Further analysis has revealed that the signal reported in Extended Data Fig. 1c of this Letter is attributed to phosphorylethanolamine, not carbamoyl phosphate. A newly developed derivatization method Show more
Further analysis has revealed that the signal reported in Extended Data Fig. 1c of this Letter is attributed to phosphorylethanolamine, not carbamoyl phosphate. A newly developed derivatization method revealed that the level of carbamoyl phosphate in these NSCLC extracts is below the detection threshold of approximately 10 nanomoles. These findings do not alter the overall conclusions of the Letter; see associated Amendment for full details. The Letter has not been corrected online. Show less
Cholesteryl ester transfer protein (CETP) inhibitor-mediated induction of HDL-cholesterol has no effect on the protection from cardiovascular disease (CVD). However, the mechanism is still unknown. Da Show more
Cholesteryl ester transfer protein (CETP) inhibitor-mediated induction of HDL-cholesterol has no effect on the protection from cardiovascular disease (CVD). However, the mechanism is still unknown. Data on the effects of this class of drugs on subclasses of HDL are either limited or insufficient. In this study, we investigated the effect of evacetrapib, a CETP inhibitor, on subclasses of HDL in patients with atherosclerotic cardiovascular disease or diabetes. Baseline and 3-month post-treatment samples from atorvastatin 40 mg plus evacetrapib 130 mg (n = 70) and atorvastatin 40 mg plus placebo (n = 30) arms were used for this purpose. Four subclasses of HDL (large HDL, medium HDL, small HDL, and preβ-1 HDL) were separated according to their size and quantified by densitometry using a recently developed native polyacrylamide gel electrophoresis (PAGE) system. Relative to placebo, while evacetrapib treatment dramatically increased large HDL and medium HDL subclasses, it significantly reduced small HDL (27%) as well as preβ-1 HDL (36%) particles. Evacetrapib treatment reduced total LDL, but also resulted in polydisperse LDL with LDL particles larger and smaller than the LDL subclasses of the placebo group. Evacetrapib reduced preβ-1 HDL and small HDL in patients with ASCVD or diabetes on statin. Preβ-1 HDL and medium HDL are negatively interrelated. The results could give a clue to understand the effect of CETP inhibitors on cardiovascular outcomes. Show less
The current study reports a new, simple and fast method using a flake-like dysprosium molybdate (Dy2MoO6; FL-DyM) nanostructured material to detect the antibiotic drug metronidazole (METZ). This nanoc Show more
The current study reports a new, simple and fast method using a flake-like dysprosium molybdate (Dy2MoO6; FL-DyM) nanostructured material to detect the antibiotic drug metronidazole (METZ). This nanocomposite material was employed on the surface of a glassy carbon electrode (GCE) to develop the electrode (FL-DyM/GCE). Further, the synthesized FL-DyM was systematically characterized by powder X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray diffraction (EDS), elemental mapping, X-ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) analyses. Cyclic (CV) and differential pulse voltammetry (DPV) techniques were used to study the electrochemical properties. The FL-DyM/GCE-based sensor demonstrated excellent selectivity and sensitivity for the detection of the drug METZ, which could be attributed to the strong affinity of FL-DyM towards the -NO2 group in METZ, and the good electrocatalytic activity and conductivity of FL-DyM. The fabrication and optimization of the working electrode were accomplished with CV and DPV obtained by scan rate and pH studies. Compared to the bare GCE and other rare-earth metal molybdates, the FL-DyM/GCE sensor displayed a superior electrocatalytic activity response for METZ detection. The sensor demonstrated a good linear relationship over the concentration range of 0.01-2363 μM. The quantification and detection limits were found to be 0.010 μM and 0.0030 μM, respectively. The FL-DyM/GCE sensor displayed excellent selectivity, repeatability, reproducibility, and stability for the detection of METZ in human urine and commercial METZ tablet samples, which validates the new technique for efficient drug sensing in practical applications. Show less
Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug s Show more
Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 ( Show less
Fusion genes are major molecular biological abnormalities in hematological malignancies. This study aimed to depict the common recurrent gene-fusion landscape in acute myeloid leukemia (AML). 3135 de Show more
