Review
Cell Biology
Zhilin Zhang, Huan Zhang, Tian Liu, Tian Chen, Daorong Wang, Dong Tang
Summary: Pancreatic cancer is associated with strong therapeutic resistance and poor prognosis, with activated pancreatic stellate cells (PSC) playing a crucial role in the malignant progression. By analyzing PSC population heterogeneity, researchers have identified two subtypes - myofibroblastic and inflammatory PSC - that cooperate to create a microenvironment suitable for cancer cell survival, potentially offering more effective treatment options for pancreatic cancer patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jianwei Fan, Lifang Duan, Nan Wu, Xiaofan Xu, Jiaqi Xin, Shengnan Jiang, Cheng Zhang, Hong Zhang
Summary: Baicalin has been shown to inhibit the activation of pancreatic stellate cells (PSCs), reduce pancreatic inflammation and fibrosis, and decrease the levels of various markers associated with fibrosis in the pancreas. It inhibits the TGF-beta 1/TGF-beta R1/TAK1/NF-kappa B signaling pathway, leading to decreased MCP-1 secretion and reduced infiltration of macrophages and inflammation cells in the pancreas. This study provides a basis for the potential use of baicalin in the prevention and treatment of chronic pancreatitis.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Matias Estaras, Remigio Martinez, Alfredo Garcia, Candido Ortiz-Placin, Juan L. Iovanna, Patricia Santofimia-Castano, Antonio Gonzalez
Summary: Pancreatic stellate cells (PSCs) proliferate actively under hypoxia and melatonin has been shown to modulate cell responses to hypoxia by inhibiting proliferation and reducing fibrosis-related protein expression. The activation of the PI3K/Akt/mTOR pathway and metabolic adaptations in PSCs under hypoxic conditions were investigated in this study. The results suggest that PSCs undergo metabolic changes under hypoxia and melatonin plays a role in modulating these changes.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Physiology
Shin Hamada, Ryotaro Matsumoto, Atsushi Masamune
Summary: Pancreatic stellate cells play a pivotal role in the development of pancreatic fibrosis and cancer by sensing systemic metabolic changes and altering cell metabolism and microenvironment.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Man Chang, Wenjuan Chen, Ruting Xia, Yangyue Peng, Pandi Niu, Hui Fan
Summary: This article reviews the interaction between chronic pancreatitis and pancreatic fibrosis, summarizes the activation mechanisms of pancreatic stellate cells, and investigates potential therapeutic strategies targeting these cells, including anti-fibrosis therapy, antioxidant therapy, and gene therapy.
Article
Endocrinology & Metabolism
Harrison T. Muturi, Hilda E. Ghadieh, Raziyeh Abdolahipour, Hannah L. Stankus, Getachew Debas Belew, James K. Liu, Marziyeh Salehi Jahromi, Abraham D. Lee, Bernhard B. Singer, Isabella Angeli-Pahim, Tejasav S. Sehrawat, Harmeet Malhi, Stefaan Verhulst, Leo A. van Grunsven, Ali Zarrinpar, Sergio Duarte, Sonia M. Najjar
Summary: This study found that loss of endothelial CEACAM1 could lead to hepatic fibrosis, and combined loss of endothelial CEACAM1 and ET1 genes could reverse this process.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Article
Cell Biology
Lara Magni, Rayhana Bouazzi, Hugo Heredero Olmedilla, Patricia S. S. Petersen, Marco Tozzi, Ivana Novak
Summary: The study reveals an important interaction between PSCs and cancer cells, involving ATP and IL-6 as key players, which activate P2X7 and IL-6 receptors, respectively, potentially serving as therapeutic targets for PDAC.
Article
Gastroenterology & Hepatology
Yu Tanaka, Shin Hamada, Ryotaro Matsumoto, Keiko Taguchi, Masayuki Yamamoto, Atsushi Masamune
Summary: Systemic Nrf2 deletion decreases pancreatic cancer progression in a mutant K-ras/p53-expressing mouse model, with pancreatic stellate cells (PSCs) playing a role in this process. Nrf2-deleted PSCs exhibit lower proliferative and migration capacity, and show reduced growth-stimulating effects on pancreatic cancer cells.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Rong Fu, Shi-Jia Zu, Yan-Jun Liu, Jia-Cheng Li, Wen-Zhen Dang, Li-Ping Liao, Li-Ping Liu, Pan-Yu Chen, He-Ming Huang, Kang-Hui Wu, Bing Zhou, Qin Pan, Cheng Luo, Yuan-Yuan Zhang, Guang-Ming Li
Summary: Liver fibrosis is a complex condition involving multiple mechanisms. This study demonstrates that the BET bromodomain inhibitor compound38 can inhibit the signaling pathways in macrophages and hepatic stellate cells, thereby decreasing inflammation and fibrosis in the liver. These findings suggest that compound38 has potential therapeutic effects for liver fibrosis.
