Article
Cell Biology
Alaknanda Emery, Kylie R. Dunning, Doan T. Dinh, Lisa K. Akison, Rebecca L. Robker, Darryl L. Russell
Summary: The ovarian follicle is a complex structure that protects and helps in the maturation and release of the oocyte. The progesterone receptor (PGR) plays a key role in regulating ovulation-related gene expression changes. The study found disrupted expression of the cellular adhesion receptor gene Sema7A in the granulosa cells of PGR-/- mice during ovulation. Furthermore, it was discovered that gonadotropins and hypoxia promote the expression of Sema7A in preovulatory follicles, resulting in an asymmetrical pattern with enriched SEMA7A protein. After an ovulatory stimulus, Sema7A expression is downregulated, the abundance of SEMA7A protein is reduced, and the asymmetrical pattern becomes more homogeneous. The study also found that adhesive receptor Itga5 is significantly increased during ovulation, while repulsive Plxnc1 receptor is inversely regulated.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Obstetrics & Gynecology
H. Jeon, Y. Choi, M. Brannstrom, J. W. Akin, T. E. Curry, M. Jo
Summary: This study shows that cortisol/glucocorticoid receptors play a crucial role in regulating steroidogenesis and the ovulatory cascade during ovulation and early luteinization in humans.
HUMAN REPRODUCTION
(2023)
Article
Multidisciplinary Sciences
Limor Man, Nicole Lustgarten Guahmich, Eleni Kallinos, Barbara Caiazza, Monica Khan, Zong-Ying Liu, Ritaben Patel, Carmen Torres, David Pepin, He S. Yang, Richard Bodine, Nikica Zaninovic, Glenn Schattman, Zev Rosenwaks, Daylon James
Summary: Superphysiologic levels of AMH may disrupt ovulatory function by accelerating follicle maturation and luteinization.
Article
Reproductive Biology
Linah Al-Alem, Muraly Puttabyatappa, Ketan Shrestha, Yohan Choi, Kathy Rosewell, Mats Brannstrom, James Akin, Misung Jo, Diane M. Duffy, Thomas E. Curry
Summary: The study found that NTS expression in the ovaries of humans and rats significantly increased during ovulation, possibly regulated by the epidermal growth factor pathway and protein kinase A pathway. NTS may regulate crucial aspects of ovulation such as vascular permeability, inflammation, and cell migration.
BIOLOGY OF REPRODUCTION
(2021)
Article
Medicine, Research & Experimental
Xiaohong Chen, Hongliang Tang, Yingye Liang, Pingting Wu, Liuhong Xie, Yao Ding, Peng Yang, Bingcai Long, Jing Lin
Summary: Acupuncture can improve ovulation dysfunction and abnormal follicular development in patients with polycystic ovary syndrome by down-regulating LncMEG3 expression, inhibiting the PI3K/AKT/mTOR pathway, reducing granulosa cell autophagy, and ultimately normalizing their proliferation, suggesting its clinical potential as a safe treatment for PCOS ovulatory dysfunction.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Reproductive Biology
Zaramasina L. Clark, Kaitlin R. Karl, Meghan L. Ruebel, Keith E. Latham, James J. Ireland
Summary: Excessive doses of FSH during ovarian stimulation may induce premature luteinization of most ovulatory-size follicles in heifers with small ovarian reserves, leading to ovarian dysfunction.
BIOLOGY OF REPRODUCTION
(2022)
Article
Chemistry, Multidisciplinary
Kuo Zhang, Yong-Hong Gao, Wei-Shen Zhong, Hui Cao, Kai Yue, Lei Wang, Hao Wang
Summary: This study investigates the fibrillogenesis process of the BIF peptide in the absence and presence of receptors (Ca2+). The fibrillogenesis of the BIF peptide is achieved through different mechanisms, including nucleation-elongation without Ca2+ and Ostwald ripening and heterogeneous secondary nucleation with Ca2+. The attachment and shape change of BIF NPs on pre-formed BIF NFs are observed, providing insights into the fast BIF process.
