Secreted proteins are important proteins in the human proteome, accounting for approximately one-tenth of the proteome. However, the prognostic value of secreted protein-related genes has not been com Show more
Secreted proteins are important proteins in the human proteome, accounting for approximately one-tenth of the proteome. However, the prognostic value of secreted protein-related genes has not been comprehensively explored in lung adenocarcinoma (LUAD). In this study, we screened 379 differentially expressed secretory protein genes (DESPRGs) by analyzing the expression profile in patients with LUAD from The Cancer Genome Atlas database. Following univariate Cox regression and least absolute shrinkage and selection operator method regression analysis, 9 prognostic SPRGs were selected to develop secreted protein-related risk score (SPRrisk), including CLEC3B, C1QTNF6, TCN1, F2, FETUB, IGFBP1, ANGPTL4, IFNE, and CCL20. The prediction accuracy of the prognostic models was determined by Kaplan-Meier survival curve analysis and receiver operating characteristic curve analysis. Moreover, a nomogram with improved accuracy for predicting overall survival was established based on independent prognostic factors (SPRrisk and clinical stage). The DESPRGs were validated by quantitative real-time PCR and enzyme-linked immunosorbent assay by using our clinical samples and datasets. Our results demonstrated that SPRrisk can accurately predict the prognosis of patients with LUAD. Patients with a higher risk had lower immune, stromal, and ESTIMATE scores and higher tumor purity. A higher SPRrisk was also negatively associated with the abundance of CD8 Show less
To explore the correlation of cytochrome B-245 alpha chain ( The study was a case-control trial. A total of 372 GAgP patients and 133 periodontally healthy controls were recruited. The The mean age of Show more
To explore the correlation of cytochrome B-245 alpha chain ( The study was a case-control trial. A total of 372 GAgP patients and 133 periodontally healthy controls were recruited. The The mean age of GAgP group and control group was (27.5±5.2) years and (28.8±7.1) years respectively. There was significant difference in age between the two groups ( Show less
Epigenetic modification of chromatin is an important step in the regulation of gene expression. The chromobox family proteins (CBXs), as epigenetic modifier, may play a vital role in tumorigenesis and Show more
Epigenetic modification of chromatin is an important step in the regulation of gene expression. The chromobox family proteins (CBXs), as epigenetic modifier, may play a vital role in tumorigenesis and cancer progression. Herein we explored the correlation between CBXs and breast cancer (BC) via the bioinformatics approach and qRT-PCR validation. Several databases, including GEPIA, TCGA, GEO, K-M plotter, STRING, DAVID, cBioPortal, CIBERSORT, and HPA were employed to analyze the expression levels of CBXs and the correlations between CBXs and prognosis (overall and recurrence-free survival) in BC. We analyzed molecular functions, genetic variations, transcription factors of CBXs, and immune cell infiltration status. ROC curve analysis was performed to determine the predictive value of CBXs. RNA extracted from 11 human BC and paired adjacent normal tissues were subjected to qRT-PCR. The mRNA expression level of CBX1-5 was significantly upregulated, while that of CBX7 was significantly downregulated in BC; no expression disparities were observed in CBX6/8 expression. Further, high mRNA expression of CBX1/2/3/4/8 correlated with advanced BC, whereas high mRNA expression of CBX6/7 correlated with early BC. High mRNA expressions of CBX1/2/3/5 predict poor OS and RFS, while higher mRNA expressions of CBX6/7 predict better OS and RFS in patients with BC. ROC curve analysis revealed that CBX3 showed excellent discriminatory ability. Gene ontology enrichment analysis showed that CBXs primarily participated in SUMOylation and post-/transcriptional regulation. Moreover, they presented varying degrees of amplification in BC tissues and were related to the infiltration of various immune cells. CBXs can serve as putative biomarkers for BC. Further studies are warranted to determine the exact molecular mechanisms underlying the action of CBXs in BC, particularly CBX1/2/3/5/7. Show less
Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activa Show more
Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway, the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR) and progesterone (PGR) induced by cAMP or estrogen plus progesterone. Similar results were obtained from Il27ra Show less
Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary Show more
Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) improves monocrotaline (MCT)-induced PAH and right heart failure; however, the underlying mechanism remains unknown. Here we speculate that ApoA5 has a protective effect in pulmonary vessels and aim to evaluate the mechanism. ApoA5 is overexpressed in an MCT-induced PAH animal model and platelet-derived growth factor (PDGF)-BB-induced proliferating PASMCs. Lung vasculature remodeling was measured by immunostaining, and PASMC proliferation was determined by cell counting kit-8 and 5-ethynyl-2'-deoxyuridine5-ethynyl-2'-deoxyuridine incorporation assays. Coimmunoprecipitation-mass spectrometry was used to investigate the probable mechanism. Next, its role and mechanism were further verified by knockdown studies. ApoA5 level was decreased in MCT-induced PAH lung as well as PASMCs. Overexpression of ApoA5 could help to inhibit the remodeling of pulmonary artery smooth muscle. ApoA5 could inhibit PDGF-BB-induced PASMC proliferation and endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78 (GRP78). After knocking down GRP78, the protecting effects of ApoA5 have been blocked. ApoA5 ameliorates MCT-induced PAH by inhibiting endoplasmic reticulum stress in a GRP78 dependent mechanism. Show less
Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that the RNA helicase DDX5 was downregulated in keratinocytes from the inflammatory skin lesio Show more
Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that the RNA helicase DDX5 was downregulated in keratinocytes from the inflammatory skin lesions in patients with atopic dermatitis and psoriasis, and that mice with keratinocyte-specific deletion of Ddx5 (Ddx5 Show less
Investigation of associated risk factors of valproic acid (VPA)-induced tremor helped in increasing tolerance and optimizing treatment scheme individually. To determine the risk factors of VPA-induced Show more
Investigation of associated risk factors of valproic acid (VPA)-induced tremor helped in increasing tolerance and optimizing treatment scheme individually. To determine the risk factors of VPA-induced tremor, with particular attention on identifying tremor-susceptible gene mutations. Epileptic patients taking VPA were divided into a tremor and a non-tremor groups. A mutation of rs9652490 in the leucine-rich repeat and immunoglobulin domain-containing Nogo-receptor-interacting protein 1 (LINGO-1) gene was determined by Sanger sequencing. Cerebellar atrophy was assessed, and various cerebellar dimensions were measured on magnetic resonance imaging (MRI) scans. One hundred and eighty-one of 200 subjects were included. Multivariate regression analysis indicated several VPA-induced tremor-related factors: females (OR = 2.718, p = 0.014), family history of tremor (OR = 7.595, p = 0.003), treatment duration (> 24 months; OR = 3.294, p = 0.002), and daily dosage (> 1,000 mg/d; OR = 19.801, p = 0.008) of VPA. Chi-square tests revealed that treatment with VPA magnesium-ER (p = 0.030) and carbamazepine combination (p = 0.040) reduced the incidence of tremor. One hundred and seventy-six gene sequencing and 86 MRI results excluded any significant difference between the two groups in the mutation of rs9652490 within LINGO-1, the ratio of cerebellar atrophy or the cerebellar-dimension values (p > 0.05). However, mutation of rs9652490 within LINGO-1 was correlated with increased cerebellar atrophy (p = 0.001), reduced cerebellar hemisphere thickness (p = 0.025), and right cerebellar hemisphere longitudinal diameter (p = 0.047). Our cohort indicated risk (female, positive family history of tremor, daily dosage > 1000 mg and treatment duration > 24 months of VPA) and protective factors (VPA magnesium-ER and combination with CBZ) of VPA-induced tremor. Mutation of rs9652490 within LINGO-1 correlated with cerebellar atrophy, neither was correlated with VPA-induced tremor. Show less
To identify the pathogenic gene variation in a Chinese family with Hereditary Multiple Exostoses (HME). By examining blood-sourced DNA and clinical manifestations of the proband and his family members Show more
