Article
Biochemistry & Molecular Biology
Anna Pieniazek, Michal Kopera, Lukasz Gwozdzinski, Krzysztof Gwozdzinski
Summary: The study found that indoxyl sulfate (IS) can cause oxidative damage and impact the progression of chronic kidney disease (CKD). IS affects oxidative stress parameters and may shorten the lifespan of red blood cells in patients.
Article
Biochemistry & Molecular Biology
Livia Alvarenga, Juliana F. Saldanha, Milena B. Stockler-Pinto, Denis Fouque, Christophe O. Soulage, Denise Mafra
Summary: This study aims to evaluate the effect of resveratrol against the damage caused by indoxyl sulfate (IS) in patients with chronic kidney disease (CKD). The results showed that resveratrol can activate the Nrf2 pathway, enhance cytoprotective response, and alleviate oxidative stress and inflammation induced by IS.
Article
Biochemistry & Molecular Biology
Hsin-Ying Lu, Hung-Lung Hsu, Chih-Han Li, Shao-Jung Li, Shing-Jong Lin, Chun-Ming Shih, Chun-Che Shih
Summary: Research suggests that H2S may inhibit the formation of AD by reducing inflammatory response, oxidative stress, and positively participating in vascular remodeling. These findings provide evidence for H2S as a novel and promising therapeutic strategy to prevent the development of AD.
Article
Medicine, Research & Experimental
Jui M. Dave, Raja Chakraborty, Aglaia Ntokou, Junichi Saito, Fatima Z. Saddouk, Zhonghui Feng, Ashish Misra, George Tellides, Robert K. Riemer, Zsolt Urban, Caroline Kinnear, James Ellis, Seema Mital, Robert Mecham, Kathleen A. Martin, Daniel M. Greif
Summary: In this study, we demonstrated that elastin insufficiency induces epigenetic changes, upregulating the NOTCH pathway in smooth muscle cells (SMCs). These findings provide potential therapeutic targets for supravalvular aortic stenosis (SVAS).
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Cardiac & Cardiovascular Systems
Xichuan Zheng, Qihong Yu, Dan Shang, Chuanzheng Yin, Dawei Xie, Tong Huang, Xiaolong Du, Wenjie Wang, Xueke Yan, Chen Zhang, Wei Li, Zifang Song
Summary: TAK1 signaling pathway plays a crucial role in the proliferation and migration of vascular smooth muscle cells (VSMCs). This study reveals that activation of TAK1 controls autophagy activation and regulates cell cycle, proliferation, and migration responses in VSMCs. This provides a potential molecular mechanism and therapeutic target for preventing transplant vasculopathy.
Review
Biochemistry & Molecular Biology
Chien-Lin Lu, Cai-Mei Zheng, Kuo-Cheng Lu, Min-Tser Liao, Kun-Lin Wu, Ming-Chieh Ma
Summary: The uremic toxin IS leads to oxidative stress in CKD patients, causing organ damage and complications such as cardiovascular diseases, renal osteodystrophy, muscle wasting, and anemia. IS-induced ROS production impairs glomerular filtration and triggers vascular smooth muscle cells transformation, contributing to muscle atrophy and bone abnormalities.
Article
Food Science & Technology
Cindy Nguyen, Amanda J. Edgley, Darren J. Kelly, Andrew R. Kompa
Summary: This study investigates the effects of the uremic toxin indoxyl sulfate (IS) on vascular endothelial function and redox balance. The results indicate that IS impairs endothelium-dependent relaxation and increases the expression of oxidative stress markers. Inhibition of the aryl hydrocarbon receptor (AhR) could be a potential therapy for cardiovascular disease in the context of chronic kidney disease (CKD).
