Ovarian cancer (OC) is the most fatal gynecologic cancer. The branched-chain First, the expression level of BCKDK in OC cell lines or tissues was determined using tissue microarray- (TMA-) based immun Show more
Ovarian cancer (OC) is the most fatal gynecologic cancer. The branched-chain First, the expression level of BCKDK in OC cell lines or tissues was determined using tissue microarray- (TMA-) based immunohistochemistry or western blotting. Then, growth curve analysis, anchorage-independent cell transformation assays, wound healing assays, cell migration assays, and tumor xenografts were used to test whether BCKDK could promote cell transformation or metastasis. Finally, the signaling pathways involved in this process were investigated by western blotting or immunoprecipitation. We found that the expression of BCKDK was upregulated in OC tissues and the high expression of BCKDK was correlated with an advanced pathological grade in patients. The ectopic overexpression of BCKDK promoted the proliferation and migration of OC cells, and the knockdown of BCKDK with shRNAs inhibited the proliferation and migration of OC ex vivo and Our results demonstrate that BCKDK promotes OC proliferation and migration by activating the MEK/ERK signaling pathway. Targeting the BCKDK-MEK axis may provide a new therapeutic strategy for treating patients with OC. 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
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
Alcohol-induced osteonecrosis of the femoral head (AIONFH) is a complicated refractory bone disease seen in the clinic. The pathogenesis of AIONFH is still controversial. Extrachromosomal circular DNA Show more
Alcohol-induced osteonecrosis of the femoral head (AIONFH) is a complicated refractory bone disease seen in the clinic. The pathogenesis of AIONFH is still controversial. Extrachromosomal circular DNA (eccDNA) elements have been indicated ubiquitously exist in eukaryotic genomes. However, the characteristics and biological functions of eccDNAs remain unclear in AIONFH. In this study, eccDNAs from AIONFH samples ( 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
Average backfat thickness (BFT) is a critical complex trait in pig and an important indicator for fat deposition and lean rate. Usually, genome-wide association study (GWAS) was used to discover quant Show more
Average backfat thickness (BFT) is a critical complex trait in pig and an important indicator for fat deposition and lean rate. Usually, genome-wide association study (GWAS) was used to discover quantitative trait loci (QTLs) of BFT in a single population. However, the power of GWAS is limited by sample size in a single population. Alternatively, meta-analysis of GWAS (metaGWAS) is an attractive method to increase the statistical power by integrating data from multiple breeds and populations. The aim of this study is to identify shared genetic characterization of BFT across breeds in pigs via metaGWAS. RESULTS: In this study, we performed metaGWAS on BFT using 15,353 pigs (5,143 Duroc, 7,275 Yorkshire, and 2,935 Landrace) from 19 populations. We detected 40 genome-wide significant SNPs (Bonferroni corrected P < 0.05) and defined five breed-shared QTLs in across-breed metaGWAS. Markers within the five QTL regions explained 7 ~ 9% additive genetic variance and showed strong heritability enrichment. Furthermore, by integrating information from multiple bioinformatics databases, we annotated 46 candidate genes located in the five QTLs. Among them, three important (MC4R, PPARD, and SLC27A1) and seven suggestive candidate genes (PHLPP1, NUDT3, ILRUN, RELCH, KCNQ5, ITPR3, and U3) were identified. QTLs and candidate genes underlying BFT across breeds were identified via metaGWAS from multiple populations. Our findings contribute to the understanding of the genetic architecture of BFT and the regulating mechanism underlying fat deposition in pigs. Show less
As an acetylcholinesterase inhibitor (AChEI), Huperzine-A (Hup-A) is marketed for treatment of mild to moderate Alzheimer's disease (AD) for decades in China. However, Hup-A causes some side effects. Show more
