Nonalcoholic fatty liver associated with impairment of kidney function in nondiabetes population

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with the increased burden of kidney. However, there is still no large population study to explore the potential relationship between NAFLD and mild kidney function damage (MKFD) after adjusted for confounding factors. This study is to test the hypothesis that NAFLD is associated with MKFD under controlling the effects of confoun-ding factors. Materials and methods: Levels of serum fasting glucose, creatinine, cholesterol, triglyceride, alanine aminotransferase and aspartate aminotransferase were analyzed from 1412 Chinese Han adults. Questionnaire and physical examination were performed to explore the potential association of NAFLD with kidney function. Results: NAFLD was associated with impairment of kidney function. Multivariate-adjusted odds ratio illustrated that, compared to subjects with normal liver, NAFLD subjects had a significantly higher risk of MKFD with or without adjusted for blood glucose and other covariates (P = 0.041). Further results from multi-interaction analysis demonstrated that the underlying mechanisms linked NAFLD with im-paired kidney function may be that they share common risk factors and similar pathological proces-ses. Conclusions: The most striking finding of this study is that NAFLD is negatively associated with kidney function, in nondiabetic population. NAFLD and MKFD may share similar risk factors and/or pathological processes

Gene 33/Mig6 Inhibits Hexavalent Chromium-Induced DNA Damage and Cell Transformation in Human Lung Epithelial Cells

Hexavalent Chromium [Cr(VI)] compounds are human lung carcinogens and environmental/occupational hazards. The molecular mechanisms of Cr(VI) carcinogenesis appear to be complex and are poorly defined. In this study, we investigated the potential role of Gene 33 (ERRFI1, Mig6), a multifunctional adaptor protein, in Cr(VI)-mediated lung carcinogenesis. We show that the level of Gene 33 protein is suppressed by both acute and chronic Cr(VI) treatments in a dose- and time-dependent fashion in BEAS-2B lung epithelial cells. The inhibition also occurs in A549 lung bronchial carcinoma cells. Cr(VI) suppresses Gene 33 expression mainly through post-transcriptional mechanisms, although the mRNA level of gene 33 also tends to be lower upon Cr(VI) treatments. Cr(VI)-induced DNA damage appears primarily in the S phases of the cell cycle despite the high basal DNA damage signals at the G2M phase. Knockdown of Gene 33 with siRNA significantly elevates Cr(VI)-induced DNA damage in both BEAS-2B and A549 cells. Depletion of Gene 33 also promotes Cr(VI)-induced micronucleus (MN) formation and cell transformation in BEAS-2B cells. Our results reveal a novel function of Gene 33 in Cr(VI)-induced DNA damage and lung epithelial cell transformation. We propose that in addition to its role in the canonical EGFR signaling pathway and other signaling pathways, Gene 33 may also inhibit Cr(VI)-induced lung carcinogenesis by reducing DNA damage triggered by Cr(VI)

Mutual Regulation Between Polo-like Kinase 3 and SIAH2 E3 Ubiquitin Ligase Defines a Regulatory Network That Fine-tunes the Cellular Response to Hypoxia and Nickel

Elevated cellular response to hypoxia, which contributes to cell transformation and tumor progression, is a prominent feature of malignant cells in solid tumors. Polo-like kinase 3 (Plk3) is a serine/threonine protein kinase known to inhibit the cellular response to hypoxia and tumorigenesis. Nickel compounds are well-established human carcinogens that induce tumorigenesis partly through their hypoxia-mimicking effects. Despite previous research efforts, the role of Plk3 in the hypoxic response induced by hypoxia or nickel is not completely understood. Here, we show that NiC

MicroRNA Expression Profiling Screen miR-3557/324-targeted CaMK/mTOR in the Rat Striatum of Parkinson\u27s Disease in Regular Aerobic Exercise