Article
Developmental Biology
Ejimedo Madogwe, Yasmin Schuermann, Dayananda Siddappa, Vilceu Bordignon, Philippe P. Roux, Raj Duggavathi
Summary: This study demonstrates that sustained ERK1/2 signaling is crucial for follicular rupture during ovulation in mice, while it is not required for cumulus expansion, oocyte meiotic maturation and luteinization.
Article
Biochemistry & Molecular Biology
Hiroshi Koike, Miyuki Harada, Akari Kusamoto, Chisato Kunitomi, Zixin Xu, Tsurugi Tanaka, Yoko Urata, Emi Nose, Nozomi Takahashi, Osamu Wada-Hiraike, Yasushi Hirota, Kaori Koga, Yutaka Osuga
Summary: This study demonstrates that Notch2 signaling is activated in granulosa cells of patients with polycystic ovary syndrome (PCOS) and regulates the expansion of cumulus-oocyte complexes (COC) in PCOS. It is also found that endoplasmic reticulum (ER) stress induces Notch signaling in granulosa cells, leading to aberrant COC expansion. Inhibition of Notch signaling blocks the ER stress-induced expression of genes associated with COC expansion and reduces the size of COCs in PCOS model mice.
Article
Multidisciplinary Sciences
Grace Aprilia Helena, Teruhiko Watanabe, Yusuke Kato, Nobuaki Shiraki, Shoen Kume
Summary: By adjusting the thawing protocol and medium composition, we successfully improved the attachment of PHH cells on the collagen matrix. Removing BSA and exposing the cells to cAMP activators such as IBMX and Forskolin enhanced PHH attachment. Activation of EPAC2 increased PHH attachment and induced bile canaliculi formation in iPS-derived hepatocytes.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Hyo-Jin Park, Bokyung Kim, Deog-Bon Koo, Dong-Seok Lee
Summary: This study revealed that PRDX1 is expressed in the ovary and during ovulation, controlling the TLR4/P38/ERK1/2 signaling activity in ovulated mice and its interaction with COCs during ovulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Takuya Kanke, Wataru Fujii, Kunihiko Naito, Koji Sugiura
Summary: The study investigated the effects of FGF signaling on cumulus expansion in mice, and found that FGFs, other than FGF8, exert suppressive effects on the process of cumulus expansion.
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2022)
Article
Multidisciplinary Sciences
Veronica Vidal, Olga Gutierrez, Ana Talamillo, Carlos Velasquez, Jose L. Fernandez-Luna
Summary: The study revealed that the interaction with elements in the tumor microenvironment, mainly activated monocytes through IL-6 secretion, and the extracellular matrix protein fibronectin, induced the Stat3 transcriptional pathway and upregulated ODZ1, promoting GBM cell migration. Blocking IL-6 receptor, inhibiting Jak kinases or knocking down Stat3 abrogated this signaling route, further confirming the role of monocyte-secreted IL-6 and fibronectin in activating the Stat3-ODZ1 axis for GBM cell migration.
SCIENTIFIC REPORTS
(2021)
Article
Reproductive Biology
You-Qiang Su, Yaoxue Yin, Jing Guo, Xuhong Gong, Yufeng Tian, Lanying Shi
Summary: The coordinated development of germline and somatic compartments in a follicle is crucial for the formation of a functional oocyte. The bi-directional communication between the oocyte and granulosa cells plays a vital role in supporting the development and function of both compartments. MTOR, a serine/threonine kinase, is emerging as a major regulator of oocyte and follicle development, controlling various aspects of their development and function.
