Melanocortin-3 and -4 receptors (MC3R and MC4R), G protein-coupled receptors, play vital roles in the regulation of energy homeostasis. To understand the functions of The full-length cDNAs of RCC In c Show more
Melanocortin-3 and -4 receptors (MC3R and MC4R), G protein-coupled receptors, play vital roles in the regulation of energy homeostasis. To understand the functions of The full-length cDNAs of RCC In conclusion, these results will assist in the further investigation of the molecular mechanisms in which MC3R and MC4R were involved in the regulation of energy homeostasis in fish. Show less
Schisandra chinensis (sc) is generally demonstrated to improve antioxidant and immune functions in mammal. The present study through physiological and transcriptome analysis revealed alterations in mu Show more
Schisandra chinensis (sc) is generally demonstrated to improve antioxidant and immune functions in mammal. The present study through physiological and transcriptome analysis revealed alterations in muscle metabolisms of triploid crucian carp (Carassius auratus) cultured at different concentrations of S. chinensis diets (sc0, sc0.125%, sc0.25%, sc0.5%, sc1%, sc2%) after 8 weeks. The serum antioxidant enzyme activities analysis showed that dietary S. chinensis could reduce oxidative stress and increase organismic antioxidant capacity. Meanwhile, the detected results of muscle components presented that the amino acids and two flavor nucleotides of GMP and IMP significantly elevated while muscle crude lipid significantly reduced in S. chinensis feeding groups. In addition, springiness, chewiness, and fiber density in S. chinensis feeding groups muscle were significantly upregulated while muscle fiber diameter and area showed an opposite trend. By comparative transcriptome analysis of the muscles, functional enrichments of differentially expressed genes showed that multiple terms were related to purine metabolism, glycerolipid metabolism, regulation of actin cytoskeleton, and peroxisome. Finally, some key hub genes such as egln, gst, ggct, su1b, pi3kr4, myh9, lpl, gcdh, mylk, and col4a were identified by weighted gene co-expression network analysis. Taken together, our findings facilitate the understanding of the molecular basis underlying the muscle quality effect of dietary S. chinensis in triploid crucian carp, which provides valuable insights into the nutritional strategies of the aquaculture industry. Show less
Mutations in MC4R are the most common genetic cause of obesity. In the reported Chinese morbid obesity cohort, 10 out of 59 harbor six MC4R variants, including Y35C, T53I, V103I, R165W, G233S, and C27 Show more
Mutations in MC4R are the most common genetic cause of obesity. In the reported Chinese morbid obesity cohort, 10 out of 59 harbor six MC4R variants, including Y35C, T53I, V103I, R165W, G233S, and C277X, among which V103I has a relatively high frequency, while other five variants are rare in the population. The prevalence of MC4R carriers in Chinese morbid obese patients (body mass index ≥ 45 kg m Show less
Chronic cerebral hypoperfusion (CCH) is a main mechanism of cerebrovascular disease and is associated with various cerebrovascular and neurodegenerative diseases, including Alzheimer's disease. Howeve Show more
Chronic cerebral hypoperfusion (CCH) is a main mechanism of cerebrovascular disease and is associated with various cerebrovascular and neurodegenerative diseases, including Alzheimer's disease. However, treatment of CCH in clinical practice is not ideal, but neurotropin (NTP) has been shown to have a neuroprotective effect. Therefore, this study examined the effect and possible mechanism of NTP in nerve injury caused by CCH. A rat CCH model was established by bilateral common carotid artery occlusion (2VO), and rats were treated with intragastric administration of NTP (200 nu/kg/day) for 28 consecutive days. After treatment, rats were subjected to the Morris water maze and novel object recognition test. Subsequently, an ELISA was applied to detect amyloid-β (Aβ) 1-40 and Aβ1-42 levels in rat hippocampal tissues, quantitative reverse transcription PCR assays were used to detect the mRNA expression levels of brain-derived neurotrophic factor (BDNF) and Trk B, and