Hormone and Metabolic Research最新文献

Alzheimer's disease (AD) is a widespread neurodegenerative disorder characterized by progressive memory and cognitive decline, posing a formidable public health challenge. This review explores the intricate interplay between two pivotal players in AD pathogenesis: β-amyloid (Aβ) and tau protein. While the amyloid cascade theory has long dominated AD research, recent developments have ignited debates about its centrality. Aβ plaques and tau NFTs are hallmark pathologies in AD. Aducanumab and lecanemab, monoclonal antibodies targeting Aβ, have been approved, albeit amidst controversy, raising questions about the therapeutic efficacy of Aβ-focused interventions. On the other hand, tau, specifically its hyperphosphorylation, disrupts microtubule stability and contributes to neuronal dysfunction. Various post-translational modifications of tau drive its aggregation into NFTs. Emerging treatments targeting tau, such as GSK-3β and CDK5 inhibitors, have shown promise in preclinical and clinical studies. Restoring the equilibrium between protein kinases and phosphatases, notably protein phosphatase-2A (PP2A), is a promising avenue for AD therapy, as tau is primarily regulated by its phosphorylation state. Activation of tau-specific phosphatases offers potential for mitigating tau pathology. The evolving landscape of AD drug development emphasizes tau-centric therapies and reevaluation of the amyloid cascade hypothesis. Additionally, exploring the role of neuroinflammation and its interaction with tau pathology present promising research directions.

The aim of the study was to assess the association between lipoprotein(a) [Lp(a)] concentration and incident type 2 diabetes. A meta-analysis of qualified studies on the relationship of low levels of Lp(a) concentration with incident type 2 diabetes was conducted. PubMed and Cochrane libraries were searched for randomized controlled trials containing data on events. Seven randomized trials with 227178 subjects were included in this analysis. We found an inverse association of the levels of Lp(a) concentration with risk of type 2 diabetes with approximately 37% lower relative risk in the group with the highest concentration compared with group with the lowest concentration. The current available evidence from prospective studies suggests that there is an inverse association between the levels of Lp(a) concentration and risk of type 2 diabetes, with a higher risk of type 2 diabetes at low levels of Lp(a) concentration. Therefore, we believe that the low levels of Lp(a) concentration is an independent predictor of incident type 2 diabetes.

The purpose of this study is to evaluate and analyze the quality of guidelines and expert consensus on clinical practice regarding metabolically associated fatty liver disease (MAFLD) over the past five years. Data from the websites were retrieved using computers. We evaluated guidelines and expert consensus on MAFLD that were officially published between January 1, 2018 and March 24, 2023. Two evaluators independently examined the literature and extracted data. The included literature on guidelines and expert consensus was then subjected to quality review and analysis using assessment tools from Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) (2016). The intraclass correlation coefficient (ICC) values of all items on the AGREE II scale for the two evaluators were greater than 0.75, indicating a high degree of agreement between their assessments. Scope and purpose (48.90%), participants (49.21%), rigor in the formulation process (56.97%), clarity of expression (90.08%), applicability (66.08%), and independence of file compiling (60.12%) were the AGREE II scoring items with the standardized average scores. Apart from the participants, the average scores of all the scoring items in the guidelines from other countries other than China were higher than those from China (|Z|+>+2.272, p+<+0.05). MAFLD guidelines must be revised to enhance their methodological quality. When creating guidelines, it is recommended that the formulators strictly adhere to the formulation and drafting standards of AGREE II and elevate the quality of the guidelines.

