In eukaryotic cells, both alternative splicing and alternative polyadenylation (APA) play essential roles in the gene regulation network. U1 small ribonucleoprotein particle (U1 snRNP) is a major comp Show more
In eukaryotic cells, both alternative splicing and alternative polyadenylation (APA) play essential roles in the gene regulation network. U1 small ribonucleoprotein particle (U1 snRNP) is a major component of spliceosome, and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3' end processing factors. However, here we show that both knockdown and overexpression of SNRPA, SNRPC, SNRNP70, and SNRPD2, the U1 snRNP proteins, promote the usage of proximal APA sites at the transcriptome level. SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate, which may reduce the repressive effects of PABPN1 on the proximal APA sites. Additionally, SNRNP70 can also promote the proximal APA sites by recruiting CPSF6, suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent. Consequently, these results reveal that, on the contrary to U1 snRNP complex, the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3' end processing machinery. Show less
To investigate associations of genetic and environmental factors with coronary artery disease (CAD), we collected medical reports, lifestyle details, and blood samples of 2113 individuals, and then us Show more
To investigate associations of genetic and environmental factors with coronary artery disease (CAD), we collected medical reports, lifestyle details, and blood samples of 2113 individuals, and then used the polymerase chain reaction (PCR)-ligase detection reaction (LDR) to genotype the targeted 102 SNPs. We adopted elastic net algorithm to build an association model that considered simultaneously genetic and lifestyle/clinical factors associated with CAD in Chinese Han population. In this study, we developed an all covariates-based model to explain the risk of CAD, which incorporated 8 lifestyle/clinical factors and a gene-score variable calculated from 3 significant SNPs (rs671, rs6751537 and rs11641677), attaining an area under the curve (AUC) value of 0.71. It was found that, in terms of genetic variants, the AA genotype of rs671 in the additive (adjusted odds ratio (OR) = 2.51, p = 0.008) and recessive (adjusted OR = 2.12, p = 0.021) models, the GG genotype of rs6751537 in the additive (adjusted OR = 3.36, p = 0.001) and recessive (adjusted OR = 3.47, p = 0.001) models were associated with increased risk of CAD, while GG genotype of rs11641677 in additive model (adjusted OR = 0.39, p = 0.044) was associated with decreased risk of CAD. In terms of lifestyle/clinical factors, the history of hypertension (unadjusted OR = 2.37, p < 0.001) and dyslipidemia (unadjusted OR = 1.82, p = 0.007), age (unadjusted OR = 1.07, p < 0.001) and waist circumference (unadjusted OR = 1.02, p = 0.05) would significantly increase the risk of CAD, while height (unadjusted OR = 0.97, p = 0.006) and regular intake of chicken (unadjusted OR = 0.78, p = 0.008) reduced the risk of CAD. A significantinteraction was foundbetween rs671 and dyslipidemia (the relative excess risk due to interaction (RERI) = 3.36, p = 0.05). In this study, we constructed an association model and identified a set of SNPs and lifestyle/clinical risk factors of CAD in Chinese Han population. By considering both genetic and non-genetic risk factors, the built model may provide implications for CAD pathogenesis and clues for screening tool development in Chinese Han population. 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
Memory deficits and loss are the earliest and most prominent features of Alzheimer's disease (AD). This study was aimed to clarify the mechanistic basis of an active fraction of
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
Hepatocellular carcinoma (HCC) is a malignancy with a dismal survival rate. The novel autoantibodies panel may provide new insights for the diagnosis of HCC. Biomarkers screened by two methods (bioinf Show more
Hepatocellular carcinoma (HCC) is a malignancy with a dismal survival rate. The novel autoantibodies panel may provide new insights for the diagnosis of HCC. Biomarkers screened by two methods (bioinformatics and the antigen-antibody system) were taken as candidate tumor-associated antigens (TAAs). Enzyme-linked immunosorbent assay was used to detect the corresponding autoantibodies in 888 samples of verification and validation cohorts. The verification cohort was used to verify the autoantibodies. Samples in the validation cohort were randomly divided into a train set and a test set with the ratio of 6:4. A diagnostic model was established by support vector machines within the train set. The test set further verified the model. Eleven TAAs were selected (AAGAB, C17orf75, CDC37L1, DUSP6, EID3, PDIA2, RGS20, PCNA, TAF7L, TBC1D13, and