Western blots were used to detect the protein expression levels of BACE1, tau, p-tau, and protein kinase B (Akt)/glycogen synthase kinase 3β (GSK3β) pathway-related proteins. The rat model of CCH was successfully established by 2VO. Behavioral tests indicated that the cognitive ability of 2VO rats was severely impaired. NTP treatment greatly ameliorated the cognitive disability, reduced Aβ1-40 and Aβ1-42 levels and tau phosphorylation, and upregulated BACE1, Trk B, and BDNF expression in the hippocampus of 2VO rats. Finally, we found that NTP markedly activated Akt/GSK3β pathway activity. NTP can ameliorate cognitive disability in CCH rats possibly by reducing Aβ accumulation and tau phosphorylation in the hippocampus. These effects of NTP may be related to the Akt/GSK3β pathway activation. NTP may be a promising new drug candidate for CCH patients. Show less
BACE1 is essential for the generation of amyloid-β (Aβ) that likely initiates the toxicity in Alzheimer's disease (AD). BACE1 activity is mainly regulated by post-translational modifications, but the Show more
BACE1 is essential for the generation of amyloid-β (Aβ) that likely initiates the toxicity in Alzheimer's disease (AD). BACE1 activity is mainly regulated by post-translational modifications, but the relationship between these modifications is not fully characterized. Here, we studied the effects of BACE1 SUMOylation on its phosphorylation and ubiquitination. We demonstrate that SUMOylation of BACE1 inhibits its phosphorylation at S498 and its ubiquitination in vitro. Conversely, BACE1 phosphorylation at S498 suppresses its SUMOylation, which results in promoting BACE1 degradation in vitro. Furthermore, an increase in BACE1 SUMOylation is associated with the progression of AD pathology, while its phosphorylation and ubiquitination are decreased in an AD mouse model. Our findings suggest that BACE1 SUMOylation reciprocally influences its phosphorylation and competes against its ubiquitination, which might provide a new insight into the regulations of BACE1 activity and Aβ accumulation. Show less
Homeobox A13 (HOXA13) has been verified as an oncogen in some malignancies. However, its role in nasopharyngeal carcinoma (NPC) is still unclear. This study aims to explore the role of HOXA13 in NPC a Show more
Homeobox A13 (HOXA13) has been verified as an oncogen in some malignancies. However, its role in nasopharyngeal carcinoma (NPC) is still unclear. This study aims to explore the role of HOXA13 in NPC and its underlying mechanism. The mRNA expression of HOXA13 in NPC was obtained from the GSE53819 and GSE64634 datasets in the Gene Expression Omnibus (GEO) database. MTT, colony formation and transwell assays and xenograft tumour models were used to investigate the effects of HOXA13 on NPC HNE1 cells in vitro and in vivo. The expression of HOXA13, epithelial-mesenchymal transition-transcription factor (EMT-TF) Snail and matrix metalloproteinase 2 (MMP-2) was detected by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The results showed that HOXA13 was upregulated in NPC. Silencing HOXA13 suppressed the proliferation, migration, and invasion of HNE1 cells, which inhibited tumour growth, while overexpression of HOXA13 induced the opposite effects. In addition, the expression of Snail and MMP-2 at the transcriptional and protein levels was associated with the expression of HOXA13. In summary, our results suggest that HOXA13 plays a role as a cancer-promoting gene in NPC. The underlying mechanism may be related to the upregulation of Snail and MMP-2. Show less
Analogues of the hepatokine fibroblast growth factor 21 (FGF21) are in clinical development for type 2 diabetes and nonalcoholic steatohepatitis (NASH) treatment. Although their glucose-lowering and i Show more
