Osteosarcoma (OS) is a disease with high mortality in children and adolescents, and metastasis is one of its important clinical features. However, the molecular mechanism of OS occurrence is not compl Show more
Osteosarcoma (OS) is a disease with high mortality in children and adolescents, and metastasis is one of its important clinical features. However, the molecular mechanism of OS occurrence is not completely clear. Thus, we screened potential biomarkers of OS and analyze their prognostic value. The Cancer Genome Atlas (TCGA) datasets were used to analyze the differential lncRNAs in patients with OS of different immune score and the lncRNAs expressed by immune cells. Cox regression was used to develop the prognosis prediction model and specify the prognosis outcomes. Risk-proportional regression model was constructed, and the samples were divided into high and low groups based on the risk scores for the survival analysis. The areas under the receiver operating characteristic (ROC) curve were calculated and the risk-score model was verified. Finally, using 4 gene sets (comprising chemokines, immune checkpoint blockades, immune activity-related genes, and immune cells), and 4 analysis tools (CIBERSORT, TIMER, XCELL and MCP) to evaluated tumor immune infiltration. Twenty-nine long non-coding ribonucleic acids (lncRNAs) were obtained from the intersection of the screened lncRNAs. Caspase recruitment domain-containing protein 8-antisense RNA 1 (CARD8-AS1), lncRNA five prime to Xist (FTX), KAT8 regulatory NSL complex unit 1-antisense RNA 1 (KANSL1-AS1), Neuroplastin Intronic Transcript 1 (NPTN-IT1), oligodendrocyte maturation-associated long intervening non-coding RNA (OLMALINC) and RPARP Antisense RNA 1 (RPARP-AS1) were found to be correlated with survival. Univariate and multivariate regression analysis showed risk score [HR (hazard ratio) 3.5, P value 0.0043; HR 3.7, P value 0.0033] and metastasis (HR 4.7, P value 6.60E-05; HR 4.8, P value 8.36E-05) were the key factors of patients with OS. The areas under curves (AUCs) of the 1-, 3-, and 5-year ROC curves of the prognostic model were 0.715, 0.729, and 0.771. The low-risk patients tended to have a high abundance of immune cells. This study showed that a risk score based on 6 lncRNAs has potential value in the prognosis of OS, and patients with low-risk scores have high immune cell infiltration and good prognosis. This study may enrich understandings of underlying mechanisms related to the occurrence and development of OS. 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
Thyroid carcinoma is the most prevalent endocrine cancer globally and the primary cause of cancer-related mortality. Epigenetic modifications are progressively being linked to metastasis. This study a Show more
Thyroid carcinoma is the most prevalent endocrine cancer globally and the primary cause of cancer-related mortality. Epigenetic modifications are progressively being linked to metastasis. This study aimed to examine whole-genome DNA methylation patterns and the gene expression profiles in thyroid cancer tissue samples using a MethylationEPIC BeadChip (850K), RNA sequencing, and a targeted bisulfite sequencing assay. The results of the Illumina Infinium human methylation kit (850K) analyses identified differentially methylated CpG locations (DMPs) and differentially methylated CpG regions (DMRs) encompassing nearly the entire genome with high resolution and depth. Gene ontology and KEGG pathway analyses revealed that the genes associated with DMRs belonged to various domain-specific ontologies, including cell adhesion, molecule binding, and proliferation. The RNA-Seq study found 1627 differentially expressed genes, 1174 of which that were up-regulated and 453 of which that were down-regulated. The targeted bisulfite sequencing assay revealed that CHST2, DPP4, DUSP6, ITGA2, SLC1A5, TIAM1, TNIK, and ABTB2 methylation levels were dramatically lowered in thyroid cancer patients when compared to the controls, but GALNTL6, HTR7, SPOCD1, and GRM5 methylation levels were significantly raised. Our study revealed that the whole-genome DNA methylation patterns and gene expression profiles in thyroid cancer shed new light on the tumorigenesis of thyroid cancer. Show less
Conjugated linoleic acid (CLA) can prevent fatty acid accumulation induced by a high-fructose diet and improve lipid metabolism disorders in patients. We aimed to investigate the effect of CLA on obes Show more
