Article
Biochemistry & Molecular Biology
Sarah Hartwick Bjorkman, Renata Oliveira Pereira
Summary: Mitochondria-derived reactive oxygen species (mtROS) can disrupt cellular redox homeostasis, but moderate mitochondrial stress may enhance the organism's ability to cope with stress. By regulating different signaling pathways, mtROS play a key role in maintaining cardiometabolic health.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Pharmacology & Pharmacy
Min Jeong Kim, Jin Mo Ku, Se Hyang Hong, Hyo In Kim, Yun Young Kwon, Joon-Sang Park, Deok Hyun Jung, Yong Cheol Shin, Seong-Gyu Ko
Summary: Prostate cancer is the second most diagnosed cancer in American men, with chemotherapy being a common treatment method. However, the study focused on investigating the molecular mechanism of JI017 in human prostate cancer cells, revealing its induction of apoptosis through the ER stress pathway. Various experiments were conducted to demonstrate that JI017 inhibits prostate cancer cell proliferation via ROS-mediated ER stress pathway and induces cell death.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Junghwan Lee, Chang-Hwa Song
Summary: Oxidative stress plays a crucial role in innate immunity against pathogens, with ROS directly attacking pathogens, regulating immune signals, inducing autophagy, and activating inflammation. The production of ROS by pathogens not only affects cell death but also the endoplasmic reticulum and mitochondria. The regulation of host defense mechanisms by ROS and the interaction between microbial pathogen-induced ROS and the ER and mitochondria remain unclear.
Article
Biochemistry & Molecular Biology
Wei Zeng, Jingping Ren, Gan Yang, Changsheng Jiang, Ling Dong, Qi Sun, Yaofang Hu, Wentao Li, Qigai He
Summary: Porcine epidemic diarrhea virus (PEDV) is an alpha-coronavirus that causes severe symptoms and high mortality in piglets. Previous studies have shown that endoplasmic reticulum (ER) stress can inhibit the replication of human coronaviruses, and this study demonstrates that PEDV can interact with ER stress and be inhibited by it. The non-structural protein 14 (nsp14) of PEDV plays a crucial role in inhibiting the ER stress marker glucose-regulated protein 78 (GRP78), and its guanine-N7-methyltransferase domain is necessary for this role. PEDV and its nsp14 also negatively regulate host translation and suppress GRP78 transcription. These findings suggest that targeting ER stress and PEDV nsp14 could be a potential approach for developing anti-PEDV drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Yanli Ma, Junchao Liu, Haimei Liu, Xinli Han, Li Sun, Hong Xu
Summary: This study demonstrates that knockout of Angptl3 gene can provide renal protection against LPS-induced AKI by regulating the ROS/GRP78 signaling pathway and alleviating renal dysfunction and podocyte apoptosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Mario Gonzalez-Gronow, Salvatore Vincent Pizzo
Summary: The 78 kDa glucose-regulated protein (GRP78) is involved in the regulation of the unfolded protein response (UPR) during cellular endoplasmic reticulum (ER) stress. It can translocate to the cell surface and function as an autoantigen, leading to the production of autoantibodies. These autoantibodies are found in various cancers and autoimmune diseases and can cross the blood-brain barrier, causing disruptions in the brain. Additionally, this study explores how csGRP78 acts as a dual compartmentalized receptor with different signaling pathways.