ZIC2). The titer of six autoantibodies (PCNA, AAGAB, CDC37L1, TAF7L, DUSP6, and ZIC2) had a significant difference in any of the pairwise comparisons among the HCC, liver cirrhosis, and normal control groups. The titer of these autoantibodies had an increasing tendency. Finally, an optimum diagnostic model was constructed with the six autoantibodies. The AUCs were 0.826 in the train set and 0.773 in the test set. The area under the curve (AUC) of this panel for diagnosing early HCC was 0.889. The diagnostic ability of the panel reduced with the progress of HCC. The positive rate of the panel in diagnosing alpha-fetoprotein (AFP)-negative patients was 75.6%. For early HCC, the sensitivity of the combination of AFP with the panel was 90.9% and superior to 53.2% of AFP alone. The novel immunodiagnosis panel combining AFP may be a new approach for the diagnosis of HCC, especially for early-HCC cases. Show less
Gut microbiome may influence tumor growth and cancer treatment efficacy, so it is a potential target for tumor prevention/treatment. This pilot study investigated the preventive and therapeutic effect Show more
Gut microbiome may influence tumor growth and cancer treatment efficacy, so it is a potential target for tumor prevention/treatment. This pilot study investigated the preventive and therapeutic effects of a probiotic strain, Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9), against murine mammary cancer. Thirty-six female mice were randomly divided into three groups (n = 12 per group): control (without tumor transplantation), model (tumor transplantation; no probiotic administration), and probiotic (30-day oral gavage of probiotic, started seven days before tumor transplantation). Changes in tumor size were recorded, and blood, tumor tissue, and stool samples were collected at the end of the trial for analyses. Comparing with the model group, the probiotic group had a significantly smaller tumor volume (p < 0.05), a higher fecal microbiota Shannon diversity index, with significant modifications in the gut microbiota structure (p < 0.05), characterized by more Alistipes sp.₂, Porphyromonadaceae bacterium₇, and Bacteroidales bacterium 55₉ (p < 0.05). Additionally, Probio-M9 administration elevated the serum IFN-γ, IL-9, IL-13, and IL-27 levels and several metabolites (e.g., pyridoxal, nicotinic acid, 3-hydroxybutyric acid, glutamine; p < 0.05), while reducing IL-5 (p < 0.05). These changes might be associated with the protective effect of Probio-M9 against mammary tumor growth. Thus, probiotic administration could harness host gut microbiome in anti-cancer responses. Show less
To investigate the aqueous levels of angiogenic factors in nonproliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and to ascertain their association with optical coher Show more
To investigate the aqueous levels of angiogenic factors in nonproliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and to ascertain their association with optical coherence tomography angiography (OCTA) metrics. This study enrolled 21 NPDR eyes with DME (NPDR/DME+), 17 NPDR eyes without DME (NPDR/DME-), and 16 diabetic eyes without retinopathy (DWR). Luminex bead-based multiplex array was used to measure the levels of 25 cytokines. OCTA system with a scan area of 3 × 3 mm was used to measure retinal thickness (RT), retinal volume (RV), superficial vessel density (SVD), deep vessel density (DVD), foveal avascular zone (FAZ) area, perimeter and acircularity index. The levels of ANGPTL4 were significantly different among the three groups ( The level of ANGPTL4 in aqueous humor of NPDR patients with DME was significantly increased and ANGPTL4 might predict RT, RV, and parafoveal DVD of DME in NPDR patients. 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
Rab21 is a GTPase protein that is functional in intracellular trafficking and involved in the pathologies of many diseases, such as Alzheimer's disease (AD), glioma, cancer, etc. Our previous work has Show more
Rab21 is a GTPase protein that is functional in intracellular trafficking and involved in the pathologies of many diseases, such as Alzheimer's disease (AD), glioma, cancer, etc. Our previous work has reported its interaction with the catalytic subunit of gamma-secretase, PS1, and it regulates the activity of PS1 via transferring it from the early endosome to the late endosome/lysosome. However, it is still unknown how Rab21 protein itself is regulated. This work revealed that Rab21 protein, either endogenously or exogenously, can be degraded by the ubiquitin-proteasome pathway and the autophagy-lysosome pathway. It is further observed that the ubiquitinated Rab21 is increased, but the total protein is unchanged in AD model mice. We further observed that overexpression of Rab21 leads to increased expression of a series of genes involved in the autophagy-lysosome pathway. We speculated that even though the ubiquitinated Rab21 is increased due to the impaired proteasome function in the AD model, the autophagy-lysosome pathway functions in parallel to degrade Rab21 to keep its protein level in homeostasis. In conclusion, understanding the characters of Rab21 protein itself help explore its potential as a target for therapeutic strategy in diseases. 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
