Melatonin (MLT), produced by the pineal gland and other tissues, is known for its anti-inflammatory effects, particularly in regulating inflammatory markers and cytokines in intestinal cells. Our study aimed to investigate how MLT influences the expression of inflammatory genes through histone modification in canine ileum epithelial cells (cIECs). In our experiment, cIECs were cultured and divided into a control group (CON) and an MLT-treatment group. MLT did not significantly affect cell growth or death in cIECs compared to the CON. However, MLT treatment led to an upregulation of CD40, ZAP70, and IL7R and a downregulation of LCK, RPL37, TNFRSF13B, CD4, CD40LG, BLNK, and CIITA at the mRNA expression level. Moreover, MLT significantly altered the NF-kappa B signaling pathway by upregulating genes, such as CD40, ZAP70, TICAM1, VCAMI, GADD45B, IRAK1, TRADD, RELA, RIPK1, and RELB, and downregulating PRKCB, LY96, CD40LG, ILIB, BLNK, and TNFRSF11A. Using ChIP-qPCR, we discovered that MLT treatment enhanced histone acetylation marks H3K9ac, H3K18ac, H3K27ac, and methylation marks H3K4me1 and H3K4me3 at the ZAP70 and CD40 gene loci (p < 0.05). Additionally, the enrichment of RNA polymerase II and phosphorylated Ser5 pol-II at these loci was increased in MLT-treated cells (p < 0.05), indicating heightened transcriptional activity. In conclusion, our findings suggest that MLT mitigates inflammation in cIECs by modulating the transcription of ZAP70 and CD40 through histone modifications, offering potential therapeutic insights for inflammatory bowel diseases.
What is the central question of this study? Butyrate can prevent diet-induced obesity through increasing energy expenditure. However, it is unclear whether β3 -adrenergic receptors (ARβ3) mediate butyrate-induced adipose lipolysis. What is the main finding and its importance? Short-term oral administration of sodium butyrate is effective in alleviating diet-induced obesity through activation of ARβ3-mediated lipolysis in white adipose tissue. Butyrate can prevent diet-induced obesity through increasing energy expenditure. However, it is unclear whether ARβ3 mediates butyrate-induced adipose lipolysis. In this study, weaned mice were were fed control (Con) or high-fat (HF) diet for 8 weeks to establish obesity. High-fat diet-induced obese mice maintained on the HF diet were divided into two subgroups; the HFB group was gavaged with 80 mg sodium butyrate (SB) per mouse every other day for 10 days, whereas the HF group received vehicle. Chromatin immunoprecipitation assay was performed to determine the status of histone H3 lysine 9 acetylation (H3K9Ac) on the promoter of the β3 -adrenergic receptor (ARβ3) gene in epididymal white adipose tissue. It was shown that five gavage doses of SB significantly alleviated HF diet-induced obesity and restored plasma leptin concentration to the control level. Protein contents of ARβ3 and PKA, as well as ATGL and p-HSL (Ser563), were significantly upregulated in the HFB group compared with the HF group. Mitochondrial oxidative phosphorylation was enhanced by SB treatment. Sodium butyrate significantly increased the expression of four out of 13 mitochondrial DNA-encoded genes and significantly upregulated the protein contents of peroxisome proliferator-activated receptor-γ coactivator 1α and COX4. Moreover, SB administration enhanced the expression of ARβ3 and its downstream signalling. The G protein-coupled receptor 43 and p-CREB (Ser133) were significantly stimulated by SB. In addition, an active transcription marker, H3K9Ac, was significantly enriched on the promoter of the ARβ3 gene. Our results indicate that short-term oral administration of SB is effective in alleviating diet-induced obesity through activation of the ARβ3-mediated lipolysis in the epididymal white adipose tissue.
To investigate the predictive value of CEA and CA19-9 in tumor progression, prognosis and neoadjuvant chemotherapy of advanced gastric cancer.Clinical data of 322 patients with advanced gastric cancer(54 cases undergoing neoadjuvant chemotherapy) from the Affiliated Oncologic Hospital of Guangzhou Medical College were reviewed. Serum CEA and CA19-9 levels were detected by electrochemiluminescence immunoassay, while the expression of CEA and CA19-9 protein in 54 pairs of tumor tissues and matched biopsies neoadjuvant chemotherapy were determined by immunohistochemistry.The expression levels of serum CEA and CA19-9 were closely related to tumor invasion, lymph node metastasis and TNM stage(all P<0.05). The 5-year cumulative survival rates of patients with serum CEA-positive and CA19-9-positive were 17.0% and 11.9%, compared with 34.6% and 34.8% of the patients with serum CEA-negative and CA19-9-negative respectively (both P<0.05). Neoadjuvant chemotherapy could down-regulate CEA and CA19-9 expressions in tumor tissues(P<0.05), while there was no significantly difference in serum level(P>0.05).The expressions of serum CEA and CA19-9 are closely associated with tumor progression and prognosis in advanced gastric cancer. However, further study should be done to evaluate their value in selecting patients to receive neoadjuvant chemotherapy.