Conjugated linoleic acid (CLA) can prevent fatty acid accumulation induced by a high-fructose diet and improve lipid metabolism disorders in patients. We aimed to investigate the effect of CLA on obesity and lipid metabolism and its possible mechanism. Eight-month-old male BKS.Cg-Dock7 CLA treatment notably reduced the dietary and water intake of db/db mice, effectively reduced body weight, and decreased serum TG and TC levels (p < 0.05). Increased expression of PPARα (p < 0.05) and decreased expression of CD36 (p < 0.001) were observed in the liver of mice that were fed CLA. CLA increased PPARα expression (p < 0.001) and decreased PPARγ (p < 0.001) and CD36 expression (p < 0.01) in HepG2 cells. Our results showed that CLA can improve lipid metabolism in obese mice through upregulation of PPARα expression and downregulation of CD36 expression. Show less
Common genetic factors likely contribute to multiple psychiatric diseases including mood and substance use disorders. Certain stable, heritable traits reflecting temperament, termed externalizing or i Show more
Common genetic factors likely contribute to multiple psychiatric diseases including mood and substance use disorders. Certain stable, heritable traits reflecting temperament, termed externalizing or internalizing, play a large role in modulating vulnerability to these disorders. To model these heritable tendencies, we selectively bred rats for high and low exploration in a novel environment [bred High Responders (bHR) vs. Low Responders (bLR)]. To identify genes underlying the response to selection, we phenotyped and genotyped 538 rats from an F Show less
Lysoforte (LFT) plays a vital role in maintaining broilers' health and intestinal morphology. However, the mechanism behind the effects of LFT improving intestinal morphology and health is still uncle Show more
Lysoforte (LFT) plays a vital role in maintaining broilers' health and intestinal morphology. However, the mechanism behind the effects of LFT improving intestinal morphology and health is still unclear. Therefore, this study was implemented to explore the central genes linked to the regulatory effect of LFT. Seventy-five newly hatched Cobb 500 male broilers were randomly divided into three groups: control, LFT500, and LFT1000 groups, with 25 chicks per group. The control chicks were provided with the basal diet, and the birds in LFT500 and LFT1000 groups were offered the same basal diet with 500 g/ton and 1,000 g/ton LFT, respectively. GSE94622 dataset consisted of the control and two LFT-treated groups (LFT500 and LFT1000). Jejuna samples were obtained from Gene Expression Omnibus (GEO). Totally 106-344 DEGs were obtained by comparing LFT500 and LFT1000 vs. control and LFT1000 vs. LFT500. Gene ontology (GO) enrichment suggested that the DEGs are mainly related to the phosphatidylethanolamine biosynthetic process and neuron projection extension. KEGG analysis suggested the DEGs were enriched in AGE-RAGE, fatty acid elongation, ECM-receptor interaction (ECMRI), glycerophospholipid metabolism, focal adhesion, unsaturated fatty acids biosynthesis, and ABC transporters. Moreover, 29 genes, such as Show less
MicroRNAs (miRNAs) are one type of noncoding RNAs that interfere with mRNA translation to downregulate gene expression, which results in posttranscriptional gene silencing. Over the past two decades, Show more
MicroRNAs (miRNAs) are one type of noncoding RNAs that interfere with mRNA translation to downregulate gene expression, which results in posttranscriptional gene silencing. Over the past two decades, miRNAs have been widely reported to impact the progression of malignant tumours by interfering with cancer initiation and progression; therefore, miRNAs represent potential new diagnostic and therapeutic tools. miR-650 is a newly identified miR, and increasing studies have demonstrated that miR-650 plays critical roles in cancer progression, such as mediating the Wnt signalling pathway/AXIN1 (axis inhibition protein 1) axis in hepatocellular carcinoma. Nevertheless, associations between the expression patterns and molecular mechanisms of miR-650 in cancer have not been comprehensively described. In this article, we review the existing evidence regarding the mechanisms by which miR-650 expression is altered and their relation to cancer. Moreover, the promising clinical application of miR-650 for diagnosis and treatment is highlighted. Show less
DEAD/H-box RNA helicases make the prominent family of helicases super family-2 which take part in almost all RNA-related processes, from initiation of transcription to RNA decay pathways. In addition Show more
