Objective
The aim of this study was to clarify the relationships among large for gestational age (LGA) and cardiometabolic risk factors.
Methods
PubMed, Web of Science, and the Cochrane Library ...databases were searched to identify studies on LGA and outcomes of interest, including BMI, blood pressure, glucose metabolism, and lipid profiles. Data were independently extracted by two reviewers. A meta‐analysis was performed using a random‐effects model. The Newcastle‐Ottawa Scale and funnel graph were used to assess the quality and publication bias, respectively.
Results
Overall, 42 studies involving 841,325 individuals were included. Compared with individuals born appropriate for gestational age, individuals born LGA had higher odds of overweight and obesity (odds ratios OR = 1.44, 95% CI: 1.31‐1.59), type 1 diabetes (OR = 1.28, 95% CI: 1.15‐1.43), hypertension (OR = 1.23, 95% CI: 1.01‐1.51), and metabolic syndrome (OR = 1.43, 95%; CI: 1.05‐1.96). No significant difference was found in hypertriglyceridemia and hypercholesterolemia. Stratified analyses showed that, compared with individuals born appropriate for gestational age, individuals born LGA had higher odds for overweight and obesity from toddler age to puberty age (toddler age: OR = 2.12, 95% CI: 1.22‐3.70; preschool: OR = 1.81, 95% CI: 1.55‐2.12; school age: OR = 1.53, 95% CI: 1.09‐2.14; puberty: OR = 1.40, 95% CI: 1.11‐1.77).
Conclusions
LGA is associated with increased odds of obesity and metabolic syndrome later in life. Future studies should focus on elucidating the potential mechanisms and identifying risk factors.
Epidemiological studies have suggested a link between vitamin D deficiency and increased risk for nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms have remained unclear. ...Here, using both clinical samples and experimental rodent models along with several biochemical approaches, we explored the specific effects and mechanisms of vitamin D deficiency in NAFLD pathology. Serum vitamin D levels were significantly lower in individuals with NAFLD and in high-fat diet (HFD)-fed mice than in healthy controls and chow-fed mice, respectively. Vitamin D supplementation ameliorated HFD-induced hepatic steatosis and insulin resistance in mice. Hepatic expression of vitamin D receptor (VDR) was up-regulated in three models of NAFLD, including HFD-fed mice, methionine/choline-deficient diet (MCD)-fed mice, and genetically obese (ob/ob) mice. Liver-specific VDR deletion significantly exacerbated HFD- or MCD-induced hepatic steatosis and insulin resistance and also diminished the protective effect of vitamin D supplementation on NAFLD. Mechanistic experiments revealed that VDR interacted with hepatocyte nuclear factor 4 α (HNF4α) and that overexpression of HNF4α improved HFD-induced NAFLD and metabolic abnormalities in liver-specific VDR-knockout mice. These results suggest that vitamin D ameliorates NAFLD and metabolic abnormalities by activating hepatic VDR, leading to its interaction with HNF4α. Our findings highlight a potential value of using vitamin D for preventing and managing NAFLD by targeting VDR.
Do embryo euploidy rates differ in the four groups of women with low prognosis as stratified by the POSEIDON criteria?
This was a retrospective cohort study of low-prognosis patients who met the ...POSEIDON criteria and underwent preimplantation genetic testing for aneuploidies (PGT-A) from January 2013 to June 2020 at the Center for Reproductive Medicine, Shandong University, China. A total of 3016 blastocysts from 1269 PGT-A cycles were included in the study. The primary outcome was the euploidy rate of the blastocysts. For each group, regression analyses were performed to quantitatively describe the relationship between maternal age and embryo euploidy rate.
The euploidy rate of embryos in women with poor ovarian response (POR) was 39.1% in total. There were 727, 1052, 275 and 962 blastocysts in groups 1, 2, 3 and 4, respectively, with corresponding embryo euploidy rates of 57.2%, 34.9%, 52.4% and 26.2% (P < 0.001). Within each group, the euploidy rate decreased with age, especially in women aged 35 years or older (i.e. groups 2 and 4).