To identify the pathogenic gene variation in a Chinese family with Hereditary Multiple Exostoses (HME). By examining blood-sourced DNA and clinical manifestations of the proband and his family members, the whole exome sequencing (WES) and Sanger sequencing were used to detect possibly pathogenic mutations. A novel heterozygous mutation (c.325dup) was identified in exon 1 of the Show less
Oral squamous cell carcinoma (OSCC), the most common type of primary malignant tumor in the oral cavity, is a lethal disease with high recurrence and mortality rates. Butyrate, a metabolite produced b Show more
Oral squamous cell carcinoma (OSCC), the most common type of primary malignant tumor in the oral cavity, is a lethal disease with high recurrence and mortality rates. Butyrate, a metabolite produced by periodontal pathogens, has been linked to oral diseases. The purpose of this study was to evaluate the effect of sodium butyrate (NaB) on the proliferation, migration, and invasion of OSCC cells Two OSCC cell lines (HSC-4 and SCC-9) were treated with NaB at different concentrations. The cell proliferation was assayed by CCK-8, ethylene deoxyuridine (EdU), and flow cytometry. Wound healing and transwell assay were performed to detect cell migration and invasion. Changes in epithelial-mesenchymal transition (EMT) markers, including E-cadherin, Vimentin, and SNAI1, were evaluated by quantitative real-time PCR (qRT-PCR), western blot, and immunofluorescent staining. The expression levels of matrix metalloproteinases (MMPs) were analyzed by qRT-PCR and gelatin zymography. Our results showed that NaB inhibited the proliferation of OSCC cells and induced cell cycle arrest at G1 phase, but NaB significantly enhanced cell migration and invasion compared with the control group. Further mechanistic investigation demonstrated that NaB induced EMT by increasing the expression of Vimentin and SNAI1, decreasing the expression of membrane-bound E-cadherin, and correspondingly promoting E-cadherin translocation from the membrane to the cytoplasm. In addition, the overexpression of MMP1/2/9/13 was closely related to NaB treatment. Our study conclude that butyrate may promote the migration and invasion of OSCC cells by inducing EMT. These findings indicate that butyrate may contribute to OSCC metastasis. Show less
Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy," which includes high fever and worsening diarrhea. Current Show more
Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy," which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD. Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance. In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn's disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%). Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event. Show less
The molecular mechanism of in hyperlipidemia-induced renal injury has not been elucidated. Angiogenin-like protein 4 (ANGPTL4) is a key regulator of lipid metabolism. The role of ANGPTL4 hyperlipidemi Show more
The molecular mechanism of in hyperlipidemia-induced renal injury has not been elucidated. Angiogenin-like protein 4 (ANGPTL4) is a key regulator of lipid metabolism. The role of ANGPTL4 hyperlipidemia-induced renal injury has not been reported. Wild type C57 mice and gene angptl4 knockout mice were fed with 60% high fat diet or normal diet respectively. The serum lipid, urinary albumin and renal pathology were tested at the 9th, 13th, 17th and 21st week with high fat diet. Elevated blood lipids in the wild-type mice with high-fat diet were found at 9th week. At the 17th week, the level of urinary albumin in high-fat fed wild type mice were significantly higher than which with normal diet, correspondingly, segmental fusion of podocyte foot process in kidney could be observed in these hyperlipidemia mice. IHC showed that the expression of ANGPTL4 in glomeruli of high-fat fed wild type mice began significant elevated since the 9th week. When given high fat diet, compared to the wild type, the gene angptl4 knockout mice showed significantly alleviated the levels of hyperlipidemia, proteinuria and effacement of podocyte foot process. Finally, the expression of ACTN4 showed remarkably lower in glomeruli podocyte of wild type mice fed high fat diet than that of wild type mice with normal diet at each time-point (P < 0.01). Differently, the expression of ACTN4 in gene angptl4 knockout mice did not happen significantly weaken when given the same dose of high fat diet. ANGPTL4 could play a role in hyperlipidemic-induced renal injury via down-regulating the expression of ACTN4 in kidney podocyte. Show less
