Effect of vitamin D, calcium, or combined supplementation on fall prevention: a systematic review and updated network meta-analysis.

BACKGROUND: The association between vitamin D supplementation and the risk of falls in older adults has been controversial. This systematic review and network meta-analysis aims to assess the efficacy of vitamin D, calcium, and combined supplementation in the prevention of falls. METHODS: Randomized controlled trials (RCTs) on the efficacy of vitamin D in fall prevention were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 9, 2023. The network meta-analysis was performed using a random effects model in R4.1.3 and Stata15.0. Heterogeneity was evaluated by the I2 statistic, and publication bias was assessed using funnel plots, Begg's test, and Egger's tests. Data were pooled and expressed as relative risk (RR) and 95% confidence interval (CI). RESULTS: A total of 35 RCTs involving 58,937 participants were included in this study, among which 11 RCTs (31.4%) applied calcium combined with vitamin D. There was low heterogeneity (I2 = 11%) among the included studies. Vitamin D supplementation at 800-1000 International Unit (IU)/d resulted in a lower risk of falls than placebo or no treatment (RR = 0.85, 95%CI: 0.74-0.95). In addition, 800-1000 IU/d of vitamin D with or without calcium were more effective in preventing falls than calcium alone. High-dose vitamin D (> 1000 IU/day) increased the risk of falls compared with 800-1000 IU/d of vitamin D. According to the subgroup analysis, daily administration of 800-1000 IU/d vitamin D was associated with a 22% reduction in the risk of falls (RR = 0.78, 95%CI:0.64-0.92), whereas intermittent vitamin D administration had no preventive effect. Furthermore, 800-1000 IU/d of vitamin D also significantly decreased the risk of falls in old adults with ≤ 50 nmol/L 25-hydroxyvitamin D [25(OH)D] (RR = 0.69, 95%CI:0.52-0.86) but not in individuals with > 50 nmol/L 25(OH)D. CONCLUSION: Vitamin D supplementation at 800-1000 IU/d is associated with a lower risk of falls among older adults. 800-1000IU/d of vitamin D has a benefit on prevention of falls in population received daily dose regimens and in population with vitamin D deficiency.

Wearable Sensor-Based Residual Multifeature Fusion Shrinkage Networks for Human Activity Recognition.

Human activity recognition (HAR) based on wearable sensors has emerged as a low-cost key-enabling technology for applications such as human-computer interaction and healthcare. In wearable sensor-based HAR, deep learning is desired for extracting human active features. Due to the spatiotemporal dynamic of human activity, a special deep learning network for recognizing the temporal continuous activities of humans is required to improve the recognition accuracy for supporting advanced HAR applications. To this end, a residual multifeature fusion shrinkage network (RMFSN) is proposed. The RMFSN is an improved residual network which consists of a multi-branch framework, a channel attention shrinkage block (CASB), and a classifier network. The special multi-branch framework utilizes a 1D-CNN, a lightweight temporal attention mechanism, and a multi-scale feature extraction method to capture diverse activity features via multiple branches. The CASB is proposed to automatically select key features from the diverse features for each activity, and the classifier network outputs the final recognition results. Experimental results have shown that the accuracy of the proposed RMFSN for the public datasets UCI-HAR, WISDM, and OPPORTUNITY are 98.13%, 98.35%, and 93.89%, respectively. In comparison with existing advanced methods, the proposed RMFSN could achieve higher accuracy while requiring fewer model parameters.

Iodine Intakes of <150 µg/day or >550 µg/day are Not Recommended during Pregnancy: A Balance Study.

BACKGROUND: Adequate iodine intake during pregnancy is critical for maintaining maternal and fetal thyroid function and development. There are only limited data from iodine-balance studies to inform iodine requirements during pregnancy. OBJECTIVES: This is an iodine-balance study conducted to explore the associations among iodine intake, excretion, and retention to provide information regarding iodine requirements during pregnancy. METHODS: A 7-d iodine-balance experiment enrolled 93 healthy pregnant Chinese women from Hebei, Tanjin, and Shandong. Duplicates of all foods and beverages consumed were systematically collected and measured for iodine content. Iodine excretion was measured by collecting 24-h urine and feces samples. Simple linear regression models were used to assess relationships between total iodine intake and iodine retention, whereas mixed effect models were used to assess the relationship between daily iodine intake and iodine retention. RESULTS: The mean ± SD age of participating pregnant women was 29 ± 2 y at a median 22 (IQR: 13-30) wk of gestation. The mean 7-d iodine retention was 43.0 ± 1060 µg/7 d. A negative iodine balance was present in 56% of women whereas 44% had a positive balance. Pregnant women with iodine intakes <150 µg/d were in negative balance whereas those with intakes >550 µg/d were in positive balance. The daily iodine intake at zero balance was 343 µg/d, which was higher in women from Shandong (492 µg/d) than in those from Hebei and Tianjin (202 µg/d). CONCLUSIONS: Iodine intake at zero balance determined in pregnant women with adequate iodine nutrition is 202 µg/d, and the calculated recommended nutrient intake (RNI) is 280 µg/d. Iodine intakes of <150 µg/d and >550 µg/d are not recommended during pregnancy. This trial was registered at clinicaltrials.gov as NCT03710148.

