Article
Cell Biology
Taichi Sugawara, Kyoko Furuse, Tetsuhisa Otani, Tomohiko Wakayama, Mikio Furuse
Summary: The study reveals that angulin-1 is responsible for forming the plasma membrane seal at tricellular contacts independently of tricellulin and claudins, maintaining the epithelial barrier function.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Carlos Ayala-Torres, Susanne M. Krug, Rita Rosenthal, Michael Fromm
Summary: Water transport in epithelia is regulated by tight junction proteins, with modulation of these proteins affecting ion and macromolecule permeability in tight and intermediate-tight epithelial cell lines. However, transepithelial water permeability is only affected in tight cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Jia-Chen E. Hu, Franziska Weiss, Christian Bojarski, Federica Branchi, Joerg-Dieter Schulzke, Michael Fromm, Susanne M. Krug
Summary: In remission of UC, tricellulin expression level and intestinal barrier functions were restored to normal after being impaired in active UC. This indicates a re-sealing of the impaired tricellular paracellular pathway and reduced uptake of antigens back to normal rates in remission of UC.
BMC GASTROENTEROLOGY
(2021)
Article
Cell Biology
Yuma Cho, Daichi Haraguchi, Kenta Shigetomi, Kenji Matsuzawa, Seiichi Uchida, Junichi Ikenouchi
Summary: This study revealed the role of tricellulin in regulating actomyosin organization at tricellular junctions, contributing to the formation of the epithelial barrier. Additionally, alpha-catenin was identified as a novel binding partner of tricellulin, bridging tricellulin attachment to actin cables and closing the gap at tricellular junctions.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Cell Biology
Karem Awad, Christian Barmeyer, Christian Bojarski, Oliver Nagel, In-Fah M. Lee, Michal R. Schweiger, Joerg-Dieter Schulzke, Roland Buecker
Summary: This study investigated the pathophysiological mechanisms of diarrhea, constipation, and antigen uptake in mixed-type irritable bowel syndrome (IBS-M). The findings showed that in IBS-M, chloride secretion was reduced and antigen permeability was increased, which contributed to a low-grade inflammation in the colon mucosa.
Article
Engineering, Environmental
Zengjin Wang, Congcong Zhang, Fengyan Huang, Xiaojing Liu, Zhiping Wang, Bing Yan
Summary: Ingestion of nanoparticles during pregnancy can be dangerous to fetal brain development, especially in early pregnancy. Experimental results show that nanoparticles can cross multiple biological barriers, and the toxicity to the fetus depends on the stages of pregnancy and fetal development.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Cell Biology
David Dubayle, Arnaud Vanden-Bossche, Tom Peixoto, Morel Jean-Luc
Summary: The earliest effect of spaceflight is an alteration in vestibular function due to microgravity. Hypergravity exposure induced by centrifugation is also able to provoke motion sickness. The blood-brain barrier (BBB) is the crucial interface between the vascular system and the brain to ensure efficient neuronal activity. Our study on mice confirms the alteration in the BBB after a short period of hypergravity exposure, suggesting dysregulation in the tight junctions of endothelial cells forming the BBB.
Article
Immunology
Xin Wang, Jia-ying Yu, Yan Sun, Heng Wang, Hu Shan, Shubai Wang
Summary: Baicalin, a bioactive extract from Scutellaria Baicalensis Georgi, has anti-inflammatory and anti-oxidative functions, and its preventive protection can improve cell apoptosis and Fluorescein sodium infiltration in the brain tissue. Baicalin can also inhibit pro-inflammatory cytokines production, up-regulate Claudin-5 and ZO-1 protein expression, reduce ROS and MDA production, promote SOD production, and activate Nrf2-mediated antioxidant stress pathway to protect blood-brain barrier damage.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Andrea E. Toth, Hans C. Helms, Andras Harazin, Kasper B. Johnsen, Charlotte Goldeman, Annette Burkhart, Maj S. Thomsen, Paul J. Kempen, Adrian Klepe, Dora V. Lipka, Peter L. Moller, Thomas L. Andresen, Mette Nyegaard, Torben Moos, Birger Brodin, Morten S. Nielsen
Summary: Sortilin acts as a crucial regulatory protein for maintaining the tightness of the blood-brain barrier (BBB). Lack of sortilin results in BBB leakage, potentially due to alterations in signalling pathways, leading to compromised connections between brain endothelial cells.
