Review
Biochemistry & Molecular Biology
Rina Fujiwara-Tani, Shiori Mori, Ruiko Ogata, Rika Sasaki, Ayaka Ikemoto, Shingo Kishi, Masuo Kondoh, Hiroki Kuniyasu
Summary: CLDN4 is a crucial component of tight junctions in epithelial cells and is overexpressed in many epithelial malignancies. Changes in CLDN4 expression are associated with epigenetic factors, inflammation, and growth factor signaling. CLDN4 plays a role in maintaining the tumor microenvironment and acts as a barrier to anticancer drug entry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Nandhini Rajagopal, Shikha Nangia
Summary: This study investigates the molecular assembly of claudins, specifically claudin-5 and claudin-15, to determine their structural and functional properties. The research findings suggest that each member of the claudin family has a unique strand architecture that requires systematic molecular-level analysis.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Toxicology
Youting Zhang, Likang Zhang, Wanwan Chen, Yuanyuan Zhang, Xiaoming Wang, Yaoyao Dong, Weixi Zhang, Xixi Lin
Summary: The impact of fine particulate matter (PM2.5) on public health has been increasingly studied, with Shp2 identified as playing a crucial role in PM2.5-induced epithelial barrier dysfunction through the ERK1/2 MAPK signaling pathway.
TOXICOLOGY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Fumisato Maesaka, Masaomi Kuwada, Shohei Horii, Shingo Kishi, Rina Fujiwara-Tani, Shiori Mori, Kiyomu Fujii, Takuya Mori, Hitoshi Ohmori, Takuya Owari, Makito Miyake, Yasushi Nakai, Nobumichi Tanaka, Ujjal Kumar Bhawal, Yi Luo, Masuo Kondoh, Kiyohide Fujimoto, Hiroki Kuniyasu
Summary: In bladder urothelial carcinoma (BUC), the overexpression of CLDN4 is associated with cancer progression. Through analyzing BUC cases, it was found that hypomethylation of CLDN4 promoter DNA increases CLDN4 expression and promotes cell proliferation, stemness, and epithelial-mesenchymal transition. Treatment with demethylating agent AZA leads to excessive CLDN4 expression, specifically the TJ-unintegrated CLDN4 monomer. The TJ-unintegrated CLDN4 binds to integrin beta 1 and enhances stemness, drug resistance, and metastatic ability of the cells, as well as exhibits an anti-apoptosis effect via FAK phosphorylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Memoona Ramzan, Christophe Philippe, Inna A. Belyantseva, Yoko Nakano, Cristina Fenollar-Ferrer, Risa Tona, Rizwan Yousaf, Rasheeda Basheer, Ayesha Imtiaz, Rabia Faridi, Zunaira Munir, Hafiza Idrees, Midhat Salman, Sophie Nambot, Antonio Vitobello, Souad Kartti, Oumaima Zarrik, P. Dane Witmer, Nara Sobreria, Azeddine Ibrahimi, Botond Banfi, Sebastien Moutton, Thomas B. Friedman, Sadaf Naz
Summary: Hereditary deafness is a heterogeneous condition with genetic factors. This study identified two families with recessive deafness caused by bi-allelic variants in the CLDN9 gene. The variants affect protein interactions and localization, pointing to CLDN9 as a deafness gene in humans.
