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.
Article
Endocrinology & Metabolism
Karin H. Nilsson, Jianyao Wu, Karin L. Gustafsson, Maha El Shahawy, Antti Koskela, Juha Tuukkanen, Jan Tuckermann, Petra Henning, Ulf H. Lerner, Claes Ohlsson, Sofia Moverare-Skrtic
Summary: Osteoblast-derived RSPO3 is a crucial regulator of vertebral trabecular bone. Our findings show that RSPO3 and estrogen regulate trabecular bone independent of each other, but that RSPO3 is necessary for a complete estrogenic effect on cortical bone.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Multidisciplinary Sciences
Jian Min, Jerome C. Nwachukwu, Charles K. Min, Jacqline W. Njeri, Sathish Srinivasan, Erumbi S. Rangarajan, Charles C. Nettles, Valeria Sanabria Guillen, Yvonne Ziegler, Shunchao Yan, Kathryn E. Carlson, Yingwei Hou, Sung Hoon Kim, Scott Novick, Bruce D. Pascal, Rene Houtman, Patrick R. Griffin, Tina Izard, Benita S. Katzenellenbogen, John A. Katzenellenbogen, Kendall W. Nettles
Summary: Efforts to improve estrogen receptor-alpha (ER)-targeted therapies in breast cancer have led to the development of dual-mechanism ER inhibitors (DMERIs) that generate full antagonism using alternate structural mechanisms, effectively suppressing ER activity and proliferation in breast cancer cells and resistance models. These findings highlight the enhanced flexibility of the ER LBD in response to DMERI binding, distinguishing them from current single-mechanism antiestrogens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Eva C. Herbst, Alessandro A. Felder, Lucinda A. E. Evans, Sara Ajami, Behzad Javaheri, Andrew A. Pitsillides
Summary: This study developed a semi-automated protocol for separating trabecular and cortical compartments in bone images obtained through X-ray micro-CT scans. The method eliminates user bias, is user-friendly across various datasets, and has been validated for use in complex bone analyses, making it a widely applicable tool in the field of skeletal research.
ROYAL SOCIETY OPEN SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Yahyea Baktiar Laskar, Pranab Behari Mazumder, Anupam Das Talukdar
Summary: Hibiscus sabdariffa, a plant rich in polyphenolic compounds, has been found to have potent estrogenic activity that exceeds popular breast cancer drugs, making it a potential prototype for designing novel Selective Estrogen Receptor Modulator molecules.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Immunology
Julien C. Marie, Edith Bonnelye
Summary: This review summarizes the impacts of estrogens on bone immune cells and their consequences on bone homeostasis, metastasis settlement into the bone, and tumor progression. The role of an orphan nuclear receptor ERRalpha on macrophages and T lymphocytes is also addressed.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Emanuele Nicastri, Franco Marinangeli, Emanuele Pivetta, Elena Torri, Francesco Reggiani, Giuseppe Fiorentino, Laura Scorzolini, Serena Vettori, Carolina Marsiglia, Elizabeth Marie Gavioli, Andrea R. Beccari, Giuseppe Terpolilli, Maria De Pizzol, Giovanni Goisis, Flavio Mantelli, Francesco Vaia, Marcello Allegretti
Summary: Raloxifene showed evidence of effect in reducing viral shedding in early mild to moderate COVID-19 patients, but did not significantly affect the need for supplemental oxygen or mechanical ventilation. The drug was well tolerated at both doses.
Review
Chemistry, Multidisciplinary
Nuria Lara-Castillo
Summary: Estrogen plays important roles in bone homeostasis, affecting bone growth, healing, and mechanical adaptation. Abrupt loss of estrogen can lead to osteoporosis. Understanding the mechanisms of estrogen action is crucial for bone health.
APPLIED SCIENCES-BASEL
(2021)
Article
Biochemistry & Molecular Biology
Rebecca K. Dirkes, Nathan C. Winn, Thomas J. Jurrissen, Dennis B. Lubahn, Victoria J. Vieira-Potter, Jaume Padilla, Pamela S. Hinton
Summary: The study found that in male mice, ERKO has a positive impact on bone density, with exercise having little effect. ERKO has a negative impact on cortical geometry, but exercise can partially reverse this effect. Neither ERKO nor exercise have an effect on sclerostin expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Karim Sahbani, Jiangping Pan, Mone Zaidi, Christopher P. Cardozo, William A. Bauman, Hesham A. Tawfeek
Summary: Abaloparatide, a modified parathyroid hormone related peptide, protects against spinal cord injury-induced bone loss by promoting bone formation, but does not prevent osteoporosis from occurring.