Adiponectin is a potent vascular protective molecule. Recent findings have suggested adiponectin resistance during early diabetes. However, the molecular mechanisms responsible remain unidentified. He Show more
Adiponectin is a potent vascular protective molecule. Recent findings have suggested adiponectin resistance during early diabetes. However, the molecular mechanisms responsible remain unidentified. Here, we took an unbiased approach to identify whether hyperlipidemic plasma molecules exist that bind and inhibit adiponectin function, contributing to adiponectin resistance and diabetic vascular injury. Adult rats were randomly assigned to receive either a normal or a high-fat diet for 8 weeks. Plasma was co-immunoprecipitated with anti-APN antibody and analyzed by mass spectrometry. The APN binding molecules and their effect upon APN biological activity were determined. As expected, the high-fat-diet increased plasma triglyceride, total cholesterol, and low-density lipoprotein. Importantly, the circulating APN level was significantly increased at this time point. Mass spectrometry identified 18 proteins with increased APN binding in hyperlipidemic plasma, among which four proteins critical in lipid metabolism, including apolipoprotein A1 (APOA1), APOA4, APOC1, and paraoxonase 1, were further investigated. Incubating recombinant APN with APOA1 markedly (P < 0.01), and incubating with APOC1 significantly (P < 0.05), inhibited APN activity as evidenced by the reduced AMPK activation in HUVECs. APOA4 and paraoxonase 1 incubation had no effect upon APN activity. Finally, plasma APOA1 was significantly increased (P < 0.05) in hyperlipidemic plasma compared with the control plasma. It was demonstrated for the first time that increased APOA1 and APOC1 in hyperlipidemic plasma binds and inhibits APN activity. This result not only identifies a novel molecular mechanism responsible for adiponectin resistance during early stage diabetes, but also provides additional new insight into the diverse/controversial (protective and harmful) functions of high-density lipoprotein. Show less
Carbon emission trading is not only a market-based instrument but also one of the government's macro-policies, which is extremely crucial to fulfilling both carbon peak attainment and carbon neutralit Show more
Carbon emission trading is not only a market-based instrument but also one of the government's macro-policies, which is extremely crucial to fulfilling both carbon peak attainment and carbon neutrality goals. For this purpose, this paper adopts a 30-region dataset for the period from 2008 to 2020 in China and employs the difference-in-difference (DID) method to quantify the effect of the carbon emission trading pilot policy (CETP) on carbon emissions on the basis of introducing industrial structure upgrading and green technology innovation as moderating variables. The results show that (1) CETP has a statistically significant dampening effect on carbon emissions, while its carbon emission reduction effect follows a significant strengthening trend as the policy year of CETP implementation is delayed. (2) CETP has a significant carbon emission reduction effect. However, its effect demonstrates a gradual decrease from the eastern to the central and finally to the western regions. (3) CETP can inhibit carbon emissions depending on industrial structure upgrading to a certain extent, and this dependence is significant in the national and eastern regions but not in the central and western regions. (4) CETP's carbon emission reduction effect is dependent on green technology innovation, which is only revealed in the western region and performs as a dampening effect in the national, eastern, and central regions, but not significantly. Show less
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. For patients with GBM, the median overall survival (OS) is 14.6 months and the 5-year survival rate is 7.2%. It is impera Show more