BIOLOGY OF REPRODUCTION
(2022)
Article
Oncology
Adam N. R. Cartwright, Shengbao Suo, Soumya Badrinath, Sushil Kumar, Johannes Melms, Adrienne Luoma, Archis Bagati, Assieh Saadatpour, Benjamin Izar, Guo-Cheng Yuan, Kai W. Wucherpfennig
Summary: The study demonstrates that MDSCs do not block early steps of T-cell activation but induce DNA damage and p53 pathway activation in CD8(+) T cells through an iNOS-dependent pathway.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Multidisciplinary Sciences
Takashi Umehara, Yasmyn E. Winstanley, Eryk Andreas, Atsushi Morimoto, Elisha J. Williams, Kirsten M. Smith, John Carroll, Mark A. Febbraio, Masayuki Shimada, Darryl L. Russell, Rebecca L. Robker
Summary: Ovarian fibrosis is identified as the underlying mechanism for impaired oocyte release, with antifibrosis drugs potentially restoring ovulation function in reproductively old or obese mice. Targeting mitochondrial metabolism with such drugs could be a viable therapeutic strategy for women with metabolic disorders or advancing age.
Article
Food Science & Technology
Shabbir Ahmed, Mst. Umme Habiba, Md. Delowar Hossain, S. A. Masudul Hoque, Md. Morshedur Rahman
Summary: This study aimed to compare the antioxidant activity of Orange Peel Powder (OPP) in ghee at different temperatures and storage periods. The results showed that OPP-treated ghee samples had lower peroxide, TBA, and FFA values compared to control samples, indicating stronger antioxidant capacity. OPP can be used as a natural source of antioxidants in ghee.
JOURNAL OF FOOD SCIENCE AND TECHNOLOGY-MYSORE
(2023)
Article
Biochemistry & Molecular Biology
Hideaki Ohtomo, Shinsuke Ito, Nicholas J. McKenzie, Michael Uckelmann, Masatoshi Wakamori, Haruhiko Ehara, Ayako Furukawa, Yasuo Tsunaka, Marika Shibata, Shun-ichi Sekine, Takashi Umehara, Chen Davidovich, Haruhiko Koseki, Yoshifum Nishimura
Summary: PRC1 and PRC2 play important roles in epigenetic gene regulation. H2A ubiquitination by PRC1 promotes H3K27 methylation by PRC2 through altering the dynamics of H3-tail and its contacts with DNA, with the linker-DNA being crucial for this process.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Shohei Takase, Takashi Hiroyama, Fumiyuki Shirai, Yuki Maemoto, Akiko Nakata, Mayumi Arata, Seiji Matsuoka, Takeshi Sonoda, Hideaki Niwa, Shin Sato, Takashi Umehara, Mikako Shirouzu, Yosuke Nishigaya, Tatsunobu Sumiya, Noriaki Hashimoto, Ryosuke Namie, Masaya Usui, Tomokazu Ohishi, Shun-ichi Ohba, Manabu Kawada, Yoshihiro Hayashi, Hironori Harada, Tokio Yamaguchi, Yoichi Shinkai, Yukio Nakamura, Minoru Yoshida, Akihiro Ito
Summary: Sickle cell disease (SCD) is caused by beta-globin gene mutations. G9a inhibitors, including RK-701, have been proposed as therapeutic agents for inducing fetal globin expression. This study describes the development of RK-701 as a selective and non-genotoxic G9a inhibitor, which upregulates BGLT3 long non-coding RNA and induces gamma-globin expression. BGLT3 is identified as an essential factor for gamma-globin induction and its universal role suggests its importance in SCD treatment.
NATURE COMMUNICATIONS
(2023)
Article
Green & Sustainable Science & Technology
Md. Delowar Hossain, Md. Abdus Salam, Shabbir Ahmed, Mst. Umme Habiba, Shahrina Akhtar, Md. Mazharul Islam, S. A. Masudul Hoque, Abu Sadeque Md. Selim, Md. Morshedur Rahman
Summary: Global warming has caused an increase in heat stress for animals, which can be measured using the Temperature Humidity Index (THI). This study examined the THI pattern and its relationship with the production performances of dairy cows in Bangladesh. The results showed that June had a higher THI value compared to January, leading to a decrease in milk production, milk fat, and protein content. However, ash content increased. Regression analysis revealed that a higher THI and rectal temperature were associated with lower milk yield.
