Article
Biochemistry & Molecular Biology
Giulia de Alteriis, Gabriella Pugliese, Antonella Di Sarno, Giovanna Muscogiuri, Luigi Barrea, Valentina Cossiga, Giuseppe Perruolo, Michele Francesco Di Tolla, Francesca Zumbolo, Pietro Formisano, Filomena Morisco, Silvia Savastano
Summary: Visceral obesity is associated with the progression of NASH. CK18 epitopes M30 and M65 are accurate markers for detecting NASH. This study found that CK18M30 and CK18M65 levels were significantly correlated with anthropometric and metabolic characteristics, liver stiffness, and indices of steatosis and fibrosis in subjects with visceral obesity. These levels could serve as good biomarkers for early identification of NASH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Toxicology
Samantha Korver, Joanne Bowen, Kara Pearson, Raymond J. Gonzalez, Neil French, Kevin Park, Rosalind Jenkins, Christopher Goldring
Summary: DILI is a common adverse effect in drug therapy, with CK18 identified as a potential new biomarker for diagnosing early-stage DILI and providing insights into the mechanism of hepatocellular injury. However, further research is needed to characterize CK18 in preclinical models of DILI, particularly in vivo rat models.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Cell Biology
Jiri Soukup, Tomas Cesak, Helena Hornychova, Monika Manethova, Ludmila Michnova, David Netuka, Barbora Vitovcova, Jan Cap, Ales Ryska, Filip Gabalec
Summary: CK-negative somatotroph tumours do not represent a distinct subtype of somatotroph tumours, and can be further subdivided according to their morphology and immunoprofile.
Article
Medical Laboratory Technology
Jagdeep Singh Bhangu, Andrea Macher-Beer, Vanessa Schimek, Bastian Garmroudi, Dietmar Tamandl, Lukas W. Unger, Thomas Bachleitner-Hofmann, Rudolf Oehler
Summary: This study explored the potential of circulating apoptosis markers in predicting treatment response in patients with colorectal cancer liver metastasis. The findings indicated that CRCLM tissues had more apoptotic cells and higher levels of circulating M30, which correlated with tumor volume. Patients with higher M30 levels before therapy had worse prognosis. The predictive potential of M30 was higher than that of the tumor markers CA19-9 or CEA.
CLINICA CHIMICA ACTA
(2023)
Article
Medicine, General & Internal
Felix Hempel, Martin Roderfeld, Lucas John Muentnich, Jens Albrecht, Ziya Oruc, Borros Arneth, Thomas Karrasch, Joern Pons-Kuehnemann, Winfried Padberg, Harald Renz, Andreas Schaeffler, Elke Roeb
Summary: Bariatric surgery is effective for treating NAFLD in morbidly obese patients, but may lead to worsening NASH and fibrosis. Monitoring ccK18 levels can help track patient progress postoperatively. Significant weight loss and reduced ccK18 levels were observed one year after surgery, but some patients did not respond well to treatment.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Jana Knorr, Benedikt Kaufmann, Maria Eugenia Inzaugarat, Theresa Maria Holtman, Lukas Geisler, Jana L. Hundertmark, Marlene Sophia Kohlhepp, Laela M. Boosheri, Daisy R. Chilin-Fuentes, Amanda Birmingham, Kathleen M. Fisch, Joel D. Schilling, Sven H. Loosen, Christian Trautwein, Christoph Roderburg, Milnevver Demir, Frank Tacke, Hal M. Hoffman, Ariel E. Feldstein, Alexander Wree
Summary: This study reveals the role of IL-18 in the development of liver fibrosis by directly affecting HSC activation, identifying IL-18 as a potential target for the treatment of liver fibrosis.
Article
Gastroenterology & Hepatology
Finn C. Derben, Bastian Engel, Kalliopi Zachou, Johannes Hartl, Bjoern Hartleben, Heike Bantel, Christoph Schramm, George N. Dalekos, Michael P. Manns, Elmar Jaeckel, Richard Taubert
Summary: The study found that measuring cytokeratin-18 cell death marker M65 levels can non-invasively detect incomplete histological remission of autoimmune hepatitis, helping to better select patients for surveillance.
LIVER INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Joanna Goralska, Urszula Razny, Anna Gruca, Anna Zdzienicka, Agnieszka Micek, Aldona Dembinska-Kiec, Bogdan Solnica, Malgorzata Malczewska-Malec
Summary: There is increasing interest in the non-invasive identification and monitoring of liver damage in obese patients. Plasma cytokeratin-18 (CK-18) fragment levels have been proposed to predict the presence of non-alcoholic steatohepatitis (NASH). This study aimed to analyze the associations of CK-18 with obesity and related complications. The findings suggest that CK-18 can distinguish between different metabolic phenotypes in obesity.
