Around 5% of patients with cirrhosis of the liver develop hepatic hydrothorax (HH). For patients with refractory HH (RHH), transjugular intrahepatic portosystemic shunt (TIPS) has been investigated in small studies. Hence, the present meta-analysis aimed to summarize the current data on the outcome of TIPS in patients with RHH.
View Article and Find Full Text PDFMachine learning has proven exceptionally competent in numerous applications of studying dynamical systems. In this article, we demonstrate the effectiveness of reservoir computing, a famous machine learning architecture, in learning a high-dimensional spatiotemporal pattern. We employ an echo-state network to predict the phase ordering dynamics of 2D binary systems-Ising magnet and binary alloys.
View Article and Find Full Text PDFThe NOD1-NOD2-RIPK2-NFKB/NF-κB pro-inflammatory axis plays a significant role in regulating the immune response to bacterial infection. However, an excess of NFKB-dependent cytokine response can be detrimental and, thus, should be kept under control to maintain the innate immune balance. In our recent study, first, we showed that bacterial infection induces the biogenesis of RIPK2 oligomers (RIPosomes) that are recruited around the bacteria to enhance an NFKB-dependent pro-inflammatory response.
View Article and Find Full Text PDFThe NOD1/2-RIPK2 is a key cytosolic signaling complex that activates NF-κB pro-inflammatory response against invading pathogens. However, uncontrolled NF-κB signaling can cause tissue damage leading to chronic diseases. The mechanisms by which the NODs-RIPK2-NF-κB innate immune axis is activated and resolved remain poorly understood.
View Article and Find Full Text PDFAutophagy is a highly conserved process that utilizes lysosomes to selectively degrade a variety of intracellular cargo, thus providing quality control over cellular components and maintaining cellular regulatory functions. Autophagy is triggered by multiple stimuli ranging from nutrient starvation to microbial infection. Autophagy extensively shapes and modulates the inflammatory response, the concerted action of immune cells, and secreted mediators aimed to eradicate a microbial infection or to heal sterile tissue damage.
View Article and Find Full Text PDFExtensive crosstalk exists between autophagy and innate immune signalling pathways. The stimuli that induce pattern recognition receptor (PRR)-mediated innate immune signalling pathways, also upregulate autophagy. The purpose of this increased autophagy is to eliminate the stimuli and/or suppress the inflammatory pathways by targeted degradation of PRRs or intermediary proteins (termed 'inflammophagy').
View Article and Find Full Text PDFThe aim of the present investigation was to formulate protein nanoparticles (PNPs) loaded suppositories for colon targeting of metronidazole (MZ), to achieve sustain release effect. PNPs were formulated via desolvation technique by utilizing 2 factorial design which results into eight formulations. The synthesized PNPs were characterized for different physicochemical and in vitro parameters .
View Article and Find Full Text PDFA novel multicomponent one-pot expeditious synthesis of highly functionalized and pharmaceutically fascinated pyranopyrazoles has been developed. This reaction occurs via tandem Knoevenagel condensation reaction of methyl aryl derivatives, 3-methyl pyrazolone and malononitrile in the presence of urea hydrogen peroxide under the physical grinding method. The present methodology offers several benefits such as available green and cheap starting materials, solvent-free, mild reaction conditions, high atom economy, eco-friendly standards, excellent yields and easy isolation of the products without column chromatographic separation.
View Article and Find Full Text PDFDZIP3/hRUL138 is a poorly characterized RNA-binding RING E3-ubiquitin ligase with functions in embryonic development. Here we demonstrate that DZIP3 is a crucial driver of cancer cell growth, migration, and invasion. In mice and zebrafish cancer models, DZIP3 promoted tumor growth and metastasis.
View Article and Find Full Text PDFIRGM is a genetic risk factor for several autoimmune diseases. However, the mechanism of IRGM-mediated protection in autoimmunity remains undetermined. The abnormal activation of type I interferon (IFN) response is one of the significant factors in the pathogenesis of several autoimmune diseases.
View Article and Find Full Text PDFActivation of the type 1 interferon response is extensively connected to the pathogenesis of autoimmune diseases. Loss of function of Immunity Related GTPase M (IRGM) has also been associated to several autoimmune diseases, but its mechanism of action is unknown. Here, we found that IRGM is a master negative regulator of the interferon response.
View Article and Find Full Text PDFNanodiamonds are novel nanosized carbon building blocks possessing varied fascinating mechanical, chemical, optical and biological properties, making them significant active moiety carriers for biomedical application. These are known as the most 'captivating' crystals attributed to their chemical inertness and unique properties posing them useful for variety of applications in biomedical era. Alongside, it becomes increasingly important to find, ascertain and circumvent the negative aspects associated with nanodiamonds.
