Article
Gastroenterology & Hepatology
Michelle M. Cooley, Diana D. H. Thomas, Kali Deans, Yajing Peng, Aurelia Lugea, Stephen J. Pandol, Luigi Puglielli, Guy E. Groblewski
Summary: The study demonstrated that down-regulation of AT-1 during pancreatitis leads to chronic ER stress and pancreatic inflammation. Loss of AT-1 induces activation of unfolded protein response pathways and causes pancreatic disease characterized by intracellular trypsin accumulation, immune cell infiltration, and fibrosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mate Sandor, Franziska G. Thiel, Margit Schmid, Alexandra Demcsak, Nataly C. Morales Granda, Balazs Csaba Nemeth, Sandor Vajda, Andre Hoerning, Miklos Sahin-Toth
Summary: Inborn mutations in the CPA1 gene may lead to misfolding of the protein and are associated with chronic pancreatitis. A novel mutation, p.G250A, was identified in a patient with pancreatic disorder, and its functional properties were similar to another mutation, p.N256K, confirming its pathogenic nature. These mutations result in reduced secretion of CPA1 and endoplasmic reticulum stress. Mutations affecting a specific loop in the protein structure exhibit secretion defects and ER stress in varying degrees, and the severity of ER stress correlates with the secretion defect.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Makoto Kawamoto, Shiro Kohi, Toshiya Abe, Mohamad Dbouk, Anne Macgregor-Das, Chiho Koi, Ki-Byung Song, Michael Borges, Ryo Sugimine, Daniel Laheru, Ralph H. Hruban, Nicholas Roberts, Alison P. Klein, Michael Goggins
Summary: Rare variants in CPB1 and CPA1 that induce endoplasmic reticulum (ER) stress are associated with increased odds of developing pancreatic cancer. Meta-analysis showed strong associations for both CPA1 and CPB1 ER-stress inducing variants with pancreatic cancer risk.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Wenrun Cai, Xugang Sun, Fanjie Jin, Di Xiao, Hui Li, Huizhi Sun, Yifei Wang, Yang Lu, Jing Liu, Chongbiao Huang, Xiuchao Wang, Song Gao, Hongwei Wang, Chuntao Gao, Tiansuo Zhao, Jihui Hao
Summary: CAFs in PDAC promote tumor angiogenesis through MEndoT, with their phenotypic transition being regulated by the PERK-eIF2 alpha-ERK1/2 axis. Pharmacological inhibition of PERK may limit the transition of CAFs, suggesting they could be therapeutic targets for improving PDAC prognosis.
Article
Cell Biology
Shaogui Wang, Xiaojuan Chao, Xiaoxiao Jiang, Tiantian Wang, Yssa Rodriguez, Ling Yang, Pal Pacher, Hong-Min Ni, Wen-Xing Ding
Summary: VMP1 plays a crucial role in the pathogenesis of pancreatitis by regulating autophagic degradation and ER stress, and its deficiency promotes inflammation and fibrosis. The study revealed the importance of VMP1 in modulating pancreatitis through the NFE2L2/Nrf2 pathway.
Article
Cell Biology
Laura L. de Freitas Chama, Frederic Ebstein, Birthe Wiesrecker, Preshit R. Wagh, Elke Hammer, Frank U. Weiss, Heike Junker, Maja Studencka-Turski, Markus M. Lerch, Elke Krueger, Matthias Sendler
Summary: Acute pancreatitis is characterized by severe systemic inflammatory response and immunoproteasome plays a protective role by clearing damaged proteins and balancing ER stress responses in the pancreas.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Kailin Li, Ji Bian, Yao Xiao, Da Wang, Lin Han, Caian He, Lan Gong, Min Wang
Summary: In recent years, there has been a significant increase in age-related diseases worldwide due to longer life expectancy. The aging pancreas undergoes various morphological and pathological changes, which can predispose individuals to diseases such as diabetes, dyspepsia, pancreatic ductal adenocarcinoma, and pancreatitis. Pancreatic senescence is associated with underlying factors including genetic damage, DNA methylation, endoplasmic reticulum stress, mitochondrial dysfunction, and inflammation. This review article discusses the alterations in morphologies and functions of the aging pancreas, particularly beta-cells, and summarizes the mechanisms of pancreatic senescence to identify potential targets for treating aging-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Charles P. Hinzman, Baldev Singh, Shivani Bansal, Yaoxiang Li, Anton Iliuk, Michael Girgis, Kelly M. Herremans, Jose G. Trevino, Vijay K. Singh, Partha P. Banerjee, Amrita K. Cheema
Summary: Cancer-derived extracellular vesicles (cEVs) play a crucial role in promoting cancer progression. This study found that cEVs can be readily internalized by normal cells and induce endoplasmic reticulum stress and protein response. Furthermore, cEVs can increase cell proliferation, migration, and invasion, regulated in part by certain biological molecules.