Blueberry extracts antagonize Aß25-35 neurotoxicity and exert a neuroprotective effect through MEK-ERK-BDNF/UCH-L1 signaling pathway in rat and mouse hippocampus.

BACKGROUND: The neuroprotective potential of blueberry (BB) extracts against Alzheimer's disease (AD) has been previously hinted at, while its exact mechanism has remained largely enigmatic. OBJECTIVE: Our study endeavored to unravel the impacts and mechanisms by which BB extracts ameliorated the learning and memory prowess of AD-afflicted mice, with a specific focus on the MEK-ERK pathway. METHODS: We employed 3-month-old APP/PS1 transgenic mice and stratified them into three distinct groups: AD+BB, AD, and control (CT). The Morris Water Maze Test (MWMT) was then administered to gauge their learning and memory faculties. In vitro experiments were executed on Aß25-35-afflicted rat hippocampal neurons, which were subsequently treated with varying concentrations of BB extracts. We then assessed the expression levels of genes and proteins integral to the MEK-ERKBDNF/UCH-L1 pathway. RESULTS: The data showed that the AD mice demonstrated compromised learning and memory faculties in MWMT. However, the AD+BB cohort showcased marked improvements in performance. Furthermore, in the AD subset, significant elevations in the expressions of MEK2 and ERK1/2 were observed, both at the mRNA and protein levels. Conversely, UCH-L1 mRNA expressions exhibited a decline, while BDNF expressions surged significantly. However, post BB extract treatment, the expressions of MEK2 and ERK1/2 were subdued, with UCH-L1 and BDNF mRNA expressions reverting to control levels. CONCLUSIONS: Our findings propounded that BB extracts could offer therapeutic promise for AD by bolstering learning and memory capacities. The unwarranted activation of the MEK-ERK pathway, coupled with the aberrant expressions of BDNF and UCH-L1, might underpin AD's pathogenesis.

Advances in phosphoproteomics and its application to COPD.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) was the third leading cause of global death in 2019, causing a huge economic burden to society. Therefore, it is urgent to identify specific phenotypes of COPD patients through early detection, and to promptly treat exacerbations. The field of phosphoproteomics has been a massive advancement, compelled by the developments in mass spectrometry, enrichment strategies, algorithms, and tools. Modern mass spectrometry-based phosphoproteomics allows understanding of disease pathobiology, biomarker discovery, and predicting new therapeutic modalities. AREAS COVERED: In this article, we present an overview of phosphoproteomic research and strategies for enrichment and fractionation of phosphopeptides, identification of phosphorylation sites, chromatographic separation and mass spectrometry detection strategies, and the potential application of phosphorylated proteomic analysis in the diagnosis, treatment, and prognosis of COPD disease. EXPERT OPINION: The role of phosphoproteomics in COPD is critical for understanding disease pathobiology, identifying potential biomarkers, and predicting new therapeutic approaches. However, the complexity of COPD requires the more comprehensive understanding that can be achieved through integrated multi-omics studies. Phosphoproteomics, as a part of these multi-omics approaches, can provide valuable insights into the underlying mechanisms of COPD.

RedEx: a method for seamless DNA insertion and deletion in large multimodular polyketide synthase gene clusters.

