Article
Chemistry, Medicinal
Xin He, Guangchao He, Zhaoxing Chu, Huanhuan Wu, Junjie Wang, Yiran Ge, Hui Shen, Shan Zhang, Jinxi Shan, Kewen Peng, Zhifeng Wei, Yi Zou, Yungen Xu, Qihua Zhu
Summary: The study identified compound4t as the first inhibitor targeting both IDO1/2 with excellent in vitro inhibitory activity. This compound demonstrated significantly stronger in vivo antitumor potency compared to existing drugs in mouse models, highlighting the advantages of IDO1/2 dual inhibitors for tumor immunotherapy. Further mechanistic studies confirmed that 4t exerts its antitumor effect by inhibiting IDO1/2.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hui Phing Ang, Suzana Makpol, Muhammad Luqman Nasaruddin, Nurul Saadah Ahmad, Jen Kit Tan, Wan Asyraf Wan Zaidi, Hashim Embong
Summary: This study examined the role of IDO and TRP-KP in lipopolysaccharide-induced delirium in a chronic cerebral hypoperfusion model. The results showed that LPS treatment led to behavior deficits and increased IDO expression, suggesting a potential therapeutic target for delirium.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Sho Okuda, Kenoki Ohuchida, Shoichi Nakamura, Chikanori Tsutsumi, Kyoko Hisano, Yuki Mochida, Jun Kawata, Yoshiki Ohtsubo, Tomohiko Shinkawa, Chika Iwamoto, Nobuhiro Torata, Yusuke Mizuuchi, Koji Shindo, Taiki Moriyama, Kohei Nakata, Takehiro Torisu, Takashi Morisaki, Takanari Kitazono, Yoshinao Oda, Masafumi Nakamura
Summary: Although chemotherapy remains important, the development of immune checkpoint blockade therapy has been revolutionary, highlighting the importance of understanding the immunological tumor microenvironment (TME). Single cell RNA-sequencing analysis of human esophageal squamous cell carcinoma samples revealed that neoadjuvant chemotherapy (NAC) enhanced the anti-tumor immune response of CD8+/CD4+ T cells, dendritic cells (DCs), and macrophages in the TME. The interaction between immune cells in the NAC(+) group via various cytokines, including IFNG, EBI3, and NAMPT, further enhanced the anti-tumor immune response.
Article
Cell Biology
Patrick Thon, Katharina Rump, Annika Knorr, Birte Dyck, Dominik Ziehe, Matthias Unterberg, Hartmuth Nowak, Lars Bergmann, Alexander Wolf, Maha Bazzi, Jennifer Orlowski, Marcus Peters, Alexander Zarbock, Thorsten Brenner, Michael Adamzik, Tim Rahmel, Bjoern Koos
Summary: We established a diagnostic assay to quantify the phosphorylation of TLR-4, which can be used in both cell culture and clinical samples of sepsis patients, enabling large-scale stratification of sepsis patients based on their TLR-4 activation status.