JOURNAL OF EXTRACELLULAR VESICLES
(2022)
Review
Biochemistry & Molecular Biology
Anna C. Lilly, Igor Astsaturov, Erica A. Golemis
Summary: Pancreatic cancer is difficult to detect and treat, resulting in poor survival outcomes. The increasing incidence of this cancer is related to aging populations, obesity, and pancreatitis. Risk factors for pancreatic cancer include signaling from fat cells, elevated levels of intrapancreatic adipocytes, inflammation from immune cells, and fibrosis caused by pancreatic obstruction and cell lysis. Further studies are needed to understand the role of adipocytes in the pre-cancerous niche and their implications in mouse models.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yixuan Zhang, Jianzhuang Wu, Yao Fu, Ranran Yu, Haochen Su, Qisi Zheng, Hao Wu, Siqi Zhou, Kun Wang, Jing Zhao, Shanshan Shen, Guifang Xu, Lei Wang, Chao Yan, Xiaoping Zou, Ying Lv, Shu Zhang
Summary: This study identified Hesperadin as a potent anti-cancer compound against pancreatic cancer (PC) by inhibiting cell growth and inducing apoptotic cell death. Mechanistic studies revealed that Hesperadin increased GADD45A expression via ATF4, leading to apoptosis. Immunohistochemical staining demonstrated the correlation between ATF4 and GADD45A expression. PC xenograft studies confirmed the inhibitory effect of Hesperadin on PC cell growth in vivo.
Article
Multidisciplinary Sciences
Balazs Csaba Nemeth, Alexandra Demcsak, Andrea Geisz, Miklos Sahin-Toth
Summary: This study found that the transcription factor DDIT3/CHOP does not play a significant role in the development of misfolding-induced chronic pancreatitis in CPA1 N256K mice, indicating it is not a viable therapeutic target.
SCIENTIFIC REPORTS
(2022)
Review
Cell Biology
Ana P. Kutschat, Steven A. Johnsen, Feda H. Hamdan
Summary: PDAC has a poor prognosis and low survival rate due to late diagnosis and chemotherapy resistance. Genomic aberrations and epigenomic changes shift cellular signaling response in pancreatic tumors. Genetic amplifications can reroute calcium signaling and confer malignant attributes to tumors.
