Article
Cardiac & Cardiovascular Systems
Javed Butler, Milton Packer, Tariq Jamal Siddiqi, Michael Boehm, Martina Brueckmann, James L. Januzzi, Subodh Verma, Ingrid Gergei, Tomoko Iwata, Christoph Wanner, Joao Pedro Ferreira, Stuart J. Pocock, Gerasimos Filippatos, Stefan D. Anker, Faiez Zannad
Summary: This study aimed to evaluate the effect of empagliflozin on patients with chronic kidney disease. It was found through a pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved that empagliflozin can reduce the risk of heart failure and heart failure-related death in patients with different risk categories.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2023)
Article
Endocrinology & Metabolism
Wisanee Wisanwattana, Kanjana Wongkrajang, Dong-yi Cao, Xiao-ke Shi, Zhong-hui Zhang, Zong-yuan Zhou, Fu Li, Qing-gang Mei, Chun Wang, Apichart Suksamrarn, Guo-lin Zhang, Fei Wang
Summary: The study showed that compounds synthesized using icariin analogs can promote estrogen biosynthesis in osteoblastic cells, enhancing bone growth and remodeling. Compound 14 activates PKG to stimulate SHP2, Src, and ERK signaling pathways, leading to increased estrogen biosynthesis, suggesting its potential for treating osteoporosis.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Caroline S. S. Johnson, Paul E. Micevych, Paul G. G. Mermelstein
Summary: Recent studies have shown that traditional estrogen receptors, alpha and beta, can also act at the cell surface in addition to their nuclear functions. Signaling from these membrane-bound estrogen receptors can rapidly affect cellular excitability and ultimately impact gene expression. The interaction between these membrane receptors and metabotropic glutamate receptors (mGluRs) plays a key role in various female functions such as reproduction and motivation.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Takeshi Iwasa, Hiroki Noguchi, Risa Tanano, Erika Yamanaka, Asuka Takeda, Kou Tamura, Hidenori Aoki, Tatsuro Sugimoto, Hikari Sasada, Takaaki Maeda, Saki Minato, Shota Yamamoto, Hiroaki Inui, Tomohiro Kagawa, Atsuko Yoshida, Ayuka Mineda, Mari Nii, Riyo Kinouchi, Kanako Yoshida, Yuri Yamamoto, Takashi Kaji
Summary: Recent studies have revealed the effects of androgens on metabolic and body weight regulation systems in females and elucidated the underlying mechanisms. Excess androgens can negatively impact metabolic functioning, appetite, and body weight regulation, increasing the risk of metabolic disorders. These effects are caused by changes in hypothalamic appetite-regulatory factors, decreased energy expenditure, skeletal muscle insulin resistance, and beta-cell dysfunction. Interestingly, these adverse effects of androgens are not observed in ovariectomized animals and post-menopausal women, suggesting a potential dependence on the estrogen milieu. The findings may provide novel strategies for sex- and age-specific treatment of metabolic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Endocrinology & Metabolism
Andre J. Scheen, Fabrice Bonnet
Summary: Type 2 diabetes mellitus is a common health condition in elderly population and is associated with increased risks of cardiovascular disease and heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown to improve cardiovascular prognosis and reduce the risk of hospitalization for heart failure. This comprehensive review analyzed the benefit-risk ratio of SGLT2i therapy in older patients with type 2 diabetes by reviewing large studies and observational cohort studies. The results showed that SGLT2is had similar benefits in reducing cardiovascular mortality and heart failure in all age groups, with potentially greater risk reduction in elderly patients.
DIABETES & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Edmund Charles Jenkins, Gabriella Casalena, Maria Gomez, Dazhi Zhao, Timothy C. Kenny, Nagma Shah, Giovanni Manfredi, Doris Germain
Summary: Dysfunctions in proteasome and protein aggregation are key features of several neurodegenerative disorders. The study found distinct effects of different selective estrogen receptor modulators (SERMs) on gene expression in the spinal cord, with raloxifene showing significant regulation of deubiquitinating enzymes, proteasome subunits and assembly factors. In a mouse model of amyotrophic lateral sclerosis, even a low dose of raloxifene reduced mutant SOD1 aggregates in females and delayed muscle strength decline. These results highlight the importance of considering sex-specific and SERM-selective effects in clinical trials for neurodegenerative diseases.