Article
Multidisciplinary Sciences
Zhiren Wang, Wenpan Li, Yanhao Jiang, Tuyen Ba Tran, Leyla Estrella Cordova, Jinha Chung, Minhyeok Kim, Georg Wondrak, Jennifer Erdrich, Jianqin Lu
Summary: This study reported an EPA nanovesicle therapeutic platform called Epacasome, which showed improved pharmacokinetics and anti-tumor activity when combined with a PD-1 inhibitor in melanoma preclinical models.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Jiangxin Liu, Jian Ren, Kun Yang, Shuang Chen, Xinni Yang, Qin-Shi Zhao
Summary: This study reports the potential of synthetic analogues from Danshen as IDO1 and TDO inhibitors in cancer immunotherapy. The most potent compound, 30, was found to inhibit cancer cell growth by promoting apoptosis. These results contribute to the clinical application of tanshinone analogues.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Chang Hyeon Kong, Keontae Park, Do Yeon Kim, Jae Youn Kim, Woo Chang Kang, Mijin Jeon, Ji Won Min, Won Hyung Lee, Seo Yun Jung, Jong Hoon Ryu
Summary: This study investigates the effects of oleanolic acid (OA) and ursolic acid (UA) on depression-like behaviors in maternal separation (MS)-induced depression-like model. It is found that OA is more effective than UA in reversing depression-like behaviors caused by maternal separation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chenfei Zhou, Yanmei Zhang, Ruiming Yan, Lei Huang, Andrew L. Mellor, Yang Yang, Xiaojing Chen, Wenfei Wei, Xiangguang Wu, Lan Yu, Luojiao Liang, Dan Zhang, Sha Wu, Wei Wang
Summary: The high levels of miR-142-5p in advanced CSCC positively correlate with IDO expression in tumor-associated lymphatic vessels. The miR-142-5p is transferred by CSCC-secreted exosomes into LECs to induce IDO expression via ARID2-DNMT1-IFN-gamma signaling, leading to CD8(+)T cell exhaustion. This study suggests that LECs play a crucial role as immune checkpoints in the TME and may be a potential new target for CSCC diagnosis and treatment.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Multidisciplinary Sciences
Cristina C. Clement, Angelo D'Alessandro, Sangeetha Thangaswamy, Samantha Chalmers, Raquel Furtado, Sheila Spada, Giada Mondanelli, Federica Ianni, Sarah Gehrke, Marco Gargaro, Giorgia Manni, Luisa Carlota Lopez Cara, Peter Runge, Wanxia Li Tsai, Sinem Karaman, Jorge Arasa, Ruben Fernandez-Rodriguez, Amanda Beck, Antonio Macchiarulo, Massimo Gadina, Cornelia Halin, Francesca Fallarino, Mihaela Skobe, Marc Veldhoen, Simone Moretti, Silvia Formenti, Sandra Demaria, Rajesh K. Soni, Roberta Galarini, Roccaldo Sardella, Gregoire Lauvau, Chaim Putterman, Kari Alitalo, Ursula Grohmann, Laura Santambrogio
Summary: 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. The authors identify 3-HKA as a biogenic amine with anti-inflammatory properties, showing its protective effects against psoriasis and nephrotoxic nephritis in mice.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Malgorzata Sobstyl, Paulina Niedzwiedzka-Rystwej, Rafal Hrynkiewicz, Dominika Bebnowska, Izabela Korona-Glowniak, Marcin Pasiarski, Barbara Sosnowska-Pasiarska, Jolanta Smok-Kalwat, Stanislaw Gozdz, Anna Sobstyl, Wojciech Polkowski, Jacek Rolinski, Ewelina Grywalska
Summary: The study demonstrated the significance of TLR2 as a biomarker in advanced stage ovarian cancer by showing significantly higher expression levels in women with more advanced OC. This research sheds light on the prognostic potential of TLR2 in developing new diagnostic approaches and increasing survival in confirmed ovarian cancer patients.
Article
Psychiatry
Rozielly Aparecida Lemes dos Santos, Silvia Regina de Lima Reis, Patricia Cristiane Gibbert, Cristina Maria de Arruda, Diego Luiz Doneda, Yohan Alves Victor de Matos, Giordano Gubert Viola, Fabricio Rios Santos, Eliangela de Lima, Ziliani da Silva Buss, Samuel Vandresen-Filho
Summary: This study investigated the antidepressant-like effects and mechanisms of action of guanosine in a mouse model of lipopolysaccharide (LPS)-induced depression. The results showed that guanosine could prevent LPS-induced depressive-like behaviors by preventing oxidative stress and the expression of IDO-1 and TNF-α in the hippocampus.
