Review
Pharmacology & Pharmacy
Dan Qiao, Ziwei Zhang, Yali Zhang, Qian Chen, Yujun Chen, Yingjue Tang, Xiong Sun, Zhipeng Tang, Yancheng Dai
Summary: Ulcerative colitis is a chronic inflammatory disease, and endoplasmic reticular stress-induced autophagy plays a crucial role in its pathogenesis. Dysregulated autophagy can lead to inflammation and disruption of the intestinal barrier, increasing the risk of colonic diseases.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Sanaz Dastghaib, P. Sravan Kumar, Sajjad Aftabi, Gautam Damera, Azadeh Dalvand, Adel Sepanjnia, Mohammad Kiumarsi, Mohamad-Reza Aghanoori, Sukhwinder Singh Sohal, Sudharsana R. Ande, Javad Alizadeh, Pooneh Mokarram, Saeid Ghavami, Pawan Sharma, Amir A. Zeki
Summary: Lung cells are exposed to internal and external stressors, leading to disruption of protein homeostasis and activation of the UPR. Dysregulation of the UPR is associated with disease development and various human conditions. Compounds targeting the UPR pathway show potential for future therapeutic interventions.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Adalberto Merighi, Laura Lossi
Summary: In addition to protein processing, the endoplasmic reticulum (ER) also plays roles in lipid synthesis, molecular transfers, and Ca2+ homeostasis. Proper protein folding and modification in the ER require molecular chaperones and a favorable environment. Disruption in ER conditions or chaperone capacity can lead to the unfolded protein response (UPR), triggering autophagy and potentially causing cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Peripheral Vascular Disease
Shibin Cheng, Zheping Huang, Sayani Banerjee, Sukanta Jash, Joel N. Buxbaum, Surendra Sharma
Summary: This study demonstrates the importance of protein aggregation in the pathophysiology of preeclampsia. The aggregation of TTR protein is found to be associated with endoplasmic reticulum stress and apoptosis. Furthermore, the use of transgenic mice provides further evidence of the link between TTR aggregation and preeclampsia-like features.
Review
Biochemistry & Molecular Biology
Morvarid Siri, Sanaz Dastghaib, Mozhdeh Zamani, Nasim Rahmani-Kukia, Kiarash Roustai Geraylow, Shima Fakher, Fatemeh Keshvarzi, Parvaneh Mehrbod, Mazaher Ahmadi, Pooneh Mokarram, Kevin M. Coombs, Saeid Ghavami
Summary: The COVID-19 pandemic is caused by the SARS-CoV-2 virus, which affects cellular and tissue homeostasis, innate immunity modulation, and clearance of viral particles. Viruses like SARS-CoV-2 can exploit autophagy and UPR mechanisms for their benefit, while mTOR, UPR, and autophagy pathways may be potential therapeutic targets for COVID-19.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Peijun Zhu, Ting Li, Qingqing Li, Yawen Gu, Yuan Shu, Kaibo Hu, Leifeng Chen, Xiaogang Peng, Jie Peng, Liang Hao
Summary: Osteosarcoma, the most common malignant bone tumor, has a poor prognosis and low sensitivity to current treatment methods. Endoplasmic reticulum stress (ERS) has been found to play a role in regulating osteosarcoma proliferation, apoptosis, and chemoresistance through the unfolded protein response (UPR) pathway. Further research on the relationship between ERS and osteosarcoma could lead to the development of more effective treatment strategies.
Article
Cell Biology
Yanan Li, Shujing Li, Huijian Wu
Summary: Cells adapt to environmental stimuli by making changes to combat injury and increase stress tolerance. If the damage is too severe to repair, cells undergo apoptosis to protect the overall population. Protein aggregation can cause serious damage to the cells, but ubiquitin plays a crucial role in clearing these abnormal proteins. Dysregulation of ubiquitin-proteasome system and autophagy can lead to the development of diseases.
Review
Immunology
Wolfgang Vivas, Sebastian Weis
Summary: Pathogens and their toxic byproducts can cause tissue damage in infected hosts, triggering stress responses such as the unfolded protein response (UPR) to limit pathogenesis. However, prolonged or excessive activation of UPR may have detrimental effects including cell death.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Noel Verjan Garcia, Kyung U. Hong, Nobuyuki Matoba
Summary: The endoplasmic reticulum (ER) plays a vital role in cell homeostasis and disruptions to its functions can lead to diseases. Dysregulated ER stress and UPR are linked to various human diseases, including inflammatory bowel disease (IBD). A recent study has shown that EPICERTIN can induce a protective UPR in colon epithelial cells, promoting mucosal healing in IBD models.
Review
Microbiology
Yuki Ishiwata-Kimata, Yukio Kimata
Summary: This article reviews the canonical and up-to-date insights regarding yeast UPR, mainly focusing on the functions and regulation of Ire1 and HAC1.