Fusion genes are major molecular biological abnormalities in hematological malignancies. This study aimed to depict the common recurrent gene-fusion landscape in acute myeloid leukemia (AML). 3135 de novo AML cases were enrolled and 36 recurrent fusion genes were assessed using multiplex-nested RT-PCR. Twenty-three distinct fusion genes were detected in 1292 (41.21%) cases. The incidence of fusion genes was higher in pediatric AML than in adult cases. The pediatric patients had higher incidences of RUNX1-RUNX1T1, KMT2A-MLLT3, KMT2A-MLLT10, KMT2A-MLLT11, KMT2A-MLLT6, and FUS-ERG, whereas KMT2A-PTD was more common in adult patients. The occurrence of molecular abnormalities involving the KMT2A gene and CBFB-MYH11 was lower in Chinese pediatric AML compared to Western reports. The incidence of RUNX1-RUNX1T1 was higher in both pediatric and adult patients in our study than in Western countries. This study provides a genetic landscape of common fusion genes in Chinese AML and confirms different incidences between age groups and races. Show less
Anacetrapib is an inhibitor of cholesteryl ester transfer protein (CETP), associated with reduction in LDL cholesterol and increase in HDL cholesterol in hypercholesterolemic patients. Anacetrapib was Show more
Anacetrapib is an inhibitor of cholesteryl ester transfer protein (CETP), associated with reduction in LDL cholesterol and increase in HDL cholesterol in hypercholesterolemic patients. Anacetrapib was not taken forward into filing/registration as a new drug for coronary artery diease, despite the observation of a ∼9% reduction in cardiovascular risk in a large phase III cardiovascular outcomes trial (REVEAL). Anacetrapib displayed no adverse effects throughout extensive preclinical safety evaluation, and no major safety signals were observed in clinical trials studying anacetrapib, including REVEAL. However, anacetrapib demonstrated a long terminal half-life in all species, thought to be due, in part, to distribution into adipose tissue. We sought to understand the dependence of anacetrapib's long half-life on adipose tissue and to explore potential mechanisms that might contribute to the phenomenon. In mice, anacetrapib localized primarily to the lipid droplet of adipocytes in white adipose tissue; in vitro, anacetrapib entry into cultured human adipocytes depended on the presence of a mature adipocyte and lipid droplet but did not require active transport. In vivo, the entry of anacetrapib into adipose tissue did not require lipase activity, as the distribution of anacetrapib into adipose was-not affected by systemic lipase inhibition using poloaxamer-407, a systemic lipase inhibitor. The data from these studies support the notion that the entry of anacetrapib into adipose tissue/lipid droplets does not require active transport, nor does it require mobilization or entry of fat into adipose via lipolysis. Show less
DHX36 is a DEAH-box helicase that resolves parallel G-quadruplex structures formed in DNA and RNA. The recent co-crystal structure of DHX36 bound G4-DNA revealed an intimate contact, but did not addre Show more
DHX36 is a DEAH-box helicase that resolves parallel G-quadruplex structures formed in DNA and RNA. The recent co-crystal structure of DHX36 bound G4-DNA revealed an intimate contact, but did not address the role of ATP hydrolysis in G4 resolving activity. Here, we demonstrate that unlike on G4-DNA, DHX36 displays ATP-independent unfolding of G4-RNA followed by ATP-dependent refolding, generating a highly asymmetric pattern of activity. Interestingly, DHX36 refolds G4-RNA in several steps, reflecting the discrete steps in forming the G4 structure. We show that the ATP-dependent activity of DHX36 arises from the RNA tail rather than the G4. Mutations that perturb G4 contact result in quick dissociation of the protein from RNA upon ATP hydrolysis, while mutations that interfere with binding the RNA tail induce dysregulated activity. We propose that the ATP-dependent activity of DHX36 may be useful for dynamically resolving various G4-RNA structures in cells. Show less
Jae Young Lee, Shebli Mehrazarin, Abdullah Alshaikh+6 more · 2019 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Histone Lys-specific demethylases (KDMs) play a key role in many biological processes through epigenetic mechanisms. However, the role of KDMs in inflammatory responses to oral bacterial infection is Show more
Histone Lys-specific demethylases (KDMs) play a key role in many biological processes through epigenetic mechanisms. However, the role of KDMs in inflammatory responses to oral bacterial infection is poorly understood. Here, we show a novel regulatory role of KDM3C in inflammatory responses to oral bacterial infection. KDM3C expression is transiently suppressed in human and mouse macrophages exposed to LPS from Show less
Intracranial aneurysm (IA) represents a cerebrovascular disorder that featured by dilation or bulging of the weakened blood vessel wall. When it ruptures, an IA leads to subarachnoid hemorrhage with h Show more