Article
Biochemistry & Molecular Biology
Jong-Chan Ahn, Su Jung Hwang, Hyo-Jong Lee, Kyu-Won Kim
Summary: The study showed that claudin-5a is crucial for establishing and maintaining the blood-neural barrier during zebrafish development. Knockdown of claudin-5a resulted in selective leakage through the BBB, decreased expression of glucose transporter 1 in cerebral microvessels, and leakiness in the blood-cerebrospinal fluid barrier, indicating overall abnormal development of the blood-neural barriers.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2021)
Article
Neurosciences
Chelsea M. Phillips, Allison M. Johnson, Svetlana M. Stamatovic, Richard F. Keep, Anuska V. Andjelkovic
Summary: This study reveals that the absence of CCM3 leads to structural defects in the brain endothelial barrier, increasing the risk of vascular leakage. The upregulation of GJA1-20 k is found to disrupt the balance between gap junctions and tight junctions, destabilizing the tight junction complex and increasing brain endothelial barrier permeability.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biotechnology & Applied Microbiology
Xiang Li, Xiaoyan Tian
Summary: Pimavanserin effectively reverses neurological deficits, brain edema, increased inflammatory response, BBB permeability, and downregulation of Claudin 5 caused by cerebral ischemia injury. Its protective effects are mediated by regulating BBB integrity in a KLF6-dependent manner.
Article
Clinical Neurology
Yosuke Hashimoto, Karine Poirier, Nathalie Boddaert, Laurence Hubert, Melodie Aubart, Anna Kaminska, Marianne Alison, Isabelle Desguerre, Arnold Munnich, Matthew Campbell
Summary: This study reports a novel mutation in the CLDN5 gene associated with alternating hemiplegia with microcephaly. The mutation leads to the conversion of the blood-brain barrier into an anion-selective channel, indicating that CLDN5 associated alternating hemiplegia is a channelopathy.
Article
Pharmacology & Pharmacy
Helena Hader, Nina A. Hering, Joerg-Dieter Schulzke, Roland Buecker, Rita Rosenthal
Summary: The study demonstrates the antagonizing effects of myrrh against IL-13-induced barrier impairment in a human intestinal cell model. This suggests the potential use of myrrh as a treatment option for inflammatory bowel disease.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Jacopo Junio Valerio Branca, Matteo Boninsegna, Gabriele Morucci, Donatello Carrino, Claudio Nicoletti, Ferdinando Paternostro, Massimo Gulisano, Leonardo Bocchi, Alessandra Pacini
Summary: With the advancements in medicine, the increase in human life expectancy has led to a higher incidence of age-associated pathologies. Among these disorders, neurodegenerative diseases have a significant impact and the protective blood-brain barrier (BBB) presents a challenge for drug delivery. However, targeting the BBB by ultrasound (US) has been shown to transiently increase its permeability and allow the delivery of therapeutics to the brain. In this study, the effects of US treatment on the BBB were investigated using cell viability assays, Western blotting analysis, oxidative stress marker evaluation, and cytological and immunofluorescence staining. The results showed that US treatment caused no toxicity to the endothelial cells and induced a transient increase in intercellular spaces, mainly due to altered distribution of the tight junction protein ZO-1. These findings suggest that US treatment could be a potential strategy for improving drug delivery to the brain.
Article
Neurosciences
Hanako Aoki, Miwa Higashi, Michi Okita, Noboru Ando, Shigeo Murayama, Kinya Ishikawa, Takanori Yokota
Summary: This study investigated the expression and function of the TK2 gene in spinocerebellar ataxia type 31 (SCA31) and compared it with mitochondrial DNA depletion syndrome (MDS). The results showed that the expression and function of TK2 were preserved in SCA31 patients, indicating a mechanism distinct from MDS.
Article
Oncology
Amina Bolatkan, Ken Asada, Syuzo Kaneko, Kruthi Suvarna, Noriko Ikawa, Hidenori Machino, Masaaki Komatsu, Shuichiro Shiina, Ryuji Hamamoto
Summary: RNA modifications have been found to play an important role in human diseases, particularly in cancer. METTL6, a member of the RNA methyltransferase family, has been identified in various cancers, but its specific role and mechanism of action remain unclear. In this study, we found that METTL6 was upregulated in hepatocellular carcinoma (HCC) and associated with poorer prognosis. Knockout of METTL6 inhibited tumor cell growth, migration, and invasion, and significantly suppressed the expression of cell adhesion-related genes. Additionally, we discovered that METTL6 is localized in the cytosol, indicating its involvement in RNA modification. These findings provide new insights into the function of RNA modifications in cancer and suggest METTL6 as a potential therapeutic target for HCC.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Microscopy
Akane Yamada, Yoichiro Nishida, Kenjiro Wake, Ayako Nakamura, Yuriko Sakamaki, Hiroya Kuwahara, Toshiki Uchihara, Takanori Yokota
Summary: This study presents the first ultrastructural demonstration of GLUT1 molecules in coated vesicles, providing an explanation for its functional relevance in transporting glucose across BCECs. The successful localization of molecules in relation to target structures in native tissue samples helps to understand their functional relevance and their relationship to ultrastructural details.