As an acetylcholinesterase inhibitor (AChEI), Huperzine-A (Hup-A) is marketed for treatment of mild to moderate Alzheimer's disease (AD) for decades in China. However, Hup-A causes some side effects. To search for new analogs or derivatives of Hup-A, we produced five Lycopodium alkaloids and two analogues by chemical synthesis: Lyconadins A-E, H-R-NOB, and 2JY-OBZ4. To systematically evaluate the therapeutic effects of the seven compounds on AD cell models. We assessed the effects of the seven compounds on cell viability via CCK-8 kit and used HEK293-hTau cells and N2a-hAPP cells as AD cell models to evaluate their potential therapeutic effects. We examined their effects on cholinesterase activity by employing the mice primary neuron. All compounds did not affect cell viability; in addition, Lyconadin A and 2JY-OBZ4 particularly increased cell viability. Lyconadin D and Lyconadin E restored tau phosphorylation at Thr231, and H-R-NOB and 2JY-OBZ4 restored tau phosphorylation at Thr231 and Ser396 in GSK-3β-transfected HEK293-hTau cells. 2JY-OBZ4 decreased the level of PP2Ac-pY307 and increased the level of PP2Ac-mL309, supporting that 2JY-OBZ4 may activate PP2A. Lyconadin B, Lyconadin D, Lyconadin E, H-R-NOB, and 2JY-OBZ4 increased sAβPPα level in N2a-hAPP cells. 2JY-OBZ4 decreased the levels of BACE1 and sAβPPβ, thereby reduced Aβ production. Seven compounds exhibited weaker AChE activity inhibition efficiency than Hup-A. Among them, 2JY-OBZ4 showed the strongest AChE inhibition activity with an inhibition rate of 17% at 10μM. Among the seven Lycopodium compounds, 2JY-OBZ4 showed the most expected effects on promoting cell viability, downregulating tau hyperphosphorylation, and Aβ production and inhibiting AChE in AD. 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
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease often caused by sarcomeric gene mutations. MYBPC3 is one of the most common genes associated with HCM. In this study, we ge Show more
Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease often caused by sarcomeric gene mutations. MYBPC3 is one of the most common genes associated with HCM. In this study, we generated a human induced pluripotent stem cell line ZZUNEUi028-A from a 19-year-old male HCM patient with c. 1504C → T in MYBPC3 gene using non-integrative Sendai viral reprogramming technology. This cell line expresses pluripotency markers, exhibits a normal male karyotype (46, XY) and can differentiate into all three germ layers in vitro. ZZUNEUi028-A can serve as a cell disease model in the understanding of HCM pathogenesis. Show less
Background Ischemic stroke is likely caused by interactions of multiple genes and environmental determinants. However, large-scale sequencing studies to discern functional genetic variants and their i Show more
Background Ischemic stroke is likely caused by interactions of multiple genes and environmental determinants. However, large-scale sequencing studies to discern functional genetic variants and their interactions with clinical and lifestyle risk factors on ischemic stroke are limited. Methods and Results We sequenced functional regions of 740 previously identified genes associated with atherosclerotic disease among 999 ischemic stroke cases and 1001 controls of Chinese ancestry. Multiple logistic regression models were used to examine the associations between variants and ischemic stroke and test interactions between variants and clinical and lifestyle risk factors. Functional variants achieving suggestive significance were replicated in an independent sample of 4724 ischemic stroke cases and 5029 controls. Driven by variant main effects, each minor allele of the correlated rs174535, rs174545, and rs3834458 variants at Show less
Alcohol abuse can lead to alcoholic hepatitis (AH), a worldwide public health issue with high morbidity and mortality. Here, we identified apolipoprotein A-IV (APOA4) as a biomarker and potential ther Show more
Alcohol abuse can lead to alcoholic hepatitis (AH), a worldwide public health issue with high morbidity and mortality. Here, we identified apolipoprotein A-IV (APOA4) as a biomarker and potential therapeutic target for AH. APOA4 expression was detected by Gene Expression Omnibus (GEO) databases, Immunohistochemistry, and qRT-PCR in AH. Bioinformatics Methods (protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Set Enrichment Analysis (GSEA) were used to show down-stream gene and pathways of APOA4 in AH. AML-12 cells were used to evaluate the biological function of APOA4 using an ELISA kit (AST, ALT, and IL-1β) and flow cytometry (ROS activity). Both in vivo and in vitro, APOA4 expression was significantly elevated in the AH model induced by alcohol (ETOH). AML-12 cell damage was specifically repaired by APOA4 deficiency, while AST, ALT, and IL-1β activity that was increased by ETOH (200 µmol, 12 h) were suppressed. APOA4 inhibition increased intracellular ROS induced by ETOH, which was detected by flow cytometry. Functional and PPI network analyses showed Fcgamma receptor (FCGR) and platelet activation signaling were potential downstream pathways. We identified 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