Review
Cardiac & Cardiovascular Systems
Sumon Roy, Robert A. Kloner, Fadi N. Salloum, Ion S. Jovin
Summary: The coexistence of cardiovascular disease and erectile dysfunction is common, possibly due to underlying endothelial dysfunction. The effects of phosphodiesterase-5 (PDE5) inhibitors on the cardiovascular system remain unclear, despite their well-established role in erectile dysfunction therapy. Preclinical studies suggest potential clinical applications for PDE5 inhibitors in cardioprotection, but attempts to translate these findings to clinical trials have faced challenges.
CARDIOVASCULAR DRUGS AND THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Sylvia C. Hewitt, Artiom Gruzdev, Cynthia J. Willson, San-Pin Wu, John P. Lydon, Niels Galjart, Francesco J. DeMayo
Summary: Receptors for estrogen and progesterone interact through Cohesin/CTCF loop extrusion at enhancers distal from regulated genes. Loss-of-function CTCF mutation in endometrial tumors indicates its importance in uterine homeostasis. Our study reveals that uterine Ctcf plays a key role in progesterone-dependent expression of uterine genes underlying optimal post-pubertal uterine development.
Article
Biochemistry & Molecular Biology
Sylvia C. Hewitt, Artiom Gruzdev, Cynthia J. Willson, San-Pin Wu, John P. Lydon, Niels Galjart, Francesco J. DeMayo
Summary: Receptors for estrogen and progesterone interact via Cohesin/CTCF loop extrusion at enhancers distal from regulated genes. Loss-of- function CTCF mutation indicates its importance in uterine homeostasis. Deleting Ctcf gene in female reproductive tissues of mice resulted in reduced uterine glands and hypoplastic uteri with decreased endometrial stroma. Ctcf deletion also altered the expression of progesterone-responsive genes, including Ihh, Fst, and Errfi1. Our findings highlight the key role of uterine Ctcf in progesterone-dependent expression and optimal post-pubertal uterine development.
Article
Endocrinology & Metabolism
Emily A. McGlade, Kalli K. Stephens, Sarayut Winuthayanon, Prashanth Anamthathmakula, Michael J. Holtzman, Wipawee Winuthayanon
Summary: In this study, the role of estrogen in the transcriptional regulation of ciliated epithelial cells in the oviduct was assessed using single-cell RNA-sequencing analysis. The results showed that estrogen had little impact on the gene expression profile of these cells. Additionally, conditional deletion of Esr1 from ciliated epithelial cells did not affect fertility or cilia formation in mice. Therefore, ESR1 expression in ciliated cells of the oviduct is dispensable for ciliogenesis and nonessential for female fertility.
Article
Anesthesiology
Kali Hankerd, Ho Koo, Kathleen E. McDonough, Jigong Wang, Ramesh Pariyar, Shao-Jun Tang, Jin Mo Chung, Jun-Ho La
Summary: This study found that gonadal hormones are critical for the development and maintenance of peripherally maintained nociplastic pain state in females. Estradiol reconstitution before injury and post-injury stimulation can restore the development of this pain state, while G protein-coupled estrogen receptor antagonism can alleviate the pain. AITC-responsive afferents contribute to the maintenance of nociplastic mechanical hypersensitivity in females.
Article
Anesthesiology
Sukhbir Kaur, Taylor M. Hickman, Angela Lopez-Ramirez, Hanna McDonald, Lauren M. Lockhart, Omar Darwish, Dayna Loyd Averitt
Summary: This study investigated the role of major estrogen estradiol (E2) in orofacial pain and found that low levels of E2 can protect against pain while high levels can exacerbate it. The study also identified that estrogen receptor alpha is involved in the sensitization of pain signaling in trigeminal sensory neurons.