Article
Biology
Hidenori Machino, Syuzo Kaneko, Masaaki Komatsu, Noriko Ikawa, Ken Asada, Ryuichiro Nakato, Kanto Shozu, Ai Dozen, Kenbun Sone, Hiroshi Yoshida, Tomoyasu Kato, Katsutoshi Oda, Yutaka Osuga, Tomoyuki Fujii, Gottfried von Keudell, Vassiliki Saloura, Ryuji Hamamoto
Summary: Low expression of microtubule affinity-regulating kinase 3 (MARK3) is associated with poor prognosis in high-grade serous ovarian carcinoma (HGSOC) patients. MARK3 overexpression inhibits cell proliferation and angiogenesis in ovarian cancer cells. Activation of the LKB1-MARK3 axis and downregulation of AP-1 and Hippo signaling target genes contribute to the modulation of cell cycle progression and angiogenesis.
COMMUNICATIONS BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Akiko Miyashita, Masaki Kobayashi, Satoru Ishibashi, Tetsuya Nagata, Ambika Chandrasekhar, Douglas W. Zochodne, Takanori Yokota
Summary: This study investigated the impact of silencing MALAT1 on the peripheral nervous system of diabetic mice. The results showed that silencing MALAT1 exacerbated the disease, indicating its important role in neuroprotection and splicing regulation in diabetic polyneuropathy. This study also demonstrated for the first time that a systemically delivered nucleotide therapy can directly influence DRG diabetic neurons and their axons.
Article
Cell Biology
Thunyarut Bannawongsil, Akane Yamada, Ayako Nakamura, Toshiki Uchihara, Takanori Yokota
Summary: This study demonstrates for the first time the neuronal redistribution of injected IgG in the mouse brain. Neuronal internalization of exogenous IgG may be advantageous especially when the therapeutic targets of monoclonal IgG are intraneuronal.
HISTOCHEMISTRY AND CELL BIOLOGY
(2022)
Letter
Clinical Neurology
Ryo Iwase, Tadashi Kanouchi, Toshitaka Yoshii, Taro Ishiguro, Takashi Hirai, Atsushi Okawa, Takanori Yokota, Nobuo Sanjo
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Taiki Matsubayashi, Miho Akaza, Yuichi Hayashi, Tsuyoshi Hamaguchi, Katsuya Satoh, Koki Kosami, Ryusuke Ae, Tetsuyuki Kitamoto, Masahito Yamada, Takayoshi Shimohata, Takanori Yokota, Nobuo Sanjo
Summary: Studies on the very early electroencephalography features prior to the emergence of generalized periodic discharges in Creutzfeldt-Jakob disease are rare. This study analyzed the EEG features of patients with sporadic CJD and found that the EEG characteristics varied among different types of CJD. The MRI results also showed differences. The findings suggest that early EEG may contribute to the early diagnosis of CJD.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Neurosciences
Kaori Taniguchi, Fumiko Yamamoto, Akiko Amano, Akira Tamaoka, Nobuo Sanjo, Takanori Yokota, Fuyuki Kametani, Wataru Araki
Summary: Recent evidence suggests that soluble amyloid-beta oligomers (AβOs) play a key role in the development of Alzheimer's disease (AD). AβOs induce neurotoxic and synaptotoxic effects by binding to certain receptors, specifically the GluN2B subunits of NMDA receptors and mGluR1. This study highlights the significance of these receptors in synaptic pathology in AD.
NEUROSCIENCE RESEARCH
(2022)
Article
Medicine, Research & Experimental
Hidetoshi Kaburagi, Tetsuya Nagata, Mitsuhiro Enomoto, Takashi Hirai, Masaki Ohyagi, Kensuke Ihara, Kie Yoshida-Tanaka, Satoe Ebihara, Ken Asada, Hiroyuki Yokoyama, Atsushi Okawa, Takanori Yokota
Summary: Neuropathic pain is a common condition with limited treatment options. This study demonstrates that a DNA/RNA heteroduplex oligonucleotide technology can effectively suppress gene expression related to neuropathic pain when delivered intravenously. This finding establishes a potential therapeutic platform for neuropathic pain and peripheral nerve disease.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Shunzaburo Ono, Masaaki Komatsu, Akira Sakai, Hideki Arima, Mie Ochida, Rina Aoyama, Suguru Yasutomi, Ken Asada, Syuzo Kaneko, Tetsuo Sasano, Ryuji Hamamoto
Summary: In this study, a deep learning-based method for automated endocardial border detection and left ventricular functional assessment in two-dimensional echocardiographic videos was developed. The method showed high accuracy in segmenting the left ventricular cavity and estimating echocardiographic indexes. Among the four segmentation methods tested, UNet++ performed the best. This method has the potential to support examiners and improve workflow in echocardiography.