Review
Biochemistry & Molecular Biology
Gregorio Bonsignore, Simona Martinotti, Elia Ranzato
Summary: The unfolded protein response (UPR) is an adaptive response triggered by endoplasmic reticulum (ER) stress for re-establishing protein homeostasis. Specific ER proteins mediate UPR activation by dissociating from chaperone Glucose-Regulated Protein 78 (GRP78). UPR can decrease ER stress, produce an ER adaptive response, block UPR if ER homeostasis is restored, or regulate apoptosis. This review focuses on molecules that target ER stress and demonstrate how UPR could be a new target in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Juan A. Fafian-Labora, Miriam Morente-Lopez, Fco Javier de Toro, Maria C. Arufe
Summary: HGPS is a deadly childhood disorder caused by a mutation on the LMNA gene, characterized by accelerated aging. Research has shown alterations in the Ca2+ signaling pathway in HGPS, possibly due to the overproduction of ROS. This opens up new therapeutic strategies for this rare disease and provides insights into pathologies involving accelerated and healthy aging.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Physiology
Jing Zhang, Feng Zhang, Yanou Wang
Summary: Diabetic cardiomyopathy is associated with mitochondrial damage, specifically due to increased mitochondria-endoplasmic reticulum (ER) contact. Hyperglycemia induces this contact in cardiomyocytes, but silencing of Mfn2 can protect against mitochondrial dysfunction, calcium overload, apoptosis, and ER stress, enhancing cardiomyocyte survival under high-glucose conditions.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Zhen-zhen Feng, Ning Luo, Ying Liu, Jian-nan Hu, Tao Ma, Yong-ming Yao
Summary: Accumulating evidence suggests the involvement of ER stress pathway in immunity, but little information has linked ER stress to Tregs. Our study demonstrated that ER stress enhances the functional activity of Tregs and revealed a critical role of the PERK branch of UPR in regulating Tregs function.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Elia Ranzato, Gregorio Bonsignore, Simona Martinotti
Summary: Malignant mesothelioma is a rare and aggressive cancer strongly linked to asbestos exposure. With limited therapeutic options, novel approaches are urgently needed. Previous studies have shown the importance of GRP78 in MPM survival, and our research suggests that BOLD-100, a specific modulator of GRP78, inhibits MPM cell growth by inducing cellular stress and cell death.
Review
Biochemistry & Molecular Biology
Shuvadeep Maity, Pragya Komal, Vaishali Kumar, Anshika Saxena, Ayesha Tungekar, Vaani Chandrasekar
Summary: Accumulation of misfolded proteins is common in neurodegenerative diseases, particularly those caused by abnormal PolyQ expansions. The disruption of protein homeostasis in the endoplasmic reticulum (ER) and activation of the unfolded protein response (UPR) pathway are linked to the development of Huntington's disease (HD). Furthermore, proteins at ER-mitochondria contact sites (MAMs) play a significant role in HD progression. This review provides updated information on UPR pathways and their involvement in HD, as well as the role of MAMs in disease progression. Therapeutic interventions focusing on ER stress response proteins and ER-mitochondrial contact proteins are discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Elizabeth Murphy, Julia Liu
Summary: Cardiomyocytes have a high density of mitochondria, which play a crucial role in energy production and cellular functions. The regulation of mitochondrial calcium and reactive oxygen species is important in the development of cardiovascular disease.
CARDIOVASCULAR RESEARCH
(2023)
Article
Food Science & Technology
Zin Zin Ei, Soottawat Benjakul, Natchaphol Buamard, Kittichate Visuttijai, Pithi Chanvorachote
Summary: Shrimp lipid (SL) has a protective effect on endothelial cell apoptosis induced by ER stress by suppressing the ER stress pathway.
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.
