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1.
Prostate ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32421868

RESUMO

BACKGROUND: Although thrombospondins 4 (THBS4) participates in controlling the biology of prostate cancer (PCa), the mechanism underlying this regulation remains unknown. Hence, this study aims to identify the regulatory effects of THBS4 on the PCa stem cell-like properties and the potential mechanism associated with the phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (Akt) pathway. METHODS: PCa stem cells were sorted and identified using flow cytometry and THBS4 expression in the identified PCa stem cells was measured using Western blot assay. THBS4 was overexpressed or silenced in PCa stem cells, following which, self-renewal, proliferation, cell cycle distribution, and apoptosis of PCa stem cells were assessed as well as tumorigenicity in vivo was evaluated. PI3K/Akt pathway inhibitor was applied to identify its involvement in the regulatory roles of THBS4 in PCa stem cells. RESULTS: THBS4 was expressed at a higher level in PCa stem cells than in PCa cells. The overexpression of THBS4 promoted the self-renewal and proliferation, curbed the apoptosis of PCa stem cells, and enhanced the in vivo tumorigenicity, which was achieved by activating the PI3K/Akt pathway. On the contrary, short-hairpin RNA-mediated silencing of THBS4 exhibited suppressive effects on those cancer stem cell (CSC)-like properties and promotive effects on their apoptosis. CONCLUSION: THBS4 silencing can impede the CSC-like properties in PCa via blockade of the PI3K/Akt pathway, which provides patients with PCa a new therapeutic target.

2.
Chem Commun (Camb) ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32426774

RESUMO

Herein, we report a tandem cycloisomerization/nucleophilic addition/cyclization of 2-amino chalcone with bifunctional nucleophiles driven by visible light. This cascade process is realized by the irradiation of a blue LED at room temperature, which provides a concise route to structurally diverse benzo[d][1,3]oxazocine scaffolds. Mechanistic studies show that the reaction is initiated with the E to Z isomerization of a C-C double bond upon the irradiation of visible light, followed by cyclization/rearomatization to generate a transient quinolinium intermediate, which is trapped by the nucleophile and cyclized to produce the polycyclic benzo[d][1,3]oxazocine.

3.
Bioconjug Chem ; 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32426977

RESUMO

Bioinspired by the morphology of osteoclast-resorbed bone surfaces, we prepared a calcium-doped titanium phosphate (Ca-TiP) coating, which consists of a nanofibrous network, on titanium (Ti) substrate via a simple two-step hydrothermal method, trying to mimic natural bone compositionally and microstructurally. The in vitro studies show that the Ca-TiP coating with synergistic features of nano-fibrous biomimetic topography and surface chemistry could elicit intensively osteogenic behavior and responses including enhanced cell adhesion, spreading and proliferation as well as alkaline phosphatase (ALP) activity and up-regulated expression of bone-related genes, which inevitably benefit to the formation of new bone and the quality of osseointegration. While compared with the two control groups in vivo, the significantly improved new bone formation in early stage and the much stronger interfacial bonding with the surrounding bone for Ca-TiP coating suggest that Ca-TiP coating modified Ti implants hold great potential for orthopedic and dental applications.

4.
Biol Trace Elem Res ; 2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32363518

RESUMO

Body iron status is likely to be associated with type 2 diabetes (T2DM) and gestational diabetes mellitus (GDM); transmembrane protease serine 6 (TMPRSS6) polymorphisms may be associated with T2DM risk through their effects on body iron status. However, it remains unknown whether the TMPRSS6 single nucleotide polymorphisms (SNPs) affect the risk of GDM development. We aimed to determine whether the TMPRSS6 SNPs rs855791 (V736A) and rs4820268 (D521D) are associated with the risk of GDM in pregnant women. The two SNPs in TMPRSS6 gene were genotyped and examined for their associations with body iron status and GDM risk in 398 unrelated Chinese Han pregnant women. The 2 TMPRSS6 SNPs rs855791 and rs4820268 were both significantly associated with serum iron and transferrin saturation (P < 0.01 for all) rather than ferritin. After adjustment for covariates, the C allele of rs4820268 was nominally and significantly associated with an increased risk of GDM (OR = 2.531; 95%CI = 1.044-6.136, P = 0.040); when concentrations of ferritin were further adjusted, the association was still significant (OR = 2.528; 95%CI = 1.043-6.126, P = 0.040). There was a significant trend (P = 0.065) in the association between the T allele of rs855791 and an increased GDM risk in this study population. The 2 TMPRSS6 SNPs rs855791 and rs4820268 were both significantly associated with serum iron and transferrin saturation, and TMPRSS6 variants might be associated with the risk of GDM. Furthermore, the effects of TMPRSS6 SNPs on the risk of GDM may not be completely explained by the mediation of body iron status. Further studies are warranted.

