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1.
Methods Mol Biol ; 2052: 373-402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31452173

RESUMO

Conventional cell cultures utilizing transformed or immortalized cell lines or primary human epithelial cells have played a fundamental role in furthering our understanding of Cryptosporidium infection. However, they remain inadequate with respect to their inability to emulate in vivo conditions, support long-term growth, and complete the life cycle of the parasite. Previously, we developed a 3D silk scaffold-based model using transformed human intestinal epithelial cells (IECs). This model supported C. parvum infection for up to 2 weeks and resulted in completion of the life cycle of the parasite. However, transformed IECs are not representative of primary human IEC.Human intestinal enteroids (HIEs) are cultures derived from crypts that contain Lgr5+ stem cells isolated from human biopsies or surgical intestinal tissues; these established multicellular cultures can be induced to differentiate into enterocytes, enteroendocrine cells, goblet cells, Paneth cells, and tuft cells. HIEs better represent human intestinal structure and function than immortalized IEC lines. Recently, significant progress has been made in the development of technologies to culture HIEs in vitro. When grown in a 3D matrix, HIEs provide a spatial organization resembling the native human intestinal epithelium. Additionally, they can be dissociated and grown as monolayers in tissue culture plates, permeable supports or silk scaffolds that enable mechanistic studies of pathogen infections. They can also be co-cultured with other human cells such as macrophages and myofibroblasts. The HIEs grown in these novel culture systems recapitulate the physiology, the 3D architecture, and functional diversity of native intestinal epithelium and provide a powerful and promising new tool to study Cryptosporidium-host cell interactions and screen for interventions ex vivo. In this chapter, we describe the 3D silk scaffold-based model using transformed IEC co-cultured with human intestinal myofibroblasts and 2D and 3D HIE-derived models of Cryptosporidium, also co-cultured with human intestinal myofibroblasts.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31568254

RESUMO

BACKGROUND: Transoral endoscopic parathyroidectomy vestibular approach for secondary hyperparathyroidism (SHPT) is controversial with regard to the time consumed, safety, and feasibility. We present our initial experience with modified transoral endoscopic parathyroidectomy vestibular approach (m-TOEPVA) procedure for SHPT using total parathyroidectomy with autotransplantation. MATERIALS AND METHODS: We retrospectively reviewed 10 patients with SHPT who underwent the m-TOEPVA procedure from December 2017 to April 2018 at our center. RESULTS: There were a total of 6 male individuals and 4 female individuals with a median age of 58.5 years. Among whom, 5 were on hemodialysis and 5 on peritoneal dialysis. The median length of hospital stay and operative time was 5 (4, 5) days, and 321.5 (302.75, 362.25) minutes, respectively. Successful removal of 4 parathyroid glands was achieved in 8 of 10 patients (80%) and, in 8 patients (8/10, 80%), the intact parathyroid hormone successfully dropped to <300 pg/mL at 3 months postoperatively. Two patients with ectopic parathyroid gland in the superior mediastinum were noted preoperatively by MIBI scan and subsequently had successful removal. Except for 1 patient with prolonged hospital stay (11 d) due to hungry bone syndrome, there were no other major complications. CONCLUSION: m-TOEPVA by total parathyroidectomy with autotransplantation for SHPT is feasible, safe, and offers optimal cosmetic results. The most valuable part is that m-TOEPVA provides direct visualization and successful removal of the ectopic parathyroid glands in the superior mediastinum.