Article
Pharmacology & Pharmacy
Sarah A. E. Rupprechter, Derek J. Sloan, Wilna Oosthuyzen, Till T. Bachmann, Adam T. Hill, Kevin Dhaliwal, Kate Templeton, Joshua Matovu, Christine Sekaggya-Wiltshire, James W. Dear
Summary: In patients on anti-TB therapy, miR-122 and K18 correlated with ALT levels and increased in cases of drug-induced liver injury (DILI). Further research is needed to determine their diagnostic and prognostic utility in this global context.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anne Menz, Timo Weitbrecht, Natalia Gorbokon, Franziska Buescheck, Andreas M. Luebke, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Doris Hoeflmayer, Soren Weidemann, Christoph Fraune, Katharina Moeller, Christian Bernreuther, Patrick Lebok, Till Clauditz, Guido Sauter, Ria Uhlig, Waldemar Wilczak, Stefan Steurer, Sarah Minner, Eike Burandt, Rainer Krech, David Dum, Till Krech, Andreas Marx, Ronald Simon
Summary: CK18 is consistently expressed in various epithelial cancers, especially adenocarcinomas. Down-regulation or loss of CK18 expression in cancers arising from CK18 positive tissues as well as CK18 neo-expression in cancers originating from CK18 negative tissues is linked to cancer progression and may reflect tumor dedifferentiation. Up-regulation of CK18 in squamous cell carcinomas was linked to high grade and lymph node metastasis.
MOLECULAR MEDICINE
(2021)
Article
Multidisciplinary Sciences
Shotaro Yamano, Tomoki Takeda, Yuko Goto, Shigeyuki Hirai, Yusuke Furukawa, Yoshinori Kikuchi, Tatsuya Kasai, Kyohei Misumi, Masaaki Suzuki, Kenji Takanobu, Hideki Senoh, Misae Saito, Hitomi Kondo, Yumi Umeda
Summary: This study investigated the carcinogenicity of titanium dioxide nanoparticles (TiO2 NPs) in rasH2 mice exposed to various doses for 26 weeks. The results showed that TiO2 NPs exposure did not increase the incidence of lung tumors or induce pulmonary fibrosis and pre-neoplastic lesions. The study also found no evidence of increased cell proliferative activity in alveolar epithelial type 2 cells.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Donghwan Kim, Inwook Choi, Sang Keun Ha, Frank J. Gonzalez
Summary: Keratins are important structural proteins that play a protective role in skin and other epithelial tissues. They are highly tissue-specific and can be used as diagnostic markers for human diseases. KRT79, a type II cytokeratin, has been identified as a regulator of hair canal morphogenesis and regeneration in skin, and its role in the liver is still unclear. However, recent studies suggest that hepatic KRT79 is controlled by PPARA and is associated with liver damage, making it a potential diagnostic marker for human liver diseases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yuqing Wang, Ayrea Hurley, Marco De Giorgi, Mark R. Tanner, Rong-Chi Hu, Michael W. Pennington, William R. Lagor, Christine Beeton
Summary: Targeting the Kv1.3 potassium channel has shown effectiveness in reducing obesity and severity of autoimmune disease in animal models. However, the delivery of Kv1.3 blockers like Stichodactyla toxin (ShK) requires injections, which affects patient compliance. A study using Adeno-Associated Virus (AAV)8 vectors to induce hepatocytes to express the Kv1.3 blocker showed promising results in mice but was ineffective in reducing obesity in mice fed a high-fat diet.
Article
Cell Biology
Alejo M. Capiglioni, Maria C. Capitani, Julieta Marrone, Raul A. Marinelli
Summary: We have demonstrated that hepatic gene transfer of human aquaporin-8 (hAQP8) improves the detoxification of ammonia to urea in normal mice and mice with impaired hepatocyte ammonia metabolism. Our findings suggest that hAQP8 gene transfer could be a potential therapeutic strategy for disorders with defective hepatic ammonia metabolism.
Article
Veterinary Sciences
Asuman Arkas Alklay, Ugur Topaloglu, Fatma Celenk, Nursin Aydin, Bayram Bayram, Omer Atalar
Summary: This study investigated the expression of cytokeratins in the mammary glands of cows during late lactation and involution periods. CK8 and CK18 were found to be strongly expressed in the alveolar and ductal epithelial cells during these periods, while CK19 was not expressed. These findings reveal the role of CK8 and CK18 in mammary epithelial differentiation and maintenance.