Biosynthesis reprograming is an important way to diversify chemical structures. The large repetitive DNA sequences existing in polyketide synthase genes make seamless DNA manipulation of the polyketide biosynthetic gene clusters extremely challenging. In this study, to replace the ethyl group attached to the C-21 of the macrolide insecticide spinosad with a butenyl group by refactoring the 79-kb gene cluster, we developed a RedEx method by combining Redαß mediated linear-circular homologous recombination, ccdB counterselection and exonuclease mediated in vitro annealing to insert an exogenous extension module in the polyketide synthase gene without any extra sequence. RedEx was also applied for seamless deletion of the rhamnose 3'-O-methyltransferase gene in the spinosad gene cluster to produce rhamnosyl-3'-desmethyl derivatives. The advantages of RedEx in seamless mutagenesis will facilitate rational design of complex DNA sequences for diverse purposes.

Pharmacological effects of Eleutherococcus senticosus on the neurological disorders.

Eleutherococcus senticosus is a medicinal plant widely used in traditional medicine and edible remedies with effects on anti-fatigue, sleep improvement, and memory enhancement. Recently, the application of E. senticosus to neurological disorders has been a focus. However, its overall pharmacological effect on neural diseases and relevant mechanisms are needed in an in-depth summary. In this review, the traditional uses and the therapeutic effect of E. senticosus on the treatment of fatigue, depression, Alzheimer's disease, Parkinson's disease, and cerebral ischemia were summarized. In addition, the underlying mechanisms involved in the anti-oxidative damage, anti-inflammation, neurotransmitter modulation, improvement of neuronal growth, and anti-apoptosis were discussed. This review will accelerate the understanding of the neuroprotective effects brought from the E. senticosus, and impetus its development as a phytotherapy agent against neurological disorders.

New advances in quantitative proteomics research and current applications in asthma.

INTRODUCTION: Asthma is the most common chronic respiratory disease and has been declared a global public health problem by the World Health Organization. Due to the high heterogeneity and complexity, asthma can be classified into different 'phenotypes' and it is still difficult to assess the phenotypes and stages of asthma by traditional methods. In recent years, mass spectrometry-based proteomics studies have made significant progress in sensitivity and accuracy of protein identification and quantitation, and are able to obtain differences in protein expression across samples, which provides new insights into the mechanisms and classification of asthma. AREAS COVERED: In this article, we summarize research strategies in quantitative proteomics, including labeled, label-free and targeted quantification, and highlight the advantages and disadvantages of each. In addition, new applications of quantitative proteomics and the current status of research in asthma have also been discussed. In this study, online resources such as PubMed and Google Scholar were used for literature retrieval. EXPERT OPINION: The application of quantitative proteomics in asthma has an important role in identifying asthma subphenotypes, revealing potential pathogenesis and therapeutic targets. But the proteomic studies on asthma are not sufficient, as most of them are in the phase of biomarker discovery.

Evaluation of SARS-CoV-2 neutralizing antibodies using a vesicular stomatitis virus possessing SARS-CoV-2 spike protein.

BACKGROUND: SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is now classified in the genus Coronavirus with closely related SARS-CoV. SARS-CoV-2 is highly pathogenic in humans and is classified as a biosafety level (BSL)-3 pathogen, which makes manipulating it relatively difficult due to its infectious nature. METHODS: To circumvent the need for BSL-3 laboratories, an alternative assay was developed that avoids live virus and instead uses a recombinant VSV expressing luciferase and possesses the full length or truncated spike proteins of SARS-CoV-2. Furthermore, to measure SARS-CoV-2 neutralizing antibodies under BSL2 conditions, a chemiluminescence reduction neutralization test (CRNT) for SARS-CoV-2 was developed. The neutralization values of the serum samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative donors against the pseudotyped virus infection evaluated by the CRNT were compared with antibody titers determined from an enzyme-linked immunosorbent assay (ELISA) or an immunofluorescence assay (IFA). RESULTS: The CRNT, which used whole blood collected from hospitalized patients with COVID-19, was also examined. As a result, the inhibition of pseudotyped virus infection was specifically observed in both serum and whole blood and was also correlated with the results of the IFA. CONCLUSIONS: In conclusion, the CRNT for COVID-19 is a convenient assay system that can be performed in a BSL-2 laboratory with high specificity and sensitivity for evaluating the occurrence of neutralizing antibodies against SARS-CoV-2.

Two-Dimensional Speckle Tracking Echocardiography Identifies Coronary Artery Disease in 690 Patients: A Retrospective Study from a Single Center.