3.
Medicine (Baltimore) ; 98(39): e17232, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574834

RESUMO

RATIONALE: To report a rare case of severe atypical hemolytic-uremic syndrome (HUS) in a patient who presented with vitreous hemorrhage and tractional retinal detachment (TRD) in both eyes. To our knowledge, this is the first reported case of atypical HUS complicated with bilateral TRD in the literature. PATIENT CONCERNS: A 20-year-old man with atypical HUS demonstrated bilateral visual acuity of hand motion at 30 cm. DIAGNOSES: Dilated fundus examination revealed diffuse intraretinal hemorrhage with vascular engorgement, neovascularization of the disc, and neovascularization elsewhere bilaterally. Fluorescein angiography revealed bilateral proliferative retinopathy, retinal hemorrhage, and a large nonperfusion area with extensive neovascularization. Intravitreal antivascular endothelial growth factor (ranibizumab) injection was administered in both eyes, but his ophthalmic condition did not improve, and TRD developed bilaterally. Therefore atypical HUS complicated with bilateral TRD was diagnosed. INTERVENTIONS: Pars plana vitrectomy was performed with panretinal photocoagulation and silicone oil tamponade in the right eye. OUTCOMES: After the pars plana vitrectomy of right eye, the retina was well-attached after surgery, but visual acuity remained poor. Visual evoked potential examination showed poor waveforms bilaterally, which suggested ischemic optic neuropathy. LESSONS: Atypical HUS can cause systemic thrombotic microangiopathy, resulting in ischemic retinal changes. These ischemic retinal changes can then cause hypoxia, which triggers production of angiogenic factors and subsequently causes retinal vascular hyperpermeability, retinal and vitreous neovascularization, fibrovascular proliferation, vitreous hemorrhage, and TRD, in a manner similar to that of other ischemia-induced proliferative retinopathies. Despite successful surgery in the right eye, our patient's visual acuity did not improve, possibly because of severe and generalized ischemia of intraocular tissue, which resulted in ischemic optic neuropathy.

4.
Arch Pathol Lab Med ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584841

RESUMO

CONTEXT.­: In prostate cancer, "tertiary" higher-grade patterns (TPs) have been associated with biochemical recurrence after radical prostatectomy. OBJECTIVE.­: To determine variation regarding definition and application of TPs. DESIGN.­: Online survey regarding TPs in a range of grading scenarios circulated to 105 experienced urologic pathologists. RESULTS.­: Among 95 respondents, 40 of 95 (42%) defined TPs as "third most common pattern" and 55 (58%) as "minor pattern/less than 5% of tumor." In a tumor with pattern 3 and less than 5% pattern 4, of the 95 respondents, 35 (37%) assigned 3+3=6 with TP4, while 56 (59%) assigned 3+4=7. In a tumor with pattern 4 and less than 5% pattern 5, of the 95 respondents, 51 (54%) assigned 4+4=8 with TP5, while 43 (45%) assigned 4+5=9. Six scenarios were presented in which the order of most common patterns was 3, 4, and 5 (Group 1) or 4, 3, and 5 (Group 2) with varying percentages. In both groups, when pattern 5 was less than 5%, we found that 98% and 93% of respondents would assign 3+4=7 or 4+3=7 with TP5. In scenarios with 15% or 25% pattern 5, most respondents (70% and 80%, respectively) would include pattern 5 as the secondary grade, that is, 3+5=8 (Group 1) or 4+5=9 (Group 2). For 85 of 95 (89%), a TP would not impact Grade Group assignment. CONCLUSIONS.­: This survey highlights substantial variation in practice patterns regarding definition and application of "tertiary" grading in radical prostatectomy specimens. High consistency was observed in 3+4=7/4+3=7 scenarios with truly minor pattern 5. These findings should inform future studies assessing the standardization and predictive value of "tertiary" patterns.

5.
J Biomed Sci ; 26(1): 72, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597574

RESUMO

BACKGROUND: Transforming growth factor (TGF) family members play important roles in the regulation of corneal integrity, and the pathogenesis of corneal fibrosis. Currently, there are no effective agents targeting TGF-ß signaling to diminish corneal fibrosis. Glucosamine (GlcN), which is widely used in the treatment of osteoarthritis, abrogates the morphologic effects of TGF-ß2 on retinal pigmented epithelial cells in a mouse disease model. Here, we sought to determine whether GlcN would exert beneficial effects against TGF-ß1-induced corneal fibrosis. METHODS: In human corneal fibroblasts (HCFs) treated with GlcN, the expression of Krüppel-like factor 4 (KLF4) and its downstream signaling effects were determined in the presence and absence of TGF-ß1 using immunoblot analysis. We further explored GlcN inhibition of fibroblast-to-myofibroblast differentiation via KLF4 siRNA. The effect of cycloheximide on KLF4 protein levels with or without GlcN administration was assessed to determine whether GlcN affects the stability of the KLF4 protein. RESULTS: In HCFs, GlcN induced the expression of KLF4, which regulated the maturation and maintenance of the ocular surface. GlcN partially suppressed the TGF-ß1-induced expression of alpha-smooth muscle actin (α-SMA) and reduced the collagen contraction capacity in HCFs, suggesting a decrease in fibroblast-to-myofibroblast differentiation. This effect appeared to be mediated through suppression of Smad2 phosphorylation and ERK-dependent signaling. The levels of KLF4 mRNA were increased by GlcN and decreased by TGF-ß1 and the TGF-ß1-induced α-SMA mRNA expression was upregulated when the KLF4 gene was silenced. GlcN also appeared to stabilize the KLF4 protein, reducing its turnover in corneal fibroblasts. CONCLUSION: These findings shed light on a novel mechanism by which GlcN suppresses TGF-ß1-induced fibroblast-to-myofibroblast differentiation through the upregulation of KLF4 expression. Current strategies for treating corneal fibrosis were not effective. Elevating KLF4 levels through the use of GlcN might provide an effective alternative to alleviate the development and progression of corneal fibrosis.