To detect whether Danlou Tablet (DLT) regulates the hypoxia-induced factor (HIF)-1α-angiopoietin-like 4 (Angptl4) mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hy Show more
To detect whether Danlou Tablet (DLT) regulates the hypoxia-induced factor (HIF)-1α-angiopoietin-like 4 (Angptl4) mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hypoxia (CIH)-induced dyslipidemia and arteriosclerosis. The mature adipocytes were obtained from 3T3-L1 cell culturation and allocated into 8 groups including control groups (Groups 1 and 5, 0.1 mL of cell culture grade water); DLT groups (Groups 2 and 6, 0.1 mL of 1,000 µg/mL DLT submicron powder solution); dimethyloxalylglycine (DMOG) groups (Groups 3 and 7, DMOG and 0.1 mL of cell culture grade water); DMOG plus DLT groups (Groups 4 and 8, DMOG and 0.1 mL of 1,000 µg/mL DLT submicron powder solution). Groups 1-4 used mature adipocytes and groups 5-8 used HIF-1 α-siRNA lentivirus-transfected mature adipocytes. After 24-h treatment, real-time polymerase chain reaction and Western blot were employed to determine the mRNA and protein expression levels of HIF-1 α and Angptl4. In animal experiments, the CIH model in ApoE Angptl4 expression was dependent on HIF-1 α, with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1 α -transfected cells. DLT inhibited HIF-1 α and Angptl4 mRNA expression (P<0.05 or P<0.01) and reduced HIF-1 α and Angptl4 protein expressions with DMOG in mature adipocytes (all P<0.01), as the effect on HIF-1 α protein also existed in the presence of siHIF-1 α (P<0.01). ApoE DLT had positive effects in improving dyslipidemia and arteriosclerosis by inhibiting Angptl4 protein level through HIF-1 α-Angptl4 mRNA signaling pathway. Show less
The prognosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) remained unsatisfactory currently, more anti-HER2 agents are needed. Here we report a phase I s Show more
The prognosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) remained unsatisfactory currently, more anti-HER2 agents are needed. Here we report a phase I study that evaluated the safety, activity, and biomarkers of LZM005, a HER2 antibody, used as a monotherapy or in combination with trastuzumab plus docetaxel in patients with HER2-positive MBC. From October 2017 to December 2019, 34 patients received LZM005 (14 monotherapy, 20 combination therapy). No DLT was observed. The common adverse events (AEs) in phase Ia included diarrhea (21.4%), infusion reaction (21.4%), and hypertriglyceridemia (21.4%), while those in phase Ib were leukopenia (85.0%), neutropenia (75.0%), anemia (60.0%), diarrhea (60.0%), and rash/pruritus (50.0%). All AEs were manageable. In phase Ia, partial response (PR) was achieved in one case (1/14, overall response rate [ORR]: 7.1%); the disease control rate was 42.90% (6/14). In phase Ib, 11 patients (55.0%) achieved PR, and eight (40.0%) had stable disease. The ORR was 100% (6/6) in trastuzumab-naive and 35.7% (5/14) in trastuzumab-pretreated patients. Biomarker analysis showed that chromatin remodeling genes KMT2B and BRWD1 were associated with better progression-free survival. LZM005 is well tolerated and shows potent activity in patients with HER2-positive MBC. Show less
Prior research has identified ANGPTL4 as a key player in the control of the body's lipid and glucose metabolism and a contributor to the onset of numerous cardiovascular conditions. Recently, it has b Show more