Article
Multidisciplinary Sciences
Laura-Sophie Beier, Ayk Waldow, Saeed Khomeijani Farahani, Roman Mannweiler, Sabine Vidal-Y-Sy, Johanna M. Brandner, Jorg Piontek, Dorothee Gunzel
Summary: The formation of tight junction (TJ) is crucial for epidermal barrier function. Manipulation of TJ barriers in reconstructed human epidermis (RHE) was achieved through knockdown of claudin-1 and -4 or by using claudin-binding fusion proteins. The study demonstrates the critical role of claudin-1 in regulating paracellular permeability in the viable epidermis.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Priscila Anhel Medrano-Gonzalezl, Franklin Cruz-Villegas, Alejandro Alarcon del Carmen, Luis Felipe Montano, Erika Patricia Rendon-Huerta
Summary: Claudin-6 overexpression is associated with an increase in the generation of cancer stem cells and dedifferentiation of epithelial cells in gastric cancer.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Multidisciplinary Sciences
Kazuto Tsukita, Manabu Kitamata, Hiroka Kashihara, Tomoki Yano, Ikuko Fujiwara, Timothy F. Day, Tatsuya Katsuno, Jaewon Kim, Fumiko Takenaga, Hiroo Tanaka, Sungsu Park, Makoto Miyata, Hitomi Watanabe, Gen Kondoh, Ryosuke Takahashi, Atsushi Tamura, Sachiko Tsukita
Summary: Liquid-liquid phase separation (LLPS) plays a role in dynamic biological phenomena. In this study, the role of LLPS in the dynamic regulation of junctional actin filaments in epithelial cells was investigated. The researchers identified a multifunctional actin nucleator called cordon bleu (Cobl) as an AJC-enriched microtubule-associated protein and conducted comprehensive in vitro and in vivo analyses. They found that apical microtubules promoted LLPS of Cobl at the AJC, leading to increased Cobl actin assembly activity and spatiotemporal regulation of junctional actin assembly for epithelial morphogenesis and paracellular barriers.
Article
Microbiology
Amanda F. Amaral, Bryan E. McQueen, Kimberly Bellingham-Johnstun, Taylor B. Poston, Toni Darville, Uma M. Nagarajan, Caroline Laplante, Tobias Kaser
Summary: This study investigates the interactions between Chlamydia trachomatis (Ct) and porcine oviduct epithelial cells (pOECs), demonstrating that pOECs are a great in vitro model for studying Ct pathogenesis, cell biology, and immunity. Ct completes its developmental cycle in pOECs, induces an immune response similar to human cells, and affects the tight junction protein claudin-4. The reduction of membrane-bound claudin-4 expression may lead to impaired epithelial barrier function and increased susceptibility to co-infections.
Article
Biochemistry & Molecular Biology
Susana Lechuga, Alexander X. Cartagena-Rivera, Afshin Khan, Bert Crawford, Vani Narayanan, Daniel E. Conway, Jaakko Lehtimaki, Pekka Lappalainen, Florian Rieder, Michelle S. Longworth, Andrei I. Ivanov
Summary: The actomyosin cytoskeleton plays a crucial role in maintaining and remodeling epithelial barriers. UNC-45A, a cytoskeletal chaperone, is found to be important in the assembly of myosin structures and the protection of the intestinal epithelial barrier. Decreased expression of UNC-45A in patients with ulcerative colitis may contribute to barrier disruption and worsen the symptoms of the disease.
Review
Pharmacology & Pharmacy
Joel Brunner, Sakthikumar Ragupathy, Gerrit Borchard
Summary: Research focuses on modulating intercellular tight junctions to enhance drug absorption and bioavailability, with challenges in commercialization. Target-specific permeation enhancers have potential clinical applications.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Patrick Carius, Annemarie Jungmann, Marco Bechtel, Alexander Grissmer, Annette Boese, Gilles Gasparoni, Abdulrahman Salhab, Ralf Seipelt, Klaus Urbschat, Clementine Richter, Carola Meier, Denisa Bojkova, Jindrich Cinatl, Joern Walter, Nicole Schneider-Daum, Claus-Michael Lehr
Summary: The study describes a novel monoclonal cell line called Arlo, derived from a polyclonal human alveolar epithelium cell line. Arlo cells exhibit enhanced barrier properties and express genes relevant to barrier integrity and homeostasis, similar to primary human alveolar epithelial cells. Additionally, Arlo cells have been successfully infected with SARS-CoV-2, suggesting potential applications beyond biopharmaceutical experimentation.
Article
Food Science & Technology
Yunika Mayangsari, Mayu Okudaira, Chinatsu Mano, Yuki Tanaka, Osamu Ueda, Tomohiro Sakuta, Yoshiharu Suzuki, Yoshinari Yamamoto, Takuya Suzuki
Summary: Research showed that DMF can enhance intestinal TJ barrier integrity by increasing the expression of occludin and claudin-1, while reducing the expression of claudin-2. This regulation involves the induction of occludin protein translation via mTOR and silencing Cldn2 mRNA via miR-16-5p.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Pharmacology & Pharmacy
Haixiong Tang, Zemin Chen, Sudan Gan, Yan Liang, Hailing Zhang, Changyun Yang, Liqin Lin, Yubiao Guo, Shiyue Li, Jing Li, Lihong Yao
Summary: This study demonstrates the crucial role of glucose transporter 1 (GLUT1) in the dysfunction of epithelial tight junctions during the development of acute lung injury (ALI).