Intracranial aneurysm (IA) represents a cerebrovascular disorder that featured by dilation or bulging of the weakened blood vessel wall. When it ruptures, an IA leads to subarachnoid hemorrhage with high disability and mortality rates. Despite the numerous studies focusing on IA ruptures, little research on IA pathogenesis has been reported. In this study, we aimed to reveal key genes related to IA formation. Four datasets from Gene Expression Omnibus data were downloaded, normalized, and separated into the IA group and the normal vessel control group for analyses. We screened for differentially expressed genes (DEGs) between groups and conducted functional enrichment, pathway enrichment, and gene set enrichment analysis analyses among significant DEGs. according to our analyses, significant DEGs majorly associate with smooth muscle system and the complement system. Among all DEGs, 5 down-regulated genes (MYH11, CNN1, MYOCD, ACTA1, and LMOD1) and 3 up-regulated genes (C1QB, C3AR1, and VSIG4) are most relevant in IA formation. Key DEGs identified in this study are related to IA pathogenesis. Among identified DEGs, LMOD1 is the most significant and merits more attention. Show less
There is a lack of understanding surrounding the molecular mechanisms involved in the development of chicken skeletal muscle in the late postnatal stage, especially in the regulation of breast muscle Show more
There is a lack of understanding surrounding the molecular mechanisms involved in the development of chicken skeletal muscle in the late postnatal stage, especially in the regulation of breast muscle development related genes, pathways, miRNAs and other factors. In this study, 12 cDNA libraries and 4 small RNA libraries were constructed from Gushi chicken breast muscle samples from 6, 14, 22, and 30 weeks. A total of 15,508 known transcripts, 25,718 novel transcripts, 388 known miRNAs and 31 novel miRNAs were identified by RNA-seq in breast muscle at the four developmental stages. Through correlation analysis of miRNA and mRNA expression profiles, it was found that 417, 370, 240, 1,418, 496, and 363 negatively correlated miRNA-mRNA pairs of Show less
Cell division cycle 20 (CDC20) is frequently overexpressed in malignant tumours and involved in the differentiation process of hematopoietic stem cells. However, the role of CDC20 in prostate cancer s Show more
Cell division cycle 20 (CDC20) is frequently overexpressed in malignant tumours and involved in the differentiation process of hematopoietic stem cells. However, the role of CDC20 in prostate cancer stem-like cells (CSCs) remains poorly understood. The expression of CDC20, CD44, β-catenin were examined in prostate cancer specimens by immunohistochemistry assay, the role of CDC20 on the stem-like properties of prostate CSCs was accessed by real-time quantitive PCR, spheroid formation, in vitro and in vivo limiting dilution assay. CDC20 was associated with malignant progression of prostate cancer, the patients with both high expression CDC20 and CD44 or β-catenin were associated with more aggressive clinicopathological features and poor prognosis. CDC20 was usually enriched in CD44 Our results indicated that CDC20 maintains the self-renewal ability of CD44 Show less
Yanjun Li, Yingyu Chen · 2019 · Advances in experimental medicine and biology · Springer · added 2026-04-24
AMPK is an evolutionarily conserved serine/threonine-protein kinase that acts as an energy sensor in cells and plays a key role in the upregulation of catabolism and inactivation of anabolism. Under v Show more
AMPK is an evolutionarily conserved serine/threonine-protein kinase that acts as an energy sensor in cells and plays a key role in the upregulation of catabolism and inactivation of anabolism. Under various physiological and pathological conditions, AMPK can be phosphorylated by an upstream kinase and bind to AMP or ADP rather than ATP, leading to its activation. Activated AMPK regulates a variety of metabolic processes, including autophagy. AMPK promotes autophagy directly by phosphorylating autophagy-related proteins in the mTORC1, ULK1, and PIK3C3/VPS34 complexes or indirectly by regulating the expression of autophagy-related genes downstream of transcription factors such as FOXO3, TFEB, and BRD4. AMPK can also upregulate the autophagic degradation of mitochondria (mitophagy), as it can induce fragmentation of damaged mitochondria in the network and promote the translocation of the autophagy machinery to damaged mitochondria. In this section, we will detail the molecular structure of AMPK, how its activity is regulated, and its pivotal role in regulating autophagy and mitophagy. Show less
Preeclampsia (PE) is a pregnancy-related syndrome characterized by hypertension and proteinuria after the 20 The expression level of MIR503HG in placental tissues, HTR-8/SVneo, and JEG3 cells was dete Show more
