Article
Gastroenterology & Hepatology
Souradipta Ganguly, German A. Eman Muench, Linshan Shang, Sara Brin Rosenthal, Gibraan Rahman, Ruoyu Wang, Yanhan Wang, Hyeok Choon Kwon, Anthony M. Diomino, Tatiana Kisseleva, Pejman Soorosh, Mojgan Hosseini, Rob Knight, Bernd Schnabl, David A. Brenner, Debanjan Dhar
Summary: Using a hyperphagic mouse model fed with a Western diet closely mimics the pathobiology and gene signature of human NASH with fibrosis and subsequent HCC. The progression from NASH to cirrhosis and HCC is dependent on diet, and switching back to a normal diet can lead to regression of NASH and improved survival.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Review
Endocrinology & Metabolism
Jeong Joo Pyo, Yongsoo Choi
Summary: Through transcriptome and proteome analysis of nonalcoholic steatohepatitis (NASH) patients and mouse models, we established NASH gene signatures and explored the pathological mechanisms of NASH. The up-regulated genes in NASH were associated with inflammation, steatosis, apoptosis, and extracellular matrix organization, while the down-regulated genes were related to metal ion response and lipid and amino acid metabolism. Cross-species analysis revealed consistently dysregulated genes between human and mouse NASH, and 14 of these genes were further validated at the protein level. Dysregulation of amino acid metabolism was identified as a significant hepatic perturbation in both human and mouse NASH.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emanuel Passos, Cidalia Pereira, Ines O. Goncalves, Ana Faria, Antonio Ascensao, Rosario Monteiro, Jose Magalhaes, Maria J. Martins
Summary: Obesity is a predictive factor for the development of nonalcoholic steatohepatitis (NASH). This study analyzed the effects of physical activity and endurance training on hepatic endoplasmic reticulum (ER) stress and oxidative stress in an animal model of high-fat diet (HFD)-induced NASH. The results suggest that physical exercise can counteract NASH-related ER stress through modulation of the hepatic IRE1 alpha-X-box binding protein 1 pathway.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Andrea Barrientos-Riosalido, Monica Real, Laia Bertran, Carmen Aguilar, Salome Martinez, David Parada, Margarita Vives, Fatima Sabench, David Riesco, Daniel Del Castillo, Cristobal Richart, Teresa Auguet
Summary: This study analyzed the expression of ATG7 gene in obesity-associated NAFLD and found that ATG7 was highly expressed in NASH patients. ATG7 may play an important role in the pathogenesis of NAFLD, especially in NASH, possibly having a protective effect.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Seonghwan Hwang, Hwayoung Yun, Sungwon Moon, Ye Eun Cho, Bin Gao
Summary: NAFLD encompasses a range of liver disorders, with NASH characterized by increased liver injury and inflammation, where neutrophils play a critical role. The review outlines the functions of neutrophils in promoting the progression of fatty liver to NASH and their potential as therapeutic targets.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Reda Albadawy, Amany Helmy Hasanin, Sara H. A. Agwa, Shaimaa Hamady, Yasmin M. Aboul-Ela, Mona Hussien Raafat, Samaa Samir Kamar, Mohamed Othman, Yahia A. Yahia, Marwa Matboli
Summary: This study investigated the pharmacological activity and potential mechanism of rosavin treatment on non-alcoholic steatohepatitis (NASH) by targeting hepatic cell death-related mRNAs and their upstream noncoding RNA regulators in NASH rats. The results showed that rosavin modulated the expression of hepatic cell death-related RNA panel and improved liver functions, lipid profile, hepatic inflammation, fibrosis, and apoptosis in NASH rats. The study suggests that rosavin may have the potential to attenuate disease progression and inhibit hepatic cell death in NASH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
He-ming Huang, Shi-jie Fan, Xiao-ru Zhou, Yan-jun Liu, Xiao Li, Li-ping Liao, Jing Huang, Cui-cui Shi, Liang Yu, Rong Fu, Jian-gao Fan, Yuan-yuan Zhang, Cheng Luo, Guang-ming Li
Summary: Givinostat demonstrated therapeutic potential in treating nonalcoholic steatohepatitis (NASH) by alleviating inflammation and attenuating hepatic fibrosis, as shown in both in vivo and in vitro studies.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Mi-Bo Kim, Yoojin Lee, Minkyung Bae, Hyunju Kang, Siqi Hu, Tho X. Pham, Ji-Young Lee, Young-Ki Park
Summary: This study demonstrated that the consumption of U.S.-grown sugar kelp can prevent obesity-related metabolic abnormalities and NASH in a mouse model. Mice fed with sugar kelp showed lower body weight, increased metabolism, reduced fat accumulation, inflammation, and fibrosis in the liver and adipose tissue compared to the control group.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2021)
