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Obesity is a complex condition that is characterized by excessive fat accumulation, which can lead to the development of metabolic disorders, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease and cardiovascular diseases. Evidence is accumulating that circulating microRNAs (miRNAs) act as a new class of endocrine factor. These miRNAs are released by many types of tissue, including adipose tissues. miRNAs might serve as endocrine and paracrine messengers that facilitate communication between donor cells and tissues with receptor cells or target tissues, thereby potentially having important roles in metabolic organ crosstalk. Moreover, many miRNAs are closely associated with the differentiation of adipocytes and are dysregulated in obesity. As such, circulating miRNAs are attractive potential biomarkers and hold promise for the development of miRNA-based therapeutics (such as miRNA mimetics, anti-miRNA oligonucleotides and exosomes loaded with miRNA) for obesity and related disorders. Here we review the latest research progress on the roles of circulating miRNAs in metabolic organ crosstalk. In addition, we discuss the clinical potential of circulating miRNAs as feasible biomarkers for the assessment of future risk of metabolic disorders and as therapeutic targets in obesity and related diseases. [ABSTRACT FROM AUTHOR]

Image denoising is a hot topic in many research fields, such as image processing and computer vision. With the development of deep learning, deep neural networks are widely used for image denoising and have achieved good effectiveness. Inspired by the characteristics of feed-forward denoising convolutional neural network (DnCNN) and biological neuron response, we propose a Symmetry-Rectifier Linear Unit (SyReLU) and further offer a corresponding SyReLU activation function, which has a better consistency with biological neuron characteristics in comparison with other activation functions, e.g. Rectifier Linear Unit (ReLU) and Leaky Rectifier Linear Unit(LReLU). Also, in order to denoise image, we use SyReLU activation function for residual learning of CNN (e.g. DnCNN). Specially, the experimental results indicate DnCNN with SyReLU can achieve better effectiveness than DnCNN with other activation functions (e.g.ReLU and LReLU) for image denosing on Set12 and BSD68 datasets. Briefly, the proposed method plays an important role in the development of activation function and is very useful in deep neural networks for image denosing. [ABSTRACT FROM AUTHOR]

Brown adipocytes and white adipocytes play important roles in systemic metabolism and energy homeostasis. Recent studies have demonstrated that white adipocytes and brown adipocytes secrete numerous adipokines and thus act as endocrine cells. However, differences in the metabolites secreted from white adipocytes and brown adipocytes have never been reported. In this study, we assessed the metabolites secreted from white adipocytes and brown adipocytes. In total, the levels of 47 metabolites in brown adipocytes were significantly different from those in white adipocytes, with 31 high and 16 low in brown adipocytes as compared with those in white adipocytes. We classified these secreted metabolites as amino acids and peptides, fatty acids, and conjugates, glycerophosphocholines, furanones, and trichloroacetic acids. In addition, we identified the glycerophospholipid metabolism activated in white adipocytes, and these differentially expressed metabolites were associated with the mitogen-activated protein kinase pathway and Janus kinase-signal transducer and activator of transcription signaling pathway according to the Ingenuity Pathway Analysis (IPA) software analysis. This study revealed novel metabolites secreted from brown adipocytes and white adipocytes, and these metabolites from adipocytes may perform specific biological functions based on the type of adipocyte that secretes them, and this forms the material basis of the interaction between adipocytes and other cells. • Differences in the metabolites secreted from white adipocytes and brown adipocytes. • 47 metabolites in brown adipocytes different from those in white adipocytes. • We revealed the material basis of the interaction between adipocytes and other cells. [ABSTRACT FROM AUTHOR]

Human obesity is related with intrinsic impairments of adipocyte lipolysis and ectopic lipid accumulation. Small regulatory RNAs, such as tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), are enriched in exosomes and play a crucial role in lipid metabolism. To determine certain tRFs for lipolysis, brown adipocytes were treated with forskolin. Using tRFs sequencing, 207 different expressed exosomal tRFs were determined. In forskolin samples, 145 downregulated and 62 upregulated tRFs were identified. Further, qRT-PCR validated that three notably upregulated tRFs (tRF-Gly-GCC-007, tRF-Gly-GCC-008, and tRF-Gly-GCC-009) were in accordance with the sequencing result. Target genes of tRFs were involved in positive regulation of protein phosphorylation and cell adhesion process by significantly downregulating UCHL1 expression, which might participate in lipolysis. This study might provide therapeutic targets and potential diagnostic biomarkers for obesity treatment. • Forskolin increases lipolysis in brown adipocyte. • Exosomal tRFs and tiRNAs is crucial for lipid metabolism under forskolin treatment. • tRF-Gly-GCC participate in lipolysis by downregulating UCHL1 expression. • tRF-Gly-GCC may provide potential diagnostic biomarkers for obesity treatment. [ABSTRACT FROM AUTHOR]

The marker genes associated with white adipocytes and brown adipocytes have been previously identified; however, these markers have not been updated in several years, and the differentiation process of preadipocytes remains relatively fixed. Consequently, there has been a lack of exploration into alternative differentiation schemes. In this particular study, we present a transcriptional signature specific to brown adipocytes and white adipocytes. Notably, our findings reveal that ZNF497, ZIC1, ZFY, UTY, USP9Y, TXLNGY, TTTY14, TNNT3, TNNT2, TNNT1, TNNI1, TNNC1, TDRD15, SOX11, SLN, SFRP2, PRKY, PAX3KLHL40, PAX3, INKA2-AS1, SOX11, and TDRD15 exhibit high expression levels in brown adipocytes. XIST, HOXA10, PCAT19, HOXA7, PLSCR3, and AVPR1A exhibited high expression levels in white adipocytes, suggesting their potential as novel marker genes for the transition from white to brown adipocytes. Furthermore, our analysis revealed the coordinated activation of several pathways, including the PPAR signaling pathway, focal adhesion, retrograde endocannabinoid signaling, oxidative phosphorylation, PI3K-Akt signaling pathway, and thermogenesis pathways, in brown adipocytes. Moreover, in contrast to prevailing culture techniques, we conducted a comparative analysis of the differentiation protocols for white preadipocytes and brown preadipocytes, revealing that the differentiation outcome remained unaffected by the diverse culture schemes employed. However, the expression levels of certain marker genes in both adipocyte types were found to be altered. This investigation not only identified potential novel marker genes for adipocytes but also examined the impact of different differentiation methods on preadipocyte maturation. Consequently, these findings offer significant insights for further research on the differentiation processes of diverse adipocyte subtypes. [ABSTRACT FROM AUTHOR]

In this study, methionine sulfoxide (MetO) was identified as an active metabolite that suppresses adipogenesis after screening obese individuals versus the normal population. MetO suppressed the gene and protein expression of CCAAT/enhancer binding protein (C/EBP) α, adipocyte fatty acid binding protein 4 (FABP4), and the nuclear receptor peroxisome proliferator‐activated receptor γ (PPARγ) during human preadipocyte (HPA) differentiation. Adipogenesis decreased following MetO treatment; however, the preadipocyte number, proliferation, and apoptosis were unaffected. The activity of phosphorylated extracellular signal‐related kinase (P‐ERK) of the mitogen‐activated protein kinase (MAPK) pathway was significantly inhibited in HPA after MetO treatment. Furthermore, treatment of preadipocytes with the selective P‐ERK1/2 agonist Ro 67‐7476 abolished the effect of MetO against adipogenesis suggesting that MetO function is dependent on the MAPK pathway. The mechanistic insights of adipogenesis suppression by MetO presented in this study shows its potential as an antiobesity drug. [ABSTRACT FROM AUTHOR]