Kidney transplantation (KT) is the best option for patients with end-stage renal disease, but recipients still have legacy bone mineral disease from the pretransplant period, especially patients with severe secondary hyperparathyroidism (sHPT). Patients who had severe sHPT and underwent KT were analyzed retrospectively. Two groups were identified (patients with severe sHPT who had parathyroidectomy or calcimimetic before KT). Bone mineral density (BMD) was measured in the first year and last follow-up at the femoral neck, total hip, and lumbar spine using the dual-energy X-ray absorptiometry (DXA). Persistent hyperparathyroidism (perHPT) incidence was significantly higher in the calcimimetic group (75% vs. 40%, p=0.007). In patients with parathyroidectomy, BMDs were higher at femoral neck (0.818±0.114 vs. 0.744±0.134, p=0.04) and lumbar spine (1.005±0.170 vs. 0.897±0.151, p=0.01) at the first assessment. The BMD comparison between patients treated with parathyroidectomy and calcimimetic found a significant difference only in the femoral neck at second evaluation (0.835±0.118 vs. 0.758±0.129; p=0.03). In multivariate, linear regression revealed a positive association between the last BMD of the femoral neck with body mass index (CC: 0.297, 95% CI, 0.002-0.017) and parathyroidectomy (CC: 0.319, 95% CI, 0.021-0.156). Parathyroidectomy is associated with a significantly better femoral neck BMD and a lower incidence of perHPT in patients with severe sHPT.

Our previous study showed that elevated preoperative thyroglobulin (pre-Tg) level predicted the risk of developing radioiodine refractory in PTC patients. In the present study, we aimed to evaluate the prognostic value of pre-Tg in papillary thyroid microcarcinoma (PTMC). After a specific inclusion and exclusion criteria were applied, a total of 788 PTMCs were enrolled from Jiangyuan Hospital affiliated to Jiangsu Institute of Nuclear Medicine between Jan 2015 and Dec 2019. Among them, 107 PTMCs were treated with radioiodine therapy (RAIT) and the response to therapy was grouped as excellent response (ER), and non-excellent response (NER: indeterminate response, IDR and biochemical incomplete response, BIR). Multivariable logistic regression was used to identify predictors for the response of RAIT in PTMCs. Higher pre-Tg levels were detected in PTMCs with RAIT as compared with PTMCs without RAIT (p=0.0018). Higher levels of pre-Tg were also found in patients with repeated RAIT as compared with patients with single RAIT (p<0.0001). Furthermore, pre-Tg level was higher in PTMC with IDR (n=16) and much higher in BIR (n=9) as compared with patients with ER (n=82, p=0.0003) after RAIT. Multivariate analysis showed that pre-Tg level over 16.79 ng/ml [OR: 6.55 (2.10-20.39), p=0.001] was the only independent predictor for NER in PTMC with RAIT. We found that high level of pre-Tg predicted a poor RAIT outcome in PTMC. Our finding explores a prospective way in identifying high-risk PTMCs with poor response to RAIT.

Little is known about axillary node metastasis of medullary thyroid cancer (MTC). To address this, a comparative study of patients with and without axillary node metastases of MTC was conducted. Among 1215 consecutive patients with MTC, 482 patients had node-negative MTC and 733 patients node-positive MTC. Among the 733 patients with node-positive MTC, 4 patients (0.5%) had axillary node metastases, all of which were ipsilateral. Patients with axillary node metastases had 5.7-6.9-fold more node metastases removed, both at the authors' institution (medians of 34.5 vs. 5 metastases; p=0.011) and in total (medians of 57 vs. 10 metastases; p=0.013), developed more frequently distant metastases (3 of 4 vs. 178 of 729 patients, or 75 vs. 24%; p=0.049), specifically to bone (2 of 4 vs. 67 of 729 patients, or 50 vs. 9%; p=0.046) and brain (1 of 4 vs. 4 of 729 patients, or 25 vs. 0.5%; p=0.027), and more often succumbed to cancer-specific death (3 of 4 vs. 52 of 729 patients, or 75 vs. 14%; p=0.005). Altogether, patients with axillary node metastases revealed 4-8-fold more node metastases in the ipsilateral lateral neck (medians of 11 vs. 3 metastases; p=0.021) and in the ipsilateral central neck (medians of 8 vs. 1 metastases; p=0.079) patients without axillary node metastases. Cancer-specific survival of patients with vs. patients without axillary node metastases of MTC was significantly shorter (means of 41 vs. 224 months; plog-rank<0.001). These findings show that patients with axillary node metastases of MTC have massive metastatic dissemination with poor survival.