Review
Gastroenterology & Hepatology
Samar H. Ibrahim
Summary: Liver sinusoidal endothelial cells (LSECs) play a crucial role in the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD) by undergoing capillarization and expressing adhesion molecules. They regulate hepatic immune cell populations by mediating leukocyte subset adhesion in NAFLD, highlighting their role in the inflammatory response.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Medicine, General & Internal
Hua-Chien Wu, Yin-Ru Hsieh, Weu Wang, Ching-Wen Chang, I-Wei Chang, Chi-Long Chen, Chun-Chao Chang, Chia-Hsuan Chang, Wei-Yu Kao, Shih-Yi Huang
Summary: This study investigated the differences in lipidomic profile features between mild and significant liver fibrosis cases in patients with morbid obesity and NASH. The results showed that the concentrations of triglycerides, cholesterol esters, phosphatidylcholine, phosphatidic acid, phosphatidylinositol, phosphatidylglycerol, and sphingomyelin were significantly lower in patients with significant fibrosis compared to those with mild fibrosis. However, the concentration of phosphatidylcholine was relatively higher in patients with stage 2-4 fibrosis. Moreover, predictive models incorporating specific lipid components showed a potential correlation between NASH fibrosis stages and liver lipid accumulation.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Endocrinology & Metabolism
Hui Xiang, Dating Sun, Xin Liu, Zhi-Gang She, Yonghong Chen
Summary: This article mainly summarizes the important impact of intestinal microbiota and its metabolites on the development of NASH. A balanced intestinal microbiota contributes to liver homeostasis, while an imbalanced microbiota may lead to NASH. Additionally, recent clinical trials and animal studies on treating NASH by regulating the intestinal microbiota through prebiotics, probiotics, synbiotics, and FMT are briefly discussed.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoyan Chen, Wenjie Shi, Yong Xie, Yunwu Wang, Qian Yao, Huajing Ke, Xuan Xu, Hui Liu, Pi Liu, Xiaojiang Zhou
Summary: This study investigates the role of Kruppel-like factor 14 (KLF14) in hepatic lipid metabolism in nonalcoholic steatohepatitis (NASH). The expression of KLF14 was found to be decreased in NASH patients and mice fed a high-fat diet. Knockdown of KLF14 promoted the progression of hepatic steatosis by downregulating fatty acid oxidation genes.
Article
Pharmacology & Pharmacy
Jiaji Hu, Hanglu Ying, Jie Yao, Longhe Yang, Wenhui Jin, Huabin Ma, Long Li, Yufen Zhao
Summary: PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated lipid accumulation and hepatic fibrosis in MCD-induced NASH mice.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiaoyan Chen, Wenjie Shi, Yong Xie, Yunwu Wang, Qian Yao, Huajing Ke, Xuan Xu, Hui Liu, Pi Liu, Xiaojiang Zhou
Summary: This study investigated the role of Kruppel-like factor 14 (KLF14) in hepatic lipid metabolism and its mechanism in nonalcoholic steatohepatitis (NASH). The expression of KLF14 was found to be decreased in NASH patients and mice fed a high-fat diet. Overexpression of KLF14 alleviated lipid accumulation and oxidative stress in the mouse model of NASH through the activation of the PPARa pathway.
Review
Chemistry, Medicinal
Ki Wung Chung, Ye Eun Cho, Seung-Jin Kim, Seonghwan Hwang
Summary: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is prevalent worldwide due to the obesity pandemic. NAFLD includes fatty liver, nonalcoholic steatohepatitis (NASH), cirrhosis, and carcinoma. Excessive fat accumulation induces fatty liver, while the progression to NASH involves various complex factors. Inflammation and fibrosis, closely associated with immune cells and immunological factors, differentiate fatty liver from NASH. Thus, understanding the immunological mechanisms contributing to NASH pathogenesis is crucial for the identification of therapeutic targets and the development of viable treatments.
ARCHIVES OF PHARMACAL RESEARCH
(2022)
Article
Cell Biology
Louise M. C. Webb, Sigrid Fra-Bido, Silvia Innocentin, Louise S. Matheson, Noudjoud Attaf, Alexandre Bignon, Julien Novarino, Nicolas Fazilleau, Michelle A. Linterman
Summary: Ageing profoundly impacts immune system by affecting Tfh cell formation, promoting early Tfh cell differentiation but not increasing GC-Tfh cells. Ageing alters TCR signalling, leading to increased expression of RBPJ, and modulation of RBPJ or Notch rescues age-associated early Tfh cell differentiation.