Article
Immunology
Maozhen Qi, Qingran Jiang, Siwei Yang, Chenxi Zhang, Jianguo Liu, Wei Liu, Pengfei Lin, Huatao Chen, Dong Zhou, Keqiong Tang, Aihua Wang, Yaping Jin
Summary: This study demonstrates that endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are novel modulators of autophagy that inhibit the intracellular survival of Trueperella pyogenes in goat endometrial epithelial cells (gEECs), potentially providing a therapeutic target for T. pyogenes infectious disease.
Article
Biology
Mateusz Kowalczyk, Edward Kowalczyk, Pawel Kwiatkowski, Lukasz Lopusiewicz, Monika Talarowska, Monika Sienkiewicz
Summary: Despite numerous scientific studies on depression, there is still no clear understanding of the causes and mechanisms of depression development. Recent research has found a strong relationship between depression and endoplasmic reticulum (ER) stress, with continuous activation of stress response pathways in patients. Therefore, recommended drugs should aim at reducing ER stress while alleviating symptoms of depression.ongoing search for drugs that can effectively reduce ER stress and relieve depression symptoms.
Article
Biochemistry & Molecular Biology
Yujie Zhong, Jiayu Liu, Dianjun Sun, Tianmin Guo, Yanpeng Yao, Xiaodong Xia, Chao Shi, Xiaoli Peng
Summary: The protective effect of dioscin on diabetic nephropathy was explored in this study. Dioscin reduced blood glucose, pancreatic injury, renal function markers and renal pathological changes. It also inhibited oxidative stress, inflammation, and apoptosis mediated by the mitochondria and ER stress, while enhancing autophagy and improving mitochondrial quality and quantity control.
Article
Biotechnology & Applied Microbiology
Phuong Thi Mai Nguyen, Yuki Ishiwata-Kimata, Yukio Kimata
Summary: The unfolded protein response (UPR) is a cellular response to deal with the accumulation of unfolded proteins in the endoplasmic reticulum (ER). This study demonstrates that constitutive induction of UPR in nonstress conditions leads to growth retardation, which can be partially rescued by weak ER stress. Additionally, the stable expression of ER-localized GFP in UPR-induced cells enhances UPR activity and promotes the production of triglycerides and heterogenous carotenoids. These findings have implications for metabolic engineering and the production of valuable lipidic molecules.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Cell Biology
Vittorio Abbonante, Alessandro Malara, Martina Chrisam, Samuele Metti, Paolo Soprano, Claudio Semplicini, Luca Bello, Valeria Bozzi, Monica Battiston, Alessandro Pecci, Elena Pegoraro, Luigi De Marco, Paola Braghetta, Paolo Bonaldo, Alessandra Balduini
Summary: Endoplasmic reticulum stress is linked to collagen retention, apoptosis, and impaired autophagy in megakaryocytes. This study highlights the interplay between genetic disorders of collagens, endoplasmic reticulum stress, and autophagy regulation in megakaryocytes.
Article
Surgery
Rebecca Mercieca-Bebber, Renee Eggins, Kilian Brown, Val J. Gebski, Kate Brewer, Lenna Lai, Lisa Bailey, Michael J. Solomon, John W. Lumley, Peter Hewett, Andrew D. Clouston, Kate Wilson, Wendy Hague, Julian Hayes, Stephen White, Matt Morgan, R. John Simes, Andrew R. L. Stevenson
Summary: This study aimed to compare the urinary, bowel, and sexual functioning of rectal cancer patients who underwent open or laparoscopic surgery. The results showed that patients who underwent open surgery had fewer symptoms in bowel and sexual functioning. However, it remains difficult to recommend one surgical approach over the other for rectal resection.
Review
Biochemistry & Molecular Biology
Sheridan L. Helman, Jie Zhou, Brie K. Fuqua, Yan Lu, James F. Collins, Huijun Chen, Christopher D. Vulpe, Gregory J. Anderson, David M. Frazer
Summary: The mammalian multicopper ferroxidases (MCFs), including ceruloplasmin, hephaestin, and zyklopen, play crucial roles in maintaining iron homeostasis in the body. They function in oxidizing, releasing, and absorbing iron ions, and have various physiological functions in different tissues. Apart from their iron-related roles, they also have other physiological functions, although many of them are not well-defined.