BACKGROUND Two-dimensional speckle tracking echocardiography (2D-STE) is a novel and non-invasive technique for the diagnosis of coronary artery disease (CAD). This retrospective study from a single center aimed to identify myocardial ischemia using 2D-STE in CAD patients identified by angiography. MATERIAL AND METHODS From March 1 to November 30, 2019, 690 patients in Beijing Hospital were enrolled. After angiography, 346 patients were diagnosed with CAD. Reduction in vessel diameter of ≥50% by stenosis in at least 1 major coronary artery or its main branch was considered CAD. Analysis of 2D-STE was performed using EchoPAC version 201. RESULTS The global strain was significantly impaired in CAD patients (P<0.01). Global longitudinal peak strain (GLPS) was analyzed in layers. For GLPS of the epicardium, the odds ratio (OR) was 1.297 (1.217-1.382; P=0.002), the area under the curve (AUC) was 0.727, and the cut-off value was -16.95; sensitivity and specificity were 73.7% and 63.0%, respectively. For GLPS of the middle layer, the OR was 1.260 (1.192-1.333; P<0.001), the AUC was 0.732, and the cut-off value was -20.95; sensitivity and specificity were 82.4% and 56.2%, respectively. For GLPS of the endocardium, the OR was 1.193 (1.137-1.251; P<0.001), the AUC was 0.708, and the cut-off value was -22.95; sensitivity and specificity were 82.9% and 52.9%, respectively. CONCLUSIONS The findings from this study support the clinical application of 2D-STE in patient populations with suspected myocardial ischemia due to CAD. Therefore, 2D-STE combined with ECG monitoring may have a future role for early screening of CAD patients.

Intra-individual and inter-individual variations in iodine intake and excretion in adult women: implications for sampling.

Iodine intake and excretion vary widely; however, these variations remain a large source of geometric uncertainty. The present study aims to analyse variations in iodine intake and excretion and provide implications for sampling in studies of individuals or populations. Twenty-four healthy women volunteers were recruited for a 12-d sampling period during the 4-week experiment. The duplicate-portion technique was used to measure iodine intake, while 24-h urine was collected to estimate iodine excretion. The mean intra-individual variations in iodine intake, 24-h UIE (24-h urinary iodine excretion) and 24-h UIC (24-h urinary iodine concentration) were 63, 48 and 55 %, respectively, while the inter-individual variations for these parameters were 14, 24 and 32 %, respectively. For 95 % confidence, approximately 500 diet samples or 24-h urine samples should be taken from an individual to estimate their iodine intake or iodine status at a precision range of ±5%. Obtaining a precision range of ±5% in a population would require twenty-five diet samples or 150 24-h urine samples. The intra-individual variations in iodine intake and excretion were higher than the inter-individual variations, which indicates the need for more samples in a study on individual participants.

Changes of hippocampus proteomic profiles after blueberry extracts supplementation in APP/PS1 transgenic mice.

Objective: To examine protein changes in the hippocampus of APP/PS1 transgenic mice after blueberry extracts (BB) intervention.Methods: Eight APP/PS1 transgenic mice were randomly assigned to Alzheimer's disease (AD)+BB group (n=4) and AD+control group (n=4). After a 16-week treatment, 2-DE and MALDI-TOF-MS were used to compare the proteomic profiles of the hippocampus in the two groups and Western blot was used to confirm the important differentially expressed proteins.Results: Twelve proteins were differentially expressed between the two groups. Nine of them were identified. Cytochrome b-c1 complex subunit 6, beta-actin, dynamin 1, and heat shock cognate 71 were up-regulated in AD+BB group, while a-enolase, stress-induced-phosphoprotein 1, malate dehydrogenase (MDH), MDH 1, and T-complex protein 1 subunit beta were down-regulated, respectively. Importantly, some of the identified proteins (e.g. dynamin 1) are known to be involved in cognitive impairment. Western blot analysis of hippocampus dynamin 1 expression confirmed the proteomic findings.Conclusions: The consumption of BB modulates the expression of proteins that are linked to the improvements of cognitive dysfunction in hippocampus of APP/PS1 transgenic mice.

Trimester-Specific Thyroid Function in Pregnant Women with Different Iodine Statuses.