6.
Acta Physiol (Oxf) ; : e13398, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31599114

RESUMO

An article recently published by Professor Wang Lin provides a insightful explanation as to why the harmonic components of radial pulse waves may be an important set of signs to reveal the state of the ventricular-arterial system.1 The important basis of the article comes from the "resonance theory" proposed by Wang et al. through a series of elegant animal studies.2,3 Here, we would like to provide further clinical references to point out the important correlation between the harmonic components of the radial pulse wave and the risk of future cardiovascular events.

7.
Eur J Pain ; 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587420

RESUMO

BACKGROUND: Population-based studies show that sleep problems and psychological symptoms may increase the risk of musculoskeletal pain onset in children / adolescents. However, there is no evidence of these associations within primary care settings, where interventions can take place. This study investigated whether children / adolescents who consulted their general practitioner for sleep problems or psychological symptoms are at higher risk of subsequent consultations for musculoskeletal conditions. METHODS: This prospective matched-cohort study used electronic medical records of children / adolescents (aged 6-19 years) from a UK primary care database. Associations between a consultation for sleep problems or psychological symptoms at baseline and a subsequent consultation for musculoskeletal conditions within the two-year follow-up were investigated using survival analysis, producing Hazard Ratios (HR) and 95% Confidence Intervals (CI) with adjustment for confounders. RESULTS: Children / adolescents who consulted for sleep problems had a significant increased risk of consultation for musculoskeletal conditions (HR = 1.72; 95% CI 1.14, 2.60), which became non-significant after adjustment for confounders (HR = 1.49; 95% CI 0.98, 2.27). Children / adolescents who consulted for psychological symptoms had a significant increased risk of consultation for musculoskeletal conditions (HR = 1.59; 95% CI 1.31, 1.93), which was attenuated after adjustment (HR = 1.39; 95% CI 1.14, 1.70). CONCLUSIONS: Children and adolescents who visit primary care for sleep problems or psychological symptoms have increased risk of future musculoskeletal consultations. Further work is needed to understand the causal mechanisms that explain these associations, before designing interventions strategies within primary care settings.

8.
Drug Des Devel Ther ; 13: 3391-3404, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576113

RESUMO

Purpose: It has been reported that approximately 40% of ALI (acute lung injury) incidence resulted from sepsis. Paclitaxel, as a classic anti-cancer drug, plays an important role in the regulation of inflammation. However, we do not know whether it has a protective effect against CLP (cecal ligation and puncture)-induced septic ALI. Our study aims to illuminate the mitigative effects of paclitaxel on sepsis-induced ALI and its relevant mechanisms. Materials and methods: The survival rates and organ injuries were used to evaluate the effects of paclitaxel on CLP mice. The levels of inflammatory cytokines were tested by ELISA. MUC1 siRNA pre-treatment was used to knockdown MUC1 expression in vitro. GO203 was used to inhibit the homodimerization of MUC1-C in vivo. The expression levels of MUC1, TLR 4 and p-NF-κB/p65 were detected by Western blot. Results: Our results showed that paclitaxel improved the survival rates and ameliorated organ injuries especially lung injury in CLP-induced septic mice. These were accompanied by reduced inflammatory cytokines in sera and BALF (bronchoalveolar lavage fluid). We also found paclitaxel could attenuate TLR 4-NF-κB/p65 activation both in lung tissues of septic mice and LPS-stimulated lung type II epithelial cell line A549. At the upstream level, paclitaxel-upregulated expression levels of MUC1 in both in vivo and in vitro experiments. The inhibitory effects of paclitaxel on TLR 4-NF-κB/p65 activation were reversed in lung tissues of septic mice pre-treated with MUC1 inhibitor and in MUC1-knockdown A549 cells. Protection of paclitaxel on sepsis-induced ALI and decrease of inflammatory cytokines were also abolished by inhibition of MUC1. Conclusion: Collectively, these results indicated paclitaxel could significantly alleviate acute lung injury in CLP-induced septic mice and LPS-stimulated lung type II epithelial cell line A549 by activating MUC1 and suppressing TLR-4/NF-κB pathway.

