Apocynin attenuates renal fibrosis via inhibition of NOXs-ROS-ERK-myofibroblast accumulation in UUO rats

Background: Oxidative stress has been identified as an important pathogenesis mechanism in the development of renal interstitial fibrosis in unilateral ureteral obstruction (UUO). Previous studies have demonstrated increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOXs) in response to UUO. We aimed to investigate whether NOXs activation was involved in the development of renal fibrosis in UUO by contribution to oxidative stress and the potential mechanism in the present study.

Methods: Apocynin, a NOXs inhibitor, was initiated immediately by gavage after UUO was performed on Wistar rats and continued until 7 days after UUO. Changes of markers of oxidative stress, renal macrophage infiltration and fibrosis, TGF-β1 expression, NOXs expression and activity, and ERK activation were evaluated.

Results: Apocynin significantly attenuated the activity of NOXs, accompanied with decreased expression of NOX2, NOX4, and oxidative stress markers in the obstructed kidneys of UUO. Additionally, collagen deposition and renal fibrosis induced by UUO were attenuated by apocynin treatment. Furthermore, apocynin treatment significantly attenuated the phosphorylation of ERK, accumulation of myofibroblast and infiltration of macrophage in obstructed kidneys. No significant effect of apocynin on UUO-induced increased TGF-β1 expression could be observed. And there was no significant change of anti-oxidants enzyme activities in the obstructed kidneys of apocynin-treated rats.

Conclusions: These results suggested that apocynin might exert beneficial effects on renal fibrosis by inhibition of NOXs activation and subsequent reduction of oxidative stress, ERK activation, and myofibroblast accumulation in UUO rats. Targeting NOXs may serve as a therapeutic strategy for the treatment of renal fibrosis.     

Association between Tooth Loss and Cognitive Function among 3063 Chinese Older Adults: A Community-Based Study

Background

Oral health has been found to be associated with cognitive function in basic research and epidemiology studies. Most of these studies had no comprehensive clinical diagnosis on cognitive function. This study firstly reported the association between tooth loss and cognitive function among Chinese older population.

Methods

The study included 3,063 community dwelling older adults aged 60 or above from the Shanghai Aging Study. Number of teeth missing was obtained from self-reporting questionnaire and confirmed by trained interviewers. Participants were diagnosed as “dementia”, “mild cognitive impairment (MCI)”, or “cognitive normal” by neurologists using DSM-IV and Petersen criteria. Multivariate logistic regression model was applied to examine the association between number of teeth missing and cognitive function.

Results

The study participants had an average of 10.2 teeth lost. Individuals with dementia lost 18.7 teeth on average, much higher than those with MCI (11.8) and cognitive normal (9.3) (p<0.001). After adjusted for sex, age, education year, living alone, body mass index, cigarette smoking, alcohol drinking, anxiety, depression, heart disease, hypertension, diabetes, and APOE-ε4, tooth loss of >16 were significantly associated with dementia with an OR of 1.56 (95%CI 1.12-2.18).

Conclusion

Having over 16 missing teeth was associated with severe cognitive impairment among Chinese older adults. Poor oral health might be considered as a related factor of neurodegenerative symptom among older Chinese population.     

Exosome and Exosomal MicroRNA:Trafficking,Sorting, and Function

Exosomes are 40–100 nm nano-sized vesicles that are released from many cell types into the extracellular space. Such vesicles are widely distributed in various body fluids. Recently,m RNAs and micro RNAs(mi RNAs) have been identified in exosomes, which can be taken up by neighboring or distant cells and subsequently modulate recipient cells. This suggests an active sorting mechanism of exosomal mi RNAs, since the mi RNA profiles of exosomes may differ from those of the parent cells. Exosomal mi RNAs play an important role in disease progression, and can stimulate angiogenesis and facilitate metastasis in cancers. In this review, we will introduce the origin and the trafficking of exosomes between cells, display current research on the sorting mechanism of exosomal mi RNAs, and briefly describe how exosomes and their mi RNAs function in recipient cells.Finally, we will discuss the potential applications of these mi RNA-containing vesicles in clinical settings.     

The ING4 Binding with p53 and Induced p53 Acetylation were Attenuated by Human Papillomavirus 16 E6

High risk subtype HPV16 early oncoprotein E6 contributes host cell immortalization and transformation through interacting with a number of cellular factors. ING4 is one member of the inhibitor of growth (ING) family of type II tumor suppressors and it has been shown to be involved in regulating p53 function. However, the effect and mechanism of HPV16 E6 on ING4 function remain elusive. In this study, we report HPV16 E6 combines with ING4 in vivo and in vitro. The ING4 induced p53 acetylation and its combining with p53 were attenuated by HPV16 E6 independent of p53 degradation. The enhancing function of ING4 on p53 mediated apoptosis was diminished when HPV16 E6 existed. These findings reveal that ING4 may be a common target of oncogenic viruses for driving host cell carcinogenesis.     