Article
Pathology
Mostafa Belghasem, Wenqing Yin, Saran Lotfollahzadeh, Xiaosheng Yang, Rosana D. Meyer, Marc A. Napoleon, Isaac E. Sellinger, Aniket Vazirani, Elena Metrikova, Asha Jose, Anna Zhebrun, Stephen A. Whelan, Norman Lee, Nader Rahimi, Vipul C. Chitalia
Summary: This study found that tryptophan-derived uremic toxins IS and Kyn mediate tubular toxicity by suppressing TMIGD1 transcription. The loss of TMIGD1 exacerbates tubular injury. In addition, C/EBPD enhances TMIGD1 promoter activity and is correlated with TMIGD1 expression in CKD models, while C/EBPD levels are negatively correlated with IS and Kyn levels.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Hui Zheng, Zhihuang Qiu, Tianci Chai, Jian He, Yuling Zhang, Chaoyun Wang, Jianqiang Ye, Xiaohui Wu, Yumei Li, Li Zhang, Liangwan Chen
Summary: The study found an association between insulin resistance (IR) and aortic dissection (AD). Insulin resistance promotes the occurrence of AD by inducing phenotypic switching of vascular smooth muscle cells. This provides a basis for further research on the mechanism of how IR results in AD and a new approach for the prevention and treatment of AD.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Langtao Wang, Zhen Yang, Sai Wang, Yumei Que, Xi Shu, Fuhua Wu, Gang Liu, Siqi Li, Pingping Hu, Hao Chen, Jian Shi, Xiaoyong Tong
Summary: This study found that the irreversible oxidation of SERCA2 C674 promotes the development of aortic aneurysm by inducing endoplasmic reticulum stress and cell apoptosis. Additionally, ER stress and SERCA2 may be potential therapeutic targets for treating aortic aneurysm.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tong Xu, Shoushuai Wang, Xiang Li, Xiuquan Li, Kaiyun Qu, Hao Tong, Ruijie Zhang, Shuling Bai, Jun Fan
Summary: The study found that lithium chloride prevented the development of AAA by inhibiting inflammation, MMPs, and superoxide production, as well as facilitating elastin synthesis. The beneficial effects of lithium chloride may be mediated through the regulation of the GSK3?/SIRT1/NF-?B cascade.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Toxicology
Anna Pieniazek, Artur Szczepocki
Summary: The findings suggest that IS induces oxidative damage to erythrocyte components, which may affect the functional properties of erythrocytes in CKD patients.
TOXICOLOGY IN VITRO
(2021)
Article
Biochemistry & Molecular Biology
Bing Zhou, Lu-Lu Wu, Fen Zheng, Nan Wu, Ai-Dong Chen, Hong Zhou, Jing-Yu Chen, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
Summary: miR-31-5p plays a crucial role in oxidative stress and VSMC migration by inhibiting FNDC5 expression, leading to increased oxidative stress and cell migration in SHR. The imbalance of miR-31-5p and FNDC5 exacerbates oxidative stress and cell migration in vascular smooth muscle cells.
Article
Plant Sciences
Yenan Mo, Dongmei Hu, Wanlin Yu, Chunlan Ji, Yin Li, Xusheng Liu, Zhaoyu Lu
Summary: This study found that Astragaloside IV (AS-IV), a component of Astragalus membranaceus, can reduce indoxyl sulfate (IS)-induced renal tubular injury by inhibiting the expression of aryl hydrocarbon receptor (AhR). This offers a new therapeutic approach to the treatment of chronic renal failure.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Alexandre Candellier, Nervana Issa, Maria Grissi, Theo Brouette, Carine Avondo, Cathy Gomila, Geremy Blot, Brigitte Gubler, Gilles Touati, Youssef Bennis, Thierry Caus, Michel Brazier, Gabriel Choukroun, Christophe Tribouilloy, Said Kamel, Cedric Boudot, Lucie Henaut
Summary: This study aimed to evaluate the influence of the uremic toxin indoxyl sulfate (IS) on the mineralization of primary human valvular interstitial cells (hVICs). The results showed that IS promotes hVIC mineralization through the activation of the AhR-dependent NF-kappa B pathway and the subsequent release of IL-6. Further research should focus on targeting inflammatory pathways to reduce the onset and progression of chronic kidney disease-related calcific aortic stenosis (CAS).
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Article
Pathology
Ryosuke Ichihara, Yukihiro Shiraki, Yasuyuki Mizutani, Tadashi Iida, Yuki Miyai, Nobutoshi Esaki, Akira Kato, Shinji Mii, Ryota Ando, Masamichi Hayashi, Hideki Takami, Tsutomu Fujii, Masahide Takahashi, Atsushi Enomoto
Summary: Recent studies have shown that cancer-associated fibroblasts (CAFs) are heterogeneous and can be categorized into cancer-promoting and -restraining CAFs. This study identifies MXRA8 as a new marker for CAFs, but the biological importance of MXRA8(+)CAF is still unclear.
PATHOLOGY INTERNATIONAL
(2022)
Article
Pathology
Kai Adachi, Yasutaka Sakurai, Masaaki Ichinoe, Masayoshi Tadehara, Akihiro Tamaki, Yurika Kesen, Takuya Kato, Shinji Mii, Atsushi Enomoto, Masahide Takahashi, Wasaburo Koizumi, Yoshiki Murakumo
Summary: CD109 expression in both tumor cells and stroma is significantly associated with the progression and prognosis of pancreatic ductal adenocarcinoma (PDAC), and may serve as a valuable prognostic marker.
Article
Oncology
Yasuyuki Mizutani, Tadashi Iida, Eizaburo Ohno, Takuya Ishikawa, Fumie Kinoshita, Yachiyo Kuwatsuka, Miwa Imai, Shinobu Shimizu, Toshihisa Tsuruta, Atsushi Enomoto, Hiroki Kawashima, Mitsuhiro Fujishiro
Summary: Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment. Recent studies have identified a subset of CAFs, called cancer-restraining CAFs (rCAFs), which can suppress cancer progression. This study aims to investigate the efficacy of a combination of the synthetic retinoid AM80 and chemotherapy drugs gemcitabine (GEM) and nab-paclitaxel (nab-PTX) in patients with advanced pancreatic cancer.