Article
Oncology
Tao Wang, Ping Chen, Scott Weir, Michael Baltezor, Frank J. J. Schoenen, Qi Chen
Summary: Compound C150 has been found to inhibit epithelial-to-mesenchymal transition in pancreatic cancer cells by inducing endoplasmic reticulum stress and increasing proteasome activity. It also induces G2/M cell cycle arrest, inhibits cell proliferation, and reduces tumor growth and ascites occurrence in a mouse model.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Roberto Beteta-Gobel, Marc Miralles, Javier Fernandez-Diaz, Raquel Rodriguez-Lorca, Manuel Torres, Paula Fernandez-Garcia, Pablo Escriba, Victoria Llado
Summary: Pancreatic cancer is a highly lethal disease with aggressive behavior and high metastatic potential. The lack of effective treatments and early detection methods makes it a major challenge in the field of oncology. Melitherapy, a novel therapeutic approach based on modifying cell membranes, has shown promise in treating various diseases, including cancer. 2-hydroxycervonic acid (HCA), a melitherapeutic agent, has been developed to induce apoptosis and cell death in pancreatic cancer cells. In vivo studies have demonstrated the efficacy of HCA, both alone and in combination with gemcitabine, without apparent toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Wang Xiao, Rong-Chang Cao, Wan-Jun Yang, Jie-Hui Tan, Ruo-Qi Liu, He-Ping Kan, Lei Zhou, Na Zhang, Zhi-Ye Chen, Xue-Mei Chen, Jia Xu, Guo-Wei Zhang, Peng Shen
Summary: This study aimed to investigate the prognostic value of endoplasmic reticulum (ER) stress-related and apoptosis-related genes in pancreatic cancer (PC) patients. The results demonstrated that upregulation of ATF6 and downregulation of EMC6 and APAF1 were associated with poor prognosis in PC patients, suggesting that these genes may serve as potential therapeutic targets.
FRONTIERS IN GENETICS
(2022)
Article
Cardiac & Cardiovascular Systems
Michael Harris, Junhui Sun, Karen Keeran, Angel Aponte, Komudi Singh, Danielle Springer, Marjan Gucek, Mehdi Pirooznia, Matthew E. Cockman, Elizabeth Murphy, Leslie M. Kennedy
Summary: This study demonstrates that deletion of Ogfod1 alters the myocardial proteome and metabolome, providing protection against ischemia-reperfusion injury.
CARDIOVASCULAR RESEARCH
(2022)
Article
Neurosciences
Dillon J. Chung, Grey P. Madison, Angel M. Aponte, Komudi Singh, Yuesheng Li, Mehdi Pirooznia, Christopher K. E. Bleck, Nissar A. Darmani, Robert S. Balaban
Summary: Mitochondrial adaptations are essential for cell function and energy balance in mammals, but the mechanisms behind these adaptations are still poorly understood. In this study, we used a model of extreme mammalian metabolism, the least shrew, to investigate mitochondrial morphology and protein composition in different organs. We found that organs with similar metabolic demand have distinct mitochondrial adaptations, suggesting that the topology of energy utilization plays a role in these adaptations.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Cell Biology
Junfang Lyu, Mehdi Pirooznia, Yuesheng Li, Jianhua Xiong
Summary: Normal tissue and organ morphogenesis require epithelial cell plasticity and conversion to a mesenchymal phenotype through a process known as epithelial-to-mesenchymal transition (EMT). This study demonstrates that EMT induced by transforming growth factor beta (TGF-beta) is accompanied by reduced fatty acid oxidation (FAO) and decreased levels of acetyl-coenzyme A (acetyl-CoA). Acetate, a short-chain fatty acid, effectively inhibits EMT and cancer cell migration by increasing acetyl-CoA levels and restoring α-tubulin acetylation. These findings suggest that acetate is a potent metabolic regulator of EMT and targeting acetate metabolism could have therapeutic potential for EMT-related pathological conditions.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Hematology
Clare Sun, Chen Yun-Ching, Aina Martinez Zurita, Maria Joao Baptista, Stefania Pittaluga, Delong Liu, Daniel Rosebrock, Satyen Harish Gohil, Nakhle S. Saba, Theresa Davies-Hill, Sarah E. M. Herman, Gad Getz, Mehdi Pirooznia, Catherine J. Wu, Adrian Wiestner
Summary: In CLL, oncogenic processes are upregulated in the lymph nodes and in cases with unmutated IGHV region. Single-cell RNA sequencing reveals 3 major cell states in CLL: quiescent, activated, and proliferating. Activated tumor cells are associated with inferior treatment-free survival and the presence of activated CD4+ memory T cells and M2 macrophages in the lymph nodes. Clonal evolution occurs in approximately half of the patients, but is not associated with AICDA expression. However, a T-cell inflamed microenvironment in the lymph nodes is associated with clonal stability.