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. For patients with GBM, the median overall survival (OS) is 14.6 months and the 5-year survival rate is 7.2%. It is imperative to develop a reliable model to predict the survival probability in new GBM patients. To date, most prognostic models for predicting survival in GBM were constructed based on bulk RNA-seq dataset, which failed to accurately reflect the difference between tumor cores and peripheral regions, and thus show low predictive capability. An effective prognostic model is desperately needed in clinical practice. We studied single-cell RNA-seq dataset and The Cancer Genome Atlas-glioblastoma multiforme (TCGA-GBM) dataset to identify differentially expressed genes (DEGs) that impact the OS of GBM patients. We then applied the least absolute shrinkage and selection operator (LASSO) Cox penalized regression analysis to determine the optimal genes to be included in our risk score prognostic model. Then, we used another dataset to test the accuracy of our risk score prognostic model. We identified 2128 DEGs from the single-cell RNA-seq dataset and 6461 DEGs from the bulk RNA-seq dataset. In addition, 896 DEGs associated with the OS of GBM patients were obtained. Five of these genes (LITAF, MTHFD2, NRXN3, OSMR, and RUFY2) were selected to generate a risk score prognostic model. Using training and validation datasets, we found that patients in the low-risk group showed better OS than those in the high-risk group. We validated our risk score model with the training and validating datasets and demonstrated that it can effectively predict the OS of GBM patients. We constructed a novel prognostic model to predict survival in GBM patients by integrating a scRNA-seq dataset and a bulk RNA-seq dataset. Our findings may advance the development of new therapeutic targets and improve clinical outcomes for GBM patients. Show less
This study aims to understand the molecular basis of manganese superoxide dismutase (MnSOD) impacts on breast cancer cell growth. Modulation of the level of MnSOD by genetic engineering led significan Show more
This study aims to understand the molecular basis of manganese superoxide dismutase (MnSOD) impacts on breast cancer cell growth. Modulation of the level of MnSOD by genetic engineering led significant changes in the expression of angiopoietin-like protein 4 (ANGPTL4) and activity of peroxisome proliferator-activated receptor α (PPARα) in MCF7 cells. PPARα agonist increased ANGPTL4 expression inhibited by MnSOD. Proliferation of MCF7 cells was inhibited by MnSOD, however, ANGPTL4 transduction into MCF7 cells with MnSOD overexpression significantly stimulated cell proliferation. MnSOD induced G0/G1 cell cycle arrest, nevertheless, ANGPTL4 transduction significantly reduced the percentage of cells in G0/G1 phase overexpressing MnSOD. In conclusion, MnSOD suppressed the expression of ANGPTL4 in breast cancer cells via the PPARα signaling pathway, and ANGPTL4 was involved in MnSOD-mediated proliferation inhibition and cell cycle arrest. Show less
Epigenetic alteration is a pivotal factor in tumor metastasis. PHD finger protein 13 (PHF13) is a recently identified epigenetic reader of H3K4me2/3 that functions as a transcriptional co-regulator. I Show more
Epigenetic alteration is a pivotal factor in tumor metastasis. PHD finger protein 13 (PHF13) is a recently identified epigenetic reader of H3K4me2/3 that functions as a transcriptional co-regulator. In this study, we demonstrate that PHF13 is required for pancreatic-cancer-cell growth and metastasis. Integrative analysis of transcriptome and epigenetic profiles provide further mechanistic insights into the epigenetic regulation of genes associated with cell metastasis during the epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor β (TGFβ). Our data suggest PHF13 depletion impairs activation of TGFβ stimulated genes and correlates with a loss of active epigenetic marks (H3K4me3 and H3K27ac) at these genomic regions. These observations argue for a dependency of TGFβ target activation on PHF13. Furthermore, PHF13-dependent chromatin regions are enriched in broad H3K4me3 domains and super-enhancers, which control genes critical to cancer-cell migration and invasion, such as SNAI1 and SOX9. Overall, our data indicate a functional and mechanistic correlation between PHF13 and EMT. Show less
An optimal lipid droplet (LD) content is essential for successful mammalian embryonic development. Salidroside (SAL) is a traditional Chinese medicine and one of the important active components of the Show more
An optimal lipid droplet (LD) content is essential for successful mammalian embryonic development. Salidroside (SAL) is a traditional Chinese medicine and one of the important active components of the Rhodiola plant. SAL possesses antioxidative, anti-aging, and cardiovascular properties. Here, we studied the effects of SAL on in vitro maturation (IVM) of porcine oocytes and the subsequent embryonic development after parthenogenetic activation (PA). We found that 100 μM of SAL had no effect on the extrusion rate of the first polar body of porcine oocytes but significantly improved the subsequent blastocyst formation rate and embryo quality. Our study further revealed that SAL treatment altered the morphology, increased the lipid content in oocytes, increased mitochondrial number. Further analysis revealed that SAL upregulated the expression of genes related to lipid metabolism (FASN, FADS1, HSL, and CPT1a) and the mitochondria function-related genes (PGC-1α). These results suggest that SAL supplementation enhances oocyte maturation and subsequent embryonic development by promoting lipid metabolism, providing the necessary energy for the aforementioned processes. Show less
