Article
Biology
Dan Luo, Ni Fan, Xiuying Zhang, Fung Yin Ngo, Jia Zhao, Wei Zhao, Min Huang, Ding Li, Yu Wang, Jianhui Rong
Summary: Targeting endoplasmic reticulum (ER) stress, inflammation, and metabolic dysfunctions may halt the pathogenesis of obesity and thereby reduce the prevalence of diabetes, cardiovascular diseases, and cancers. The present study found that plant-derived celastrol can ameliorate inflammation and lipid accumulation in obesity by suppressing ER stress, inflammation, and lipogenesis. Celastrol also promotes hepatic lipolysis and restores the expression of genes related to ER stress, inflammation, and lipid metabolism. In addition, the study identified the protein GRP78 as a target for celastrol binding, and the binding of celastrol to GRP78 inhibits its chaperone activity and reduces ER stress.
Article
Cell Biology
Su Woo Kim, Byeong-Yun Ahn, Thi Thuy Vy Tran, Jung-Hoon Pyun, Jong-Sun Kang, Young- Eun Leem
Summary: Doxorubicin is an anti-cancer drug that is widely used but has cardiotoxic side effects. Recent research has found that Doxorubicin induces cardiotoxicity through endoplasmic reticulum stress. The protein arginine methyltransferases 1 (PRMT1) plays a crucial role in Doxorubicin-induced cardiotoxicity in cardiomyocytes.
CELLULAR SIGNALLING
(2022)
Article
Nutrition & Dietetics
Hwa-Young Lee, Geum-Hwa Lee, Young Yoon, The-Hiep Hoang, Han-Jung Chae
Summary: Research shows that IBF-R, an extract from Rhus verniciflua, can effectively regulate weight gain, reduce adipogenic gene expression in white adipose tissue, and enhance genes related to fatty acid oxidation in diet-induced obese mice. Additionally, IBF-R administration inhibits obesity-related inflammations linked to redox-based post-translational modifications of IRE1 alpha.
Article
Multidisciplinary Sciences
Yovita Permata Budi, Yi-Hsuan Li, Chien Huang, Mu-En Wang, Yi-Chun Lin, De-Shien Jong, Chih-Hsien Chiu, Yi-Fan Jiang
Summary: The study aims to investigate the role of autophagy in obesity-induced insulin resistance. The findings suggest that a high-fat diet promotes insulin resistance, inhibits autophagy, induces ER stress, and apoptosis in adipose tissue. Autophagy suppression may indirectly cause insulin resistance through ER stress or apoptosis.
Article
Toxicology
Wei-Ting Chang, Yu-Wen Lin, Chung-Han Ho, Zhih-Cherng Chen, Ping-Yen Liu, Jhih-Yuan Shih
Summary: The study found that dapagliflozin can alleviate doxorubicin-induced cardiomyocyte apoptosis in diabetic conditions, potentially preventing cardiac toxicity in diabetic cancer patients receiving doxorubicin treatment.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Endocrinology & Metabolism
Pim P. van Krieken, Timothy S. Odermatt, Marcela Borsigova, Matthias Bluher, Stephan Wueest, Daniel Konrad
Summary: The study investigates the role of gp130 cytokine signaling in white adipose tissue browning in obesity, revealing the regulatory mechanism of gp130 cytokines on Ucp1 expression, providing a new insight for the treatment of obesity.
MOLECULAR METABOLISM
(2021)
Article
Oncology
Violet Kayamba
Summary: Upper gastrointestinal (UGI) cancers are common and have significant associations with certain types of food. Fruit and vegetables are believed to reduce UGI cancer risk, while processed foods increase the risk. Specific diets may be associated with reduced cancer risk, but their effectiveness in high-risk locations is unclear.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Terry L. Davidson, Richard J. Stevenson
Summary: This paper presents a theoretical model and supporting evidence that links the consumption of a Western-style diet (high in saturated fats and sugar) to impaired control of hunger and satiety signals in the brain, particularly in the hippocampus. The findings suggest that consuming such a diet can lead to pathophysiological issues, impair hippocampal-dependent learning and memory, and weaken behavioral control by hunger and satiety cues. It is hypothesized that these consequences may contribute to a vicious cycle of further diet intake, obesity, and potential cognitive decline.