Analogues of the hepatokine fibroblast growth factor 21 (FGF21) are in clinical development for type 2 diabetes and nonalcoholic steatohepatitis (NASH) treatment. Although their glucose-lowering and insulin-sensitizing effects have been largely unraveled, the mechanisms by which they alleviate liver injury have only been scarcely addressed. Here, we aimed to unveil the mechanisms underlying the protective effects of FGF21 on NASH using APOE*3-Leiden.CETP mice, a well-established model for human-like metabolic diseases. Liver-specific FGF21 overexpression was achieved in mice, followed by administration of a high-fat high-cholesterol diet for 23 weeks. FGF21 prevented hepatic lipotoxicity, accompanied by activation of thermogenic tissues and attenuation of adipose tissue inflammation, improvement of hyperglycemia and hypertriglyceridemia, and upregulation of hepatic programs involved in fatty acid oxidation and cholesterol removal. Furthermore, FGF21 inhibited hepatic inflammation, as evidenced by reduced Kupffer cell (KC) activation, diminished monocyte infiltration, and lowered accumulation of monocyte-derived macrophages. Moreover, FGF21 decreased lipid- and scar-associated macrophages, which correlated with less hepatic fibrosis as demonstrated by reduced collagen accumulation. Collectively, hepatic FGF21 overexpression limits hepatic lipotoxicity, inflammation, and fibrogenesis. Mechanistically, FGF21 blocks hepatic lipid influx and accumulation through combined endocrine and autocrine signaling, respectively, which prevents KC activation and lowers the presence of lipid- and scar-associated macrophages to inhibit fibrogenesis. Show less
To assess the causal role of lipid traits and lipid-lowering agents in inflammatory bowel disease (IBD). Univariable mendelian randomization (MR) and multivariable MR (MVMR) analyses were conducted to Show more
To assess the causal role of lipid traits and lipid-lowering agents in inflammatory bowel disease (IBD). Univariable mendelian randomization (MR) and multivariable MR (MVMR) analyses were conducted to evaluate the causal association between low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and IBD. Drug-targeted MR analyzed the effects of lipid-lowering drugs on IBD, and network MR was used to analyze potential mediation effects. The levels of HDL-C had an inverse relationship with the risk of Crohn's disease (CD, OR: 0.85, 95% CI: 0.73-0.98, Our study suggested a causal association between HDL-C and IBD, UC and CD. Genetically proxied inhibition of Show less
Heterosis, also known as hybrid vigor, is widely used in aquaculture, but the molecular causes for this phenomenon remain obscure. Here, we conducted a transcriptome analysis to unveil the gene expres Show more
Heterosis, also known as hybrid vigor, is widely used in aquaculture, but the molecular causes for this phenomenon remain obscure. Here, we conducted a transcriptome analysis to unveil the gene expression patterns and molecular bases underlying thermo-resistant heterosis in Crassostrea gigas ♀ × Crassostrea angulata ♂ (GA) and C. angulata ♀ × C. gigas ♂ (AG). About 505 million clean reads were obtained, and 38,210 genes were identified, of which 3779 genes were differentially expressed between the reciprocal hybrids and purebreds. The global gene expression levels were toward the C. gigas genome in the reciprocal hybrids. In GA and AG, 95.69% and 92.00% of the differentially expressed genes (DEGs) exhibited a non-additive expression pattern, respectively. We observed all gene expression modes, including additive, partial dominance, high and low dominance, and under- and over-dominance. Of these, 77.52% and 50.00% of the DEGs exhibited under- or over-dominance in GA and AG, respectively. The over-dominance DEGs common to reciprocal hybrids were significantly enriched in protein folding, protein refolding, and intrinsic apoptotic signaling pathway, while the under-dominance DEGs were significantly enriched in cell cycle. As possible candidate genes for thermo-resistant heterosis, GRP78, major egg antigen, BAG, Hsp70, and Hsp27 were over-dominantly expressed, while MCM6 and ANAPC4 were under-dominantly expressed. This study extends our understanding of the thermo-resistant heterosis in oysters. Show less
Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA) metabolism-related genes play an important role in the development of cancers. We assessed the associations of genetic v Show more
Polycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines (TSNA) metabolism-related genes play an important role in the development of cancers. We assessed the associations of genetic variants in genes involved in the metabolism of PAHs and TSNA with risk of squamous cell carcinoma of the head and neck (SCCHN) in European populations using two published genome-wide association study datasets. In the single-locus analysis, we identified two SNPs (rs145533669 and rs35246205) in CYP2B6 to be associated with risk of SCCHN (P = 1.57 × 10 Show less
Studies have shown that environmental carcinogens exerted an important function in the high incidence of esophageal cancer (EC). Nitrosamines have been identified as important environmental carcinogen Show more
Studies have shown that environmental carcinogens exerted an important function in the high incidence of esophageal cancer (EC). Nitrosamines have been identified as important environmental carcinogens for EC. This study aimed to investigate the metabolic disturbances and new key toxicological markers in the malignant transformation process of normal esophageal epithelial cells (Het-1A) induced by MNNG (N-methyl-N'-nitro-N-nitrosoguanidine). Untargeted metabolomic and lipidomic profiling analysis by using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) were applied to explore the metabolic network alterations of Het-1A cells. The metabolomic results showed that significant alterations were observed in metabolic signatures between different generations (P5, P15, P25, P35) and the control cell group (P0). A total of 48 differential endogenous metabolites were screened and identified, mainly containing fatty acids, amino acids, and nucleotides. The differential metabolites were predominantly linked to the pathway of biosynthesis of unsaturated fatty acids metabolism. The cell lipidomic profiling revealed that the most differential lipids contained fatty acids (FAs), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and phosphatidylserines (PS). The enrichment of the lipidomic pathway also confirmed that the lipid metabolism of biosynthesis of unsaturated fatty acids was the significant variation during the cell malignant transformation. Furthermore, we detected the expression of the upstream regulatory enzymes related to the unsaturated fatty acids to explore the regulation mechanism. The expression of stearoyl-CoA desaturase (SCD), ELOVL fatty acid elongase 1 (ELOVL1) promoted, and fatty acid desaturase 1 (FADS1) inhibited the key fatty acids of unsaturated fatty acids metabolism compared to the control cell group. Overall, our results revealed that lipid fatty acid metabolism was involved in the malignant transformation of Het-1A cells induced by MNNG and deepened the awareness of the carcinogenic mechanism of environmental exposure pollutants. Show less
Echinacoside (ECH), a phenylethanoid glycoside, has protective activity in neurodegenerative disease, including anti-inflammation and antioxidation. However, the effects of ECH in Alzheimer's disease Show more
Echinacoside (ECH), a phenylethanoid glycoside, has protective activity in neurodegenerative disease, including anti-inflammation and antioxidation. However, the effects of ECH in Alzheimer's disease (AD) are not very clear. This present study investigates the role and mechanism of ECH in the pathological process of AD. APP/PS1 mice treated with ECH in 50 mg/kg/day for 3 months. Morris water maze, nesting test, and immunofluorescence staining used to observe whether ECH could improve AD pathology. Western blot used to study the mechanism of ECH improving AD pathology. The results showed that ECH alleviated the memory impairment of APP/PS1 mice by reducing the time of escape latency as well as increasing the times of crossing the platform and rescued the impaired ability to construct nests. In addition, ECH significantly reduced the deposition of senile plaques in the brain and decreased the expression of BACE1 in APP/PS1 mice through activating PI3K/AKT/Nrf2/PPARγ pathway. Furthermore, ECH decreased ROS formation, GP91 and 8-OHdG expression, upregulated the expression of SOD1 and SOD2 as well as activating the PI3K/AKT/Nrf2 signaling pathway. Moreover, ECH inhibited glia cells activation, pro-inflammatory cytokine IL-1β and TNF-α release, NLRP3 inflammasome formation through TXNIP/Trx-1 signaling pathway. In conclusion, this paper reported that ECH improved cognitive function, inhibited oxidative stress, and inflammatory response in AD. Therefore, we suggest that ECH may considered as a potential drug for AD treatment. Show less