Background: Preterm birth (PTB) is the primary cause of infant morbidity and mortality. Moreover, previous studies have established that PTB is related to premature cervical ripening. However, the underlying mechanism remains to be elucidated. This study sought to identify differentially expressed metabolites and investigate their potential biological functions in PTB. Methods: Pregnant C57BL/6 J mice were treated with either LPS or normal saline and cervical alterations before labor were detected by staining. Metabolic profiles in the plasma of PTB and control mice were examined through non-targeted metabonomics analyses, quantitative polymerase chain reaction and immunofluorescence staining were performed on human cervical smooth cells. Results: The study demonstrated that the mRNA and protein levels of α-SMA, SM-22, and calponin in cervical smooth muscle cells of PTB mice were lower while OR was higher at both mRNA and protein levels compared to the CTL group. A total of 181 differentially expressed metabolites were analyzed, among them, 96 were upregulated, while 85 were downregulated in the PTB group. Differentially expressed metabolites may play a role in STAT3, RhoA, mTOR, TGF-β, and NK-κB signaling pathways. Furthermore, when treated with taurine, the levels of α-SMA and SM-22 in human cervical smooth muscle cells were elevated, whereas that of connexin-43 was decreased. Conclusion: Our study highlighted the changes of metabolites in the peripheral blood changed prior to PTB and revealed that these differentially expressed metabolites might participate in the development of premature cervical ripening. Taurine was identified as an important metabolite may modulate human cervical smooth muscle cells. Our study provided new insights into the mechanism underlying premature cervical ripening in PTB. [ABSTRACT FROM AUTHOR]

• Obesity-induced chronic inflammation and metabolic abnormalities are highly relevant to the functional dysregulation of macrophages, especially under obese conditions. • We employed metabolomic approaches to examine the metabolic responses of macrophages to high glucose, high fat and their coexistence, aiming to delineate the molecular mechanisms of nutritional factors on macrophage activation and obesity-related diseases from a metabolic perspective. • Our findings revealed that different nutritional conditions could reprogram key metabolism in macrophages. • We identified a metabolite derived from macrophages, Long-Chain Phosphatidylcholine (LPC), which exerts beneficial effects on obese mice. • This finding reveals a potential dialogue mechanism between macrophages and adipocytes. Obesity-induced chronic inflammation and metabolic abnormalities are highly relevant to the functional dysregulation of macrophages, especially under obese conditions. Hyperglycemia and hyperlipidemia, central to obesity, directly alter macrophage activity. However, the impacts of different nutritional cues on the intricate metabolic networks in macrophages remain unclear. In this study, we employed metabolomic approaches to examine the metabolic responses of macrophages to high glucose, high fat and their coexistence, aiming to delineate the molecular mechanisms of nutritional factors on macrophage activation and obesity-related diseases from a metabolic perspective. Our findings revealed that different nutritional conditions could reprogram key metabolism in macrophages. Additionally, we identified a metabolite derived from macrophages, Long-Chain Phosphatidylcholine (LPC), which exerts beneficial effects on obese mice. It ameliorates the obesity phenotype and improves glucose metabolism profiles. This discovery suggests that LPC has a significant therapeutic potential in the context of obesity-induced metabolic dysfunctions. Our study unveils the metabolic phenotype of macrophages in high-fat and high-sugar environments and uncovers a macrophage-derived metabolite that significantly ameliorates the obesity phenotype. This finding reveals a potential dialogue mechanism between macrophages and adipocytes, shedding light on the complex interplay of immune and metabolic systems in obesity. This discovery not only enhances our understanding of obesity's underlying mechanisms but also opens up new avenues for therapeutic interventions targeting macrophage-adipocyte interactions. [ABSTRACT FROM AUTHOR]

Background: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people’s quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity.However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear.We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography–mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA.We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1.Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.Aims: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people’s quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity.However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear.We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography–mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA.We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1.Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.Methods: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people’s quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity.However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear.We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography–mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA.We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1.Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.Results: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people’s quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity.However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear.We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography–mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA.We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1.Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.Conclusions: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people’s quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity.However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear.We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography–mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA.We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1.Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.Graphic Abstract: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people’s quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity.However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear.We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography–mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA.We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1.Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity. [ABSTRACT FROM AUTHOR]

Abstract: Pro-inflammatory cytokine production after nociceptive stimuli is pivotal for hyperalgesia. As macrophage migration inhibitory factor (MIF), a pleiotropic cytokine produced mainly by nonneuronal tissue, has been involved in the regulation of neuronal functions, herein we examined the role for MIF in formalin-induced inflammatory pain model. MIF critically contributed to nociceptive behaviors following formalin injection. Specifically, spinal administration of a MIF inhibitor (ISO-1) prevented and reversed flinching responses in rats. Further examination showed that levels of both MIF and the MIF receptor CD74 were substantially increased within the ipsilateral spinal cord dorsal horn after formalin administration. Mechanistic studies revealed that MIF upregulated the expression of the spinal NMDA receptor subunit NR2B via the MAPK signaling pathway. Moreover, microglial cells were found to be the major source of spinal MIF after formalin administration by fluorescence colocalization. These data highlight spinal MIF plays a critical role in the pathogenesis of formalin-induced inflammatory pain and suggest MIF may be a potential target for therapy of such pathological condition. [Copyright &y& Elsevier]

Summary: Background: Issues associated with the analgesic failure are major contributors to diminished postoperative health quality. The aim of this survey was to investigate the risk factors associated with anaesthesiologists for inadequate postoperative pain management, i.e. ≥3cm in a 10cm gauge of Visual Analog Scale. Methods: A total of 1162 confidential questionnaires were sent by mail to anaesthesiologists in clinical hospitals. Information was queried on the incidence of inadequate postoperative pain management with different length of experience in anaesthesia, reasons for such incidence and possible rescue treatments after the occurrence of the incidence, and knowledge in terms of analgesia protocols. Education background and working settings were requested as the contributing factors. Results: In 813 returned questionnaires, 798 were completed and the data were valid for analysis (68.7% valid response rate). Approximately 43% reported encountered at least one or more incidents of inadequate postoperative analgesia. All positive answers indicated inadequate postoperative analgesia was related to types of surgery. A multiple logistic regression (r 2 =0.74, P <0.0001) analysis revealed that age, length of anaesthesia experience, education background and work environment are four risk factors in contributing to the incidence. Patient-controlled analgesia is the first choice for postoperative pain therapy, and opioids are preferred as the rescue drugs for inadequate postoperative analgesia. Conclusions: Inadequate postoperative analgesia occurs widely. Age, length of anaesthesia experience, education background and the working environment of anaesthesiologists are risk factors for inadequate postoperative pain control. [Copyright &y& Elsevier]

Summary: Background: Pain after uterine curettage has not been clearly evaluated. This study was designed to investigate the hypothesis that flurbiprofen axetil used prior to curettage on abortion could decrease 50% pain from uterine contraction. Methods: Ninety seven ASA physical status I–II patients, undergoing elective uterine apoxesis, were allocated to this randomized double-blind controlled study and assigned into one of two groups (n =45). In the flurbiprofen group, patients received an i.v. injection of flurbiprofen 50mg in 5ml 10min prior to propofol anesthesia. The control group received the same volume of saline injection. Morphine 0.04mg/kg was used as the rescue drug for uncontrolled pain. Visual analog scale for analgesia at rest, satisfaction with analgesia, morphine consumption and side effects were recorded. Results: A total of 87 patients completed the study. The intention-to-treat number of patients was 45 in each group. Flurbiprofen group evidenced effective analgesia (vs. saline P =0.019), with better satisfaction (P =0.015), lower incidence of nausea, dizziness and drowsiness, pruritus, dry mouth and uterine bleeding than the saline control. The flurbiprofen group consumed less morphine in 1h 0.6mg (interquartile 0.1–1.2), vs. saline group 3.7mg (interquartile 1.5–4.6) (P =0.049). The number of patients needed to treat was 2 in the flurbiprofen group. Conclusion: Preoperative flurbiprofen axetil 50mg is a clinically effective analgesic means after uterine curettage on abortion. [Copyright &y& Elsevier]