DEAD/H-box RNA helicases make the prominent family of helicases super family-2 which take part in almost all RNA-related processes, from initiation of transcription to RNA decay pathways. In addition to these RNA-related activities, in recent years a certain number of these helicases are reported to play important roles in anti-viral immunity through various ways. Along with RLHs, endosomal TLRs, and cytosolic DNA receptors, many RNA helicases including DDX3, DHX9, DDX6, DDX41, DHX33, DDX60, DHX36 and DDX1-DDX21-DHX36 complex act as viral nucleic acid sensors or co-sensors. These helicases mostly follow RLHs-MAVS and STING mediated signaling cascades to trigger induction of type-I interferons and pro-inflammatory cytokines. Many of them also function as downstream adaptor molecules (DDX3), segments of stress and processing bodies (DDX3 and DDX6) or negative regulators (DDX19, DDX24, DDX25, DDX39A and DDX46). On the contrary, many studies indicated that several DEAD/H-box helicases such as DDX1, DDX3, DDX6, DDX24, and DHX9 could be exploited by viruses to evade innate immune responses, suggesting that these helicases seem to have a dual function as anti-viral innate immune mediators and viral replication cofactors. In this review, we summarized the current knowledge on several representative DEAD/H-box helicases, with an emphasis on their functions in innate immunity responses, involved in their anti-viral and pro-viral roles. Show less
Developmental dysplasia of the hip (DDH) is a common anomaly leading to adult osteoarthritis. Environmental and genetic factors contribute to DDH, but its exact genetic mechanism is unclear. In this s Show more
Developmental dysplasia of the hip (DDH) is a common anomaly leading to adult osteoarthritis. Environmental and genetic factors contribute to DDH, but its exact genetic mechanism is unclear. In this study, we used whole exome sequencing to identify the causative gene of a DDH pedigree. A rare missense variant in KANSL1 (c.C767T; p.S256F) was identified as the pathogenic cause of DDH. Subsequent mutation screening showed another missense variant in 1 of 200 sporadic patients. Kansl1-mutated mice showed reduced chondrocytes in the acetabulum and a decrease in the cartilage matrix, which may be DDH phenotype-related abnormalities. Furthermore, functional studies showed that cell proliferation was delayed and Mmp13 expression was abnormally upregulated in chondrocytes differentiated from Kansl1 mutant mouse embryonic stem cells. In conclusion, our findings suggest that KANSL1 is a novel pathogenic gene for DDH. The identification of KANSL1 variants has great diagnostic value for identifying individuals with DDH. KEY MESSAGES: Developmental dysplasia of the hip (DDH) is a common anomaly causing adult osteoarthritis. Environmental and genetic factors contribute to DDH, but its exact genetic mechanism is unclear. Using high-throughput whole exome sequencing, we found a novel variant in KANSL1 that was co-inherited by all severely affected individuals diagnosed with DDH from a three-generation family. Further analysis revealed that a Kansl1 variant in mice reduced the number of chondrocytes and decreased cartilage matrix, and mouse embryonic stem differentiation assay showed cartilage defects. These findings indicate a direct association between KANSL1 and hip development, expanding the pathogenic gene spectrum in DDH and providing insight into potential new targets for diagnosing and treating hip dysplasia. Show less
The epithelial-mesenchymal transition (EMT) is an important pathological process in the occurrence of pulmonary fibrosis. Changes in histone methylation modifications of key genes play an important ro Show more
The epithelial-mesenchymal transition (EMT) is an important pathological process in the occurrence of pulmonary fibrosis. Changes in histone methylation modifications of key genes play an important role in this process. As a histone methyltransferase, the regulatory mechanism and role of SET domain bifurcated 1 (SETDB1) in pulmonary fibrosis remain unclear. We found that SETDB1 inhibited EMT and that cells attenuated the expression of SETDB1 to relieve this inhibition during transforming growth factor-β (TGF-β)-induced EMT. Silencing SETDB1 expression significantly enhanced the mesenchymal phenotype induced by TGF-β and the expression and deposition of fibronectin and significantly reduced the expression of E-cadherin. The decrease in E-cadherin expression and the induction of EMT led to increased lipid reactive oxygen species (ROS) and ferrous ions, which induced ferroptosis. Chromatin immunoprecipitation (ChIP) results showed that SETDB1 regulates the expression of Snai1 by catalyzing the histone H3 lysine 9 trimethylation (H3K9me3) of Snai1, the main transcription factor that initiates the process of EMT, and thus, indirectly regulates E-cadherin. Surprisingly, when examining the effect of overexpressed SETDB1 on EMT, we found that overexpressed SETDB1 alleviated EMT and also caused ferroptosis. We suggest that the overexpression of SETDB1 partially reverses the mesenchymal phenotype to an epithelial state, while those cells that fail to reverse are depleted by ferroptosis. In conclusion, the histone methylase SETDB1 regulates Snai1 epigenetically, driving EMT gene reprogramming and ferroptosis in response to TGF-β. However, there are unexplored links between the epigenetic reprogramming and transcriptional processes that regulate EMT in a TGF-β-dependent manner. Show less