Review
Biochemistry & Molecular Biology
Iona J. MacDonald, Chien-Chung Huang, Shan-Chi Liu, Yen-You Lin, Chih-Hsin Tang
Summary: The CCN family of matricellular proteins play essential roles in processes like angiogenesis, wound healing, and inflammation, particularly in the inflammatory pathologies of rheumatoid arthritis and osteoarthritis. Several proteins within the CCN family are thought to be potential therapeutic targets for these diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Shih-Ya Hung, Chih-Yang Lin, Cheng-Chieh Yu, Hsien-Te Chen, Ming-Yu Lien, Yu-Wen Huang, Yi-Chin Fong, Ju-Fang Liu, Shih-Wei Wang, Wei-Cheng Chen, Chih-Hsin Tang
Summary: Chondrosarcoma is a malignant bone tumor with high metastatic potential and resistance to conventional treatments. Visfatin, an adipokine, has been found to promote chondrosarcoma cell migration and lung metastasis through the induction of MMP-2 and activation of the AP-1 transcription factor. Targeting visfatin may be a promising strategy for treating metastatic chondrosarcoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Iona J. MacDonald, Hsiao-Chi Tsai, An-Chen Chang, Chien-Chung Huang, Shun-Fa Yang, Chih-Hsin Tang
Summary: Osteoblasts and osteoclasts are crucial in the bone turnover cycle, and melatonin shows promising therapeutic potential for both osteoporosis and osteolytic bone metastasis by regulating bone metabolism, bone cell differentiation, and bone resorption.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nutrition & Dietetics
Fang-Ju Cheng, Thanh-Kieu Huynh, Chia-Shin Yang, Dai-Wei Hu, Yi-Cheng Shen, Chih-Yen Tu, Yang-Chang Wu, Chih-Hsin Tang, Wei-Chien Huang, Yeh Chen, Chien-Yi Ho
Summary: The study demonstrates that hesperetin and hesperidin have the potential to inhibit SARS-CoV-2 infection by blocking the cellular entry process. They can reduce the binding of the S protein to the cellular receptor and decrease the expression of related proteins, thereby inhibiting the viral infection.
Article
Biochemistry & Molecular Biology
Tsung-Ju Wu, Sunny Li-Yun Chang, Chih-Yang Lin, Chao-Yang Lai, Xiu-Yuan He, Chun-Hao Tsai, Chih-Yuan Ko, Yi-Chin Fong, Chen-Ming Su, Chih-Hsin Tang
Summary: IL-17 increases monocyte adhesion in OA synovium by reducing miR-5701 expression and enhancing VCAM-1 production. These findings improve our understanding of IL-17's impact on OA progression and provide insights for the design of more effective OA treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Chien-Chi Lu, Hsiao-Chi Tsai, Dong-Ying Yang, Shih-Wei Wang, Ming-Hsui Tsai, Chun-Hung Hua, Kwei-Jing Chen, Michael Yuan-Chien Chen, Ming-Yu Lien, Chih-Hsin Tang
Summary: The inflammatory chemokine CCL4 promotes angiogenesis and metastasis in oral squamous cell carcinoma (OSCC) by upregulating Angpt2 expression and activating MEK, ERK, and STAT3 signaling pathways. Inhibiting CCL4 may be a potential strategy for treating OSCC by targeting angiogenesis and metastasis.
Article
Cell Biology
Tien-Huang Lin, Sunny Li-Yun Chang, Pham Minh Khanh, Nguyen Thi Nha Trang, Shan-Chi Liu, Hsiao-Chi Tsai, An-Chen Chang, Jo-Yu Lin, Po-Chun Chen, Ju-Fang Liu, Jeng-Hung Guo, Chun-Lin Liu, Hsi-Chin Wu, Chih-Hsin Tang
Summary: Apelin plays a positive role in prostate cancer metastasis and is positively correlated with tumor progression and metastasis. It promotes cell migration and invasion by inhibiting TIMP2 expression. The signaling pathway of c-Src/PI3K/Akt and the synthesis of miR-106a-5p are controlled by apelin to regulate TIMP2 production and cell motility. Blocking apelin can inhibit prostate cancer metastasis in a mouse model.
Article
Cell Biology
Chang-Yu Song, Sunny Li-Yun Chang, Chih-Yang Lin, Chun-Hao Tsai, Shang-Yu Yang, Yi-Chin Fong, Yu-Wen Huang, Shih-Wei Wang, Wei-Cheng Chen, Chih-Hsin Tang
Summary: New treatments for chondrosarcoma are crucial due to its poor prognosis, and factors like PDGF and visfatin play significant roles in tumor development and angiogenesis. Research has shown that visfatin promotes chondrosarcoma angiogenesis by modulating miR-1264 expression, potentially offering a new therapeutic approach for the treatment of chondrosarcoma.
