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41.
    
Intestinal cell dysfunctions involved in obesity and associated diabetes could be correlated with impaired intestinal cell development. To date, the molecular mechanisms underlying these dysfunctions have been poorly investigated because of the lack of a good model for studying obesity. The main aim of this study was to investigate the effects of lipotoxicity on intestinal cell differentiation in small intestinal organoid platforms, which are used to analyze the regulation of cell differentiation. Mouse intestinal organoids were grown in the presence/absence of high palmitate concentrations (0.5 mM) for 48 h to simulate lipotoxicity. Palmitate treatment altered the expression of markers involved in the differentiation of enterocytes and goblet cells in the early (Hes1) and late (Muc2) phases of their development, respectively, and it modified enterocytes and goblet cell numbers. Furthermore, the expression of enteroendocrine cell progenitors (Ngn3) and I cells (CCK) markers was also impaired, as well as CCK-positive cell numbers and CCK secretion. Our data indicate, for the first time, that lipotoxicity simultaneously influences the differentiation of specific intestinal cell types in the gut: enterocytes, goblet cells and CCK cells. Through this study, we identified novel targets associated with molecular mechanisms affected by lipotoxicity that could be important for obesity and diabetes therapy.  相似文献   
42.
    
Cancer is a set of diseases characterized by several hallmark properties, such as increased angiogenesis, proliferation, invasion, and metastasis. The increased angiogenic activity constantly supplies the tumors with nutrients and a plethora of cytokines to ensure cell survival. Along these cytokines is a newly discovered protein, called irisin, which is released into the circulation after physical exercise. Irisin is the product of fibronectin type III domain-containing protein 5 (FNDC5) proteolytic cleavage. Recently it has been the topic of investigation in several types of cancer. In this study, we conducted a systematic review and meta-analysis to investigate its implication in different types of cancer. Our results suggest that irisin expression is decreased in cancer patients, thus it can be used as a valid biomarker for the diagnosis of several types of cancer. In addition, our results indicate that irisin may have an important role in tumor progression and metastasis since it is involved in multiple signaling pathways that promote cell proliferation and migration.  相似文献   
43.
    
We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system.  相似文献   
44.
    
Intestinal organoids are used to analyze the differentiation of enteroendocrine cells (EECs) and to manipulate their density for treating type 2 diabetes. EEC differentiation is a continuous process tightly regulated in the gut by a complex regulatory network. However, the effect of chronic hyperglycemia, in the modulation of regulatory networks controlling identity and differentiation of EECs, has not been analyzed. This study aimed to investigate the effect of glucotoxicity on EEC differentiation in small intestinal organoid platforms. Mouse intestinal organoids were cultured in the presence/absence of high glucose concentrations (35 mM) for 48 h to mimic glucotoxicity. Chronic hyperglycemia impaired the expression of markers related to the differentiation of EEC progenitors (Ngn3) and L-cells (NeuroD1), and it also reduced the expression of Gcg and GLP-1 positive cell number. In addition, the expression of intestinal stem cell markers was reduced in organoids exposed to high glucose concentrations. Our data indicate that glucotoxicity impairs L-cell differentiation, which could be associated with decreased intestinal stem cell proliferative capacity. This study provides the identification of new targets involved in new molecular signaling mechanisms impaired by glucotoxicity that could be a useful tool for the treatment of type 2 diabetes.  相似文献   
45.
    
