Article
Cell Biology
Melanie Jannaway, Drishya Iyer, Diandra M. Mastrogiacomo, Kunyu Li, Derek C. Sung, Ying Yang, Mark L. Kahn, Joshua P. Scallan
Summary: Research shows that the loss of Flt4 specifically in lymphatic cells inhibits the formation of specialized button junctions in multiple tissues and impairs interstitial absorption. Knockdown of FLT4 in human lymphatic endothelial cells results in disrupted NOTCH1 expression and activation, while overexpression of the NOTCH1 intracellular domain in Flt4 knockout vessels rescues the formation of button junctions and absorption of interstitial molecules. These findings reveal the importance of VEGFR3 and NOTCH1 signaling in the development of button junctions during postnatal development and may have clinical implications for lymphatic diseases with impaired VEGFR3 signaling.
Article
Multidisciplinary Sciences
Ayumi Inoue Nagahara, Jun Homma, Bikei Ryu, Hidekazu Sekine, Yuhei Higashi, Tatsuya Shimizu, Takakazu Kawamata
Summary: This study constructed cell sheets containing a network of lymphatic endothelial cells (LECs) by co-culturing LECs and adipose-derived stem cells (ASCs) and evaluated their lymphangiogenesis-promoting ability through transplantation into rats. The results showed that cell sheets with a specific cell ratio generated networks with more branches and longer branch lengths.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Zhilin Li, Salli Antila, Harri Nurmi, Dmitri Chilov, Emilia A. Korhonen, Shentong Fang, Sinem Karaman, Britta Engelhardt, Kari Alitalo
Summary: The recent discovery of lymphatic vessels in the dura mater has potential implications for alternative therapeutics in CNS disorders. However, inhibiting the VEGF-C/VEGFR3 signaling pathway does not affect the development of CNS autoimmunity, suggesting that dural lymphatic vessels do not directly contribute to CNS autoimmunity.
SCIENCE IMMUNOLOGY
(2023)
Article
Oncology
Hanhao Zheng, Changhao Chen, Yuming Luo, Min Yu, Wang He, Mingjie An, Bowen Gao, Yao Kong, Yiyao Ya, Yan Lin, Yuting Li, Keji Xie, Jian Huang, Tianxin Lin
Summary: In patients with lymph node metastatic bladder cancer, lncRNA BCYRN1 was found to be significantly upregulated in urinary exosomes and associated with BCa LN metastasis. BCYRN1 enhances lymphatic metastasis of BCa by activating Wnt/β-catenin signaling and promoting VEGF-C secretion. Blocking VEGFR3 can impair BCYRN1-induced LN metastasis.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Junzhuang Chang, Bingqing Guo, Yan Gao, Wei Li, Xiaoyu Tong, Yi Feng, Nashat Abumaria
Summary: Studies have confirmed the presence of a functional network of meningeal lymphatic vessels in the brain. This study aimed to investigate whether lymphatic vessels also extend deep into the brain parenchyma and whether they are regulated by stressful life events. Through various imaging techniques, the researchers demonstrated the existence of lymphatic vessels deep in the brain parenchyma and characterized their features in different brain regions. They also found that chronic stress and corticosterone treatment could regulate the length, area, and diameter of these lymphatic vessels in specific brain areas.
Correction
Multidisciplinary Sciences
Eric Song, Tianyang Mao, Huiping Dong, Ligia Simoes Braga Boisserand, Salli Antila, Marcus Bosenberg, Kari Alitalo, Jean-Leon Thomas, Akiko Iwasaki
Summary: A correction to this paper has been published with the provided link.
Article
Critical Care Medicine
Jianwen Liao, Mingchao Zhang, Zichuan Shi, Hao Lu, Lichen Wang, Weijia Fan, Xiaoguang Tong, Hua Yan
Summary: This study investigated the effects of ketoprofen, 9-cis retinoic acid (RA), and vascular endothelial cell growth factor-C (VEGF-C) on brain edema after traumatic brain injury (TBI). The results showed that these substances can improve the function of meningeal lymphatic vessels, promote brain edema absorption, reduce neuroinflammation, and improve neurological function.
JOURNAL OF NEUROTRAUMA
(2023)
Review
Biochemistry & Molecular Biology
Boksik Cha, Sungjin Moon, Wantae Kim
Summary: The lymphatic vasculature plays a critical role in regulating fluid balance, intestinal lipid absorption, and immune surveillance in the human body, while dysfunction can lead to various diseases. Understanding the mechanisms of lymphatic vascular development is important for expanding knowledge and providing new therapeutic perspectives. The Hippo-YAP/TAZ signaling pathway has emerged as a key player in regulating lymphatic specification and maturation.