Prior research has identified ANGPTL4 as a key player in the control of the body's lipid and glucose metabolism and a contributor to the onset of numerous cardiovascular conditions. Recently, it has been shown that ANGPTL4 also plays a critical role in tumor growth and progression. Nowadays, the number of EGFR-TKI resistant patients is increasing, and it is important to investigate the role of ANGPTL4 in regulating gefitinib resistance in PC9/GR non-small-cell lung cancer (NSCLC). The expression of ANGPTL4 in A549, PC9, H1975, BEAS-2B and PC9/GR cells was verified by Western blot and qRT-PCR assays, and the effect of gefitinib on the proliferative ability of each cell was probed by CCK-8 assay. By using shRNA to inhibit ANGPTL4 expression in cells, the effect of ANGPTL4 on cell migratory ability was examined and the effect of ANGPTL4 on cellular gefitinib sensitivity was confirmed using the CCK-8 assay and the edu proliferation test. Mouse transplantation tumors were constructed, and the effect of ANGPTL4 on cellular gefitinib sensitivity was investigated in vivo by flow cytometry, Tunel staining assay, immunohistochemical staining, and ROS fluorescence staining assay. ANGPTL4 expression in homoRNA overexpression cells was constructed, and the changes in the expression levels of ASC\NLRP3\Caspase 8 pathway and focal and apoptotic proteins were investigated in vitro, in vivo, afterknockdown and overexpression of ANGPTL4 expression by Westen blot assay. ANGPTL4 was highly expressed in PC9/GR cells. Interfering with ANGPTL4 expression resulted in decreased proliferation and migration ability, decreased resistance to gefitinib, and increased scorching and apoptosis in PC9/GR cells. Interfering with ANGPTL4 expression in PC9/GR cells was shown to promote sensitivity to gefitinib and to mediate the NLRP3/ASC/Caspase 8 pathway to induce cell scorching and apoptosis. ANGPTL4 promotes gefitinib resistance in PC9/GR cells by regulating the NLRP3/ASC/Caspase 8 pathway to inhibit scorch death. ANGPTL4 may be an effective new target for inhibiting EGFR-TKI resistance in lung adenocarcinoma cells. Show less
Bile acid metabolites have been increasingly recognized as pleiotropic signaling molecules that regulate cardiovascular functions, but their role in mesenchymal stromal cells (MSC)-based therapy has n Show more
Bile acid metabolites have been increasingly recognized as pleiotropic signaling molecules that regulate cardiovascular functions, but their role in mesenchymal stromal cells (MSC)-based therapy has never been investigated. It is found that overexpression of farnesoid X receptor (FXR), a main receptor for bile acids, improves the retention and cardioprotection of adipose tissue-derived MSC (ADSC) administered by intramyocardial injection in mice with myocardial infarction (MI), which shows enhanced antiapoptotic, proangiogenic, and antifibrotic effects. RNA sequencing, LC-MS/MS, and loss-of-function studies reveal that FXR overexpression promotes ADSC paracrine angiogenesis via Angptl4. FXR overexpression improves ADSC survival in vivo but fails in vitro. By performing bile acid-targeted metabolomics using ischemic heart tissue, 19 bile acids are identified. Among them, cholic acid and deoxycholic acid significantly increase Angptl4 secretion from ADSC overexpressing FXR and further improve their proangiogenic capability. Moreover, ADSC overexpressing FXR shows significantly lower apoptosis by upregulating Nqo-1 expression only in the presence of FXR ligands. Retinoid X receptor α is identified as a coactivator of FXR. It is first demonstrated that there is a bile acid pool in the myocardial microenvironment. Targeting the bile acid-FXR axis may be a novel strategy for improving the curative effect of MSC-based therapy for MI. 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
Diffuse large B-cell lymphoma (DLBCL) is the main pathological type of non-Hodgkin lymphoma (NHL). Chromobox (CBX) family proteins are classical components of polycomb group (PcG) complexes in many ca Show more
Diffuse large B-cell lymphoma (DLBCL) is the main pathological type of non-Hodgkin lymphoma (NHL). Chromobox (CBX) family proteins are classical components of polycomb group (PcG) complexes in many cancer types, resulting in accelerated carcinogenesis. Nevertheless, the prognostic, functional and expression significance of these CBX family members in DLBCL remain unclear and elusive. CBX transcriptional levels were confirmed using Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer Cell Line Encyclopedia (CCLE) databases. The protein levels of CBX family members were analysed using The Human Protein Atlas (HPA) database. Information on the PPI network, functional enrichment, drug sensitivity, prognostic value, miRNA network, protein structure, genetic alteration and immune cell infiltration were generated using the GeneMANIA, Metascape, GSCALite, GEPIA, PDB, cBioPortal, and TIMER databases, and the