5.
Org Lett ; 22(10): 4006-4009, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32367722

RESUMO

The highly efficient copper-catalyzed enantioselective alkynylation of the remote C(sp3)-H bond on linear primary sulfonamides is presented here using a radical relay strategy. The chiral box-copper complex, which is used to recapture the in-situ-generated alkyl radical via a 1,5-HAT strategy, is the key to success, affording the chiral alkynes after a following reductive elimination. A general substrate scope, mild conditions, and excellent regio- and enantioselective control are demonstrated in this method.

6.
Biol Trace Elem Res ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32418160

RESUMO

Women with gestational diabetes mellitus (GDM) may have lower serum selenium levels than healthy controls, which may be associated with preterm birth. We explored the association of serum selenium levels in early pregnancy with the risk of GDM and preterm birth among Chinese women. We included 398 women with a singleton pregnancy, who were followed up prospectively from the first prenatal visit until delivery. Serum selenium levels were measured in the first trimester. After delivery, data concerning mothers and their children were sourced from medical records by researchers who were blind to the participants' selenium status. Of the 398 women, 71 (17.8%) had GDM, 21(5.3%) had preterm birth, and 266 (66.8%) had selenium deficiency (serum selenium < 70 µg/L). Women in the upper three quartiles of serum selenium level did not have a significantly lower risk of GDM or preterm birth than those in the lowest quartile after adjustment for covariates (all p > 0.05). When serum selenium levels were classified as normal or deficient, the risk of GDM or preterm birth among women with normal serum selenium levels was still not lower than that of women with deficient serum selenium levels after adjustment for covariates (all p > 0.05). Although selenium deficiency was common in the Chinese women in our cohort, our results indicate that low serum selenium level during early pregnancy may not be a strong predictor of the risk of GDM and preterm birth. However, our sample size was small, and future studies with larger populations are warranted.

7.
J Vasc Access ; : 1129729820920103, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32372684

RESUMO

BACKGROUND: Many studies suggested that the optimal cephalic vein diameter for wrist radio-cephalic arteriovenous fistula construction should be at least 2 mm to predict successful maturation and primary patency. However, our experience has shown that many patients with smaller cephalic vein diameter (≤2 mm) in the neutral state (without a tourniquet) also have good clinical outcomes. The aim of this study was to identify predictors that affect primary survival of new wrist radio-cephalic arteriovenous fistula in patients with cephalic vein diameter ≤2 mm. METHODS: We performed a retrospective review of 50 patients with preoperative cephalic vein diameters ≤2 mm in the neutral state who underwent wrist radio-cephalic arteriovenous fistula construction between September 2016 and October 2019. Internal diameters of the cephalic vein and radial artery, venous distensibility, peak systolic velocity, and resistance index of the radial artery were determined by ultrasound examination before wrist radio-cephalic arteriovenous fistula placement. Patients were divided into two groups: failure and survival. RESULTS: The radio-cephalic arteriovenous fistula survival rate was 68% from the time of radio-cephalic arteriovenous fistula creation until the end of the study. Univariate analysis showed that larger venous distensibility (p < 0.001), non-diabetic kidney disease (p = 0.009), and slower peak systolic velocity of the radial artery (p = 0.033) were predictive factors for primary radio-cephalic arteriovenous fistula survival. Multivariate regression analysis revealed good venous distensibility (odds ratio = 9.637, 95% confidence interval = 1.893-49.050, p = 0.006) and non-diabetic kidney disease (odds ratio = 0.148, 95% confidence interval = 0.033-0.660, p = 0.012) to be independent predictors for primary radio-cephalic arteriovenous fistula survival. Receiver operating characteristic analysis showed that venous distensibility >0.52 mm (sensitivity: 70.6%, specificity: 68.8%) was the best cut-off value to predict primary radio-cephalic arteriovenous fistula survival. CONCLUSION: When cephalic veins with diameter ≤2 mm are found, venous distensibility should be used to aid in the surgery decision-making process. The outcome of wrist radio-cephalic arteriovenous fistula survival would be significantly improved through the use of cephalic vein with venous distensibility >0.52 mm.

