Publications by authors named "Ushodaya Mattam"

Mitochondrial maladaptation is a hallmark of heart failure, contributing to impaired energy production and contractile dysfunction. Understanding the bioenergetics of cardiomyocytes under healthy and pathological conditions is critical for characterizing mitochondrial maladaptation. While adult cardiomyocytes from rodents are a widely used model, recent studies have reported oligomycin insensitivity in these cells, a phenomenon often overlooked.

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  • Recent studies show that hepatokines, like ITIH3, play a role in regulating liver health and the progression of non-alcoholic fatty liver disease (NAFLD) to more severe forms like NASH.
  • Research found that levels of ITIH3 decrease as NAFLD worsens, indicating its potential as a biomarker for disease severity.
  • Overexpression of ITIH3 in animal models led to reduced liver fat, while its knockdown increased fat accumulation, suggesting that ITIH3 could offer new treatment options for liver diseases.
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Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease that predominantly affects women. LAM cells carry mutations, causing mTORC1 hyperactivation and uncontrolled cell growth. mTORC1 inhibitors stabilize lung function; however, sustained efficacy requires long-term administration, and some patients fail to tolerate or respond to therapy.

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  • Tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) are diseases linked to mutations in TSC1 and TSC2, leading to the growth of tumors in various organs, especially affecting women’s lungs in the case of LAM.
  • Recent research using single-cell RNA sequencing in LAM patients revealed that specific genes involved in sphingolipid biosynthesis were activated, with significant increases in key enzymes like acid ceramidase (ASAH1) in TSC2-null cells.
  • Combining the enzyme inhibitor ARN14976 with rapamycin showed promise in reducing tumor growth and cell viability in experimental models, pointing toward new therapeutic strategies targeting abnormal sphingolipid pathways in TSC and
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Mitochondria empower the liver to regulate lipid homeostasis by enabling fatty acid oxidation during starvation and lipogenesis during nutrient-rich conditions. It is unknown if mitochondria can seamlessly regulate these two distinct processes or if two discrete populations of mitochondria achieve these two functions in the liver. For the first time in the liver, we report the isolation of two distinct populations of mitochondria from male Wistar rats on an ad-libitum diet: cytoplasmic mitochondria and lipid droplet-associated mitochondria.

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Aging leads to the diminished pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH). Kisspeptin (Kp), the upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis, regulates GnRH synthesis and release through its cognate receptor, G-protein coupled receptor 54 (GPR54). In turn, GnRH regulates GPR54 expression.

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Human MIA40, an intermembrane space (IMS) import receptor of mitochondria harbors twin CX9C motifs for stability while its CPC motif is known to facilitate the import of IMS bound proteins. Site-directed mutagenesis complemented by MALDI on in vivo hMIA40 protein shows that a portion of MIA40 undergoes reversible S-glutathionylation at three cysteines in the twin CX9C motifs and the lone cysteine 4 residue. We find that HEK293T cells expressing hMIA40 mutant defective for glutathionylation are compromised in the activities of complexes III and IV of the Electron Transport Chain (ETC) and enhance Reactive Oxygen Species (ROS) levels.

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It has become amply clear that mitochondrial function defined by quality, quantity, dynamics, homeostasis, and regulated by mitophagy and mitochondrial biogenesis is a critical metric of human aging and disease. As a consequence, therapeutic interventions that can improve mitochondrial function can have a profound impact on human health and longevity. Kisspeptins are neuropeptides belonging to the family of metastasis suppressors that are known to regulate functions like fertility, reproduction, and metabolism.

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Dengue virus infections, which have been reported in nearly 140 countries, pose a significant threat to human health. The genome of dengue virus encodes three structural and seven nonstructural (NS) proteins along with two untranslated regions, one each on both ends. Among them, dengue protease (NS3) plays a pivotal role in polyprotein processing and virus multiplication.

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  • Aging negatively impacts the circadian timing system in mammals, leading to dysfunction, which has been observed in studies involving aging and Parkinson's disease models.
  • Research involving proteomic analysis identified varying expression levels of core clock gene proteins at different times of day in various brain regions of both young and aging rats, highlighting changes associated with age and disease.
  • Melatonin administration appears to help modulate the protein profiles linked to circadian rhythms, suggesting its potential as a treatment for circadian dysfunction and promoting better health in aging populations.
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  • The circadian system in the SCN is linked to serotonin levels and clock gene expression, with the study focusing on circadian dysfunction in Parkinson's disease using a rat model.
  • Significant reductions in levels of serotonin and its metabolites were observed in the RIPD model, alongside altered rhythmic patterns and increased serotonin breakdown.
  • Melatonin administration helped restore the daily rhythm of certain clock genes, demonstrating its potential neuroprotective effects in the context of Parkinson's disease.
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Aging is associated with changes in several basic parameters of circadian rhythms in mammals leading to circadian dysfunction. The hypothalamic Suprachiasmatic nucleus (SCN) regulates neuronal, endocrine and behavioral rhythms through the expression of various clock genes and release of melatonin from pineal gland. In the present study, we investigated the effect of aging on daily rhythms of various clock genes such as rPer1, rPer2, rCry1, rCry2 and rBmal1 in the SCN of male Wistar rats.

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