TAB182 (also named TNKS1BP1), a binding protein of tankyrase 1, has been found to participate in DNA repair. Our previous study has revealed the involvement of TAB182 in the radioresistance of esophag Show more
TAB182 (also named TNKS1BP1), a binding protein of tankyrase 1, has been found to participate in DNA repair. Our previous study has revealed the involvement of TAB182 in the radioresistance of esophageal squamous cell carcinoma (ESCC) cells. However, whether TAB182 contributes to the ESCC tumorigenesis and progression remains unclear. In this study, we found that highly expressed TAB182 is closely associated with a poor prognosis of patients with ESCC. TAB182 silencing reduced ESCC cell proliferation and invasion in vitro, tumorigenicity and metastasis in vivo. RNA-seq and IP-MS analysis revealed that TAB182 could affect the β-catenin signaling pathway via interacting with β-catenin. Furthermore, TAB182 prevented β-catenin to be phosphorylated by GSK3β and recruited four and a half of LIM-only protein 2 (FHL2), which thereby promoted β-catenin nucleus translocation to result in activation of the downstream targets transcription in ESCC cells. Our findings demonstrate that TAB182 enhances tumorigenesis of esophageal cancer by promoting the activation of the β-catenin signaling pathway, which provides new insights into the molecular mechanisms by which TAB182 accelerates progression of ESCC. Show less
The pro-inflammatory factor interleukin-8 (IL-8) is related to poor prognosis in hepatocellular carcinoma (HCC) patients. Interleukin-8 enhanced HCC invasion by upregulating Snail and Twist1, whether Show more
The pro-inflammatory factor interleukin-8 (IL-8) is related to poor prognosis in hepatocellular carcinoma (HCC) patients. Interleukin-8 enhanced HCC invasion by upregulating Snail and Twist1, whether this modulation relies on microRNAs (miR) is unclear. In this study, hsa-miR-370-3p was screened as candidate miRNA targeting Snail and Twist1, and its expression was downregulated by IL-8. Luciferase assays and RNA electrophoretic mobility shift assays were used to evaluate the interaction between miR-370-3p and targeted mRNAs. Coimmunoprecipitation, luciferase, and ChIP assays were undertaken to investigate the mechanisms underlying IL-8-mediated modification of miR-370-3p. Gain- and loss-of-function studies, Transwell assays, and a xenograft nude mouse model were used to investigate pro- and antitumor activities. Interleukin-8 and miR-370-3p levels were analyzed for clinical relevance in HCC patients. Our results showed that HCC patients with high levels of IL-8 experienced more metastasis and shorter survival. Interleukin-8 induced epithelial-mesenchymal transition and promoted liver cancer cell migration, invasion, and metastasis both in vitro and in vivo. MicroRNA-370-3p interacted with its cognate mRNA within the 3'-UTR regions of Twist1 and Snail mRNA directly and specifically and attenuated IL-8 protumoral effects on liver cancer cells. Interleukin-8 negatively modulated miR-370-3p through signal transducer and activator of transcription 3 (STAT3) activation by recruiting histone deacetylase 1 (HDAC1) to miR-370-3p promoter. The STAT3 and HDAC antagonists inhibited liver cancer cell migration and invasion. Patients with high miR-370-3p and low IL-8 levels had longer overall survival. In conclusion, our study elucidated a novel axis IL-8/STAT3/miR-370-3p/Twist1 and Snail relying on HDAC1 recruitment, which showed both diagnostic and therapeutic potentials of miR-370-3p in HCC metastasis. Show less
Cell experiments were implemented in this research to investigate the molecular mechanism by which H19 affected senescence of human DFs (HDFs). By conducting luciferase assay, we analyzed the relation Show more
