The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Christian Lino L Cardenas - One of the best experts on this subject based on the ideXlab platform.
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structural and functional analysis of female Sex Hormones against sars cov2 cell entry
Social Science Research Network, 2020Co-Authors: Jorge Aguilar Pineda, Mazen Albaghdadi, Gonzalo Davila Delcarpio, Badhin Gomez Valdez, Mark E Lindsay, Rajeev Malhotra, Wei Jiang, Karin Vera Lopez, Christian Lino L CardenasAbstract:Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in Sex Hormones. However, the precise mechanisms by which female Sex Hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further observed that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV2 thereby blocking its entry into cells. In a mouse model, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female Sex Hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19. Funding: Dr. Lino Cardenas is supported by the MGH Physician-Scientist Development Award and the MGH Department of Medicine Pilot Translational Research Grant. Dr. Malhotra is supported by a COVID-19 Fast Grant (fastgrants.org), NHLBI R01 HL142809, the American Heart Association grant 18TPA34230025, and the Wild Family Foundation. Dr. Lindsay is supported by the Fredman Fellowship, the Toomey Fund for Aortic Dissection Research, the Hassenfeld Fellowship and NIH/NHLBI R01HL130113. Dr. Davila-Del Carpio, Dr. Aguilar Pineda and Dr. Vera Lopez are supported by the COVID-19 Fast Grant (0371-VRINV-2020) from the Vicerrectorado de Investigacion de la Universidad Catolica de Santa Maria, Arequipa, Peru. Conflict of Interest: Authors declare no competing interests. Ethical Approval: All experiments involving mice were approved by the Partners Subcommittee on Research Animal Care. Personnel from the laboratory carried out all experimental protocols under strict guidelines to insure careful and consistent handling of the mice.
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structural and functional analysis of female Sex Hormones against sars cov2 cell entry
bioRxiv, 2020Co-Authors: Jorge Alberto Aguilarpineda, Mazen Albaghdadi, Wanlin Jiang, Karin Vera J Lopez, Gonzalo Davila Delcarpio, Badhin Gomez Valdez, Mark E Lindsay, Rajeev Malhotra, Christian Lino L CardenasAbstract:Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in Sex Hormones. However, the precise mechanisms by which female Sex Hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further observed that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV2 thereby blocking its entry into cells. In a mouse model, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female Sex Hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.
Irshad H Chaudry - One of the best experts on this subject based on the ideXlab platform.
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gender and Sex Hormones influence the response to trauma and sepsis potential therapeutic approaches
Clinics, 2006Co-Authors: Martin K Angele, Markus C Frantz, Irshad H ChaudryAbstract:Several clinical and experimental studies have demonstrated gender dimorphism in immune and organ responsiveness and in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses have been shown to be depressed in males following trauma-hemorrhage, whereas they were aintained/enhanced in proestrus females. Furthermore, Sex Hormones have been shown to be responsible for this gender-specific immune response following adverse circulatory conditions. More specifically, studies indicate that androgens produce immunodepression following trauma-hemorrhage in males. In contrast, female Sex steroids appear to exhibit immunoprotective properties following trauma and severe blood loss. With regard to the underlying mechanisms, receptors for Sex Hormones have been identified on various immune cells suggesting direct effects of these Hormones on the immune cells. Alternatively, indirect effects of Sex Hormones, ie, modulation of cardiovascular responses or androgen- and estrogen-synthesizing enzymes, might contribute to gender-specific immune responses. Recent studies indicate that Sex Hormones, eg, dehydroepiandrosterone (DHEA), also modulate the function of peripheral blood mononuclear cells in surgical patients. Thus, the immunomodulatory properties of Sex Hormones/receptor antagonists/Sex steroid synthesizing enzymes following trauma-hemorrhage suggests novel therapeutic strategies for the treatment of immunodepression in surgical patients.
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female Sex Hormones regulate macrophage function after trauma hemorrhage and prevent increased death rate from subsequent sepsis
Annals of Surgery, 2002Co-Authors: Markus W Knoferl, Martin K Angele, Martin G Schwacha, Alfred Ayala, Michael D Diodato, William G Cioffi, Kirby I Bland, Irshad H ChaudryAbstract:ObjectiveTo determine whether reduction of circulating female Sex Hormones by ovariectomy causes suppression of macrophage (Mφ) function after trauma-hemorrhage and increases susceptibility to subsequent sepsis.Summary Background DataStudies indicate that immune functions are markedly depressed in m
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effect of gender and Sex Hormones on immune responses following shock
Shock, 2000Co-Authors: Martin K Angele, Irshad H Chaudry, Martin G Schwacha, Alfred AyalaAbstract:Several clinical and experimental studies show a gender dimorphism of the immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses are depressed in males after trauma-hemorrhage, whereas they are unchanged or enhanced in females. Sex Hormones contribute to this gender-specific immune response after adverse circulatory conditions. Specifically, studies indicate that androgens are responsible for the immunodepression after trauma-hemorrhage in males. In contrast, female Sex steroids seem to exhibit immunoprotective properties after trauma and severe blood loss, because administration of estrogen prevents the androgen-induced immunodepression in castrated male mice. Nonetheless, the precise underlying mechanisms for these immunomodulatory effects of Sex steroids after shock remain unknown. Although testosterone depletion, testosterone receptor antagonism, or estrogen treatment has been shown to prevent the depression of immune functions after trauma-hemorrhage, it remains to be established whether differences in the testosterone-estradiol ratio are responsible for the immune dysfunction. Furthermore, Sex hormone receptors have been identified on various immune cells, suggesting direct effects. Thus, the immunomodulatory properties of Sex Hormones after trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.
