic markers by qPCR. Oxidative stress and profibrotic markers were measured using confocal imaging and flow cytometry. In RFbs, we also examined fibrotic cell proliferation and collagen deposition using proliferation assays and Sirius red staining. Our findings show that Ang II significantly increases FGFR1, AT Show less

Elicitation of the tumor-eliminating immune response is a major challenge, as macrophages- constituting a major component of solid tumor mass- play important roles in development, maintenance and tumor regression. The macrophage-expressed Toll-Like Receptors (TLRs) enhance macrophage function and their ability to activate T cells via secretion of cytokines, which may help in tumor regression. IL-27, a member of the IL-12 family of cytokines, is shown to exhibit anti-tumor and anti-angiogenic activities. Herein, we developed B16BL6 melanoma model in C75BL/6 mouse to dissect the crosstalk between TLRs and IL-27 in tumors. We report existence of a novel TLR- IL-27 feed-forward loop, whereby TLRs and IL-27 up-regulated each other's expression, which we found perturbed during melanoma tumorigenesis. Intra-tumoral injection of Imiquimod, a TLR7/8 ligand, reduced the tumor burden; the anti-tumor effect was reversed upon IL-27 and IL-27R silencing by intra-tumorally administered, lentivirally expressed IL-27 and IL-27R shRNA. The reduced tumor growth was accompanied by significantly fewer Treg cells but increased IFN-γ and granzyme B expression by CD8 Show less

Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disorder characterized by the presence of multiple osseous prominences. It can occur sporadically or within families (22 - 56%). Two genes, EXT1 and EXT2 located respectively at 8q24 and 11p11-p12, have been isolated to cause HME. It can cause gross deformity of limbs and growth disturbance which is quite a common complication. Malignant transformation to chondrosarcoma can also occur. Neurological presentations are rare and usually happened due to direct compression of a peripheral nerve or nerve root or less often the spinal cord. This case is possibly the first case of HME described from Bangladesh, presented with dorsal cord compression. Decompression was done and the complaints of myelopathy were improved. Show less

Multiple gene defects cause Batten disease. Accelerated apoptosis accounts for neurodegeneration in the late infantile and juvenile forms that are due to defects in the CLN3 and CLN2 genes. Extensive neuronal death is seen in CLN2- and CLN3-deficient human brain as well as in CLN6-deficient sheep brain and retina. When neurons in late infantile and juvenile brain survive, they manage to do so by upregulating the neuroprotective molecule Bcl-2. The CLN3 gene has antiapoptotic properties at the molecular level. We show that the CLN2 gene is neuroprotective: it enhances growth of NT2 cells and maintains survival of human postmitotic hNT neurons. Conversely, blocking CLN3 or CLN2 expression in hNT neurons with adenoviral antisense-CLN3 or antisense-CLN2-AAV2 constructs causes apoptosis. The drug flupirtine is a triaminopyridine derivative that acts as a nonopioid analgesic. Flupirtine upregulates Bcl-2, increases glutathione levels, activates an inwardly rectifying potassium channel, and delays loss of intermitochondrial membrane calcium retention capacity. We show that flupirtine aborts etoposide-induced apoptosis in CLN1-, CLN2-, CLN3-, and CLN6-deficient as well as normal lymphoblasts. Flupirtine also prevents the death of CLN3- and CLN2-deficient postmitotic hNT neurons at the mitochondrial level. We show that a mechanism of neuroprotection exerted by flupirtine involves complete functional antagonism of N-methyl-D-aspartate or N-methyl-D-aspartate-induced neuronal apoptosis. Flupirtine may be useful as a drug capable of halting the progression of neurodegenerative diseases caused by dysregulated apoptosis. Show less