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Idris, M. M.

Publications and source records attributed to Idris, M. M..

11 recordsLinked to original sources

Hepatic Stellate Cell Exosomes Resolve Fibrosis in Mice Livers via Enriched Metabolic and Regenerative Signaling Molecules

BackgroundHepatic stellate cells (HSC) are Vitamin A storing non-parenchymal cells of the liver. During injury and inflammation, HSCs are the major contributors of excessive extracellular matrix (ECM) leading to Liver Fibrosis (LF). Emerging evidence suggests a fibrosis-independent role of these cells as key regulators of liver homeostasis and liver regeneration, emphasising on the dual role of HSCs in liver. HSCs are known to secrete several growth factors through which they largely execute their functions. However, the role of secretome (exosomes) from early activated or undifferentiated HSCs in a fibrotic milieu nor its composition are completely understood. MethodsLX-2 cells were cultured in low to no serum conditions and their isolated exosomes were transplanted into fibrotic severe combined immune deficient (SCID) mice livers, followed by post-transplantation analysis of the liver tissue and compared to the untreated controls. Total proteomic profiling of cell and exosomal cargo was performed using mass spectrometry and the data analysed and compared with the total HSC cell proteome. ResultsSignificant reduction in collagen in the transplanted mice livers compared to untreated fibrotic controls was observed with both the cells and exosomes transplantation. Comparative analysis revealed distinct enrichment of proteins and signaling pathways associated with extracellular matrix regulation, cellular communication, and metabolism in exosomes. Notably, these pathways are prominently represented in the exosomal fraction, suggesting a selective packaging of functional mediators. ConclusionThis study suggests the potential role of HSCs in regulating the complex liver homeostasis via exosomal network of proteins that contribute significantly to liver repair by ECM remodelling and growth factor-mediated signalling to regulate metabolism, fibrosis and liver regeneration. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/721862v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@99bbf4org.highwire.dtl.DTLVardef@1029dd0org.highwire.dtl.DTLVardef@c6f578org.highwire.dtl.DTLVardef@1dba81_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

Aging compromises Zebrafish caudal fin regeneration by disrupting Regenerative gene networks and Cellular metabolism

Zebrafish are widely recognized as a powerful vertebrate model for studying epimorphic regeneration due to their remarkable ability to restore complex tissues. However, regenerative efficiency declines with age, potentially due to alterations in gene regulatory networks and cellular metabolism. In the present study, we investigated the molecular and bioenergetic basis of age-associated regenerative decline by comparing young adult (<1 year) and old adult (>3 years) zebrafish during caudal fin regeneration. To further examine the contribution of mitochondrial function, mitochondrial dysfunction was experimentally induced using rotenone (20 nM), a mitochondrial Complex I inhibitor. Regenerative progression was assessed morphologically at 12hpa, 1dpa, 2dpa, 3dpa, and 7dpa, revealing a pronounced delay in fin regrowth in aged and rotenone-treated fish compared with young controls. Behavioral analysis indicated subtle but non-significant changes across experimental groups. Gene expression analysis using quantitative real-time PCR revealed age- and mitochondria-associated dysregulation of key regenerative gene families involved in developmental patterning, extracellular matrix organization, cellular signaling, and mitochondrial metabolism. Proteomic profiling further identified differential expression of proteins associated with mitochondrial bioenergetics, extracellular matrix remodeling, and signaling pathways required for blastema formation and tissue outgrowth. Ultrastructural examination by transmission electron microscopy revealed pronounced mitochondrial abnormalities, including enlarged mitochondria with fragmented or disrupted cristae, in aged and rotenone-treated regenerating tissues. Collectively, our integrative analysis establishes a mechanistic link between aging, mitochondrial dysfunction, and compromised regenerative capacity in zebrafish. The findings provide broader insights into metabolic constraints underlying age-related decline in regenerative potential in vertebrates.

developmental biology↗

Small molecule influence on Caudal fin regeneration in Zebrafish: A proteomic based study