Objectives: Whether the maternal vitamin D deficiency is associated with preeclampsia is still an argument. We aimed to assess the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of preeclampsia in a Chinese population and systematically evaluate published evidence on this association.Methods: We conducted a nested case-control study involving 122 pregnant women with preeclampsia and 488 pregnant women whose blood pressure was within the normal range (as controls). For further meta-analysis, 20 studies and our study were included for the final pooled analysis, involving 39,031 participants and 3305 preeclampsia cases with various ethnicities.Results: The results showed that 65.6% of women with preeclampsia had serum 25(OH)D concentrations <50.0 nmol L-1 compared with 55.3% of women in controls. The 25(OH)D concentrations were significantly lower in women with preeclampsia than controls [Median (IQR), women with preeclampsia versus controls: 43.3 (35.5, 55.2) versus 47.5 (37.6, 60.4) nmol L-1, p = .014]. For women with 25(OH)D concentrations <50.0 nmol L-1, they had a 65% increase in preeclampsia risk (95% CI = 1.02-2.69), as compared with women with 25(OH)D concentrations from 50.0 to 74.9 nmol L-1. Further, meta-analysis showed that low 25(OH)D concentrations were associated with a significantly increased risk of preeclampsia by 62% (pooled OR = 1.62, 95%CI = 1.36-1.94), and the risk effect of low 25(OH)D concentrations existed in most subgroups.Conclusions: Low 25(OH)D concentration in pregnancy was significantly associated with preeclampsia risk, and it may serve as biomarkers for the surveillance of high-risk pregnant women. [ABSTRACT FROM AUTHOR]

In recent years, the obese and overweight population has increased rapidly, which has become a worldwide public health problem. However, effective medication is lacking. Our previous study identified a novel peptide, PDBSN (GLSVADLAESIMKNL), that could significantly restrict adipocyte differentiation in vitro, but its in vivo function has not been determined. Thus, in this study, we encapsulated the peptide into liposomes attached with two ligands (visceral-adipose-tissue-targeting peptide and cell-penetrating peptide) to improve stability and specificity. We then tested the peptide's function in HFD (high-fat diet)-induced obese mice and found that PDBSN could reduce weight gain and improve insulin resistance as well as lipid homeostasis. These results suggest that PDBSN may be a potential candidate for anti-obesity drug discovery. • Previous study identified a peptide PDBSN restrict visceral adipocyte differentiation in vitro. • We encapsulated the peptide into liposomes attached with two ligands to improve stability and specificity. • Liposome-encapsulated peptide PDBSN ameliorates high-fat-diet-induced obesity and improves metabolism homeostasis. [ABSTRACT FROM AUTHOR]

Aim: Most positional head deformities can be treated conservatively with postural correction training or a head orthosis ('helmet'). We aimed to investigate whether infants with helmet therapy have cosmetic improvement in head deformity.Methods: A total of 376 infants at age 2-40 months who were diagnosed with mild-moderate-severe positional head deformity were enrolled. Among these infants, 101 infants were treated with helmet therapy or postural correction training. After matching by infant's age and time of therapy, three retrospective cohort studies of 56 infants were conducted for infants with plagiocephaly, brachycephaly and asymmetrical brachycephaly, respectively. The cephalic ratio (CR), radial symmetry index (RSI), cranial vault asymmetry (CVA) and cranial vault asymmetry index (CVAI) were compared between two groups before and after treatment.Results: Before treatment, no significant differences in CR, RSI, CVA and CVAI between groups were found. After treatment, compared with the postural correction training group, the helmet therapy group had significant improvements in CR, RSI, CVA or CVAI (Plagiocephaly: PCVA = 0.017, PCVAI = 0.028; Brachycephaly: PCR = 0.002; Asymmetrical brachycephaly: PRSI = 0.002, PCVA  < 0.001, PCVAI  < 0.001). Moreover, there was no significant difference in head circumference growth between the groups.Conclusions: Helmet therapy may be more effective in the treatment of mild-moderate-severe positional head deformity than postural correction training in infants. And helmet therapy may not hinder head circumference growth. [ABSTRACT FROM AUTHOR]

Background: Handwriting ability is related to many neuronal functions, such as visual-perceptual skills, orthographic coding, motor planning and execution, kinesthetic feedback and visual-motor coordination. To date, there is no specific assessment tool for to assess preschool children's handwriting ability in Mainland China. Our study aimed to develop a tool to assess the handwriting ability of children aged 5–6 years old in Mainland China and to analyze its reliability and validity. Methods: The investigation comprised three phases: 1) original tool generation, 2) tool revision, 3) reliability analysis (i.e., interrater, test-retest) and validity analysis (i.e., content, criterion). Results: The sample included a total of 482 children. The internal consistency (Cronbach alpha) was 0.74. The test-retest correlation coefficients ranged from 0.38 to 0.80. As expected, our data showed an improving trend in handwriting, and differences in respect to age and gender. When compared with the 'handwriting difficulty' group, each subtest score of children in the 'normal' group showed significant differences (p < 0.05). The correlation validity, compared with the visual-motor integration development test (VMI), was 0.17–0.52. Conclusion: The Handwriting Test for Preschool Children (HT-PRE), which is a newly developed handwriting screening tool for preschool children aged 5–6 years old in Mainland China, has displayed a very good internal consistency, acceptable test-retest reproducibility, and good criterion-based validity, and has also shown good application prospects for handwriting difficulty screening in a clinical setting. [ABSTRACT FROM AUTHOR]

A method is described for the determination of the CCAAT/enhancer binding protein alpha (C/EBPα) which is a regulator in adipocyte differentiation. The method is based on quenching of the red fluorescence (with excitation/emission maxima at 548/562 nm) of Cy3-labeled DNA if it becomes adsorbed on positively charged gold nanoparticles (AuNPs). Fluorescently labeled dsDNA that can bind C/EBPα is introduced as a fluorescent probes. The dsDNA is electrostatically adsorbed on the positively charged AuNPs to quench their fluorescence. In the presence of C/EBPα, it will bind dsDNA which then diffuses away. The fluorescence of the AuNPs becomes restored. The fluorescent signal increases linearly in the 0.05 to 600 ng·mL−1 μM C/EBPα concentration range, and the detection limit is 29 pg·mL−1. The method is specific and was applied to analyze cell lysates and in-situ. [ABSTRACT FROM AUTHOR]

Background: Genome‐wide association studies (GWAS) have identified several genetic variants affecting gestational glucose metabolism. However, information regarding their known associations with gestational diabetes mellitus (GDM) risk remains scarce. Methods: This study examined the associations of 12 gestational glucose metabolism‐related variants with GDM risk in a Chinese population (964 GDM cases, 1021 controls). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis. Results: Rs10830963 in melatonin receptor 1B (MTNR1B) was found to be associated with an increased risk of GDM, after adjusting for age, prepregnancy body mass index, parity, abnormal pregnancy history, and family history of diabetes (OR 1.20; 95% CI 1.05‐1.36; P = 0.007). Compared with women with a family history of diabetes, there was a significant association of rs7936247 with GDM risk among pregnant women without a family history of diabetes (OR 1.20; 95% CI 1.04‐1.38; P = 0.014; Pheterogeneity = 0.035). Further functional annotations showed that rs10830963 and rs7936247 fell in the functional elements of human pancreatic islets. Genotype‐phenotype associations indicated that the variants may contribute to GDM risk by affecting the expression of nearby or distant genes. Conclusions: The findings of this study suggest that rs10830963 and rs7936247 may be markers for susceptibility to GDM in a Chinese population. Additional studies are warranted to validate our findings and clarify the underlying mechanism. [ABSTRACT FROM AUTHOR]

Interest in the high folate status of pregnant women has increased due to its role in the prevention of neural tube defects (NTDs). The effect of increased red blood cell (RBC) folate status during the second trimester of pregnancy on gestational diabetes mellitus (GDM) remains unclear. We measured RBC folate concentrations by competitive protein‐binding assay and obtained clinical information from electronic medical records. Logistic regression analysis was used to explore the associations of RBC folate concentrations with risks of gestational diabetes mellitus (GDM). We further assessed the potential nonlinear relations between continuous log‐transformed RBC folate concentrations and GDM risk by using the restricted cubic splines. We observed high RBC folate concentrations in GDM patients compared to control group [median (interquartile range, IQR), GDM vs. controls: 1,554.03 (1,240.54–1,949.99) vs. 1,478.83 (1,124.60–1,865.71) nmol/L, p = .001]. Notably, high folate concentrations were significantly associated with an increased risk of GDM [RR per 1‐SD increase: 1.16 (1.03, 1.30), p = .012] after adjustment for maternal age, parity, and body mass index (BMI) at enrollment. In the restricted cubic spline model, a test of the null hypothesis of the linear relationship was rejected (p = .001). Our study firstly showed that maternal RBC folate concentrations during the second trimester of pregnancy increase the risk of GDM in a Chinese population. Further randomized clinical trials (RCTs) are warranted to confirm the adverse effect. [ABSTRACT FROM AUTHOR]