Editorial Material
Immunology
Patricia Ame, Helene Dumortier, Marion Espeli, Pierre Milpied, Nicolas Fazilleau
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Dirk Baumjohann, Nicolas Fazilleau
Summary: Tfh cells are essential for potent humoral immune responses, and their differentiation and memory maintenance are influenced by various factors, including interactions with APCs, costimulatory and coinhibitory pathways, and cytokines. Understanding the differentiation and memory maintenance of Tfh cells is crucial for a deeper understanding of immune responses and vaccine development.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Fanny Martinez, Julien Novarino, Jose Enrique Mejia, Nicolas Fazilleau, Meryem Aloulou
Summary: Environmental factors and age can affect the efficiency of the immune system, especially the decline in immune cells and cellular immunity in the elderly. Immunosenescence affects T and B cells, leading to weakened lymphocyte responses to vaccines and pathogens.
IMMUNOLOGY LETTERS
(2021)
Article
Dermatology
Maud Maho-Vaillant, Corine Perals, Marie-Laure Golinski, Vivien Hebert, Frederique Caillot, Claire Mignard, Gaetan Riou, Marie Petit, Manuelle Viguier, Michael Hertl, Olivier Boyer, Sebastien Calbo, Nicolas Fazilleau, Pascal Joly
Summary: The study showed that rituximab significantly decreased DSG-specific memory B cells and eliminated anti-DSG antibody-secreting cells in patients in complete remission. In contrast, corticosteroids did not affect the frequency or phenotype of DSG-specific memory B cells, and anti-DSG antibody-secreting cells were still detected after treatment, even in patients in remission. Additionally, rituximab decreased DSG-specific T follicular helper cells, which remained stable after corticosteroid treatment.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Katy Diallo, Numa Simons, Souraya Sayegh, Michel Baron, Yannick Degboe, Jean-Frederic Boyer, Andrey Kruglov, Sergei Nedospasov, Julien Novarino, Meryem Aloulou, Nicolas Fazilleau, Arnaud Constantin, Alain Cantagrel, Jean-Luc Davignon, Benjamin Rauwel
Summary: The study shows that the binding of anti-TNF biologics to tmTNF can reduce the severity of arthritis by increasing the expression of anti-inflammatory markers and decreasing inflammation. This suggests a complementary explanation for the effects of anti-TNF biologics in treating inflammatory diseases and opens the door to studies on new arginase-1-dependent therapeutic targets.
Review
Immunology
Stephanie C. Eisenbarth, Dirk Baumjohann, Joe Craft, Nicolas Fazilleau, Cindy S. Ma, Stuart G. Tangye, Carola G. Vinuesa, Michelle A. Linterman
Summary: Tfh and Tfh-like cells guide B cell differentiation in secondary lymphoid tissues, playing essential roles in humoral immunity. They produce diverse combinations of cytokines and chemokine receptors to promote the generation of antibodies with different properties.
TRENDS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Ph. Kemoun, I. Ader, V. Planat-Benard, C. Dray, N. Fazilleau, P. Monsarrat, B. Cousin, J. Paupert, M. Ousset, A. Lorsignol, I. Raymond-Letron, B. Vellas, P. Valet, T. Kirkwood, J. Beard, L. Penicaud, L. Casteilla
Summary: Research on healthy ageing emphasizes the importance of understanding the balance between stability and instability in the body, guiding the development of new preventive and therapeutic strategies.
AGEING RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Cui Yang, Gaetan Blaize, Remi Marrocco, Nelly Rouquie, Cyrielle Bories, Mylene Gador, Suzanne Melique, Emeline Joulia, Mehdi Benamar, Anne S. Dejean, Helene Daniels-Treffandier, Paul E. Love, Nicolas Fazilleau, Abdelhadi Saoudi, Renaud Lesourne
Summary: This study reveals the role of the protein THEMIS in regulating different subsets of CD4(+) T cells. THEMIS promotes T(H)1 cell responses and contributes to the development of autoimmune responses.
