Article
Pharmacology & Pharmacy
Vivek Kumar Pandey, Alpana Mathur, Mohammad Fareed Khan, Poonam Kakkar
Summary: ER stress leads to the degradation of glucose transporter proteins, resulting in complex glucose metabolism. The PERK axis plays a crucial role in regulating the expression and translocation of hepatic glucose transporters.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Qiuya Wu, Duanfang Zhou, Zhengze Shen, Bo Chen, Gang Wang, Lihong Wu, Limei Zhang, Xiaoli Li, Lie Yuan, Yuanli Wu, Na Qu, Weiying Zhou
Summary: VPS34-IN1 is a specific selective inhibitor of Class III Phosphatidylinositol 3-kinase (PI3K) and has been shown to exhibit a significant antitumor effect in leukemia and liver cancer. In this study, the researchers focused on the anticancer effect and potential mechanism of VPS34-IN1 in estrogen receptor positive (ER+ ) breast cancer. The results showed that VPS34-IN1 inhibited the viability of ER+ breast cancer cells by inducing apoptosis through the activation of the PERK/ATF4/CHOP pathway of ER stress. These findings provide new insights and potential treatment strategies for ER+ breast cancer.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tae Woo Kim
Summary: This study examines the anti-inflammatory and anti-cancer effects of fisetin, a natural flavonoid. The results show that fisetin can reduce inflammation and induce cancer cell death through ER stress. It also overcomes radiation resistance and induces cell death in liver cancer cells. Therefore, fisetin combined with radiation may be a powerful immunotherapy strategy to overcome resistance in an inflammatory tumor microenvironment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Zhaolin Gao, Min Li, Fei Yao, Xiaobo Xia, Tianqi Duan, Jingzhuo Meng, Yanxia Huang, Ye He, Adonira Saro, Jufang Huang
Summary: The study investigated the effects and underlying mechanisms of valdecoxib on retinal ischemia-reperfusion injury and oxygen-glucose deprivation/recovery injury. The results showed that valdecoxib protected R28 cells by reducing cell apoptosis and exerted a protective effect on retinas by inhibiting retinal ganglion cell apoptosis. In addition, valdecoxib reversed the expression of certain proteins induced by glaucomatous model and the reversal was mediated by the PERK-ATF4-CHOP pathway. These findings suggest that valdecoxib protects against glaucomatous injury by inhibiting ER stress-induced apoptosis via the PERK-ATF4-CHOP pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Sanghwa Kim, Minji Lee, Yeonhwa Song, Su-Yeon Lee, Inhee Choi, I-Seul Park, Jiho Kim, Jin-sun Kim, Kang mo Kim, Haeng Ran Seo
Summary: The expression of ASS1 was higher in HCC spheroids than in monolayer cells, and high levels of ASS1 were associated with favorable overall survival in Korean HCC patients. Bidirectional interactions between ASS1 ER stress responses in HCC-derived spheroids limit HCC progression. Overexpression of ASS1 inhibited tumor growth and enhanced the efficacy of anti-HCC chemotherapy via activation of the PERK/eIF2 alpha/ATF4/CHOP axis, independent of p53 and arginine metabolism.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jiunn-Chang Lin, Pei-Ming Yang, Tsang-Pai Liu
Summary: The study identified lncRNA ZFAS1 as a potential biomarker for sorafenib therapy resistance in HCC, and showed that sorafenib induces ER stress and the unfolded protein response pathways through the PERK/ATF4/ZFAS1 signaling axis. This finding suggests a new direction for the treatment and prognosis of HCC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Integrative & Complementary Medicine
Xiaobo Hu, Tingting Duan, Zhuan Wu, Cifei Tang, Zhaohui Cao
Summary: The natural isoflavone puerarin has shown potential in preventing apoptosis of MIN6 cells by inhibiting the PERK-eIF2 alpha-ATF4-CHOP axis under ER stress conditions. This effect may be mediated by the inactivation of the JAK2/STAT3 signal pathway. Further understanding of the mechanisms behind puerarin's effects could lead to its development as a potential antidiabetic drug.
AMERICAN JOURNAL OF CHINESE MEDICINE
(2021)
Article
Oncology
Shengnan Sun, Yong Yi, Zhi-Xiong Jim Xiao, Hu Chen
Summary: Colorectal cancer (CRC) is the fourth most common cancer and p53 mutations are present in 43% of CRC cases. This study found that ER stress can induce apoptosis in p53 null colon cancer cells through the upregulation of TAp73a protein. The PERK-ATF4 signaling pathway is involved in ER stress-induced TAp73a expression and the promotion of colon cancer cell apoptosis. Therefore, targeting prolonged ER stress or upregulation of TAp73a may be a potential therapeutic strategy for colon cancer.