It is well‐established that the mass and function of human brown adipose tissue (BAT) declines with age. A key factor involved in age‐related impairment of BAT is oxidative stress; however, there is a paucity of studies to date that have explored this relationship. Here, we characterized the age‐related molecular and functional alterations in BAT in vivo in mice of different ages, and treated human brown adipocytes with H2O2 to dissect the direct effect of oxidative stress in vitro. We further explored the structural and functional changes in BAT in an oxidative stress‐induced mouse model of aging. We found that the progressive deterioration of BAT was linked to oxidative stress, and observed that the adipogenesis and thermogenic program were significantly impaired upon H2O2 treatment in vitro. Moreover, antioxidant supplementation (e.g., vitamin E) attenuated oxidative stress and rescued BAT activity decline, suggesting that age‐related injury in BAT function can be partly alleviated by antioxidant treatment. Finally, we found that oxidative stress‐induced BAT dysfunction is linked to the enhancement of autophagy. These results point to oxidative stress as being an important factor in age‐dependent functional impairment of BAT. [ABSTRACT FROM AUTHOR]

Objectives: Currently, brown adipose tissue (BAT) is a therapeutic target in obesity and diabetes, but the mechanism of BAT activation remains unclear. Because increasing emphasis has been placed on the role of intracellular peptides in biological processes, we conducted a study to gain insight into the mechanism of BAT activation by using a peptidomic approach and then attempted to identify peptides that are capable of activating BAT. Methods: In the present study, we generated the peptidomic profile of the intracellular peptides in brown adipocytes treated with forskolin (FSK) using a peptidomic approach. Then, the differentially expressed peptides were evaluated via Gene Ontology (GO) enrichment, KEGG pathway, and protein–protein interaction (PPI) network analysis. Finally, we selected candidate peptides for further validation via assessing the expression levels of UCP‐1 and PGC‐1α in brown adipocytes exposed to the peptides. Results: A total of 4,370 peptides were identified, of which 951 were upregulated and 379 were downregulated after FSK treatment. Bioinformatic analysis demonstrated that the ECM‐receptor interaction GO term was the most enriched and that collagen alpha‐related proteins exhibited the highest degree of PPI. Four peptides separately derived from TSC22 domain family protein 1 (T22D1), bromodomain and WD repeat‐containing protein 1 (BRWD1), protein piccolo (PCLO), and collagen alpha‐1 (III) chain (CO3A1) increased the expression levels of UCP‐1 and PGC‐1α. Conclusions: ECM‐receptor interaction may play an important role in the process of FSK‐stimulated BAT activation, and the pT22D1tide, pBRWD1tide, pPCLOtide, and pCO3A1tide peptides potentially promote BAT thermogenesis. 1.BAT activation is a therapeutic target in obesity and diabetes.2.Intracellular peptides may participate in the process of BAT thermogenesis.3.Some peptides exhibit the potential to activate BAT. [ABSTRACT FROM AUTHOR]

Abstract Obesity rates have risen rapidly over the past several decades and obesity is now a global public health challenge. The reduction of excessive adipogenesis is thought to be an effective intervention for obesity and obesity-related metabolic diseases such as type 2 diabetes. In this study, a novel peptide PDBSN was identified that functions to suppress adipogenesis. In both human preadipocytes and mouse adipose-derived stem cells (ADSCs), PDBSN exhibited a suppressive effect on the accumulation of lipids and the expression of genes as well as their corresponding proteins (CCAAT/enhancer binding protein (C/EBP)β, C/EBPα and nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ)) relevant to adipogenic cell differentiation. Although adipogenesis decreased, the preadipocyte number and proliferation were not influenced by the PDBSN treatment. Apoptosis and the cell cycle were also determined to not have a role in the action of PDBSN. Mechanistically, the activity of the AMPK (adenosine 5ʹ-monophosphate-activated protein kinase) pathway was markedly increased upon PDBSN treatment. Moreover, treatment of preadipocytes with compound C, a selective AMPK inhibitor, abolished the effect of PDBSN in anti-adipogenesis, suggesting that the function of PDBSN relied on the AMPK pathway. These results suggest an effective role for PDBSN in suppressing adipogenesis and show potential for anti-obesity drug discovery. Highlights • A novel peptide termed PDBSN reduces adipogenesis by suppressing adipogenic differentiation. • PDBSN functioned through the regulation of AMPK pathway. [ABSTRACT FROM AUTHOR]

Folate supplementation is recommended before and during early pregnancy to prevent neural tube defects, but the effect of red blood cell (RBC) folate on large for gestational age (LGA) is still unknown. We performed a nested case‐control study including 542 LGA cases and 1,084 appropriate for gestational age (AGA) controls to examine the association of RBC folate concentrations with risk of LGA. Then, male offspring of dams fed basic folic acid (2 mg/kg, control) or 10‐fold folic acid (20 mg/kg, HFol) diet before and during pregnancy were used to explore the effect of high folate intake on birth weight and long‐term effects. We observed higher RBC folate concentrations in the cases compared to controls (p = 0.039). After adjustment for maternal age, BMI at enrollment, gestational weeks at enrollment, gestational weeks at delivery and infant gender, higher RBC folate levels were significantly associated with increased risk of LGA (Ptrend = 0.003). Interestingly, male offspring of HFol dams showed the higher birth weight, elevated levels of post loading blood glucose at 9 and 13 weeks post‐weaning and increased triglyceride (TG) and total cholesterol (TC) levels at 17 weeks post‐weaning. Furthermore, we observed that high folate intake increased the proliferation and differentiation of adipose cells. Our results suggest that maternal high folate intake confers the risk of LGA birth and accelerates the development of obesity in male offspring. Our results suggest that maternal high folate intake confers the risk of LGA birth and accelerates the development of obesity in male offspring. [ABSTRACT FROM AUTHOR]

Abstract Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans. Conversely, its level was induced during the differentiation course of human white pre-adipocytes derived from visceral fat. miR-199a-3p expression was relatively abundant in interscapular BAT (iBAT) and differentially regulated in the activated and aging BAT in mice. Additionally, miR-199a-3p expression level in human brown adipocytes was observed decreased upon thermogenic activation and increased by aging-related stimuli. Using primary pre-adipocytes, miR-199a-3p over-expression was capable of attenuating lipid accumulation and adipogenic gene expression as well as impairing brown adipocytes’ metabolic characteristics as revealed by decreased mitochondrial DNA content and respiration. Suppression of miR-199a-3p by a locked nucleic acid (LNA) modified-anti-miR led to increased differentiation and thermogenesis in human brown adipocytes. By combining target prediction and examination, we identified mechanistic target of rapamycin kinase (mTOR) as a direct target of miR-199a-3p that affected brown adipogenesis and thermogenesis. Our results point to a novel role for miR-199a-3p and its downstream effector mTOR in human brown adipocyte differentiation and maintenance of thermogenic characteristics, which can be manipulated as therapeutic targets against obesity and its related metabolic disorders. Highlights • miR-199a-3p expression was decreased during brown adipocyte differentiation in mice and human. • miR-199a-3p expression was differentially regulated in the activated and aging BAT in mice or brown adipocytes in vitro. • miR-199a-3p negatively regulated lipid accumulation and thermogenic program in human brown adipocytes. • miR-199a-3p directly targeted human 3′UTR of mTOR mRNA, which affected brown adipogenesis and thermogenic capacity. [ABSTRACT FROM AUTHOR]