Endothelial dysfunction is common in diabetes. Apolipoprotein (apo) A-IV functions to antagonize inflammation and oxidative stress. The present study aimed to investigate the relationship between flow Show more
Endothelial dysfunction is common in diabetes. Apolipoprotein (apo) A-IV functions to antagonize inflammation and oxidative stress. The present study aimed to investigate the relationship between flow-mediated dilation (FMD) and serum apoA-IV level in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 84 T2DM patients with chest discomfort were enrolled in this study. Their baseline characteristics and clinical parameters were documented. Endothelial function of the participants was evaluated by examining FMD of brachial artery. The severity of coronary atherosclerosis was determined by quantitative coronary angiography. Serum apoA-IV levels were measured by ELISA. These diabetic patients were dichotomized into low FMD (n = 42) and high FMD (n = 42) groups. Serum apoA-IV levels were significantly higher in high FMD group than in low FMD group (29.96 ± 13.17 vs 17.69 ± 9.16 mg/dL, P < 0.001). Moreover, the patients were also categorized into three apoA-IV tertile groups. FMD was significantly different across three apoA-IV tertiles (P < 0.001). Serum apoA-IV levels were positively correlated to FMD (r = 0.469, P < 0.001). Logistic regression analysis was performed to determine risk factors for low FMD. apoA-IV levels together with the risk factor hsCRP remained significantly to be independent determinants of low FMD (P < 0.01). Linear regression analysis was performed, and apoA-IV levels together with total-to-HDL cholesterol ratio were independently correlated with FMD (P < 0.01). Serum apoA-IV levels are associated with FMD, suggesting that apoA-IV protects endothelial function in patients with T2DM. Show less
Salivary adenoid cystic carcinoma (SACC) is a malignant tumor, which is characterized by a higher incidence of distant metastasis. The aim of this study was to investigate the role and mechanism of pr Show more
Salivary adenoid cystic carcinoma (SACC) is a malignant tumor, which is characterized by a higher incidence of distant metastasis. The aim of this study was to investigate the role and mechanism of protein kinase D1 (PKD1) in regulating the epithelial-mesenchymal transition (EMT) and promotes the metastasis in SACC. We analyzed the expression of PKD1 in 40 SACC patients and different metastatic potential cell lines. Then, we investigated whether the migration and growth of SACC were regulated by PKD1 using shRNA interference or inhibition of kinase active in vitro cell. Moreover, the mechanism by which PKD1 regulates the stability of Snail protein was determined. Finally, nude mice were used to testify the function of PKD1 via tail vein injection. PKD1 was correlated with metastasis and poor prognosis of SACC patients. PKD1 inhibition attenuated proliferation, migration, invasion, and EMT of SACC cells. Conversely, kinase active PKD1 could induce EMT and promoted cell migration in human HSG cell. Furthermore, downregulation of PKD1 regulated Snail via phosphorylation at Ser-11 on Snail protein and promotion of proteasome-mediated degradation, and reduced lung metastasis in vivo. Our results suggest that PKD1 induces the EMT and promotes the metastasis, which illustrate that PKD1 may be a potential prognostic biomarker and serve as a potential therapeutic target for SACC patients. Show less
Liver cancer is the fifth most prevalent malignant tumor, while hepatocellular carcinoma represents the most prevalent subtype worldwide. Previous studies have associated the chromobox family, critica Show more
Liver cancer is the fifth most prevalent malignant tumor, while hepatocellular carcinoma represents the most prevalent subtype worldwide. Previous studies have associated the chromobox family, critical components of epigenetic regulatory complexes, with development of many malignancies owing to their role in inhibiting differentiation and promoting proliferation of cancer cells. However, little is known regarding their function in development and progression of hepatocellular carcinoma. In the present study, we analyzed differential expression, prognostic value, immune cell infiltration, and gene pathway enrichment of chromobox family in hepatocellular carcinoma patients. Next, we performed Pearson's correlation analysis to determine the relationships between chromobox family proteins with tumor-immune infiltration. Results revealed that high expression of CBX1, CBX2, CBX3, CBX6, and CBX8 was associated with poor survival rates of