Article
Oncology
Sen Liu, Xu Chen, Tianxin Lin
Summary: The article summarizes the molecular mechanisms of lymphatic metastasis in bladder cancer, including lymphangiogenesis, noncoding RNAs, and microenvironment-associated molecules. Newly discovered radiomics and genomics approaches have improved the preoperative diagnostic accuracy of lymph node metastasis, potentially leading to promising therapeutic strategies.
Article
Cell Biology
Ying Zhang, Conghui Zhang, Lixi Li, Xinjun Liang, Peng Cheng, Qing Li, Xiaoyan Chang, Kun Wang, Shuai Huang, Yueqiang Li, Yanyan Liu, Gang Xu
Summary: This study demonstrated a close relationship between lymphangiogenesis and renal fibrosis, with M1 macrophages predominately transdifferentiating into LECs. The VEGF-C/VEGFR3 signaling pathway was found to downregulate macrophage autophagy, promoting M1 macrophage polarization. These results suggest that M1 macrophages play a role in promoting lymphangiogenesis in renal fibrosis microenvironment, with VEGF-C/VEGFR3 pathway activating macrophage M1 polarization by suppressing macrophage autophagy.
CELL DEATH & DISEASE
(2021)
Article
Immunology
Qian Li, Yan Chen, Weixi Feng, Jiachen Cai, Junying Gao, Feifei Ge, Tiantian Zhou, Ze Wang, Fengfei Ding, Charles Marshall, Chengyu Sheng, Yongjie Zhang, Mingkuan Sun, Jingping Shi, Ming Xiao
Summary: Recent progress on the central lymphatic system has revealed the function of perivascular spaces and meningeal lymphatic vessels in clearing senescent astrocytes from the aging brain. Blocking meningeal lymphatic drainage leads to impaired clearance and increased neuroinflammation, while enhancing meningeal lymphatic vessel diameter improves clearance and mitigates neuroinflammation. The findings suggest that meningeal lymphatics could be a therapeutic target for age-related brain disorders.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Gastroenterology & Hepatology
Shao-Jung Hsu, Chihao Zhang, Jain Jeong, Seong-il Lee, Matthew McConnell, Teruo Utsumi, Yasuko Iwakiri
Summary: This study demonstrated that enhancing meningeal lymphatic drainage can reduce neuroinflammation and ameliorate hepatic encephalopathy, suggesting a new therapeutic strategy for the treatment of HE.
Article
Biochemistry & Molecular Biology
Svitlana Skoroplyas, Ondrej Vasicek, Michaela Chorvatova, Petra Dad'ova, Katerina Lehka, Lukas Kubala
Summary: Pseurotin D has the potential to inhibit DTH reaction through inhibiting the activation and differentiation of both T cells and B cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Immunology
Adri Chakraborty, Raghavendra Upadhya, Timaj A. Usman, Ashok K. Shetty, Joseph M. Rutkowski
Summary: The study investigated the impact of chronic VEGFR-3 signaling on adipose neuro-connections and neuroprotection in neurons both in vivo and in vitro. Results showed that chronic VEGFR-3 activation in adipose tissue decreased dendrite length, terminal branches, and volume, but increased dendrite branching. Furthermore, VEGFR-3 signaling provided neuroprotection in challenged neurons and improved dendritic arbor complexity, suggesting a synergistic impact on neurosensitization and neuroprotection during stress.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Biochemistry & Molecular Biology
Laura Alderfer, Elizabeth Russo, Adriana Archilla, Brian Coe, Donny Hanjaya-Putra
Summary: This study demonstrates that low matrix elasticity primes the formation of lymphatic cord-like structures directed by a high concentration of VEGF-C, resulting in the upregulation of key lymphatic markers and activation of matrix metalloproteinases. By tuning the matrix stiffness and VEGF-C concentration, the signaling pathways of CLS formation can be regulated in a synthetic matrix, providing useful insights for lymphatic biology research and tissue regeneration approaches.
