Maternal gestational diabetes in singleton pregnancies conceived by ART may be modified by periconceptional B vitamins

BackgroundThe risk of maternal gestational diabetes mellitus (GDM) may be influenced by pregnancies conceived through assisted reproductive technology (ART). However, the influence of the dosage of B vitamins (folate, vitamin B6 and vitamin B12) on GDM weren’t considered. Thus, we hypothesized that periconceptional B vitamins could modify maternal GDM in singleton pregnancies conceived by ART.MethodsThis study is a prospective cohort study using data from 3,252 women with singleton pregnancies and received a 75 g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation. We included an interaction term in the multivariable logistic and linear regression models, respectively, to test our hypothesis.ResultsWomen who underwent ART were significantly associated with the incidence of GDM compared with spontaneous pregnancy women. The adjusted odds ratio (aOR) was 1.59, and the 95% confidence interval (CI) was 1.08–2.34. ART pregnancies also elevated OGTT (oral glucose tolerance test) 1-h blood glucose levels and OGTT 2-h blood glucose levels (P < 0.05). A positive association between dietary vitamin B6 (aOR = 1.60, 95% CI: 1.13–2.27), dietary vitamin B12 (aOR = 1.88, 95% CI: 1.34–2.64) and dietary folate (aOR = 1.66, 95% CI: 1.19–2.32) with GDM risk comparing the highest to the lowest quartile (all Ptrend < 0.001). The aORs of GDM for inadequate (< 400 μg/day), adequate (400–800 μg/day), and excessive (> 800 μg/day) supplemental folate intake were 1.00, 0.93, and 1.30, respectively (Ptrend = 0.033). Since only the supplemental folate illustrates a statistically significant interaction with ART (P for interaction < 0.05), the association between ART and GDM and OGTT blood glucose levels stratifying by supplemental folate were further evaluated. These increased risks of GDM (aOR = 1.62, 95% CI: 1.39–3.39) and the regression coefficients (β) of 1-h blood glucose (β = 0.76, 95% CI: 0.39–1.13) and 2-h blood glucose (β = 0.60, 95% CI: 0.29–0.92) in the multiple linear regression model were significant only in the ART group with excessive supplemental folate (> 800 μg/day).ConclusionThe risk of GDM is significantly elevated, particularly among those women who conceived ART with the intake of excessive supplemental folate (> 800 μg/day)

Case report: Treatment of Wilson’s disease by human amniotic fluid administration

BackgroundWilson’s disease (WD) is not an uncommon genetic disease in clinical practice. However, the current WD therapies have limitations. The effectiveness of stem cell therapy in treating WD has yet to be verified, although a few animal studies have shown that stem cell transplantation could partially correct the abnormal metabolic phenotype of WD. In this case report, we present the therapeutic effect of human amniotic fluid containing stem cells in one WD patient.Case presentationA 22-year-old Chinese woman was diagnosed with WD 1 year ago in 2019. The available drugs were not effective in managing the progressive neuropsychiatric symptoms. We treated the patient with pre-cultured human amniotic fluid containing stem cells. Amniotic fluid was collected from pregnant women who underwent induced labor at a gestational age of 19–26 weeks, and then, the fluid was cultured for 2 h to allow stem cell expansion. Cultured amniotic fluid that contained amniotic fluid derived stem cells (AFSC) in the range of approximately 2.8–5.5 × 104/ml was administrated by IV infusion at a rate of 50–70 drops per minute after filtration with a 300-mu nylon mesh. Before the infusion of amniotic fluid, low-molecular-weight heparin and dexamethasone were successively administrated. The patient received a total of 12 applications of amniotic fluid from different pregnant women, and the treatment interval depended on the availability of amniotic fluid. The neuropsychiatric symptoms gradually improved after the stem cell treatment. Dystonia, which included tremor, chorea, dysphagia, dysarthria, and drooling, almost disappeared after 1.5 years of follow-up. The Unified Wilson’s Disease Rating Scale score of the patient decreased from 72 to 10. Brain magnetic resonance imaging (MRI) showed a reduction in the lesion area and alleviation of damage in the central nervous system, along with a partial recovery of the lesion to the normal condition. The serum ceruloplasmin level was elevated from undetectable to 30.8 mg/L, and the 24-h urinary copper excretion decreased from 171 to 37 μg. In addition, amniotic fluid transplantation also alleviates hematopoietic disorders. There were no adverse reactions during or after amniotic fluid administration.ConclusionAmniotic fluid administration, through which stem cells were infused, significantly improves the clinical outcomes in the WD patient, and the finding may provide a novel approach for managing WD effectively

Site-Mutation of Hydrophobic Core Residues Synchronically Poise Super Interleukin 2 for Signaling: Identifying Distant Structural Effects through Affordable Computations

A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with which to get insight about how to utilize allosteric effect to achieve desirable protein functions. By examining the dynamic network and the allosteric pathways related to those mutated residues using various computational approaches, we found that nanosecond time scale all-atom molecular dynamics simulations can identify the dynamic network as efficient as an ensemble algorithm. The differentiated pathways for the six core residues form a dynamic network that outlines the area of structure alteration. The results offer potentials of using affordable computing power to predict allosteric structure of mutants in knowledge-based mutagenesis.This work was supported by the Natural Science Foundation of China (No. 20475019 & 21473065 to Yanfang Cui), and Wuhan Science and Technology R&D Program (No. 201060623259 & No. 200860423220 to Yanfang Cui)

An empowerment-based, healthy dietary behavioral intervention to ameliorate functional constipation

