Mitochondria are highly dynamic and undergo constant fusion and fission that are essential for maintaining physiological functions of cells. Although dysfunction of mitochondria has been implicated ...in tumorigenesis, little is known about the roles of mitochondrial dynamics in metastasis, the major cause of cancer death. In the present study, we found a marked upregulation of mitochondrial fission protein dynamin-related protein 1 (Drp1) expression in human invasive breast carcinoma and metastases to lymph nodes. Compared with non-metastatic breast cancer cells, mitochondria also were more fragmented in metastatic breast cancer cells that express higher levels of total and active Drp1 and less mitochondrial fusion protein 1 (Mfn1). Silencing Drp1 or overexpression of Mfn1 resulted in mitochondria elongation or clusters, respectively, and significantly suppressed metastatic abilities of breast cancer cells. In contrast, silencing Mfn proteins led to mitochondrial fragmentation and enhanced metastatic abilities of breast cancer cells. Interestingly, these manipulations of mitochondrial dynamics altered the subcellular distribution of mitochondria in breast cancer cells. For example, silencing Drp1 or overexpression of Mfn1 inhibited lamellipodia formation, a key step for cancer metastasis, and suppressed chemoattractant-induced recruitment of mitochondria to lamellipodial regions. Conversely, silencing Mfn proteins resulted in more cell spreading and lamellipodia formation, causing accumulation of more mitochondria in lamellipodia regions. More importantly, treatment with a mitochondrial uncoupling agent or adenosine triphosphate synthesis inhibitor reduced lamellipodia formation and decreased breast cancer cell migration and invasion, suggesting a functional importance of mitochondria in breast cancer metastasis. Together, our findings show a new role and mechanism for regulation of cancer cell migration and invasion by mitochondrial dynamics. Thus targeting dysregulated Drp1-dependent mitochondrial fission may provide a novel strategy for suppressing breast cancer metastasis.
Aim: Most guidelines recommend metformin as first‐line therapy in patients with type 2 diabetes. However, the choice of a second‐line drug lacks consistent consensus. We aimed to assess available ...information of antidiabetic drugs added to metformin on the change in glycated haemoglobin A1c (A1C), risk of hypoglycaemia and change in body weight.
Methods: PubMed and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) written in English through December 2011. We analysed direct and indirect comparisons of different treatments using Bayesian network meta‐analysis.
Results: Thirty‐nine RCTs involving 17 860 individuals were included. Glucagon‐like peptide‐1 (GLP‐1) analogues resulted in greater decrease in A1C compared with sulfonylureas, glinides, thiazolidinediones, α‐glucosidase inhibitors and DPP‐4 inhibitors −0.20% (95% CI −0.34 to −0.04%), −0.31% (95% CI −0.61 to −0.02%), −0.20% (95% CI −0.38 to −0.00), −0.36% (95% CI −0.64 to −0.07%), −0.32% (95% CI −0.47 to −0.17%), respectively and was comparable with basal insulin and biphasic insulin. A1C decrease was greater for sulfonylureas compared with DPP‐4 inhibitors −0.12% (−0.23 to −0.03%), and for biphasic insulin compared with glinides (−0.36%; 95% CI −0.82 to −0.11%). Compared with placebo, the risk of hypoglycaemia was increased in the sulfonylureas, glinides, basal insulin and biphasic insulin. Weight increase was seen with sulfonylureas, glinides, thiazolidinediones, basal insulin and biphasic insulin, and weight loss was seen with α‐glucosidase inhibitors and GLP‐1 analogues.
Conclusions: Biphasic insulin, GLP‐1 analogues and basal insulin were ranked the top three drugs in terms of A1C reduction. GLP‐1 analogues did not increase the risk of hypoglycaemia and resulted in a significant decrease in body weight. Most oral antidiabetic drugs had similar effects on A1C, but some agents had a lower risk of hypoglycaemia and body weight gain.
Directly Placed Restorative Materials Schwendicke, F.; Göstemeyer, G.; Blunck, U. ...
Journal of Dental Research,
06/2016, Letnik:
95, Številka:
6
Book Review, Journal Article
Recenzirano
For restoring cavitated dental lesions, whether carious or not, a large number of material combinations are available. We aimed to systematically review and synthesize data of comparative dental ...restorative trials. A systematic review was performed. Randomized controlled trials published between 2005 and 2015 were included that compared the survival of ≥2 restorative and/or adhesive materials (i.e., no need for restorative reintervention). Pairwise and Bayesian network meta-analyses were performed, with separate evaluations for cervical cavitated lesions and load-bearing posterior cavitated lesions in permanent and primary teeth. A total of 11,070 restorations (5,330 cervical, 5,740 load bearing) had been placed in 3,633 patients in the included trials. Thirty-six trials investigated restoration of cervical lesions (all in permanent teeth) and 36 of load-bearing lesions (8 in primary and 28 in permanent teeth). Resin-modified glass ionomer cements had the highest chance of survival in cervical cavitated lesions; composites or compomers placed via 2-step self-etch and 3-step etch-and-rinse adhesives were ranked next. Restorations placed with 2-step etch-and-rinse or 1-step self-etch adhesives performed worst. For load-bearing restorations, conventional composites had the highest probability of survival, while siloranes were found least suitable. Ambiguity remains regarding which adhesive strategy to use in load-bearing cavitated lesions. Most studies showed high risk of bias, and several comparisons were prone for publication bias. If prioritized for survival, resin-modified glass ionomer cements might be recommended to restore cervical lesions. For load-bearing ones, conventional or bulk fill composites seem most suitable. The available evidence is quantitatively and qualitatively insufficient for further recommendations, especially with regard to adhesive strategies in posterior load-bearing situations. Moreover, different material classifications might yield different findings on the same materials. Future trials should aim for sufficient power, longer follow-up times, and high internal validity to prove or refute differences between certain material combinations. An agreed material classification for future syntheses is desirable.
