Article
Gastroenterology & Hepatology
Taixiong Xue, Lin Yue, Guonian Zhu, Zui Tan, Hongyao Liu, Cailing Gan, Chen Fan, Xingping Su, Yuting Xie, Tinghong Ye
Summary: In this study, a phenylacrylic acid derivative, FA11, was synthesized and found to have excellent antifibrotic activity, making it a potential candidate for the treatment of liver fibrosis.
LIVER INTERNATIONAL
(2023)
Article
Immunology
Ting-Ting Li, Xiao-Wei Su, Lin-Lin Chen, Wan-Nian Zhang, Jun-Ping Zhang, Yan Wang, Wei-Heng Xu
Summary: Hepatic fibrosis is a stage of chronic liver disease that can lead to cirrhosis or liver cancer. The activation of hepatic stellate cells (HSCs) is a crucial event in fibrosis development and inhibiting this activation has been shown to alleviate fibrosis. Roxarsone, an organoarsenic additive used in livestock production, has been found to inhibit HSC activation and improve liver function in a mouse model of fibrosis. These findings suggest that Roxarsone could be a potential treatment for liver fibrosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Chen Shuai, Guo-qing Xia, Fei Yuan, Sheng Wang, Xiong-wen Lv
Summary: CD39 plays a role in alcoholic liver disease by regulating HSC activation and fibrosis development, and its blockade can prevent these processes. The findings suggest that ATP-adenosine signaling is a novel therapeutic target for alcoholic liver disease.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Na Jiang, Jing Zhang, Jian Ping, Lieming Xu
Summary: This article investigates the role of salvianolic acid B (Sal B) in autophagy of hepatic stellate cells (HSCs) in liver fibrosis. The study shows that TGF-beta 1 induces autophagosome formation and flux in HSCs, while Sal B inhibits autophagy and activation of HSCs by suppressing autophagosome formation and flux. Furthermore, Sal B inhibits TGF-beta 1-induced autophagy and activation of HSCs by downregulating the MAPK signaling pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Nutrition & Dietetics
You-Jung Hong, Gil-Hwan Kim, Yongdo Park, Hye-Jin Jo, Min-Woo Nam, Dong-Gu Kim, Hwangeui Cho, Hyun-Joo Shim, Jong-Sik Jin, Hyunsoo Rho, Chang-Yeob Han
Summary: This study demonstrates that Suaeda glauca extract (SGE) has therapeutic effects on liver fibrosis. SGE supplementation reduces liver fibrosis induced by CCl4, decreases HSC activation and inflammation, and improves blood biochemical parameters. The anti-fibrotic effects of SGE are mediated through the inhibition of TGF beta 1-Smad2/3 signaling in HSCs.
Article
Pharmacology & Pharmacy
Zhiyong Li, Zhilei Wang, Fang Dong, Wei Shi, Wenzhang Dai, Jing Zhao, Qiang Li, Zhi-E Fang, Lutong Ren, Tingting Liu, Ziying Wei, Wenqing Mou, Li Lin, Yan Yang, Xiaohe Xiao, Li Ma, Zhaofang Bai
Summary: Liver fibrosis is characterized by abnormal proliferation of connective tissue in the liver due to various pathogenic factors. The study demonstrates that germacrone (GER) can inhibit liver fibrosis by regulating multiple signaling pathways, including reducing ROS release to protect hepatocytes and inhibiting HSC activation through TGF-beta/Smad and apoptosis pathways. GER shows potential as a therapeutic drug for the treatment of liver fibrosis.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Parasitology
Ping Huang, Huihui Ma, Yun Cao, Tingzheng Zhan, Tingting Zhang, Xinyi Wang, Yanan Zhang, Jing Xu, Chaoming Xia
Summary: This study demonstrates the crucial role of hepatic stellate cells (HSCs) regulated by the TGF-beta 1/Smad signaling pathway in liver fibrosis during Schistosoma japonicum infection.