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Desislava Kolchakova, Dzhemal Moten, Tsvetelina Batsalova, Balik Dzhambazov
Summary: Claudins play a crucial role in cell migration and metastasis, making them potential therapeutic targets for cancer treatment. Experimental results show that anti-claudin-12 antibodies and inhibitory peptides can significantly reduce the migration and proliferation of claudin-12 expressing cells, suggesting their potential in inhibiting cancer cell migration.
Review
Biology
Makoto Osanai, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara
Summary: Retinoic acid (RA), an active metabolite of vitamin A, plays a crucial role in cell fate decisions. Cytochrome P450 family 26A1, B1, and C1 (CYP26A1, B1, and C1) enzymes protect cells from RA exposure by converting it into rapidly excreted derivatives. High expression levels of CYP26 enzymes in various types of cancer suggest their potential as therapeutic targets for CYP26-expressing malignancies.
MEDICAL MOLECULAR MORPHOLOGY
(2023)
Article
Medicine, Research & Experimental
Hiroaki Shima, Goro Kutomi, Yoko Kuga, Asaka Wada, Fukino Satomi, Kiminori Sato, Daisuke Kyuno, Noriko Nishikawa, Satoko Uno, Hidekazu Kameshima, Tosei Ohmura, Tadashi Hasegawa, Ichiro Takemasa
Summary: The benefit of a taxane-first sequence and adriamycin and cyclophosphamide (AC) in patients with non-clinical complete response (non-cCR) to pertuzumab, trastuzumab, and docetaxel (PTD) was investigated. A high pathological clinical response (pCR) rate was observed for the taxane-first sequence. Some patients achieved pCR without cCR after PTD alone, indicating additional antitumor effects after AC.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2023)
Article
Biology
Midori Sato, Ayano Inoue, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai
Summary: This study is the first to show increased expression of endocan in precancerous dysplastic lesions and malignancy of the cervix. The data suggest that a high expression level of endocan potentially contributes to the development of cervical squamous neoplasia of the uterus.
MEDICAL MOLECULAR MORPHOLOGY
(2023)
Article
Biology
Yusaku Kubota, Akira Takasawa, Yusuke Ono, Tomoyuki Aoyama, Kumi Takasawa, Akinori Tada, Kazufumi Magara, Taro Murakami, Fuminori Daimon, Soh Yamamoto, Shota Sato, Yutaro Hiratsuka, Daisuke Kyuno, Makoto Osanai
Summary: Invasive pulmonary aspergillosis (IPA) is a common form of invasive fungal infection (IFI), but it is challenging to identify the fungal species and select appropriate treatments. This study describes the pathophysiology of severe respiratory failure caused by a mixed infection of IPA and candidiasis. Scanning electron microscopy (SEM) and DNA sequencing were used to analyze formalin-fixed paraffin-embedded (FFPE) tissues, providing evidence of the mixed fungal infection at a focal site. This technique shows promise for studying IFI pathophysiology.
MEDICAL MOLECULAR MORPHOLOGY
(2023)
Review
Biology
Sakura Kamiya, Yuna Nakamori, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai
Summary: In this review, the potential of targeting the vitamin D metabolizing enzyme CYP24A1 as a therapy for various tumors is discussed. Vitamin D deficiency impairs its physiological function in target cells, leading to various pathologies including cancer. Additionally, elevated expression of CYP24A1 has been shown to promote carcinogenesis by reducing the bioavailability of vitamin D metabolites. Therefore, vitamin D metabolism-blocking therapy may be feasible for various types of human malignancies that express constitutive CYP24A1.
MEDICAL MOLECULAR MORPHOLOGY
(2023)
Article
Oncology
Sakura Kamiya, Yuna Nakamori, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Yusuke Ono, Kazufumi Magara, Makoto Osanai
Summary: Vitamin D is essential for the human body and plays a role in calcium metabolism and homeostasis. It is associated with carcinogenesis in various organs, including breast carcinoma, where the expression of the vitamin D metabolizing enzyme CYP24A1 is increased. This study demonstrates that CYP24A1 promotes the oncogenic properties of breast carcinoma cells and its suppression enhances cell death sensitivity to anticancer drugs, suggesting the potential of CYP24A1 inhibition as a novel therapy in breast cancer.