Preeclampsia (PE) is a pregnancy-related syndrome characterized by hypertension and proteinuria after the 20 The expression level of MIR503HG in placental tissues, HTR-8/SVneo, and JEG3 cells was determined by quantitative real-time PCR; western blot detected the relevant protein expression levels in HTR-8/SVneo and JEG3 cells; flow cytometry determined cell apoptosis and cell cycle of HTR-8/SVneo and JEG3 cells; trophoblast cell proliferation, invasion, and migration of HTR-8/SVneo and JEG3 cells were measured by CCK-8, transwell invasion, and wound healing assays, respectively. The highly expressed MIR503HG was detected in PE placental tissues compared to normal placental tissues. MIR503HG overexpression suppressed cell proliferation, invasion, and migration of HTR-8/SVneo and JEG3 cells, while knockdown of MIR503HG increased trophoblast cell proliferation, invasion, and migration. Flow cytometry results showed that MIR503HG overexpression induced apoptosis and caused cell cycle arrest at the G Our results showed that MIR503HG inhibited the proliferation, invasion, and migration of HTR-8/SVneo and JEG3 cells, which may be related to the pathogenesis of PE. Show less
Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q22;q21), resulting in a PML-RARA fusion that is the master driver of APL. A few cases that cannot be identified with PML-RARA by using Show more
Acute promyelocytic leukemia (APL) is characterized by t(15;17)(q22;q21), resulting in a PML-RARA fusion that is the master driver of APL. A few cases that cannot be identified with PML-RARA by using conventional methods (karyotype analysis, FISH, and RT-PCR) involve abnormal promyelocytes that are fully in accordance with APL in morphology, cytochemistry, and immunophenotype. To explore the mechanisms involved in pathogenesis and recurrence of morphologically diagnosed APL, we performed comprehensive variant analysis by next-generation sequencing in 111 pediatric patients morphologically diagnosed as APL. Structural variant (SV) analysis in 120 DNA samples from both diagnosis and relapse stage identified 95 samples with RARA rearrangement (including 94 with PML-RARA and one with NPM-RARA) and two samples with KMT2A rearrangement. In the eligible 13 RNA samples without any RARA rearrangement at diagnosis, one case each with CPSF6-RARG, NPM1-CCDC28A, and TBC1D15-RAB21 and two cases with a TBL1XR1-RARB fusion were discovered. These uncovered fusion genes strongly suggested their contributions to leukemogenesis as driver alternations and APL phenotype may arise by abnormalities of other members of the nuclear receptor superfamily involved in retinoid signaling (RARB or RARG) or even by mechanisms distinct from the formation of aberrant retinoid receptors. Single-nucleotide variant (SNV) analysis in 77 children (80 samples) with RARA rearrangement showed recurrent alternations of primary APL in FLT3, WT1, USP9X, NRAS, and ARID1A, with a strong potential for involvement in pathogenesis, and WT1 as the only recurrently mutated gene in relapsed APL. WT1, NPM1, NRAS, FLT3, and NSD1 were identified as recurrently mutated in 17 primary samples without RARA rearrangement and WT1, NPM1, TP53, and RARA as recurrently mutated in 9 relapsed samples. The survival of APL with RARA rearrangement is much better than without RARA rearrangement. Thus, patients morphologically diagnosed as APL that cannot be identified as having a RARA rearrangement are more reasonably classified as a subclass of AML other than APL, and individualized treatment should be considered according to the genetic abnormalities. Show less
Estrogen is very important to the differentiation of B lymphocytes; B lymphopoiesis induced by OVX was supposedly involved in osteoporosis. But the effects of B lymphocytes on the osteogenic different Show more
Estrogen is very important to the differentiation of B lymphocytes; B lymphopoiesis induced by OVX was supposedly involved in osteoporosis. But the effects of B lymphocytes on the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) are not clear. In this study, we detected bone quality and bone loss in a trabecular bone by electronic universal material testing machine and microcomputed tomography (micro-CT) in OVX and splenectomized-ovariectomy (SPX-OVX) rats. Additionally, changes in lymphocytes (B lymphocyte, CD4 Show less
Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in myosin-binding protein C3 ( MYBPC3) resulting in a premature termination codon (PTC). The underlying mechanisms of how PTC mutati Show more
Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in myosin-binding protein C3 ( MYBPC3) resulting in a premature termination codon (PTC). The underlying mechanisms of how PTC mutations in MYBPC3 lead to the onset and progression of HCM are poorly understood. This study's aim was to investigate the molecular mechanisms underlying the pathogenesis of HCM associated with MYBPC3 PTC mutations by utilizing human isogenic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Isogenic iPSC lines were generated from HCM patients harboring MYBPC3 PTC mutations (p.R943x; p.R1073P_Fsx4) using genome editing. Comprehensive phenotypic and transcriptome analyses were performed in the iPSC-CMs. We observed aberrant calcium handling properties with prolonged decay kinetics and elevated diastolic calcium levels in the absence of structural abnormalities or contracile dysfunction in HCM iPSC-CMs as compared to isogenic controls. The mRNA expression levels of MYBPC3 were significantly reduced in mutant iPSC-CMs, but the protein levels were comparable among isogenic iPSC-CMs, suggesting that haploinsufficiency of MYBPC3 does not contribute to the pathogenesis of HCM in vitro. Furthermore, truncated MYBPC3 peptides were not detected. At the molecular level, the nonsense-mediated decay pathway was activated, and a set of genes involved in major cardiac signaling pathways was dysregulated in HCM iPSC-CMs, indicating an HCM gene signature in vitro. Specific inhibition of the nonsense-mediated decay pathway in mutant iPSC-CMs resulted in reversal of the molecular phenotype and normalization of calcium-handling abnormalities. iPSC-CMs carrying MYBPC3 PTC mutations displayed aberrant calcium signaling and molecular dysregulations in the absence of significant haploinsufficiency of MYBPC3 protein. Here we provided the first evidence of the direct connection between the chronically activated nonsense-mediated decay pathway and HCM disease development. Show less
A typical feature of the contextual fear memory is increased fear generalization with time. Though much attention has been given to the neural structures that underlie the long-term consolidation of a Show more
A typical feature of the contextual fear memory is increased fear generalization with time. Though much attention has been given to the neural structures that underlie the long-term consolidation of a contextual fear memory, the molecular mechanisms regulating fear generalization remain unclear. We observed that retrieval of contextual fear in a novel context at a remote time point increased coupling of neuronal nitric oxide synthase (nNOS) with postsynaptic density-95 (PSD-95) and c-Fos expression in the anterior cingulate cortex (ACC). Disrupting nNOS-PSD-95 coupling in the ACC decreased the expression of Histone deacetylase 2 (HDAC Show less
Tubulointerstitial fibrosis (TIF) is the main pathologic feature of end-stage renal disease. Epithelial-mesenchymal transition (EMT) of proximal tubular cells (PTCs) is one of the most significant fea Show more
Tubulointerstitial fibrosis (TIF) is the main pathologic feature of end-stage renal disease. Epithelial-mesenchymal transition (EMT) of proximal tubular cells (PTCs) is one of the most significant features of TIF. MicroRNAs play critical roles during EMT in TIF. However, whether miRNAs can be used as therapeutic targets in TIF therapy remains undetermined. We found that miR-30e, a member of the miR-30 family, is deregulated in TGF-β1-induced PTCs, TIF mice and human fibrotic kidney tissues. Moreover, transcription factors that induce EMT, such as snail, slug, and Zeb2, were direct targets of miR-30e. Using a cell-based miR-30e promoter luciferase reporter system, Schisandrin B (Sch B) was selected for the enhancement of miR-30e transcriptional activity. Our results indicate that Sch B can decrease the expression of snail, slug, and Zeb2, thereby attenuating the EMT of PTCs during TIF by upregulating miR-30e, both in vivo and in vitro. This study shows that miR-30e can serve as a therapeutic target in the treatment of patients with TIF and that Sch B may potentially be used in therapy against renal fibrosis. Show less
Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUS Show more
Mitogen-activated protein kinases (MAPKs) are key regulators of signal transduction and cell responses. Abnormalities in MAPKs are associated with multiple diseases. Dual-specificity phosphatases (DUSPs) dephosphorylate many key signaling molecules, including MAPKs, leading to the regulation of duration, magnitude, or spatiotemporal profiles of MAPK activities. Hence, DUSPs need to be properly controlled. Protein post-translational modifications, such as ubiquitination, phosphorylation, methylation, and acetylation, play important roles in the regulation of protein stability and activity. Ubiquitination is critical for controlling protein degradation, activation, and interaction. For DUSPs, ubiquitination induces degradation of eight DUSPs, namely, DUSP1, DUSP4, DUSP5, DUSP6, DUSP7, DUSP8, DUSP9, and DUSP16. In addition, protein stability of DUSP2 and DUSP10 is enhanced by phosphorylation. Methylation-induced ubiquitination of DUSP14 stimulates its phosphatase activity. In this review, we summarize the knowledge of the regulation of DUSP stability and ubiquitination through post-translational modifications. Show less
Currently, brown adipose tissue (BAT) is a therapeutic target in obesity and diabetes, but the mechanism of BAT activation remains unclear. Because increasing emphasis has been placed on the role of i Show more