View Article and Find Full Text PDFNanoparticles (NPs) have been found to be potential targeted and controlled release drug delivery systems. Various drugs can be loaded in the NPs to achieve targeted delivery. Chitosan NPs being biodegradable, biocompatible, less toxic and easy to prepare, are an effective and potential tool for drug delivery.
View Article and Find Full Text PDFThe cellular stresses, genetic mutations, and environmental factors can critically affect the protein quality control checkpoints resulting in protein misfolding. Molecular chaperones play a crucial role in maintaining the healthy proteome by refolding the misfolded proteins into the native functional conformations. However, if they fail to refold the misfolded proteins into the native state, they are targeted by proteolytic systems for degradation.
View Article and Find Full Text PDFIRGM is an established genetic risk factor for Crohn disease (CD) and several other inflammatory disorders. However, the mechanisms employed by IRGM to restrain the inflammation are not known. In our recent study, we showed that IRGM negatively regulates NLRP3 inflammasome activation.
View Article and Find Full Text PDFAutophagy
May 2019
The formation of protein aggregates is linked to several diseases collectively called proteinopathies. The mechanisms and the molecular players that control the turnover of protein aggregates are not well defined. We recently showed that TRIM16 acts as a key regulatory protein to control the biogenesis and degradation of protein aggregates.
View Article and Find Full Text PDFSeveral large-scale genome-wide association studies genetically linked IRGM to Crohn's disease and other inflammatory disorders in which the IRGM appears to have a protective function. However, the mechanism by which IRGM accomplishes this anti-inflammatory role remains unclear. Here, we reveal that IRGM/Irgm1 is a negative regulator of the NLRP3 inflammasome activation.
View Article and Find Full Text PDFProtein misfolding and protein aggregation are linked to several diseases commonly called as proteinopathies, which include cancer. Understanding the mechanisms of proteostasis could provide newer strategies to combat proteinopathies. We have recently demonstrated a new mechanism where we found that TRIM16 (tripartite motif-containing protein 16) utilizing NRF2-p62 axis and autophagy streamlines the safe disposal of misfolded proteins to maintain protein homeostasis.
View Article and Find Full Text PDFSequestration of protein aggregates in inclusion bodies and their subsequent degradation prevents proteostasis imbalance, cytotoxicity, and proteinopathies. The underlying molecular mechanisms controlling the turnover of protein aggregates are mostly uncharacterized. Herein, we show that a TRIM family protein, TRIM16, governs the process of stress-induced biogenesis and degradation of protein aggregates.
View Article and Find Full Text PDFThe advancement of the biological production of nanoparticles using herbal extracts performs a significant role in nanotechnology discipline as it is green and does not engage harsh chemicals. The objective of the present investigation was to extract flavonoids in the mode of apple extract and synthesize its silver nanoparticles and ultimately nanoparticles loading into hydrogels. The presence of flavonoids in apple extract was characterized by preliminary testing like dil.
View Article and Find Full Text PDFCoactivator-associated arginine methyltransferase 1 (CARM1) is known to promote estrogen receptor (ER)α-mediated transcription in breast cancer cells. To further characterize the regulation of ERα-mediated transcription by CARM1, we screened CARM1-interacting proteins by yeast two-hybrid. Here, we have identified an E3 ubiquitin ligase, DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3), as a novel CARM1-binding protein.
View Article and Find Full Text PDFAutophagy constitutes a major cell-protective mechanism that eliminates damaged components and maintains energy homeostasis via recycling nutrients under normal/stressed conditions. Although the core components of autophagy have been well studied, regulation of autophagy at the transcriptional level is poorly understood. Herein, we establish ZKSCAN3, a zinc finger family DNA-binding protein, as a transcriptional repressor of autophagy.
View Article and Find Full Text PDFsGC (soluble guanylate cyclase) is the main mediator of NO signalling. Biochemical and physiological studies suggest that, besides NO, in vivo regulation of sGC involves direct interaction with other proteins. Using yeast two-hybrid screening, we identified that the multidomain LGN (Leu-Gly-Asn repeat-enriched protein) interacts with both α1 and β1 sGC subunits.
View Article and Find Full Text PDFBackground: Glyoxalase I is a metalloenzyme of the glyoxalase pathway that plays a central role in eliminating the toxic metabolite methyglyoxal. The protozoan parasite Leishmania donovani possesses a unique trypanothione dependent glyoxalase system.
Principal Findings: Analysis of the L.
Curr Drug Targets
November 2008
Trypanosomatids are pathogenic protozoa of the order Kinetoplastida. A unique feature of these parasitic protozoa is the presence of a unique dithiol trypanothione (N(1), N(8) -bis(glutathionyl)spermidine) and the flavoenzyme trypanothione reductase. This is in contrast to human and other eukaryotes, which contain ubiquitous glutathione/glutathione reductase system.
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