REVIEWS IN ENDOCRINE & METABOLIC DISORDERS
(2022)
Article
Nutrition & Dietetics
Susan E. Swithers, G. R. Bonanno, Janet Figueroa, Jean A. Welsh, Allison C. Sylvetsky
Summary: Recent studies using NHANES data have used inconsistent approaches to identify and categorize low-calorie sweetened beverages (LCSBs), leading to potential reliability issues and impacting the interpretation of dietary and health correlates in published analyses.
Article
Ophthalmology
Shuizhen Shi, Chun Ding, Shuang Zhu, Fan Xia, Seth E. Buscho, Shengguo Li, Massoud Motamedi, Hua Liu, Wenbo Zhang
Summary: In this study, the role of PERK in ischemia-induced retinopathy was investigated using a mouse model of oxygen-induced retinopathy (OIR). The results showed that inhibition of PERK reduced retinal neovascularization and retinal ganglion cell loss, restored astrocyte network, and promoted revascularization. Therefore, PERK inhibition may provide an effective therapeutic intervention for alleviating retinal neovascularization and preventing neuron loss during retinal ischemia.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Review
Nutrition & Dietetics
Faidon Magkos
Summary: Studies suggest that calorie restriction and weight loss have similar beneficial effects in individuals without obesity as in those with obesity, including reduced fat deposition, increased insulin sensitivity, and improved insulin clearance rate, leading to lower blood glucose and insulin levels.
Review
Food Science & Technology
Luigi Barrea, Matteo Megna, Sara Cacciapuoti, Evelyn Frias-Toral, Gabriella Fabbrocini, Silvia Savastano, Annamaria Colao, Giovanna Muscogiuri
Summary: Psoriasis is a chronic immune-mediated skin disease influenced by genetic and lifestyle factors. Nutrition and obesity are significant contributors to its pathogenesis and severity. Certain diets with anti-inflammatory properties, such as the very-low-calorie ketogenic diet (VLCKD), may improve clinical severity by reducing weight and systemic inflammation.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Hongyan Li, Yanzhi Zeng, Xinyu Zheng, Guangjun Wang, Jingjing Tian, Wangbao Gong, Yun Xia, Kai Zhang, Zhifei Li, Wenping Xie, Jun Xie, Ermeng Yu
Summary: The study found that betaine promotes the growth of mandarin fish and can alleviate oxidative stress and ER stress caused by a high-carbohydrate diet, as well as reduce autophagy and apoptosis.
Article
Multidisciplinary Sciences
Merly C. Vogt, Oliver Hobert
Summary: Exposure to adverse nutritional and metabolic environments during critical periods of development can have lasting effects on individuals and their descendants. However, the specific signaling pathways and mechanisms responsible for these effects are still not well understood. Through experiments with Caenorhabditis elegans, researchers have discovered that changes in DAF-16/FoxO activity, a downstream target of insulin/IGF-1 receptor signaling, are responsible for metabolic programming phenotypes. The study also found that DAF-16/FoxO acts in somatic tissues, rather than directly in the germline, to initiate and manifest these programming effects.