Article
Biochemistry & Molecular Biology
Akira Sakai, Masaaki Komatsu, Reina Komatsu, Ryu Matsuoka, Suguru Yasutomi, Ai Dozen, Kanto Shozu, Tatsuya Arakaki, Hidenori Machino, Ken Asada, Syuzo Kaneko, Akihiko Sekizawa, Ryuji Hamamoto
Summary: Diagnostic support tools based on AI have shown high performance in medical fields, but lack of explanatory power in AI decisions makes it challenging to establish trust with medical professionals. Visualizing the internal representation of deep neural networks can enhance explanation and boost confidence in AI decisions. Using deep learning-based explainable representation improves the performance of fetal cardiac ultrasound screening, providing evidence of the potential of explainable AI to augment examiner capabilities.
Review
Biochemical Research Methods
Ryuji Hamamoto, Ken Takasawa, Norio Shinkai, Hidenori Machino, Nobuji Kouno, Ken Asada, Masaaki Komatsu, Syuzo Kaneko
Summary: The analysis of super-enhancers (SEs) is important for understanding the molecular mechanisms of cancer and other diseases. Machine learning technology is used to analyze SEs and integrate them with other data, providing a comprehensive understanding of SE analysis in medical biology. The accuracy of existing machine learning methods on benchmark datasets and the issues and future directions of SE analysis are also discussed.
BRIEFINGS IN BIOINFORMATICS
(2023)
Meeting Abstract
Oncology
Amina Bolatkan, Ken Asada, Syuzo Kaneko, Hidenori Machino, Ryuji Hamamoto
Review
Chemistry, Multidisciplinary
Zhiyuan Shi, Yong Hu, Xin Li
Summary: Controlled drug delivery systems that can respond to mechanical force offer a unique solution for on-demand drug activation and release. Among various mechanical stimuli, ultrasound (US) has advantages in achieving spatiotemporally controlled drug release. Traditional US-triggered drug release relies on heat-induced phase transitions or chemical transformations, while the cutting-edge approach of Sonopharmacology leverages polymer mechanochemistry. The remaining challenges and potential future directions in this field are also discussed.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Lijie Zheng, Yuanzheng Chen, Xun Gu, Yingying Li, Hanqing Zhao, Wenjun Shao, Tao Ma, Chuanbin Wu, Qingqing Wang
Summary: In this study, a novel dosage form consisting of dissolving microneedles and an adhesive transdermal patch was developed for the treatment of rheumatoid arthritis. In vitro and in vivo experiments demonstrated that the combination of drugs delivered by this dosage form effectively reduced joint inflammation and damage.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Kyungjik Yang, Hwa Seung Han, Seung Hwan An, Kyung Hoon Park, Keonwook Nam, Shinha Hwang, Yuyeon Lee, Sung Yeon Cho, Taehyung Kim, Deokyeong Choe, Sang Won Kim, Wonkyu Yu, Hyunah Lee, Jiyong Park, Sangguan You, Dong- Gyu Jo, Ki Young Choi, Young Hoon Roh, Jae Hyung Park
Summary: This study developed CP-loaded CS microcapsules to enhance the oral bioavailability of CP through controlled gastrointestinal delivery. The optimized microcapsules exhibited desirable physicochemical properties, showed anti-photoaging effects via antioxidant activity, and achieved controlled release in the gastrointestinal tract. This research provides a simple and economical approach for enhancing the oral bioavailability of CP for customized bioactive compound administration.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Huiyang Li, Shuo Liu, Wenjin Dai, Bingmei Yao, Yong Zhou, Sujia Si, Hairong Yu, Riguang Zhao, Fang Jin, Liqun Jiang
Summary: Changes in bodily fluid pressures are crucial in diseases like high-altitude pulmonary edema (HAPE). Researchers have developed hydrostatic pressure-sensitive multivesicular liposomes (PSMVLs) that can release drugs in response to pressure changes, with potential applications in HAPE treatment. Animal experiments showed that this system provides better protection for lung tissues and respiratory function, reducing the occurrence of pulmonary edema.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Qian Hu, Hongbing Lan, Yinmei Tian, Xiaonan Li, Mengmeng Wang, Jiao Zhang, Yulin Yu, Wei Chen, Li Kong, Yuanyuan Guo, Zhiping Zhang