Cell experiments were implemented in this research to investigate the molecular mechanism by which H19 affected senescence of human DFs (HDFs). By conducting luciferase assay, we analyzed the relations between H19 and miR-296-5p and between miR-296-5pand IGF2. Ectopic expression and silencing experiments were performed to assess their effects on the growth and senescence of HDFs. β-Gal, DUSP6, p21, and p16 were utilized as markers for evaluating cell senescence. H19 and IGF2 were downregulated but miR-296-5p was upregulated in the aging HDFs. Mechanistic analysis showed that H19 bound to miR-296-5p to upregulate the miR-296-5p target, IGF2, and that activating the PI3K/mTOR pathway and upregulating AQP3 expression in HDFs. H19 upregulation or miR-296-5p downregulation facilitated the viability but restrained the senescence of HDFs, accompanied with reductions in the expression of cell senescence markers. Knockdown of IGF2 expression counteracted the effects induced by miR-296-5p inhibition, while inhibited PI3K/mTOR pathway reversed the impacts of IGF2 overexpression on HDFs. In summary, our data provided a novel insight into the anti-senescent mechanism of H19 in HDFs, offers a better understanding of cellular mechanisms during the process of aging. Show less
Long-term use of olanzapine, an antipsychotic drug, induces hypertriglyceridemia, resulting in a higher risk of cardiovascular disease. However, the effects and underlying mechanisms of short-term use Show more
Long-term use of olanzapine, an antipsychotic drug, induces hypertriglyceridemia, resulting in a higher risk of cardiovascular disease. However, the effects and underlying mechanisms of short-term use of olanzapine on circulating triglyceride levels remain poorly understood. Here, the role of apolipoprotein A5 (apoA5), a regulator of triglyceride metabolism, was investigated in olanzapine-induced hypertriglyceridemia. Our multi-center clinical study recruited 36 schizophrenia patients who received short-term (8 weeks) of olanzapine. Besides, female C57BL/6J mice were treated with olanzapine (3 mg/kg/day versus 6 mg/kg/day) for 6 weeks. We demonstrated that short-term use of olanzapine increased plasma triglyceride and decreased plasma apoA5 levels in the patients and mice, with a negative correlation between the two factors. However, no obesity was observed in the patients and mice. Interestingly, olanzapine increased hepatic apoA5 protein in the mice, without significant changes in hepatic Show less
Betaine is more efficient than choline and methionine methyl donors, as it can increase nitrogen storage, promote fat mobilisation and fatty acid oxidation and change body fat content and distribution Show more
Betaine is more efficient than choline and methionine methyl donors, as it can increase nitrogen storage, promote fat mobilisation and fatty acid oxidation and change body fat content and distribution. Lipid is absorbed primarily in the small intestine after consumption, which is also the basis of lipid metabolism. This study was conducted to establish a mouse model of obesity in Kunming mice of the same age and similar body weight, and to assess the effect of betaine on the intestinal protein expression profile of mice using a proteomic approach. Analysis showed that betaine supplementation reversed the reduction in expression of proteins related to lipid metabolism and transport in the intestine of mice induced by a high-fat diet (HFD). For example, the addition of betaine resulted in a significant upregulation of microsomal triglyceride transfer protein (Mttp), apolipoprotein A-IV (Apoa4), fatty-acid-binding protein 1 (Fabp1) and fatty-acid-binding protein 2 (Fabp2) expression compared to the HFD group (p < 0.05), which exhibited accelerated lipid absorption and then translocation from the intestine into the body’s circulation, in addition to a significant increase in Acetyl-CoA acyltransferase (Acaa1a) protein expression, hastening lipid metabolism in the intestine (p < 0.05). Simultaneously, a significant reduction in protein expression of alpha-enolase 1 (Eno1) as the key enzyme for gluconeogenesis in mice in the betaine-supplemented group resulted in a reduction in lipid synthesis in the intestine (p < 0.05). These findings provide useful information for understanding the changes in the protein profile of the small intestine in response to betaine supplementation and the potential physiological regulation of diets’ nutrient absorption. Show less
Several studies have found that pathological imbalance of alterative splicing (AS) events is associated with cancer susceptibility. carcinogenicity. Nevertheless, the relationship between heritable va Show more