JOURNAL OF PSYCHIATRIC RESEARCH
(2023)
Article
Microbiology
Axel Dietschmann, Sebastian Schruefer, Stefanie Westermann, Fiona Henkel, Kirstin Castiglione, Ralf Willebrand, Jasmin Adam, Jurgen Ruland, Roland Lang, Donald C. Sheppard, Julia Esser-von-Bieren, Daniel Radtke, Sven Krappmann, David Voehringer
Summary: Eosinophilia is associated with various inflammatory diseases, such as allergic bronchopulmonary aspergillosis (ABPA). It has been shown that direct interaction between eosinophils and Aspergillus fumigatus is essential for the activation of eosinophils, which then secrete multiple proinflammatory mediators. The PI3K-AKT-mTOR pathway plays a crucial role in A. fumigatus-induced eosinophil activation.
Article
Cell Biology
Chengtao Sun, Mengzhen Li, Lian Zhang, Feifei Sun, Huimou Chen, Yanjie Xu, Yingxia Lan, Li Zhang, Suying Lu, Jia Zhu, Junting Huang, Juan Wang, Yang Hu, Yanfen Feng, Yizhuo Zhang
Summary: This study found that IDO1 is upregulated in DLBCL and associated with poor prognosis and low overall survival. Inhibition of IDO1 can suppress DLBCL cell proliferation and prevent tumor formation. IDO1 inhibition induces cell cycle arrest and apoptosis by regulating factors associated with p53.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Wenjian Yao, Xiaohai Cui, Haodong Peng, Yongkang Zhang, Xiangbo Jia, Sen Wu, Jian Zhao
Summary: This study found that IDO1 expression was abnormally elevated in esophageal carcinoma (EC) and positively correlated with overall survival. IDO1 promoted the proliferation and migration of EC cells, and regulated the progression of EC by controlling the expression of chemokine CXCL10. This finding may provide a theoretical basis for precise therapies for EC.
CELL DEATH DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Piumi B. Wickramasinghe, Shuwen Qian, Lyndsey E. Langley, Chen Liu, Lin Jia
Summary: Accumulating evidence suggests that alcohol overconsumption is associated with insulin resistance, and this study investigated the role of hepatocyte toll-like receptor 4 (TLR4) in alcohol-induced insulin resistance. The findings indicate that hepatocyte TLR4 is both required and sufficient for the development of insulin resistance caused by alcohol overconsumption.
Article
Obstetrics & Gynecology
Daiki Hiratsuka, Shizu Aikawa, Yasushi Hirota, Yamato Fukui, Shun Akaeda, Takehiro Hiraoka, Mitsunori Matsuo, Yutaka Osuga
Summary: This study analyzed the epigenetic marks in dormant and activated blastocysts. It was found that cell cycle-related transcripts were affected during blastocyst activation, DNA methylations accumulated in downregulated genes in the activated blastocysts, and global alterations of histone H3 trimethylations occurred between the dormant and activated blastocysts. These findings reveal the regulatory roles of DNA methylation and histone modification in preimplantation blastocyst activation.
REPRODUCTIVE SCIENCES
(2023)
Article
Obstetrics & Gynecology
Mari Uehara, Osamu Hiraike, Mana Hirano, Miyuki Harada, Kaori Koga, Noriko Yoshimura, Sakae Tanaka, Yutaka Osuga
Summary: This study aimed to evaluate atherosclerosis-related biomarkers in perimenopausal women with endometriosis and their association with the risk of cardiovascular disease.
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
(2022)
Article
Obstetrics & Gynecology
Chihiro Ishizawa, Yasushi Hirota, Rei Iida, Tetsuaki Kaku, Tomoyuki Hirata, Yamato Fukui, Erika Omura, Shun Akaeda, Takehiro Hiraoka, Mitsunori Matsuo, Yutaka Osuga
Summary: This study aimed to investigate the efficacy of levonorgestrel-releasing intrauterine system (LNG-IUS) in improving menorrhagia-specific health-related quality of life (HR-QOL) in patients with symptomatic adenomyosis. The study found that LNG-IUS treatment effectively improved menorrhagia-specific HR-QOL in patients with incipient type adenomyosis, but its efficacy was decreased in patients with advanced type adenomyosis. LNG-IUS treatment also improved blood hemoglobin levels in incipient type adenomyosis but not in advanced type. Dysmenorrhea and heavy menstrual bleeding (HMB)-related anemia were associated with HR-QOL impairment, and LNG-IUS treatment may relieve these symptoms and improve HR-QOL. The use of magnetic resonance imaging should be reinforced to predict LNG-IUS efficacy in improving HR-QOL in patients with adenomyosis.