correlation of these factors with CBX expression levels in DLBCL was assessed. CBX1/2/3/5/6/8 mRNA levels were significantly enhanced in DLBCL tissues compared to corresponding normal tissues. CBX1/3/4/5/8 protein expression levels were obviously increased, whereas CBX7 was obviously decreased. This difference might be attributed to miRNA regulation based on the miRNA network. Overall survival (OS) analysis showed that CBX levels were not correlated with prognosis in DLBCL patients, indicating that CBXs are not good biomarkers for DLBCL patients. Furthermore, functional enrichment analyses indicated that CBXs were closely related to DNA duplex unwinding, covalent chromatin modification, and histone lysine methylation. The levels of CBXs were also significantly associated with diverse immune cell infiltration in DLBCL. This study reveals that dysregulated CBXs are involved in DLBCL development and might represent potential therapeutic targets for DLBCL. 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
Rong Li, Wenqiang Zhu, Piaopiao Huang+4 more · 2022 · Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · added 2026-04-24
Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of non-alcoholic fatty liver disease (NAFLD), whereas the mechanism for ola Show more
Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of non-alcoholic fatty liver disease (NAFLD), whereas the mechanism for olanzapine-induced NAFLD remains unknown. Excessive hepatic fat accumulation is the basis for the pathogenesis of NAFLD, which results from the disturbance of TG metabolism in the liver. Apolipoprotein A5 (ApoA5) is a key regulator for TG metabolism in vivo that promotes TG accumulation in hepatocytes, thereby resulting in the development of NAFLD. However, there are no data indicating the role of apoA5 in olanzapine-induced NAFLD. Therefore, this study aims to investigate the role of apoA5 in olanzapine-induced NAFLD. This study was carried out via animal studies, cell experiment, and ApoA5 gene knockdown experiment. Six-week-old male C57BL/6J mice were randomized into a control group, a low-dose group, and a high-dose group, which were treated by 10% DMSO, 3 mg/(kg·d) olanzapine, and 6 mg/(kg·d) olanzapine, respectively for 8 weeks. The lipid levels in plasma, liver function indexes, and expression levels of ApoA5 were detected. HepG2 cells were treated with 0.1% DMSO (control group), 25 μmol/L olanzapine (low-dose group), 50 μmol/L olanzapine (medium-dose group), and 100 μmol/L olanzapine (high-dose group) for 24 h. HepG2 cells pretreated with 100 μmol/L olanzapine were transfected with siRNA and scrambled siRNA (negative control), respectively. We observed the changes in lipid droplets within liver tissues and cells using oil red O staining and fat deposition in liver tissues using HE staining. The mRNA and protein levels of ApoA5 were determined by real-time PCR and Western blotting, respectively. After intervention with 3 and 6 mg/(kg·d) olanzapine for 8 weeks, there was no significant difference in body weight among the 3 groups ( The short-term intervention of olanzapine does not significantly increase body weight of mice, but it can directly induce hypertriglyceridemia and NAFLD in mice. Olanzapine inhibits hepatic apoA5 secretion but does not affect hepatic apoA5 synthesis, resulting in the pathogenesis of NAFLD. Inhibition of apoA5 secretion plays a key role in the development of olanzapine-related NAFLD, which may serve as an intervention target for this disease. Show less
Agouti-related protein (AgRP) is a neuropeptide synthesized by AgRP/NPY neurons and transcribed as 132 amino acids in humans and 142 amino acids (AgRP1) in Japanese seabass (
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
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
Minghui Bao, Haotong Li, Jianping Li · 2022 · Journal of cellular and molecular medicine · Blackwell Publishing · added 2026-04-24
Aldosterone-producing adenoma (APA) is a common cause of secondary hypertension. This study aimed to explore the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network to uncover molecular mecha Show more