8.
Int J Mol Sci ; 21(10)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429048

RESUMO

Indoxyl sulfate (IS) is a chronic kidney disease (CKD)-specific renal osteodystrophy metabolite that affects the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a transcription factor promoting osteoclastogenesis. However, the mechanisms underlying the regulation of NFATc1 by IS remain unknown. It is intriguing that the Aryl hydrocarbon receptor (AhR) plays a key role in osteoclastogenesis, since IS is an endogenous AhR agonist. This study investigates the relationship between IS concentration and osteoclast differentiation in Raw 264.7 cells, and examines the effects of different IS concentrations on NFATc1 expression through AhR signaling. Our data suggest that both osteoclastogenesis and NFATc1 are affected by IS through AhR signaling in both dose- and time-dependent manners. Osteoclast differentiation increases with short-term, low-dose IS exposure and decreases with long-term, high-dose IS exposure. Different IS levels switch the role of AhR from that of a ligand-activated transcription factor to that of an E3 ubiquitin ligase. We found that the AhR nuclear translocator may play an important role in the regulation of these dual functions of AhR under IS treatment. Altogether, this study demonstrates that the IS/AhR/NFATc1 signaling axis plays a critical role in osteoclastogenesis, indicating a potential role of AhR in the pathology and abnormality of bone turnover in CKD patients.

9.
Int J Mol Sci ; 21(7)2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32252330

RESUMO

Vascular calcification, which involves the deposition of calcifying particles within the arterial wall, is mediated by atherosclerosis, vascular smooth muscle cell osteoblastic changes, adventitial mesenchymal stem cell osteoblastic differentiation, and insufficiency of the calcification inhibitors. Recent observations implied a role for mesenchymal stem cells and endothelial progenitor cells in vascular calcification. Mesenchymal stem cells reside in the bone marrow and the adventitial layer of arteries. Endothelial progenitor cells that originate from the bone marrow are an important mechanism for repairing injured endothelial cells. Mesenchymal stem cells may differentiate osteogenically by inflammation or by specific stimuli, which can activate calcification. However, the bioactive substances secreted from mesenchymal stem cells have been shown to mitigate vascular calcification by suppressing inflammation, bone morphogenetic protein 2, and the Wingless-INT signal. Vitamin D deficiency may contribute to vascular calcification. Vitamin D supplement has been used to modulate the osteoblastic differentiation of mesenchymal stem cells and to lessen vascular injury by stimulating adhesion and migration of endothelial progenitor cells. This narrative review clarifies the role of mesenchymal stem cells and the possible role of vitamin D in the mechanisms of vascular calcification.

10.
Int Immunopharmacol ; 84: 106500, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32311669

RESUMO

BACKGROUND: Mast cells (MCs) mediate a key role in allergic diseases. Detailed studies of how the neuroleptic drug pimozide affects MC activity are lacking. The aim of this study was to investigate pimozide inhibition of immunoglobulin E (IgE)-mediated MC activation and MC-mediated allergic responses. METHOD: MCs were stimulated with anti-dinitrophenyl (DNP) IgE antibodies and DNP-horse serum albumin (HSA) antigen (Ag), and anti-allergic pimozide effects were detected by measuring ß-hexosaminidase levels. Morphological changes were observed histologically. In vivo pimozide effects were assessed in passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-sensitized active systemic anaphylaxis mouse (ASA) model experiments. Levels of phosphorylated (p-) SYK (spleen tyrosine kinase) and MAPKs (mitogen-activated protein kinases) were detected in western blots. RESULTS: We found that pimozide inhibited MC degranulation, reduced MC release of ß-hexosaminidase dose-dependently in activated RBL-2H3 (IC50: 13.52 µM) and bone marrow derived MC (BMMC) (IC50: 42.42 µM), and reduced MC morphological changes. The IgE/Ag-induced migration effect was suppressed by pimozide treatment dose-dependently. Pimozide down-regulated IgE/Ag-induced phosphorylation of SYK and MAPKs in activated MCs. Moreover, pimozide attenuated allergic reactions in PCA and ASA model mice, and decreased MC populations among splenic cells. CONCLUSIONS: The antipsychotic drug pimozide can suppress IgE-mediated MC activation in vitro and in vivo and should be considered for repurposing to suppress MC-mediated diseases.