Abstract
Regional water allocation is of great importance to regional coordinated development. Therefore, this paper constructs a data-driven model for regional water allocation analysis to address ...the existing problems of the imbalance between water supply and demand, irrational utilization of water resources and water scarcity. Firstly, a classification of regional water allocation case is constructed through cluster analysis to obtain similar regions with the same salient characteristics. Then, the regions in the same category are divided into regions to be predicted and other regions, and the similarity of water resources allocation between regions to be predicted and other regions is calculated. The Criteria Importance Through Intercriteria Correlation (CRITC) method is used to calculate the weighted values of each index and forecast water demands of regions to be predicted. Finally, an example analysis of water allocation of each city in Hubei province in 2020 was carried out, and the results indicated that when the water allocation of each city in Hubei province was divided into 4 categories, the water allocation characteristics of different cities are presented. The relative errors of the predicted water demand do not exceed 5%, which is highly accurate and can provide decision support for rational water allocation.
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) resets their identity back to an embryonic age and, thus, presents a significant hurdle for modeling late-onset disorders. In ...this study, we describe a strategy for inducing aging-related features in human iPSC-derived lineages and apply it to the modeling of Parkinson’s disease (PD). Our approach involves expression of progerin, a truncated form of lamin A associated with premature aging. We found that expression of progerin in iPSC-derived fibroblasts and neurons induces multiple aging-related markers and characteristics, including dopamine-specific phenotypes such as neuromelanin accumulation. Induced aging in PD iPSC-derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility, such as pronounced dendrite degeneration, progressive loss of tyrosine hydroxylase (TH) expression, and enlarged mitochondria or Lewy-body-precursor inclusions. Thus, our study suggests that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models.
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•Reprogramming rejuvenates old donor fibroblasts by erasing age-related markers•Differentiation of old donor iPSCs is not sufficient to trigger memory of age•Progerin induces age-associated phenotypes in iPSC-derived fibroblasts and neurons•Progerin reveals late-onset disease phenotypes in iPSC-based models of genetic PD
The induction of aging-related features in human iPS-derived cells through expression of progerin addresses one of the major limitations of human iPS-based disease modeling and enables analysis of late-onset phenotypes in conditions such as Parkinson’s disease.
To report successful management of a case of persistent keratoconus-related hydrops with a Descemet membrane endothelial keratoplasty (DMEK) patch graft.
A case of corneal hydrops persisting for 7 ...months treated with DMEK was identified. The following information was collected: demographic data, surgical indications, clinical course, diagnostic tests, and clinical outcome.
A 55-year-old patient with an established diagnosis of keratoconus was followed for 7 months without improvement in his acute corneal hydrops. Because of excellent vision and central corneal clarity, the patient was treated with a 5-mm DMEK covering the Descemet membrane tear, developing cataract secondary to the procedure, but with resolution of his corneal hydrops. An uncorrected visual acuity of 20/25 was achieved after uncomplicated cataract extraction.
DMEK, although technically challenging, can be considered for patients with persistent hydrops with preservation of corneal clarity and contour in areas of the uninvolved cornea.
Visual fatigue has become a public health issue, while the relevant retinal mechanism and characteristics of blue light that induce visual fatigue have been rarely studied. In the retina, both short ...wavelength-sensitive (S) cones and melanopsin-containing intrinsically photoreceptive retinal ganglion cells (ipRGCs) are sensitive to blue light, and their responses are opposite in pupil mediation. Thus, effects of blue-enriched white light with different S-cone-opic Equivalent Daylight Illuminance (EDI) on visual fatigue was investigated, maintaining the same melanopic EDI to avoid interferences of melanopsin-containing ipRGCs. Two white illuminants (one with low S-cone-opic EDI, the other with high S-cone-opic EDI) were characterized based on α-opic EDI with the same correlated colour temperature and illuminance. Melanopic EDI was lower than S-cone-opic EDI of these two illuminants. Psychological, visual, physiological and cognitive performances were measured to investigate visual fatigue. Results showed that blue-enriched white light with high S-cone-opic EDI can induce visual fatigue. Participants felt more discomfort in their eyes under high S-cone-opic EDI along with the decline of tear film stability and changes of heart rhythm. Furthermore, the reaction time in a memory task increased significantly under high S-cone-opic EDI. The findings provide new insights into the optimization of indoor lighting environments for human health.
Air water harvesting (AWH) is a prospective way to make people live in extreme conditions, such as arid desert and remote islands. However, the refrigeration-based AWH suffers from ineffectiveness at ...low humidity, while the current sorption-based solar driven AWH has low area specific water production. To provide affordable water, it is essential to design universal and scalable systems to effectively capture moisture from air year-round with less energy consumption at different locations. Here we develop a theoretical framework and demonstrate a scalable prototype on the sorption-based AWH. The prototype adopts a temperature-insensitive and RH-broadband desiccant, achieving a large water harvesting capacity in different regions. Scalable modular sorbers with sinusoidal honeycomb structure are used. The prototype harvests ca. 38.5 kg fresh water per day, consuming ca.7.2 MJ heat/kg fresh water. The performance analyses show that our device can harvest freshwater universally, which is a promising solution to relieve the thirsty world.
•The entire mechanisms of AWH from materials level to system scale level are shown.•A thermodynamic chart is first constructed on a modular sorption-based AWHs.•High water harvesting capacities are proved all year round at various areas.
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