Dietary and addictive small molecules play a significant role in altering in vivo conditions. Due to their minuscule size, these molecules can seamlessly traverse tissues and cellular membranes, influencing key biological processes such as cellular growth, differentiation, and intracellular communication, which are crucial for tissue regeneration. The zebrafish (Danio rerio) serves as an excellent model for studying regenerative growth due to its remarkable ability to regrow amputated appendages. In this study, we systematically evaluated the effect of small molecules, including ethanol (0.5%), glucose (1%), and NaCl (0.2%), on zebrafish caudal fin regeneration over a 7-day period. Regenerative growth analysis indicated delayed fin regrowth across all treated groups, with ethanol exposure showing the most significant impairment. Behavioural assessments revealed significant stress-induced locomotor alterations in treated groups, with the ethanol-exposed group exhibiting the most pronounced reduction in total distance moved and velocity. Proteomic profiling using label-free quantification (LFQ) identified 113, 257, and 178 differentially expressed proteins in ethanol, glucose, and NaCl-treated groups, respectively. Subsequent validation using the iTRAQ labeling approach confirmed 16 commonly dysregulated proteins across all conditions, highlighting a shared molecular response associated with stress and repair mechanisms. Pathway enrichment analysis mapped differentially expressed proteins to various canonical signaling pathways, including GP6 signaling, mitochondrial dysfunction, RHO GTPase cycling, antigen processing, and metabolic regulation. Ingenuity Pathway Analysis (IPA) further revealed associations with disease and function networks specific to each treatment condition. Our findings provide valuable insights into how metabolic and ionic perturbations influence zebrafish fin regeneration at the molecular level, offering a deeper understanding of tissue repair mechanisms under stressed conditions.

developmental biology↗

Exploration of phosphoproteomic association during epimorphic regeneration

Unravelling the intricate patterns of site-specific protein phosphorylation during Epimorphic regeneration holds the key to unlocking the secrets of tissue complexity. Understanding these precise modifications and their impact on protein function could shed light on the remarkable regenerative capacity of tissues, with potential implications for therapeutic interventions. In this study we have systematically mapped the global phosphorylation modifications within regenerating tissue of zebrafish caudal fins, elucidating the intricate landscape of signalling pathway associate with the regeneration process. A total of 74 and 440 proteins were found undergoing differentially phosphorylated during the process of regeneration from 12hpa to 7dpa against control based on TiO2 column enrichment and immuno precipitation using phosphoserine, phosphothreonine and phosphotyrosine antibodies respectively. Interestingly 95% of the proteins identified from TiO2 enrichment method were also found to be identified through the phosphoprotein antibody pull down method impacting the high accuracy and significance of the methods and greater association of the 70 proteins undergoing differential phosphorylation during the process of regeneration. Whole mount immunohistochemistry analysis reveals high association of phosphorylation at 1dpa, 2dpa and 3 dpa regeneration time points. Based on network pathway analysis it was evident that Fc Receptor-mediated Phagocytosis in Macrophages and Monocytes, Actin cytoskeleton signaling, HGF signaling and Insulin receptor signaling are the most highly associated network pathways for regeneration through differential phosphorylation. This research enhances our comprehension on protein post-translational modification in the context of zebrafish caudal fin tissue regeneration, shedding light on its prospective application in the field of regenerative medicine.

developmental biology↗

A proteomic perspective and involvement of cytokines in SARS-CoV-2 infection

Infection with the SARS-CoV-2 virus results in manifestation of several clinical observations from asymptomatic to multi-organ failure. Biochemically, the serious effects are due to what is described as cytokine storm. The initial infection region for COVID-19 is the nasopharyngeal/oropharyngeal region which is the site where samples are taken to examine the presence of virus. We have earlier shown that several defensin genes are down regulated in cells from this region in patients who tested positive in the RTPCR test. We have now carried out detailed proteomic analysis of the nasopharyngeal/oropharyngeal swab samples collected from normal individuals and those tested positive for SARS-CoV-2 by RTPCR, involving high throughput quantitative proteomics analysis. Several proteins like annexins, cytokines and histones were found differentially regulated in the host human cells following SARS-CoV-2 infection. Genes for these proteins were also observed to be differentially regulated when their expression was analyzed. Majority of the cytokine proteins were found to be up regulated in the infected individuals. Cell to Cell signaling interaction, Immune cell trafficking and inflammatory response pathways were found associated with the differentially regulated proteins based on network pathway analysis.