11.
Phytother Res ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32255545

RESUMO

Malignant tumor endangers seriously the health of all mankind. Multidrug resistance (MDR) is one of the main causes of clinical tumor chemotherapy failure. Curcumin (CUR) has not only antitumor activity but also reversing tumor MDR effect. CUR reverses tumor MDR via regulating related signal pathways or corresponding expressed proteins or gene. When combined with chemotherapeutic agents, CUR can be a chemotherapeutic sensitive agent to enhance chemotherapy efficacy and weaken tumor MDR. On the other hand, to improve the MDR reversal effect of CUR, its derivatives have been extensively studied. Therefore, this article mainly focuses on reviewing the application of CUR and its derivatives in MDR and its mechanism of reversing MDR.

12.
Nanotechnology ; 31(32): 324001, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32315989

RESUMO

In high-voltage direct current (HVDC) transmission systems, electric charge accumulates on insulator surfaces, causing surface electric field distortion and flashover voltage reduction. Therefore, studying a material that can improve the insulator surface insulation strength is of great engineering value. In this work, several types of metal nanoparticles with different particle sizes and concentrations are doped into epoxy resin. The experimental phenomena enables some interesting conclusions: when no agglomeration of doped nanoparticles occurs, a higher doping concentration provides a better insulation performance. The larger the doping particle size is, the lower the insulation performance. Additionally, under the same conditions, different types of metal nanoparticles lead to slightly different results after doping. Especially after doping with low concentration (approximately 120 parts per million (ppm)) and small particle size (approximately 10 nm) nanocopper particles, the insulator surface charge accumulation was effectively suppressed, and the flashover voltage was significantly improved. Our analysis suggests that it may be related to the single-electron tunneling phenomenon. Relevant results provide a new way to improve the surface insulation strength of insulators in the future.

13.
Science ; 367(6482): 1135-1140, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32139544

RESUMO

Stacking solar cells with decreasing band gaps to form tandems presents the possibility of overcoming the single-junction Shockley-Queisser limit in photovoltaics. The rapid development of solution-processed perovskites has brought perovskite single-junction efficiencies >20%. However, this process has yet to enable monolithic integration with industry-relevant textured crystalline silicon solar cells. We report tandems that combine solution-processed micrometer-thick perovskite top cells with fully textured silicon heterojunction bottom cells. To overcome the charge-collection challenges in micrometer-thick perovskites, we enhanced threefold the depletion width at the bases of silicon pyramids. Moreover, by anchoring a self-limiting passivant (1-butanethiol) on the perovskite surfaces, we enhanced the diffusion length and further suppressed phase segregation. These combined enhancements enabled an independently certified power conversion efficiency of 25.7% for perovskite-silicon tandem solar cells. These devices exhibited negligible performance loss after a 400-hour thermal stability test at 85°C and also after 400 hours under maximum power point tracking at 40°C.