ObjectiveTo explore the boost effect on ameliorating functional constipation in elderly patients through empowerment-based, healthy dietary behavioral intervention.DesignIn this randomized parallel group study, elderly patients with functional constipation were recruited and assigned to the experimental and control groups at a ratio of 1:1. The control group received routine intervention. The experimental group received 3-month empowerment-based intervention. The results were evaluated based on the Healthy Lifestyle and Personal Control Questionnaire (HLPCQ) and Cleveland Clinic Constipation Score (CCS). GraphPad Prism (Version 9) software was used for the statistical analysis.SettingAs the world's population ages, functional constipation in the elderly has attracted widespread attention. The practical behavioral intervention to ameliorate constipation are worth exploring.ParticipantsSixty elderly patients with functional constipation.ResultsThe study results showed no significant difference in the baseline data between the two groups (P > 0.05). After the intervention, the scores of HLPCQ (77.90 ± 14.57 vs. 61.11 ± 13.64) and CCS (7.48 ± 3.73 vs. 9.70 ± 3.07) in the experimental group were significantly higher than those in the control group (P < 0.05).ConclusionThe results showed that empowerment-based intervention can effectively strengthen the healthy dietary behavior of elderly patients. Through patient empowerment, the subjective initiative and willingness to communicate were boosted in the experimental group. Their symptoms of functional constipation improved considerably better than in the control group

Irisin Is Controlled by Farnesoid X Receptor and Regulates Cholesterol Homeostasis

ObjectiveThe aim of this study was to investigate whether the nuclear receptor farnesoid X receptor (FXR) could regulate FNDC5/Irisin expression and the role of Irisin in hyperlipidemia and atherosclerosis in ApoE-/- mice.Methods and ResultsWe treated primary human hepatocytes, HepG2 cells, and Rhesus macaques with FXR agonist (CDCA, GW4064, and ivermectin). FNDC5 expression was highly induced by CDCA and GW4064 in hepatocytes, HepG2 cells, and the circulating level of Irisin increased in Rhesus macaques. Luciferase reporter and CHIP assays were used to determine whether FXR could regulate FNDC5 promoter activity. Irisin-ApoE-/- and ApoE-/- mice were used to study the metabolic function of Irisin in dyslipidemia and atherosclerosis. Irisin-ApoE-/- mice showed improved hyperlipidemia and alleviated atherosclerosis as compared with ApoE-/- mice. Irisin upregulated the expression of Abcg5/Abcg8 in liver and intestine, which increased the transport of biliary cholesterol and fecal cholesterol output.ConclusionActivation of FXR induces FNDC5 mRNA expression in human and increased the circulating level of Irisin in Rhesus macaques. FNDC5/Irisin is a direct transcriptional target of FXR. Irisin may be a novel therapeutic strategy for dyslipidemia and atherosclerosis

Synergistic Effects of VOx−Pt Probed by the Oxidation of Propane on VOx/Pt(111)

电子邮件地址:[email protected]; [email protected]/Pt(111), which was grown layer-by-layer and exhibited a well-defined structure, was used as a model catalytic surface to study the intrinsic catalytic activity of Pt, as well as the effect of VOx additive, for the oxidation of propane. A special sample system was designed to ensure a reliable analysis of the trace amount of model catalytic reaction products. The results show that the catalytic activities for the oxidation of C3H8 on the Pt(ill) surface as adding VOx are suppressed apparently at temperatures below 400 K, but enhanced significantly at temperatures above 400 K. Maximum reaction rates are achieved at a VOx coverage of about 0.3 ML at the test temperatures of 423 and 473 K. The infrared reflection-absorption spectroscopy (IRAS) results show that the redox property of the VOx-Pt is much better than that of the bulklike VOx. This is confirmed by CO poisoning tests, in that the oxidation of VOx/Pt(111) is significantly suppressed by the coadsorbed CO. The kinetic data demonstrate that there are at least two catalytically active sites, metallic Pt and VOx-Pt interface, for the activation and oxidation of C3H8. The promotion effects of VOx on Pt for the oxidation of C3H8 can be attributed to the synergy between VOx and Pt.National Basic Research Program of China (973 program) 2010CB732303 2013CB933102 Major Project of the Chinese Ministry of Education 309019 National Natural Science Foundation of China 20923004 21033006 21073149 21273178 Program for Changjiang Scholars and Innovative Research Team in University IRT1036 Ph.D. Programs Foundation of the Chinese Ministry of Education 2011012111001

Catalytic Promiscuity of O-GlcNAc Transferase Enables Unexpected Metabolic Engineering of Cytoplasmic Proteins with 2-Azido-2-deoxy-glucose

O-GlcNAc transferase (OGT) catalyzes the installation of N-acetylglucosamine (GlcNAc) O-linked to nucleocytoplasmic proteins (O-GlcNAc) within multicellular eukaryotes. OGT shows surprising tolerance for structural changes in the sugar component of its nucleotide sugar donor substrate, uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). Here, we find that OGT uses UDP-glucose to install O-linked glucose (O-Glc) onto proteins only 25-fold less efficiently than O-GlcNAc. Spurred by this observation, we show that OGT transfers 2-azido-2-deoxy-d-glucose (GlcAz) in vitro from UDP-GlcAz to proteins. Further, feeding cells with per-O-acetyl GlcAz (AcGlcAz), in combination with inhibition or inducible knockout of OGT, shows OGT-dependent modification of nuclear and cytoplasmic proteins with O-GlcAz as detected using microscopy, immunoblot, and proteomics. We find that O-GlcAz is reversible within cells, and an unidentified cellular enzyme exists to cleave O-Glc that can also process O-GlcAz. We anticipate that AcGlcAz will prove to be a useful tool to study the O-GlcNAc modification. We also speculate that, given the high concentration of UDP-Glc within certain mammalian tissues, O-Glc may exist within mammals and serve as a physiologically relevant modification