OBJECTIVES: To explore trimester-specific thyroid function changes under different iodine statuses throughout pregnancy. METHODS: A cross-sectional study was conducted to assess the pregnancy iodine status, and 2,378 healthy pregnant women covering all 3 trimesters were recruited. Urinary iodine concentration (UIC) was measured by collecting spot urine samples. Blood samples were collected to evaluate thyroid function. Thyroid B-ultrasonography was conducted to measure the thyroid volume (Tvol). RESULTS: The median UIC was 168 µg/L (111-263 µg/L). The UIC, free triiodothyronine (FT3), and free thyroxine (FT4) were significantly decreased as the pregnancy progressed (p < 0.001, p for trend <0.001), while Tvol increased (p < 0.001, p for trend <0.001). Thyrotropin (TSH) was significantly different between the 3 trimesters and showed an upward trend (p < 0.001), but the p for trend was not significant (p for trend = 0.88). After stratification by UIC, there were no significant differences in serum TSH, FT4, or FT3 level between UIC groups. Tvol was significantly higher in the UIC ≥500 µg/L group in the first trimester (ß: 2.41, 95% CI: 1.09-3.72, p <0.001), as well as in the 250 ≤ UIC < 500 µg/L group (ß: 1.65, 95% CI: 0.61-2.70, p < 0.001) and UIC ≥500 µg/L group (ß: 3.35, 95% CI: 1.96-4.74, p < 0.001) in the third trimester. CONCLUSIONS: No difference was observed in TSH, FT3, or FT4 among the different iodine status groups throughout pregnancy. Tvol increased as the pregnancy progressed, and it was especially higher in the UIC ≥500 µg/L group in the first and third trimesters.

Thyroglobulin can be a functional biomarker of iodine deficiency, thyroid nodules, and goiter in Chinese pregnant women.

BACKGROUND AND OBJECTIVES: Thyroglobulin (Tg) is considered a sensitive indicator of iodine status for children and adults, but its usefulness for pregnant women is unknown. The aim of this study was attempting to explore the relationship between Tg and iodine status and the association between elevated Tg and thyroid diseases. METHODS AND STUDY DESIGN: A total of 2163 pregnant women were recruited in this study. The ratio of urine iodine concentration and urine creatinine concentration (UI/Cr) was measured in spot urine samples. Serum thyroid hormones and thyroglobulin were measured. Thyroid nodules and thyroid volume were diagnosed by ultrasound. RESULTS: The geometric mean of serum Tg was significantly higher in the UI/Cr <100 µg/g group (10.94 [2.47] µg/L) and the UI/Cr >500 µg/g group (11.48 [2.35] µg/L) than in the 150-249 µg/g group (9.64 [2.32] µg/L). The generalized linear model analysis showed that Serum log(10) Tg concentration was much higher in the UI/Cr <100 µg/g group (ß=0.052, p=0.026) than in the 150-249 µg/g group. Multivariate logistic regression models demonstrated that elevated Tg may be a risk factor for both goiter (OR=8.30) and thyroid nodules (OR=2.73). CONCLUSIONS: Pregnant women with UI/Cr <100 µg/g have a higher Tg, and those with elevated Tg concentrations have a higher risk of thyroid nodules and goiter. Tg can be a functional biomarker of iodine deficient, thyroid nodules and goiter.

[Electrolytic drinking water improves the metabolism of uric acid in the SD rats with hyperuricemia].

OBJECTIVE: To investigate the effects of electrolytic drinking water on the hyperuricemia and the potential mechanism. METHODS: The 6-week-old SD rats were induced as the animal model with hyperuricemia by yeast extract(10 g/kg) and adenine(100 g/kg) gavage(twice per day) combined with oxygen oxazine acid potassium(300 mg/kg, the 1~(st), 5~(th) and 10~(th )day) i. p. Then the rats were supplied electrolytic drinking water in different dosages(1 mL, 2 mL and 3 mL) by gavage for 7 days. Weight was measured at regular intervals. The 24-hour urine was sampled by metabolic cage for the measurements of uric acid, creatinine and urea nitrogen levels. The parameters for the uric acid clearance were calculated. The serum was sampled after execution for the determination of serum uric acid, creatinine. The activities of xanthine oxidase and adenine dehydrogenase were detected. The morphological measurements of stomach and kidney were completed. RESULTS: The hyperuricemia model was successfully induced by this method. In the intervention, the pH of urine was significantly elevated along with the electrolytic drinking water intake(P<0. 01). The excretion of uric acid in the rats with hyperuricemia was significantly increased while administrated with electrolytic drinking water. The effects of improving uric acid excretion were enhanced along with the intake of electrolytic drinking water. The levels of serum uric acid(group Model, Model+Treatment 1, Model+Treatment 2 and Model+Treatment 3: 693. 7 µmol/L, 668. 1 µmol/L, 642. 5 µmol/L, 633. 1 µmol/L), urine uric acid(5740. 0 µmol/L, 5894. 1 µmol/L, 5562. 3 µmol/L, 5083. 2 µmol/L) and urea nitrogen(11. 40 mmol/L, 10. 47 mmol/L, 9. 54 mmol/L, 8. 93 mmol/L) were significantly decreased in the model rats with high dose intervention(P<0. 05). Clearance of uric acid was obviously increased(9. 27%, 10. 40%, 10. 44%, 11. 13%, P<0. 05). However, no pathological change was observed among the three groups with intervention. CONCLUSION: The electrolytic drinking water intake is benefit for the excretion of uric acid of hyperuricemia rat. Enhancing alkalization of urine is considered as the important mechanism of the beneficial effects.