Highlights • This study provides an overview of lncRNAs and mRNAs expression in the skeletal muscle from db/db mice for the first time. • LncRNAs Gm15441 and Foxo6os showed the consistent expression patterns in IR mouse models and palmitate-treated cell model. • Coexpression and Spearman correlation analysis reveal Gm15441 participates in regulating skeletal muscle insulin signaling. Abstract T2DM is a global health problem that seriously lowers the quality of life and insulin resistance makes a considerable contribution to the pathophysiology of T2DM. Long noncoding RNAs (lncRNAs) have emerged as important regulators in glucose and lipid metabolism. However, comprehensive analysis of lncRNAs in db/db mice skeletal muscle and their potential roles involved in skeletal muscle insulin resistance (IR) remains poorly characterized. Here, we identified 331 lncRNAs, 172 upregulated and 159 downregulated (|fold change|>2, q<0.05), differentially expressed in db/db mice skeletal muscle. Gene Ontology analysis, Pathway analysis and Gene Set Enrichment Analysis of network gene expression revealed the potential functions of dysregulated lncRNAs may involve skeletal muscle function, fatty acid metabolism and the PPAR signaling pathway. In addition, differentially expressed lncRNAs were verified in skeletal muscle from the widely known IR mouse models (db/db and ob/ob mice). Further validation of lncRNAs in C2C12 myotubes exposed with various concentrations of palmitate uncovered that lncRNAs were responsive to palmitate exposure at the high concentrations (0.5mM and 0.75mM). Coexpression analysis revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. Moreover, we characterized two candidate lncRNAs Gm15441 and 3110045C21Rik by a comprehensive examination of their genomic context and validated their expression with neighboring genes (Txnip and Ddr2) by the Spearman correlation analysis. Collectively, these findings improve our understanding of lncRNAs that mediate skeletal muscle insulin resistance in diabetes and represent potential molecular therapeutic targets to improve insulin sensitivity and associated metabolic diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: Whether maternal vitamin D deficiency is associated with gestational diabetes remains controversial. This meta-analysis aimed to systematically evaluate published evidence on the association between maternal vitamin D status and the risk of gestational diabetes. Methods: We retrieved relevant articles from the PubMed, Medline and Embase databases up to May 2017 for observational studies investigating the association between vitamin D status and the risk of gestational diabetes. Odds ratios (OR) or risk ratios (RR) from individual studies were pooled using the fixed and random effect models. Results: The meta-analysis of 29 observational studies included 28,982 participants, of which 4,634 were diagnosed with gestational diabetes, and showed that maternal vitamin D insufficiency was associated with a significantly increased risk of gestational diabetes by 39% (pooled OR = 1.39, 95%CI = 1.20-1.60) with moderate heterogeneity (I2 = 50.2%; P = 0.001). Moreover, the 25(OH)D level was significantly lower in gestational diabetes cases than in controls with a pooled effect of -4.79 nmol/L (95% CI = -6.43, -3.15). Significant heterogeneity was also detected (I2 = 65.0%, P < 0.001). Further subgroup analysis indicated that this association was also evident in most subpopulations. Conclusion: This meta-analysis indicated a significant association between vitamin D insufficiency and increased risk of gestational diabetes. Further well-designed large-scale clinical trials are essential to verify this association. [ABSTRACT FROM AUTHOR]

The purposes of this study are to investigate the prevalence of nonresponsive feeding practice (NRFP) and child's eating behavior (CEB) and to explore the hypothetical association between child's weight status, NRFP and CEB for 1- to 6-year-old children. In this study, 2423 caregivers of 1- to 6-year-old children are from the Nanjing Maternal and Child Health Hospital who completed the self-report questionnaires about their NRFP and CEB as well as their children's sociodemographic data. Chi-square test and multiple regression analyses were used to examine the correlation between child's weight status and NRFP and CEB. The total prevalence of overweight and obesity was 15.2 and 7.3%, respectively. High prevalence of CEB problems and NRFP was detected at 2- and 5-year-old children. Moreover, maternal NRFP was significantly positively associated with CEB. The regression and correlation analysis revealed CEB and maternal NRFP are closely associated with BMI. For instance, refusing new food (OR = 3.57, 95%CI, 1.37-9.33, 1.5-year-old) and restriction (OR = 3.01, 95%CI, 1.34-6.76) are likely to be associated with underweight. Preferring junk food (OR = 4.892, 95%CI, 1.71-14.01, 1-year-old) and inattention (OR = 2.24, 95%CI, 1.16-4.35, 1-year-old) are prone to be overweight and obese, and pressure (OR = 0.23, 95%CI, 0.06-0.91, 1-year-old) is less likely to be associated with underweight.Conclusion: The findings provide strong evidence for the correlation between NRFR and CEB, and this indicates that prevention and intervention of unhealthy weight should start in early life. However, further research is necessary to gain an understanding of the impact of NRFP on CEB and weight. What is known: • Responsive feeding practice is crucial to the formation of eating behavior, and poor practice is associated with the current epidemics of childhood obesity and underweight. What is new: • The findings provide a strong evidence for the correlation between NRFR and CEB. • This finding indicates that NRFR and CEB are associated with child's unhealthy weight. [ABSTRACT FROM AUTHOR]

Background/Aims: Vitamin D deficiency has been shown to be associated with a greater prevalence of anemia in various healthy and diseased populations by a great deal of observational studies. However, less work has been done to explore this association in pregnant women. The aim of this study was to evaluate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of gestational anemia in a large, nested case-control study. Methods: The serum 25(OH)D concentrations was measured by enzyme immunoassay in 775 pregnant women affected with anemia and 1550 controls. Logistic regression analysis was conducted to assess the association of 25(OH)D concentrations with risk of gestational anemia. Results: We found the 25(OH)D concentrations was significantly lower in women affected with anemia than in controls. Logistic regression analyses showed that women with 25(OH)D concentrations < 25.0 nmol/L, from 25.0 to 37.4 nmol/L and from 37.5 to 49.9 nmol/L all had increased risk of anemia when compared with women with concentrations from 50.0 to 74.9 nmol/L. And the risk of anemia was significantly increased with the decreasing concentrations of the serum 25(OH)D in a dose-dependent manner (P for trend = 0.012). For women with concentrations < 50.0 nmol/L, they had an 80% increase in anemia risk (95% CI = 1.45-2.25) after adjustment for confounders. We also observed a nonlinear relationship between the serum 25(OH)D and anemia, with a threshold for 25(OH)D of 50.0 nmol/L existed for anemia. Conclusion: Maternal serum 25(OH)D < 50.0 nmol/L may be a risk factor for gestational anemia, and it should be monitored for the high-risk pregnant women. [ABSTRACT FROM AUTHOR]

A novel endogenous peptide cleaved from 197-213 AA of β-casein, named β-casein 197, was identified by tandem mass spectrometry. β-casein 197 constituted a significant proportion of the peptide content in preterm milk. This study investigated the antibacterial effects and mechanisms against common pathogenic bacteria. Six bacterial strains were selected for this study: Escherichia coli, Staphylococcus aureus, Yersinia enterocolitica, Listeria monocytogenes, Klebsiella pneumonia and Bacillus subtilis. After synthesis, serial twofold dilutions of β-casein 197 were added to select for sensitive bacteria. The disk diffusion method and analysis of bacterial staining were used to identify antibacterial effect, while DNA-binding, scanning electron microscopy and transmission electron microscopy were used to explore antimicrobial mechanisms. Disk diffusion showed that E. coli, S. aureus and Y. enterocolitica were sensitive to the β-casein 197. In addition, live/dead fluorescent staining also confirmed antibacterial effects. Scanning electron and transmission electron microscopy revealed affected extracellular and intracellular structure for three species of bacteria, while a DNA-binding assay showed that the antimicrobial activity did not occur through DNA binding. This study suggests that β-casein 197 has antimicrobial activity against common pathogenic bacteria in newborns with infection. The peptide induced membrane permeabilization but did not bind to genomic DNA. Based on our findings, β-casein 197 has potential clinical value for preventing infections of premature infants. [ABSTRACT FROM AUTHOR]