hepatocellular carcinoma patients. These five factors were used to build prognostic gene models using LASSO Cox regression analysis. Results indicated that high expression of CBX2 and CBX3 proteins was significantly associated with poor prognosis for hepatocellular carcinoma patients. The resulting nomogram revealed that CBX3 and T stages were significantly correlated with prognosis of hepatocellular carcinoma patients. Notably, predictive CBX3 was strongly correlated with immune cell infiltration. Furthermore, results from functional enrichment analysis revealed that CBX3 was mainly involved in regulation of methylation of Histone H3-K27. Collectively, these findings suggest that CBX3 could be a biomarker for predicting prognosis of hepatocellular carcinoma patients. Show less
Alzheimer's disease (AD) is a neurodegenerative disorder mainly affecting old population. In this study, two Tau overexpressing cell lines (SH-SY5Y/Tau and HEK293/Tau), N2a/SweAPP cell line, and 3× Tr Show more
Alzheimer's disease (AD) is a neurodegenerative disorder mainly affecting old population. In this study, two Tau overexpressing cell lines (SH-SY5Y/Tau and HEK293/Tau), N2a/SweAPP cell line, and 3× Transgene (APPswe/PS1M146V/TauP301L) mouse primary nerve cell lines were used as AD models to study the activity and molecular mechanism of macelignan, a natural compound extracted from 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
The effects of cholamine, a raw material for synthesis of some active lipids, are unknown in poultry. To address this, 180 52-wk-old Hyline laying hens were randomly divided into 3 groups (20 replicat Show more
The effects of cholamine, a raw material for synthesis of some active lipids, are unknown in poultry. To address this, 180 52-wk-old Hyline laying hens were randomly divided into 3 groups (20 replicates per group with three hens per replicate). The control group and the treatment groups (treatment 1 and 2) were fed basal diet and the diet supplemented with 500 or 1,000 mg of cholamine per kilogram of the diet for 35 d, respectively. The data showed that supplementary cholamine significantly lowered egg production, daily feed intake, serum high-density lipoprotein cholesterol level, liver index, and the percentages of C15:0 and C20:0 in fatty acid composition of liver, significantly elevated hepatic triglyceride content, the ratio of villus height to crypt depth (P < 0.05), and the percentage of C18:2n-6 and the ratio of n-6 to n-3 polyunsaturated fatty acids in liver fat (P < 0.10). Moreover, supplementary cholamine altered the relative abundance of some intestinal bacteria with a decrease in the alpha biodiversity (P < 0.10). Additionally, transcriptome analysis on the livers of the treatment vs. the control groups identified 1,151 up- and 914 down-regulated differentially expressed genes (DEGs), and pathway analysis revealed that the suppressed Notch signaling pathway and the enhanced Oxidative phosphorylation pathway were enriched with DEGs. Particularly, fat absorption, transport and oxidative phosphorylation-related DEGs (e.g., FABP1, APOA4, and PCK1) were significantly induced, but fatty acid synthesis, and lipid package and secretion-related DEGs (e.g., FASN, SCD, and MTTP) were not. In conclusion, supplementary cholamine may lower egg production by promoting hepatic lipid deposition and reducing abundances of beneficial intestinal bacteria and microfloral biodiversity in laying hens. Show less
Lung adenocarcinoma (LUAD) is one of the main causes of cancer-related mortality, with a strong tendency to metastasize early. Transforming growth factor-β (TGF-β) signaling is a powerful regulator to Show more
Lung adenocarcinoma (LUAD) is one of the main causes of cancer-related mortality, with a strong tendency to metastasize early. Transforming growth factor-β (TGF-β) signaling is a powerful regulator to promote metastasis of LUAD. Here, we screened long non-coding RNAs (lncRNAs) responsive to TGF-β and highly expressed in LUAD cells, and finally obtained our master molecular LINC00152. We proved that the TGF-β promoted transcription of LINC00152 through the classical TGF-β/SMAD3 signaling pathway and maintained its stability through the RNA-binding protein HuR. Moreover, LINC00152 increased ZEB1, SNAI1 and SNAI2 expression via increasing the interactions of HuR and these transcription factors, ultimately promoting epithelial-mesenchymal transition of LUAD cell and enhancing LUAD metastasis in vivo. These data provided evidence that LINC00152 induced by TGF-β promotes metastasis depending HuR in lung adenocarcinoma. Designing targeting LINC00152 and HuR inhibitors may therefore be an effective therapeutic strategy for LUAD treatment. Show less
