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Updated Friday, 03 December 2021

2021 ◽  
Vol 12 ◽  
Author(s):  
Mei Qiu ◽  
Li-Min Zhao ◽  
Ze-Lin Zhan

Recently, Lin and colleagues assessed the safety of sodium-glucose cotransporter 2 inhibitors (SGLT2is) by a meta-analysis [1], in which the authors assessed 16 kinds of adverse events (AE) reported in the published articles based on 10 randomized controlled trials. We conducted a further meta-analysis and targeted the association between use of SGLT2is and occurrences of various kinds of serious AE published in the Clinical Trials website (clinicaltrials.gov). Our meta-analysis revealed that use of SGLT2is was not significantly associated with occurrences of 980 kinds of serious AE but was significantly associated with lower risks of 29 kinds of serious AE, especially including several important respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease, sleep apnoea syndrome, and pneumonia). These findings may cause more studies to evaluate the possibilities of gliflozins being used for prevention of these specific diseases.


2021 ◽  
Vol 12 ◽  
Author(s):  
Changxi Han ◽  
Shaojian Lin ◽  
Xingyu Lu ◽  
Li Xue ◽  
Zhe Bao Wu

Macrophages are one of the most common infiltrating immune cells and an essential component of tumor microenvironment. Macrophages and the soluble cytokines and chemokines produced play an important role in tumorigenesis, progression, invasion and metastasis in solid tumors. Despite the multiple studies in other solid tumors, there is little known about macrophages in pituitary adenomas. Recently, studies about pituitary adenoma-infiltrated macrophages have been emerging, including the immunohistochemical and immunophenotypic analysis of the pituitary adenomas and further studies into the mechanism of the crosstalk between macrophages and tumor cells in vivo and in vitro. These studies have offered us new insights into the polarization of macrophages and its role in tumorigenesis, progression and invasion of pituitary adenomas. This review describes the advances in the field of pituitary adenoma-infiltrated macrophages and the prospect of targeting macrophages as cancer therapy in pituitary adenoma.


2021 ◽  
Vol 12 ◽  
Author(s):  
Flavia Tramontana ◽  
Sofia Battisti ◽  
Nicola Napoli ◽  
Rocky Strollo

Epidemiological evidence shows clear gender disparities in the Coronavirus 2019 Disease (COVID-19) severity and fatality. This may reflect the contribution of gender-related factors, such as sex hormones, to COVID-19 pathogenesis. However, the mechanism linking gender disparities to COVID-19 severity is still poorly understood. In this review, we will pinpoint several elements involved in COVID-19 pathogenesis that are regulated by the two main sex hormones, estrogen and androgen. These include tissue specific gene regulation of SARS-CoV2 entry factors, innate and adaptive immune responses to infection, immunometabolism, and susceptibility to tissue injury by cytopathic effect or hyper-inflammatory response. We will discuss the mechanistic link between sex hormone regulation of COVID-19 pathogenetic factors and disease severity. Finally, we will summarize current evidence from clinical studies and trials targeting sex hormones and their signalling in COVID-19. A better understanding of the role of sex hormones in COVID-19 may identify targets for therapeutic intervention and allow optimization of treatment outcomes towards gender-based personalised medicine.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wenjing Ni ◽  
Yue Yuan ◽  
Xiaoqiu Chu ◽  
Guofang Chen ◽  
Xue Han ◽  
...  

ObjectiveTo assess the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperparathyroidism (PHPT), and to investigate whether MWA can improve the bone turnover and renal function.MethodsA total of 20 consecutive PHPT patients with 21 parathyroid lesions treated with MWA in our center from May 2019 to March 2021 were recruited in this study. Serum parathyroid hormone (PTH), calcium and phosphorus levels before MWA and at 20 minutes, 4 hours, 1 day, 3 months, 6 months and 12 months after MWA were measured. Bone turnover biomarkers, renal function and lesion volume with volume reduction rate (VRR) before MWA and at the last follow-up were compared. Any complication related with MWA was evaluated. The technical and clinical success rates of MWA in the treatment of PHPT were calculated. Clinical success was defined as normal serum PTH and calcium without PHPT-associated manifestations at more than 6 months after ablation. Technical success was defined as complete ablation indicated by immediate postoperative contrast-enhanced ultrasound.ResultsThe serum PTH, calcium and phosphorus levels at their respective follow-up time points dropped significantly after MWA (P <0.05). The volume of parathyroid lesions at the final examination was significantly reduced, compared with pre-ablation volume (P <0.001), with a median VRR reaching 89%. The technical and clinical success rates were 100% and 63.6%, respectively. Substantial changes of bone turnover biomarkers were observed before and after MWA (P <0.05), but the differences in renal function were not statistically significant. No major complications were reported in all cases. Pre-MWA serum PTH, lesion volume, maximum diameter of lesion and ablation time were significantly different between patients with successful and failed MWA.ConclusionsPHPT can be effectively and safely treated by ultrasound-guided MWA, as proven by drop in serum PTH and reduction in the volume of parathyroid adenomas. Besides, MWA can impede bone remodeling to suppress hyperparathyroidism in the condition of PHPT.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ines Foessl ◽  
J. H. Duncan Bassett ◽  
Åshild Bjørnerem ◽  
Björn Busse ◽  
Ângelo Calado ◽  
...  