Article
Food Science & Technology
Anderson Fellyp Avelino Diniz, Brena Freire de Oliveira Claudino, Daiany Maria Claudino Francelino, Edvaldo Balbino Alves Junior, Paula Benvindo Ferreira, Francisco Fernandes Lacerda Junior, Barbara Cavalcanti Barros, Ray Ravilly Alves Arruda, Adriano Francisco Alves, Leonia Maria Batista, Bagnolia Araujo da Silva
Summary: Obesity is an energy imbalance that leads to various pathophysiological conditions, including gastrointestinal diseases, and is associated with overexpression of oxidative stress and pro-inflammatory cytokines. Arthorpira platensis (AP), an alga with anti-inflammatory and antioxidant activities, showed preventive effects on oxidative stress and interleukin-1 & beta; (IL-1 & beta;) levels in the ileum of rats fed a hypercaloric diet. The supplementation of AP prevented underproduction of antioxidant enzymes, overexpression of oxidative stress, and an increase in IL-1 & beta; levels in obese rats, making it a promising therapeutic alternative in the treatment of inflammatory bowel diseases aggravated by obesity.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Review
Pharmacology & Pharmacy
Madison M. Crutcher, Trevor R. Baybutt, Jessica S. Kopenhaver, Adam E. Snook, Scott A. Waldman
Summary: This article discusses emerging pathways and drug targets for the treatment of colorectal cancer. The shift to the cancer stem cell model and potential targets involving Wnt, NF-kappa B, phosphodiesterases, RAS, and guanylyl cyclase C are explored. The current utility of checkpoint inhibitors and evolving immunological options are also examined. According to expert opinion, surgery and current systemic cytotoxic therapies are not sufficient to treat the full spectrum of CRC, especially in metastatic or treatment-refractory cases. The identification of new targets and novel treatment administration methods, such as immuno-oncologic options and stem cell-targeting therapies, may improve survival for patients with metastatic CRC.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Genetics & Heredity
Amir Hossein Saeidian, Leila Youssefian, Jianhe Huang, Andrew Touati, Hassan Vahidnezhad, Luke Kowal, Matthew Caffet, Tamara Wurst, Jagmohan Singh, Adam E. Snook, Ellen Ryu, Paolo Fortina, Sharon F. Terry, Jonathan G. Schoenecker, Jouni Uitto, Qiaoli Li
Summary: This study reports the genetic findings from an international cohort of patients with heritable ectopic mineralization. Multiple gene variants were identified, including 159 distinct variants in the ABCC6 gene. The functional assessment of these variants highlighted the importance of determining pathogenicity through appropriate experimental systems.
GENETICS IN MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Jeffrey A. Rappaport, Ariana A. Entezari, Adi Caspi, Signe Caksa, Aakash V. Jhaveri, Timothy J. Stanek, Adam Ertel, Joan Kupper, Paolo M. Fortina, Steven B. McMahon, James B. Jaynes, Adam E. Snook, Scott A. Waldman
Summary: The study revealed the corepression of GUCY2C ligand transcription by beta-catenin/TCF signaling and provided genomic strategies to reestablish hormone expression. This mechanism reflects a novel pathophysiological step in tumorigenesis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Jeffrey A. Rappaport, Ariana A. Entezari, Adam E. Snook, Scott A. Waldman
Article
Dermatology
Luke Kowal, Jianhe Huang, Hongbin Luo, Jagmohan Singh, Adam E. Snook, Jouni Uitto, Qiaoli Li
Summary: This study characterized the pathogenicity of three human ABCC6 missense variants in a mouse model of pseudoxanthoma elasticum. Two of the variants were found to be benign, while one was shown to be pathogenic. These results elucidate the functional consequences of ABCC6 missense variants in patients with pseudoxanthoma elasticum.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Claudia Capparelli, Timothy J. Purwin, McKenna Glasheen, Signe Caksa, Manoela Tiago, Nicole Wilski, Danielle Pomante, Sheera Rosenbaum, Mai Q. Nguyen, Weijia Cai, Janusz Franco-Barraza, Richard Zheng, Gaurav Kumar, Inna Chervoneva, Ayako Shimada, Vito W. Rebecca, Adam E. Snook, Kim Hookim, Xiaowei Xu, Edna Cukierman, Meenhard Herlyn, Andrew E. Aplin
Summary: Cellular plasticity plays a crucial role in tumor heterogeneity and phenotype switching. SOX10 is involved in the phenotypic switching of cutaneous melanoma, and cIAP1/2 inhibitors can selectively induce cell death in SOX10-deficient cells.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
John C. Flickinger Jr, Jagmohan Singh, Yanki Yarman, Robert D. Carlson, Joshua R. Barton, Scott A. Waldman, Adam E. Snook
Summary: This study assessed the immunogenicity of an Lm vaccine against the colorectal tumor antigen GUCY2C. The results showed that the Lm vaccine had strong immunogenicity against Lm-derived peptides, but weak immunogenicity against GUCY2C. By altering the stability of the peptide ligands, the immunogenicity of GUCY2C could be restored. These findings suggest that optimizing target antigen competitiveness or using alternative immunization regimens may be necessary to maximize the clinical utility of Lm-based vaccines.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Daniel S. Lefler, Adam E. Snook, Babar Bashir
Summary: In luminal gastrointestinal tumors, immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4 have shown promise in treatment. The effectiveness of these drugs depends on specific biomarkers and interactions with the tumor microenvironment and other therapies.