Psoriasis is a chronic inflammatory skin disorder related to dyslipidemia, with decreased high-density lipoprotein (HDL). Various cell types express phospholipid transfer protein (PLTP) as well as cho Show more
Psoriasis is a chronic inflammatory skin disorder related to dyslipidemia, with decreased high-density lipoprotein (HDL). Various cell types express phospholipid transfer protein (PLTP) as well as cholesteryl ester transfer protein (CETP). Their elevated levels among transgenic (Tg) mice led to reduced HDL and a higher risk of atherosclerosis (AS). This study examined whether elevated CETP and PLTP could aggravate psoriasis in a psoriasis vulgaris mouse model. The back skins of CETP-Tg, PLTP-Tg, and C57BL/6 male mice, aged six to 8 weeks, were shaved for imiquimod cream (IMQ) (5%) treatment for five consecutive days. The clinical pathological parameters were rated independently using the modified target lesion psoriasis severity score. The skin sections stained with hematoxylin-eosin were scored by the Baker score. Epidermal thickening and differentiation and inflammatory factor infiltration were determined by immunohistochemistry. Inflammatory cytokine levels were measured using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. This work employed SPSS Statistics Version to conduct statistical analyses. In this study, CETP-Tg and PLTP-Tg mice had higher clinical and histological scores than wild-type (WT) mice. Immunohistochemistry of the epidermis and dermis revealed a high proportion of proliferating cell nuclear antigen (PCNA) positivity within psoriatic skin lesions of CETP-Tg and PLTP-Tg mice compared with WT mice. Interferon-α (IFN-α), interleukin-1β (IL-1β), IL-6, IL-17A, IL-17F, IL-22, and IL-23p19 mRNA levels increased within CETP-Tg and PLTP-Tg mice compared with WT counterparts. In comparison with WT mice, plasma tumor necrosis factor-α (TNF-α) levels, rather than IL-6 levels, were increased in CETP-Tg and PLTP-Tg mice. Elevated CETP and PLTP aggravate psoriasis in a imiquimod-induced mouse model. Show less
DNA methylation plays a significant role in transducing external environmental signals to a cellular response in reptiles; however, whether the methylation patterns are conserved across species remain Show more
DNA methylation plays a significant role in transducing external environmental signals to a cellular response in reptiles; however, whether the methylation patterns are conserved across species remains unclear. Here, we examined the genome-wide DNA methylation differentiation between male and female hatchling gonads of the temperature-dependent sex determination (TSD) Mauremys mutica (M. mutica) using methylation-dependent restriction-site associated DNA sequencing (MethylRAD-seq) to test differentially methylated genes underlying sexual development. Several categories, including heat-shock genes (HSP90A, HSP30C), histone- (KDM8) and ubiquitin-related genes (TRIM39), kinases (WNK3), and gonad differentiation or gonadal-development-related genes (HSD17B8, HSD17B12), were identified as candidates for future study. Additionally, we identified several regulatory pathways potentially mediating TSD thermosensitivity such as the GnRH signaling pathway and calcium signaling pathway. These findings provide evidence that sexually dimorphic DNA methylation may be associated with sex determination or sex differentiation in TSD M. mutica. Show less
Nitrite is a ubiquitous toxic compound in aquatic ecosystems and has negative effects on aquatic organisms. The intestine and the trillions of microbes that inhabit it, play an integral role in mainta Show more
Nitrite is a ubiquitous toxic compound in aquatic ecosystems and has negative effects on aquatic organisms. The intestine and the trillions of microbes that inhabit it, play an integral role in maintaining digestive and immune functions. However, the effects of nitrite on intestinal health and microflora have been poorly investigated. Therefore, the present study evaluated the response of intestinal histology, immunity, digestive enzyme activities and microbiota to nitrite exposure in Bufo gargarizans tadpoles. The results showed that nitrite caused damage to the intestine and impaired digestive performance. Significant changes in the transcriptional profiles of genes involved in oxidative stress (sod, gpx and hsp), inflammation, and immunity (socs3, il-27, il-1β and il-17d) were observed in the NO Show less