Article
Neurosciences
Jie Cui, Ghania Ait-Ghezala, Kumar Sambamurti, Feng Gao, Yong Shen, Rena Li
Summary: This study identified an estrogen-specific BACE1 transcriptional regulation pathway, providing new clues for the study of sex differences and AD pathology, from cell and animal models to AD patients.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Lu-qi Wang, Zhao Qian, Hai-lan Ma, Meng Zhou, Hu-die Li, Chang-peng Cui, Da-li Luo, Xue-lian Li, Bai-yan Li
Summary: This study reveals the crucial role of KCa1.1 in modulating neuroexcitation in the female-specific subpopulation of myelinated Ah-type baroreceptor neurons, showing that estrogen deficiency can increase KCa1.1 channel protein expression and weaken neuroexcitation.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Biology
Kazuaki Nishimura, Kiyoshi Yoshino, Naofumi Ikeda, Kazuhiko Baba, Kenya Sanada, Yasuki Akiyama, Haruki Nishimura, Kentaro Tanaka, Satomi Sonoda, Hiromichi Ueno, Mitsuhiro Yoshimura, Takashi Maruyama, Toru Hachisuga, Yoichi Ueta
Summary: This study provides the first evidence that estrogen regulates the dynamic changes in oxytocin levels in the hypothalamus. The study also shows that these changes vary between sexes. Additionally, estrogen has significant effects on oxytocin expression and gene expression levels.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Noriaki Yamada, Yoshihiro Asano, Masashi Fujita, Satoru Yamazaki, Atsushi Inanobe, Norio Matsuura, Hatasu Kobayashi, Seiko Ohno, Yusuke Ebana, Osamu Tsukamoto, Saki Ishino, Ayako Takuwa, Hidetaka Kioka, Toru Yamashita, Norio Hashimoto, Dimitar P. Zankov, Akio Shimizu, Masanori Asakura, Hiroshi Asanuma, Hisakazu Kato, Yuya Nishida, Yohei Miyashita, Haruki Shinomiya, Nobu Naiki, Kenshi Hayashi, Takeru Makiyama, Hisakazu Ogita, Katsuyuki Miura, Hirotsugu Ueshima, Issei Komuro, Masakazu Yamagishi, Minoru Hone, Koichi Kawakami, Tetsushi Furukawa, Akio Koizumi, Yoshihisa Kurachi, Yasushi Sakata, Tetsuo Minamino, Masafumi Kitakaze, Seiji Takashima
Article
Biochemistry & Molecular Biology
Hidetaka Kioka, Hisakazu Kato, Takeshi Fujita, Yoshihiro Asano, Yasunori Shintani, Satoru Yamazaki, Osamu Tsukamoto, Hiromi Imamura, Mikihiko Kogo, Masafumi Kitakaze, Yasushi Sakata, Seiji Takashima
Review
Biochemistry & Molecular Biology
Osamu Tsukamoto
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Multidisciplinary Sciences
Kenta Kamikubo, Osamu Tsukamoto, Yuki Uyama-Saito, Ryohei Oya, Tomoya Tsubota, Noboru Fujino, Yoshihiro Asano, Hisakazu Kato, Ken Matsuoka, Seiji Takashima
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2020)
Article
Multidisciplinary Sciences
Miki Imazu, Hiroki Fukuda, Hideaki Kanzaki, Makoto Amaki, Takuya Hasegawa, Hiroyuki Takahama, Tatsuro Hitsumoto, Osamu Tsukamoto, Toshisuke Morita, Shin Ito, Masafumi Kitakaze
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Yohei Miyashita, Osamu Tsukamoto, Ken Matsuoka, Kenta Kamikubo, Yuki Kuramoto, Hai Ying Fu, Tomoya Tsubota, Hirona Hasuike, Toshio Takayama, Hiroaki Ito, Tatsuro Hitsumoto, Chisato Okamoto, Hidetaka Kioka, Ryohei Oya, Haruki Shinomiya, Hideyuki Hakui, Yasunori Shintani, Hisakazu Kato, Masafumi Kitakaze, Yasushi Sakata, Yoshihiro Asano, Seiji Takashima
Summary: Enhancers like CR9 respond to mechanical loads in cardiomyocytes by upregulating natriuretic peptides expressions, and can be affected by drugs inducing cardiac hypertrophy or failure.
Article
Neurosciences
Ryohei Oya, Osamu Tsukamoto, Takashi Sato, Hisakazu Kato, Ken Matsuoka, Kazuo Oshima, Takefumi Kamakura, Yumi Ohta, Takao Imai, Seiji Takashima, Hidenori Inohara
Summary: The organ of Corti contains hair cells (HCs) and inner sulcus cells (ISCs) that exhibit cellular shape changes resembling neural epithelia, with MYL12 phosphorylation by smooth muscle MLCK potentially contributing to the apical constriction-like cellular shape change of HCs.
JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Haruki Shinomiya, Hisakazu Kato, Yuki Kuramoto, Nozomi Watanabe, Toshihiro Tsuruda, Tadaaki Arimura, Yohei Miyashita, Yoshiki Miyasaka, Tomoji Mashimo, Ayako Takuwa, Daisuke Motooka, Daisuke Okuzaki, Ken Matsuoka, Osamu Tsukamoto, Hideyuki Hakui, Noriaki Yamada, Jong-Kook Lee, Hidetaka Kioka, Masafumi Kitakaze, Seiji Takashima, Yasushi Sakata, Yoshihiro Asano
Summary: This study generated knock-in rats with Tmem43 p.S358L mutation and established induced pluripotent stem cells from patients, shedding light on the role of aberrant accumulation of TMEM43(S358L) in the pathogenesis of ACM, which affects transmural gene expression within the myocardium.