Hypoxia is the leading cause of death in cardiomyocytes. Cells respond to oxygen deprivation by activating cytoprotective programs, such as mitochondrial connexin43 (mCx43) overexpression and the opening of mitochondrial KATP channels, aimed to reduce mitochondrial dysfunction. In this study we used an in vitro model of CoCl2-induced hypoxia to demonstrate that mCx43 and KATP channels cooperate to induce cytoprotection. CoCl2 administration induces apoptosis in H9c2 cells by increasing mitochondrial ROS production, intracellular and mitochondrial calcium overload and by inducing mitochondrial membrane depolarization. Diazoxide, an opener of KATP channels, reduces all these deleterious effects of CoCl2 only in the presence of mCx43. In fact, our results demonstrate that in the presence of radicicol, an inhibitor of Cx43 translocation to mitochondria, the cytoprotective effects of diazoxide disappear. In conclusion, these data confirm that there exists a close functional link between mCx43 and KATP channels.  相似文献   
46.
Rods of commercially pure titanium were machined using standard oil-based emulsion and cryogenic cooling, and were then coated with sphene (CaTiSiO5) bioceramic by spray coating using an automatic airbrush. The sphene bioceramic was synthesized in-situ starting from a suspension of polysiloxane that used as SiO2 precursor, CaCO3 and TiO2 nanoparticles. The suspension was deposited on the machined substrates, which were heat treated up to 950?°C in order to promote the formation of sphene ceramic. The produced coated prototypes were characterized to evaluate the effect of the machining conditions on surface roughness and microstructure of the substrate, and thereby their effect on coating adhesion. Nanoindentation tests were employed to determine the hardness and elastic modulus of the coating through its thickness. Results showed that the reduced amount of defects on the surface of the cryo-machined substrates, contributed to increase the hardness, elastic modulus and adhesion strength of the coating-substrate interfaces compared to standard machined samples, therefore improving adhesion of the coating to the underlying substrate.  相似文献   
47.
Greywater is the part of domestic wastewater that is free of faeces. The volume and concentration of this separately collected wastewater flow depend on the consumer behaviour and vary according to its source. The average amount of greywater produced per day in a German household is 70 l per person, which is more than 50% of the total wastewater production [5]. This figure corresponds with the average figures provided for Chinese households (80 l per person/day, GB/T 50331-2002), but significantly exceeds the South African average of 20 l per person and day [1].Compared to domestic wastewater, greywater generally contains less organic pollutants, less nutrients but a high amount of tensides. The effluent from bath tubs, showers or wash hand basins contains for example a by approx. two decimal orders lower number of total and faecal coliform bacteria (Escherichiacoli) [2] and [6].Due to its relatively low content of pollutants, greywater is easy to treat with MBRs. The pollutants contained are decomposed by the bacteria of the activated sludge tank. The following membrane filtration unit separates the treated greywater from the activated sludge. The treated greywater is of high quality and hygienically safe so that it can be reused, alone or combined with rain water, for toilet flushing water, laundry washing or for irrigation purposes.Within the scope of the SANSED II research project HUBER has been successful in adapting the MBR system for greywater treatment to the specific conditions in Vietnam and testing the system in operation in a small city in the Mekong delta, South Vietnam. The wastewater from kitchen sinks and the bathrooms of a dormitory on the campus of Can Tho University was clarified in the HUBER GreyUse® plant over a period of three months. The project aim was the production of high quality service water from greywater for safe reuse as toilet flush water.  相似文献   
48.
The distinct effects of the estrogen and progestin components of hormonal therapy on the metabolism of apolipoprotein (apo) B‐containing lipoproteins have not been studied. We enrolled eight healthy postmenopausal women in a placebo‐controlled, randomized, double‐blind crossover study. Each subject received placebo, conjugated equine estrogen (CEE, 0.625 mg/day) and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day) for 8 weeks in a randomized order, with a 4‐week washout between phases. Main outcomes were the fractional catabolic rate (FCR) and production rate (PR) of apo B100 in triglyceride‐rich lipoproteins (TRL), intermediate‐density lipoproteins (IDL) and low ‐density lipoprotein (LDL) and of apo B48 in TRL. Compared to placebo, CEE increased TRL apo B100 PR (p = 0.04). CEE also increased LDL apo B100 FCR (p = 0.02), but this effect was offset by a significant increase in LDL apo B100 PR (p = 0.04). Adding MPA to CEE negated the CEE effects resulting in no significant changes in TRL apo B100 PR and LDL apo B100 FCR and PR relative to placebo. Relative to placebo, during CEE there was a trend toward a reduction in plasma apo B48 concentrations and PR (p = 0.07 and p = 0.12, respectively). Compared with CEE, CEE + MPA significantly increased TRL apo B48 FCR (p = 0.02) as well as apo B48 PR (p = 0.01), resulting in no significant changes in apo B48 concentration. Estrogen and progestin have independent and opposing effects on the metabolism of the atherogenic apo B100‐ and apo B48‐containing lipoproteins.  相似文献   
49.
Background Supporting medical decision making is a complex task, that offers challenging research issues to Artificial Intelligence (AI) scientists. The Case-based Reasoning (CBR) methodology has been proposed as a possible means for supporting decision making in this domain since the 1980s. Nevertheless, despite the variety of efforts produced by the CBR research community, and the number of issues properly handled by means of this methodology, the success of CBR systems in medicine is somehow limited, and almost no research product has been fully tested and commercialized; one of the main reasons for this may be found in the nature of the problem domain, which is extremely complex and multi-faceted. Materials and methods In this environment, we propose to design a modular architecture, in which several AI methodologies cooperate, to provide decision support. In the resulting context CBR, originally conceived as a well suited reasoning paradigm for medical applications, can extend its original roles, and cover a set of additional tasks. Results and conclusions As an example, in the paper we will show how CBR can be exploited for configuring the parameters relied upon by other (reasoning) modules. Other possible ways of deploying CBR in this domain will be the object of our future investigations, and, in our opinion, a possible research direction for people working on CBR in the health sciences.  相似文献   
50.
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