Article
Genetics & Heredity
Yuyou Yang, Naibo Feng, Li Liang, Rong Jiang, Yiming Pan, Nana Geng, Mengtian Fan, Xiaoli Li, Fengjin Guo
Summary: This study confirmed the important role of PGRN in regulating the estrogen signal, maintaining bone homeostasis. Our findings may provide a new strategy for the treatment of osteoporosis and maintaining bone homeostasis.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Pharmacology & Pharmacy
Adam Olaitan Abdulkareem, Priya Tiwari, Zahid Rasool Lone, Hina Iqbal, Satish Gupta, Rajesh Kumar Jha, Debabrata Chanda, Kumaravelu Jagavelu, Kashif Hanif
Summary: This study investigated the ameliorative effects of ormeloxifene, a selective estrogen receptor modulator, in pulmonary hypertension. The results showed that ormeloxifene promoted the synthesis of 17β-estradiol, alleviated inflammation, and improved the NOX4/HO1/Nrf/PPAR gamma/PGC-1 alpha axis, thereby attenuating pulmonary hypertension.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Engineering, Biomedical
Cecilia E. Ramirez, Abel Hurtado-Macias, Roberto Talamantes, Edgardo Flores, Hector Perez Ladron de Guevar, J. Ivan Delgado, Ruben Anguiano Estrella, Juan Manuel Riestra, Jesus Maximo Montes, Karen Esmonde-White, Martha Vardaki, J. Gonzalez-Hernandez, Juan M. Viveros
Summary: This study characterizes the anatomy, structural, surface morphological, chemical composition, and nanomechanical properties of ostrich and equine trabecular bone for potential use in guided bone regeneration surgeries. Ostrich bone shows promising properties for native tissue scaffolds, with similarities to human trabecular bone that could reduce stress shielding. These findings contribute to innovative advancements in biomedical research and applications.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2021)
Review
Oncology
V. Craig Jordan
Summary: Following the approval of oral contraceptives, the pharmaceutical industry sought new opportunities for reproductive regulation, leading to the discovery of the compound ICI 46,474 for the treatment of breast cancer. Despite initial patent setbacks in the USA, tamoxifen eventually found success in treating breast cancer, becoming a major advancement in cancer therapy.
ENDOCRINE-RELATED CANCER
(2021)
Article
Microbiology
Renu Sudhakar, Navin Adhikari, Saniya Pamnani, Abhipsa Panda, Manish Bhattacharjee, Zeba Rizvi, Sadaf Shehzad, Dinesh Gupta, Puran Singh Sijwali
Summary: Despite the challenges posed by drug-resistant parasite strains, repurposing existing drugs for malaria treatment is an attractive option. Bazedoxifene, a selective estrogen receptor modulator, has shown potent inhibitory activity against Plasmodium falciparum and Plasmodium berghei. It inhibits the formation of hemozoin, a byproduct of hemoglobin degradation by the malaria parasite, and could potentially be repurposed as an antimalarial drug.
MICROBIOLOGY SPECTRUM
(2022)
Article
Gastroenterology & Hepatology
Gudmundur Vignir Sigurdsson, Susanne Schmidt, Dan Mellstrom, Claes Ohlsson, Robert Saalman, Mattias Lorentzon
Summary: Young adult men with childhood-onset IBD have decreased bone quality in both cortical and trabecular bone structures compared to age- and height-matched controls. This has implications for their skeletal health and quality of life.
INFLAMMATORY BOWEL DISEASES
(2023)
Article
Endocrinology & Metabolism
Xiaoyu Xu, Haisheng Yang, Whitney A. Bullock, Maxim A. Gallant, Claes Ohlsson, Teresita M. Bellido, Russell P. Main
Summary: Age-related bone loss is caused by imbalanced bone turnover and decreased skeletal mechanoadaptation. Estrogen receptors, ER alpha and ER beta, play crucial roles in osteoprotective regulation. Previous studies focused on ER alpha but the role of Ot-ER beta in bone mass regulation is still unknown. This study found that Ot-ER beta regulates bone (re)modeling and mechanical signal response differently in males and females.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Medicine, Legal
Adeline Blanchot, Maria Cristina Antal, Alice Ameline, Laurie Gheddar, Nadia Arbouche, Jean-Sebastien Raul, Pascal Kintz
Summary: This article discusses the complex problem of determining fetal death causes for forensic pathologists. The authors present a case of an unexpected birth during a party, highlighting the importance of toxicological analysis in cases of fetal death and the collaborative work between forensic and fetal pathologists and toxicologists.
FORENSIC SCIENCE INTERNATIONAL
(2023)
Article
Immunology
Aidan Barrett, Piotr Humeniuk, Christina Drevinge, Carmen Corciulo, Julie Weidner, Madeleine Radinger, Hans Carlsten, Julia M. Scheffler, Ulrika Islander
Summary: Compared to men, women have a higher prevalence of adult-onset asthma, and previous studies have shown that testosterone inhibits while estrogen worsens allergen-induced airway inflammation. However, the exact effects of estrogen on immune responses in asthma are not well understood. Clarifying the impact of physiological levels of estrogen on immune responses would help in developing improved treatment strategies.