Euploidy rates were more favourable in groups 1 and 3, of a young age, re-emphasizing that oocyte quality is the primary factor determining embryo euploidy rate. The study's findings demonstrated the reasonability of categorizing women with POR by the POSEIDON criteria depending on female age and ovarian reserve biomarkers. These results also provide information for women with POR in different subgroups so they can receive proper counselling on the possible prognosis.
A robust and efficient Ni@NC-T quasi-molecular catalyst with highly coordinated Ni-N5 site was prepared by post-metallization of a pre-synthesized N-doped carbon (NC-T) support. The optimum ...Ni@NC-1100 catalyst exhibited an extremely high FE toward CO formation (>99%) at −0.72 V vs. reversible hydrogen electrode (RHE). Of interest is the FECO maintained above 96% over a wide potential window from −0.52 V to −1.12 V, outperforming almost all prior pyrolyzed Ni-N-C-based catalysts.
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•A robust and efficient Ni@NC-T quasi-molecular catalyst was prepared.•The Ni@NC-1100 catalyst contains abundant highly coordinated Ni-N5 sites.•It exhibits an extremely high FECO (>99 %) at −0.72 V vs. RHE.•FECO is above 96 % over a wide potential window from −0.52 V to −1.12 V.•DFT calculation proves that the NiN4 with axial pyrrolic-N is the active site.
Electrochemical production of high value-added CO from CO2 on transition metal-nitrogen-carbon (M−N−C) catalysts is a promising approach to achieve carbon neutral economy, yet the quest for robust catalysts is driven by achieving > 96 % CO faradaic efficiency (FE) under low overpotential and wide potential range. Herein, we report a novel synthetic approach involving post-metallization of the pre-synthesized N-doped carbon (NC-T) support for the fabrication of robust and efficient Ni@NC-T quasi-molecular catalysts toward CO2 electroreduction reaction (CO2RR). The optimum Ni@NC-1100 catalyst exhibited an extremely high FECO > 99 % at −0.72 V vs. reversible hydrogen electrode (RHE). Of interest is the FECO maintained above 96 % over a wide potential window from −0.52 V to −1.12 V. Density functional theory (DFT) calculation validated that the presence of axial pyrrolic-N significantly enhances the Ni-N5 active site for CO2 activation, resulting in the lowest activation energy for the *COOH intermediate generation compared to other axial ligands.
We previously showed that the vitamin D receptor (VDR) plays a crucial role in acute inflammatory bowel disease and that intestinal fibrosis is a common complication of Crohn’s disease (CD). ...Epithelial–mesenchymal transition (EMT) is an important hallmark of fibrogenesis through which epithelial cells lose their epithelial phenotype and transform into mesenchymal cells. It is known that the VDR plays an essential role in epithelial integrity and mitochondrial function, but its role in intestinal fibrosis remains unknown. Here, we investigated whether the VDR is involved in epithelial mitochondrial dysfunction that results in EMT in intestinal fibrosis. Using human CD samples, intestine-specific VDR-KO mice, and fibroblast cellular models, we showed that the expression of the VDR was significantly lower in intestinal stenotic areas than in nonstenotic areas in patients with chronic CD. Genetic deletion of the VDR in the intestinal epithelium exacerbated intestinal fibrosis in mice administered with dextran sulfate sodium or 2,4,6-trinitrobenzene sulfonic acid, two experimental colitis inducers. In addition, we found that vitamin D dietary intervention regulated intestinal fibrosis by modulating the intestinal expression of the VDR. Mechanistically, knocking down the VDR in both CCD-18Co cells and human primary colonic fibroblasts promoted fibroblast activation, whereas VDR overexpression or VDR agonist administration inhibited fibroblast activation. Further analysis illustrated that the VDR inhibited EMT in the HT29 cell model and that mitochondrial dysfunction mediated epithelial integrity and barrier function in VDR-deficient epithelial cells. Together, our data for the first time demonstrate that VDR activation alleviates intestinal fibrosis by inhibiting fibroblast activation and epithelial mitochondria-mediated EMT.