Background/Aims: Pro-angiogenic factors VEGF and IL-8 play a major role in modulating the migratory potential of endothelial cells. The goal of this study was to investigate the effect of autocrine VEGF and IL-8 in the form of self-conditioned medium (CM) on human umbilical vein endothelial cells (HUVECs). Methods: Enzyme-linked immunosorbent assay (ELISA) examined the automatic secretion of VEGF and IL-8 protein by HUVECs. Western blot, small interfering RNA (siRNA), pulldown and Transwell assays were used to explore the role and the mechanism of autocrine VEGF and IL-8 in migration of HUVECs. Results: Neutralizing VEGF and IL-8 in CM significantly abrogated CM-induced migration of HUVECs. Autocrine VEGF and IL-8 increased Src phosphorylation, Rac1 activity and PAK1 phosphorylation in a time dependent manner. Additionally, blocking Rac1 activity with Rac1 siRNA largely abolished autocrine VEGF and IL-8-induced cell migration. Vav2 siRNA suppressed autocrine VEGF and IL-8-induced Rac1 activation and cell migration. Furthermore, blocking Src signaling with PP2, a specific inhibitor for Src, markedly prevented autocrine VEGF and IL-8-induced Vav2 and Rac1 activation as well as consequently cell migration. PAK1 siRNA also significantly abolished autocrine VEGF and IL-8-induced cell migration. Conclusions: We demonstrated for the first time that autocrine VEGF and IL-8 promoted endothelial cell migration via the Src/Vav2/Rac1/PAK1 signaling pathway. This finding reveals the molecular mechanism in the increase of endothelial cell migration induced by autocrine growth factors and cytokines, which is expected to provide a novel therapeutic target in vascular diseases. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to determine the expression profile of plasma microRNAs in nonsyndromic cleft lip (NSCL) and their clinical significance as biomarkers. Methods Agilent human miRNA microarray chips were used to analyze three NSCL plasma samples (mixed as CL group) and three normal plasma samples (mixed as Control group). Six selected plasma miRNAs were validated using qRT-PCR between another 13 CL and 11 healthy children. The receiver operating characteristic (ROC) curve analysis was applied for three elevated miRNAs, miR-16-2-3p, miR-365a-3p and miR-877-5p. Their target genes were further assessed using gene ontology and pathway analysis. Results The plasma miRNA differentially expressed (fold change ≥2) amounted to 305. In particular, it had been validated that miR-16-2-3p, miR-365a-3p and miR-877-5p were elevated in NSCL plasma samples. ROC curve analysis revealed that each microRNA was able to significantly discriminate NSCL subjects from normal controls. Gene ontology and pathway analysis revealed that many processes over-represented in CL are related to system development process, regulation of nitrogen compound metabolic process, FoxO signaling pathway and the ErbB signaling pathway. Conclusion Our study demonstrated that plasma miR-16-2-3p, miR-365a-3p and miR-877-5p might become biomarkers to diagnose NSCL and dysregulation of these miRNAs might be involved in the progression of NSCL. [ABSTRACT FROM AUTHOR]

The Developmental Eye Movement (DEM) test is commonly used as a clinical visual-verbal ocular motor assessment tool to screen and diagnose reading problems at the onset. No established norm exists for using the DEM test with Mandarin Chinese-speaking Chinese children. This study aims to establish the normative values of the DEM test for the Mandarin Chinese-speaking population in China; it also aims to compare the values with three other published norms for English-, Spanish-, and Cantonese-speaking Chinese children. A random stratified sampling method was used to recruit children from eight kindergartens and eight primary schools in the main urban and suburban areas of Nanjing. A total of 1,425 Mandarin Chinese-speaking children aged 5 to 12 years took the DEM test in Mandarin Chinese. A digital recorder was used to record the process. All of the subjects completed a symptomatology survey, and their DEM scores were determined by a trained tester. The scores were computed using the formula in the DEM manual, except that the “vertical scores” were adjusted by taking the vertical errors into consideration. The results were compared with the three other published norms. In our subjects, a general decrease with age was observed for the four eye movement indexes: vertical score, adjusted horizontal score, ratio, and total error. For both the vertical and adjusted horizontal scores, the Mandarin Chinese-speaking children completed the tests much more quickly than the norms for English- and Spanish-speaking children. However, the same group completed the test slightly more slowly than the norms for Cantonese-speaking children. The differences in the means were significant (P<0.001) in all age groups. For several ages, the scores obtained in this study were significantly different from the reported scores of Cantonese-speaking Chinese children (P<0.005). Compared with English-speaking children, only the vertical score of the 6-year-old group, the vertical-horizontal time ratio of the 8-year-old group and the errors of 9-year-old group had no significant difference (P>0.05); compared with Spanish-speaking children, the scores were statistically significant (P<0.001) for the total error scores of the age groups, except the 6-, 9-, 10-, and 11-year-old age groups (P>0.05). DEM norms may be affected by differences in language, cultural, and educational systems among various ethnicities. The norms of the DEM test are proposed for use with Mandarin Chinese-speaking children in Nanjing and will be proposed for children throughout China. [ABSTRACT FROM AUTHOR]

Background Previous studies reported that miR-1908 was highly expressed in mature human adipocytes. Adipokines tumor necrosis factor α (TNF-α) that was known to activate NF-kappaB signaling could affect the expression of miR-1908 in adipocytes. However, little is known about the underlying mechanisms. Methods In this study, we identified miR-1908 promoter using polymerase chain reaction (PCR) from human genomic DNA. Bioinformatic analysis was applied to predict the NF-kappaB binding sites in miR-1908 promoter. Real-time PCR, dual luciferase reporter assay, Mutagenesis analysis and electrophoretic mobility shift assay (EMSA) were performed to demonstrate the function of NF-kappaB binding sites in miR-1908 promoter. Results 1243 bp miR-1908 promoter located in the intron of host gene fatty acid desaturase 1 (FADS1). Bioinformatic analysis revealed the presence of two putative NF-kappaB binding sites. TNF-α restricts miR-1908 expression in preadipocytes, and TNF-α decreases miR-1908 promoter activity in HEK293T cells. In addition, those two NF-kappaB transcription factor binding sites in miR-1908 promoter were functional. Conclusion Our findings demonstrated that miR-1908 has its own transcription unit, and revealed the transcriptional mechanisms of miR-1908 expression based on NF-kappaB signaling. This study offers a theoretical basis for understanding the transcriptional mechanism of miR-1908 expression and may provide a new strategy for obesity clinical therapy. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. It can serve as key co-activators of proteins involved in transcriptional regulation. Studies have found that white and brown adipocytes both originate from the mesoderm. However, it remains unclear whether lncRNAs function during adipogenesis or in energy metabolism in brown adipose tissue (BAT) and white adipose tissue (WAT). In this study, we used lncRNA microarray technology to evaluate differences in the lncRNA expression profiles of WAT and BAT. We observed 735 up-regulated and 877 down-regulated lncRNAs (fold change >4.0). To reveal the potential functions of these lncRNAs, we applied GO and pathway analyses to study the differentially expressed lncRNAs. We found that AK142386 and AK133540 may affect adipogenesis and metabolism. Our data indicate that AK142386 and AK133540 may be involved in BAT and WAT development through their target genes Hoxa3 and Acad10. Together, we have identified numerous lncRNAs and these lncRNAs can potentially serve as a required component for proper adipogenesis. [ABSTRACT FROM AUTHOR]

Methylphenidate (MPH) is a central nervous system stimulant that is widely used to treat attention deficit hyperactivity disorder (ADHD) and has been shown to improve attention, cognitive function and behaviors in both patients and animal models of ADHD. Even among normal healthy people, MPH can facilitate the consolidation of memories and improve declarative memory. Using microarray techniques, we aimed to find new pharmacology profile of MPH. A Làt maze experiment showed that locomotor activity and non-selective attention were affected by 2 weeks of exposure to MPH. Then, we identified long non-coding RNA (lncRNA) signatures in the prefrontal cortex of rats; 461 up-regulated lncRNAs and 97 down-regulated lncRNAs were found in the MPH-exposed group compared with the control group using fold-change >1.5. GO and KEGG pathway analyses indicated biological functions related to the metabolism of neural chemical compounds and nerve cell development. Furthermore, we reported changes in uc.173+ related to the UBE2B gene, which may affect neurite outgrowth and axonal regeneration. At the same time, MRAK081997 associated with the DHFR gene may be involved in axon regeneration in the rodent central nervous system through DNA methylation. Our study showed distinct expression profiles of lncRNAs in the normal rat prefrontal cortex after exposure to MPH, offering information for further research of MPH and may suggesting a new therapeutic target for ADHD. [ABSTRACT FROM AUTHOR]