Fatty acid composition contributes greatly to the nutritional value of meat, and breeds/strains are important factors affecting the composition of fatty acid. Recently, few studies have focused on the Show more
Fatty acid composition contributes greatly to the nutritional value of meat, and breeds/strains are important factors affecting the composition of fatty acid. Recently, few studies have focused on the fatty acid composition in breast muscle of different duck breeds. Therefore, the objective of the present study was to compare the fatty acid composition and lipid metabolism-related genes expression in breast muscle of Jianchang duck (J), Cherry Verry duck (CV) and 3 crossbred strains (BH1, BH2 and MC♂ × (BGF2♂ × GF2♀)♀ (MBG)). Our results showed that the breast muscle of J had the highest contents of C22:1(n-9) but the lowest ratios of Ʃ-omega 6 (Ʃn-6)/Ʃ-omega 3 (Ʃn-3), Ʃ-mono-unsaturated fatty acid (ƩMUFA)/Ʃ-saturated fatty acid (ƩSFA) and Ʃ-polyunsaturated fatty acid (ƩPUFA)/ƩSFA. The ƩPUFA/ƩSFA ratio was higher in breast muscle of MBG than in that of BH2 and CV, and the contents of C22:1(n-9), ƩMUFA and ƩPUFA were higher in BH1 than in BH2 and CV. Furthermore, the mRNA levels of SCD1, FADS2, ELOVL2, and ELOVL5 were significantly higher in MBG (P < 0.05), while those of FASD1 and ACACA were significantly higher in BH1 than in BH2 and CV (P < 0.05). Principal component analysis showed that fatty acids variation exhibited extensive positive loading on principal components (PCs). Correlation analysis showed that PC1 and PC3 of BH1, as well as PC1 of MBG were correlated with the mRNA levels of ACACA and FABP3, respectively. Thus, it could be concluded that the breast muscles of MBG and BH1 have better fatty acid composition, which was closely related to the increased expression levels of SCD1, FADS2, ELOVL2, and ELOVL5 genes in MBG but FADS1 and ACACA in BH1. Moreover, these results also showed that crossbreeding could optimize the composition of fatty acid in breast muscle of ducks. Show less
Mounting evidence has linked both obesity and metabolic disorders with dysbiosis of the gut microbiota. Dietary inulin is conducive to modulating this dysbiosis, and represents a potential means to im Show more
Mounting evidence has linked both obesity and metabolic disorders with dysbiosis of the gut microbiota. Dietary inulin is conducive to modulating this dysbiosis, and represents a potential means to improve disorders of glucose and lipid metabolism. However, the mechanisms underlying these improvements are largely unclear. Obese ob/ob mice were fed a standard chow, a low fiber diet (LFD) or a high fiber diet (HFD) for 4 weeks, and the body weight, fecal short chain fatty acids (SCFAs) level, and plasma and liver lipid profiles were analyzed. Oral glucose tolerance testing, and gut microbiota sequencing were also conducted. Dietary inulin improved the dysbiosis of the gut microbiota, attenuated the decrease in phylum Bacteroidetes, repressed the increase of phylum Firmicutes, and led to an increase in the ratio of Firmicutes/Bacteroidetes. At the family level, inulin promoted the expansion of SCFAs-producing Ruminococcaceae and Lachnospiraceae bacteria, which increased the fecal SCFAs concentrations. At the genus level, inulin increased the levels of Bacteroides and Bifidobacteria. Furthermore, our results revealed that there was enhanced expression of angiopoietin-like protein 4 (ANGPTL4), which might be induced by the higher production of SCFAs, and this may underlie the improvements in the disorders of glucose and lipid metabolism seen in mice with added dietary inulin. In conclusion, inulin may ameliorate metabolic disorders by remodeling the gut microbiota and increasing the production of SCFAs, which might be mediated by the ANGPTL4-related signaling pathway. Interventions targeting the gut microbiota warrant further investigation as a novel therapy for metabolic diseases. PRACTICAL APPLICATIONS: Mounting evidence has linked both obesity and metabolic disorders with dysbiosis of the gut microbiota. Dietary inulin is conducive to modulating this dysbiosis, and represents a potential means to improve disorders of glucose and lipid metabolism. However, the mechanisms underlying these improvements are largely unclear. In the present study, we investigated the effects of dietary fiber (inulin) on metabolic homeostasis using ob/ob mice. The results of our study demonstrate that inulin-induced remodeling of the gut microbiota resulted in increased production of short chain fatty acids (SCFAs), leading to the enhanced expression of angiopoietin-like protein 4 (ANGPTL4), which improved the glucose and lipid metabolism. Our results suggest that the gut microbiota, SCFAs and ANGPTL4 pathway at least partially mediate the beneficial effects of inulin on metabolic disorders in ob/ob mice. Show less