Several studies have found that pathological imbalance of alterative splicing (AS) events is associated with cancer susceptibility. carcinogenicity. Nevertheless, the relationship between heritable variation in AS events and carcinogenicity has not been extensively explored. Here, we downloaded AS event signatures, transcriptome profiles, and matched clinical information from The Cancer Genome Atlas (TCGA) database, identified the prognostic AS-related events Show less
The Apolipoprotein A5 (APOA5) rs662799 was significantly associated with blood lipid level at genome-wide significance level. Whether dynamic changes of adiposity influence the effect of lipid loci on Show more
The Apolipoprotein A5 (APOA5) rs662799 was significantly associated with blood lipid level at genome-wide significance level. Whether dynamic changes of adiposity influence the effect of lipid loci on long-term blood lipid profile remains unclear. We assessed interactions of 5-year body mass index (BMI) change and rs662799 genotypes with risk of incident dyslipidemia and longitudinal changes in serum lipids in a prospective cohort. We included 4329 non-dyslipidemia participants aged ≥ 40 years at baseline from a well-defined community-based cohort and followed up for an average of 5 years. BMI and blood lipids were measured at baseline and follow-up. The association of each rs662799 A-allele with risk of incident dyslipidemia was stronger along with the increase in BMI change level, with the odds ratios (OR) increasing from 1.03 in the lowest tertile of BMI change (< 0.02 kg/m BMI changes significantly modulate rs662799 genetic contribution to dyslipidemia and long-term lipid profile, which provide new evidence for personalized clinical management of lipids according to individual genetic background. Show less
Developing wearable flexible biosensors with excellent electrical conductivity and outstanding flexibility simultaneously for disease diagnosis and health monitoring is a current hot topic in the fiel Show more
Developing wearable flexible biosensors with excellent electrical conductivity and outstanding flexibility simultaneously for disease diagnosis and health monitoring is a current hot topic in the field of sensor research. In this study, nitrogen-doped graphene (N-Gr) and gold nanoparticles (AuNPs) were successively deposited onto ITO-PET flexible conductive films by chemical deposition, and then a flexible electrochemical immunosensor with high sensitivity and selectivity was constructed for detecting depression markers by exploiting the high affinity between AuNPs and the sulfhydryl groups of depression marker (DM) antibody. Due to the composite of N-Gr, AuNPs and ITO-PET, the prepared flexible sensor can maintain a relatively stable electrical signal response regardless of the deformation such as spiral, rolling, and bending, without shedding or fracture of the N-Gr and AuNPs, and can also significantly amplify the electrochemical response signal of the immunosensor. Under optimized experimental conditions, the fabricated immunosensor showed good linearity over a wide range of 0.023-300.00 ng/mL with a low detection limit of 0.010 ng/mL (3σ, n = 5), when it was used for the determination of depression markers-human Apo-A4 in 100% whole serum samples. The flexibility of the constructed immunosensor and the stability and sensitivity of biomolecular analysis are expected to be further made into implantable depression marker in-situ monitoring probe with the help of micro-machining technology, which will develop a promising method for objective, efficient and accurate clinical diagnosis of depression. Show less
Senile osteoporosis is one of the major health problems in an aging society. Decreased bone formation due to osteoblast dysfunction may be one of the causes of aging-related bone loss. With increasing Show more
Senile osteoporosis is one of the major health problems in an aging society. Decreased bone formation due to osteoblast dysfunction may be one of the causes of aging-related bone loss. With increasing evidence suggesting that multiple microRNAs (miRNAs) play important roles in osteoblast function, the relationship between miRNAs and senile osteoporosis has become a popular research topic. Previously, we confirmed that mechanoresponsive miR-138-5p negatively regulated bone anabolic action. In this study, the miR-138-5p level was found to be negatively correlated with BMD and osteogenic markers in bone specimens of senile osteoporotic patients by bioinformatic analysis and experimental verification. Furthermore, high miR-138-5p levels aggravated the decrease of aged osteoblast differentiation Show less