Background/Aims: MicroRNA-29b (miR29b) has been previously identified in early mouse embryos through miRNA microarray analysis. Recent research has indicated that miR29b participates in DNA methylation by regulating DNA methyltransferase 3a/3b (Dnmt3a/3b) expression. However, the expression pattern and biological function of miR29b in mouse preimplantation embryonic development remain unknown. Methods: In this study, we examined the expression patterns of miR29b and Dnmt3a/3b in mouse early embryos at different developmental stages. Subsequently, expression and localization of DNMT3A/3B protein was analyzed in mouse early embryos by immunofluorescence staining. The biological function of miR29b in mouse early embryos was analyzed by microinjection of commercially available miRNA-specific inhibitors and mimics. Results: Our data showed that Dnmt3a/3b mRNA expression is negatively regulated by miR29b in mouse early embryos. Immunofluorescence analysis revealed that DNMT3A/3B protein expression is predominantly localized within the nucleoplasm of embryos. Alterations to the activity of miR29b could change the DNA methylation levels in mouse preimplantation embryos and lead to a developmental blockade, from the morula to the blastocyst stage. Conclusion: These results indicated a role for the miR29b-Dnmt3a/3b-DNA methylation axis in mouse early embryonic development, and we provide evidence that miR29b is indispensable for mouse early embryonic development. This study contributes to a preliminary understanding of the role of miR29b during mouse embryonic development. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Obesity and the related metabolic syndrome have emerged as major public health issues in modern society. miRNAs have been shown to play key roles in regulating obesity-related metabolic syndrome, and some miRNAs regulated by adiponectin were identified as novel targets for controlling adipose tissue inflammation. miR-378 is a candidate target that was shown to be involved in adipose differentiation, mitochondrial metabolism and systemic energy homeostasis. However, little is known about the regulatory mechanisms of miR-378 expression. To better understand the physiological role of miR-378 in obesity and metabolic syndrome, it is crucial that we understand the regulation of miR-378 gene expression in human adipocytes. Methods: In this study, we investigated the effects of adipokines and inflammatory cytokines on miR-378 expression using Real-time PCR and the potential regulatory mechanisms using luciferase reporter assays and electrophoretic mobility shift assay (EMSA). Results: We found that adipokines and cytokines upregulated miR-378 expression primarily through SREBP and C/EBP binding sites in the miR-378 promoter region. Conclusion: Our findings showed that adipokines induced miR-378 expression and revealed the most likely mechanism of adipokine-induced miR-378 dysregulation in human adipocytes. miRNAs have been shown to function in regulating obesity-related metabolic syndrome, and miR-378 may be a novel target for controlling adipose tissue inflammation. This study offers a theoretical basis for understanding systemic adipose tissue inflammation and may provide new strategies for clinical treatment. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Vitrification significantly improves the rates of blastocyst survival and clinical pregnancy following frozen embryo transfer (FET). However, ice crystal formation during the freezing process reduces the blastocyst survival rate. Artificial shrinkage (AS) prior to blastocyst vitrification decreases the formation of ice crystals, increasing the blastocyst survival rate. The aim of this study was to identify an efficient AS method to improve blastocyst survival rates following vitrification. Method: Use of the 29-gauge needle AS and Laser pulse AS methods prior to vitrification was compared in terms of the impacts on the rates of blastocyst survival in FET cycles, blastocyst hatching, clinical pregnancy after transfer, embryo implantation, abortion, gestational duration and birth weight. Result: In total, 438 blastocysts in 219 cycles were thawed, resulting in survival of 407 (92.9 %). Of these, 213 cycles were transferred, resulting in 129 clinical pregnancies (60.6 %) and 140 successful births. There were no differences between the two methods in the rates of blastocyst survival, clinical pregnancy, embryo implantation and abortion. However, the 29-gauge needle AS group was associated with a significantly lower blastocyst hatching rate (83.6 % vs. 91.2 %), shorter average gestational duration (37.36 ± 2.34 vs. 38.06 ± 1.76), and higher premature birth rate (40.00 % vs. 21.15 %) compared with Laser pulse AS group. Conclusion: No significant differences in the effectiveness of the two methods applied prior to blastocyst vitrification were observed before birth, while after birth, a significantly improved clinical outcome was obtained with laser pulse AS indicating that this is a more effective pre-processing method for blastocyst vitrification. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. Method and Results: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c) were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852) that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Conclusion: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Obesity is associated with a low-grade inflammation of white adipose tissue, which can subsequently lead to insulin resistance, impaired glucose tolerance, and even diabetes. MicroRNAs (miRNAs) have been implicated as negative regulators controlling diverse biological processes at the level of post-transcriptional repression. miR-146b is an intergenic miRNA that can regulate the inflammatory process by attenuating cytokine signaling via the nuclear factor-κB pathway. In this study, we focused on investigating the expression of miR-146b in mature human adipocytes and their response to proinflammatory cytokines. Our results showed that miR-146b was highly expressed in the mature adipocytes. The mature human adipocytes responded to proinflammatory cytokines ( TNF-α and IL-6) by highly increasing the expression of miR-146b. We cloned and identified a potential promoter of the transcriptional regulation of miR-146b. Interestingly, a fragment about 950-bp length upstream sequences of miR-146b had apparent transcription activity. In addition, the increase in miR-146b promoter activity by TNF-α and IL-6 was also effectively elevated. Our results indicated that a novel role for miR-146b in adipose tissue inflammation and miR-146b may be an important mediator in the process of obesity complications via its own transcription mechanism. [ABSTRACT FROM AUTHOR]

Highlights: [•] Expression profiles of LncRNAs between brown adipose tissue and skeletal muscle. [•] 704 up-regulated and 896 down-regulated lncRNAs were identified. [•] Analysis of dysregulated LncRNAs. [•] AK003288 may affect energy metabolism. [•] Find new therapeutic target for combatting obesity. [ABSTRACT FROM AUTHOR]

Abstract: Recent findings indicate that microRNAs (miRNAs) are involved in the regulatory network of adipogenesis and obesity. Thus far, only a few human miRNAs are known to function as adipogenic regulators, fanning interest in studies on the functional role of miRNAs during adipogenesis in humans. In a previous study, we used a microarray to assess miRNA expression during human preadipocyte differentiation. We found that expression of the miR-26b was increased in mature adipocytes. MiR-26b is an intronic miRNA located in the intron of CTDSP1 (carboxy terminal domain, RNA polymerase II, polypeptide A, small phosphatase 1). Target prediction and Renilla luciferase analyses revealed the phosphatase and tensin homolog gene (PTEN) as a putative target gene. In this study, we found that miR-26b was gradually upregulated during adipocyte differentiation. To understand the roles of miR-26b in adipogenesis, we adopted a loss-of-function approach to silence miR-26b stably in human preadipocytes. We found that miR-26b inhibition effectively suppressed adipocyte differentiation, as evidenced by decreased lipid droplets and the ability of miR-26b to decrease mRNA levels of adipocyte-specific molecular markers and triglyceride accumulation. Furthermore, the cell growth assay revealed that miR-26b inhibition promoted proliferation. Nevertheless, it had no effect on apoptosis. Taken together, these data indicate that miR-26b may be involved in adipogenesis and could be targeted for therapeutic intervention in obesity. [Copyright &y& Elsevier]

Abstract: Sevoflurane is a general anesthetic commonly used in the pediatric setting because it is sweet-smelling, nonflammable, fast acting and has a very short recovery time. Although recent clinical data suggest that early anesthesia exposure is associated with subsequent learning and memory problems, it is difficult to determine the exact scope of developmental neurotoxicity associated with exposure to specific anesthetics such as sevoflurane. This is largely due to inconsistencies in the literature. Thus, in the present studies we evaluated the effect of early life exposure to sevoflurane (1%, 2%, 3% or 4%) on adulthood memory impairment in Sprague-Dawley rats. Animals were exposed to different regimens of sevoflurane anesthesia on postnatal days (PNDs) 3, 7, or 14 or at 7 weeks (P7W) of age and spatial memory performance was assessed in adulthood using the Morris Water Maze (MWM). Rats exposed to sevoflurane exhibited significant memory impairment which was concentration and exposure duration dependent. Disruption of MWM performance was more severe in animals exposed on both PNDs 3 and 7 than in animals exposed on both PNDs 3 and 14. The younger the animal's age at the time of exposure, the more significant the effect on later MWM performance. Compared to the neonates, animals exposed at P7W were relatively insensitive to sevoflurane: memory was impaired in this group only after repeated exposures to low doses or single exposures to high doses. Early life exposure to sevoflurane can result in spatial memory impairments in adulthood and the shorter the interval between exposures, the greater the deficit. [Copyright &y& Elsevier]