Review
Pharmacology & Pharmacy
Adi Caspi, Ariana A. Entezari, Madison Crutcher, Adam E. Snook, Scott A. Waldman
Summary: Colorectal cancer is a major cause of mortality in the USA, and while current therapies focus on generic treatment, there is a growing need for effective targets and biomarkers. Guanylyl cyclase C, which regulates intestinal homeostasis and is universally expressed in advanced metastatic colorectal tumors, has emerged as a promising target and biomarker for gastrointestinal malignancies.
PERSONALIZED MEDICINE
(2022)
Article
Immunology
John C. Flickinger, Ross E. Staudt, Jagmohan Singh, Robert D. Carlson, Joshua R. Barton, Trevor R. Baybutt, Jeffrey A. Rappaport, Alicja Zalewski, Amanda Pattison, Scott A. Waldman, Adam E. Snook
Summary: Strategies to enhance immunity to self/neoantigens expressed by cancers are urgently needed. This study explored a prime-boost strategy combining a chimeric adenoviral vector and recombinant Listeria monocytogenes to amplify GI cancer antigen GUCY2C-specific immunity. The combination enhanced the efficacy of effector CD8(+) T cells without toxicity and resistance to pre-existing immunity.
Review
Pharmacology & Pharmacy
Madison M. Crutcher, Adam E. Snook, Scott A. Waldman
Summary: Colorectal cancer is the second leading cause of cancer-related death worldwide. Survival rates vary across stages and targeted therapies have improved overall survival. However, further research is needed to develop effective biomarkers for guiding treatment decisions and monitoring treatment response.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2022)
Meeting Abstract
Hematology
Ruchi P. Patel, Guido Ghilardi, Patrizia Porazzi, Steven Yang, Dean Qian, Raymone Pajarillo, Michael Wang, Yunlin Zhang, Stephen J. Schuster, Stefan K. Barta, Aditya Nimmagadda, Adam Snook, Nicholas A. Siciliano, Marco Ruella
Review
Immunology
Robert Hughes, Adam E. Snook, Adam C. Mueller
Summary: Pancreatic cancer is a highly aggressive and therapy-resistant cancer with an immunosuppressive tumor microenvironment. Previous attempts at utilizing immunotherapies have been unsuccessful in treating pancreatic cancer. Unlike other cancers, radiation therapy has limited success in stimulating immune responses in pancreatic cancer due to the common pathways of fibrosis and chronic inflammation activated by radiation therapy, resulting in immune suppression. Targeting these pathways may improve outcomes by utilizing the cytotoxic and immune-activating aspects of radiation therapy.
Article
Medicine, Research & Experimental
Joshua R. Barton, Annie K. Londregran, Tyler D. Alexander, Ariana A. Entezari, Shely Bar-Ad, Lan Cheng, Angelo C. Lepore, Adam E. Snook, Manuel Covarrubias, Scott A. Waldman
Summary: GUCY2C signaling in neuropod cells plays a crucial role in visceral pain, and FDA-approved GUCY2C agonists can alleviate visceral pain in patients with chronic constipation syndromes. Studies on neural currents and action potentials indicate that neuropod cells, enriched with GUCY2C receptors, have significant regulatory effects.
JOURNAL OF CLINICAL INVESTIGATION
(2023)