Article
Cell Biology
Sahar Keshvari, Berit Genz, Ngari Teakle, Melanie Caruso, Michelle F. Cestari, Omkar L. Patkar, Brian W. C. Tse, Kamil A. Sokolowski, Hilmar Ebersbach, Julia Jascur, Kelli P. A. MacDonald, Gregory Miller, Grant A. Ramm, Allison R. Pettit, Andrew D. Clouston, Elizabeth E. Powell, David A. Hume, Katharine M. Irvine
Summary: Resident and recruited macrophages play a crucial role in the development and proliferation of the liver. Previously, the use of a macrophage colony stimulating factor (CSF1)-Fc fusion protein has been shown to promote hepatocyte proliferation and repair in acute hepatic injury in mice. In this study, the impact of CSF1-Fc on the resolution of advanced fibrosis and liver regeneration was investigated using a toxin-induced model of chronic liver injury and fibrosis in mice. The findings suggest that CSF1-dependent macrophages contribute to both the initiation and resolution of fibrotic injury, and that CSF1-Fc has therapeutic potential in the treatment of human liver disease.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biochemistry & Molecular Biology
Lu Cao, Kim R. Bridle, Ritu Shrestha, Prashanth Prithviraj, Darrell H. G. Crawford, Aparna Jayachandran
Summary: Gallbladder cancer is a highly aggressive form of biliary tract cancer, and current clinical trials are examining the effectiveness of immune checkpoint inhibitors as monotherapy. However, only select patients respond to these treatments. This study investigates the molecular mechanisms that contribute to resistance to immune checkpoint blockade and identifies epithelial-to-mesenchymal transition and cancer stem cells as key factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Elizabeth M. Brunt, Andrew D. Clouston, Zachary Goodman, Cynthia Guy, David E. Kleiner, Carolin Lackner, Dina G. Tiniakos, Aileen Wee, Matthew Yeh, Wei Qiang Leow, Elaine Chng, Yayun Ren, George Goh Boon Bee, Elizabeth E. Powell, Mary Rinella, Arun J. Sanyal, Brent Neuschwander-Tetri, Zobair Younossi, Michael Charlton, Vlad Ratziu, Stephen A. Harrison, Dean Tai, Quentin M. Anstee
Summary: The study reveals poor agreement among expert hepatopathologists regarding the number of ballooned hepatocytes seen on the same digitized histology images. This has implications for the diagnosis of nonalcoholic steatohepatitis (NASH) and the requirements for demonstrating 'NASH resolution' in support of drug efficacy in clinical trials. Artificial intelligence-based approaches may offer a more reliable way to assess hepatocyte ballooning.
JOURNAL OF HEPATOLOGY
(2022)
Review
Oncology
Daniel A. Butcher, Kelli J. Brandis, Haolu Wang, Liam Spannenburg, Kim R. Bridle, Darrell HG. Crawford, Xiaowen Liang
Summary: The aim of this meta-analysis was to evaluate the effect of pre-liver transplantation transarterial chemoembolisation (TACE) on long-term survival and complications of hepatocellular carcinoma (HCC) patients. The study found that patients treated with TACE had similar outcomes to non-TACE patients, but they had worse prognostic features.
Article
Gastroenterology & Hepatology
Rish K. Pai, Vipul Jairath, Malcolm Hogan, Guangyong Zou, Oyedele A. Adeyi, Quentin M. Anstee, Bashar A. Aqel, Cynthia Behling, Elizabeth J. Carey, Andrew D. Clouston, Kathleen Corey, Brian G. Feagan, David E. Kleiner, Christopher Ma, Stefanie C. McFarlane, Mazen Noureddin, Vlad Ratziu, Mark A. Valasek, Zobair M. Younossi, Stephen A. Harrison, Rohit Loomba
Summary: After extensive training and discussion among a group of experienced pathologists, we improved the reliability of multiple existing NAFLD histologic indices and fibrosis staging systems. Hepatocyte ballooning and MDBs showed the strongest correlation with disease activity and were used to develop the expanded NAS. Further validation, including evaluation of responsiveness, is still needed.
Article
Pathology
Vanessa Young, Andrew Clouston, Sophie Corbett-Burns, Peter Russell
INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY
(2023)
Letter
Hematology
Motoko Koyama, Luke Samson, Kathleen S. Ensbey, Shuichiro Takahashi, Andrew D. Clouston, Paul J. Martin, Geoffrey R. Hill
Article
Biochemistry & Molecular Biology
Daniela Goncalves Monteiro, Gautam Rishi, Declan M. Gorman, Guillaume Burnet, Randy Aliyanto, K. Johan Rosengren, David M. Frazer, V. Nathan Subramaniam, Richard J. Clark
Summary: This study investigated the interaction mechanism between the iron homeostatic regulator protein HFE and transferrin receptor 1 (TFR1). Peptides based on the binding interface between HFE and TFR1 were generated and shown to interfere with the HFE/TFR1 interaction. Stabilization of the helical structure of these peptides did not increase their ability to disrupt the HFE/TFR1 interaction. These peptide inhibitors provide useful tools for studying the functional role of HFE in hepcidin regulation.