Review
Biochemistry & Molecular Biology
Jianhong An, Tingting Jiang, Ling Qi, Keping Xie
Summary: Pancreatic fibrosis is caused by excessive deposition of collagen and fibronectin extracellular matrix in the pancreatic tissue due to repeated injury in chronic pancreatic diseases. The pathophysiology involves acinar cell injury, duct dysfunction, stellate cell activation, and persistent inflammatory response. The role of acinar cells in pancreatic fibrosis and potential clinical significance are discussed.
CYTOKINE & GROWTH FACTOR REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Matias Estaras, Manuel R. Gonzalez-Portillo, Miguel Fernandez-Bermejo, Jose M. Mateos, Daniel Vara, Gerardo Blanco-Fernandez, Diego Lopez-Guerra, Vicente Roncero, Gines M. Salido, Antonio Gonzalez
Summary: The study demonstrates that melatonin at pharmacological concentrations can diminish the proliferation of pancreatic stellate cells subjected to hypoxia by modulating the cell cycle, apoptosis, and the activation of crucial MAPKs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Dakota R. Kamm, Kyle S. McCommis
Summary: Hepatic stellate cells (HSCs) play critical roles in the normal liver and in response to injury. They are activated during liver injury and produce extracellular matrix in liver fibrosis. In the absence of injury, HSCs are in a quiescent state and store retinoids or vitamin A-containing metabolites. They also enhance the inflammatory response and express growth factors crucial for liver development and regeneration. Recent studies have identified diverse phenotypic alterations and unique subpopulations of HSCs.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Review
Pharmacology & Pharmacy
Man Wang, Lei Li, Yannan Xu, Juan Du, Changquan Ling
Summary: Non-alcoholic fatty liver disease (NAFLD) is a common disease due to the global increase in obesity, dyslipidemia, hypertension, and type 2 diabetes mellitus. The role of hepatic stellate cells (HSCs) in inflammation and fibrosis in NAFLD needs further investigation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Wei Peng, Shiwen Zhang, Wei Zhou, Xinchen Zhao, Kexue Wang, Chengxu Yue, Xinyu Wei, Siyan Pang, Wei Dong, Sulian Chen, Changjie Chen, Qingling Yang, Wenrui Wang
Summary: This study evaluated the effect of sorafenib-loaded layered double hydroxide nanocomposite (LDH-SRF) on hepatic stellate cells (HSCs). Results showed that LDH-SRF was efficiently internalized by HSCs and induced apoptosis. Furthermore, LDH-SRF exhibited significantly higher apoptosis rate and migration inhibition rate compared to sorafenib alone. In vivo experiments showed that LDH-SRF reduced inflammatory infiltrate and collagen fiber deposition. The study suggests that LDH-SRF has better anti-fibrotic effect and inhibits the proliferation and activation of HSCs.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Toxicology
Zhiren Li, Di Lu, Tong Jin, Xinjuan Liu, Jianyu Hao
Summary: The research found that nicotine can promote the occurrence of pancreatic fibrosis in chronic pancreatitis by activating pancreatic stellate cells.
TOXICOLOGY LETTERS
(2021)
Article
Surgery
Menghua Dai, Qiaofei Liu, Cheng Xing, Xiaodong Tian, Feng Cao, Wenbo Tang, Shaocheng Lv, Yongsu Ma, Dongxin Zhang, Jorg Kleeff, Yinmo Yang, Rong Liu, Qiang He, Fei Li, Guangming Li, Junchao Guo, Quan Liao, Yupei Zhao
Summary: The study found that early drain removal did not significantly decrease the incidence of grade 2-4 complications for patients undergoing pancreaticoduodenectomy with low or intermediate risk. There were no significant differences between the two groups in terms of comprehensive complication index, B/C grade pancreatic fistula incidence, total medical expenses, and postoperative in-hospital stay.
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.