Obesity is one of the most serious public health challenges. Recently, we found that flaxseed polysaccharides (FPs) had an anti-obesity effect through promoting lipid metabolism, but the obesity-inhib Show more
Obesity is one of the most serious public health challenges. Recently, we found that flaxseed polysaccharides (FPs) had an anti-obesity effect through promoting lipid metabolism, but the obesity-inhibiting pathway of FP is still unclear. In this study, after FP intervention in an obese rat model, a transcriptome study was performed to further investigate how FP intervention alters the gene expression of colonic epithelial tissues (CETs). The results showed that there were 3785 genes differentially expressed due to the FP intervention, namely 374 downregulated and 3411 upregulated genes. After analyzing all the differentially expressed genes, two classical KEGG pathways were found to be related to obesity, namely the PPAR-signaling pathway and energy metabolism, involving genes Show less
Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activa Show more
Appropriate decidualization is of great importance for embryo implantation, placental development and successful pregnancy. Although it has been well-acknowledged that decidualization relies on activation of progesterone-mediated signaling pathway, the exact mechanisms have not been elucidated. Here, we demonstrated that both IL-27 and IL27RA were highly expressed in decidua than those in endometrium during secretory phase. Estrogen plus progesterone significantly upregulated the expression of IL-27 and IL-27RA in endometrium stromal cells (ESCs). In addition, inhibiting IL-27 signaling with IL-27 neutralization antibody (anti-IL-27) suppressed the expression of decidualization-related molecules, receptors of estrogen (gene coded by ESR) and progesterone (PGR) induced by cAMP or estrogen plus progesterone. Similar results were obtained from Il27ra Show less
Asthma is an airway disease characterized by airflow limitation and various additional clinical manifestations. Repeated inflammatory stimulation of the airways leads to epithelial-mesenchymal transit Show more
Asthma is an airway disease characterized by airflow limitation and various additional clinical manifestations. Repeated inflammatory stimulation of the airways leads to epithelial-mesenchymal transition (EMT) which aggravates subepithelial fibrosis during the process of airway remodelling and enhances resistance to corticosteroids and bronchodilators in refractory asthma. There is growing evidence that IL-27 modulates airway remodelling, however, the molecular mechanisms involving IL-27 and EMT are poorly understood. The objective of this study was to investigate the effects of IL-27 on ovalbumin (OVA)-challenged asthmatic mice in vivo and TGF-β1-induced EMT in 16HBE cells in vitro. Airway inflammation, mucus secretion, and collagen deposition were analysed by conventional pathological techniques. The ratio of Th17 and Th9 cells in the spleen of mice was measured using flow cytometry, ELISA was performed for cytokine analysis to identify EMT-related molecules and signalling pathways, and other molecular and cellular techniques were used to explore the functional mechanism involving IL-27 and EMT. Airway inflammation in asthmatic mice was significantly alleviated by IL-27, with downregulation of RhoA and ROCK, upregulation of E-cadherin, and a decrease of vimentin and α-SMA expression, compared to asthmatic mice. Moreover, the frequency of Th17 and Th9 cells in the spleen of asthmatic mice decreased following treatment with IL-27. In TGF-β1-induced 16HBE cells, the addition of IL-27 was shown to inhibit EMT, based on the expression of E-cadherin, vimentin, and α-SMA. Intranasal administration of IL-27 attenuates airway inflammation and EMT in a murine model of allergic asthma possibly by downregulating the RhoA/ROCK signalling pathway. Show less
