Upregulating Nonneuronal Cholinergic Activity Decreases TNF Release from Lipopolysaccharide-Stimulated RAW264.7 Cells

Nonneuronal cholinergic system plays a primary role in maintaining homeostasis. It has been proved that endogenous neuronal acetylcholine (ACh) could play an anti-inflammatory role, and exogenous cholinergic agonists could weaken macrophages inflammatory response to lipopolysaccharide (LPS) stimulation through activation of α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR). We assumed that nonneuronal cholinergic system existing in macrophages could modulate inflammation through autocrine ACh and expressed α7nAChR on the cells. Therefore, we explored whether LPS continuous stimulation could upregulate the nonneuronal cholinergic activity in macrophages and whether increasing autocrine ACh could decrease TNF release from the macrophages. The results showed that, in RAW264.7 cells incubated with LPS for 20 hours, the secretion of ACh was significantly decreased at 4 h and then gradually increased, accompanied with the enhancement of α7nAChR expression level. The release of TNF was greatly increased from RAW264.7 cells at 4 h and 8 h exposure to LPS; however, it was suppressed at 20 h. Upregulating choline acetyltransferase (ChAT) expression through ChAT gene transfection could enhance ACh secretion and reduce TNF release from the infected RAW264. 7cells. The results indicated that LPS stimulation could modulate the activity of nonneuronal cholinergic system of RAW264.7 cells. Enhancing autocrine ACh production could attenuate TNF release from RAW264.7 cells

Role of <i>IL-4</i> Gene Polymorphisms in HBV-Related Hepatocellular Carcinoma in a Chinese Population

<div><p>Background</p><p>Interleukin-4 (IL-4) is best known as an important mediator and modulator of immune and inflammatory responses. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer, and genetic variations in the <i>IL-4</i> gene may be associated with the risk of hepatitis B virus (HBV)-related HCC. However, few studies have been conducted on their association.</p><p>Objectives</p><p>To clarify the effects of <i>IL-4</i> gene polymorphisms on the risk of HBV-related HCC, two common variants, −590C/T (rs2243250) and −33C/T (rs2070874), and their relationship with HBV-related disease risk were investigated in a Chinese population.</p><p>Methods</p><p><i>IL-4</i> −590C/T and −33C/T polymorphisms were examined in 154 patients with HBV-related HCC, 62 patients with HBV-induced liver cirrhosis (LC), 129 patients with chronic hepatitis B (CHB), and 94 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing.</p><p>Results</p><p>Overall, no significant differences were observed regarding the <i>IL-4</i> −590C/T and −33C/T polymorphism genotypes, alleles, or haplotypes between the patient groups and the healthy controls. However, the CC genotypes of <i>IL-4</i> −590C/T and −33C/T polymorphisms were observed to be significantly associated with CHB in subgroup analysis in males [CC versus TT (OR: 4.193, 95% CI: 1.094–16.071, <i>P</i> = 0.037; and OR: 3.438, 95% CI: 1.032–11.458, <i>P</i> = 0.044) and CC versus TT+CT (OR: 4.09, 95% CI: 1.08–15.49, <i>P</i> = 0.038; and OR: 3.43, 95% CI: 1.04–11.28, <i>P</i> = 0.042)].</p><p>Conclusions</p><p>These findings suggest that genetic variants in <i>IL-4</i> −590C/T and −33C/T polymorphisms may be a risk factor for CHB in Chinese males but not for HBV-related LC or HCC.</p></div

Hierarchical Assembly of α‑Fe₂O₃ Nanosheets on SnO₂ Hollow Nanospheres with Enhanced Ethanol Sensing Properties

We present the preparation of a hierarchical nanoheterostructure consisting of inner SnO₂ hollow spheres (SHS) surrounded by an outer α-Fe₂O₃ nanosheet (FNS). Deposition of the FNS on the SHS outer surface was achieved by a facile microwave hydrothermal reaction to generate a double-shell SHS@FNS nanostructure. Such a composite with novel heterostructure acted as a sensing material for gas sensors. Significantly, the hierarchical composites exhibit excellent sensing performance toward ethanol, which is superior to the single component (SHS), mainly because of the synergistic effect and heterojunction

LINC00152 promotes cell cycle progression in hepatocellular carcinoma via miR-193a/b-3p/CCND1 axis

<p>Long intergenic non-coding RNA 00152 (LINC00152) is aberrantly expressed in various human malignancies and plays an important role in the pathogenesis. Here, we found that LINC00152 is upregulated in hepatocellular carcinoma (HCC) tissues as compared to adjacent non-neoplastic tissues; gain-and-loss-of-function analyses in vitro showed that LINC00152 facilitates HCC cell cycle progression through regulating the expression of CCND1. LINC00152 knockdown inhibits tumorigenesis in vivo. MS2-RIP analysis indicated that LINC00152 binds directly to miR-193a/b-3p, as confirmed by luciferase reporter assays. Furthermore, ectopic expression of LINC00152 partially halted the decrease in CCND1 expression and cell proliferation capacity induced by miR-193a/b-3p overexpression. Thus, LINC00152 acts as a competing endogenous RNA (ceRNA) by sponging miR-193a/b-3p to modulate its target gene, CCND1. Our findings establish a ceRNA mechanism regulating cell proliferation in HCC via the LINC00152/miR-193a/b-3p/CCND1 signalling axis, and identify LINC00152 as a potential therapeutic target for HCC.</p

Genotype and allele frequencies of −589C/T and −33C/T polymorphisms between HBV-related patients and healthy controls.

a<p>Adjusted by age and gender;</p>b<p>Dominant model: CT+CC versus TT;</p>c<p>Recessive model: CC versus TT+CT.</p><p>Genotype and allele frequencies of −589C/T and −33C/T polymorphisms between HBV-related patients and healthy controls.</p