Article
Immunology
Zhicheng Hu, Pradeep Kumar Kopparapu, Meghshree Deshmukh, Anders Jarneborn, Priti Gupta, Abukar Ali, Ying Fei, Cecilia Engdahl, Rille Pullerits, Majd Mohammad, Tao Jin
Summary: In this study using a mouse model of Staphylococcus aureus bacteremia, aging and TLR2 deficiency were found to impair immune responses in distinct patterns. Mortality was mainly controlled by aging, while weight loss and kidney abscess formation were more TLR2 dependent. Aging increased mortality independent of TLR2 expression.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Priti Gupta, Karin Horkeby, Hans A. Carlsten, Petra A. Henning, Cecilia A. Engdahl
Summary: The incidence of rheumatoid arthritis (RA) increases during menopause when estrogen levels decrease. Estrogen treatment can reduce the pathogenicity of IgG by increasing sialylation, inhibiting binding to the Fc gamma receptor. However, estrogen treatment has negative side effects, so selective estrogen receptor modulators (SERMs) with minimal side effects have been developed. In this study, the impact of the SERM bazedoxifene on IgG and serum protein sialylation was investigated.
Article
Multidisciplinary Sciences
Yiwen Jiang, Karin Horkeby, Petra Henning, Jianyao Wu, Lina Lawenius, Cecilia Engdahl, Priti Gupta, Sofia Moverare-Skrtic, Karin H. H. Nilsson, Ellis Levin, Claes Ohlsson, Marie K. K. Lagerquist
Summary: Estradiol (E2) has different effects on reproductive and non-reproductive tissues, and the sensitivity to E2 varies among tissues. The study aimed to determine the role of membrane estrogen receptor alpha (mER α) signaling in modulating E2 sensitivity. Ovariectomized mice lacking mER α signaling and wildtype (WT) littermates were treated with different doses of E2 for three weeks. The results showed that loss of mER α signaling reduced sensitivity to physiological E2 treatment in both non-reproductive tissues and uterus, and enhanced the effect of high-dose E2 treatment in uterus.
SCIENTIFIC REPORTS
(2023)
Article
Endocrinology & Metabolism
Suchita Desai, Jianyao Wu, Karin Horkeby, Maria Norgard, Claes Ohlsson, Sara H. Windahl, Cecilia Engdahl
Summary: Mechanical loading enhances bone strength and counteracts arthritis-induced inflammation-mediated bone loss in female mice. It is unknown whether nonsteroidal anti-inflammatory drugs (NSAIDs; eg, COX-2 inhibitors) can reduce inflammation without affecting the loading-associated bone formation in male mice. The aim of this study was to investigate if loading combined with a COX-2 inhibitor (NS-398) could prevent arthritis-induced bone loss and inflammation in male mice. The results showed that loading prevented arthritis-induced bone loss and NS-398 reduced knee swelling without affecting the bone-protective effects of loading.
Article
Endocrinology & Metabolism
Claes Ohlsson, Maria Nethander, Anna-Karin Norlen, Matti Poutanen, Elias Freyr Gudmundsson, Thor Aspelund, Sigurdur Sigurdsson, Henrik Ryberg, Vilmundur Gudnason, Asa Tivesten
Summary: This study found an inverse association between serum levels of DHEA and testosterone and coronary artery calcification in elderly men, partially independently from each other. These results raise the question whether androgens produced by both the adrenals and the testes may contribute to male cardiovascular health.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Rheumatology
C. Drevinge, J. M. Scheffler, J. Nordqvist, C. Engdahl, H. Carlsten, U. Islander
SCANDINAVIAN JOURNAL OF RHEUMATOLOGY
(2023)
Article
Endocrinology & Metabolism
Priti Gupta, Tibor Saghy, Jauquline Nordqvist, Jonas Nilsson, Hans Carlsten, Karin Horkeby, Petra Henning, Cecilia Engdahl
Summary: This study aims to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Chloe Pasin, Camila R. Consiglio, Jana S. Huisman, Ann-Marie G. de Lange, Hannah Peckham, Enriqueta Vallejo-Yaguee, Irene A. Abela, Ulrika Islander, Nadia Neuner-Jehle, Maria Pujantell, Olivia Roth, Melanie Schirmer, Burcu Tepekule, Marius Zeeb, Anna Hachfeld, Karoline Aebi-Popp, Roger D. Kouyos, Sebastian Bonhoeffer
Summary: Although sex and gender play important roles in health and immunity, they are seldom considered in clinical practice and public health. We have identified six bottlenecks that hinder the inclusion of sex and gender considerations from basic science to clinical practice, precision medicine, and public health policies. Guidelines are provided for researchers, scientific journals, funding agencies, and academic institutions to address these bottlenecks.
ROYAL SOCIETY OPEN SCIENCE
(2023)
Article
Endocrinology & Metabolism
Hannah Collden, Malin Hagberg Thulin, Andreas Landin, Karin Horkeby, Marie Lagerquist, Jianyao Wu, Karin H. Nilsson, Louise Grahnemo, Matti Poutanen, Henrik Ryberg, Liesbeth Vandenput, Claes Ohlsson
Summary: Progesterone levels in males with advanced prostate cancer have been identified as a potential predictor for treatment effect. This study found that progesterone levels remained high in orchiectomized male mice, with the highest levels observed in white adipose tissue and the gastrointestinal tract. Additionally, dietary intake of progesterone, particularly from female animals of reproductive age, was found to contribute to tissue levels of progesterone in male mice. These findings suggest that food containing high levels of progesterone may be a significant source of progesterone in males, possibly affecting men undergoing androgen deprivation therapy for prostate cancer.