KAFKAS UNIVERSITESI VETERINER FAKULTESI DERGISI
(2022)
Article
Nutrition & Dietetics
Junta Nakahara, Yasunori Masubuchi, Kazumi Takashima, Yasunori Takahashi, Ryo Ichikawa, Tomohiro Nakao, Mihoko Koyanagi, Robert R. Maronpot, Toshinori Yoshida, Shim-mo Hayashi, Makoto Shibutani
Summary: The study found that 0.1% CUR improved anti-anxiety behavior and altered gene expression in the hippocampus, while 0.5% CUR increased oxidative stress and neuroinflammation-related genes. Low doses of CUR may have a preventive use in mitigating stress disorders, but high doses could induce neuroinflammation that hinders its behavioral effects.
NUTRITION RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Risako Yamashita, Yasunori Takahashi, Kazumi Takashima, Hiromu Okano, Ryota Ojiro, Qian Tang, Satomi Kikuchi, Mio Kobayashi, Bunichiro Ogawa, Meilan Jin, Reiji Kubota, Yoshiaki Ikarashi, Toshinori Yoshida, Makoto Shibutani
Summary: The study found dose-related accumulation of Pb in the offspring brain after developmental exposure, leading to sustained neural damage and neuroinflammatory responses in adulthood. Suppressed differentiation of type-3 neural progenitor cells was observed, resulting in an increased number of immature granule cells in adulthood. Additionally, induction of cellular senescence of SGZ cells due to Pb genotoxicity was suggested.
Article
Toxicology
Kenji Nakamura, Yuji Ishii, Shinji Takasu, Takehiko Nohmi, Makoto Shibutani, Kumiko Ogawa
Summary: This study clarified the role of chromosome aberrations (CAs) in chemical-induced carcinogenesis using a rat model with acetamide, a non-mutagenic hepatocarcinogen. Results showed that CAs induced by acetamide played a pivotal role in hepatocarcinogenesis in rats via micronucleus formation, highlighting the potential of chromosome rearrangements in chemical carcinogenesis.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Oncology
Mohamed Elbadawy, Yomogi Sato, Takashi Mori, Yuta Goto, Kimika Hayashi, Megumi Yamanaka, Daigo Azakami, Tsuyoshi Uchide, Ryuji Fukushima, Toshinori Yoshida, Makoto Shibutani, Mio Kobayashi, Yuta Shinohara, Amira Abugomaa, Masahiro Kaneda, Hideyuki Yamawaki, Tatsuya Usui, Kazuaki Sasaki
Summary: The study revealed that trametinib has anti-tumor effects on bladder cancer organoids, inhibiting cell viability even at low concentrations. Trametinib also induces differentiation of organoid cells from basal to luminal, suppressing tumor growth, and shows enhanced sensitivity in combination with YAP inhibitor or carboplatin.
CANCER BIOLOGY & THERAPY
(2021)
Article
Environmental Sciences
Ayumi Eguchi, Sayaka Mizukami, Misato Nakamura, Sousuke Masuda, Hirotada Murayama, Masashi Kawashima, Mari Inohana, Rei Nagahara, Mio Kobayashi, Risako Yamashita, Suzuka Uomoto, Emi Makino, Ryoichi Ohtsuka, Naofumi Takahashi, Shim-Mo Hayashi, Robert R. Maronpot, Makoto Shibutani, Toshinori Yoshida
Summary: The study suggests that MNZ may induce steatosis-related hepatocarcinogenesis in HFD-fed rats by inducing DNA double-strand breaks and modulating autophagy.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Hiromu Okano, Kazumi Takashima, Yasunori Takahashi, Ryota Ojiro, Qian Tang, Shunsuke Ozawa, Bunichiro Ogawa, Mihoko Koyanagi, Robert R. Maronpot, Toshinori Yoshida, Makoto Shibutani
Summary: The present study investigated the role of neuroinflammation and brain oxidative stress induced by neonatal treatment with lipopolysaccharides (LPS) on the development of autism spectrum disorder (ASD)-like behaviors and disruptive hippocampal neurogenesis in rats by exploring the chemopreventive effects of alpha-glycosyl isoquercitrin (AGIQ) as an antioxidant.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Gastroenterology & Hepatology
Mio Kobayashi, Risako Yamashita, Ryo Ichikawa, Makoto Shibutani, Toshinori Yoshida
Summary: The clumps of epithelial cells found in a mouse model of ulcerative colitis were likely derived from stem cells or their daughter progenitor cells. These clumps expressed stem cell markers and showed potential for mucosal healing.