Article
Oncology
Yasuhiro Fujisawa, Takamichi Ito, Hiroshi Kato, Hiroyuki Irie, Tatsuya Kaji, Takeo Maekawa, Jun Asai, Yuki Yamamoto, Taku Fujimura, Yasuo Nakai, Masahito Yasuda, Kanako Matsuyama, Ikko Muto, Shigeto Matsushita, Hiroshi Uchi, Yoshiyuki Nakamura, Jiro Uehara, Koji Yoshino
Summary: In Japanese patients with advanced melanoma treated with BRAF and MEK inhibitor combination therapy, the response rate for the entire cohort was 75.0%, with patients achieving complete response having the best survival rates. The most common relapse site was the brain, and more than half of the patients experienced grade III/IV pyrexia.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Ophthalmology
Yusuke Mitsuoka, Takeshi Soma, Kazuichi Maruyama, Kohji Nishida
Summary: The case report describes a 65-year-old female patient with rheumatic keratitis who developed a Fusarium infection leading to endophthalmitis during tocilizumab therapy. Despite initial positive response to anti-fungal treatment, corneal infiltration, worsening hypopyon, and vitreous opacity were observed post-tocilizumab infusion. Surgical intervention with penetrating keratoplasty and vitrectomy was required for resolution of symptoms. Close monitoring of ocular conditions is recommended during systemic tocilizumab administration to mitigate the risk of infection.
Article
Biochemistry & Molecular Biology
Kazuichi Maruyama, Kazuhito Yoneda, Sunao Sugita, Yoshimi Yamamoto, Masato Koike, Christoph Peters, Yasuo Uchiyama, Kohji Nishida
Summary: CTLA-2α can suppress angiogenesis by inhibiting endothelial cell proliferation in ocular tissue, while it is unable to suppress cytokine secretion from inflammatory cells. Further research is needed to explore the potential of CTLA-2α as a new antiangiogenic treatment for various conditions, including age-related macular degeneration.
Article
Ophthalmology
Yukiko Terada, Toshikatsu Kaburaki, Hiroshi Takase, Hiroshi Goto, Satoko Nakano, Yoshitsugu Inoue, Kazuichi Maruyama, Kazunori Miyata, Kenichi Namba, Koh-Hei Sonoda, Yutaka Kaneko, Jiro Numaga, Masaya Fukushima, Noe Horiguchi, Mitsunao Ide, Fumie Ehara, Dai Miyazaki, Eiichi Hasegawa, Manabu Mochizuki
Summary: This study aimed to determine the clinical characteristics of anterior uveitis caused by HSV, VZV, and CMV, finding significant differences between CMV-associated AU and the other two types. Symptoms like ocular hyperemia, pain, blurring of vision, and signs like keratic precipitates were more common in HSV-AU and VZV-AU compared to CMV-AU.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jun Asai
Summary: Podoplanin is a glycoprotein receptor that is highly expressed in normal skin and plays a crucial role in various pathological skin conditions, including psoriasis, chronic inflammation, wound healing, and skin cancer. It is involved in epidermal hyperproliferation, IL-17 secretion, re-epithelialization, and tumor cell migration and epithelial-mesenchymal transition. In addition, its expression in peritumoral cells can predict aggressive behavior and poor prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Ophthalmology
Kenichi Namba, Hiroshi Takase, Yoshihiko Usui, Fumihiko Nitta, Kazuichi Maruyama, Sentaro Kusuhara, Masaki Takeuchi, Atsushi Azumi, Ryoji Yanai, Yutaka Kaneko, Eiichi Hasegawa, Kei Nakai, Hidekazu Tsuruga, Kazuo Morita, Toshikatsu Kaburaki
Summary: In Japanese clinical practice, many patients with recurrent non-infectious uveitis accompanying VKH disease or sarcoidosis require long-term use of systemic corticosteroids, suggesting that reducing corticosteroids is challenging in patients with difficulty suppressing inflammation.
JAPANESE JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Ophthalmology
Kazuichi Maruyama, Chiharu Iwahashi, Noriyasu Hashida, Nobuyuki Ohguro, Kohji Nishida
Summary: The study investigated diffuse large B-cell lymphoma lesions with CNS involvement in patients with VRL during long-term clinical courses. Over 60% of the VRL patients had CNS lesions, which were not associated with the optic pathway or visual cortex. Clinicians should carefully examine CNS lesions occurring in both forebrain- and hindbrain-originating tissues during a patient's clinical course.
JAPANESE JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Cell & Tissue Engineering
Nobuhiko Shiraki, Kazuichi Maruyama, Ryuhei Hayashi, Akiko Oguchi, Yasuhiro Murakawa, Tomohiko Katayama, Toru Takigawa, Susumu Sakimoto, Andrew J. Quantock, Motokazu Tsujikawa, Kohji Nishida
Summary: The study found that cells with characteristics resembling microglia naturally develop in eye-like SEAM organoids derived from human-induced pluripotent stem cells. These unique cells are PAX6-positive and possess some mesoderm characteristics.