Article
Oncology
Goro Kutomi, Hiroaki Shima, Daisuke Kyuno, Fukino Satomi, Asaka Wada, Yoko Kuga, Minoru Okazaki, Akira Okazaki, Hideji Masuoka, Toshihiko Mikami, Yuichi Yuyama, Takashi Matsuno, Tosei Ohmura, Hidekazu Kameshima, Toru Mizuguchi, Ichiro Takemasa
Summary: The purpose of this study was to evaluate the rate of positive surgical margins for supine magnetic resonance imaging (MRI) before breast-conserving surgery (BCS). The study found that 18.8% of patients who underwent supine MRI prior to BCS had positive margins, which is similar to the rate with prone MRI. Patients with breast cancers larger than T2 did not have an increased risk of positive margins. In conclusion, supine MRI is a reliable method for assessing the extent of resection in breast cancer.
MOLECULAR AND CLINICAL ONCOLOGY
(2023)
Article
Biology
Kazufumi Magara, Akira Takasawa, Keisuke Kikuchi, Taro Sugawara, Taro Murakami, Daisuke Kyuno, Yusuke Ono, Kumi Takasawa, Yasunao Numata, Shigeru Sasaki, Hiroshi Nakase, Tadashi Hasegawa, Makoto Osanai
Summary: Crystal-storing histiocytosis (CSH) is a rare disorder characterized by histiocyte infiltration and abnormal accumulation of crystalline structures, often occurring with lymphoproliferative-plasma cell disorders (LP-PCD) as background diseases. The diagnosis of CSH is challenging as optical microscopy alone may not be sufficient for identifying the crystals in infiltrating histiocytes. This case report highlights the atypical course of systemic CSH with multifocal fibrosclerosis, diagnosed through ultrastructural observation using transmission electron microscopy (TEM) and scanning electron microscopy (SEM) in pathological autopsy. Additionally, scanning electron microscopic observations using formalin-fixed and paraffin-embedded (FFPE) tissue from biopsy specimens before death successfully identified the crystalline structures. Early detection and treatment of CSH may be facilitated by SEM observation of histiocytic infiltrative lesions using FFPE tissue.
MEDICAL MOLECULAR MORPHOLOGY
(2023)
Article
Multidisciplinary Sciences
Daisuke Kyuno, Masatoshi Tateno, Yusuke Ono, Kazufumi Magara, Kumi Takasawa, Akira Takasawa, Makoto Osanai
Summary: In this study, the autopsy findings of two cases of sudden death due to COVID-19-related cardiomyopathies were reported. The study found common pathological findings in both hearts, which included decreased staining intensity, loss of rhabdomeres, and multivacuolation in cardiomyocytes. These findings could aid in diagnosing sudden death due to COVID-19-related cardiomyopathy, even when standard staining techniques show few findings.
Meeting Abstract
Oncology
Asaka Wada, Goro Kutomi, Yoshihiko Hirohashi, Daisuke Kyuno, Hiroaki Shima, Yoko Kuga, Toshihiko Torigoe, Ichiro Takemasa
Meeting Abstract
Oncology
Akira Takasawa, Taishi Akimoto, Kumi Takasawa, Daisuke Kyuno, Makoto Osanai
Meeting Abstract
Oncology
Daisuke Kyuno, Akira Takasawa, Kumi Takasawa, Kazufumi Magara, Makoto Osanai
Meeting Abstract
Oncology
Kazufumi Magara, Akira Takasawa, Kumi Takasawa, Daisuke Kyuno, Makoto Osanai
Article
Infectious Diseases
Hazuki Ito, Ryuichiro Kakizaki, Keisuke Harada, Daisuke Kyuno, Terufumi Kubo, Naofumi Bunya, Takehiko Kasai, Shuji Uemura, Eichi Narimatsu
Summary: This study reported a case of disseminated mucormycosis in a COVID-19 patient during hospitalization. The patient experienced severe respiratory failure, intra-abdominal hemorrhage, and septic shock before death.
Meeting Abstract
Oncology
Akira Takasawa, Taishi Akimoto, Kumi Takasawa, Daisuke Kyuno, Makoto Osanai