PARASITES & VECTORS
(2022)
Review
Immunology
Mahima Kapoor, Subashchandrabose Chinnathambi
Summary: Tau protein is involved in Alzheimer's disease due to its detachment from microtubules and formation of insoluble intracellular aggregates. Recent studies indicate the expulsion of Tau seeds in the extracellular domain and their prion-like spread between neurons. The cytokine Transforming Growth Factor-beta 1 (TGF-beta 1) plays a role in immunomodulation and neuroprotection in the brain and is also involved in cytoskeletal reorganization. Targeting extracellular Tau using TGF-beta-triggered microglia-mediated approach could be a strategy to combat Alzheimer's disease.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Pharmacology & Pharmacy
Bingbing Zhao, Siwei Li, Zuoming Guo, Zhe Chen, Xinying Zhang, Changqing Xu, Junting Chen, Can Wei
Summary: The study showed that DRD2 inhibition can reduce oxidative damage and fibrotic proliferation in diabetic HSCs, partially through the TGF-beta 1/Smads and NF kappa B pathways.
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Shiwei Wang, Lingling He, Fan Xiao, Meixin Gao, Herui Wei, Junru Yang, Yang Shu, Fuyang Zhang, Xiaohui Ye, Ping Li, Xiaohua Hao, Xingang Zhou, Hongshan Wei
Summary: GLT25D1 is upregulated in hepatic stellate cells (HSCs) during liver fibrosis and promotes the progression of fibrosis by affecting HSC activation and collagen stability.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Article
Medicine, Research & Experimental
Jing Zhang, Na Jiang, Jian Ping, Lieming Xu
Summary: The study reveals that TGF-beta 1 can induce HSCs activation and enhance autophagy flux, which can be reversed by inhibiting autophagy or MAPK signaling pathways, suggesting that TGF-beta 1-induced autophagy is involved in the activation of JS1 cells via ERK and JNK signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Mahendra Jadhao, Chun-Lin Chen, Wangta Liu, Dhanashri Deshmukh, Wei-Ting Liao, Jeff Yi-Fu Chen, Ritesh Urade, Eing-Mei Tsai, Sheng-Kai Hsu, Li-Fang Wang, Chien-Chih Chiu
Summary: This study investigated the impact of phthalate exposure on angiogenesis in triple-negative breast cancer cells. The findings revealed that exposure to phthalates induced angiogenesis in breast cancer cells. Additionally, the overexpression of the glycoprotein endoglin (ENG) was found to be associated with tumor development and growth, and knocking down ENG inhibited phthalate-induced angiogenesis. Targeting ENG could potentially serve as an alternative treatment for controlling angiogenesis, limiting metastasis, and inhibiting cancer progression.
Review
Gastroenterology & Hepatology
Tatjana Seitz, Claus Hellerbrand
Summary: Hepatic fibrosis is a protective response to liver injury, but persistent damaging mechanisms can lead to liver fibrosis and eventual cirrhosis. Cirrhosis is a major risk factor for hepatocellular cancer, and treating hepatic fibrosis remains a challenge.
LIVER INTERNATIONAL
(2021)
Article
Pharmacology & Pharmacy
Shirong Li, Anjian Xu, Yanmeng Li, Chunting Tan, Giuseppe La Regina, Romano Silvestri, Haoyan Wang, Wenjie Qi
Summary: The study demonstrated that RS4651 alleviates BLM-induced pulmonary fibrosis in mice by inhibiting the TGF-beta 1/SMAD signaling pathway. RS4651 administration decreased collagen deposition and alpha-SMA levels in the lungs of mice, while inhibiting proliferation and migration of MRC-5 cells, as well as alpha-SMA and pSMAD2 expression. RNA-sequencing data identified SMAD7 as the target gene, and further experiments showed that RS4651 upregulates SMAD7 expression to inhibit fibrosis progression.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Qing-song Chen, Ai Shen, Jiang-wen Dai, Ting-ting Li, Wei-feng Huang, Kun Shi, Yi Deng, Long Pan, Xu-fu Wei, Zhong-jun Wu
Summary: The study revealed that IL37 can alleviate hepatic ischemia reperfusion injury by modulating autophagy and apoptosis, potentially through the regulation of the AMPK/mTOR/ULK1 signaling complex.