Article
Ophthalmology
Kazuichi Maruyama, Song Mei, Hirokazu Sakaguchi, Chikako Hara, Atsuya Miki, Zaixing Mao, Ryo Kawasaki, Zhenguo Wang, Susumu Sakimoto, Noriyasu Hashida, Andrew J. Quantock, Kinpui Chan, Kohji Nishida
Summary: This study quantifies choroidal vessels in pathological eyes using optical coherence tomography and deep-learning analysis. The 3D visualization and quantification provided by this method allows for the diagnosis and differentiation of choroidal diseases. The results show high sensitivity and specificity in distinguishing between pathological and healthy choroids.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2022)
Article
Ophthalmology
Yuki Hamano, Kazuichi Maruyama, Yoshinori Oie, Naoyuki Maeda, Shizuka Koh, Noriyasu Hashida, Kohji Nishida
Summary: This study used CASIA-2 to investigate for the first time the morphological changes in the anterior segment of the eye in VKH patients, revealing that these changes may affect visual acuity and the astigmatic axis. Assessing corneal morphology is essential in determining the cause of visual function deterioration in VKH patients.
JAPANESE JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Ophthalmology
Kosuke Miyazawa, Susumu Sakimoto, Masanori Kanai, Akihiko Shiraki, Shizuka Takahashi, Nobuhiko Shiraki, Kazuichi Maruyama, Hirokazu Sakaguchi, Kohji Nishida
Summary: This study evaluated the macular vessel tortuosity using OCTA after ERM surgery and found that the change in vessels around the macula becoming more linear was associated with visual outcomes postoperatively.
Article
Cell & Tissue Engineering
Yu Yoshinaga, Takeshi Soma, Shohei Azuma, Kazuichi Maruyama, Yoshiko Hashikawa, Tomohiko Katayama, Yuzuru Sasamoto, Hiroshi Takayanagi, Naoki Hosen, Takashi Shiina, Kazumasa Ogasawara, Ryuhei Hayashi, Kohji Nishida
Summary: This study investigated the impact of human leukocyte antigen (HLA) on corneal epithelial cell sheet (CEPS) transplantation. The results showed that there was no difference in immune response to CEPS between HLA-matched and -unmatched peripheral blood mononuclear cells. Additionally, programmed death ligand 1 was identified to have an immunosuppressive effect on CEPS under inflammatory conditions.
Article
Medicine, General & Internal
Hiroyuki Komatsu, Yoshihiko Usui, Kinya Tsubota, Risa Fujii, Takefumi Yamaguchi, Kazuichi Maruyama, Ryo Wakita, Masaki Asakage, Hiroyuki Shimizu, Naoyuki Yamakawa, Naoya Nezu, Koji Ueda, Hiroshi Goto
Summary: Comprehensive proteomic analysis revealed altered vitreous protein expression levels that can discriminate ocular sarcoidosis from other forms of uveitis. Neutrophil gelatinase-associated lipocalin (NGAL) and junctional adhesion molecules B (JAMB) were identified as potential biomarkers for ocular sarcoidosis, serving as an auxiliary tool for its diagnosis.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, General & Internal
Noriyasu Hashida, Kazunobu Asao, Chikako Hara, Andrew J. Quantock, Ryotaro Saita, Hiroyuki Kurakami, Kazuichi Maruyama, Kohji Nishida
Summary: The study demonstrated that elevated serum levels of mtDNA and HMGB1 were associated with the clinical activities of CSC, indicating that serum mtDNA and HMGB1 could serve as biomarkers for the acute phase of the disease, allowing for the prediction of disease onset and determination of disease severity.
FRONTIERS IN MEDICINE
(2022)
Article
Ophthalmology
Reiko Kobayashi, Noriyasu Hashida, Kazuichi Maruyama, Kohji Nishida
Summary: The aim of this study was to evaluate the usefulness of specular microscopy as a diagnostic tool for CMV corneal endotheliitis. Through the study of 104 patients with infectious corneal endotheliitis, iridocyclitis, and retinitis, it was found that 22% of the cases observed owl's eye cells through specular microscopy, which was related to the occurrence of CMV endotheliitis. Specular microscopy can be used as a useful tool for diagnosing and monitoring CMV corneal endotheliitis.
ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
(2022)