9.
Medicine (Baltimore) ; 98(40): e17269, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577718

RESUMO

This study examined the characteristics of norovirus (NoV) gastroenteritis associated with convulsions in children and its molecular epidemiology. From July 2006 through December 2015, NoV infection was confirmed by the genome detection using reverse transcriptase polymerase chain reaction. Viral genotyping with strain validation was achieved using sequence analyses with Basic Local Alignment Search Tool genome identification. The patients' clinical features were assessed retrospectively, focusing on convulsive disorders. The diagnosis of encephalitis followed the International Encephalitis Consortium. Seizures occurred in 52 (20.9%) of 249 NoV infections. GII.4 Den_Haag_2006b (n = 22, 42.3%) and GII.4 Sydney 2012 (n = 10, 19.2%) were major variants correlated with convulsions. Patient with convulsions tend to have GII.4 genotype infection (P < .001), short vomiting (≤2 days) (P < .001), and no fever (P = .002). Compared to GII.4 Den_Haag_2006b, the GII.4 Sydney 2012-associated convulsions had similar manifestations except without significant winter preponderance (P = .049). The NoV infection with convulsions had less febrile course, specific genotype (GII.4) infections, and with shorter symptom of vomiting. Continuous surveillance is important for uncommon disease associated with emerging NoV strain infections. The prevention of NoV diseases requires the development of vaccines targeting highly virulent variants.

10.
Org Lett ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580692

RESUMO

By introducing a carbon functionality at 2-position of chromane, the formal asymmetric functionalization of the 3-position of 2-substituted chromane has been realized via a highly chemo-, regio-, and stereoselective organocatalytic cascade reaction in a sequential one-pot manner involving an E1cB mechanism governed ring-opening process. Critical to our success was the design of a chiral dipeptide-based bifunctional acid-base organocatalyst, which exhibited high catalytic activity at low catalyst loading (1-0.1 mol %), leading to biologically interesting polyheterocyclic compounds.

11.
J Bone Miner Metab ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31583541

RESUMO

INTRODUCTION: The aim of this study was to develop an algorithm to identify high-risk populations of fragility fractures in Taiwan. MATERIALS AND METHODS: A total of 16,539 postmenopausal women and men (age ≥ 50 years) were identified from the Taiwan Osteoporosis Survey database. Using the Taiwan FRAX® tool, the 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) and the individual intervention threshold (IIT) of each participant were calculated. Subjects with either a probability above the IIT or those with MOF ≥ 20% or HF ≥ 9% were included as group A. Subjects with a bone mineral density (BMD) T-score at femoral neck based on healthy subjects of ≤ - 2.5 were included in group B. We tested several cutoff points for MOF and HF so that the number of patients in group A and group B were similar. A novel country-specific hybrid intervention threshold along with an algorithm was generated to identify high fracture risk individuals. RESULTS: 3173 (19.2%) and 3129 (18.9%) participants were categorized to groups A and B, respectively. Participants in group B had a significantly lower BMD (p < 0.001), but clinical characteristics, especially the 10-year probability of MOF (p < 0.001) or HF (p < 0.001), were significantly worse in group A. We found the algorithm generated from the hybrid intervention threshold is practical. CONCLUSION: The strategy of generating an algorithm for fracture prevention by novel hybrid intervention threshold is more efficient as it identifies patients with a higher risk of fragility fracture and could be a template for other country-specific policies.