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE (“GEnomics of MusculoSkeletal Traits translational Network”) Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art technologies to investigate bone properties in humans and animals – including their strengths and weaknesses. New research methodologies are outlined and future strategies are discussed to combine phenotypic with rapidly developing –omics data in order to advance musculoskeletal research and move towards “personalised medicine”.


2021 ◽  
Vol 12 ◽  
Author(s):  
Florence Scheffler ◽  
Albane Vandecandelaere ◽  
Marion Soyez ◽  
Dorian Bosquet ◽  
Elodie Lefranc ◽  
...  

IntroductionOocyte quality contributes to the development of an optimal embryo and thus a successful pregnancy. The objective of this study was to analyse the association between oocyte cohort quality and the follicular levels of growth hormone (GH), insulin-like growth factor 1 (IGF1), 25-hydroxy vitamin D (25OHD), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4) and antithyroid antibodies, as a function of intracytoplasmic sperm injection (ICSI) outcomes.Material and methodsWe conducted a prospective comparative pilot study from January 2013 to December 2017. 59 ICSI cycles constituted an abnormal oocyte cohort (n=34 cycles, in which more than 50% of oocytes presented at least one morphological abnormality) and a normal oocyte cohort (n=25 cycles, in which 50% or less of the oocytes presented at least one morphological abnormality). GH, IGF1, 25OHD, TSH, fT3, fT4 and antithyroid antibodies were measured in follicular fluid.ResultsThe fertilisation rate was lower in the abnormal oocyte cohort (65.5% vs. 80%, respectively, p=0.012). Oocytes’ proportion with at least one abnormality was 79.4% in the abnormal oocyte cohort and 29.0% in the normal oocyte cohort. The mean number of morphological abnormalities per oocyte was significantly higher in the abnormal oocyte cohort. The follicular levels of GH (4.98 vs. 2.75 mIU/L, respectively; p <0.01) and IGF1 (72.1 vs. 54.2 ng/mL, respectively; p=0.05) were higher in the normal oocyte cohort. There was no association with follicular levels of TSH, fT3, fT4, antithyroid antibodies, or 25OHD.ConclusionOocyte cohort quality appears to be associated with follicular levels of GH and IGF1.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xuelun Zou ◽  
Leiyun Wang ◽  
Linxiao Xiao ◽  
Zihao Xu ◽  
Tianxing Yao ◽  
...  

BackgroundTo investigate the relationship between different classes of obesity and stroke, we conducted a stratified Mendelian randomization (MR) study.MethodsThe body mass index (BMI) data of 263,407 Europeans with three classes of obesity (obesity class I, 30 kg/m2 ≤ BMI < 35 kg/m2; obesity class II, 35 kg/m2 ≤ BMI < 40 kg/m2; obesity class III, 40 kg/m2 ≤ BMI) were extracted from the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Summary-level data of stroke and its subtypes [ischemic stroke (IS) and intracerebral hemorrhage (ICH)] were obtained from the genome-wide association study (GWAS) meta-analysis, which was performed by the MEGASTROKE consortium. MR methods were used to identify the causal relationships.ResultsThe MR analysis revealed that both obesity class I [odds ratio (OR) = 1.08, 95% CI: 1.05–1.12, p = 1.0 × 10-5] and obesity class II (OR = 1.06, 95% CI: 1.03–1.09, p = 1 × 10-4) were significantly positively related to IS, while obesity class III was not (OR = 1.01, 95% CI: 0.96–1.06, p = 0.65). In contrast to IS, there was no class of obesity associated with ICH risk. Further examination of the relationship between obesity classification and IS subtypes revealed that certain degrees of obesity were related to large artery stroke (LAS) (OR = 1.14, 95% CI: 1.04–1.24, p = 2.8 × 10-3 for class I; OR = 1.08, 95% CI: 1.01–1.16, p = 0.002 for class II) and cardioembolic stroke (CES) (OR = 1.11, 95% CI: 1.02–1.20, p = 0.02 for class I; OR = 1.08, 95% CI: 1.02–1.15, p = 0.007 for class II).ConclusionsA higher risk of IS, but not ICH, could be linked to obesity classes I and II. A strong association between LAS and CES and obesity was observed among all IS subtypes in the obese population.


2021 ◽  
Vol 12 ◽  
Author(s):  
Christopher S. Hong ◽  
Aladine A. Elsamadicy ◽  
Adeniyi Fisayo ◽  
Silvio E. Inzucchi ◽  
Pallavi P. Gopal ◽  
...  

