Embryo implantation is a complex process in which multiple molecules acting together under strict regulation. Studies showed the production of various adipokines and their receptors in the embryo and uterus, where they can influence the maternal-fetal transmission of metabolites and embryo implantation. Therefore, these cytokines have opened a novel area of study in the field of embryo–maternal crosstalk during early pregnancy. In this respect, the involvement of adipokines has been widely reported in the regulation of both physiological and pathological aspects of the implantation process. However, the information about the role of some recently identified adipokines is limited. This review aims to highlight the role of various adipokines in embryo–maternal interactions, endometrial receptivity, and embryo implantation, as well as the underlying molecular mechanisms.
Davoud Jafari-Gharabaghlou, Mostafa Vaghari-Tabari, Hajar Oghbaei, Laura Lotz, Reza Zarezadeh, Yeganeh Rastgar Rezaei, Mahnaz Ranjkesh, Mohammad Nouri, Amir Fattahi, Saba Nikanfar, and Ralf Dittrich
Daniel Bell, Julia Hale, Cara Go, Ben G Challis, Tilak Das, Brian Fish, and Ruth T Casey
Primary hyperparathyroidism (pHPT) is a common endocrine disorder that can be cured by parathyroidectomy; patients unsuitable for surgery can be treated with cinacalcet. Availability of surgery may be reduced during COVID-19, and cinacalcet can be used as bridging therapy. In this single-centre retrospective analysis, we investigated the utility and safety of cinacalcet in patients with pHPT receiving cinacalcet between March 2019 and July 2020, including pre-parathyroidectomy bridging. We reviewed and summarised the published literature. Cinacalcet dosages were adjusted by endocrinologists to achieve target calcium < 2.70 mmol/L. Eighty-six patients were identified, with the most achieving target calcium (79.1%) with a mean dose of 39.4 mg/day (±17.1 mg/day) for a median duration of 35 weeks (1–178 weeks). Calcium was normalised in a median time of 5 weeks. The majority of patients commenced cinacalcet of 30 mg/day (78 patients) with the remainder at 60 mg/day (8 patients). Forty-seven patients commencing lower dose cinacalcet (30 mg/day) achieved target calcium without requiring 60 mg/day. Baseline PTH was significantly higher in patients requiring higher doses of cinacalcet. 18.6% of patients reported adverse reactions and 4.7% discontinued cinacalcet. Patients treated with cinacalcet pre-parathyroidectomy required a higher dose and fewer achieved target calcium compared to medical treatment with cinacalcet alone. Post-operative calcium was similar to patients who were not given pre-parathyroidectomy cinacalcet. In summary, cinacalcet at an initial dose of 30 mg/day is safe and useful for achieving target calcium in patients with symptomatic or severe hypercalcaemia in pHPT, including those treated for pre-parathyroidectomy. We propose a PTH threshold of >30 pmol/L to initiate at a higher dose of 60 mg/day.
Ren-Lei Ji, Lu Huang, Yin Wang, Ting Liu, Si-Yu Fan, Min Tao, and Ya-Xiong Tao
Melanocortin-3 receptor (MC3R) is a regulator of energy homeostasis, and interaction of MC3R and melanocortin-2 receptor accessory protein 2 (MRAP2) plays a critical role in MC3R signaling of mammals. However, the physiological roles of MC3R in teleosts are not well understood. In this study, qRT-PCR was used to measure gene expression. Radioligand binding assay was used to study the binding properties of topmouth culter MC3R (caMC3R). Intracellular cAMP generation was determined by RIA, and caMC3R expression was quantified with flow cytometry. We showed that culter mc3r had higher expression in the CNS. All agonists could bind and stimulate caMC3R to increase dose dependently intracellular cAMP accumulation. Compared to human MC3R, culter MC3R showed higher constitutive activity, higher efficacies, and R max to alpha-melanocyte-stimulating hormone (α-MSH), des-α-MSH, and adrenocorticotrophic hormone. Both caMRAP2a and caMRAP2b markedly decreased caMC3R basal cAMP production. However, only caMRAP2a significantly decreased cell surface expression, B max, and R max of caMC3R. Expression analysis suggested that MRAP2a and MRAP2b might be more important in regulating MC3R/MC4R signaling during larval period, and reduced mc3r, mc4r, and pomc expression might be primarily involved in modulation of MC3R/MC4R in adults. These data indicated that the cloned caMC3R was a functional receptor. MRAP2a and MRAP2b had different effects on expression and signaling of caMC3R. In addition, expression analysis suggested that MRAP2s, receptors, and hormones might play different roles in regulating culter development and growth.
