Article
Biochemical Research Methods
Alina Schrimpf, Olivia Knappe, Natalia Qvartskhava, Gereon Poschmann, Kai Stuehler, Hans Jurgen Bidmon, Tom Luedde, Dieter Haeussinger, Boris Goerg
Summary: This study investigates the molecular alterations in the brain associated with cerebral impairment in hyperammonemic disorders. Through transcriptomics and proteomics analysis, the researchers identified genes and proteins whose expressions were altered in a brain region-specific way in the brains of mice with systemic hyperammonemia. Further analyses of selected candidates revealed their roles in oxidative stress, cell proliferation, heme metabolism, senescence, RNA quality control, and disturbed iron homeostasis, suggesting their potential relevance in cerebral dysfunction in hyperammonemic disorders.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Hanan A. Ogaly, Rehab F. Abdel-Rahman, Marawan Abd Elbaset Mohamed, O. A. Ahmed-Farid, Marwa S. Khattab, Reham M. Abd-Elsalam
Summary: This study found that thymol has a neuroprotective effect against neurotoxicity and cognitive deterioration caused by hepatic encephalopathy. Thymol supplementation improved liver function, reduced serum ammonia levels, and improved locomotor and cognitive deficits. It modulated oxidative stress, neurotransmitters, and brain ATP levels, and ameliorated histopathological damage, astrocyte swelling, and brain edema. Thymol also downregulated NF-kB and upregulated GFAP expression, and promoted CREB and BDNF expression, as well as increased brain cAMP levels.
Article
Gastroenterology & Hepatology
Rajiv Jalan, Christopher F. Rose
Summary: The clinical progress in managing hepatic encephalopathy lags behind basic research, making current criteria for definition, classification, diagnosis, and grading difficult to apply reproducibly. Studies suggest that hepatic encephalopathy may be irreversible in many patients, requiring further research into neuronal injury and death mechanisms for future drug development. Lactulose, currently considered the standard of care, has poor clinical evidence for all severity levels of hepatic encephalopathy, and ethical consideration should be given to placebo-controlled trials.
JOURNAL OF HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rafael Ochoa-Sanchez, Farzaneh Tamnanloo, Christopher F. Rose
Summary: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with liver disease, reversible in theory but leading to persistent neurological complications in some patients post-liver transplantation. These enduring complications impact quality of life and healthcare costs, highlighting the need for further understanding of the underlying mechanisms.
NEUROCHEMICAL RESEARCH
(2021)
Review
Medicine, Research & Experimental
Yuan Li, Ying Ma, Qing-Ya Dang, Xin-Rong Fan, Chu-Ting Han, Shang-Zhong Xu, Peng-Yun Li
Summary: Mitochondria play a crucial role in cellular function, regulating ATP synthesis, oxidative stress, calcium cycling, and apoptosis. Mitochondrial dysfunction is a key mechanism in various diseases, including cardiovascular disorders. Advances in assessment methods have improved our understanding of mitochondrial structure, function, biogenesis, and energy production, leading to the identification of new drug targets and therapeutic strategies for mitochondrial dysfunction-related disorders.
Article
Cell & Tissue Engineering
Gianluca L. Russo, Giovanna Sonsalla, Poornemaa Natarajan, Christopher T. Breunig, Giorgia Bulli, Juliane Merl-Pham, Sabine Schmitt, Jessica Giehrl-Schwab, Florian Giesert, Martin Jastroch, Hans Zischka, Wolfgang Wurst, Stefan H. Stricker, Stefanie M. Hauck, Giacomo Masserdotti, Magdalena Goetz
Summary: Astrocyte-to-neuron conversion is a promising avenue for neuronal replacement therapy, with mitochondrial proteins playing a crucial role in the process. Early activation of genes encoding mitochondrial proteins significantly improves conversion efficiency, particularly for neuron-enriched antioxidant proteins.
Article
Biochemistry & Molecular Biology
Lin Han, Yao Zhang, Jia Li, Yao Xiao, Mei Lu, Yunlong Li, Min Wang
Summary: The study demonstrated that phloretin effectively improves mitochondrial function and attenuates HFD-induced hepatic steatosis through the AMPK-dependent signaling pathway by promoting fatty acid beta-oxidation and improving mitochondrial function.
Review
Gastroenterology & Hepatology
Wouter Claeys, Lien Van Hoecke, Sander Lefere, Anja Geerts, Xavier Verhelst, Hans Van Vlierberghe, Helena Degroote, Lindsey Devisscher, Roosmarijn E. Vandenbroucke, Christophe Van Steenkiste
Summary: Hepatic encephalopathy (HE) is a neurological complication of liver dysfunction and portosystemic shunting, highly prevalent in cirrhosis patients and associated with poor outcomes. New insights into peripheral origins in HE have led to innovative treatments like fecal microbiota transplantation, but central nervous system perturbations have not been fully considered. This review proposes a holistic approach, describing HE as a global dysfunction of the neurogliovascular unit, impacting blood flow, nutrient supply, blood-brain barrier function, and leading to accumulation of neurotoxic substances. Taking a broader view of central nervous system alterations in liver disease could aid in further research into HE pathophysiology and development of specific therapeutic strategies targeting central nervous system damage.