12.
ACS Nano ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31577417

RESUMO

Metal-enhanced fluorescence (MEF) considerably enhances the luminescence for various applications, but its performance largely depends on the dielectric spacer between the fluorophore and plasmonic system. It is still challenging to produce a defect-free spacer having an optimized thickness with a sub-nanometer accuracy that enables reusability without affecting the enhancement. In this study, we demonstrate the use of atomically thin hexagonal boron nitride (BN) as an ideal MEF spacer owing to its multifold advantages over the traditional dielectric thin films. With rhodamine 6G as a representative fluorophore, it largely improves the enhancement factor (up to ∼95 ± 5), sensitivity (10-8 M), reproducibility, and reusability (∼90% of the plasmonic activity is retained after 30 cycles of heating at 350 °C in air) of MEF. This can be attributed to its two-dimensional structure, thickness control at the atomic level, defect-free quality, high affinities to aromatic fluorophores, good thermal stability, and excellent impermeability. The atomically thin BN spacers could increase the use of MEF in different fields and industries.

13.
BMC Plant Biol ; 19(1): 413, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590655

RESUMO

BACKGROUND: Taxus spp. produces the anticancer drug, taxol, and hence is planted as an industrial crop in China. APETALA2/ethylene response element binding proteins (AP2/EREBPs) are the key regulators of plant development, growth, and stress responses. Several homologues control taxol biosynthesis. Identifying the AP2/EREBP proteins from Taxus is important to increase breeding and production and clarify their evolutionary processes. RESULTS: Among the 90 genes from multi Taxus chinensis transcriptome datasets, 81 encoded full-length AP2-containing proteins. A domain structure highly similar to that of angiosperm AP2/EREBPs was found in 2 AP2, 2 ANT, 1 RAV, 28 dehydration-responsive element-binding proteins, and 47 ethylene-responsive factors contained, indicating that they have extremely conservative evolution processes. A new subgroup protein, TcA3Bz1, contains three conserved AP2 domains and, a new domain structure of AP2/EREBPs that is different from that of known proteins. The new subtype AP2 proteins were also present in several gymnosperms (Gingko biloba) and bryophytes (Marchantia polymorpha). However, no homologue was found in Selaginella moellendorffii, indicating unknown evolutionary processes accompanying this plant's evolution. Moreover, the structures of the new subgroup AP2/EREBPs have different conserved domains, such as B3, zf-C3Hc3H, and agent domains, indicating their divergent evolution in bryophytes and gymnosperms. Interestingly, three repeats of AP2 domains have separately evolved from mosses to gymnosperms for most of the new proteins, but the AP2 domain of Gb_11937 has been replicated. CONCLUSION: The new subtype AP2/EREBPs have different origins and would enrich our knowledge of the molecular structure, origin, and evolutionary processes of AP2/EREBP transcription factors in plants.

14.
J Food Drug Anal ; 27(4): 860-868, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31590757

RESUMO

The continuous re-isolation of the known and non-applicable compounds that is time-consuming and wasting resources is still a critical problem in the discovery of bioactive entities from natural resources. To efficiently address the problem, high performance liquid chromatography-diode array detector-microfractionation (HPLC-DAD-microfractionation) guided by disk agar diffusion assay was developed, and the active compounds were further identified using the tandem mass spectrometry (MS/MS)-based molecular networking. Of 150 fungal strains screened, the methanolic extracts of Phoma herbarum PPM7487, Cryptosporiopsis ericae PPM7405, and Albifimbria verrucaria PPM945 exhibited potent antimicrobial activity against Candida albicans SC5314 and Cryptococcus neoformans H99 in the preliminary agar diffusion assay. The concept of OSMAC (one strain many compounds) was employed in the fungal cultures in order to enrich the diversity of the 2nd metabolites in this study. HPLC coupled with off-line bioactivity-directed profiling of the extracts enabled a precise localization of the compounds responsible for the conspicuous antimicrobial activity. The purified active compounds were identified based mainly on MS/MS database, and further supported by 13C nuclear magnetic resonance (NMR) spectral data compared to the literatures. In addition to nineteen known compounds, a new trichothecene derivative 1, namely trichoverrin D, was isolated and identified through this protocol. The antifungal activities of all the pure isolates were evaluated, and the structure activity relationships were also inferred. This report has demonstrated the combination of HPLC microfractination and MS/MS coupled by NMR spectral dereplication for speeding up the antimicrobial natural products discovery process.