This study aimed to screen the target miRNAs and to investigate the differential miR-3557/324-targeted signal mechanisms in the rats’ model of Parkinson’s disease (PD) with regular aerobic exercise. Rats were divided into sedentary control PD group (SED-PD, n = 18) and aerobic exercise PD group (EX-PD, n = 22). After 8 weeks of regular aerobic exercise, a 6-hydroxydopamine- (6-OHDA-) induced PD lesion model was constructed. Preregular aerobic exercises enhanced the injury resistance of rats with 6-OHDA-induced PD. The rotational behavior after injection of apomorphine hydrochloride was alleviated. Under the scanning electron microscopy, we found the neurons, axons, and villi of the striatum were clearly and tightly arranged, and neurons and axons significantly becoming larger. Tyrosine hydroxylase (TH) was increased significantly and α-synuclein protein expression was reduced in the EX-PD group compared to the SED-PD group. Screening from miRNA microarray chip, we further found upregulation of miR-3557 and downregulation of miR-324 were closely related to the calcium-modulating signaling pathway, remitting the progress of Parkinson’s disease on aerobic exercise. Compared to the SED-PD group, Ca2+/calmodulin dependent protein kinase II (CaMK2α) was upregulated, but CaMKV and voltage-dependent anion-selective channel protein 1 (Vdac1) were significantly downregulated in the EX-PD group. Additionally, phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) expression were activated, and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) expression was upregulated in the EX-PD group. Conclusions: the adaptive mechanism of regular aerobic exercise delaying neurodegenerative diseases and lesions was that miR-3557/324 was activated to regulate one of its targets CaMKs signaling pathways. CaMKs, coordinated with mTOR pathway-related gene expression, improved UCH-L1 level to favor for delaying neurodegeneration or improving the pathogenesis of PD lesions

Gene 33/Mig6 Regulates Apoptosis and the DNA Damage Response through Independent Mechanisms

Gene 33 (Mig6, ERRFI1) is an inducible adaptor/scaffold protein whose expression can be induced by both stress and mitogenic signals. It contains multiple domains for protein-protein interaction and is involved in a broad spectrum of cellular functions. Gene 33 promotes apoptosis in a cell type-dependent manner. A recent study has linked Gene 33 to the DNA damage response (DDR) induced by hexavalent chromium [Cr(VI)]. Here we show that Gene 33 induces apoptosis via both c-Abl/p73 and EGFR/AKT-dependent pathways in lung epithelial and lung carcinoma cells. Ectopic expression of Gene 33 also triggers DDR in an ATM-dependent fashion and through pathways with or without association with apoptosis. We observed significant presence of Gene 33 in the nucleus and chromatin. We show that the nuclear localization of Gene 33 is dependent on its 14-3-3 binding domain. We find that the chromatin localization of Gene 33 is, at least in part, dependent on its EBD motif. Our data also show that Gene 33 may regulate chromatin targeting of c-Abl and EGFR. Moreover, we observed strong association of Gene 33 with histone H2AX and that Gene 33 promotes interaction between ATM and histone H2AX without triggering DNA damage. Our study reveals novel nuclear functions of Gene 33, which mediate DDR and apoptosis through independent mechanisms. Given our previous finding that Gene 33 depletion promotes Cr(VI)-induced DNA damage, our data suggest that Gene 33 may foster DNA repair by activating DDR

Malondialdehyde Suppresses Cerebral Function by Breaking Homeostasis between Excitation and Inhibition in Turtle Trachemys scripta

The levels of malondialdehyde (MDA) are high in the brain during carbonyl stress, such as following daily activities and sleep deprivation. To examine our hypothesis that MDA is one of the major substances in the brain leading to fatigue, the influences of MDA on brain functions and neuronal encodings in red-eared turtle (Trachemys scripta) were studied. The intrathecal injections of MDA brought about sleep-like EEG and fatigue-like behaviors in a dose-dependent manner. These changes were found associated with the deterioration of encoding action potentials in cortical neurons. In addition, MDA increased the ratio of γ-aminobutyric acid to glutamate in turtle's brain, as well as the sensitivity of GABAergic neurons to inputs compared to excitatory neurons. Therefore, MDA, as a metabolic product in the brain, may weaken cerebral function during carbonyl stress through breaking the homeostasis between excitatory and inhibitory neurons

Sequence Stratigraphy of Fine-Grained “Shale” Deposits: Case Studies of Representative Shales in the USA and China