Currently, brown adipose tissue (BAT) is a therapeutic target in obesity and diabetes, but the mechanism of BAT activation remains unclear. Because increasing emphasis has been placed on the role of intracellular peptides in biological processes, we conducted a study to gain insight into the mechanism of BAT activation by using a peptidomic approach and then attempted to identify peptides that are capable of activating BAT. In the present study, we generated the peptidomic profile of the intracellular peptides in brown adipocytes treated with forskolin (FSK) using a peptidomic approach. Then, the differentially expressed peptides were evaluated via Gene Ontology (GO) enrichment, KEGG pathway, and protein-protein interaction (PPI) network analysis. Finally, we selected candidate peptides for further validation via assessing the expression levels of UCP-1 and PGC-1α in brown adipocytes exposed to the peptides. A total of 4,370 peptides were identified, of which 951 were upregulated and 379 were downregulated after FSK treatment. Bioinformatic analysis demonstrated that the ECM-receptor interaction GO term was the most enriched and that collagen alpha-related proteins exhibited the highest degree of PPI. Four peptides separately derived from TSC22 domain family protein 1 (T22D1), bromodomain and WD repeat-containing protein 1 (BRWD1), protein piccolo (PCLO), and collagen alpha-1 (III) chain (CO3A1) increased the expression levels of UCP-1 and PGC-1α. ECM-receptor interaction may play an important role in the process of FSK-stimulated BAT activation, and the pT22D1tide, pBRWD1tide, pPCLOtide, and pCO3A1tide peptides potentially promote BAT thermogenesis. Show less
High fructose feeding changes fibroblast growth factor 21 (FGF21) regulation. Lactobacillus rhamnosus GG (LGG) supplementation reduces fructose-induced non-alcoholic fatty liver disease (NAFLD). The a Show more
High fructose feeding changes fibroblast growth factor 21 (FGF21) regulation. Lactobacillus rhamnosus GG (LGG) supplementation reduces fructose-induced non-alcoholic fatty liver disease (NAFLD). The aim of this study was to determine the role of FGF21 and underlying mechanisms in the protective effects of LGG. FGF21 knockout (KO) mice and C57BL/6 wild type (WT) mice were fed 30% fructose for 12 weeks. LGG was administered to the mice in the last 4 weeks during fructose feeding. FGF21-adiponectin (ADPN)-mediated hepatic lipogenesis and inflammation were investigated. FGF21 expression was robustly increased after 5-weeks of feeding and significantly decreased after 12-weeks of feeding in fructose-induced NAFLD mice. LGG administration reversed the depressed FGF21 expression, increased adipose production of ADPN, and reduced hepatic fat accumulation and inflammation in the WT mice but not in the KO mice. Hepatic nuclear carbohydrate responsive-element binding protein (ChREBP) was increased by fructose and reduced by LGG, resulting in a reduction in the expression of lipogenic genes. The methylated form of protein phosphatase 2A (PP2A) C, which dephosphorylates and activates ChREBP, was upregulated by fructose and normalized by LGG. Leucine carboxyl methyltransferase-1, which methylates PP2AC, was also increased by fructose and decreased by LGG. However, those beneficial effects of LGG were blunted in the KO mice. Hepatic dihydrosphingosine-1-phosphate, which inhibits PP2A, was markedly increased by LGG in the WT mice but attenuated in the KO mice. LGG decreased adipose hypertrophy and increased serum levels of ADPN, which regulates sphingosine metabolism. This beneficial effect was decreased in the KO mice. LGG administration increases hepatic FGF21 expression and serum ADPN concentration, resulting in a reduced ChREBP activation through dihydrosphingosine-1-phosphate-mediated PP2A deactivation, and subsequently reversed fructose-induced NAFLD. Thus, our data suggest that FGF21 is required for the beneficial effects of LGG in reversal of fructose-induced NAFLD. Show less
Jin-Juan Liu, Hong-Fa Yang, Yong-Jian Li+1 more · 2019 · Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · added 2026-04-24
To investigate the expression of β-catenin in the skin lesions of patients with systemic scleroderma (SSc) and its effect on epithelial-mesenchymal transition (EMT) of human epidermal keratinocytes. T Show more