Article
Food Science & Technology
Zhou Li, Chen Chen, Pan Ying, Ji-jun Gu, Lian-jie Dou, Huang Dan, Xuan-min Zou, Tian-yue Guan, Zhang Chao, Jia-hu Hao
Summary: This study using a JEG-3 cell model found that both BPA and BPS can reduce the synthesis of placental estradiol (E2) and may activate endoplasmic reticulum stress by increasing ROS levels.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Endocrinology & Metabolism
Shaunaci A. Stevens, Maria K. Gonzalez Aguiar, Allyson L. Toro, Esma I. Yerlikaya, Siddharth Sunilkumar, Ashley M. VanCleave, Jessica Pfleger, Elisa A. Bradley, Scot R. Kimball, Michael D. Dennis
Summary: The interplay between endoplasmic reticulum stress and inflammation contributes to cardiovascular disease progression. This study identifies REDD1, a stress response protein, as a missing link that connects the development of endoplasmic reticulum stress with increased production of proinflammatory cytokines in the hearts of obese mice.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Cell Biology
Yuanyang Chen, Sihao Zheng, Zhiwei Wang, Xin Cai, Yanjia Che, Qi Wu, Shun Yuan, Xiaohan Zhong
Summary: This study demonstrated that ART treatment prolonged the survival time of mice in the HT group, reduced inflammatory cell infiltration in heart tissue, and lowered CD4+CD8+ T cell proportions in spleen and lymph nodes. Additionally, ART treatment inhibited oxidative stress damage in heart tissue and myocardial apoptosis. In cell experiments, ART slowed down BMDC development and maturation by inhibiting endoplasmic reticulum stress-related protein expression.
MEDIATORS OF INFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Yu Wu, Xiaomei Fan, Sha Chen, Ling Deng, Lu Jiang, Shaonan Yang, Zhi Dong
Summary: The aim of this study was to investigate the protective mechanism of geraniol against cerebral ischemia-reperfusion injury (CIRI). The results showed that geraniol effectively attenuated cerebral infarction and pathological injury, reduced ER-stress-related protein expression and apoptosis occurrence, and increased anti-apoptotic protein expression, suggesting a protective effect against CIRI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Xiao-xuan Yu, Meng-yuan Zhu, Jia-rong Wang, Hui Li, Po Hu, Ying-jie Qing, Xiang-yuan Wang, Hong-zheng Wang, Zhan-yu Wang, Jing-yan Xu, Qing-long Guo, Hui Hui
Summary: The study shows that LW-213 effectively inhibits the growth of CTCL cells and induces apoptosis. The mechanisms involve ROS formation, calcium release, and activation of different signaling pathways.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Multidisciplinary Sciences
Davy Vanhoutte, Tobias G. Schips, Alexander Vo, Kelly M. Grimes, Tanya A. Baldwin, Matthew J. Brody, Federica Accornero, Michelle A. Sargent, Jeffery D. Molkentin
Summary: The Thbs family of proteins, particularly Thbs1, plays a critical role in regulating adult cardiomyocyte size in the stressed heart through activation of PERK-eIF2 alpha -ATF4-induced autophagy.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Xiaohua Lu, Ge Yan, Sabine M. Klauck, Edmond Fleischer, Anette Klinger, Yoshikazu Sugimoto, Letian Shan, Thomas Efferth
Summary: MCC1734 demonstrates cytotoxicity towards multidrug-resistant cancer cell lines with different mechanisms, bypassing P-glycoprotein-mediated resistance. It affects cell function through various pathways, including cell cycle regulation, mitochondrial function, apoptosis signaling, and endoplasmic reticulum stress. The anti-cancer effects of MCC1734 are further supported by in vivo studies using human xenograft tumors transplanted to zebrafish.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Dermatology
Andrezza Telles Westin, Luiz Gustavo Gardinassi, Edson Garcia Soares, Joao Santana Da Silva, Eduardo Antonio Donadi, Cacilda Da Silva Souza
Summary: The study found that non-aggressive basal cell carcinoma subtypes exhibit HLA-G expression, with more HLA-G-positive inflammatory cells than tumor cells. Different locations and subtypes of BCC show differences in cytokine expression, consistent with the induction of HLA-G expression.
ARCHIVES OF DERMATOLOGICAL RESEARCH
(2022)
Article
Immunology
Tianhao Xu, Alexander Schutte, Leandro Jimenez, Andre N. A. Goncalves, Ashleigh Keller, Matthew E. Pipkin, Helder Nakaya, Renata M. Pereira, Gustavo J. Martinez
Summary: Kdm6b is essential for the proper generation and function of effector CD8(+) T cells, with its deficiency impacting effector cell generation and function, as well as recall response of memory CD8(+) T cells. The study suggests Kdm6b as a potential therapeutic target for diseases with dysregulated effector responses by regulating chromatin accessibility in effector-associated genes.
JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Tianhao Xu, Renata M. Pereira, Gustavo J. Martinez
Summary: Naive CD8(+) T cells clonally expand and differentiate into distinct cell fates upon encountering their cognate antigen in vivo, regulated by transcription factors and epigenetic modulators. Multiple models have been proposed to explain the differentiation of CTLs, but none fully recapitulate the experimental evidence. This review article summarizes the latest research on the epigenetic regulation of CTL differentiation and presents a combined model to contemplate them.
JOURNAL OF IMMUNOLOGY
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
Karina Dias Teixeira, Mazhar Adli, John Doench, Gordon W. Laurie
Article
Cell Biology
Guilherme A. Melo, Carolina Caloba, Gabrielle Brum, Thais O. Passos, Gustavo J. Martinez, Renata M. Pereira
Summary: This review discusses the diverse roles of PcG proteins in T cell biology, focusing on the regulation of T cell development, CD4 T cell differentiation, and CD8 T cell fate determination by PRC1 and PRC2 in the context of infections and cancer.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Mauro Cesar Cafundo Morais, Diogo Silva, Matheus Marques Milagre, Maykon Tavares de Oliveira, Thais Pereira, Joao Santana Silva, Luciano da F. Costa, Paola Minoprio, Roberto Marcondes Cesar Junior, Ricardo Gazzinelli, Marta de Lana, Helder Nakaya
Summary: In this study, a machine learning approach based on a random forest algorithm was developed for the detection and counting of T. cruzi trypomastigotes in mobile phone images. The method achieved high precision, sensitivity, and area under the ROC curve when tested on a dataset of blood smear samples captured using a mobile device camera. Automating image analysis acquired with a mobile device can reduce costs and improve efficiency in the use of optical microscopes.
Article
Immunology
Vanessa Neitzke-Montinelli, Carolina Caloba, Guilherme Melo, Bianca B. Frade, Enzo Caramez, Luciano Mazzoccoli, Andre N. A. Goncalves, Helder I. Nakaya, Renata M. Pereira, Miriam B. F. Werneck, Joao P. B. Viola
Summary: This study established a novel in vitro CD8 T cell activation and culture regimen to generate differentiated cells consistent with central memory-like cells. In vitro memory cells provided long-term immunological protection and showed potential for immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Sandra Regina Maruyama, Carlos Alessandro Fuzo, Antonio Edson R. Oliveira, Luana Aparecida Rogerio, Nayore Tamie Takamiya, Gabriela Pessenda, Enaldo Vieira de Melo, Angela Maria da Silva, Amelia Ribeiro Jesus, Vanessa Carregaro, Helder I. Nakaya, Roque Pacheco Almeida, Joao Santana da Silva
Summary: In this study, mRNA sequencing was used to analyze peripheral blood samples from patients with visceral leishmaniasis, revealing thousands of differentially expressed genes and identifying important signaling pathways and cell types involved in the immunopathological processes of the disease. Additionally, lncRNA expression analysis was performed for the first time in visceral leishmaniasis, uncovering the significant role of lncRNAs in the disease's development.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Juliana C. Costa-Madeira, Gabrielly B. Trindade, Paulo H. P. Almeida, Joao S. Silva, Vanessa Carregaro
Summary: A key aspect of immunity against Leishmania parasites is the development of an optimal T cell response, which can be compromised during chronic infection, leading to T cell exhaustion. Multiple factors, including parasite load, infection duration, and host immunity, contribute to T cell exhaustion. This can result in disease progression and acquired resistance to conventional drugs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Aline Cavalcanti de Queiroz, Gisele Barbosa, Victoria Regina Thomaz de Oliveira, Helio de Mattos Alves, Marina Amaral Alves, Vanessa Carregaro, Joao Santana da Silva, Eliezer Jesus Barreiro, Magna Suzana Alexandre-Moreira, Lidia Moreira Lima
Summary: Leishmaniasis is a neglected disease and current treatment methods have limitations. LASSBio-1491, a potential drug candidate, showed promising pharmacokinetic properties and demonstrated effective treatment against leishmaniasis in vitro and in vivo.