Letter
Gastroenterology & Hepatology
Ralf Weiskirchen
Article
Chemistry, Multidisciplinary
Okan Tezcan, Asmaa Said Elshafei, Karina Benderski, Elena Rama, Maike Wagner, Diana Moeckel, Robert Pola, Michal Pechar, Tomas Etrych, Saskia von Stillfried, Fabian Kiessling, Ralf Weiskirchen, Steffen Meurer, Twan Lammers
Summary: Multidrug resistance (MDR) reduces the efficacy of chemotherapy by inducing drug efflux pumps and altering the tumor microenvironment (TME) composition, limiting drug delivery. Multidrug-resistant tumors displayed a more mesenchymal phenotype, increased collagen production, enriched TME, and enhanced vascular perfusion. Drug carriers accumulated more efficiently in resistant tumors but had a limited ability to penetrate the interstitium. Microenvironmental drug resistance affected liposomal doxorubicin performance more than free doxorubicin.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Nutrition & Dietetics
Bodo C. C. Melnik, Swen Malte John, Pedro Carrera-Bastos, Loren Cordain, Claus Leitzmann, Ralf Weiskirchen, Gerd Schmitz
Summary: This review evaluates the impact of cow milk on breast carcinogenesis by linking recent epidemiological evidence and new insights into the molecular signaling of milk and its constituents in breast cancer pathogenesis. Recent prospective cohort studies support the association between cow's milk consumption and the risk of estrogen receptor-alpha-positive breast cancer. Milk contains various components that can increase systemic insulin-like growth factor 1, insulin, and estrogen signaling, promoting breast cancer. Potential oncogenic components of commercial milk include exosomal microRNAs, bovine meat and milk factors, aflatoxin M1, bisphenol A, pesticides, and micro- and nanoplastics. Individuals with certain gene mutations and genetic polymorphisms may be at increased risk for milk-induced breast cancer.
CURRENT NUTRITION REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Bodo C. Melnik, Rudolf Stadler, Ralf Weiskirchen, Claus Leitzmann, Gerd Schmitz
Summary: Epidemiological evidence suggests a link between cow's milk consumption and the risk of DLBCL. This review explores the role of milk-related agents, such as milk-derived exosomes (MDEs) and their microRNAs (miRs), in lymphomagenesis. MDE miRs during breastfeeding can upregulate BCL6 and suppress BLIMP1, promoting B cell proliferation. After weaning, the decline in MDE miR signaling leads to a decrease in BCL6 expression and an increase in BLIMP1-mediated B cell maturation. However, the consumption of pasteurized cow's milk in adults may maintain high BLC6/BLIMP1 ratio and facilitate B cell de-differentiation, potentially contributing to B cell lymphomagenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Guoxun Chen, Sabine Weiskirchen, Ralf Weiskirchen
Summary: Vitamin A is a micronutrient that plays crucial roles in vision, cell growth, reproduction, and immunity. Deficiency and excess consumption of vitamin A both have severe health consequences. Despite being the first lipophilic vitamin discovered over a century ago and the definition of its biological roles, there are still unresolved issues related to vitamin A.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Immunology
Sandro Capellmann, Roland Sonntag, Herdit Schueler, Steffen K. Meurer, Lin Gan, Marlies Kauffmann, Katharina Horn, Hiltrud Koenigs-Werner, Ralf Weiskirchen, Christian Liedtke, Michael Huber
Summary: Mast cells (MCs) are heterogeneous immune cells with different protease repertoires and receptor expressions. A new cell line, PMC-306, derived from primary peritoneal MCs, can be used to study PMC function and tumorigenic processes associated with MC leukemia.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Cell Biology
Ralf Weiskirchen
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Erawan Borkham-Kamphorst, Steffen K. Meurer, Ralf Weiskirchen
Summary: The CCN protein family plays important biological functions in cell adhesion, migration, cell cycle progression, and control of extracellular matrix production and degradation. In the liver, CCN proteins are particularly involved in hepatic injury, disease, and remodeling. This study focused on CCN5/WISP2 and found that it is highly expressed in hepatic stellate cells, myofibroblasts, and portal myofibroblasts, while it is absent in hepatocytes. CCN5 upregulation during hepatic fibrosis induces endoplasmic reticulum stress, unfolded protein response, and apoptosis in portal myofibroblasts, potentially acting as a control mechanism against excessive fibrotic responses.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Kiara Gaeberlein, Sarah K. Schroeder, Indrajit Nanda, Claus Steinlein, Thomas Haaf, Eva M. Buhl, Patrick Sauvant, Vincent Sapin, Armand Abergel, Ralf Weiskirchen
Summary: The rat hepatic stellate cell line PAV-1, established two decades ago, is a cellular model for studying hepatic retinoic acid metabolism. Despite being able to store retinyl esters and synthesize retinoic acid, this cell line has been overlooked. Genetically characterized established cell lines, like PAV-1, are valuable for biomedical research as working with in vivo models becomes more complicated.
