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
Many single nucleotide polymorphisms (SNPs) have been reported to be associated with migraine susceptibility. However, evidences for their associations with migraine endophenotypes or subtypes are sca Show more
Many single nucleotide polymorphisms (SNPs) have been reported to be associated with migraine susceptibility. However, evidences for their associations with migraine endophenotypes or subtypes are scarce. We aimed to investigate the associations of pre-identified migraine susceptibility loci in Taiwanese with migraine endophenotypes or subtypes, including chronic migraine and allodynia. The associations of six SNPs identified from our previous study, including TRPM8 rs10166942, LRP1 rs1172113, DLG2 rs655484, GFRA1 rs3781545, UPP2 rs7565931, and GPR39 rs10803531, and migraine endophenotypes, including chronic migraine and allodynia were tested. Significant associations in the discovery cohort were validated in the replication cohort. The adjusted odds ratios (aOR) were calculated after controlling for confounders. In total, 1904 patients (mean age 37.5 ± 12.2 years old, female ratio: 77.7%) including 1077 in the discovery cohort and 827 in the replication cohort were recruited. Of them, 584 (30.7%) had chronic migraine. Of the 6 investigated SNPs, TRPM8 rs10166942 T allele-carrying patients were more likely to have chronic migraine than non-T allele carriers in both discovery and replication cohorts and combined samples (33.7% vs. 25.8%, p = 0.004, aOR = 1.62). In addition, T allele carriers reported more allodynic symptoms than non-T allele carriers (3.5 ± 3.7 vs. 2.6 ± 2.8, p < 0.001). However, allodynia severity did not differ between episodic and chronic migraine patients. No further correlations between genetic variants and endophenotypes were noted for the other SNPs. TRPM8 may contribute to the pathogenesis of chronic migraine. However, our study did not support allodynia as a link between them. The underlying mechanisms deserve further investigations. 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
Neuromuscular junction is a synapse between motoneurons and skeletal muscles, where acetylcholine receptors (AChRs) are concentrated to control muscle contraction. Studies of this synapse have contrib Show more
Neuromuscular junction is a synapse between motoneurons and skeletal muscles, where acetylcholine receptors (AChRs) are concentrated to control muscle contraction. Studies of this synapse have contributed to our understanding of synapse assembly and pathological mechanisms of neuromuscular disorders. Nevertheless, underlying mechanisms of NMJ formation was not well understood. To this end, we took a novel approach - studying mutant genes implicated in congenital myasthenic syndrome (CMS). We showed that knock-in mice carrying N88K, a prevalent CMS mutation of Rapsyn (Rapsn), died soon after birth with profound NMJ deficits. Rapsn is an adapter protein that bridges AChRs to the cytoskeleton and possesses E3 ligase activity. In investigating how N88K impairs the NMJ, we uncovered a novel signaling pathway by which Agrin-LRP4-MuSK induces tyrosine phosphorylation of Rapsn, which is required for its self-association and E3 ligase activity. Our results also provide insight into pathological mechanisms of CMS. 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
Alopecia or hair loss is a complex polygenetic and psychologically devastating disease affecting millions of men and women globally. Since the gene annotation and environmental knowledge is limited fo Show more
Alopecia or hair loss is a complex polygenetic and psychologically devastating disease affecting millions of men and women globally. Since the gene annotation and environmental knowledge is limited for alopecia, a systematic analysis for the identification of candidate biomarkers is required that could provide potential therapeutic targets for hair loss therapy. We designed an interactive framework to perform a meta-analytical study based on differential expression analysis, systems biology, and functional proteomic investigations. We analyzed eight publicly available microarray datasets and found 12 potential candidate biomarkers including three extracellular proteins from the list of differentially expressed genes with a Our integrative approach helps to prioritize the biomarkers that ultimately lessen the economic burden of experimental studies. It will also be valuable to discover mutants in genomic data in order to increase the identification of new biomarkers for similar problems. Show less
Recent studies implicate a strong association between elevated plasma branched-chain amino acids (BCAAs) and insulin resistance (IR). However, a causal relationship and whether interrupted BCAA homeos Show more
Recent studies implicate a strong association between elevated plasma branched-chain amino acids (BCAAs) and insulin resistance (IR). However, a causal relationship and whether interrupted BCAA homeostasis can serve as a therapeutic target for diabetes remain to be established experimentally. In this study, unbiased integrative pathway analyses identified a unique genetic link between obesity-associated IR and BCAA catabolic gene expression at the pathway level in human and mouse populations. In genetically obese ( Show less
The aberrant expression of ceroid-lipofuscinosis 3 (CLN3) has been reported in a variety of human malignancies. However, the role of CLN3 in the progression and prognosis of hepatocellular carcinoma ( Show more