Article
Biochemistry & Molecular Biology
Ryohei Oya, Osamu Tsukamoto, Tatsuro Hitsumoto, Naoya Nakahara, Chisato Okamoto, Ken Matsuoka, Hisakazu Kato, Hidenori Inohara, Seiji Takashima
Summary: This study found that enhancing the expression of skeletal muscle-specific myosin regulatory light chain kinase (skMLCK) through gene transfer can increase muscle contraction strength and improve muscle function in patients with amyotrophic lateral sclerosis (ALS).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Hideyuki Hakui, Hidetaka Kioka, Yohei Miyashita, Shunsuke Nishimura, Ken Matsuoka, Hisakazu Kato, Osamu Tsukamoto, Yuki Kuramoto, Ayako Takuwa, Yusuke Takahashi, Shigeyoshi Saito, Kunio Ohta, Hiroshi Asanuma, Hai Ying Fu, Haruki Shinomiya, Noriaki Yamada, Tomohito Ohtani, Yoshiki Sawa, Masafumi Kitakaze, Seiji Takashima, Yasushi Sakata, Yoshihiro Asano
Summary: Familial dilated cardiomyopathy (DCM) is caused by mutations in more than 50 genes, but the genetic causes of 60 to 80% of cases remain unknown. This study identified homozygous truncating mutations in the BAG5 gene as a cause of inherited DCM, with potential implications for genetic testing and gene therapy in DCM cases.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Chisato Okamoto, Osamu Tsukamoto, Takuya Hasegawa, Tatsuro Hitsumoto, Ken Matsuoka, Seiji Takashima, Makoto Amaki, Hideaki Kanzaki, Chisato Izumi, Shin Ito, Masafumi Kitakaze
Summary: The study found that in individuals with normal plasma BNP levels, low BNP levels are associated with insulin resistance and LV concentric remodelling.
Article
Cardiac & Cardiovascular Systems
Tatsuro Hitsumoto, Osamu Tsukamoto, Ken Matsuoka, Junjun Li, Li Liu, Yuki Kuramoto, Shuichiro Higo, Shou Ogawa, Noboru Fujino, Shohei Yoshida, Hidetaka Kioka, Hisakazu Kato, Hideyuki Hakui, Yuki Saito, Chisato Okamoto, Hijiri Inoue, Jo Hyejin, Kyoko Ueda, Takatsugu Segawa, Shunsuke Nishimura, Yoshihiro Asano, Hiroshi Asanuma, Akiyoshi Tani, Riyo Imamura, Shinsuke Komagawa, Toshio Kanai, Masayuki Takamura, Yasushi Sakata, Masafumi Kitakaze, Jun-ichi Haruta, Seiji Takashima
Summary: This study demonstrates that dysregulation of cMLCK contributes to the development of cardiac systolic dysfunction in humans, and restoring cMLCK activity could serve as a novel myotropic therapy for advanced systolic heart failure.
Article
Biochemistry & Molecular Biology
Shohei Yashirogi, Takemasa Nagao, Yuya Nishida, Yusuke Takahashi, Tasneem Qaqorh, Issei Yazawa, Toru Katayama, Hidetaka Kioka, Tsubasa S. Matsui, Shigeyoshi Saito, Yuki Masumura, Osamu Tsukamoto, Hisakazu Kato, Hiromichi Ueda, Osamu Yamaguchi, Kenta Yashiro, Satoru Yamazaki, Seiji Takashima, Yasunori Shintani
Summary: AMP-activated protein kinase (AMPK) regulates microtubule (MT) accumulation through CLIP-170 phosphorylation at intercalated disks in cardiomyocytes, impacting cell shape and aspect ratio.
Article
Cardiac & Cardiovascular Systems
Hiroko Takahama, Hiroshi Asanuma, Osamu Tsukamoto, Shin Ito, Masafumi Kitakaze
IJC HEART & VASCULATURE
(2019)
Article
Cardiac & Cardiovascular Systems
Akihiko Hodatsu, Noboru Fujino, Yuki Uyama, Osamu Tsukamoto, Atsuko Imai-Okazaki, Satoru Yamazaki, Osamu Seguchi, Tetsuo Konno, Kenshi Hayashi, Masa-aki Kawashiri, Yoshihiro Asano, Masafumi Kitakaze, Seiji Takashima, Masakazu Yamagishi