[Analysis of medication regularity of traditional Chinese medicine prescriptions for gastropyretic excessiveness diabetes based on data mining].

To analyze the medication regularity of traditional Chinese medicine(TCM) prescriptions for gastropyretic excessiveness diabetes recorded in Chinese Medicine Prescriptions Dictionary. A total of 103 eligible prescriptions were input into the system platform, and the Apriori algorithm was used to analyze their medication regularity. The 103 prescriptions for gastropyretic excessiveness diabetes were selected from the system, and 29 herb medicines were found with frequency of usage more than 8. Totally 33 commonly used herbal pairs(support degree≥10), twenty-three 3-herb core combinations(support degree≥8, confidence values≥0.5), and twenty-one 4-herb core combinations(confidence values≥0.5) were discovered after the medication regularity analysis by Apriori algorithm. The herbal medicine combinations with the highest correlation degree were discovered after the association rule analysis on the 103 prescriptions(support degree≥10, confidence values≥0.5). The four properties, five tastes, channel distributions and frequency of dose of the 103 prescriptions were also obtained after the corresponding analysis. According to the analysis and summary of the above data, the combination of Trichosanthis Radix, Anemarrhenae Rhizoma, Coptidis Rhizoma and Ophiopogonis Radix could reflect the medication regularity of TCM prescriptions for gastropyretic excessiveness diabetes to a certain degree, which is of great significance in guiding value in clinic.

The long non-coding RNA-ROR promotes osteosarcoma progression by targeting miR-206.

The long intergenic non-protein coding RNA regulator of reprogramming (lncRNA-ROR) has been reported to play crucial regulatory roles in the pathogenesis and progression of multiple cancers. However, whether ROR is associated with the initiation and development of osteosarcoma (OS) remains unclear. Here, we found that ROR expression level was significantly up-regulated in OS tissue samples compared to adjacent normal tissues, and the elevated ROR was closely correlated with advanced tumour-node-metastasis (TNM) stage and lymph node metastasis and poor overall survival rate. Functional assays showed that ROR knockdown suppressed the OS cell proliferation, colony formation, migration and invasion in vitro, and retarded tumour growth in vivo. In addition, miR-206 was verified to be a target miRNA of ROR using bioinformatics online program and luciferase report assay. miR-206 inhibition partially rescued the inhibitory effects on OS cells induced by ROR knockdown. In conclusion, these results suggested that ROR function as an oncogene in OS by sponging miR-206 and might be a potential therapeutic target for patients with OS.

Protection against the Neurotoxic Effects of ß-Amyloid Peptide on Cultured Neuronal Cells by Lovastatin Involves Elevated Expression of α7 Nicotinic Acetylcholine Receptors and Activating Phosphorylation of Protein Kinases.

The treatment of neurodegenerative diseases with statins has drawn increasing attention, but the related molecular mechanisms remain elusive. To examine the pleiotropic cholesterol-independent effects of statins in connection with the treatment of Alzheimer disease, we probed the influence of lovastatin on the metabolism of amyloid precursor protein (APP), expression of nicotinic acetylcholine receptors (nAChRs), and activity of mitogen-activated protein kinase (MAPK) in primary cultured neurons and SH-SY5Y cells overexpressing human APP670/671. Lovastatin attenuated the neurotoxic effects of ß-amyloid peptide (Aß) and affected the metabolism of APP, reducing levels of Aß1 to Aß42 and ß-site amyloid precursor protein-cleaving enzyme 1; enhancing those of αAPP, disintegrin metalloproteinase domain-containing protein 10, and ß-site amyloid precursor protein-cleaving enzyme 2; and up-regulating expression of α7 nAChR and stimulating phosphorylation of extracellular signal-regulated kinase (ERK)1/2. Interestingly, methyllycaconitine, an antagonist of α7 nAChR, attenuated this effect on αAPP, but not on phospho-ERK1/2; whereas U0126, an inhibitor of MAPK/ERK kinase/ERK, blocked both the elevated expression of α7 nAChR and enhanced secretion of αAPP. Our findings indicate that lovastatin up-regulates expression of α7 nAChR by a mechanism involving activation of the MAPK/ERK pathway, which may result in diminished production of Aß.