Article
Gastroenterology & Hepatology
Hiroki Kobayashi, Krystyna A. Gieniec, Tamsin R. M. Lannagan, Tongtong Wang, Naoya Asai, Yasuyuki Mizutani, Tadashi Iida, Ryota Ando, Elaine M. Thomas, Akihiro Sakai, Nobumi Suzuki, Mari Ichinose, Josephine A. Wright, Laura Vrbanac, Jia Q. Ng, Jarrad Goyne, Georgette Radford, Matthew J. Lawrence, Tarik Sammour, Yoku Hayakawa, Sonja Klebe, Alice E. Shin, Samuel Asfaha, Mark L. Bettington, Florian Rieder, Nicholas Arpaia, Tal Danino, Lisa M. Butler, Alastair D. Burt, Simon J. Leedham, Anil K. Rustgi, Siddhartha Mukherjee, Masahide Takahashi, Timothy C. Wang, Atsushi Enomoto, Susan L. Woods, Daniel L. Worthley
Summary: In colorectal cancer, ACTA2(+) cancer-associated fibroblasts (CAFs) emerge through proliferation from intestinal pericryptal leptin receptor (Lepr)(+) cells. These Lepr-lineage CAFs express melanoma cell adhesion molecule (MCAM), which is inversely associated with patient survival. Knockout of stromal Mcam attenuates orthotopically injected colorectal tumoroid growth and improves survival through decreased tumor-associated macrophage recruitment. The fibroblast MCAM interacts with interleukin-1 receptor 1 to promote macrophage chemotaxis.
Review
Biochemistry & Molecular Biology
Kaname Uno, Shohei Iyoshi, Masato Yoshihara, Kazuhisa Kitami, Kazumasa Mogi, Hiroki Fujimoto, Mai Sugiyama, Yoshihiro Koya, Yoshihiko Yamakita, Akihiro Nawa, Tomohiro Kanayama, Hiroyuki Tomita, Atsushi Enomoto, Hiroaki Kajiyama
Summary: This review highlights the significance of accumulating ascites, EOC cells in the form of spheroids, and interaction with non-malignant host cells in epithelial ovarian cancer (EOC). The formation of spheroids allows EOC cells to become resistant against anoikis and gain the ability to invade and metastasize. Additionally, hetero-cellular spheroids composed of non-malignant cells are shown to have a higher adhesion ability. Understanding the mechanisms of spheroid formation and interactions with non-malignant cells in ascites is crucial for improving the prognosis of EOC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kazuhisa Kitami, Masato Yoshihara, Satoshi Tamauchi, Mai Sugiyama, Yoshihiro Koya, Yoshihiko Yamakita, Hiroki Fujimoto, Shohei Iyoshi, Kaname Uno, Kazumasa Mogi, Yoshiki Ikeda, Akira Yokoi, Nobuhisa Yoshikawa, Kimihiro Nishino, Kaoru Niimi, Akihiro Nawa, Atsushi Enomoto, Hiroaki Kajiyama
Summary: The study found that vitamin D inhibited the transformation of ovarian cancer cells into mesothelial cells and restored the normal state of mesothelial cells, thereby suppressing ovarian cancer dissemination. Vitamin D suppressed thrombospondin-1 expression by competing with Smad3, which played a significant role in preventing ovarian cancer dissemination.
Correction
Biochemistry & Molecular Biology
Tadashi Iida, Yasuyuki Mizutani, Nobutoshi Esaki, Suzanne M. Ponik, Brian M. Burkel, Liang Weng, Keiko Kuwata, Atsushi Masamune, Seiichiro Ishihara, Hisashi Haga, Kunio Kataoka, Shinji Mii, Yukihiro Shiraki, Takuya Ishikawa, Eizaburo Ohno, Hiroki Kawashima, Yoshiki Hirooka, Mitsuhiro Fujishiro, Masahide Takahashi, Atsushi Enomoto
Article
Biochemistry & Molecular Biology
Tadashi Iida, Yasuyuki Mizutani, Nobutoshi Esaki, Suzanne M. Ponik, Brian M. Burkel, Liang Weng, Keiko Kuwata, Atsushi Masamune, Seiichiro Ishihara, Hisashi Haga, Kunio Kataoka, Shinji Mii, Yukihiro Shiraki, Takuya Ishikawa, Eizaburo Ohno, Hiroki Kawashima, Yoshiki Hirooka, Mitsuhiro Fujishiro, Masahide Takahashi, Atsushi Enomoto
Summary: Induced expression of the glycosylphosphatidylinositol-anchored protein Meflin in cancer-associated fibroblasts (CAFs) improved chemosensitivity in pancreatic ductal adenocarcinoma (PDAC) in mice. A synthetic retinoid, Am80, effectively induced Meflin expression in CAFs, enhancing PDAC sensitivity to chemotherapy.