OBJECTIVESCholestatic liver diseases are characterized by hepatocellular damage, cholangiocyte proliferation, and progressive fibrosis. Bile duct ligation (BDL) is widely used to resemble liver ...injuries induced by cholestasis. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α) was reported to play a critical role in multiple biological responses. Nevertheless, whether PGC1α is involved in bile acid metabolism and biliary disorders remains unclear. This study aimed to investigate the effect of PGC1α on hepatic responses after cholestatic injury.MATERIALS AND METHODSWild-type mice were subjected to BDL or sham surgery for 14 days and human liver specimens from patients with primary biliary cholangitis (PBC) were collected to detect the expression of PGC1α. Hepatic-specific PGC1α knockout mice (HKO) were constructed and subjected to BDL, in which the effects of PGC1α on cholestatic liver injury were demonstrated by biochemical and histopathological assessments, immunoblotting, and metabolomics.RESULTSThe expression of PGC1α was upregulated in the liver of PBC patients and murine models. Both in vivo and in vitro experiments supported the protective effects of PGC1α on cholestasis-induced hepatocyte injury. Infiltrated inflammatory cells after BDL were decreased in HKO mice. Inhibited Wnt/β-Catenin pathway and enhanced Notch signaling promoted transdifferentiation of hepatic progenitor cells (HPC)/ hepatocytes into cholangiocytes, leading to the greater ductular reaction observed in the HKO mice. But bile acids metabolism and mitochondrial function were not affected due to hepatic PGC1α deficiency in cholestasis.CONCLUSIONSHepatic-specific deletion of PGC1α regulated liver regeneration by promoting ductular reactions, thereby exerting protective effects against BDL-induced liver injury, which could be a new potential therapeutic target.
Background
Helicobacter pylori, a gram‐negative bacterium persisting on the gastric mucosa, is involved in the pathogenesis of a variety of gastric diseases. Leukocyte cell‐derived chemotaxin 2 ...(LECT2) treatment increased the phagocytic capacity of lymphocytes and improved immune function in bacterial infection. Whether the immune cells infected with H. pylori are affected by LECT2 is unclear.
Methods
Bone marrow‐derived dendritic cells (BMDCs) from wild‐type C57BL/6 mice, CD209a knockout mice, or LECT2 knockout mice were exposed to H. pylori at a multiplicity of infection of 10 for 24 h. The maturity of DCs and the cytokines secreted by DCs were analyzed by flow cytometry, western blot, and real‐time PCR. The signaling pathway underlying CD209a activation after LECT2 treatment were also detected.
Results
LECT2 treatment promoted H. pylori‐induced BMDC maturation and produced a high level of anti‐inflammatory cytokine (IL‐10) but a low level of pro‐inflammatory cytokine (IL‐23p40). Moreover, LECT2‐pretreated DCs shifted the development of pro‐inflammatory Th1/Th17 cells to Treg cells. CD209a mediated LECT2‐induced maturation and secretion of DC in H. pylori‐primed BMDCs. LECT2 was further confirmed to induce the secretion of certain cytokines via CD209a‐JNK/P38 MAPK pathway.
Conclusion
This study reveals that LECT2 modulated the functions of H. pylori‐primed DCs in a CD209a‐dependent manner, which might hinder the clearance of H. pylori and contribute to its colonization.