Review
Cell Biology
Sabine Weiskirchen, Sarah K. K. Schroeder, Eva Miriam Buhl, Ralf Weiskirchen
Summary: The cultivation of cells in a favorable artificial environment has become an essential tool in cellular and molecular biology research. However, cell lines are often affected by misidentification, contamination, and specific biological and chemical hazards. This review offers an introduction to common problems encountered in cell culture laboratories and provides guidelines for preventing and addressing these issues.
Review
Biochemistry & Molecular Biology
Isabella Lurje, Nadine T. Gaisa, Ralf Weiskirchen, Frank Tacke
Summary: Fibrosis, a pathological scar tissue formation, can occur in various organs due to different etiologies and contributes to global morbidity and mortality. Common mechanisms involve sustained injury to parenchymal cells triggering a deregulated wound healing response. The transformation of fibroblasts into myofibroblasts with excessive extracellular matrix production is a hallmark of the disease, along with complex cellular interactions involving immune cells, endothelial cells, and parenchymal cells. Mediators such as growth factors, cytokines, and danger-associated molecular patterns play important roles in fibrosis across organs.
MOLECULAR ASPECTS OF MEDICINE
(2023)
Article
Cell Biology
Julia Otto, Anna Verwaayen, Christian Penners, Jana Hundertmark, Cheng Lin, Carina Kallen, Daniela Paffen, Tobias Otto, Hilmar Berger, Frank Tacke, Ralf Weiskirchen, Yulia A. Nevzorova, Matthias Bartneck, Christian Trautwein, Roland Sonntag, Christian Liedtke
Summary: Hepatocellular carcinoma (HCC) is a severe malignancy with limited treatment options. The development of HCC involves chronic liver inflammation and liver fibrosis. This study reveals the role of Cyclin E1 (CCNE1) and Cdk2 genes in Hepatic Stellate Cells (HSCs) in liver fibrogenesis and hepatocarcinogenesis.
CELL DEATH & DISEASE
(2023)
Review
Immunology
Sarah K. Schroeder, Natalie Gasterich, Sabine Weiskirchen, Ralf Weiskirchen
Summary: Human 25-kDa Lipocalin 2 (LCN2) was initially thought to be a circulating protein that transports small lipophilic molecules. However, further studies have shown its bacteriostatic properties, involvement in innate immunity, and regulation of various biological processes. The understanding of LCN2 receptors and their mechanisms is still lacking.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marinela Krizanac, Paola Berenice Mass Sanchez, Sarah K. Schroeder, Ralf Weiskirchen, Anastasia Asimakopoulos
Summary: Perilipin 5 (PLIN5) is a lipid droplet coat protein highly expressed in oxidative tissues. It is regulated by peroxisome proliferator-activated receptors (PPARs) and cellular lipid status. Previous research focused on its role in non-alcoholic fatty liver disease (NAFLD) and lipid metabolism regulation. Limited studies connected PLIN5 to hepatocellular carcinoma (HCC), where its expression is upregulated. This study explores the regulation of PLIN5 by cytokines involved in HCC and NAFLD progression, revealing IL-6-induced upregulation mediated by the JAK/STAT3 signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Gastroenterology & Hepatology
Ralf Weiskirchen