Nelumbo nucifera (N. nucifera), a kind of edible Chinese herbal, has been studied in treating hyperlipidemia. However, the hypolipidemic mechanism of N. nucifera remains unknown. Aims of this review: Show more
Nelumbo nucifera (N. nucifera), a kind of edible Chinese herbal, has been studied in treating hyperlipidemia. However, the hypolipidemic mechanism of N. nucifera remains unknown. Aims of this review: We aimed to screen the effective constituent of N. nucifera alkaloids and elucidated the potential mechanism for treating hyperlipidemia. A triple combination strategy of UHPLC-MS We comprehensively investigated the characterization of N. nucifera alkaloids by using UHPLC-LTQ-Orbitrap MS 35 compounds were identified from N. nucifera alkaloid extraction by UHPLC-LTQ-Orbitrap MS O-nornuciferine and N. nucifera alkaloids had exibited significant effects in hyperlipidemia. The candidate genes were LDLR, LPL and ANGPTL4, etc. It was most likely that they adjusted lipid metabolism by modulating expression levels of various key factors which were involved in bile secretion, glycerolipid metabolism, sphingolipid metabolism and PPAR signaling pathway, and so on. This study clarified the hypolipidemic mechanism of the alkaloids in N. nucifera, and laid a foundation for the subsequent development of clinical application and better quality of N. nucifera. Show less
Shixin Ding, Liu Yang, Lei Huang+8 more · 2022 · Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · Elsevier · added 2026-04-24
Glucocorticoid (GC) exposure can lead to deterioration of the structure and function of hippocampal neurons and is closely involved in Alzheimer's disease (AD). Amyloid-β (Aβ) overproduction is an imp Show more
Glucocorticoid (GC) exposure can lead to deterioration of the structure and function of hippocampal neurons and is closely involved in Alzheimer's disease (AD). Amyloid-β (Aβ) overproduction is an important aspect of AD pathogenesis. Our study mainly investigated the mechanism of chronic GC exposure in accelerating Aβ production in primary cultured hippocampal neurons from APP/PS1 mice. The results indicated that chronic dexamethasone (DEX, 1 μM) significantly accelerated neuronal damage and Aβ accumulation in hippocampal neurons from APP/PS1 mice. Meanwhile, DEX exposure markedly upregulated APP, NCSTN, BACE1 and p-Tau/Tau expression in hippocampal neurons from APP/PS1 mice. Our study also indicated that chronic DEX exposure significantly increased intracellular Ca Show less
Physiological modulation of melanocortin-4 receptor (MC4R) signaling by MRAP2 proteins plays an indispensable role in appetite control and energy homeostasis in the central nervous system. Great inter Show more
Physiological modulation of melanocortin-4 receptor (MC4R) signaling by MRAP2 proteins plays an indispensable role in appetite control and energy homeostasis in the central nervous system. Great interspecies differences of the interaction and regulation of melanocortin receptors by MRAP protein family have been reported in several diploid vertebrates but never been investigated in the tetrapod amphibian Xenopus laevis. Here, we performed phylogenetic and synteny-based analyses to explore the evolutionary aspects of dual copies of X. laevis MC4R (xlMC4R) and MRAP2 (xlMRAP2) proteins. Our data showed that xlMRAPs directly interacted with xlMC4Rs on the cell surface as a functional antiparallel dimeric topology and pharmacological studies suggested a homology specific regulatory pattern of the melanocortin system in X. laevis. Show less
LINGO-1 may be involved in the pathogenesis of cerebral ischemia. However, its biological function and underlying molecular mechanism in cerebral ischemia remain to be further defined. In our study, m Show more
LINGO-1 may be involved in the pathogenesis of cerebral ischemia. However, its biological function and underlying molecular mechanism in cerebral ischemia remain to be further defined. In our study, middle cerebral artery occlusion/reperfusion (MACO/R) mice model and HT22 cell oxygen-glucose deprivation/reperfusion (OGD/R) were established to simulate the pathological process of cerebral ischemia in vivo and in vitro and to detect the relevant mechanism. We found that LINGO-1 mRNA and protein were upregulated in mice and cell models. Down-regulation LINGO-1 improved the neurological symptoms and reduced pathological changes and the infarct size of the mice after MACO/R. In addition, LINGO-1 interference alleviated apoptosis and promoted cell proliferation in HT22 of OGD/R. Moreover, down-regulation of LINGO-1 proved to inhibit nuclear translocation of p-NF-κB and reduce the expression level of p-JAK2 and p-STAT3. In conclusion, our data suggest that shLINGO-1 attenuated ischemic injury by negatively regulating NF-KB and JAK2/STAT3 pathways, highlighting a novel therapeutic target for ischemic stroke. Show less