The aberrant expression of ceroid-lipofuscinosis 3 (CLN3) has been reported in a variety of human malignancies. However, the role of CLN3 in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. In this study, we found that CLN3 was frequently upregulated in HCC clinical samples and HCC-derived cell lines and was significantly correlated with an APF serum level ≥20 μg/L, a tumour size ≥5 cm, multiple tumours, and the absence of encapsulation. Kaplan-Meier showed that CLN3 upregulation predicted shorter recurrence-free survival (RFS) and overall survival (OS) time in HCC patients. Cox regression analysis revealed that CLN3 upregulation was an independent risk factor for RFS and OS. A functional study demonstrated that the knockdown of CLN3 expression profoundly suppressed the growth and metastasis of HCC cells both in vitro and in vivo. Mechanistic investigation revealed that the EGFR/PI3K/AKT pathway was essential for mediating CLN3 function. In conclusion, our results provide the first evidence that CLN3 contributes to tumour progression and metastasis and offer a potential prognostic predictor and therapeutic target for HCC. 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
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
Lead optimization of the diphenylpyridylethanamine (DPPE) and triphenylethanamine (TPE) series of CETP inhibitors to improve their pharmaceutical profile is described. Polar groups at the
Growth and fat deposition are important economic traits due to the influence on production in pigs. In this study, a dataset of 1200 pigs with 345,570 SNPs genotyped by sequencing (GBS) was used to co Show more
Growth and fat deposition are important economic traits due to the influence on production in pigs. In this study, a dataset of 1200 pigs with 345,570 SNPs genotyped by sequencing (GBS) was used to conduct a GWAS with single-marker regression method to identify SNPs associated with body weight and backfat thickness (BFT) and to search for candidate genes in Landrace and Yorkshire pigs. A total of 27 and 13 significant SNPs were associated with body weight and BFT, respectively. In the region of 149.85-149.89 Mb on SSC6, the SNP (SSC6: 149876737) for body weight and the SNP (SSC6: 149876507) for BFT were in the same locus region (a gap of 230 bp). Two SNPs were located in the DOCK7 gene, which is a protein-coding gene that plays an important role in pigmentation. Two SNPs located on SSC8: 54567459 and SSC11: 33043081 were found to overlap weight and BFT; however, no candidate gene was found in these regions. In addition, based on other significant SNPs, two positional candidate genes, NSRP1 and CADPS, were proposed to influence weight. In conclusion, this is the first study report using GBS data to identify the significant SNPs for weight and BFT. A total of four particularly interesting SNPs and one potential candidate genes (DOCK7) were found for these traits in domestic pigs. This study improves our knowledge to better understand the complex genetic architecture of weight and BFT, but further validation studies of these candidate loci and genes are recommended in pigs. 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
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
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
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
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
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
Tripartite motif-containing protein 7 (TRIM7), which is involved in the biosynthesis of glycogen, has been reported to drive lung tumorigenesis. In the present study, we aimed to examine the expressio Show more
Tripartite motif-containing protein 7 (TRIM7), which is involved in the biosynthesis of glycogen, has been reported to drive lung tumorigenesis. In the present study, we aimed to examine the expression, roles and underlying molecular mechanisms of TRIM7 in hepatocellular carcinoma (HCC) development. Real-time PCR and immunohistochemical staining were performed to test the expression of TRIM7 in HCC tissues. Cell proliferation, cell cycle and tumorigenicity experiments were conducted to determine the function of TRIM7. The results showed that TRIM7 expression was elevated in human HCC tissues and that TRIM7 expression was significantly associated with tumor size, pTNM stage, serum α-fetoprotein (AFP) concentration, serum hepatitis B virus (HBV) DNA copy number and overall survival (OS) of HCC patients. TRIM7 knockdown inhibited the proliferation of HCC cells in vitro and in vivo. TRIM7 knockdown also induced a G1/S checkpoint in HCC cell lines. Additionally, TRIM7 knockdown led to decreased phosphorylated p38 (p-p38) and increased expression of p53 and p21. Ectopic expression of TRIM7 promoted HCC cell proliferation, cell cycle progression and p38 activation, but not in the presence of the p38 inhibitor SB203580. Moreover, TRIM7 overexpression enhanced the polyubiquitination and degradation of dual specificity phosphatase 6 (DUSP6). DUSP6 overexpression abolished the promotional effect of TRIM7 overexpression on HCC cell proliferation and the activation of p38. Furthermore, HBV X protein (HBx), a protein coded by HBV, was demonstrated to upregulate TRIM7 expression. Collectively, TRIM7 overexpression may contribute to the highly proliferative characteristics of HCC cells, and targeting TRIM7 might be a potential strategy for HCC treatment. 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
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
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
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
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
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
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
Microbial fuel cells (MFCs) are eco-friendly bio-electrochemical reactors that use exoelectrogens as biocatalyst for electricity harvest from organic biomass, which could also be used as biosensors fo Show more
Microbial fuel cells (MFCs) are eco-friendly bio-electrochemical reactors that use exoelectrogens as biocatalyst for electricity harvest from organic biomass, which could also be used as biosensors for long-term environmental monitoring. Glucose and xylose, as the primary ingredients from cellulose hydrolyzates, is an appealing substrate for MFC. Nevertheless, neither xylose nor glucose can be utilized as carbon source by well-studied exoelectrogens such as 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