Inflammatory responses are pivotal incidences in hepatic metabolic derangements. However, the underlying mechanism remains elusive. The present study aimed to evaluate the role of peroxisome ...proliferator‐activated receptor‐gamma, coactivator 1 alpha (PGC1α) in IL10‐mediated anti‐inflammatory response, and its role in hepatic steatosis and insulin resistance. Hepatocyte‐specific PGC1α knock‐in (LivPGC1α) mice and the control mice were fed high‐fat diet (HFD) for 8 weeks. IL‐10 neutralizing antibody was injected into the liver of PGC1α mice. A variety of biological and histological approaches were applied to assess hepatic function. We demonstrated that hepatic PGC1α expression was significantly reduced in mice fed HFD. LivPGC1α livers exhibited enhanced gene expressions involving mitochondrial function, and favored an accelerated lipid metabolism upon HFD. Meanwhile, LivPGC1α mice revealed improved hepatic steatosis and insulin resistance. Mechanistically, PGC1α bound and activated the promotor region of IL‐10, thereby attenuating inflammatory response in the liver. Administration of IL10 neutralizing antibody to LivPGC1α mice abolished PGC1α‐mediated anti‐inflammatory effects in mice. Further, IL‐10 neutralizing antibody intervention aggravated hepatic steatosis and insulin resistance in LivPGC1α mice. Taken together, our data indicated that hepatic‐specific overexpression of PGC1α exerts a beneficial role in the regulation of hepatic steatosis and insulin resistance via enhancing IL10‐mediated anti‐inflammatory response. Pharmacological activation of PGC1α‐IL10 axis may be promising for the treatment of fatty liver diseases.
Embryo transfer, one of the most essential procedures in assisted reproductive technology, plays a vital role in the success of
fertilization and intracytoplasmic sperm injection. During the last ...decades, the strategies for embryo transfer have changed dramatically. In this review, we evaluate the efficacy and safety of several current embryo transfer strategies including fresh versus frozen embryo transfer, cleavage- versus blastocyst-stage embryo transfer, and single- versus double-embryo transfer. Available evidence indicates that the freeze-only strategy improves the live birth rate after the first embryo transfer in high responders while making no difference in normal responders. The risk of ovarian hyperstimulation syndrome is significantly reduced in the freeze-only strategy. Fresh blastocyst-stage embryo transfer increased live birth rate compared to cleavage-stage embryo transfer. The best embryo transfer strategy is one which tailors to individual circumstances and preferences.
Granulocyte colony stimulating factor (GCSF) is a cytokine with immunomodulation effects. However, little is known about its role in metabolic diseases. In the current study, we aimed to explore the ...role of GCSF in nonalcoholic fatty liver disease (NAFLD). Male GCSF
mice were used to investigate the function of GCSF in vivo after high-fat diet (HFD). Primary hepatocytes were used for evaluating the function of GCSF in vitro. Liver immune cells were isolated and analyzed by flow cytometry. Our results showed that GCSF administration significantly increased serum triglyceride (TG) levels in patients. Circulating GCSF was markedly elevated in HFD-fed mice. GCSF
mice exhibited alleviated HFD-induced obesity, insulin resistance, and hepatic steatosis. Extra administration of GCSF significantly aggravated palmitic acid (PA)-induced lipid accumulation in primary hepatocytes. Mechanically, GCSF could bind to granulocyte colony stimulating factor receptor (GCSFR) and regulate suppressors of cytokine signaling 3, Janus kinase, signal transducer and activator of transcription 3 (SOCS3-JAK-STAT3) pathway. GCSF also enhanced hepatic neutrophils and macrophages infiltration, thereby modulating NAFLD. These findings suggest that GCSF plays an important regulatory role in NAFLD and may be a potential therapeutic target for NAFLD.
We found GCSF was involved in lipid metabolism and NAFLD development. GCSF administration increased serum triglyceride levels in patients. GCSF deficiency alleviated HFD-induced insulin resistance and hepatic steatosis in mice. GCSF could directly act on hepatocytes through GCSFR-SOCS3-JAK-STAT3 pathway, and regulate the infiltration of immune cells into the liver to indirectly modulate NAFLD. Our finding indicates that GCSF may provide new strategies for the treatment of NAFLD.
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