Article
Multidisciplinary Sciences
Julia T. Castro, Patrick Azevedo, Marcilio J. Fumagalli, Natalia S. Hojo-Souza, Natalia Salazar, Gregorio G. Almeida, Livia I. Oliveira, Lidia Faustino, Lis R. Antonelli, Tomas G. Marcal, Marconi Augusto, Bruno Valiate, Alex Fiorini, Bruna Rattis, Simone G. Ramos, Mariela Piccin, Osvaldo Campos Nonato, Luciana Benevides, Rubens Magalhaes, Bruno Cassaro, Gabriela Burle, Daniel Doro, Jorge Kalil, Edson Durigon, Andres Salazar, Otavia Caballero, Helton Santiago, Alexandre Machado, Joao S. Silva, Flavio da Fonseca, Ana Paula Fernandes, Santuza R. Teixeira, Ricardo T. Gazzinelli
Summary: This study generated a chimeric protein (SpiN) that can elicit specific T cell responses and provide strong protection against SARS-CoV-2 infection. The results suggest that vaccine formulations that induce effector T cells specific for the nucleocapsid antigen and receptor binding domain of SARS-CoV-2 can improve COVID-19 vaccines and potentially overcome immune escape by variants of concern.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Carolina T. Rath, Aislan C. Vivarini, Jose Vitorino dos Santos, Jorge M. Medina, Alessandra M. Saliba, Jeremy C. Mottram, Ana Paula C. A. Lima, Teresa Cristina Calegari-Silva, Renata M. Pereira, Ulisses G. Lopes
Summary: The protozoan parasite Leishmania (L.) amazonensis requires TLR3 for its intracellular growth. TLR3(-/-) mouse macrophages showed restricted infection, reduced levels of IFN1 beta and IL-10, and increased levels of IL-12 compared to wild-type macrophages. Inhibition of TLR3 cleavage or infection by CPB-deficient mutant L. (L.) mexicana resulted in reduced parasite load and restricted expression of IFN1 beta and IL-10. Furthermore, the dsRNA sensor molecule PKR cooperates with TLR3 signaling to enhance the expression of IL-10 and IFN1 beta and promote parasite survival.
INFECTION AND IMMUNITY
(2022)
Article
Biochemistry & Molecular Biology
Jessica F. C. Cordeiro, Talita M. Fernandes, Diana M. Toro, Pedro da Silva-Neto, Vinicius E. Pimentel, Malena M. Perez, Jonatan C. S. de Carvalho, Thais F. C. Fraga-Silva, Camilla N. S. Oliveira, Jamille G. M. Argolo, Augusto M. Degiovani, Fatima M. Ostini, Enrico F. Puginna, Joao S. da Silva, Isabel K. F. M. Santos, Vania L. D. Bonato, Cristina R. B. Cardoso, Marcelo Dias-Baruffi, Lucia H. Faccioli, Eduardo A. Donadi, Carlos A. Sorgi, Ana P. M. Fernandes
Summary: The study evaluated the levels of plasma soluble HLA-G (sHLA-G) in COVID-19 patients and healthy controls. The results showed increased levels of sHLA-G in COVID-19 patients, which correlated with disease severity. However, the levels decreased in critically ill patients, possibly indicating immune exhaustion. sHLA-G also exhibited positive correlation with other disease mediators IL-6, IL-8, and IL-10.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Elena Montes-Cobos, Victoria C. Bastos, Clarice Monteiro, Joao C. R. de Freitas, Heiny D. P. Fernandes, Clarice S. Constancio, Danielle A. S. Rodrigues, Andreza M. D. S. Gama, Vinicius M. Vidal, Leticia S. Alves, Laura Zalcberg-Renault, Guilherme S. de Lira, Victor A. Ota, Carolina Caloba, Luciana Conde, Isabela C. Leitao, Amilcar Tanuri, Orlando D. C. Ferreira, Renata M. Pereira, Andre M. Vale, Terezinha M. Castineiras, Dominique Kaiserlian, Juliana Echevarria-Lima, Marcelo T. Bozza
Summary: This study investigates the immune response of immunocompetent COVID-19 patients with prolonged infection. The results show that despite similar viral loads and symptoms to mildly symptomatic patients, long-term carriers exhibit weaker systemic IFN-I responses and lower levels of circulating pDCs and NK cells at disease onset. Interestingly, no defects in antigen-specific cytotoxic T cell responses were observed in these patients, and their circulating antibodies displayed higher affinity against different variants of the SARS-CoV-2 Spike protein. These findings contribute to our understanding of essential host protective mechanisms during prolonged viral infection to control tissue damage.
Article
Biology
Carolina Torturella Rath, Aislan de Carvalho Vivarini, Renata M. Pereira, Ulisses Gazos Lopes
Summary: Phlebotomine vectors, such as sand flies, can transmit Leishmania parasites and RNA viruses like the arbovirus Icoaraci Phlebovirus (ICOV) to humans. Research shows that ICOV exacerbates protozoan infections by modulating cytokine expression, highlighting the importance of developing and standardizing efficient viral production and quantification techniques. This standardized approach is a valuable tool for studying the interaction between host cells and Phlebovirus, as well as co-infections, providing insights into intracellular signaling pathways.