Koolen-de Vries syndrome (KdVS) is a rare disorder caused by haploinsufficiency of KAT8 regulatory NSL complex subunit 1 (KANSL1), which is characterized by intellectual disability, heart failure, hyp Show more
Koolen-de Vries syndrome (KdVS) is a rare disorder caused by haploinsufficiency of KAT8 regulatory NSL complex subunit 1 (KANSL1), which is characterized by intellectual disability, heart failure, hypotonia, and congenital malformations. To date, no effective treatment has been found for KdVS, largely due to its unknown pathogenesis. Using siRNA screening, we identified KANSL1 as an essential gene for autophagy. Mechanistic study shows that KANSL1 modulates autophagosome-lysosome fusion for cargo degradation via transcriptional regulation of autophagosomal gene, STX17. Kansl1 Show less
Nonalcoholic fatty liver disease (NAFLD), one of the risk factors for hepatitis, cirrhosis, and even hepatic carcinoma, has been a global public health problem. The polyphenol compound theaflavin-3,3' Show more
Nonalcoholic fatty liver disease (NAFLD), one of the risk factors for hepatitis, cirrhosis, and even hepatic carcinoma, has been a global public health problem. The polyphenol compound theaflavin-3,3'-digallate (TF3), mainly extracted from black tea, has been reported to produce an effect on hypoglycemic and antilipid deposition Show less
Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. Lipid levels are regarded as a major risk factor for CAD, and epigenetic mechanisms might be Show more
Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. Lipid levels are regarded as a major risk factor for CAD, and epigenetic mechanisms might be involved in the regulation of CAD development. This study was designed to investigate the association between the DNA methylation status of 8 lipid metabolism-related genes and the risk of CAD in the Chinese Han population. A total of 260 individuals were sampled in this study, including 120 CAD cases and 140 normal healthy controls. DNA methylation status was tested via targeted bisulfite sequencing. The results indicated a significant association between hypomethylation of the APOC3, CETP and APOC1 gene promoters and the risk of CAD. Individuals with higher methylation levels of the APOA5 and LIPC gene promoters had increased risks for CAD. In addition, ANGPTL4 methylation level was significantly associated with CAD in males but not females. There were no significant differences in the methylation levels of the APOB and PCSK9 gene promoters between CAD patients and controls. The methylation status of the APOC3, APOA5, LIPC, CETP and APOC1 gene promoters may be associated with the development of CAD. Show less
Pleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TP Show more
Pleural effusion is a common clinical condition caused by several respiratory diseases, including tuberculosis and malignancy. However, rapid and accurate diagnoses of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remain challenging. Although monocytes have been confirmed as an important immune cell in tuberculosis and malignancy, little is known about the role of monocytes subpopulations in the diagnosis of pleural effusion. Pleural effusion samples and peripheral blood samples were collected from 40 TPE patients, 40 MPE patients, and 24 transudate pleural effusion patients, respectively. Chemokines (CCL2, CCL7, and CX3CL1) and cytokines (IL-1β, IL-17, IL-27, and IFN-γ) were measured by ELISA. The monocytes phenotypes were analyzed by flow cytometry. The chemokines receptors (CCR2 and CX3CR1) and cytokines above in different monocytes subsets were analyzed by real-time PCR. Receiver operating characteristic curve analysis was performed for displaying differentiating power of intermediate and nonclassical subsets between tuberculous and malignant pleural effusions. CCL7 and CX3CL1 levels in TPE were significantly elevated in TPE compared with MPE and transudate pleural effusion. Cytokines, such as IL-1β, IL-17, IL-27, and IFN-γ, in TPE were much higher than in other pleural effusions. Moreover, CD14 CD14 and CD16 markers on monocytes could be potentially used as novel diagnostic markers for diagnosing TPE and MPE. Show less