15.
Physiol Rep ; 7(19): e14252, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31591828

RESUMO

This investigation explored the hypothesis that whether the coefficient of variation of the fourth harmonic amplitude of the radial pulse wave (C4CV) predicts the risk of macrovascular and microvascular events in patients with type 2 diabetes mellitus (T2DM). Radial pulse wave and brachial blood pressure were measured at baseline in 2324 patients with T2DM and C4CV was calculated using the Fourier series method. Macrovascular and microvascular events during follow-up were determined by medical records. We plotted the Kaplan-Meier curve and performed a Cox proportional hazard model and a log-rank test to estimate the effectiveness of C4CV as a risk predictor. We divided patients into quartile groups based on C4CV (<4.3%, 4.3% to 6.8%, 6.8% to 11.4%, and >11.4%). Compared with patients with C4CV < 4.3%, patients with C4CV> 11.4% had a double incidence of macrovascular events (hazard ratio, 2.13; 95% CI, 1.70-2.67) and microvascular events (hazard ratio, 2.08; 95% CI, 1.67-2.58), and the incidence of cardiovascular death was three times (hazard ratio, 3.03; 95% CI, 1.10-8.83). The Cox regression analysis demonstrated that the risk of both macrovascular and microvascular outcomes increases with the increase in quartile level of C4CV value (P < 0.0001). These associations remained after adjustment for age, gender, smoking, systolic blood pressure, diastolic blood pressure, dyslipidemia, diabetes duration, Hba1c, and cardiovascular disease (P < 0.0001). C4CV is a novel independent predictor of cardiovascular mortality, macrovascular events, and microvascular events in patients with T2DM.

16.
Medicine (Baltimore) ; 98(38): e16973, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567932

RESUMO

BACKGROUND: As the most important component of cardiovascular disease, coronary heart disease (CHD) is closely related to psychological factors such as anxiety. Anxiety, whether present before or after the onset of illness, can lead to many serious consequences. The aim of this systematic review and meta-analysis was to assess the prevalence of and potential risk factors for anxiety after coronary heart disease (post-CHD anxiety). METHOD: Systematic searches were performed in electronic databases including China National Knowledge Infrastructure (CNKI), Wanfang, Technology Journal database (VIP), PubMed, Web of Science, Embase and Medline. RESULT: Thirteen studies were included. With regard to cross-sectional studies, the prevalence of post-CHD anxiety was P = .37, 95% CI (0.26-0.49). The overall analysis among cohort studies revealed that the prevalence of post-CHD anxiety was P = .50, 95% CI (0.05-0.95). Among the 11 potential risk factors, low education level [OR = 1.46, 95% CI (1.05-2.02)] and long duration of disease [OR = 2.05, 95% CI (1.05-4.00)] were statistically significant. CONCLUSION: There is high heterogeneity between studies and many defects; thus, further research is required to support these results. Attention should be paid to post-CHD anxiety, and clinical caring should include psychological counselling and imparting disease-related knowledge to patients with a long disease duration and low educational background.


Assuntos
Transtornos de Ansiedade/epidemiologia , Infarto do Miocárdio/psicologia , Transtornos de Ansiedade/psicologia , China/epidemiologia , Humanos , Prevalência , Fatores de Risco
17.
Biomaterials ; 225: 119517, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31580968

RESUMO

An in vitro model of intestinal epithelium with an immune component was bioengineered to mimic immunologic responses seen in inflammatory bowel disease. While intestinal immune phenomena can be modeled in transwells and 2D culture systems, 3D tissue models improve physiological relevance by providing a 3D substrate which enable migration of macrophages towards the epithelium. An intestinal epithelial layer comprised of non-transformed human colon organoid cells and a subepithelial layer laden with monocyte-derived macrophages was bioengineered to mimic native intestinal mucosa cell organization using spongy biomaterial scaffolds. Confluent monolayers with microvilli, a mucus layer, and infiltration of macrophages to the basal side of the epithelium were observed. Inflammation, induced by E. coli O111:B4 lipopolysaccharide and interferon γ resulted in morphological changes to the epithelium, resulting in ball-like structures, decreased epithelial coverage, and increased migration of macrophages to the epithelium. Analysis of cytokines present in the inflamed tissue model demonstrated significantly upregulated secretion of pro-inflammatory cytokines that are often associated with active inflammatory bowel disease, including CXCL10, IL-1ß, IL-6, MCP-2, and MIP-1ß. The macrophage layer enhanced epithelial and biochemical responses to inflammatory insult, and this new tissue system may be useful to study and develop potential therapies for inflammatory bowel disease.