Review
Pharmacology & Pharmacy
Luca Antonioli, Pal Pacher, Gyorgy Hasko
Summary: The adenosine system plays a crucial role in resolving inflammation by regulating inflammatory cell activity for an effective transition. Pharmacological strategies based on the adenosine system have opened up a new area of research in resolving inflammation.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Marta Alonso-Nocelo, Laura Ruiz-Canas, Patricia Sancho, Kivanc Gorgulu, Sonia Alcala, Coral Pedrero, Mireia Vallespinos, Juan Carlos Lopez-Gil, Marina Ochando, Elena Garcia-Garcia, Sara Maria David Trabulo, Paola Martinelli, Patricia Sanchez-Tomero, Carmen Sanchez-Palomo, Patricia Gonzalez-Santamaria, Lourdes Yuste, Sonja Maria Wormann, Derya Kabacaoglu, Julie Earl, Alberto Martin, Fernando Salvador, Sandra Valle, Laura Martin-Hijano, Alfredo Carrato, Mert Erkan, Laura Garcia-Bermejo, Patrick C. Hermann, Hana Algul, Gema Moreno-Bueno, Christopher Heeschen, Francisco Portillo, Amparo Cano, Bruno Sainz
Summary: LOXL2 plays an important role in pancreatic ductal adenocarcinoma (PDAC), with its loss inhibiting metastasis and prolonging overall survival, while overexpression promotes tumor growth and decreases overall survival. Macrophage-secreted OSM is an inducer of LOXL2 expression, with targeting macrophages affecting its expression and collagen fiber alignment.
Correction
Geriatrics & Gerontology
Mohanraj Rajesh, Partha Mukhopadhyay, Sandor Batkai, Muhammad Arif, Zoltan V. Varga, Csaba Matyas, Janos Paloczi, Andrea Lehocki, Gyorgy Hasko, Pal Pacher
Article
Geriatrics & Gerontology
Mohanraj Rajesh, Partha Mukhopadhyay, Sandor Batkai, Muhammad Arif, Zoltan V. Varga, Csaba Matyas, Janos Paloczi, Andrea Lehocki, Gyorgy Hasko, Pal Pacher
Summary: Diabetes promotes cardiovascular aging and inflammation, which leads to the development of cardiomyopathy/heart failure. CB2 receptor activation can attenuate the pathological changes associated with atherosclerosis, myocardial infarction, stroke, and hepatic cardiomyopathy. In this study, the role of CB2 receptor signaling in myocardial dysfunction, oxidative/nitrative stress, inflammation, cell death, remodeling, and fibrosis associated with diabetic cardiomyopathy was explored in type 1 diabetic mice. CB2 receptor activation can alleviate diabetes-induced myocardial tissue injury and preserve the functional contractile capacity of the myocardium.
Article
Substance Abuse
Shani Abraham, Chad Lindo, Jessica Peoples, Amanda Cox, Erika Lytle, Vu Nguyen, Meeti Mehta, Jose D. Alvarez, Shibu Yooseph, Pal Pacher, Steven N. Ebert
Summary: This study investigates the effects of binge alcohol consumption on gene expression patterns during heart development. The findings suggest that binge drinking disrupts the expression of several genes, particularly transcription factors and signaling molecules. The study identifies Wnt7a as a potential key gene in the development of congenital heart defects caused by maternal binge alcohol consumption.
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Article
Medicine, General & Internal
Artur Rebelo, Jumber Partsakhashvili, Ulrich Ronellenfitsch, Endres John, Joerg Kleeff, Joerg Ukkat
Summary: This study analyzed the outcome of emergency thoracic endovascular aortic repair (TEVAR) in the treatment of primary and secondary aortic pathologies. The results showed that in-hospital mortality and morbidity were still considerable after emergency TEVAR. Pre- and postoperative levels of hemoglobin, creatinine, and lactate may be valuable in predicting patient outcomes.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Health Care Sciences & Services
Yoshiaki Sunami, Ulrich Ronellenfitsch, Jorg Kleeff, Artur Rebelo
Summary: This study aims to evaluate the impact of FAP expression on survival and clinical characteristics in gastrointestinal tumors. A systematic review and meta-analysis will be conducted to compare patients with and without FAP overexpression in terms of postoperative survival, histological differentiation, tumor invasion, lymph node metastases, and distant metastases. The expected results will provide new evidence on the prognostic value of FAP in gastrointestinal tumors.
JMIR RESEARCH PROTOCOLS
(2023)
Review
Oncology
Artur Rebelo, Joerg Kleeff, Yoshiaki Sunami
Summary: This review provides an in-depth understanding of metabolic reprogramming and the mevalonate pathway in pancreatic cancer. It emphasizes the role of cholesterol metabolism in cancer progression and explores potential therapeutic approaches targeting these processes. The review also highlights promising pharmaceutical candidates for pancreatic cancer therapy.