14.
Int J Mol Sci ; 21(5)2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32111067

RESUMO

Vascular calcification (VC) is highly associated with cardiovascular disease and all-cause mortality in patients with chronic kidney disease. Dysregulation of endothelial cells and vascular smooth muscle cells (VSMCs) is related to VC. Sirtuin-1 (Sirt1) deacetylase encompasses a broad range of transcription factors that are linked to an extended lifespan. Sirt1 enhances endothelial NO synthase and upregulates FoxOs to activate its antioxidant properties and delay cell senescence. Sirt1 reverses osteogenic phenotypic transdifferentiation by influencing RUNX2 expression in VSMCs. Low Sirt1 hardly prevents acetylation by p300 and phosphorylation of ß-catenin that, following the facilitation of ß-catenin translocation, drives osteogenic phenotypic transdifferentiation. Hyperphosphatemia induces VC by osteogenic conversion, apoptosis, and senescence of VSMCs through the Pit-1 cotransporter, which can be retarded by the sirt1 activator resveratrol. Proinflammatory adipocytokines released from dysfunctional perivascular adipose tissue (PVAT) mediate medial calcification and arterial stiffness. Sirt1 ameliorates release of PVAT adipokines and increases adiponectin secretion, which interact with FoxO 1 against oxidative stress and inflammatory arterial insult. Conclusively, Sirt1 decelerates VC by means of influencing endothelial NO bioavailability, senescence of ECs and VSMCs, osteogenic phenotypic transdifferentiation, apoptosis of VSMCs, ECM deposition, and the inflammatory response of PVAT. Factors that aggravate VC include vitamin D deficiency-related macrophage recruitment and further inflammation responses. Supplementation with vitamin D to adequate levels is beneficial in improving PVAT macrophage infiltration and local inflammation, which further prevents VC.

15.
Biomater Sci ; 8(7): 1802-1814, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32163070

RESUMO

Upconversion nanoparticles (UCNPs) have been widely employed for tumor imaging using magnetic resonance imaging (MRI) and upconversion luminescence (UCL) imaging. The short blood clearance time and immunogenicity of UCNPs have limited their further application in vivo. We have designed UCNPs camouflaged with an exterior red blood cell (RBC) membrane coating (RBC-UCNPs) to solve these problems. Moreover, because of some intrinsic disadvantages of MRI and UCL imaging, we investigated the use of pretargeted RBC-UCNPs for positron-emission tomography (PET) imaging to obtain more comprehensive information. Our data showed that RBC-UCNPs retained the immunity feature from the source cells and the superior optical and chemical features from the pristine UCNP cores. The tumor-targeting ability of RBC-UCNPs was enhanced by binding 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000] (DSPE-PEG-FA) molecules onto the cell membranes. PET imaging with short half-life radionuclides to visualize the RBC-UCNPs was successfully realized by a combination of pre-targeting and in vivo click chemistry. Blood chemistry, hematology, and histologic analysis suggested good in vivo biocompatibility of the RBC-UCNPs. Our method provides a new potential biomedical application of biomimetic nanoparticles.

16.
J Mater Chem B ; 8(13): 2627-2635, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32129372

RESUMO

Radiotherapy is a commonly used method for curing cancers that appear on or just below the skin. Because of the dose build-up effect of X-rays, boluses made of various materials such as silica and wax are clinically applied on patients to increase the skin dose for an enhanced therapeutic effect. However, these commercial boluses can't conform well to the skin's surface with some curvature, resulting in radiation dose attenuation/loss at the lesion location. To address this limitation, we have developed a nano-titanium dioxide (nTiO2)-incorporated polyurethane/polyacrylamide (TPU/PAAm) hydrogel with multi-functions for fabricating a desirable bolus. The obtained hydrogel exhibits excellent mechanical, adhesive and self-healing properties and can fit closely to the surface of patients with any 3D curvature, eliminating the air gap which is a common problem for commercial boluses applied on patients. In particular, it is encouraging that when using the bolus made of TPU/PAAm hydrogel, the dose distribution including dose coverage, conformability and homogeneity within the planning target volume (PTV) is far superior to that when using the commercial bolus. A sufficient dose shifts toward the surface of the head model and is located only in the lesion site, demonstrating that TPU-PAAm hydrogel can provide an optimal dose distribution and be clinically effective for treating superficial tumors. Furthermore, nTiO2 particles feature uniform dispersion at the nanometer level in hydrogel after being modified by 2,2-bis(hydroxymethyl)propionic acid (DMPA) based on coordination chemistry, endowing the hydrogel with long-acting antibacterial ability. The good cell affinity of TPU-PAAm hydrogel is also confirmed in this study, further ensuring that the TPU-PAAm hydrogel prepared here is a desirable candidate as a tissue equivalent with the advantages of convenient use and effectiveness in radiotherapy.