Review
Pharmacology & Pharmacy
Xin Liu, Haolu Wang, Xinyao Liu, Kim Bridle, Darrell Crawford, Xiaowen Liang
Summary: Immunomodulators can improve the prognostic marker of cholestasis (ALP level) in patients with PSC, especially in those with worse liver function. However, the clinical benefits of immunomodulators are controversial and inconclusive.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Oncology
Charlotte Lemech, Keith Dredge, Darryn Bampton, Edward Hammond, Andrew Clouston, Nigel J. Waterhouse, Amanda C. Stanley, Lucie Leveque-El Mouttie, Grace M. Chojnowski, Andrew Haydon, Nick Pavlakis, Matthew Burge, Michael P. Brown, David Goldstein
Summary: This study evaluated the safety, efficacy, and pharmacodynamics of pixatimod and nivolumab in immunologically cold cancers. The combination therapy showed some antitumor activity in the MSS mCRC cohort, indicating the need for further investigation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Medicine, General & Internal
Anthony J. Deacon, Naeman N. Goetz, Nicholas Weber, Andrew Clouston, Enoka Gonsalkorala, Catherine Baskerville, Barbara Leggett
Summary: Hematological malignancies can cause liver dysfunction through various mechanisms, and paraneoplastic hepatitis is an extremely rare presentation. We present a case of paraneoplastic hepatitis caused by nodular lymphocyte-predominant Hodgkin lymphoma, which improved after treatment.
JOURNAL OF MEDICAL CASE REPORTS
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Rish Pai, Vipul Jairath, Malcolm Hogan, Guangyong Zou, Oyedele Adeyi, Quentin Anstee, Bashar Aqel, Cynthia Behling, Elizabeth Carey, Andrew Clouston, Kathleen Corey, Brian Feagan, David E. Kleiner, Christopher Ma, Stefanie McFarlane, Mazen Noureddin, Vlad Ratziu, Mark Valasek, Zobair Younossi, Stephen Harrison, Rohit Loomba
JOURNAL OF HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Christina Nalkurthi, Wayne A. Schroder, Michelle Melino, Katharine M. Irvine, Melanie Nyuydzefe, Wei Chen, Jing Liu, Michele W. L. Teng, Geoffrey R. Hill, Patrick Bertolino, Bruce R. Blazar, Gregory C. Miller, Andrew D. Clouston, Alexandra Zanin-Zhorov, Kelli P. A. MacDonald
Summary: By administrating a selective ROCK2 inhibitor, the prevention and reversal of hepatic fibrosis can be achieved through its effects on pro-inflammatory immune cell function. This study sheds light on the therapeutic potential of ROCK2 targeting in chronic liver disease and provides insights into the cellular and molecular pathways driving liver fibrosis.
Article
Medicine, Research & Experimental
Marijn A. Scheijde-Vermeulen, Lennart A. Kester, Liset Westera, Bastiaan B. J. Tops, Friederike A. G. Meyer-Wentrup
Summary: This study aimed to evaluate the feasibility of integrating state-of-the-art sequencing techniques and flow cytometry into the diagnostic workup of pediatric lymphoma. The results showed that this integration is not only feasible but also provides additional diagnostic information.
LABORATORY INVESTIGATION
(2024)
Article
Medicine, Research & Experimental
Enrico Berrino, Sara Erika Bellomo, Anita Chesta, Paolo Detillo, Alberto Bragoni, Amedeo Gagliardi, Alessio Naccarati, Matteo Cereda, Gianluca Witel, Anna Sapino, Benedetta Bussolati, Gianni Bussolati, Caterina Marchi
Summary: Formalin-fixed paraffin-embedded (FFPE) samples are crucial for tissue-based analysis in precision medicine, but the quality of these samples can affect the reliability of sequencing data. The use of acid-deprived fixatives guarantees the highest DNA preservation and sequencing performance, enabling more complex molecular profiling of tissue samples.
LABORATORY INVESTIGATION
(2024)
Article
Medicine, Research & Experimental
Roope A. Kallionpaa, Sirkku Peltonen, Kim My Le, Eija Martikkala, Mira Jaaskelainen, Elnaz Fazeli, Pilvi Riihila, Pekka Haapaniemi, Anne Rokka, Marko Salmi, Ilmo Leivo, Juha Peltonen
Summary: This study investigated the immune microenvironment of cutaneous neurofibromas (cNFs) in patients with neurofibromatosis 1 (NF1). The results showed that cNFs have substantial populations of T cells and macrophages, which may be tumor-specific. T cell populations in cNFs were found to be different from those in the skin, and cNFs exhibited lower expression of proteins related to T cell-mediated immunity compared to the skin.
LABORATORY INVESTIGATION
(2024)