Serum iodine concentration in pregnant women and its association with urinary iodine concentration and thyroid function.

OBJECTIVE: This study aims to evaluate the association of serum iodine concentration (SIC) with urinary iodine concentration (UIC) and thyroid function in pregnant women, as well as to provide the reference range of SIC of pregnant women in iodine-sufficiency area. METHODS: Pregnant women were enrolled in the Department of Obstetrics, Tanggu Maternity Hospital, Tianjin from March 2016 to May 2017. Fasting venous blood and spot urine samples were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), UIC and SIC were measured. RESULTS: One thousand and ninety-nine participants were included in this study. The median UIC was 156 µg/L. The median SIC was 108 µg/L, and the 95% reference interval for SIC was 65.6-164.7 µg/L. SIC was positively correlated with UIC (r = 0.12, P < 0.001), FT3 (r = 0.23, P < 0.001), and FT4 (r = 0.50, P < 0.001) and was inversely correlated with TSH (r = -0.14, P < 0.001). Pregnant women with a SIC < 79.9 µg/L had a higher risk of hypothyroxinemia compared to those with higher SIC (OR = 2.44, 95% CI: 1.31-4.75). Those having SIC > 138.5 µg/L were more likely to have thyrotoxicosis than those with lower SIC values (OR = 13.52, 95% CI: 4.21-43.36). CONCLUSIONS: Serum iodine level is associated with UIC and thyroid function in pregnant women. Low SIC was associated with increased risk for iodine deficiency and hypothyroxinemia, while high SIC was related to excess and thyrotoxicosis.

Serum Iodine Is Correlated with Iodine Intake and Thyroid Function in School-Age Children from a Sufficient-to-Excessive Iodine Intake Area.

BACKGROUND: An alternative feasible and convenient method of assessing iodine intake is needed. OBJECTIVE: The aim of this study was to examine the utility of serum iodine for assessing iodine intake in children. METHODS: One blood sample and 2 repeated 24-h urine samples (1-mo interval) were collected from school-age children in Shandong, China. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), total iodine (StI), and non-protein-bound iodine (SnbI) concentrations and urine iodine (UIC) and creatinine (UCr) concentrations were measured. Iodine intake was estimated based on two 24-h urine iodine excretions (24-h UIE). Associations between serum iodine and other factors were analyzed using the Spearman rank correlation test. Receiver operating characteristic (ROC) curves were used to illustrate diagnostic ability of StI and SnbI. RESULTS: In total, 1686 children aged 7-14 y were enrolled. The median 24-h UIC for the 2 collections was 385 and 399 µg/L, respectively. The median iodine intake was estimated to be 299 µg/d and was significantly higher in boys than in girls (316 µg/d compared with 283 µg/d; P < 0.001). StI and SnbI were both positively correlated with FT4 (ρ = 0.30, P < 0.001; and ρ = 0.21, P < 0.001), Tg (ρ = 0.21, P < 0.001; and ρ = 0.19, P < 0.001), 24-h UIC (ρ = 0.56, P < 0.001; and ρ = 0.47, P < 0.001), 24-h UIE (ρ = 0.46, P < 0.001; and ρ = 0.49, P < 0.001), urine iodine-to-creatinine ratio (ρ = 0.58, P < 0.001; and ρ = 0.62, P < 0.001), and iodine intake (ρ = 0.49, P < 0.001; and ρ = 0.53, P < 0.001). The areas under the ROC curves for StI and SnbI for the diagnosis of excessive iodine intake in children were 0.76 and 0.77, respectively. The optimal StI and SnbI threshold values for defining iodine excess in children were 101 and 56.2 µg/L, respectively. CONCLUSIONS: Serum iodine was positively correlated with iodine intake and the serum FT4 concentration in children. It is a potential biomarker for diagnosing excessive iodine intake in children. This trial was registered at clinicaltrials.gov as NCT02915536.