Abstract: Background: Congenital heart defects (CHD) are the most common form of malformation during embryonic development. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of maternal serum miRNAs and their correlation with fetal CHD. Methodology/principle findings: We systematically performed SOLiD sequencing followed by individual quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays to identify and validate the expression of maternal serum miRNAs at 18–22weeks of gestation. Four miRNAs (miR-19b, miR-22, miR-29c and miR-375) were found to be significantly up-regulated in pregnant women with fetal CHD, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.79, 0.671, 0.767 and 0.693, respectively. Furthermore, the combination of the four miRNAs using multiple logistic regression analysis showed a larger AUC (0.813) that was more efficient for the early detection of fetal CHD. Conclusions/significance: We identified and validated a class of four maternal serum miRNAs which could act as novel non-invasive biomarkers for the prenatal detection of fetal CHD. [Copyright &y& Elsevier]

An important question about adipogenesis is how master adipogenesis factors (defined as being able to initiate adipogenesis when expressed alone) peroxisome proliferator-activated receptor (PPAR) initiate adipogenesis only in differentiating preadipocytes. The objective of our research was to find previously unidentified factors that are unique or highly enriched in cells of the adipocyte lineage during adipogenesis that may provide functional tissue specificity to preadipocytes. We reasoned that such factors may alter expression profile specifically in obese individuals. Omental adipose tissues were obtained from obese and non-obese male patients undergoing emergency abdominal surgery. mRNAs extracted from either group were used for suppression subtraction hybridization (SSH). Genes corresponding to mRNAs enriched in obese versus non-obese patients were identified through sequencing and further analyzed for tissue distribution. Out of ~20 genes, we found several that showed clear fat cell specific expression patterns. In this study, we functionally studied one of these genes, previously designated as open reading frame C10orf116. Our data demonstrated that C10orf116 is highly expressed in adipose tissue and is localized primarily within the nucleus. Over-expression studies in 3T3-L1 cells indicated that it up-regulates the levels of CCAAT/enhancer binding protein α (C/EBPα) and PPARγ and promotes adipogenic differentiation starting from the early stage of adipogenesis. Over-expressed in omental tissues from obese patients, C10orf16 manifested the characteristics of an adipocyte lineage-specific nuclear factor that can modulate the master adipogenesis transcription factors early during differentiation. Further studies of this factor should help reveal tissue-specific events leading to fat cell development at the transcriptional level. [ABSTRACT FROM AUTHOR]

Introduction: Pre-eclampsia (PE), a severe pregnancy-specific disease characterized by the new onset of hypertension, proteinuria, edema, and a series of other systematic disorders, is a state of widespread mitochondrial dysfunction of the placenta. Methods: We compared the morphology of mitochondria in pre-eclamptic and normotensive placentae using electron microscopy. To reveal the systematic protein expression changes of placental mitochondria that might explain the pathogenesis of PE, we performed iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on differentially expressed placental mitochondria proteins from 4 normotensive and 4 pre-eclamptic pregnancies. Bioinformatics analysis was used to find the relative processes that these differentially expressed proteins were involved in. Three differentially expressed proteins were chosen to confirm by Western blotting and immunohistochemistry. Results: Morphological data demonstrated degenerative and apoptotic changes in the mitochondria of pre-eclamptic placentae. We found four proteins were upregulated and 22 proteins were downregulated in pre-eclamptic placentae compared with normotensive placentae. Bioinformatics analysis showed that these proteins were involved in many critical processes in the development of pre-eclampsia such as apoptosis, fatty acid oxidation, the respiratory chain, reactive oxygen species generation, the tricarboxylic acid cycle and oxidative stress. Conclusions: This preliminary work provides a better understanding of the proteomic alterations of mitochondria from pre-eclamptic placentae and may aid in our understanding of the importance of mitochondria in the development of pre-eclampsia. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Epoxide hydrolases are involved in detoxifying and excreting the environmental chemicals, which are associated with decreased semen quality and male infertility. We hypothesized that polymorphisms in epoxide hydrolases may be associated with risk of oligozoospermia and asthenospermia. Design and methods: In this study, 468 fertile controls and 672 idiopathic male infertile patients were recruited. SNPstream and TaqMan assay were used to genotype four single nucleotide polymorphisms in EPHX1 and EPHX2. The semen analysis was performed by computer-assisted semen analysis system. Results: Our results demonstrated that rs1042064 of EPHX2 was significantly associated with decreased risk of oligozoospermia (OR=0.65, 95% CI: 0.44–0.98) and asthenospermia (OR=0.66, 95% CI: 0.46–0.94). Conclusions: Our results provided evidence that genetic variants in epoxide hydrolases may modify the risk of oligozoospermia and asthenospermia in Han-Chinese population. [Copyright &y& Elsevier]

Abstract: Uncoupling proteins, a family of proton carriers located in the inner mitochondrial membrane, have important functions in energy metabolism and free radical generation that are relevant to mitochondrial function. Five family members have been identified, UCP1–5, that have distinct tissue distributions, and differences and similarities in physiological function. Uncoupling protein 4 (UCP4) is highly expressed and has a unique function in brain. UCP4 appears to be involved with metabolism in neurons and adipocytes, but conclusions on this protein have been controversial. Here, we used Caenorhabditis elegans to explore the functions of ucp-4, particularly in fat metabolism. Our results showed that UCP4 knockdown induced an obese phenotype and impaired the insulin-like pathway, possibly via oxidative stress in C. elegans. This highlights the importance of studying the role of ucp-4 in fat metabolism. [Copyright &y& Elsevier]

Background: The pre- and postnatal detection rate, incidence, clinical characteristics and outcomes of congenital heart disease (CHD) have been studied in developed countries for many years, but rarely have large-scale studies been reported in Chinese populations. The aim of the present study was to investigate the pre- and postnatal detection rates, incidence, clinical characteristics and outcomes of CHD in a Chinese hospital in order to improve the future screening and treatment of CHD. Methods: Fetuses without risk factors for CHD were screened using basic cardiac ultrasound examination (BCUE). Fetuses with suspected cardiac malformation revealed by BCUE and fetuses with risk factors were screened using extended cardiac ultrasound examination. Outcomes recorded from fetal, neonatal and postmortem records over 4 years (2006-2009) included: therapeutic termination of pregnancy, spontaneous abortions or stillbirths, deaths at birth or in the neonatal period (before 28 days of age), and rate of birth and clinical characteristics of newborns. Results: A total of 34 071 fetuses were screened for CHD during a period of 4 years, of which 173 fetuses were screened for CHD using BCUE and 301 fetuses were screened using extended cardiac ultrasound examination. The incidence of fetal CHD increased from 1.1% in 2006 to 2.4% in 2009 ( P < 0.05), yielding an overall incidence of 1.5% (523/34 071). Of the fetuses with CHD, 48.2% (252/523) died before 28 days of age (including intra-uterine death and termination of pregnancy), 51.8% (271/523) lived more than 28 days and the incidence of live newborns with CHD was 0.80% (271/34071). Conclusions: The prevalence of CHD was quite common in this Chinese hospital. Detailed profiles of CHD suggest that, while training programs in obstetric screening at this hospital were beneficial, prenatal intervention, treatment and care of fetal CHD were inefficient and should be strengthened in China. [ABSTRACT FROM AUTHOR]

Abstract: In our previous study, peripheral inflammatory stimulation evoked production of macrophage migration inhibitory factor (MIF) in the spinal cord and found spinal microglia are the major source of MIF in this context. Given the contribution of the activated-microglia to the inflammatory neuropathy plus the role for upregulated COX 2 expression and PGE2 production in the severity of clinical manifestations of these neuroinflammatory conditions, we herein tested the hypothesis that in vitro MIF stimulation to spinal microglia could result in an activation of COX 2–PGE2 system by MIF–CD74 interaction. We found MIF played roles in evoking COX 2 mRNA and protein expression in a dose-dependent manner correspondingly in changes in PGE2 level in the cultured rat microglia, but these changes could be inhibited by genetic deletion of CD74. Finally, MIF-induced COX 2–PGE2 activation could be blocked by selective inhibitors of p44/p42 and p38 MAPKs. These data highlight MIF/CD74 interaction induces upregulation of COX 2 expression and PGE2 secretion in primary rodent microglia, and further this effect is associated with downstream activation of p38 and p44/p42 signaling cascades, and favors the role of MIF as a novel pathway for microglia-associated neuroinflammation. [Copyright &y& Elsevier]