Expression pattern of NLRP3 and its related cytokines in the lung and brain of avian influenza virus H9N2 infected BALB/c mice

Background

H9N2 avian influenza virus (AIV) becomes the focus for its ability of transmission to mammals and as a donor to provide internal genes to form the new epidemic lethal influenza viruses. Residue 627 in PB2 has been proven the virulence factor of H9N2 avian influenza virus in mice, but the detailed data for inflammation difference between H9N2 virus strains with site 627 mutation is still unclear. The inflammasome NLRP3 is recently reported as the cellular machinery responsible for activation of inflammatory processes and plays an important role during the development of inflammation caused by influenza virus infection.

Methods

In this study, we investigated the expression pattern of NLRP3 and its related cytokines of IL-1β and TNF-α in BALB/c mice infected by H9N2 AIV strains with only a site 627 difference at both mRNA and protein levels at different time points.

Results

The results showed that the expression level of NLRP3, IL-1β and TNF-α changed in the lung and brain of BALB/c mice after infection by V_K627 and rV_K627E. The immunohistological results showed that the positive cells of NLRP3, IL-1β and TNF-α altered the positive levels of original cells in tissues and infiltrated inflammatory cells which caused by H9N2 infection.

Conclusions

Our results provided the basic data at differences in expression pattern of NLRP3 and its related cytokines in BALB/c mice infected by H9N2 influenza viruses with only a site 627 difference. This implied that NLRP3 inflammasome plays a role in host response to influenza virus infection and determines the outcome of clinical manifestation and pathological injury. This will explain the variable of pathological presentation in tissues and enhance research on inflammation process of the AIV H9N2 infection.

     

Reducing stem bending increases the height growth of tall pines

The hypothesis was tested that upper limits to height growth in trees are the result of the increasing bending moment of trees as they grow in height. The increasing bending moment of tall trees demands increased radial growth at the expense of height growth to maintain mechanical stability. In this study, the bending moment of large lodgepole pine (Pinus contorta Dougl. Ex Loud. var. latifolia Engelm.) was reduced by tethering trees at 10 m height to counter the wind load. Average bending moment of tethered trees was reduced to 38% of control trees. Six years of tethering resulted in a 40% increase in height growth relative to the period before tethering. By contrast, control trees showed decreased height growth in the period after tethering treatment. Average radial growth along the bole, relative to height growth, was reduced in tethered trees. This strongly suggests that mechanical constraints play a crucial role in limiting the height growth of tall trees. Analysis of bending moment and basal area increment at both 10 m and 1.3 m showed that the amount of wood added to the stem was closely related to the bending moment produced at these heights, in both control and tethered trees. The tethering treatment also resulted in an increase in the proportion of latewood at the tethering height, relative to 1.3 m height. For untethered control trees, the ratio of bending stresses at 10 m versus 1.3 m height was close to 1 in both 1998 and 2003, suggesting a uniform stress distribution along the outer surface of the bole.     

Genetics and Resistance Mechanism of the Cucumber (Cucumis sativus L.) Against Powdery Mildew

Journal of Plant Growth Regulation - Powdery mildew (PM) is one of the most severe foliar diseases in cucumbers (Cucumis sativus L.), but the inheritance of PM resistance remains unclear. The...     

露天煤矿排土场边坡植被组成特征及其群落稳定性评价

研究植被恢复过程中植物群落组成、结构及稳定性的变化,可进一步了解到植物群落的演替过程及规律。采用空间代时间的方法对内蒙古锡林郭勒盟北电胜利露天煤矿4个排土场边坡人工恢复植被进行群落调查,在此基础上采用多样性指数与优化后的M.Godron稳定性指数对植物物种组成、物种多样性及其群落稳定性进行分析,探究不同恢复年限排土场边坡植被在恢复过程中群落特征及稳定性变化特征。结果表明：（1）排土场边坡植物物种组成共有16科44属56种,植物群落组成较简单,其中禾本科种类最多,生长型以草本植物为主。（2）随着恢复年限的增加,植物生活型由一、二年生转变为多年生,坡面优势种由人工种植植物转变为本土植物。（3）整体看,随着恢复年限增加,物种多样性呈下降趋势,群落稳定性整体呈上升趋势。（4）由于不同坡向土壤微环境差异,北坡恢复效果及稳定性好于南坡。本研究在一定程度上可为露天煤矿排土场边坡人工修复过程中植物物种及合理配置模式的选择提供科学依据。