Hong Jiang, WenJie Yang, QingFang Sun, Chang Liu, and LiuGuan Bian
The adverse effects of hypercortisolism on the human brain have been highlighted in previous studies of Cushing’s disease (CD). However, the relative alterations in regional hypercortisolism in the brain remain unclear. Thus, we investigated regional volumetric alterations in CD patients. We also analyzed the associations between these volumetric changes and clinical characteristics. The study participants comprised of active CD (n = 60), short-term-remitted CD (n = 28), and long-term-remitted CD (n = 32) patients as well as healthy control subjects (n = 66). Gray matter volumes (GMVs) were measured via voxel-based morphometry. The GMVs of substructures were defined using the automated anatomical labeling (AAL) atlas. Trends toward normalization in GMV were found in most brain substructures of CD patients. Different trends, including enlarged, irreversible, and unaffected, were observed in the other subregions, such as the amygdala, thalamus, and caudate. Morphological changes in GMVs after the resolution of hypercortisolism are a complex phenomenon; the characteristics of these changes significantly differ within the brain substructures.
Yusen Liu, Ruiwen Chi, Yujie Jiang, Bicheng Chen, Youli Chen, and Zengrui Chen
Triglyceride glycemic (TyG) index is a novel tool for assessing insulin resistance (IR). Recently, TyG index as a potential biomarker for gestational diabetes mellitus (GDM) has been studied, but its performance is yet inconclusive. Thus, we performed this systemic review and meta-analysis to evaluate the performance of TyG index in predicting GDM.
Studies published before March 1, 2021, with comparison of TyG index between GDM patients and healthy controls were retrieved from multiple databases (PubMed, Web of Science, The Cochrane Library, and Embase). The mean difference (MD) of TyG index in GDM patients and healthy controls was pooled using random-effect models.
Differentiation of TyG index between patients with GDM and controls showed significant results. Overall, there is a four-fold increase in TyG index in GDM patients compared with controls (MD: 0.22, 95% CI: 0.07–0.36, P = 0.003; I 2 = 71%, P = 0.009). In subgroup analyses according to gestational time, TyG index in the second trimester predicted GDM with low heterogeneity (MD: 0.26, 95% CI: 0.15–0.37, P < 0.001; I 2 = 0%, P = 0.54), while no such correlation was found in the first trimester.
TyG index, especially in the second trimester, could be a promising biomarker for predicting GDM.
Ann R Webb, Rehab Alghamdi, Richard Kift, and Lesley E Rhodes
A systematic review of publications addressing change in vitamin D status (25-hydroxyvitamin D (25OHD)) after exposure to UV radiation identified 2001 independent peer-reviewed publications. Of these, 21 used artificial sources of UV radiation, met all inclusion criteria and were quality assured; 13 publications used solar radiation and met sufficient inclusion criteria to be retained as supporting evidence; 1 further included publication used both solar and artificial sources. The review consistently identified that low dose, sub-erythemal doses are more effective for vitamin D synthesis than doses close to a minimum erythema dose; increasing skin area exposed increases the amount of vitamin D synthesised although not necessarily in a linear manner; constant dosing leads to a dose-dependent plateau in 25OHD, and dose–response is greatest at the start of a dosing regime; there is a large interpersonal variation in response to UV exposure. Fourteen of the studies using artificial sources of radiation were used to determine a dose–response relationship for change in 25OHD on whole-body exposure to repeated sub-erythemal doses of UV radiation, taking the form Δ25OHD (nmol/L) = A ln(standard vitamin D dose) + B. This helps quantify our understanding of UV as a source of vitamin D and enables exposure regimes for safe synthesis of vitamin D to be assessed. Specific studies of people with pigmented skin (Fitzpatrick skin types 5 and 6) were rare, and this dose–response relationship is only applicable to white-skinned individuals as skin type is a determinant of response to UV radiation. Findings provide information for vitamin D guidance updates.
Agnieszka Adamska, Paulina Tomczuk-Bobik, Anna Beata Popławska-Kita, Katarzyna Siewko, Angelika Buczyńska, Piotr Szumowski, Łukasz Żukowski, Janusz Myśliwiec, Monika Zbucka-Krętowska, Marcin Adamski, and Adam Jacek Krętowski
Treatment with radioactive iodine (RAI) in women with differentiated thyroid cancer is associated with decreased serum concentrations of anti-Müllerian hormone (AMH); however, other markers have not been investigated. Therefore, this study aimed to evaluate the effect of RAI treatment on antral follicle count (AFC) and the serum concentration of inhibin B, follicle-stimulating hormone (FSH), and AMH in women with papillary thyroid cancer (PTC) treated with RAI. We examined 25 women at a median age of 33 years treated with a single dose of RAI. We divided the participants into women over (n = 11) and under 35 years of age (n = 14). Serum concentrations of inhibin B, FSH, AMH, and AFC were assessed at baseline and 1 year after RAI treatment. We found decreased AFC (P = 0.03), serum levels of AMH (P < 0.01), inhibin B (P = 0.03), but not FSH (P = 0.23), 1 year after RAI treatment in comparison to baseline in the whole group. When we compared serum levels of AMH in younger vs older women separately, we observed a significant reduction of this hormone’s serum level after RAI treatment in both groups (P < 0.01; P = 0.04, respectively). We concluded that RAI treatment significantly impacts the functional ovarian reserve in premenopausal women with PTC.