Liver sinusoidal endothelial cells (LSECs) serve as sentinel cells to detect microbial infection and actively contribute to regulating immune responses for surveillance against intrahepatic pathogens. Show more
Liver sinusoidal endothelial cells (LSECs) serve as sentinel cells to detect microbial infection and actively contribute to regulating immune responses for surveillance against intrahepatic pathogens. We recently reported that hepatitis B e antigen (HBeAg) stimulation could induce LSEC maturation and abrogate LSEC-mediated T cell suppression in a TNF-α and IL27 dependent manner. However, it remains unclear how HBeAg deficiency during HBV infection influences LSEC immunoregulation function and intrahepatic HBV-specific CD8 T cell responses. The function of LSECs in regulating effector T cell response, intrahepatic HBV-specific CD8 T cell responses and HBV viremia were characterized in both HBeAg-deficient and -competent HBV hydrodynamic injection (HDI) mouse models. LSECs isolated from HBeAg-deficient HBV HDI mice showed a reduced capacity to promote T cell immunity Our study underlines that HBeAg is indispensable for HBV-induced LSEC maturation to trigger intrahepatic HBV-specific T cell activation, and provides a new mechanism to elucidate the intrahepatic immune microenvironment regulation upon HBV exposure. Show less
The most hostile form of urologic cancer, clear cell renal cell carcinoma (ccRCC), has a high fatality rate and poor prognosis due to tumor metastasis at initial presentation. The complex process driv Show more
The most hostile form of urologic cancer, clear cell renal cell carcinoma (ccRCC), has a high fatality rate and poor prognosis due to tumor metastasis at initial presentation. The complex process driving ccRCC metastasis is still unknown, though. In this study, we demonstrate that Spindle and kinetochore-associated protein 1 (SKA1) expression is significantly upregulated in ccRCC tissues and associated with aggressive clinicopathologic characteristics. Functionally, SKA1 knockdown on ccRCC cells reduced cancer cell motility both Show less
The molecular mechanisms of uric acid (UA)-induced liver injury has not been clearly elucidated. In this study, we aimed to investigate the effect and action mechanisms of UA in liver injury. We analy Show more
The molecular mechanisms of uric acid (UA)-induced liver injury has not been clearly elucidated. In this study, we aimed to investigate the effect and action mechanisms of UA in liver injury. We analyzed the damaging effect of UA on mouse liver and L02 cells and subsequently performed metabolomics studies on L02 cells to identify abnormal metabolic pathways. Finally, we verified transcription factors that regulate related metabolic enzymes. UA directly activated the hepatic NLRP3 inflammasome and Bax apoptosis pathway invivo and invitro. Related metabolites in the arginine biosynthesis pathway (or urea cycle), l-arginine and l-argininosuccinate were decreased, and ammonia was increased in UA-stimulated L02 cells, which was mediated by carbamoyl phosphate synthase 1 (CPS1), argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) downregulation. UA upregulated hypoxia inducible factor-1alpha (HIF-1α) invivo and invitro, and HIF-1α inhibition alleviated the UA-induced ASS downregulation and hepatocyte injury. In conclusion, UA upregulates HIF-1α and inhibits urea cycle enzymes (UCEs). This leads to liver injury, with evidence of hepatocyte inflammation, apoptosis and oxidative stress. Show less
Agricultural use of neonicotinoid insecticides, neuroactive nitroguanidine compounds, has been detected everywhere in the global, posing significant hazard to nontarget organisms. This work studied th Show more
Agricultural use of neonicotinoid insecticides, neuroactive nitroguanidine compounds, has been detected everywhere in the global, posing significant hazard to nontarget organisms. This work studied the developmental neurotoxicity of zebrafish larvae exposed to imidacloprid (IMI) and thiamethoxam (THM), ranging from 0.05 µg L Show less
Transcriptional factors, such as Snail, Slug, and Smuc, that cause epithelial-mesenchymal transition are thought to regulate the expression of Ezrin, Radixin, and Moesin (ERM proteins), which serve as Show more