The Chromobox (CBX) family members were involved in a variety of physiological and oncological processes through the regulation of the epigenetic modification of chromatin. However, the comprehensive Show more
The Chromobox (CBX) family members were involved in a variety of physiological and oncological processes through the regulation of the epigenetic modification of chromatin. However, the comprehensive analysis of the CBX family in head and neck squamous cell carcinoma (HNSC) is lacking. In this work, we used multiple online databases and tools to investigate the roles of CBX family in aspects of gene expression, prognostic evaluation, genetic alteration, immune micro-environment of tumor, and status of methylation. The mRNA expression levels of CBX1, CBX3, and CBX5 were aberrantly increased in patients with HNSC, while CBX7 was aberrantly decreased. Higher expression of CBX7 was significantly associated with longer OS. Within the 5-11% of genetic alteration rate of CBXs, CBX3 ranked the highest and CBX5/7 ranked the lowest. SPRR1B, S100A7, CASP14, CDSN, LCE3D were the top 5 neighbor genes with the strongest association with CBXs in HNSC patients. Signaling pathways such as epidermal cell differentiation, cornification, and peptide cross-linking were demonstrated to have a strong association with CBX genes. The profiles of immune cell infiltration had high similarity for the group of HNSC patients stratified by expression of CBXs. The methylation levels of CBX1 and CBX5 significantly decreased, while that of CBX7 significantly increased in HNSC samples when compared with normal tissue. In conclusion, the CBX family showed its valuation for further investigation in HNSC. Our research highlighted that CBX7 had the potential to be a novel diagnostic and prognostic biomarker for patients with HNSC. Show less
IL-17D is a new member of the IL-17 family. Currently, it is believed that IL-17D can directly act on immune cells or may indirectly modulate immune responses by regulating cytokine expression. Herein Show more
IL-17D is a new member of the IL-17 family. Currently, it is believed that IL-17D can directly act on immune cells or may indirectly modulate immune responses by regulating cytokine expression. Herein, we hypothesized that IL-17D regulates the expression of chemokines in intestinal epithelial cells, in turn modulating the immune response within intestinal mucosa under hyperoxia. To explore this notion, newborn rats were divided into a hyperoxia group (85 % O Show less
Idiopathic pulmonary fibrosis (IPF) is characterized by lung scarring and has no effective treatment. Fibroblast-to-myofibroblast differentiation and myofibroblast proliferation and migration are majo Show more
Idiopathic pulmonary fibrosis (IPF) is characterized by lung scarring and has no effective treatment. Fibroblast-to-myofibroblast differentiation and myofibroblast proliferation and migration are major clinical manifestations of this disease; hence, blocking these processes is a practical treatment strategy. Here, highly upregulated Show less
Single nucleotide polymorphisms that affect RNA modification (RNAm-SNPs) may have functional roles in coronary artery disease (CAD). The aim of this study was to identify RNAm-SNPs in CAD susceptibili Show more
Single nucleotide polymorphisms that affect RNA modification (RNAm-SNPs) may have functional roles in coronary artery disease (CAD). The aim of this study was to identify RNAm-SNPs in CAD susceptibility loci and highlight potential risk factors. CAD-associated RNAm-SNPs were identified in the CARDIoGRAMplusC4D and UK Biobank genome-wide association studies. Gene expression and circulating protein levels affected by the RNAm-SNPs were identified by QTL analyses. Cell experiments and Mendelian randomization (MR) methods were applied to test whether the gene expression levels were associated with CAD. We identified 81 RNAm-SNPs that were associated with CAD or acute myocardial infarction (AMI), including m The present study identified RNAm-SNPs in CAD susceptibility genes, gene expression and circulating proteins as risk factors for CAD and suggested that RNA modification may play a role in the pathogenesis of CAD. Show less