DIGESTIVE DISEASES AND SCIENCES
(2022)
Article
Toxicology
Ryota Ojiro, Yousuke Watanabe, Hiromu Okano, Yasunori Takahashi, Kazumi Takashima, Qian Tang, Shunsuke Ozawa, Fumiyo Saito, Yumi Akahori, Meilan Jin, Toshinori Yoshida, Makoto Shibutani
Summary: The neurotoxic patterns of VPA differ between developmental and postpubertal exposure, with developmental exposure affecting genes related to nervous system development and postpubertal exposure impacting genes related to neuronal differentiation and projection. The hippocampal dentate gyrus may be a sensitive target of developmental neurotoxicants after puberty.
JOURNAL OF APPLIED TOXICOLOGY
(2022)
Article
Toxicology
Saori Shimizu, Natsuno Maeda, Yasunori Takahashi, Suzuka Uomoto, Keisuke Takesue, Ryota Ojiro, Qian Tang, Shunsuke Ozawa, Hiromu Okano, Kazumi Takashima, Gye-Hyeong Woo, Toshinori Yoshida, Makoto Shibutani
Summary: The 28-day exposure of young-adult rats to aluminum chloride (AlCl3) resulted in differential effects on hippocampal neurogenesis compared to developmental exposure. AlCl3 targeted neural stem cells and neural progenitor cells, leading to disrupted neurogenesis.
JOURNAL OF APPLIED TOXICOLOGY
(2022)
Article
Toxicology
Kazumi Takashima, Kota Nakajima, Saori Shimizu, Ryota Ojiro, Qian Tang, Hiromu Okano, Yasunori Takahashi, Shunsuke Ozawa, Meilan Jin, Tomoya Yoshinari, Toshinori Yoshida, Yoshiko Sugita-Konishi, Makoto Shibutani
Summary: Maternal oral exposure to sterigmatocystin affects hippocampal neurogenesis in offspring by inducing DNA double-strand breaks and oxidative DNA damage, leading to neurogenesis suppression. Various signaling pathways and mechanisms are involved in either promoting or inhibiting neurogenesis.
TOXICOLOGY LETTERS
(2021)
Article
Toxicology
Yasunori Takahashi, Hiromu Okano, Kazumi Takashima, Ryota Ojiro, Qian Tang, Shunsuke Ozawa, Bunichiro Ogawa, Gye-Hyeong Woo, Toshinori Yoshida, Makoto Shibutani
Summary: Drinking alcohol during pregnancy can cause harm to the fetus. Studies on rats have shown that high doses of ethanol can disrupt hippocampal neurogenesis and suppress synaptic plasticity. Ethanol exposure also induces neuroinflammation.
TOXICOLOGY LETTERS
(2022)
Article
Toxicology
Ryo Ichikawa, Sosuke Masuda, Junta Nakahara, Mio Kobayashi, Risako Yamashita, Suzuka Uomoto, Ohshima Kanami, Yuko Itoi, Makoto Shibutani, Toshinori Yoshida
Summary: This study investigated the effects of autophagy inducer carbamazepine (CBZ) on early hepatocarcinogenesis induced by a high-fat diet and streptozotocin. The results showed that inhibition of autophagy and induction of NADPH oxidase subunit might contribute to the development of early hepatocellular carcinoma in this model.
JOURNAL OF TOXICOLOGICAL SCIENCES
(2022)
Review
Pathology
Toshinori Yoshida, Mio Kobayashi, Suzuka Uomoto, Kanami Ohshima, Emika Hara, Yoshitaka Katoh, Naofumi Takahashi, Takanori Harada, Tatsuya Usui, Mohamed Elbadawy, Makoto Shibutani
Summary: The development of in vitro toxicity assessment methods using cultured cells has gained popularity for promoting animal welfare in animal experiments. This article briefly discusses the current status of hepatoxicity assessment using human and rat-derived hepatocytes, focusing on the liver organoid method. It also proposes how toxicologic pathologists should assess toxicity regarding the distribution of undifferentiated and differentiated cells in the organoid.
JOURNAL OF TOXICOLOGIC PATHOLOGY
(2022)
Meeting Abstract
Oncology
Misato Miyai, Maky Otsuka, Ayaka Tsuchimoto, Makoto Shibutani, Katsuhide Igarashi
Article
Veterinary Sciences
Mio Kobayashi, Toshinori Yoshida, Risako Yamashita, Rho Ichikawa, Junta Nakahara, Kazuki Nakamura, Hiromu Okano, Yasunori Takahashi, Nanao Ito, Makoto Shibutani
Summary: A case of cutaneous squamous cell carcinoma was found in a 17-year-old female koala at a zoo, with histopathological identification showing invasive features and metastatic lesions in the lung and axillary lymph node. This is the first reported case of SCC in a koala digit.
JOURNAL OF VETERINARY MEDICAL SCIENCE
(2021)