【Objective】 The aim of present study was to investigate the expression pattern,correlation with clinicopathologic variables and biologic functions of SYK(L),and to explore its possible effects on the invasion and metastasis of human hepatocellular carcinoma(HCC).【Methods】 The expression of SYK(L) was detected in 211 cases of HCC tissues and adjacent non-tumor liver tissues by immunohistochemistry.The relationship between the expression statues of SYK(L) and clinicopathological characteristics was analyzed.Then,we used an in vitro Matrigel assay to evaluate the effect of SYK(L) on cell invasiveness.Moreover,the correlation between SYK(L) and MMP9 protein levels in the 211 HCC tissues was further analyzed.【Results】 The high-expression rate of SYK(L) was significantly lower in HCC tissues than in adjacent non-tumor tissues(41.2% vs.92.4%;P 0.001);moreover,SYK(L) expression was significantly associated with the preoperative AFP level(P = 0.012),tumor size(P = 0.034),satellite nodule(P = 0.015),vascular invasion(P = 0.003) and tumor differentiation(P = 0.005).Matrigel assay in vitro demonstrated that SYK(L) exhibited markedly decreased the HCC cells invasion,and the semi-quantitative RT-PCR analyses showed that SYK(L) expression lowered MMP2 and MMP9 mRNA level.In addition,there was an inverse correlation between the protein levels of SYK(L) and MMP9 in the 211 HCC tissues(r =-0.601,P 0.001).【Conclusion】 Down-regulation of SYK(L) protein expression may be involved in the carcinogenesis and metastasis of HCC.
Objective
To study the prognostic value of dual oxidase 1(DUOX1) gene in hepatocellular carcinoma(HCC).
Methods
Reverse transcription polymerase chain reaction (RT-PCR) analysis were used to detect the expression of DUOX1 mRNA in 7 HCC cell lines, one normal liver cell line, specimen of normal liver tissues in 30 cases and paired specimen of neoplastic with matched adjacent non-neoplastic liver tissues in 103 cases. The correlation of the DUOX1 mRNA expression in neoplastic tissues were analyzed with clinicopathological and prognostic factors.
Results
DUOX1 mRNA was expressed in MHCC-97H, MHCC-97L and BEL7402 cell lines, but not in HepG2, Hep3B, SMMC-7721, Chang liver and LO2 cell line. The expression of DUOX1 mRNA was not found in all 30 normal liver tissues. The positive rates of DUOX1 expression in neoplastic tissues was higher than in adjacent non-neoplastic tissues(53.4% vs 14.5%, P <0.01), respectively. Univariate analysis indicated that factors affecting overall survival were gender, age, tumor size, satellite nodule, tumor thrombus in the portal vein, TNM stage and DUOX1 expression status in neoplastic tissues. Multivariate analysis indicated that independent factors affecting overall survival were tumor size, tumor thrombus in the portal vein and DUOX1 expression status.
Conclusions
DUOX1 expression in HCC neoplastic tissues is an independent factor affecting the prognosis of patients with HCC after tumor resection. DUOX1 may play a role in liver carcinogenesis.
Key words:
NADPH oxidase; Hepatocellular Carcinoma; Prognosis; DUOX1
Betaine serves as an animal and human nutrient which has been heavily investigated in glucose and lipid metabolic regulation, yet the underlying mechanisms are still elusive. In this study, feeding sows with betaine-supplemented diets during pregnancy and lactation increased cholesterol content and low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SR-BI) gene expression, but decreasing bile acids content and cholesterol-7a-hydroxylase (CYP7a1) expression in the liver of weaning piglets. This was associated with the significantly elevated serum betaine and methionine levels and hepatic S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) content. Concurrently, the hepatic nuclear transcription factor liver X receptor LXR was downregulated along with activated signal protein AMP-activated protein kinase (AMPK). Moreover, a chromatin immunoprecipitation assay showed lower LXR binding on CYP7a1 gene promoter and more enriched activation histone marker H3K4me3 on LDLR and SR-BI promoters. These results suggest that gestational and lactational betaine supplementation modulates hepatic gene expression involved in cholesterol metabolism via an AMPK/LXR pathway and histone modification in the weaning offspring.
Enzymatic synthesis of β-nicotinamide mononucleotide (NMN) from D-ribose has garnered widespread attention due to its cheap material, the use of mild reaction conditions, and the ability to produce highly pure products with the desired optical properties. However, the overall NMN yield of this method is impeded by the low activity of rate-limiting enzymes. The ribose-phosphate diphosphokinase (PRS) and nicotinamide phosphoribosyltransferase (NAMPT), that control the rate of the reaction, were engineered to improve the reaction efficacy. The actives of mutants PRS-H150Q and NAMPT-Y15S were 334% and 57% higher than that of their corresponding wild-type enzymes, respectively. Furthermore, by adding pyrophosphatase, the byproduct pyrophosphate which can inhibit the activity of NAMPT was degraded, leading to a 6.72% increase in NMN yield. Following with reaction-process reinforcement, a high yield of 8.10 g L
Hepatic steatosis is characterized by substantial disruption in the liver's lipid level regulation. Konjac glucomannan (KGM) is acknowledged as a nutritious food that has the potential to prevent hyperlipidemia. This study utilized lipidomics and transcriptomics to investigate the efficacy of KGM in alleviating high-fat diet-induced hepatic steatosis by regulating lipid homeostasis. The findings indicated that supplementation of KGM for a duration of 10 weeks led to significant decreases in body weight, liver weight, and epididymal fat tissue weight. Furthermore, improvements in lipid concentrations in plasma and liver samples were observed, along with enhancements in glucose tolerance and the mitigation of liver damage. Additionally, lipidomics analysis revealed that the primary differential lipid metabolites were mainly associated with fatty acid metabolism pathways. Transcriptomic analysis showed that KGM significantly altered the gene expression of the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the liver. Moreover, KGM demonstrated a significant regulatory impact on the hepatic expression of PPARγ, potentially mitigating hepatic steatosis through modulation of the PPARγ-mediated lipid metabolism pathway. In conclusion, these findings suggest that KGM effectively mitigates steatosis by modulating hepatic lipid metabolites and controlling PPARγ-mediated genes in the liver.
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