Transcriptional factors, such as Snail, Slug, and Smuc, that cause epithelial-mesenchymal transition are thought to regulate the expression of Ezrin, Radixin, and Moesin (ERM proteins), which serve as anchors for efflux transporters on the plasma membrane surface. Our previous results using lung cancer clinical samples indicated a correlation between Slug and efflux transporter MRP2. In the current study, we aimed to evaluate the relationships between MRP2, ERM proteins, and Slug in lung cancer cells. HCC827 cells were transfected by Mock and Slug plasmid. Both mRNA expression levels and protein expression levels were measured. Then, the activity of MRP2 was evaluated using CDCF and SN-38 (MRP2 substrates). HCC827 cells transfected with the Slug plasmid showed significantly higher mRNA expression levels of MRP2 than the Mock-transfected cells. However, the mRNA expression levels of ERM proteins did not show a significant difference between Slug-transfected cells and Mock-transfected cells. Protein expression of MRP2 was increased in Slug-transfected cells. The uptake of both CDCF and SN-38 was significantly decreased after transfection with Slug. This change was abrogated by treatment with MK571, an MRP2 inhibitor. The viability of Slug-transfected cells, compared to Mock cells, significantly increased after incubation with SN-38. Thus, Slug may increase the mRNA and protein expression of MRP2 without regulation by ERM proteins in HCC827 cells, thereby enhancing MRP2 activity. Inhibition of Slug may reduce the efficacy of multidrug resistance in lung cancer. Show less
Chunhua Liu, Wei Zhang, Guozheng Xu+5 more · 2022 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
The risk of high-grade gliomas is lower in young females, however, its incidence enhances after menopause, suggesting potential protective roles of female sex hormones. Hormone oscillations after meno Show more
The risk of high-grade gliomas is lower in young females, however, its incidence enhances after menopause, suggesting potential protective roles of female sex hormones. Hormone oscillations after menopause have received attention as a possible risk factor. Little is known about risk factors for adult gliomas. We examined the association of the aging brain after menopause, determining the risk of gliomas with proteomics and the MALDI-MSI experiment. Menopause caused low neurotransmitter levels such as GABA and ACH, high inflammatory factor levels like il-1β, and increased lipid metabolism-related levels like triglycerides in the brain. Upregulated and downregulated proteins after menopause were correlated with differentially expressed glioma genes, such as ACTA2, CAMK2D, FNBPIL, ARL1, HEBP1, CAST, CLIC1, LPCAT4, MAST3, and DOCK9. Furthermore, differential gene expression analysis of monocytes showed that the downregulated gene LPCAT4 could be used as a marker to prevent menopausal gliomas in women. Our findings regarding the association of menopause with the risk of gliomas are consistent with several extensive cohort studies. In view of the available evidence, postmenopausal status is likely to represent a significant risk factor for gliomas. Show less
Non-ischemic cardiomyopathy (NICM) can cause left ventricular dysfunction through interstitial fibrosis, which corresponds to the failure of cardiac tissue remodeling. Recent evidence implicates monoc Show more
Non-ischemic cardiomyopathy (NICM) can cause left ventricular dysfunction through interstitial fibrosis, which corresponds to the failure of cardiac tissue remodeling. Recent evidence implicates monocytes/macrophages in the etiopathology of cardiac fibrosis, but giving their heterogeneity and the antagonizing roles of macrophage subtypes in fibrosis, targeting these cells has been challenging. Here we focus on WWP2, an E3 ubiquitin ligase that acts as a positive genetic regulator of human and murine cardiac fibrosis, and show that myeloid specific deletion of WWP2 reduces cardiac fibrosis in hypertension-induced NICM. By using single cell RNA sequencing analysis of immune cells in the same model, we establish the functional heterogeneity of macrophages and define an early pro-fibrogenic phase of NICM that is driven by Ccl5-expressing Ly6c Show less