Article
Oncology
Sho Okuda, Kenoki Ohuchida, Koji Shindo, Taiki Moriyama, Jun Kawata, Koji Tamura, Masafumi Sada, Kinuko Nagayoshi, Yusuke Mizuuchi, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura
Summary: The main risk factor for recurrence of esophageal squamous cell carcinoma (ESCC) after surgery is LY, and the combination of LY and pathologic lymph node metastasis (pN) leads to a higher recurrence rate. Patients with LY before surgery following neoadjuvant chemotherapy (NAC) may require adjuvant treatment postoperatively.
Article
Hematology
Jack Chovanec, Ilker Tunc, Jason Hughes, Joseph Halstead, Allyson Mateja, Yihui Liu, Michael P. O'Connell, Jiwon Kim, Young Hwan Park, Qinlu Wang, Quang Le, Mehdi Pirooznia, Neil N. Trivedi, Yun Bai, Yuzhi Yin, Amy P. Hsu, Joshua McElwee, Sheryce Lassiter, Celeste Nelson, Judy Bandoh, Thomas DiMaggio, Julij Selb, Matija Rijavec, Melody C. Carter, Hirsh D. Komarow, Vito Sabato, Joshua Steinberg, Kurt M. Hafer, Elizabeth Feuille, Christopher S. Hourigan, Justin Lack, Paneez Khoury, Irina Maric, Roberta Zanotti, Patrizia Bonadonna, Lawrence B. Schwartz, Joshua D. Milner, Sarah C. Glover, Didier G. Ebo, Peter Korosec, George H. Caughey, Erica H. Brittain, Ben Busby, Dean D. Metcalfe, Jonathan J. Lyons
Summary: Basal serum tryptase (BST) levels >20 ng/mL are a minor criterion for the diagnosis of systemic mastocytosis. Genetic trait H alpha T leads to elevated BST levels due to overexpression of TPSAB1 gene. The study provides personalized clinical reference values and demonstrates the clinical utility of tryptase genotyping.
Letter
Gastroenterology & Hepatology
Kinuko Nagayoshi, Yusuke Mizuuchi, Koji Tamura, Masafumi Sada, Kohei Nakata, Kenoki Ohuchida, Masafumi Nakamura
COLORECTAL DISEASE
(2023)
Article
Cell Biology
Helen Eachus, Lara Oberski, Jack Paveley, Irina Bacila, John-Paul Ashton, Umberto Esposito, Fayaz Seifuddin, Mehdi Pirooznia, Eran Elhaik, Marysia Placzek, Nils P. Krone, Vincent T. Cunliffe
Summary: This article investigates glucocorticoid resistance commonly observed in depression, which has been linked to reduced expression and/or function of the glucocorticoid receptor (GR). By comparing the brain methylomes and transcriptomes of wild-type and GR-mutant zebrafish, the authors identify 249 differentially methylated regions (DMRs) regulated by GR. They also find GR-regulated genes associated with chaperone-mediated protein folding, circadian rhythm regulation, metabolism regulation, and behavior, which are known to be related to unipolar depression and anxiety. The findings provide insights into the molecular mechanisms through which GR mediates stress responses in the adult zebrafish brain and support the use of the zebrafish GR mutant as a model for studying affective disorders.
DISEASE MODELS & MECHANISMS
(2023)
Article
Orthopedics
Sayuri Hayashida, Naoki Ikenaga, Kohei Nakata, So Nakamura, Toshiya Abe, Noboru Ideno, Makoto Endo, Shoko Noguchi, Yoshinao Oda, Masafumi Nakamura
Summary: A case report of a patient with extraskeletal mesenchymal chondrosarcoma undergoing multiple robotic pancreatectomies for recurrent pancreatic metastasis, achieving successful outcomes.
ASIAN JOURNAL OF ENDOSCOPIC SURGERY
(2023)
Article
Surgery
Koji Tamura, Takashi Ueki, Hiromichi Nakayama, Yusuke Watanabe, Masafumi Sada, Kinuko Nagayoshi, Yusuke Mizuuchi, Kenoki Ohuchida, Hitoshi Ichimiya, Masafumi Nakamura
Summary: The purpose of this study was to evaluate the treatment strategy for appendiceal tumors (ATs), including laparoscopic surgery (LS), and identify preoperative predictors of malignancy. The study found that clinical symptoms, tumor markers, and imaging features can serve as predictors of malignancy. LS is a feasible and effective method for the diagnosis and treatment of ATs.