Article
Chemistry, Medicinal
Yosuke Nishigaya, Shohei Takase, Tatsunobu Sumiya, Ko Kikuzato, Tomohiro Sato, Hideaki Niwa, Shin Sato, Akiko Nakata, Takeshi Sonoda, Noriaki Hashimoto, Ryosuke Namie, Teruki Honma, Takashi Umehara, Mikako Shirouzu, Hiroo Koyama, Minoru Yoshida, Akihiro Ito, Fumiyuki Shirai
Summary: The study focused on identifying novel inhibitors of lysine methyltransferase G9a for cancer epigenetics. Using HTS hit rac-10a from the chemical library of the University of Tokyo, the researchers established the structure-activity relationship of substrate-competitive inhibitors. Further optimization led to the discovery of compound 26j as a potent inhibitor of G9a/GLP with selective inhibition against other methyltransferases. Compound 26j demonstrated dose-dependent attenuation of H3K9me2 levels, tumor growth inhibition in vitro, and inhibition of tumor initiation and growth in a mouse model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nan Liu, Tsuyoshi Konuma, Rajal Sharma, Deyu Wang, Nan Zhao, Lingling Cao, Ying Ju, Di Liu, Shuai Wang, Almudena Bosch, Yifei Sun, Siwei Zhang, Donglei Ji, Satoru Nagatoishi, Noa Suzuki, Masaki Kikuchi, Masatoshi Wakamori, Chengcheng Zhao, Chunyan Ren, Thomas Jiachi Zhou, Yaoyao Xu, Jamel Meslamani, Shibo Fu, Takashi Umehara, Kouhei Tsumoto, Satoko Akashi, Lei Zeng, Robert G. Roeder, Martin J. Walsh, Qiang Zhang, Ming-Ming Zhou
Summary: Histone lysine acylation, such as acetylation and crotonylation, plays a crucial role in gene transcription, but our understanding has been limited to transcriptional activation. This study reveals that histone H3 lysine 27 crotonylation (H3K27cr) is involved in gene transcriptional repression. The YEATS domain of GAS41 selectively recognizes H3K27cr in chromatin and forms a complex with SIN3A-HDAC1 co-repressors. The proto-oncogenic transcription factor MYC recruits the GAS41/SIN3A-HDAC1 complex to repress genes, including the cell-cycle inhibitor p21.
Article
Cell Biology
Kota Noritsugu, Takehiro Suzuki, Kosuke Dodo, Kenji Ohgane, Yasue Ichikawa, Kota Koike, Satoshi Morita, Takashi Umehara, Kenji Ogawa, Mikiko Sodeoka, Naoshi Dohmae, Minoru Yoshida, Akihiro Ito
Summary: TEAD transcription factors regulate the transcriptional output of Hippo signaling by phosphorylating YAP and TAZ as coactivators. Recent studies have shown that cysteine palmitoylation also plays a role in regulating TEAD activity. This study discovers lysine long-chain fatty acylation as another post-translational modification of TEADs. Lysine fatty acylation enhances the interaction between TEADs and YAP/TAZ, contributing to their transcriptional activity. Interestingly, lysine fatty acylation of TEADs increases upon Hippo signaling activation, despite a decrease in cysteine acylation. These findings provide new insights into the regulation of TEAD activity through fatty-acyl modifications.
Review
Genetics & Heredity
Nando Dulal Das, Hideaki Niwa, Takashi Umehara
Summary: The dynamic regulation of histone methylation and demethylation is crucial for gene expression regulation. Abnormal expression of histone lysine demethylases has been linked to various diseases, including intractable cancers, thus making them promising therapeutic targets. Recent advancements in epigenomics and chemical biology have resulted in the development of potent, specific, and in vivo effective small-molecule demethylase inhibitors. This review highlights emerging small-molecule inhibitors targeting histone lysine demethylases and their progress towards drug discovery.