biochemistry↗

Gramicidin S and Melittin - Potential anti-viral therapeutic peptides to treat SARS-CoV-2 infection

The COVID19 pandemic has resulted in multipronged approaches for treatment of the disease. Since de novo discovery of drugs is time consuming, repurposing of molecules is now considered as one of the alternative strategies to treat COVID19. Antibacterial peptides are being recognized as attractive candidates for repurposing to treat viral infections. In this study, we describe the anti-SARS-CoV-2 activity of gramicidin S and melittin peptides obtained from Bacillus brevis and bee venom respectively. Our in vitro antiviral assay results showed significant decrease in the viral load compared to the untreated group with no/very less cytotoxicity. The EC50 values for gramicidin S and melittin are calculated as 1.571g and 0.656g respectively. Both the peptides treated to the SARS-CoV-2 infected Vero cells showed viral clearance from 12 hours onwards with a maximal clearance after 24 hours post infection. Based on proteome analysis it was found that more than 250 proteins were found to be differentially regulated in the gramicidin S and melittin treated SARS-CoV-2 infected Vero cells against control SARS-CoV-2 infected Vero cells after 24 and 48 hours post infection. The identified proteins were found to be associated in the metabolic and mRNA processing of the Vero cells post-treatment and infection. Both these peptides could be attractive candidates for repurposing to treat SARS-CoV-2 infection.

cell biology↗

Understanding the complexity of Epimorphic Regeneration in zebrafish: A Transcriptomic and Proteomic approach.

Genomic and Proteomic changes play a crucial role in perpetuating regeneration of complex tissues through differentiation and growth. The complex Epimorphic regeneration of zebrafish caudal fin tissue is hasty and absolute. This study was executed to understand the role of various genes/proteins involved in the regeneration of zebrafish caudal fin tissue through differential expression analysis. High throughput transcriptomics analysis involving Next Generation Sequencing approach and iTRAQ based quantitative proteomics analyses were performed on the regenerating tissue samples for various regenerating time points. Based on our study 1408 genes and 661 proteins were found differentially regulated in the regenerating caudal fin tissue for having at least 1-log fold change in their expression at 12hpa, 1, 2, 3 and 7dpa stages against control non-regenerating tissue. Interleukin, SLC, PRMT, HOX, neurotransmitter and several novel genes were found to be associated with regeneration for its differential regulation during the mechanism. Based on the network and pathway analysis the differentially regulated genes and proteins were found allied with activation of cell proliferation, cell viability, cell survival & cell movement and inactivation of organismal death, morbidity, necrosis, death of embryo & cell death. Network pathways such as Cancer & development disorder, Cell signaling molecular transport, organismal injury & abnormalities and Cellular development, growth & proliferation were found most significantly associated with the zebrafish caudal fin regeneration mechanism. This study has mapped a detailed insight of the genes/proteins expression associated with the epimorphic regeneration more profoundly.

developmental biology↗

Transcriptome and Proteome analysis of Hemidactylus frenatus during initial stages of tail regeneration

Epimorphic regeneration of appendages is a complex and complete phenomenon found in selected animals. Hemidactylus frenatus, the common house gecko has the remarkable ability to regenerate the tail tissue upon autotomy involving epimorphic regeneration mechanism. This study has identified and evaluated the molecular changes at gene and protein level during the regeneration of tail tissue. Based on next generation transcriptomics and De novo analysis the transcriptome and proteome library of the gecko tail tissue was generated. A total of 417 genes and 128 proteins were found to be associated with the regeneration of gecko tail tissue upon amputation at 1, 2 and 5-day post amputation against control, 0dpa through differential analysis. The differentially expressed genes and proteins expressed a similar pattern for the commonly identified 36 genes/proteins involved in regeneration of the tail tissue. Similarly, the expression analysis of 50 genes were further validated involving real time PCR to authenticate the transcriptomics analysis. 327 genes/proteins identified from the study showed association for GP6 signaling pathway, Protein kinase A signaling, Telomerase signaling BAG2 signaling, paxiling signaling, VEGF signaling network pathways based on network pathway analysis. This study empanelled list of genes/proteins associated with tail tissue regeneration and its association for the mechanism.