Article
Biology
Jeremy Argenty, Nelly Rouquie, Cyrielle Bories, Suzanne Melique, Valerie Duplan-Eche, Abdelhadi Saoudi, Nicolas Fazilleau, Renaud Lesourne, Sarah Russell
Summary: T-cell populations have the ability to proliferate, but different T-cell subsets show different proliferation characteristics. This study found that the microtubule-associated protein LIS1 plays an important role in T-cell proliferation, and its deficiency can lead to cell division blockage, abnormal chromosome separation, and cell death.
Article
Dermatology
Manuelle Viguier, Corine Perals, Beatrice Poirier, Maxime Battistella, Francois Aubin, Herve Bachelez, Jean-Luc Pretet, Tarik Gheit, Massimo Tommasino, Antoine Touze, Marie-Lise Gougeon, Nicolas Fazilleau
Summary: Lichen planus (LP) is a chronic inflammatory disease characterized by CD8(+) T-cell infiltrate, and HPV16-specific CD8(+) T-cells are involved in different clinical forms of LP. Lichen sclerosus et atrophicus (LSA) has a different immune response, with oligoclonal TCRVss6(+) CTL repertoire.
EXPERIMENTAL DERMATOLOGY
(2023)
Article
Biology
Xavier Mas-Orea, Lea Rey, Louise Battut, Cyrielle Bories, Camille Petitfils, Anne Abot, Nadine Gheziel, Eve Wemelle, Catherine Blanpied, Jean-Paul Motta, Claude Knauf, Frederick Barreau, Eric Espinosa, Meryem Aloulou, Nicolas Cenac, Matteo Serino, Lionel Mouledous, Nicolas Fazilleau, Gilles Dietrich
Summary: Immune cell-derived enkephalins play a crucial role in maintaining gut homeostasis and normal behavior in mice, and defects in this system can mimic major symptoms of irritable bowel syndrome. These findings provide new insights into the classification and treatment of intestinal diseases.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Zeinab Dalloul, Marie Best, Pauline Chenuet, Iman Dalloul, Sandrine Le Noir, Dieudonnee Togbe, Mylene Gador, Bernhard Ryffel, Valerie FJ Quesniaux, Yolla El Makhour, Francois Boyer, Jean-Claude Aldigier, Jeanne Cook-Moreau, Nicolas Fazilleau, Michel Cogne
Summary: The study discovered that BET inhibitors have complex effects on B cell and T cell polarization, reducing antibody production by B cells while increasing the number of Th2 cells and secretion of corresponding cytokines. In a mouse model, JQ1 did not affect eosinophil infiltration but worsened Th2 cytokine production, exacerbating clinical symptoms.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Review
Geriatrics & Gerontology
I. Ader, L. Penicaud, S. Andrieu, J. R. Beard, N. Davezac, C. Dray, N. Fazilleau, P. Gourdy, S. Guyonnet, R. Liblau, A. Parini, P. Payoux, C. Rampon, I. Raymond-Letron, Y. Rolland, P. de Souto Barreto, P. Valet, N. Vergnolle, F. Sierra, B. Vellas, Louis Casteilla
Summary: The search for solutions to optimize healthy aging and increase health span is a major challenge facing society. The World Health Organization now prioritizes a novel healthcare model based on integration and a shift in research and care towards maintaining optimal functional levels. However, there is a lack of an integrative global strategy that combines longitudinal and experimental cohorts with an innovative understanding of physiological functioning.
JOURNAL OF FRAILTY & AGING
(2021)
Article
Geriatrics & Gerontology
Y. Santin, S. Lopez, I Ader, S. Andrieu, N. Blanchard, A. Carriere, L. Casteilla, B. Cousin, N. Davezac, P. De Souto Barreto, C. Dray, N. Fazilleau, D. Gonzalez-Dunia, P. Gourdy, S. Guyonnet, N. Jabrane-Ferrat, O. Kunduzova, F. Lezoualc'h, R. Liblau, L. O. Martinez, C. Moro, P. Payoux, L. Penicaud, V Planat-Benard, C. Rampon, Y. Rolland, J-P Schanstra, F. Sierra, P. Valet, A. Varin, N. Vergnolle, B. Vellas, J. Vina, B. P. Guiard, A. Parini
Summary: Aging is a major risk factor for chronic diseases, and efforts are now focused on promoting healthy aging by identifying early biological markers associated with functional status. The INSPIRE program aims to discover mechanisms of accelerated aging and predict frailty and pathological aging using a cohort of SWISS mice. This comprehensive study will provide valuable insights into the role of dietary and exercise interventions in influencing the rate of biological aging and identifying targets for healthy aging promotion.
JOURNAL OF FRAILTY & AGING
(2021)