Article
Biotechnology & Applied Microbiology
Nando D. Das, Jen-Chien Chang, Chung-Chau Hon, S. Thomas Kelly, Shinsuke Ito, Marina Lizio, Bogumil Kaczkowski, Hisami Watanabe, Keisuke Katsushima, Atsushi Natsume, Haruhiko Koseki, Yutaka Kondo, Aki Minoda, Takashi Umehara
Summary: This study found that H4K5acK8ac and H3K27ac signals have some overlap in binding to the super-enhancer transcription factor BRD4 at higher levels, but they also have distinct specificities, especially in glioblastoma stem-like cell lines. Deletion of H4K5acK8ac-preferred super-enhancers associated with MYCN and NFIC resulted in a reduction in stem-like properties.
Article
Multidisciplinary Sciences
Masaki Kikuchi, Satoshi Morita, Masatoshi Wakamori, Shin Sato, Tomomi Uchikubo-Kamo, Takehiro Suzuki, Naoshi Dohmae, Mikako Shirouzu, Takashi Umehara
Summary: In this study, the authors discovered that p300/CBP recognizes and acetylates histone H4 N-terminal tail (NT) acetylation (ac) in a nucleosome, and also acetylates non-H4 histone NTs within the same nucleosome. The authors propose a model in which p300/CBP replicates histone N-terminal tail acetylation within the H3-H4 tetramer and transfers it to the H2B-H2A dimers to activate context-dependent gene transcription through local nucleosome destabilization.
NATURE COMMUNICATIONS
(2023)
Article
Developmental Biology
Md Mazharul Islam, Takashi Umehara, Natsumi Tsujita, Masanori Koyago, Masayuki Shimada
Summary: This study demonstrates that exogenous cholesterol treatment can enhance the quality of frozen-thawed bull sperm by restoring the cholesterol balance in sperm plasma and organelle membranes. The addition of exogenous cholesterol protects the plasma membrane and maintains mitochondrial function, thereby improving sperm motility and fertility. Therefore, the application of cholesterol after thawing is a promising option for improving the fertility of frozen-thawed sperm.
MOLECULAR HUMAN REPRODUCTION
(2023)
Article
Obstetrics & Gynecology
Shingo Tonai, Tomoya Nakanishi, Manami Yamaoka, Asako Okamoto, Masayuki Shimada, Yasuhisa Yamashita
Summary: This study revealed that transferrin-iron complex (Holo-TF) played a crucial role in the developmental competence of porcine oocytes. Addition of Holo-TF during pre-IVM significantly improved the developmental potential and embryo yield.
REPRODUCTIVE MEDICINE AND BIOLOGY
(2023)
Article
Chemistry, Medicinal
Yosuke Nishigaya, Shohei Takase, Tatsunobu Sumiya, Ko Kikuzato, Tomohiro Sato, Hideaki Niwa, Shin Sato, Akiko Nakata, Takeshi Sonoda, Noriaki Hashimoto, Ryosuke Namie, Teruki Honma, Takashi Umehara, Mikako Shirouzu, Hiroo Koyama, Minoru Yoshida, Akihiro Ito, Fumiyuki Shirai
Summary: Identification of structurally novel inhibitors of lysine methyltransferase G9a was performed using high-throughput screening and molecular analysis. Compound 26j (RK-701) was identified as a potent and selective inhibitor of G9a/GLP, showing dose-dependent attenuation of H3K9me2 levels and tumor growth inhibition in vitro and in a mouse model of hepatocellular carcinoma.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yosuke Nishigaya, Shohei Takase, Tatsunobu Sumiya, Ko Kikuzato, Tomohiro Sato, Hideaki Niwa, Shin Sato, Akiko Nakata, Takeshi Sonoda, Noriaki Hashimoto, Ryosuke Namie, Teruki Honma, Takashi Umehara, Mikako Shirouzu, Hiroo Koyama, Minoru Yoshida, Akihiro Ito, Fumiyuki Shirai
Summary: The study successfully identified a novel G9a inhibitor with important significance in cancer epigenetics. Starting from a compound called rac-10a obtained from the chemical library, the structure-activity relationship of the substrate-competitive inhibitors was established using X-ray crystallography and fragment molecular orbital calculations. Further optimization led to the identification of compound 26j (RK-701), which showed potent inhibition of G9a/GLP with high selectivity and demonstrated significant inhibition of tumor growth in vitro and in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)