LANGENBECKS ARCHIVES OF SURGERY
(2023)
Article
Surgery
Yusuke Mizuuchi, Yoshitaka Tanabe, Masafumi Sada, Koji Tamura, Kinuko Nagayoshi, Shuntaro Nagai, Yusuke Watanabe, Sadafumi Tamiya, Kenoki Ohuchida, Kohei Nakata, Toru Nakano, Masafumi Nakamura
Summary: This study aims to determine the predictive value of N3 nodal involvement in patients with Stage III colon cancer (CC) and whether its prognostic implications vary with tumor location. The results showed that N3 lymph node metastasis is an independent predictor of poor prognosis in Stage III CC patients, and the risk of recurrence varies by tumor location, with N3 right-sided CCs having poorer prognoses than N3 left-sided CCs.
LANGENBECKS ARCHIVES OF SURGERY
(2023)
Meeting Abstract
Critical Care Medicine
B. P. Matthew, A. Lebron, Y. Chen, M. Pirooznia, S. Rollison, T. A. Worthy, A. M. Jones, P. Julien-Williams, M. Y. Chen, J. Moss, H. Wen
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
T. E. Andargie, I. Tunc, K. Singh, F. Seifuddin, H. Kong, M. Pirooznia, M. Jang, S. Agbor-Enoh
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Medicine, Research & Experimental
Jing Wu, Komudi Singh, Amy Lin, Allison M. Meadows, Kaiyuan Wu, Vivian Shing, Maximilian Bley, Shahin Hassanzadeh, Rebecca D. Huffstutler, Mark S. Schmidt, Luz P. Blanco, Rong Tian, Charles Brenner, Mehdi Pirooznia, Mariana J. Kaplan, Michael N. Sack
Summary: This study reveals that nicotinamide riboside (NR) can suppress autophagy and attenuate type I interferon (IFN-beta) release in myeloid cells, exerting anti-inflammatory effects. The mechanism of action involves NR's dependency on NAD(+) and its modulation of inosine signaling. These findings suggest NR as a potential adjunct for the management of systemic lupus erythematosus (SLE).
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biotechnology & Applied Microbiology
Bohu Pan, Luyao Ren, Vitor Onuchic, Meijian Guan, Rebecca Kusko, Steve Bruinsma, Len Trigg, Andreas Scherer, Baitang Ning, Chaoyang Zhang, Christine Glidewell-Kenney, Chunlin Xiao, Eric Donaldson, Fritz J. Sedlazeck, Gary Schroth, Gokhan Yavas, Haiying Grunenwald, Haodong Chen, Heather Meinholz, Joe Meehan, Jing Wang, Jingcheng Yang, Jonathan Foox, Jun Shang, Kelci Miclaus, Lianhua Dong, Leming Shi, Marghoob Mohiyuddin, Mehdi Pirooznia, Ping Gong, Rooz Golshani, Russ Wolfinger, Samir Lababidi, Sayed Mohammad Ebrahim Sahraeian, Steve Sherry, Tao Han, Tao Chen, Tieliu Shi, Wanwan Hou, Weigong Ge, Wen Zou, Wenjing Guo, Wenjun Bao, Wenzhong Xiao, Xiaohui Fan, Yoichi Gondo, Ying Yu, Yongmei Zhao, Zhenqiang Su, Zhichao Liu, Weida Tong, Wenming Xiao, Justin M. Zook, Yuanting Zheng, Huixiao Hong
Summary: This study systematically evaluates the reproducibility of inherited variants with whole genome sequencing (WGS) and identifies the impact of different factors on variant call quality. The findings show that bioinformatics pipelines have a larger impact on reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs) are more reproducible than small insertions and deletions (indels), and increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30x.