Feifei Cheng, Noel Yat Hey Ng, Claudia Ha Ting Tam, Yuying Zhang, Cadmon King Poo Lim, Guozhi Jiang, Alex Chi Wai Ng, Tiffany Tse Ling Yau, Lai Ping Cheung, Aimin Xu, Juliana C N Chan, and Ronald C W Ma
Women with polycystic ovary syndrome (PCOS) have an increased risk of developing type 2 diabetes. FGF19, FGF21 and lipocalin-2 have emerged as important markers of metabolic risk. This study aims to compare the levels of FGF19, FGF21 and lipocalin-2 between subjects with or without PCOS, and to investigate the relationship between proteins and diabetes progression. In this nested case–control cohort study, 128 Chinese PCOS women and 128 controls were recruited and followed-up. All subjects underwent the oral glucose tolerance test for the evaluation of glycaemic status. Baseline serum protein levels were measured using ELISA. Compared with controls, PCOS subjects had higher levels of FGF19 (P < 0.001) and FGF21 (P = 0.022), but had lower lipocalin-2 (P < 0.001). In total, 20.8% of PCOS and 9.2% of controls developed diabetes over a mean duration of 10.4 ± 1.2 and 11.3 ± 0.5 years, respectively. Logistic regression analyses suggested FGF19 was positively associated with diabetes progression in controls, after adjusting for age, follow-up duration, waist and fasting glucose (P = 0.026, odds ratio (OR) (95% CI): 7.4 (1.3–43.6)), and the positive relationship between FGF21 and diabetes progression in controls was attenuated by adjusting for age and follow-up duration (P = 0.183). Lipocalin-2 was positively correlated with diabetes progression in PCOS group (P = 0.026, OR (95% CI)): 2.5 (1.1–5.6)); however, this became attenuated after adjusting for waist and fasting glucose (P = 0.081). In conclusion, there is differential expression of FGF19, FGF21, and lipocalin-2 in PCOS. The serum level of FGF19, and FGF21 is associated with diabetes progression in women without PCOS, while lipocalin-2 was related to diabetes progression in PCOS women.
Chun-feng Lu, Wang-shu Liu, Xiao-qin Ge, Feng Xu, Jian-bin Su, Xue-qin Wang, and Yan Wang
Adenosine deaminase (ADA) is essential for the differentiation and maturation of lymphocytes, while lymphocytes infiltration in thyroid tissue is a vital pathological feature of Graves’ disease (GD). The aim of the present study was to compare the concentration of ADA between healthy controls (HC) and patients with GD, and evaluate the association between ADA and GD.
A total of 112 GD patients and 77 matched HC were enrolled in this study. Each participant was examined for thyroid hormones and autoantibodies, ADA concentration, and thyroid ultrasonography.
Serum ADA levels in GD patients were significantly higher than that in HC subgroup (P < 0.001). In GD patients, serum ADA levels were positively associated with serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb) levels, and total thyroid gland volume (thyroid VolT) and negatively associated with serum thyroid-stimulating hormone receptor (TSH) levels (all P < 0.05). There were no similar correlations in the HC subgroup. Multiple linear regression analysis suggested that serum TSH, FT3, and ADA levels played an important role in serum TRAb levels.
Our results demonstrated that serum ADA levels were closely associated with GD.
Yutong Zou, Lijun Zhao, Junlin Zhang, Yiting Wang, Yucheng Wu, Honghong Ren, Tingli Wang, Rui Zhang, Jiali Wang, Yuancheng Zhao, Chunmei Qin, Huan Xu, Lin Li, Zhonglin Chai, Mark E Cooper, Nanwei Tong, and Fang Liu
To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN).
A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least 1 year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group: 286.02 ± 46.66 μmol/L (n = 98); Q2 group: 358.23 ± 14.03 μmol/L (n = 99); Q3 group: 405.50 ± 14.59 μmol/L (n = 98) and Q4 group: 499.14 ± 56.97μmol/L (n = 98). Renal outcome was defined by progression to end-stage renal disease (ESRD). Kaplan–Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes.
During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%). No significant difference between SUA level and the risk of progression of DN (P = 0.747) was shown in the Kaplan–Meier survival analysis. In multivariable-adjusted model, hazard ratios for developing ESRD were 1.364 (0.621–2.992; P = 0.439), 1.518 (0.768–3.002; P = 0.230) and 1.411 (0.706–2.821; P = 0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P = 0.652).
No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improving ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.