To investigate the expression of β-catenin in the skin lesions of patients with systemic scleroderma (SSc) and its effect on epithelial-mesenchymal transition (EMT) of human epidermal keratinocytes. The expression of β-catenin, Snail1 and E-cadherin in the skin lesions sample of 45 SSc patients and normal skin sample from 20 healthy adults was detected with SP immunohistochemistry. HaCaT, the human epidermal keratinocytes, were treated with different concentrations of Wnt10b (0 ng/mL (control), 2 ng/mL and 4 ng/mL) for 48 h. then detected the localization of β-catenin in HaCaT cells by immunofluorescence assay, determined the mRNA levels of Snail1 and Snail2 in HaCaT cells by real-time fluorescent quantitative PCR, detected the proteins expression of β-catenin, Vimentin, N-cadherin and E-cadherin in HaCaT cells by Western blot. The positive rates of β-catenin, Snail1 and E-cadherin in skin lesions of SSc patients were 100%, 88.89% and 2.22% respectively, while in healthy adult skin, the corresponding positive rates were 0%, 10.00%, and 95.00%. The difference between the two groups was significant. Compared with control group, treatment with different concentrations of Wnt10b (2 ng/mL and 4 ng/mL) induced up-regulation of β-catenin expression and promoted translocation of β-catenin from cytoplasm to nucleus, increased the mRNA levels of Snail1 and Snail2 ( Abnormally activated Wnt/β-catenin signaling pathway and abnormally expressed EMT-related proteins are observed in SSc lesions. Activation of Wnt/β-catenin signaling pathway may promote EMT in HaCaT cells. Show less
The goal of this work was to investigate the molecular profiles and metastasis markers in Chinese patients with gastric carcinoma (GC). In total, we performed whole exome sequencing (WES) on 74 GC pat Show more
The goal of this work was to investigate the molecular profiles and metastasis markers in Chinese patients with gastric carcinoma (GC). In total, we performed whole exome sequencing (WES) on 74 GC patients with tumor and adjacent normal formalin-fixed, paraffin-embedded (FFPE) tissue samples. The mutation spectrum of these samples showed a high concordance with TCGA and other studies on GC. PTPRT is significantly associated with metastasis of GC, suggesting its predictive role in metastasis of GC. Patients carrying BRCA2 mutations tend not to metastasize, which may be related to their sensitivity to chemotherapy. Mutations in MACF1, CDC27, HMCN1, CDH1 and PDZD2 were moderately enriched in peritoneal metastasis (PM) samples. Furthermore, we found two genomic regions (1p36.21 and Xq26.3) were associated with PM of GC, and patients with amplification of 1p36.21 and Xq26.3 have a worse prognosis (P = 0.002, 0.01, respectively). Our analysis provides GC patients with potential markers for single and combination therapies. Show less
Advanced non-small cell lung cancer (NSCLC) leads to a high death rate in patients and is a major threat to human health. NSCLC induces an immune suppressive microenvironment and escapes from immune s Show more
Advanced non-small cell lung cancer (NSCLC) leads to a high death rate in patients and is a major threat to human health. NSCLC induces an immune suppressive microenvironment and escapes from immune surveillance Show less
Natural and synthetic progestins in receiving streams can disrupt the normal endocrine systems of fish. Norethindrone (NET) is a widely used synthetic progestin that often appears in wastewater efflue Show more
Natural and synthetic progestins in receiving streams can disrupt the normal endocrine systems of fish. Norethindrone (NET) is a widely used synthetic progestin that often appears in wastewater effluents. For this research, adult female western mosquitofish (Gambusia affinis) were exposed to NET at three concentrations. The effects of NET on the following biological factors were evaluated: the histology of the ovaries and livers, the anal fin morphology, and transcription of genes related to steroidogenesis signaling pathways in the livers. After 42 d exposure to NET at 33.0 ng L Show less
The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to Show more
The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to optimize fuel mobilization and storage. Specifically, increased brain-melanocortin signaling or negative energy balance promotes lipid mobilization by increasing sympathetic nervous system input to adipose tissue. In contrast, calorie-independent mechanisms favoring energy storage are less understood. Here, we demonstrate that reduction of brain-melanocortin signaling actively promotes fat mass gain by activating the lipogenic program and adipocyte and endothelial cell proliferation in white fat depots independently of caloric intake via efferent nerve fibers conveyed by the common hepatic branch of the vagus nerve. Those vagally regulated obesogenic signals also contribute to the fat mass gain following chronic high-fat diet feeding. These data reveal a physiological mechanism whereby the brain controls energy stores that may contribute to increased susceptibility to obesity. Show less
We introduce the indications, technique, results of our experience using donor's RGEA as interposition vessel to solve hepatic artery reconstruction problems in P-LDLT. A retrospective analysis of P-L Show more