Danlou tablet (DLT), the traditional Chinese medicine has been commonly used for dyslipidemia, atherosclerosis, and coronary heart disease. Whether it was effective against vascular injury caused by C Show more
Danlou tablet (DLT), the traditional Chinese medicine has been commonly used for dyslipidemia, atherosclerosis, and coronary heart disease. Whether it was effective against vascular injury caused by CIH has remained unknown. The aim of the current study was to observe the effects of DLT on chronic intermittent hypoxia (CIH)-induced vascular injury via regulation of blood lipids and to explore potential mechanisms. Sixteen 12-week-old male ApoE CIH exposure increases serum lipid levels, decreases serum LPL activity, and exacerbates atherosclerosis. Both Angptl4-ab and DLT treatment reversed the changes in lipid concentration, LPL activity, and atherosclerosis caused by CIH. In the epididymal fat pad, CIH exposure decreased the expression of FIH-1 and increased the expression of HIF-1, whereas DLT treatment increased the expression of FIH-1 and LPL and inhibited the expression of HIF-1 and Angptl4. In heart tissue, the expression levels of LPL and Angptl4 were not affected by modeling or treatment. DLT improved vascular damage by improving the increase in blood lipids induced by CIH, potentially by upregulating FIH-1 and downregulating HIF-1 and Angptl4 in adipose tissue. Therefore, DLT may be a promising agent for the prevention and treatment of CIH-induced vascular injury. Show less
O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O Show more
O-linked N-acetyl-glucosamine glycosylation (O-GlcNAcylation) of intracellular proteins is a dynamic process broadly implicated in age-related disease, yet it remains uncharacterized whether and how O-GlcNAcylation contributes to the natural aging process. O-GlcNAc transferase (OGT) and the opposing enzyme O-GlcNAcase (OGA) control this nutrient-sensing protein modification in cells. Here, we show that global O-GlcNAc levels are increased in multiple tissues of aged mice. In aged liver, carbamoyl phosphate synthetase 1 (CPS1) is among the most heavily O-GlcNAcylated proteins. CPS1 O-GlcNAcylation is reversed by calorie restriction and is sensitive to genetic and pharmacological manipulations of the O-GlcNAc pathway. High glucose stimulates CPS1 O-GlcNAcylation and inhibits CPS1 activity. Liver-specific deletion of OGT potentiates CPS1 activity and renders CPS1 irresponsive to further stimulation by a prolonged fasting. Our results identify CPS1 O-GlcNAcylation as a key nutrient-sensing regulatory step in the urea cycle during aging and dietary restriction, implying a role for mitochondrial O-GlcNAcylation in nutritional regulation of longevity. Show less
Exploration of lead compounds against Parkinson's disease (PD), a neurodegenerative disease, is of great important. Dioscin, a bioactive natural product, shows various pharmacological effects. However Show more
Exploration of lead compounds against Parkinson's disease (PD), a neurodegenerative disease, is of great important. Dioscin, a bioactive natural product, shows various pharmacological effects. However, the activities and mechanisms of dioscin against PD have not been well investigated. In this study, the tests on 6-hydroxydopamine (6-OHDA)-induced PC12 cells and rats were carried out. The results showed that dioscin dramatically improved cell viability, decreased reactive oxygen species (ROS) levels, improved motor behavior and tyrosine hydroxylase(TH) levels and restored the levels of glutathione (GSH) and malondialdehyde (MDA) in rats. Mechanism investigation showed that dioscin not only markedly increased the expression level of dual- specificity phosphatase 6 (DUSP6) by 1.87-fold in cells and 2.56-fold in rats, and decreased phospho-extracellular regulated protein kinases (p-ERK) level by 2.12-fold in cells and 2.34-fold in rats, but also increased the levels of nuclear factor erythroid2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), superoxide dismutase (SOD) and decreased the levels of kelch-1ike ECH-associated protein l (Keap1) in vitro and in vivo. Furthermore, DUSP6 siRNA transfection experiment in PC12 cells validated the protective effects of dioscin against PD via regulating DUSP6 to adjust the Keap1/Nrf2 pathway. Our data supported that dioscin has protection against PD in regulating oxidative stress via DUSP6 signal, which should be considered as an efficient candidate for the treatment of PD in the future. Show less