Granular cell tumors of the pituitary belong to a rare family of neoplasms, arising from the posterior pituitary gland. Although considered benign, they may cause significant morbidity and residual disease after resection can lead to poor clinical outcomes. Currently, there is no known medical therapy for any posterior pituitary gland tumor, in part due to sparse molecular characterization of these lesions. We report data from whole exome sequencing of a case of granular cell tumor of the pituitary, performed under an institutional review board approved protocol. A 77 year-old female underwent resection of an incidentally diagnosed pituitary mass that was causing radiographic compression of the optic nerves with a subclinical temporal field defect and central hypothyroidism. The pathology of the resected specimen demonstrated a granular cell tumor of the posterior pituitary gland. Whole-exome sequencing revealed mutations predicted to be deleterious in key oncogenes, SETD2 and PAX8, both of which have been described in other cancers and could potentially be amenable to targeted therapies with existing approved drugs, including immune checkpoint inhibitors and histone deacetylase inhibitors, respectively. To our knowledge, this is the first comprehensive genomic characterization of granular cell tumor of the posterior pituitary gland. We report mutations in oncogenes predicted to be deleterious and reported in other cancers with potential for therapeutic targeting with existing pharmacologic agents. These data provide new insights into the molecular pathogenesis of GCT of the pituitary and may warrant further investigation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lin-Yu Jin ◽  
Chen Guo ◽  
Shuai Xu ◽  
Hai-Ying Liu ◽  
Xin-Feng Li

The absence of leptin results in contrasting growth pattern of appendicular and axial bone growth in ob/ob mice. Endochondral bone formation is an important procedure of growth plate determining the bone growth, where this procedure is also regulated by estrogen and its receptor (ER) signaling pathway. The present study is undertaken to explore the roles of ERs in regulating the different growth patterns in ob/ob mice. In this study, C57BL/6 female mice were used as wild-type (WT) mice; ob/ob mice and WT mice were age-matched fed, and bone length is analyzed by X-ray plain film at the 12 weeks old. We confirm that ob/ob mice have shorter femoral length and longer spine length than WT mice (p < 0.05). The contrasting expression patterns of chondrocyte proliferation proteins and hypertrophic marker proteins are also observed from the femur and spinal growth plate of ob/ob mice compared with WT mice (p < 0.01). Spearman’s analysis showed that body length (axial and appendicular length) is positively related to the expression level of ERα in growth plate. Three-week-old female ob/ob mice are randomized divided into three groups: 1) ob/ob + ctrl, 2) ob/ob + ERα antagonist (MPP), and 3) ob/ob + ERβ antagonist (PHTPP). Age-matched C57BL/6 mice were also divided into three groups, same as the groups of ob/ob mice. MPP and PHTPP were administered by intraperitoneal injection for 6 weeks. However, the results of X-ray and H&E staining demonstrate that leptin deficiency seems to disturb the regulating effects of ER antagonists on longitudinal bone growth. These findings suggested that region-specific expression of ERα might be associated with contrasting phenotypes of axial and appendicular bone growth in ob/ob mice. However, ER signaling on longitudinal bone growth was blunted by leptin deficiency in ob/ob mice, and the underlying association between ERs and leptin needs to be explored in future work.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yixuan Wu ◽  
Haiying Liu ◽  
Jianqiao Liu

BackgroundNo studies have been done to examine the efficacy of IVF and intrauterine insemination (IUI) for the treatment of young patients with unexplained infertility and low ovarian reserve, although it is becoming an increasingly significant indication for in-vitro fertilization (IVF). The goal of this research was to compare the efficacy of IVF with IUI on Poseidon group 3 patients with unexplained infertility (PG3&UI).MethodsThis was a retrospective analysis of PG3&UI patients who had IVF/intracytoplasmic sperm injection (ICSI) or IUI at the Third Affiliated Hospital of Guangzhou Medical University between January 1, 2015, and March 31, 2021. To equalize the baseline characteristics of the IVF/ICSI and IUI groups, propensity score matching (PSM) was utilized. Intention-to-treat (ITT) and per-protocol (PP) analyses were used to compare the differences in live births. To discover variations in time to biochemical pregnancy leading to live birth, Kaplan-Meier curves were produced. To evaluate the expenses per live birth between two procedures, a cost-effective analysis was done.ResultsAccording to ITT analysis, the live birth rate for the IVF/ICSI group was substantially higher than the cumulative live birth rate (CLBR) for the IUI group (22.6% (38/168) vs. 11.3% (19/168), RR 2.00, 95% CI 1.20-3.32, P = 0.006). In the PP analysis, the live birth rate was 23.0% (38/165) in the IVF/ICSI group and 11.7% (19/162) in the IUI group (RR = 1.96, 95% CI 1.18-3.26, P = 0.007). When censored at 365 days, the Kaplan-Meier analysis revealed that the IVF/ICSI group had a higher live birth rate than the IUI group (log-rank test χ²= 6.025; P = 0.014). However, when the two groups were censored at 180 days, the live birth rates were not substantially different (log-rank test χ²= 3.847; P = 0.05). The number of hospital visits per live birth in the IUI group was higher than in the IVF/ICSI group (85 vs. 48). The overall cost of a live birth was comparable across the two groups (¥132242 vs. ¥131611), while the medical expenses for a live delivery from IVF/ICSI were higher than those from IUI (¥118955 vs. ¥108279).ConclusionsThe livebirth rate per IVF/ICSI cycle with at most one embryo transfer is higher than the CLBR of IUI, with fewer hospital visits and similar expenses.


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