Article
Multidisciplinary Sciences
Shun Minatoguchi, Shoji Saito, Kazuhiro Furuhashi, Yuriko Sawa, Masaki Okazaki, Yuko Shimamura, Ahmad Baseer Kaihan, Yusaku Hashimoto, Yoshinari Yasuda, Akitoshi Hara, Yasuyuki Mizutani, Ryota Ando, Noritoshi Kato, Takuji Ishimoto, Naotake Tsuboi, Nobutoshi Esaki, Makoto Matsuyama, Yukihiro Shiraki, Hiroki Kobayashi, Naoya Asai, Atsushi Enomoto, Shoichi Maruyama
Summary: This study reveals a subset of PMC marked by Meflin, which is functionally distinct from classic pericytes and myofibroblasts. The findings highlight the importance of elucidating PMC heterogeneity.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Yuji Kumagai, Junko Nio-Kobayashi, Seiichiro Ishihara, Atsushi Enomoto, Masashi Akiyama, Ryosuke Ichihara, Hisashi Haga
Summary: “Collective invasion of cancer cells as a cell cluster is associated with metastasis and worse prognosis. In this study, different subclones with varying invasive potentials were established from human skin squamous carcinoma cells. The highly invasive subclone exhibited a hermetically sealed and narrow intercellular space, localized interferon-beta, and activated STAT1, leading to collective invasion. On the other hand, the low-invasive subclone with deficient STAT1 activity had non-sealed and wide intercellular spaces. The coexistence of high- and low-invasive subclones resulted in collective invasion with the high-invasive cells leading the invasion front. Tissue microarray analysis further supported the role of STAT1 in collective invasion in human skin squamous cell carcinoma.”
Article
Biochemistry & Molecular Biology
Katsuya Onishi, Seiichiro Ishihara, Masayuki Takahashi, Akihiro Sakai, Atsushi Enomoto, Kentaro Suzuki, Hisashi Haga
Summary: Stiffness of the extracellular matrix plays a vital role in regulating biological responses, and this study identifies nuclear diphosphorylated myosin regulatory light chain (2P-MRLC) as a critical mediator in suppressing apoptosis in response to substrate stiffness. The kinase ZIPK and actin fiber formation are involved in promoting the nuclear localization of 2P-MRLC in response to stiff substrates. 2P-MRLC, in turn, regulates the expression of MafB and inhibits apoptosis in response to substrate stiffness, revealing a new mechanism in mechanotransduction.
Article
Nutrition & Dietetics
Takayuki Inoue, Bin Fu, Miwako Nishio, Miyako Tanaka, Hisashi Kato, Masashi Tanaka, Michiko Itoh, Hajime Yamakage, Kozue Ochi, Ayaka Ito, Yukihiro Shiraki, Satoshi Saito, Masafumi Ihara, Hideo Nishimura, Atsuhiko Kawamoto, Shian Inoue, Kumiko Saeki, Atsushi Enomoto, Takayoshi Suganami, Noriko Satoh-Asahara
Summary: The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) involves metabolic stress and inflammatory stimuli. In this study, we found that Taxifolin treatment effectively prevented hepatic steatosis, chronic inflammation, and liver fibrosis in a NASH murine model. Taxifolin inhibited lipid accumulation in hepatocytes and increased brown adipose tissue activity. Furthermore, Taxifolin treatment after NASH development could prevent the development of liver tumors. These findings indicate the pleiotropic effects of Taxifolin for NASH treatment.
Review
Oncology
Hiroyoshi Y. Tanaka, Takuya Nakazawa, Atsushi Enomoto, Atsushi Masamune, Mitsunobu R. Kano
Summary: Pancreatic cancer is difficult to treat and novel treatment strategies are urgently needed. The use of nanomedicines is being explored as a potential solution, but the fibrotic barrier in pancreatic cancer hinders their delivery. This review discusses strategies to overcome this barrier and highlights gaps in our understanding.
Meeting Abstract
Critical Care Medicine
A. Suzuki, K. Sakamoto, Y. Nakahara, A. Enomoto, J. Hino, A. Ando, M. Inoue, N. Omote, M. Kusaka, J. Fukihara, N. Hashimoto
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Meeting Abstract
Critical Care Medicine
N. Hashimoto, K. Sakamoto, Y. Nakahara, N. Omote, A. Ando, M. Inoue, A. Suzuki, J. Fukihara, M. Kusaka, K. Wakahara, A. Enomoto
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