developmental biology↗

Properties and effect of Ittar in mice behavior and neurological functions

Fragrances are generally synthetic, natural or a combination of both. Ittar or Attar is a natural fragrance material synthesized from plants which were majorly used by people worldwide as a matter of pride, deodorization and attractant. The effect and role of using Ittar on mammalian system is still not known at the behavioral and neurological level. This study was aimed to understand the constituents and the effect of Ittar on mice by measuring their behavioral and neurological changes upon exposure to Ittar. Batches of animals were exposed to ten different types of Ittar for 1, 2 and 3 weeks respectively. Behavior of the animals exposed to the Ittar perfumes were analyzed against the control animals behavior for physiological activities. Also, the expression level of neurotransmitter such as Dopamine, 5-HIAA, HVA and Serotonin were evaluated based on HPLC analysis. Based on this study it was found that all the ten Ittars were different for its different constituents with some basic overlapping molecules among them. The neurotransmitter such as DOPA, 5-HT, Homovanillic Acid and Serotonin were found non-significantly increased in the total brain after a three week long continuous exposures of Ittar to the animal. Histological analysis of the ittar exposed mice skin showed mild to massive changes in both epidermal and dermal layers characterized with intense infiltration of inflammatory cells, hyperplasia, hyperchromasia and edema formation against control animals in few of the Ittars. From this study it is evident that Ittar increases mood of the animal through the up-regulation of various neurotransmitter but subtle effect on the skin because of the presence of various chemical constituents of the Ittar. Based on this study it is evident that use of Ittar as fragrance might be beneficial at the molecular level and it will be appropriate to apply without direct exposure to skin.

neuroscience↗

Functional Role of Annexins in Zebrafish Caudal Fin Regeneration: A Gene Knockdown Approach in Regenerating Tissue.

Regeneration is an adaptive phenomenon with wide biological implications spread heterogeneously in almost all the organism including human beings. The ability of regeneration varies from species to species for its impediment. Epimorphic regeneration of zebrafish caudal fin tissue is most widely studied regeneration mechanism for its discrete and rapid regenerative capability. Several genes/proteins were found to be associated with zebrafish caudal fin tissue regeneration. Here, we have evaluated the functional role of Annexin 2a and 2b genes in adult zebrafish caudal fin tissue undergoing regeneration using a novel CRSISPR-Cas9 gene knock down approach. Knock down of both the genes individually elicited in decelerated regeneration and down regulation of target genes and its partner genes/proteins such as ANXA1a, ANXA5b and ANXA13. This study validates a novel gene targeting approach and the possible role of annexin in regeneration mechanism.

developmental biology↗

Toxicity of TiO2, SiO2, ZnO, CuO, Au and Ag engineered nanoparticles on hatching and early nauplii of Artemia sp.

The potential of environmental release enhances with increased commercial applications of the nanomaterials. A simple and efficient test to estimate the acute toxicity of nanoparticles is carried out in this work using Artemia species and their hatching rate. We have tested six different engineered nanoparticles (silver, gold, copper oxide, zinc oxide, titanium dioxide and silicon nanoparticles) and three soluble salts (CuSO4, ZnSO4 and AgNO3) on Artemia sp. The physiochemical properties of the nanoparticles involved in this study are estimated and their properties in normal water and marine water were analyzed. Hydrated and bleached Artemia cysts were allowed to hatch in continuously aerated, filtered sterile salt water containing nanoparticles; hatching of viable nauplii vs total hatchlings were recorded. In parallel, Standard Artemia toxicity test was conducted on the nauplii monitoring the viability. A comparison of results obtained in both experiments is discussed. The toxicity of the nanoparticles was compared and the order of toxicity is estimated as Ag>CuO>ZnO>Au>TiO2>SiO2.

ecology↗