Article
Surgery
Anouk E. J. Latenstein, Lianne Scholten, Hasan Ahmad Al-Saffar, Bergthor Bjornsson, Giovanni Butturini, Giovanni Capretti, Nikolaos A. Chatzizacharias, Chris Dervenis, Isabella Frigerio, Tom K. Gallagher, Silvia Gasteiger, Asif Halimi, Knut J. Labori, Greta Montagnini, Luis Munoz-Bellvis, Gennaro Nappo, Andrej Nikov, Elizabeth Pando, Matteo de Pastena, Jesus M. De La Pena-Moral, Dejan Radenkovic, Keith J. Roberts, Roberto Salvia, Francisco Sanchez-Bueno, Chiara Scandavini, Mario Serradilla-Martin, Stefan Stattner, Ales Tomazic, Martin Varga, Hana Zavrtanik, Alessandro Zerbi, Mert Erkan, Jorg Kleeff, Mickael Lesurtel, Marc G. Besselink, Jose M. Ramia-Angel
Summary: This study analyzed data from patients undergoing total pancreatectomy in 43 centers in 16 European countries, finding an in-hospital mortality rate of 5% and a complication rate of 25%. The study also identified age, blood loss, and surgical center volume as major factors contributing to in-hospital mortality.
Meeting Abstract
Gastroenterology & Hepatology
Buket Yigit, Ekin Ozgonul, Omer Yaman, Burge Ulukan, Yagmur Cetin Tas, Berna Morova, Musa Aydin, Yigit Uysalli, Elif Demirtas, Mert Erkan, Yasemin Gursoy Ozdemir, Sercin Karahuseyinoglu, Cihan Yurdaydin, Murat Akyildiz, Abhishek Sheth, Hale Kirimlioglu, Murat Dayangac, Onur Ferhanoglu, Alper Kiraz, Mujdat Zeybel
JOURNAL OF HEPATOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Thais Gazzi, Benjamin Brennecke, Kenneth Atz, Claudia Korn, David Sykes, Gabriel Forn-Cuni, Patrick Pfaff, Roman C. Sarott, Matthias Westphal, Yelena Mostinski, Leonard Mach, Malgorzata Wasinska-Kalwa, Marie Weise, Bradley L. Hoare, Tamara Miljus, Maira Mexi, Nicolas Roth, Eline J. Koers, Wolfgang Guba, Andre Alker, Arne C. Rufer, Eric A. Kusznir, Sylwia Huber, Catarina Raposo, Elisabeth A. Zirwes, Anja Osterwald, Anto Pavlovic, Svenja Moes, Jennifer Beck, Matthias Nettekoven, Irene Benito-Cuesta, Teresa Grande, Faye Drawnel, Gabriella Widmer, Daniela Holzer, Tom van der Wel, Harpreet Mandhair, Michael Honer, Jurgen Fingerle, Joerg Scheffel, Johannes Broichhagen, Klaus Gawrisch, Julian Romero, Cecilia J. Hillard, Zoltan V. Varga, Mario van der Stelt, Pal Pacher, Jurg Gertsch, Christoph Ullmer, Peter J. McCormick, Sergio Oddi, Herman P. Spaink, Mauro Maccarrone, Dmitry B. Veprintsev, Erick M. Carreira, Uwe Grether, Marc Nazare
Summary: This study reports the development of a novel fluorescent CB2R agonist probe that can detect CB2R in living cells and zebrafish larvae. These findings contribute to the clinical translatability of CB2R-based drugs.
Article
Surgery
Thilo Welsch, Benjamin Muessle, Sandra Korn, Dorothee Sturm, Ulrich Bork, Marius Distler, Xina Graehlert, Anna Klimova, Nicole Trebesius, Axel Kleespies, Stefan Kees, Stefan Beckert, Daniel Reim, Helmut Friess, Malik Elwerr, Joerg Kleeff, Octavian Popescu, Hubertus Schmitz-Winnenthal, Monika Janot-Matuschek, Waldemar Uhl, Georg F. Weber, Maximilian Brunner, Henriette Golcher, Robert Gruetzmann, Juergen Weitz
Summary: This study suggests that a prophylactic falciform ligament wrap may be effective in preventing postpancreatectomy haemorrhage from the hepatic artery or gastroduodenal artery stump.
BRITISH JOURNAL OF SURGERY
(2022)
Article
Oncology
Sebastian Krug, Laura Mattheis, Monika Haemmerle, Jonas Rosendahl, Joerg Kleeff, Patrick Michl
Summary: Patients with Wnt/ss-β-catenin activation may benefit from combination therapy with atezolizumab and bevacizumab regardless of potential predictive markers for immune checkpoint inhibition.