Alzheimer's disease (AD) causes progressive decline of memory and cognitive deficits. Because of its complicated pathogenesis, the prevention and therapy of AD remain an enormous challenge. It has bee Show more
Alzheimer's disease (AD) causes progressive decline of memory and cognitive deficits. Because of its complicated pathogenesis, the prevention and therapy of AD remain an enormous challenge. It has been reported that catalpol possessed neuroprotective effects against AD. However, the involved mechanism still needs to be intensively studied. Therefore, the effects of catalpol on N2a/APP695swe cells and APP/PS1 mice were identified in the current study. Catalpol could improve cytotoxicity according to CCK-8 assay and ameliorate cellular morphological changes in N2a/APP695swe cells. Neuronal structural damage in the hippocampal CA1 region of APP/PS1 AD mice was improved according to HE staining and immunohistochemistry of NeuN. Meanwhile, catalpol administration ameliorated cognitive deficits confirmed by behavior performance of APP/PS1 mice. Hoechst 33,342 staining and Annexin V-FITC/PI double staining demonstrated that catalpol could reduce apoptosis in N2a/APP695swe cells. Likewise, TUNEL staining also manifested that catalpol significantly reduced apoptosis in hippocampal CA1 region of APP/PS1 mice. Catalpol administration also could improve mitochondrial functions indicated by the ameliorative mitochondrial morphology, the decreased ROS generation, and the increased MMP in N2a/APP695swe cells. Subsequently, catalpol restrained oligomerization of Aβ Show less
Arctigenin (Arc) is a phenylpropanoid dibenzylbutyrolactone lignan in Arctium lappa L, which has been widely applied as a traditional Chinese herbal medicine for treating inflammation. In the present Show more
Arctigenin (Arc) is a phenylpropanoid dibenzylbutyrolactone lignan in Arctium lappa L, which has been widely applied as a traditional Chinese herbal medicine for treating inflammation. In the present study, we explored the neuroprotective effect and the potential mechanisms of arctigenin against LPS-evoked neuroinflammation, neurodegeneration, and memory impairments in the mice hippocampus. Daily administration of arctigenin (50 mg/kg per day, i.g.) for 28 days revealed noticeable improvements in spatial learning and memory deficits after exposure to LPS treatment. Arctigenin prevented LPS-induced neuronal/synaptic injury and inhibited the increases in Abeta (Aβ) generation and the levels of amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1). Moreover, arctigenin treatment also suppressed glial activation and reduced the production of proinflammatory cytokines. In LPS-treated BV-2 microglial cells and mice, activation of the TLR4 mediated NF-κB signaling pathway was significantly suppressed by arctigenin administration. Mechanistically, arctigenin reduced the LPS-induced interaction of adiponectin receptor 1 (AdipoR1) with TLR4 and its coreceptor CD14 and inhibited the TLR4-mediated downstream inflammatory response. The outcomes of the current study indicate that arctigenin mitigates LPS-induced apoptotic neurodegeneration, amyloidogenesis and neuroinflammation as well as cognitive impairments, and suggest that arctigenin may be a potential therapeutic candidate for neuroinflammation/neurodegeneration-related diseases. Show less
Post-translational modifications (PTMs) are a covalent processing process of proteins after translation. Proteins are capable of playing their roles only after being modified, so as to maintain the no Show more
Post-translational modifications (PTMs) are a covalent processing process of proteins after translation. Proteins are capable of playing their roles only after being modified, so as to maintain the normal physiological function of cells. As a key modification of protein post-translational modification, ubiquitination is an essential element, which forms an enzyme-linked reaction through ubiquitin-activating enzyme, ubiquitin binding enzyme, and ubiquitin ligase, aiming to regulate the expression level and function of cellular proteins. Nedd4 family is the largest group of ubiquitin ligases, including 9 members, such as Nedd4-1, Nedd4L (Nedd4-2), WWP1, WWP2, ITCH, etc. They could bind to substrate proteins through their WW domain and play a dominant role in the ubiquitination process, and then participate in various pathophysiological processes of cardiovascular diseases (such as hypertension, myocardial hypertrophy, heart failure, etc.). At present, the role of Nedd4L in the cardiovascular field is not fully understood. This review aims to summarize the progress and mechanism of Nedd4L in cardiovascular diseases, and provide potential perspective for the clinical treatment or prevention of related cardiovascular diseases by targeting Nedd4L. Show less