Review
Gastroenterology & Hepatology
Dominique Thabut, Charlotte Bouzbib, Lucy Meunier, Manon Haas, Nicolas Weiss, Alexandre Louvet, Francois Imbert-Bismut, Fanny Mochel, Yann Nadjar, Antoine Santiago, Thierry Thevenot, Veronique Duhalde, Frederic Oberti, Claire Francoz, Audrey Coilly, Marie-Noelle Hilleret, Pascal Lebray, Amelie Liou-Schischmanoff, Louise Barbier, Christophe Duvoux, Georges-Philippe Pageaux, Michael Bismuth, Damien Galanaud, Thomas De Broucker, Jean-Francois Cadranel, Vincent Leroy, Vincent Di Martino, Dominique Larrey, Christophe Camus, Olivier Scatton, Victor De Ledinghen, Ariane Mallat, Marika Rudler, Christophe Bureau
Summary: Hepatic encephalopathy (HE) is a frequent and severe complication of liver disease that often goes undiagnosed due to a lack of understanding and consensus on diagnosis. Non-specific symptoms and comorbidities in cirrhotic patients make differential diagnosis challenging. Guidelines are provided to assist clinicians in diagnosing and treating HE. Liver transplantation may be indicated for HE, but its reversibility post-transplantation and the consequences in patients with other neurological disorders remain controversial.
LIVER INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Yisang Yoon, Hakjoo Lee, Marilen Federico, Shey-Shing Sheu
Summary: Mitochondrial permeability transition (MPT) is a phenomenon that leads to mitochondrial dysfunction and cell injury. The opening of a mega-channel called the permeability transition pore (PTP) is responsible for MPT. Mitochondrial fission and fusion play a role in regulating MPT. There may also exist a non-conventional form of MPT that is insensitive to certain inhibitors.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2023)
Article
Biochemistry & Molecular Biology
Xiaomin Zhao, Jianxiong Guo, Xinyue Wang, Jiadi Lin, Zhihao Liu, Chunmei Xu, Di Zhang, Dewen Tong
Summary: TGEV infection reduces circBIRC6-2 levels, leading to a decrease in mitochondrial calcium, membrane potential, and mPTP opening. Furthermore, we identified an interaction between the novel protein BIRC6-236aa encoded by circBIRC6-2 and VDAC1, suggesting that BIRC6-236aa destabilizes the VDAC1-CypD complex and inhibits mPTP opening.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Gastroenterology & Hepatology
Leen Z. Hasan, George Y. Wu
Summary: Hepatic encephalopathy is a devastating complication of chronic liver disease with high mortality rates, and current treatment modalities, while promising, are limited by study design and lack of safety data.Various treatment options targeting gut microbiota, oxidative stress, and neurotransmitter modulation have shown promise but more research is needed to address their limitations.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2021)
Article
Biochemical Research Methods
Katerina Kroupina, Chantal Bemeur, Christopher F. Rose
Summary: Hepatic encephalopathy is a decline in brain function caused by liver insufficiency. The liver's reduced ability to clear ammonia plays a crucial role in the development of hepatic encephalopathy. Cirrhotic patients require high protein intake, but this can increase the accumulation of ammonia, worsening hepatic encephalopathy. Finding a nutritional solution that provides sufficient protein doses without increasing the risk of hepatic encephalopathy is necessary.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Cell Biology
Catherine A. Bellissimo, Luca J. Delfinis, Meghan C. Hughes, Patrick C. Turnbull, Shivam Gandhi, Sara N. DiBenedetto, Fasih A. Rahman, Peyman Tadi, Christina A. Amaral, Ali Dehghani, James N. Cobley, Joe Quadrilatero, Uwe Schlattner, Christopher G. R. Perry
Summary: This study aimed to determine whether the prospective mitochondrial-enhancing compound Olesoxime can prevent early-stage mitochondrial stress in limb and respiratory muscle from D2.mdx mice. Results showed that Olesoxime selectively preserved or maintained muscle sensitivity to creatine, reduced creatine kinase release, and improved some indices of muscle quality.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anamika, Surendra K. Trigun
Summary: The study found that in the hippocampus of MoHE rats, there was a significant decrease in SIRT3 expression and activity, accompanied by mitochondrial dysfunction and oxidative stress. However, treatment with the SIRT3 activator honokiol (HKL) could restore these mitochondrial abnormalities, indicating the important role of SIRT3 in the pathogenesis of MoHE.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2021)