Aldosterone-producing adenoma (APA) is a common cause of secondary hypertension. This study aimed to explore the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network to uncover molecular mechanism underlying APA. The mRNA and lncRNA expression data of APA and adjacent adrenal gland (AAG) from GSE60044, GSE64957 and GSE101894 were obtained from the Gene Expression Omnibus (GEO) database to analyse differentially expressed genes (DEGs) and lncRNAs (DElncs). Hub genes were identified by robust rank aggregation (RRA) and protein-protein interaction (PPI) network analysis. The miRcode and miRWalk network tools were used to construct the ceRNA network. 1526 upregulated and 1512 downregulated DEGs were identified, which are mainly enriched in extracellular matrix and Ca Show less
Glioma is one of the most common intracranial malignancies that plagues people around the world. Despite current improvements in treatment, the prognosis of glioma is often unsatisfactory. Necroptosis Show more
Glioma is one of the most common intracranial malignancies that plagues people around the world. Despite current improvements in treatment, the prognosis of glioma is often unsatisfactory. Necroptosis is a form of programmed cell death. As research progresses, the role of necroptosis in tumors has gradually attracted the attention of researchers. And lncRNA is regarded as a critical role in the development of cancer. Therefore, this study is aimed at establishing a prognostic model based on necroptosis-associated lncRNAs to accurately assess the prognosis and immune response of patients with glioma. The RNA sequences of glioma patients and normal brain samples were downloaded from The Cancer Genome Atlas (TCGA) and GTEx databases, respectively. The coexpression analysis was performed to identify the necroptosis-related lncRNAs. Then, we utilized LASSO analysis following univariate Cox analysis to construct a prognostic model. Subsequently, we applied the Kaplan-Meier curve, time-dependent receiver operating characteristics (ROC), and univariate and multivariate Cox regression analyses to assess the effectiveness of this model. And the functional enrichment analyses and immune-related analyses were employed to investigate the potential biological functions. A validation set was obtained from the Chinese Glioma Genome Atlas (CGGA) database. And qRT-PCR was employed to further validate the expression levels of selected necroptosis-associated lncRNAs. Seven necroptosis-related lncRNAs (FAM13A-AS1, JMJD1C-AS1, LBX2-AS1, ZBTB20-AS4, HAR1A, SNHG14, and LINC00900) were determined to construct a prognostic model. The area under the ROC curve (AUC) was 0.871, 0.901, and 0.911 at 1, 2, and 3 years, respectively. The risk score was shown to be an important independent predictor in both univariate and multivariate Cox regression analyses. Through functional enrichment analyses, we found that the differentially expressed genes (DEGs) were mainly enriched in protein binding and signaling-related biological functions and immune-associated pathways. In conclusion, we established and validated a novel necroptosis-related lncRNA signature, which could accurately predict the overall survival of glioma patients and serve as potential therapeutic targets. Show less
Cistanche deserticola Ma (cistanche) is a traditional herb with a wide range of therapeutic properties. However, no evidence of cistanche's effect on adipogenesis has been found. The effect of cistanc Show more
Cistanche deserticola Ma (cistanche) is a traditional herb with a wide range of therapeutic properties. However, no evidence of cistanche's effect on adipogenesis has been found. The effect of cistanche that promotes the adipogenesis of 3T3-L1 preadipocytes was proved by using MTT spectrophotometry, Nile Red staining, Oil Red O staining and transcriptome sequencing technology. The mRNA level of key transcription factors for adipogenesis such as PPAR, AP2 and LPL were examined by RT-PCR. The results showed that the intracellular lipid content in cistanche treated cells were notably increased when compared with the non-treated cells. Between the differentiation and cistanche treated groups, the expression of adipogenesis related genes such as grow hormone releasing hormone (Ghrp), BCL2/adenovirus E1B interacting protein 3 (Bnip3) and Gastric inhibitory polypeptide receptor (Gipr) were significantly increased. Our findings also verified that cistanche promoted adipogenesis, which was accompanied by up-regulated level of Bnip3 and PPAR. This study could uncover new signaling pathways involved in adipogenesis regulation. 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
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