17.
J Am Chem Soc ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32150404

RESUMO

Metal halide perovskites show promise for light-emitting diodes (LEDs) owing to their facile manufacture and excellent optoelectronic performance, including high color purity and spectral stability, especially in the green region. However, for blue perovskite LEDs, the emission spectrum line width is broadened to over 25 nm by the coexistence of multiple reduced-dimensional perovskite domains, and the spectral stability is poor, with an undesirable shift (over 7 nm) toward longer wavelengths under operating conditions, degradation that occurs due to phase separation when mixed halides are employed. Here we demonstrate chloride insertion-immobilization, a strategy that enables blue perovskite LEDs, the first to exhibit narrowband (line width of 18 nm) and spectrally stable (no wavelength shift) performance. We prepare bromide-based perovskites and then employ organic chlorides for dynamic treatment, inserting and in situ immobilizing chlorides to blue-shift and stabilize the emission. We achieve sky-blue LEDs with a record luminance over 5100 cd/m2 at 489 nm, and an operating half-life of 51 min at 1500 cd/m2. By device structure optimization, we further realize an improved EQE of 5.2% at 479 nm and an operating half-life of 90 min at 100 cd/m2.

18.
Chem Senses ; 45(3): 195-202, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32010937

RESUMO

Neuropeptide S (NPS) is an endogenous peptide recently recognized to be presented in the brainstem and believed to play an important role in maintaining memory. The deletion of NPS or NPS receptor (NPSR) in mice shows a deficit in memory formation. Our recent studies have demonstrated that central administration of NPS facilitates olfactory function and ameliorates olfactory spatial memory impairment induced by muscarinic cholinergic receptor antagonist and N-methyl-D-aspartate receptor antagonist. However, it remains to be determined if endogenous NPS is an indispensable neuromodulator in the control of the olfactory spatial memory. In this study, we examined the effects of NPSR peptidergic antagonist [D-Val5]NPS (10 and 20 nmol, intracerebroventricular) and nonpeptidergic antagonist SHA 68 (10 and 50 mg/kg, intraperitoneal) on the olfactory spatial memory using computer-assisted 4-hole-board olfactory spatial memory test in mice. Furthermore, immunofluorescence was employed to identify the distributions of c-Fos and NPSR immunoreactive (-ir) neurons in olfactory system and hippocampal formation known to closely relate to the olfactory spatial memory. [D-Val5]NPS dosing at 20 nmol and SHA 68 dosing at 50 mg/kg significantly decreased the number of visits to the 2 odorants interchanged spatially, switched odorants, in recall trial, and simultaneously reduced the percentage of Fos-ir in NPSR-ir neurons, which were densely distributed in the anterior olfactory nucleus, piriform cortex, subiculum, presubiculum, and parasubiculum. These findings suggest that endogenous NPS is a key neuromodulator in olfactory spatial memory.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32109631

RESUMO

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the CATCH-LIFE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n=2600 patients) and July 2018 through January 2019 (n=1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P=.04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared to patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P<.001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P<.001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension.

20.
Int J Mol Sci ; 21(3)2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32024140

RESUMO

Vascular calcification (VC) is an important complication among patients of advanced age, those with chronic kidney disease, and those with diabetes mellitus. The pathophysiology of VC encompasses passive occurrence of physico-chemical calcium deposition, active cellular secretion of osteoid matrix upon exposure to metabolically noxious stimuli, or a variable combination of both processes. Epigenetic alterations have been shown to participate in this complex environment, through mechanisms including DNA methylation, non-coding RNAs, histone modifications, and chromatin changes. Despite such importance, existing reviews fail to provide a comprehensive view of all relevant reports addressing epigenetic processes in VC, and cross-talk between different epigenetic machineries is rarely examined. We conducted a systematic review based on PUBMED and MEDLINE databases up to 30 September 2019, to identify clinical, translational, and experimental reports addressing epigenetic processes in VC; we retrieved 66 original studies, among which 60.6% looked into the pathogenic role of non-coding RNA, followed by DNA methylation (12.1%), histone modification (9.1%), and chromatin changes (4.5%). Nine (13.6%) reports examined the discrepancy of epigenetic signatures between subjects or tissues with and without VC, supporting their applicability as biomarkers. Assisted by bioinformatic analyses blending in each epigenetic component, we discovered prominent interactions between microRNAs, DNA methylation, and histone modification regarding potential influences on VC risk.

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