The aim of the study was to evaluate the efficacy of anthropometric, metabolic, and endocrine abnormalities as predictors of estimated average glucose and other biomarkers of dysglycemia in women with different phenotypes of polycystic ovary syndrome (PCOS). This cross-sectional study included 648 women with PCOS and 330 controls. A single protocol of investigation was applied for all subjects. PCOS women were divided by phenotypes according to the Rotterdam criteria. Biomarkers of dysglycemia were considered dependent variables and anthropometric, lipid, and hormone alterations as independent variables using univariate and multivariate logistic regressions. Univariate logistic regression analysis, controlled for age and BMI, showed that many biomarkers of dysglycemia could be predicted by anthropometric, lipid, and endocrine variables. Multivariate logistic models showed that in non-PCOS women estimated average glucose (eAG) was predicted by lower TSH levels (OR=0.39; p=0.045); fasting glucose was predicted by increased T (OR=2.3). For PCOS, phenotype A, eAG was predicted by decreased HDL-C (OR=0.17, p=0.023) and high levels of free estradiol (OR=7.1, p<0.001). Otherwise, in PCOS, phenotype D, eAG was predicted by higher levels of HDL-C. The current study demonstrated that eAG was poorly predicted by anthropometric, lipid, and hormone parameters. Nevertheless, without adding significant benefits, it was comparable with other established markers of dysglycemia in women with different PCOS phenotypes.

Melatonin (5-methoxy-acetyl tryptamine) is a sleep-inducing hormone, and the pineal gland produces it in response to the circadian clock of darkness. In the body, MT1 and MT2 receptors are mostly found, having an orthosteric pocket and ligand binding determinants. Melatonin acts by binding on melatonin receptors, intracellular proteins, and orphan nuclear receptors. It inhibits adenyl cyclase and activates phospholipase C, resulting in gene expression and an intracellular alteration environment. Melatonin signaling pathways are also associated with other intracellular signaling pathways, i. e., cAMP/PKA and MAPK/ERK pathways. Relative expression of different proteins depends on the coupling profile of G protein, accounting pharmacology of the melatonin receptor bias system, and mediates action in a Gi-dependent manner. It shows antioxidant, antitumor, antiproliferative, and neuroprotective activity. Different types of melatonin agonists have been synthesized for the treatment of sleeping disorders. Researchers have developed therapeutics that target melatonin signaling, which could benefit a wide range of medical conditions. This review focuses on melatonin receptors, pharmacology, and signaling cascades; it aims to provide basic mechanical aspects of the receptor's pharmacology, melatonin's functions in cancer and neurodegenerative diseases, and any treatments and drugs designed for these diseases. This will allow a basic comparison between the receptors in question, highlighting any parallels and differences that may exist and providing fundamental knowledge about these receptors to future researchers.

The influence of metabolic syndrome (MetS) on long-term prognosis of patients with myocardial infarction (MI), the most severe type of coronary artery disease, remains not fully determined. This systematic review and meta-analysis were conducted to investigate the association between MetS and long-term clinical outcomes of patients with MI. A systematic search of Medline, Web of Science, and Embase databases from inception to June 25, 2023, was conducted to obtain eligible studies. Only studies with follow-up duration for at least one year were considered. A random-effects model was utilized to pool the results, accounting for heterogeneity. Ten observational studies were included, which included 33 197 patients with MI. Among them, 17 244 (51.9%) were with MetS at baseline. During a follow-up duration of 12 to 48 months (mean: 22.5 months), patients with MetS were associated with higher incidence of major adverse cardiovascular events [risk ratio (RR): 1.35. 95% confidence interval (CI): 1.19 to 1.54, p<0.001; I2=64%] and all-cause deaths (RR: 1.34, 95% CI: 1.18 to 1.52, p<0.001; I2=23%), as compared to those without MetS at baseline. Subgroup analyses showed that the results were not significantly affected by study characteristics such as study country, design, type of MI, mean age of the patients, treatment with percutaneous coronary intervention, follow-up durations, or study quality scores (p for subgroup difference all>0.05). In patients with MI, MetS may be a risk factor of poor long-term prognosis.