Article
Biochemistry & Molecular Biology
Sheng-Yen Hsiao, Chih-Hsin Tang, Po-Chun Chen, Tien-Huang Lin, Chia-Chia Chao
Summary: Melatonin exhibits antitumor activities against bladder cancer by inhibiting the epithelial-mesenchymal transition process and autophagy of bladder cancer cells. Melatonin treatment also slightly prolongs the survival of tumor-bearing mice.
Article
Cell Biology
Trung-Loc Ho, Chih-Hsin Tang, Sunny Li-Yun Chang, Chun-Hao Tsai, Hsien-Te Chen, Chen-Ming Su
Summary: Skeletal muscle atrophy is caused by muscle wasting or reductions in protein associated with aging, injury, and inflammatory processes. The study found an association between HMGB1 and IL-18 signaling in skeletal muscle atrophy, and the HMGB1/IL-18 axis may be a potential target for the treatment of this condition.
Editorial Material
Biochemistry & Molecular Biology
Chih-Hsin Tang
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Liang-Wei Lin, Shih-Wei Wang, Wei-Chien Huang, Thanh Kieu Huynh, Chao-Yang Lai, Chih-Yuan Ko, Yi-Chin Fong, Jie-Jen Lee, Shun-Fa Yang, Chih-Hsin Tang
Summary: Neovascular age-related macular degeneration (AMD) is a disease characterized by abnormal blood vessel growth in the retina, leading to severe vision loss. The presence of certain markers in the retinas of AMD patients suggests a contribution of endothelial progenitor cells (EPCs) in this pathogenesis. This study explores the potential of melatonin, a hormone produced in the retina, to inhibit EPC angiogenesis in neovascular AMD. The results demonstrate that melatonin can effectively inhibit the formation of EPC blood vessels and shows promise as a potential treatment for neovascular AMD.
Article
Biochemistry & Molecular Biology
Yu-Hsiang Chang, Yuan-Li Huang, Hsiao-Chi Tsai, An-Chen Chang, Chih-Yuan Ko, Yi-Chin Fong, Chih-Hsin Tang
Summary: This study aims to investigate the role of miRNAs in CCL2-mediated MMP expression and cell motility in human osteosarcoma. The results demonstrate a positive correlation between CCL2 or MMP-3 levels and osteosarcoma metastasis, and stimulation of osteosarcoma cells with CCL2 enhances migration and invasion abilities. Additionally, CCL2 enhances MMP-3-dependent cell motility by inhibiting miR-3659 synthesis.
Article
Biochemistry & Molecular Biology
Jui-Chieh Chen, Hsun-Chang Shih, Chih-Yang Lin, Jeng-Hung Guo, Cheng Huang, Hsiu-Chen Huang, Zhi-Yong Chong, Chih-Hsin Tang
Summary: Chondrosarcoma, the second most common bone cancer, is difficult to treat surgically when it is high-grade and metastatic. Doxorubicin (Dox) is commonly used in chemotherapy, but drug resistance hampers its effectiveness. This study found that the apelin (APLN) pathway is highly activated in Dox-resistant cells and in high-grade chondrosarcoma tissues. Inhibition of the APLN axis has shown therapeutic benefits in other cancers, and this study suggests that targeting APLN may improve the treatment of chondrosarcoma by overcoming drug resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Environmental Sciences
Chih-Chun Chuang, Kai Wang, Yi-Sun Yang, Edy Kornelius, Chih-Hsin Tang, Chia-Yi Lee, Hsiang-Wen Chien, Shun-Fa Yang
Summary: The study investigates the correlation between single-nucleotide polymorphisms (SNP) of HOX transcript antisense intergenic RNA (HOTAIR) and the clinical characteristics of diabetic retinopathy (DR). The results indicate that HOTAIR SNP rs12427129 and rs1899663 are strongly associated with the presence of DR, especially in female patients with proliferative diabetic retinopathy (PDR).
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)