The goal of this interventional study is to Assess the safety and tolerability of atovaquone in combination with standard radiation therapy (RT) for the treatment of pediatric patients with newly diagnosed pediatric high-grade glioma/diffuse midline glioma/diffuse intrinsic pontine glioma (pHGG/DMG/DIPG).
The secondary aim is to assess the safety and tolerability of longer-term atovaquone treatment for pediatric patients with relapsed or progressed pHGG/DMG/DIPG and medulloblastoma (MB) or pHGG/DMG/DIPG after completion of RT and before progression.

Start Date01 Oct 2024

Sponsor / Collaborator

Emory University

NCT06294912 / RecruitingPhase 1

A Controlled Human Malaria Infection Study to Evaluate the Antimalarial Activity of MK-7602 Against Plasmodium Falciparum Blood Stage Infection in Healthy Adult Participants

The purpose of this study is to assess the antimalarial activity, pharmacokinetics, and safety of MK-7602 in healthy adults following Plasmodium falciparum (P. falciparum) infection.

Start Date18 Apr 2024

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT05974267 / RecruitingPhase 2

Phase 2a Proof-of-Concept, Multicenter, Randomized, Open Label Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of a Single Dose of the Combination M5717-pyronaridine as Chemoprevention in Asymptomatic Adults and Adolescents With Plasmodium Falciparum Malaria Infection (CAPTURE-2)

This study will evaluate the efficacy and safety of a single dose of M5717 plus pyronaridine tetraphosphate in clearing current Plasmodium falciparum infection and protecting against recurrent infections in asymptomatic adults and adolescents. The study will also assess the duration of protection provided by different doses of M5717 plus pyronaridine and the additional contribution of M5717 to the duration of protection using external study data.

Start Date28 Nov 2023

Sponsor / Collaborator

Merck Healthcare KGaA

100 Clinical Results associated with Electron transport complex III

100 Translational Medicine associated with Electron transport complex III

0 Patents (Medical) associated with Electron transport complex III

Literatures (Medical) associated with Electron transport complex III

21 Jul 2024·Alcohol and Alcoholism

Chronic binge alcohol mediated hepatic metabolic adaptations in SIV-infected female rhesus macaques

Article

Author: Gallegos, Eden M ; Simon, Liz ; Molina, Patricia E

AbstractAimsAs the interactions of alcohol and HIV/SIV infection and their impact on liver metabolic homeostasis remain to be fully elucidated, this study aimed to determine alcohol-mediated hepatic adaptations of metabolic pathways in SIV/ART-treated female rhesus macaques fed a nutritionally balanced diet.MethodsMacaques were administered chronic binge alcohol (CBA; 13–14 g ethanol/kg/week for 14.5 months; n = 7) or vehicle (VEH; n = 8) for 14.5 months. Livers were excised following an overnight fast. Gene and protein expression, enzymatic activity, and lipid content were determined using frozen tissue and histological staining was performed using paraffin-embedded tissue.ResultsCBA/SIV macaques showed increased hepatic protein expression of electron transport Complex III and increased gene expression of glycolytic (phosphofructokinase and aldolase) and gluconeogenic (pyruvate carboxylase) enzymes and of genes involved in lipid turnover homeostasis (perilipin 1, peroxisome proliferator-activated receptor gamma, carbohydrate responsive binding protein, and acetyl-CoA carboxylase B) as compared to that of livers from the VEH/SIV group. Plasma triglyceride concentration had a significant positive association with liver triglyceride content in the CBA/SIV group.ConclusionsThese results reflect CBA-associated alterations in expression of proteins and genes involved in glucose and lipid metabolism homeostasis without significant evidence of steatosis or dysglycemia. Whether these changes predispose to greater liver pathology upon consumption of a high fat/high sugar diet that is more aligned with dietary intake of PWH and/or exposure to additional environmental factors warrants further investigation.

21 Jul 2023·Nature communicationsQ1 · CROSS-FIELD

MOF-mediated histone H4 Lysine 16 acetylation governs mitochondrial and ciliary functions by controlling gene promoters.

Q1 · CROSS-FIELD

ArticleOA

Author: Li, Haimin ; Chandel, Navdeep S ; Wang, Dongmei ; Dou, Yali ; Yi, Rui

Histone H4 lysine 16 acetylation (H4K16ac), governed by the histone acetyltransferase MOF, orchestrates gene expression regulation and chromatin interaction. However, the roles of MOF and H4K16ac in controlling cellular function and regulating mammalian tissue development remain unclear. Here we show that conditional deletion of Mof in the skin, but not Kansl1, causes severe defects in the self-renewal of basal epithelial progenitors, epidermal differentiation, and hair follicle growth, resulting in barrier defects and perinatal lethality. MOF-regulated genes are highly enriched for essential functions in the mitochondria and cilia. Genetic deletion of Uqcrq, an essential subunit for the electron transport chain (ETC) Complex III, in the skin, recapitulates the defects in epidermal differentiation and hair follicle growth observed in MOF knockout mouse. Together, this study reveals the requirement of MOF-mediated epigenetic mechanism for regulating mitochondrial and ciliary gene expression and underscores the important function of the MOF/ETC axis for mammalian skin development.

01 Apr 2022·Neuroscience Bulletin

Mitochondrial Reactive Oxygen Species Elicit Acute and Chronic Itch via Transient Receptor Potential Canonical 3 Activation in Mice

Article

Author: Kim, Wheedong ; Lee, Pa Reum ; Oh, Seog Bae ; Kim, Yong Ho ; Lee, Kihwan ; Jang, Jun Ho ; Vang, Hue ; Kim, Seong-Ah

Mitochondrial reactive oxygen species (mROS) that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities. Here, we explored whether mROS overproduction induces itch through transient receptor potential canonical 3 (TRPC3), which is sensitive to ROS. Intradermal injection of antimycin A (AA), a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction, produced robust scratching behavior in naïve mice, which was suppressed by MitoTEMPO, a mitochondria-selective ROS scavenger, and Pyr10, a TRPC3-specific blocker, but not by blockers of TRPA1 or TRPV1. AA activated subsets of trigeminal ganglion neurons and also induced inward currents, which were blocked by MitoTEMPO and Pyr10. Besides, dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10, and also by resveratrol, an antioxidant. Taken together, our results suggest that mROS elicit itch through TRPC3, which may underlie chronic itch, representing a potential therapeutic target for chronic itch.

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