Radiotherapy is one of the main strategies for the treatment of esophageal squamous cell carcinoma (ESCC). However, treatment failure often occurs due to the emergence of radioresistance. In this stud Show more
Radiotherapy is one of the main strategies for the treatment of esophageal squamous cell carcinoma (ESCC). However, treatment failure often occurs due to the emergence of radioresistance. In this study, we report a key regulator of radiation sensitivity, termed TAB182 that may become an ideal biomarker and therapeutic target to overcome radioresistance. By applying qRT-PCR and immunohistochemical staining, the expression of TAB182 was detected in patient tissues. We next assessed the influence of TAB182 downregulation to radiosensitivity using clonogenic survival assay and γ-H2A.X foci analysis in TE-1, TE-10, and radioresistant TE-1R cell lines after ionizing radiation. To unveil the mechanism underlying, TAB182 interacting proteins were identified by mass spectrometry following co-immunoprecipitation. Furthermore, flow cytometry and western blot assay were applied to validate the identified proteins. Our results demonstrated that the expression of TAB182 is higher in cancer tissues than normal tissues and elevated expression of TAB182 correlates with poor outcomes of postoperative radiotherapy. Downregulation of TAB182 sensitized cancer cells to ionizing radiation, particularly in radioresistant TE-1R cells that spontaneously overexpress TAB182. Mechanically, TAB182 interacts with FHL2 to induce G2-M arrest through wiring the CHK2/CDC25C/CDC2 signaling pathway. Finally, overexpression of shRNA-resistant TAB182 restored the checkpoint and radioresistance. TAB182 potentiates the radioresistance of ESCC cells by modulating the G2-M checkpoint through its interaction with FHL2. Thus, TAB182 may become an ideal biomarker and therapeutic target of ESCC radiotherapy. Show less
Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been devel Show more
Hepatocellular carcinoma (HCC) is highly malignant; nearly half of the new cases and deaths are in China. The poor prognosis of HCC is mainly due to late diagnosis; many new biomarkers have been developed for HCC diagnosis. However, few markers are quickly translated into clinical practice; early and differential diagnosis of HCC from cirrhosis and/or hepatitis is still a clinical challenge. Metabolomics and biochemical methods were used to reveal specific serum biomarkers of HCC. Most of the elevated metabolites in HCC and HBV patients were overlapped compared with controls. Urea was the specifically elevated serum biomarker of HCC patients. Moreover, urea combined with AFP and CEA can improve the sensitivity of HCC diagnosis. The plasma ammonia of HCC patients was significantly higher than healthy controls. Co-culture cell model revealed normal liver cells cooperated with cancer cells to metabolize ammonia into urea. The urea metabolism in cancer cells marginally depended on the expression of CPS1. However, the expression of CPS1 did not change with ammonium chloride, which might regulate the urea cycle through enzyme activity. The urea cycle could detoxify high concentrations of ammonia to promote cancer cell proliferation. Therefore, urea was a by-product of ammonia metabolism and could be a potential serum biomarker for HCC. The combined application of metabolomics and biochemical methods can discover new biomarkers for the early diagnosis of HCC and be quickly applied to clinical diagnosis. Show less
Glioma is regarded as an aggressive lethal primary brain tumor. Jumonji domain containing 1C (JMJD1C) is a H3K9 demethylase which participates in the progression of various tumors, but its specific fu Show more
Glioma is regarded as an aggressive lethal primary brain tumor. Jumonji domain containing 1C (JMJD1C) is a H3K9 demethylase which participates in the progression of various tumors, but its specific function and underlying mechanism in glioma development remain undefined, which is the purpose of our work. We initially assessed JMJD1C expression in glioma tissues and cells using the assays of RT-qPCR and immunohistochemistry. Meanwhile, the H3K9 level at the microRNA (miR)-302a promoter region was measured by chromatin immunoprecipitation assay, while luciferase-based reporter assay was performed for validation of the binding affinity between miR-302a and methyltransferase-like 3 (METTL3). The effect of METTL3 on suppressor of cytokine signaling 2 (SOCS2) was subsequently analyzed by MeRIP-RT-qPCR. Finally, a xenograft tumor model was established in nude mice, followed by measurement of tumor-associated macrophages using flow cytometry. JMJD1C was poorly expressed in glioma tissues. Furthermore, JMJD1C increased miR-302a expression through promoting H3K9me1 demethylation at the miR-302a promoter region. miR-302a was identified to target METTL3, which could inhibit SOCS2 expression via m6A modification. JMJD1C promoted M1 macrophage polarization and suppressed the growth of glioma xenografts through the miR-302a/METTL3/SOCS2 axis both in vivo and in vitro. In conclusion, JMJD1C could enhance M1 macrophage polarization to inhibit the onset of glioma, bringing a new insight into the contribution of JMJD1C to the pathobiology of glioma, with possible implications for targeted therapeutic method. Show less