We introduce the indications, technique, results of our experience using donor's RGEA as interposition vessel to solve hepatic artery reconstruction problems in P-LDLT. A retrospective analysis of P-LDLT for children with metabolic diseases from June 2013 to November 2018 in our center was carried out. The arterial conditions, reconstruction methods, and prognosis were analyzed. A total of 73 children with metabolic diseases underwent P-LDLT during the period. The LLF was the main graft, accounting for 71.2%. The donor's RGEA was utilized in five cases. There were three children with OTCD and two children with deficiency of CPS1 and MSUD, respectively. In three cases, the grafts' left hepatic arteries were anastomosed with the recipients' PHA using donors' RGEA as interposition vessel. In other two cases, the donors' RGEA was interposed between graft's MHA and the recipient's bifurcation of PHA and GDA. The average follow-up time was 19.7 ± 15.9 month. There were two cases of artery thrombosis or occlusion, and the incidence was 2.7%. No arterial complications occurred in children using RGEA (follow-up time 5.0 ± 3.4 months). In P-LDLT for patients with metabolic diseases, the application of RGEA as an interposition vessel can solve caliber mismatch and short arteries problem and achieve good results. Compared with traditional arterial anastomosis, it may reduce the incidence of arterial complications. Show less
Sixuan Qu, Zhaoli Yang, Hongdi Tao+4 more · 2019 · Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology · added 2026-04-24
Objective To investigate the expression of semaphorin 6D (SEMA6D) and Snail and their clinicopathological implications in gastric cancer. Methods 54 cases of gastric cancer tissues and 26 paracancerou Show more
Objective To investigate the expression of semaphorin 6D (SEMA6D) and Snail and their clinicopathological implications in gastric cancer. Methods 54 cases of gastric cancer tissues and 26 paracancerous gastric mucosa were collected for detecting the expression of SEMA6D and Snail by immunohistochemistry and Western blot analysis. The co-localization of SEMA6D and Snail was observed by immunofluorescence double staining and laser scanning confocal microscopy. The correlation between SEMA6D and Snail and their relationships with the clinicopathological features of the patients were analyzed. Results Compared with the paracancerous gastric mucosa, the protein expression of SEMA6D and Snail in the gastric cancer significantly increased, and there was a significant co-localization of SEMA6D and Snail in gastric cancer. Further statistical analysis showed that the expression of SEMA6D and Snail in gastric cancer was positively correlated with the degree of differentiation, invasion, lymph node metastasis and TNM stage. Conclusion The high expression of SEMA6D and Snail in gastric cancer are related to the malignant clinicopathological indexes of gastric cancer. Show less
Persistent pulmonary hypertension of the newborn (PPHN) is a severe clinical problem among neonatal intensive care unit (NICU) patients. The genetic pathogenesis of PPHN is unclear. Only a few genetic Show more
Persistent pulmonary hypertension of the newborn (PPHN) is a severe clinical problem among neonatal intensive care unit (NICU) patients. The genetic pathogenesis of PPHN is unclear. Only a few genetic polymorphisms have been identified in infants with PPHN. Our study aimed to investigate the potential genetic etiology of PPHN. This study recruited PPHN patients admitted to the NICU of the Children's Hospital of Fudan University from Jan 2016 to Dec 2017. Exome sequencing was performed for all patients. Variants in reported PPHN/pulmonary arterial hypertension (PAH)-related genes were assessed. Single nucleotide polymorphism (SNP) association and gene-level analyses were carried out in 74 PPHN cases and 115 non-PPHN controls with matched baseline characteristics. Among the patient cohort, 74 (64.3%) patients were late preterm and term infants (≥ 34 weeks gestation) and 41 (35.7%) were preterm infants (< 34 weeks gestation). Preterm infants with PPHN exhibited low birth weight and a high frequency of bronchopulmonary dysplasia, respiratory distress syndrome (RDS) and mortality. Nine patients (only one preterm infant) were identified as harboring genetic variants, including three with pathogenic/likely pathogenic variants in TBX4 and BMPR2 and six with variants of unknown significance in BMPR2, SMAD9, TGFB1, KCNA5 and TRPC6. Three SNPs (rs192759073, rs1047883 and rs2229589) in CPS1 and one SNP (rs1044008) in NOTCH3 were significantly associated with PPHN (p < 0.05). CPS1 and SMAD9 were identified as risk genes for PPHN (p < 0.05). In this study, we identified genetic variants in PPHN patients, and we reported CPS1, NOTCH3 and SMAD9 as risk genes for late preterm and term PPHN in a single-center Chinese cohort. Our findings provide additional genetic evidence of the pathogenesis of PPHN and new insight into potential strategies for disease treatment. Show less