REPRODUCTIVE SCIENCES
(2023)
Article
Obstetrics & Gynecology
Iwaho Kikuchi, Mikio Momoeda, Takafumi Ujihira, Michiyo Iguchi, Kaori Koga, Mineto Morita
Summary: The aim of this study was to evaluate the safety and operability of GM142 adhesion barrier in patients undergoing surgery for benign gynecologic disease. The results showed that the barrier had a low incidence of adverse events and was easy to insert and position. No intestinal obstruction or gelatin-specific IgE antibodies were observed.
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
(2023)
Article
Obstetrics & Gynecology
Osamu Hiraike, Kaori Koga, Fuminori Taniguchi, Tasuku Harada, Toshiyuki Takeshita, Mitsuru Shiota, Yutaka Osuga
Summary: Based on two national cross-sectional surveys in Japan, the use of laparoscopic power morcellator (LPM) for uterine fibroid treatment was studied. The surveys revealed an increase in the number of surgeries performed with LPM, but a low incidence of postoperative malignancy. However, the possibility of malignant diseases cannot be completely excluded despite extensive preoperative diagnosis.
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
(2023)
Article
Cell Biology
Yamato Fukui, Yasushi Hirota, Shizu Aikawa, Akihiko Sakashita, Ryoko Shimizu-Hirota, Norihiko Takeda, Chihiro Ishizawa, Rei Iida, Tetsuaki Kaku, Tomoyuki Hirata, Takehiro Hiraoka, Shun Akaeda, Mitsunori Matsuo, Yutaka Osuga
Summary: Infertility affects 15% of couples worldwide, with recurrent implantation failure (RIF) being a major issue in IVF-ET programs. This study revealed that a uterine gene network regulated by the polycomb repressive complex 2 (PRC2) controls embryo implantation. Dysregulation of PRC2 components and target genes was observed in patients with RIF. Knockout mice studies showed that stromal Ezh2 plays a crucial role in female fertility. This research highlighted the importance of the EZH2-PRC2-H3K27me3 axis in preparing the endometrium for successful embryo invasion.
CELL DEATH & DISEASE
(2023)
Article
Medicine, General & Internal
Evdokia Dimitriadis, Daniel L. Rolnik, Wei Zhou, Guadalupe Estrada-Gutierrez, Kaori Koga, Rossana P. V. Francisco, Clare Whitehead, Jon Hyett, Fabricio da Silva Costa, Kypros Nicolaides, Ellen Menkhorst
Summary: Pre-eclampsia is a life-threatening disease unique to humans during pregnancy and is a major cause of morbidity and mortality for mothers and newborns. Survivors of pre-eclampsia have an increased risk of stroke, cardiovascular disease, and diabetes, while babies from pre-eclamptic pregnancies are at greater risk of preterm birth, perinatal death, neurodevelopmental disability, and cardiovascular and metabolic diseases later in life.
NATURE REVIEWS DISEASE PRIMERS
(2023)
Article
Obstetrics & Gynecology
Ayako Hashimoto, Takayuki Iriyama, Seisuke Sayama, Asuka Okamura, Kosuke Kato, Tatsuya Fujii, Kaori Kubota, Mari Ichinose, Kenbun Sone, Keiichi Kumasawa, Takeshi Nagamatsu, Yasushi Hirota, Yutaka Osuga
Summary: This study aimed to identify the characteristics of uterine adenomyosis lesions associated with increased obstetric complications through imaging findings. The results showed that patients with diffuse type adenomyosis were more likely to experience spontaneous second-trimester miscarriage, preterm premature rupture of membranes, and preeclampsia. In addition, patients with extrinsic type adenomyosis had a higher risk of placental malposition. Therefore, imaging evaluation of adenomyosis before conception or early in pregnancy may be useful for assessing obstetrical risks.
JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
(2023)
Review
Endocrinology & Metabolism
Hiroshi Ishikawa, Tatsuya Kobayashi, Meika Kaneko, Yoshiko Saito, Makio Shozu, Kaori Koga
Summary: Uterine fibroids are benign tumors characterized by abundant extracellular matrix and hormone-dependent growth. MED12 gene mutations are common and have a significant impact on tumor development. Understanding the function of MED12 mutations is crucial for developing new treatment options.
JOURNAL OF MOLECULAR ENDOCRINOLOGY
(2023)
Article
Obstetrics & Gynecology
Takehiro Hiraoka, Yutaka Osuga, Yasushi Hirota
Summary: Recurrent implantation failure (RIF) is a challenging problem in assisted reproductive technology (ART), and understanding the effects of uterine abnormalities on endometrial receptivity is important. This review discusses the impact of various uterine pathologies on defective embryo implantation and suggests potential treatments for RIF patients. Further studies are needed to fully understand the pathophysiology of abnormal endometrial receptivity and optimize ART treatments.
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
(2023)
Article
Obstetrics & Gynecology
Kaori Koga, Motoko Fukui, Masaki Fujisawa, Yoshimi Suzukamo
Summary: This study aimed to investigate the impact of uterine fibroid diagnosis/treatment status on quality of life (QOL) and work productivity in women living in Japan. The results showed that women with ongoing treatment for uterine fibroids had a high proportion of moderate to severe symptoms and reduced QOL. However, women with past treatment experienced improved QOL.
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
(2023)
Correction
Medicine, General & Internal
Evdokia Dimitriadis, Daniel L. Rolnik, Wei Zhou, Guadalupe Estrada-Gutierrez, Kaori Koga, Rossana P. V. Francisco, Clare Whitehead, Jon Hyett, Fabricio da Silva Costa, Kypros Nicolaides, Ellen Menkhorst
NATURE REVIEWS DISEASE PRIMERS
(2023)
Article
Obstetrics & Gynecology
Shota Ishikawa, Hiroshi Ishikawa, Mika Sato, Akiko Nagasawa, Yoshiya Suzuki, Jun Okayama, Emiri Nakada, Akiko Omoto, Makio Shozu, Kaori Koga
Summary: The aim of this study was to identify the symptoms and relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. The study found that factors such as massive postpartum hemorrhage, shock, impaired consciousness, and hysterectomy were associated with acute adrenal insufficiency.
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
(2023)
Article
Endocrinology & Metabolism
Mari Uehara, Osamu Wada-Hiraike, Kaori Koga, Naoko Yamamoto, Mana Hirano, Miyuki Harada, Yasushi Hirota, Yutaka Osuga
Summary: This study aimed to predict whether menstruation would resume in perimenopausal women after discontinuation of Dienogest (DNG) using serum estradiol and follicle-stimulating hormone (FSH) levels. The results showed that menstruation resumed when estradiol levels were >=17 pg/mL and FSH levels were <100 mIU/mL. This study provides useful criteria for deciding when to stop DNG in perimenopausal patients.
Article
Endocrinology & Metabolism
Mari Uehara, Osamu Wada-Hiraike, Kaori Koga, Naoko Yamamoto, Mana Hirano, Miyuki Harada, Yasushi Hirota, Yutaka Osuga
Summary: This case-control study used serum estradiol and follicle-stimulating hormone (FSH) levels to provide useful criteria for deciding when to halt Dienogest (DNG) therapy in perimenopausal women.