An interaction between hypoxia and immunity has been confirmed in tumor tissue. However, there is no combined biomarker for diagnosis on this basis. Therefore, we developed a scoring formula based on Show more
An interaction between hypoxia and immunity has been confirmed in tumor tissue. However, there is no combined biomarker for diagnosis on this basis. Therefore, we developed a scoring formula based on markers of hypoxia and immunity. Firstly, the hypoxia-immune formula of lung adenocarcinoma (LUAD) was derived using LASSO-Cox regression in three cohorts from public database, and the corresponding score was calculated for each patient. The formula is as follows: combined hypoxia and immune index (CIHI) = LDHA expression × 0.2252 + GAPDH expression × 0.0727 + ANGPTL4 expression × 0.0724 + VEGFC expression × 0.1911 + DKK1 expression × 0.1355 + ADM expression × 0.0588 + BTK expression × -0.1659. Meanwhile, patients were divided into groups according to high and low CIHI, and expression profiles of hypoxia markers and immune markers were analyzed in different groups. CIHI was used to confirm that patients with high CIHI represented a state of hypoxia Show less
Chordoma is a rare bone cancer with an unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have bee Show more
Chordoma is a rare bone cancer with an unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have been associated with chordoma susceptibility in familial and sporadic chordoma. However, the genetic susceptibility of chordoma remains largely unknown. In this study, we investigated rare germline genetic variants in genes involved in TBXT/chordoma-related signaling pathways and other biological processes in chordoma patients from North America and China. We identified variants that were very rare in general population and internal control datasets and showed evidence for pathogenicity in 265 genes in a whole exome sequencing (WES) dataset of 138 chordoma patients of European ancestry and in a whole genome sequencing (WGS) dataset of 80 Chinese patients with skull base chordoma. Rare and likely pathogenic variants were identified in 32 of 138 European ancestry patients (23%), including genes that are part of notochord development, PI3K/AKT/mTOR, Sonic Hedgehog, SWI/SNF complex and mesoderm development pathways. Rare pathogenic variants in COL2A1, EXT1, PDK1, LRP2, TBXT and TSC2, among others, were also observed in Chinese patients. We identified several rare loss-of-function and predicted deleterious missense variants in germline DNA from patients with chordoma, which may influence chordoma predisposition and reflect a complex susceptibility, warranting further investigation in large studies. Show less
miRNAs play critical roles in the regulation of many cardiovascular diseases. However, its role and potential mechanism in cardiac injury caused by obstructive sleep apnea (OSA) remain poorly elucidat Show more
miRNAs play critical roles in the regulation of many cardiovascular diseases. However, its role and potential mechanism in cardiac injury caused by obstructive sleep apnea (OSA) remain poorly elucidated. In the present study, we aimed to investigate the effects of miR-3574 on cardiomyocyte injury under intermittent hypoxia (IH). We confirmed that IH inhibited cell viability, induced cell apoptosis and suppressed miR-3574 expression in the H9c2. miR-3574 overexpression could ameliorate the effects of IH on the cell viability and cell apoptosis in the H9c2. Axin1 was a target gene of miR-3574, and miR-3574 overexpression reduced the expression of Axin1. miR-3574 could inhibit the IH-induced cardiomyocyte injury via downregulating Axin1. However, Axin1 could partially reverse these effects of miR-3574. Our study first reveals that miR-3574 could alleviate IH-induced cardiomyocyte injury by targeting Axin1, which may function as a novel and promising therapy target for OSA-associated cardiovascular diseases. H9c2 were exposed to IH condition. CCK-8 assay was applied to determine cell viability of H9c2. qRT-PCR was conducted to measure the expression level of mRNA and miRNA. Western blot assay was then performed to detect the protein levels. Finally, we used dual-luciferase reporter assay identify the potential target of miR-3574. Show less