Julia Sacher - One of the best experts on this subject based on the ideXlab platform.
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Sex Hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods
Frontiers in Neuroscience, 2015Co-Authors: Claudia Barth, Arno Villringer, Julia SacherAbstract:Sex Hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between Sex Hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how Sex Hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in Sex Hormones influence functional connectivity, neurotransmission and brain structure in vivo.
Susan F Greenhut - One of the best experts on this subject based on the ideXlab platform.
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measurement of steroid Sex Hormones in serum a comparison of radioimmunoassay and mass spectrometry
Steroids, 2002Co-Authors: Joanne F Dorgan, Thomas R Fears, Robert P Mcmahon, Lisa Aronson Friedman, Blossom H Patterson, Susan F GreenhutAbstract:Concern has been raised about the adequacy of radioimmunoassays to measure steroid Sex Hormones in population studies. We compared steroid Sex hormone measurements in serum by radioimmunoassay with mass spectrometry. Four male and four female serum pools with known relative concentrations of steroid Sex Hormones were measured multiple times by both methods. Because measurements are expected to increase linearly with concentration for each Sex, we examined whether the linear regressions of hormone measurements on concentration were the same for radioimmunoassay and mass spectrometry. Estradiol, estrone, androstenedione, testosterone, and dehydroepiandrosterone sulfate were measured in female pools; testosterone, dihydrotestosterone, androstenedione, and dehydroepiandrosterone sulfate were measured in male pools. Regression slopes for radioimmunoassay and mass spectrometry measurements were comparable for all Hormones except androstenedione, which had a steeper slope when measured by mass spectrometry (P ≤ 0.02). Intercepts for radioimmunoassay and mass spectrometry were similar and close to zero for estradiol, androstenedione, dehydroepiandrosterone sulfate, and in male samples, testosterone. For testosterone in female samples, estrone, and dihydrotestosterone, radioimmunoassay and mass spectrometry intercepts differed significantly. Standard deviations of individual measurements by radioimmunoassay and mass spectrometry differed by hormone and serum concentration; neither method consistently measured hormone concentrations with less variability. Our findings suggest that although absolute concentrations may differ for some Hormones, radioimmunoassay and mass spectrometry can yield similar estimates of between subject differences in serum concentrations of most steroid Sex Hormones commonly measured in population studies. Relative power of studies using radioimmunoassay and mass spectrometry will depend on the Hormones measured and their serum concentrations.
Joanne F Dorgan - One of the best experts on this subject based on the ideXlab platform.
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body mass index serum Sex Hormones and breast cancer risk in postmenopausal women
Journal of the National Cancer Institute, 2003Co-Authors: Timothy J Key, Paul N Appleby, Joanne F Dorgan, Frank Z Stanczyk, Gillian K Reeves, Andrew W Roddam, Christopher Longcope, Hugh E Stephenson, Roni T Falk, Rosetta MillerAbstract:Body mass index, serum Sex Hormones, and breast cancer risk in postmenopausal women. Background: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum Sex hormone concentrations. Methods: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other Sex Hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case- control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two- sided. Results: Breast cancer risk increased with increasing BMI (P-trend = .002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m(2) increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-Sex hormone-binding globulin- bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for Sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. Conclusion: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.
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measurement of steroid Sex Hormones in serum a comparison of radioimmunoassay and mass spectrometry
Steroids, 2002Co-Authors: Joanne F Dorgan, Thomas R Fears, Robert P Mcmahon, Lisa Aronson Friedman, Blossom H Patterson, Susan F GreenhutAbstract:Concern has been raised about the adequacy of radioimmunoassays to measure steroid Sex Hormones in population studies. We compared steroid Sex hormone measurements in serum by radioimmunoassay with mass spectrometry. Four male and four female serum pools with known relative concentrations of steroid Sex Hormones were measured multiple times by both methods. Because measurements are expected to increase linearly with concentration for each Sex, we examined whether the linear regressions of hormone measurements on concentration were the same for radioimmunoassay and mass spectrometry. Estradiol, estrone, androstenedione, testosterone, and dehydroepiandrosterone sulfate were measured in female pools; testosterone, dihydrotestosterone, androstenedione, and dehydroepiandrosterone sulfate were measured in male pools. Regression slopes for radioimmunoassay and mass spectrometry measurements were comparable for all Hormones except androstenedione, which had a steeper slope when measured by mass spectrometry (P ≤ 0.02). Intercepts for radioimmunoassay and mass spectrometry were similar and close to zero for estradiol, androstenedione, dehydroepiandrosterone sulfate, and in male samples, testosterone. For testosterone in female samples, estrone, and dihydrotestosterone, radioimmunoassay and mass spectrometry intercepts differed significantly. Standard deviations of individual measurements by radioimmunoassay and mass spectrometry differed by hormone and serum concentration; neither method consistently measured hormone concentrations with less variability. Our findings suggest that although absolute concentrations may differ for some Hormones, radioimmunoassay and mass spectrometry can yield similar estimates of between subject differences in serum concentrations of most steroid Sex Hormones commonly measured in population studies. Relative power of studies using radioimmunoassay and mass spectrometry will depend on the Hormones measured and their serum concentrations.