The fine-grained “shale” deposits host a vast amount of unconventional oil and gas resources. This chapter examines the variations in lithofacies, patterns of well logs, geochemistry, and mineralogy in order to construct a sequence stratigraphic framework of the representative marine Barnett, Woodford, Marcellus, Mowry, and Niobrara fine-grained “shales” (USA) and the marine Longmaxi shale and lacustrine Chang7 lacustrine shale (China). Practical methods are proposed in order to recognize the sequence boundaries, the flooding surfaces, the parasequences and parasequence sets, the system tracts, and variation patterns of facies and rock properties. The case studies for the sequence stratigraphy in the USA and China have revealed that the transgressive systems tract (TST) and the early highstand systems tract (EHST, if identifiable) of fine-grained “shales” have been deposited in anoxic settings. TST and EHST of the siliciclastic “shales” are characterized by high gamma ray, high TOC, and high quartz content, while TST and EHST of the carbonate-dominated fine-grained “shales” are characterized by low gamma ray, organic lean, and carbonate rich fine-grained deposits. The lithofacies, geochemistry, mineralogy, depositional evolution, and reservoir development have been predicted and correlated within a sequence stratigraphic framework for the suggested cases. The best reservoir with the best completion quality is developed in TST and HST in both siliciclastic-dominated and carbonate-dominated fine-grained “shales.

An insight into the mechanism and evolution of shale reservoir characteristics with over-high maturity

AbstractOver-high maturity is one of the most vital characteristics of marine organic-rich shale reservoirs from the Lower Paleozoic in the south part of China. The organic matter (OM) in shale gas reservoirs almost went through the entire thermal evolution. During this wide span, a great amount of hydrocarbon was available and numerous pores were observed within the OM including kerogen and solid bitumen/pyrobitumen. These nanopores in solid bitumen/pyrobitumen can be identified using SEM. The imaging can be dissected and understood better based on the sequence of diagenesis and hydrocarbon charge with the shape of OM and pores. In terms of the maturity process showed by the various typical cases, the main effects of the relationship between the reservoir porosity and organic carbon abundance are interpreted as follows: the change and mechanism of reservoirs properties due to thermal evolution are explored, such as gas carbon isotope from partial to complete rollover zone, wettability alteration from water-wet to oil-wet and then water-wet pore surface again, electrical resistivity reversal from the increasing to decreasing stage, and nonlinearity fluctuation of rock elasticity anisotropy. These indicate a possible evolution pathway for shale gas reservoirs from the Lower Paleozoic in the southern China, as well as the general transformation processes between different shale reservoirs in thermal stages

Suggestions on the development strategy of shale gas in China

AbstractFrom the aspects of shale gas resource condition, main exploration and development progress, important breakthrough in key technologies and equipment, this paper systematically summarized and analyzed current situation of shale gas development in China and pointed out five big challenges such as misunderstandings, lower implementation degree and higher economic uncertainty of shale gas resource, and still no breakthrough in exploration and development core technologies and equipment for shale gas buried depth more than 3500 m, higher cost and other non-technical factors that restrict the development pace. Aiming at the above challenges, we put forward five suggestions to promote the shale gas development in China: (1) Make strategies and set goals according to our national conditions and exploration and development stages. That is, make sure to realize shale gas annual production of 20 × 109 m3, and strives to reach 30 × 109 m3. (2) Attach importance to the research of accumulation and enrichment geological theory and exploration & development key engineering technologies for lower production and lower pressure marine shale gas reservoir, and at the same time orderly promote the construction of non-marine shale gas exploration & development demonstration areas. (3) The government should introduce further policies and set special innovation funds to support the companies to carry out research and development of related technologies and equipment, especially to strengthen the research and development of technology, equipment and process for shale gas bellow 3500 m in order to achieve breakthrough in deep shale gas. (4) Continue to promote the geological theory, innovation in technology and management, and strengthen cost control on drilling, fracturing and the whole process in order to realize efficient, economic and scale development of China's shale gas. (5) Reform the mining rights management system, establish information platform of shale gas exploration and development data, and correctly guide the non-oil and gas companies to participate in shale gas exploration and development