Summary: Coacervate droplets formed through liquid-liquid phase separation have potential as delivery vesicles for therapeutics. However, their lack of physiological stability and membranes are challenges. In this study, polylysine-polynucleotide complex coacervate droplets with favorable stability were formulated to concentrate molecules and nanoparticles. Phospholipid membranes were further coated on the droplets to create coacervate-based artificial protocells (ArtPC) with membrane-like structures. These biofunctional ArtPC effectively reduced blood uric acid levels and prevented renal injuries.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Xiaowei Wang, Hongwei Lu, Fang Luo, Dan Wang, Apeng Wang, Xuelei Wang, Wenkai Feng, Xiaobo Wang, Jiayi Su, Mingliang Liu, Guimin Xia
Summary: Four novel lipid-like GEM diesters were synthesized and encapsulated into liposomes to improve the antitumor efficacy of Gemcitabine. The liposomes loaded with dimyristoyl GEM (LipodmGEM) showed enhanced cellular uptake, improved inhibition of cell migration, and a greatly extended half-life compared to free Gemcitabine. LipodmGEM successfully enriched the drug in the tumor and exhibited excellent anticancer efficacy in vivo with negligible systemic toxicity.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Pengyu Li, Jieyi Pan, Yating Dong, Yingying Sun, Yalong Wang, Kang Liao, Yili Chen, Xin Deng, Shihui Yu, Haiyan Hu
Summary: Chronic pulmonary infection caused by Pseudomonas aeruginosa is a serious public health problem with high mortality rates. In this study, infection-microenvironment responsive nanoparticles were developed to eradicate biofilms and inhibit virulence. These nanoparticles showed promising results in treating chronic pulmonary infections.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Yajing Sun, Ze Lu, John A. Taylor, Jessie L. S. Au
Summary: A recent development in cancer chemotherapy is the use of cytotoxics to induce tumor-specific immune response through immunogenic cell death (ICD). This study describes a method that utilizes immunostaining and machine-learning to identify cells with ecto-CRT in intact 3-dimensional tissues. The method was successfully applied to study drug-induced ICD in human bladder cancer.
JOURNAL OF CONTROLLED RELEASE
(2024)
Review
Chemistry, Multidisciplinary
Rafat Ali, Shantanu Sen, Rohil Hameed, Aamir Nazir, Sandeep Verma
Summary: This review provides a focused overview of emerging strategies for delivering gasotransmitters in a controlled and sustained manner to reestablish neurophysiological homeostasis.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Jing Chen, Xinyi Zhang, Jinshen Zhang, Zhaoxia Wang, Guilan Zhu, Ming Geng, Jinmiao Zhu, Yajun Chen, Wei Wang, Youcui Xu
Summary: In this study, a multifunctional responsive hydrogel system was developed for synergistic reoxygenation and chemo/photothermal therapy. The hydrogel system showed both therapeutic effects against metastatic breast cancer and wound infection, making it a promising strategy for treating and preventing tumor recurrence and associated wound infection.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Baoshan Huang, Na Zhang, Xinying Qiu, Rui Zeng, Shuimiao Wang, Mengxia Hua, Qing Li, Kaihui Nan, Sen Lin
Summary: This study revealed that robust ROS can oxidize mitochondrial DNA (ox-mtDNA) and cause its release into the cytosol, resulting in the activation of NLRP3 inflammasome. By using the mitochondria-targeted antioxidant SkQ1 and a novel mitochondria-targeted nanoparticle (SkQ1 NP), it was found that mitochondrial ROS scavenging could in situ inhibit DED-induced mtDNA oxidation and suppress NLRP3-mediated inflammation.
JOURNAL OF CONTROLLED RELEASE
(2024)
Article
Chemistry, Multidisciplinary
Wenqi Liu, Cheng Hu, Linyu Long, Shuyi He, Wen Zhang, Zhicun Wang, Li Yang, Yunbing Wang
Summary: Myocardial infarction is the leading cause of cardiovascular mortality, and current treatment methods have limitations. This study developed a smart carrier that can release different therapeutic substances for different pathological processes, effectively improving cardiac function, promoting cardiac repair, and preventing ventricular remodeling.
JOURNAL OF CONTROLLED RELEASE
(2024)