18.
Am J Surg Pathol ; 43(11): 1445-1461, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31600176

RESUMO

TFEB is overexpressed in TFEB-rearranged renal cell carcinomas as well as in renal tumors with amplifications of TFEB at 6p21.1. As recent literature suggests that renal tumors with 6p21.1 amplification behave more aggressively than those with rearrangements of TFEB, we compared relative TFEB gene expression in these tumors. This study included 37 TFEB-altered tumors: 15 6p21.1-amplified and 22 TFEB-rearranged (including 5 cases from The Cancer Genome Atlas data set). TFEB status was verified using a combination of fluorescent in situ hybridization (n=27) or comprehensive molecular profiling (n=13) and digital droplet polymerase chain reaction was used to quantify TFEB mRNA expression in 6p21.1-amplified (n=9) and TFEB-rearranged renal tumors (n=19). These results were correlated with TFEB immunohistochemistry. TFEB-altered tumors had higher TFEB expression when normalized to B2M (mean: 168.9%, n=28), compared with non-TFEB-altered controls (mean: 7%, n=18, P=0.005). Interestingly, TFEB expression in tumors with rearrangements (mean: 224.7%, n=19) was higher compared with 6p21.1-amplified tumors (mean: 51.2%, n=9; P=0.06). Of note, classic biphasic morphology was only seen in TFEB-rearranged tumors and when present correlated with 6.8-fold higher TFEB expression (P=0.00004). Our results suggest that 6p21.1 amplified renal tumors show increased TFEB gene expression but not as much as t(6;11) renal tumors. These findings correlate with the less consistent/diffuse expression of downstream markers of TFEB activation (cathepsin K, melan A, HMB45) seen in the amplified neoplasms. This suggests that the aggressive biological behavior of 6p21.1 amplified renal tumors might be secondary to other genes at the 6p21.1 locus that are co-amplified, such as VEGFA and CCND3, or other genetic alterations.

19.
Chin Med Sci J ; 34(3): 194-198, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601302

RESUMO

Objective To depict imaging anatomy of bronchial artery (BA) using multidetector CT-angiography (MDCTA) and evaluate the value of MDCTA for management of hemoptysis patients requiring admission to emergency room. Methods We retrospectively studied the clinical and radiological data of patients with severe hemoptysis (≥100 ml of expectorated blood in a 24-hour period) requiring admission to emergency room from Jan 1, 2013 to Dec 31, 2015. Patients' images of MDCTA, treatment modalities, and outcome were discussed. Results A total of 108 patients underwent MDCTA scans. Etiology of hemoptysis was mainly bronchiectasis (44%), tuberculosis sequelae (26%) and tumor (18%). MDCTA visualized 197 traceable BAs and also suggested the involvement of 35 nonbronchial systemic arteries. The mean diameter of BAs, measured at the level of the bronchial bifurcation in the mediastinum, was 2.8±1.2 mm. The mean diameter of BAs, for 52 patients who only received conservative treatment, was 2.9±1.1 mm, and was not significantly larger than that of BAs for 56 patients who underwent bronchial artery embolization (BAE) for continued bleeding which did not resolve after conservative treatment (2.7±1.1 mm, P = 0.94). The technical success rate of embolization was 95% (53/56). Clinical success rate during follow-up was achieved in 50 (94%) of 53 patients who had undergone embolization. Conclusions MDCTA provides useful information for identifying the anatomical characteristics of bleeding-related BAs and nonbronchial systemic arteries for the management of patients with severe hemoptysis. However, MDCTA could not determine the individuals who need BAE through measuring diameter of BAs.

20.
New Phytol ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595506

RESUMO

As sessile organisms, plants are exposed to diverse abiotic and biotic stresses, and thus have developed complex signaling mechanisms that orchestrate multiple stress responses. Plant peptides have recently emerged as key signaling molecules of stress responses, not only to mechanical wounding and pathogen infection but also to nutrient imbalance, drought and high salinity. The currently identified stress-related signaling peptides in plants are derived from proteolytic processing of protein precursors. Here, we review these protein-derived peptides and the evidences for their functions in stress signaling. We recommend potential research directions that could clarify their roles in stress biology, and propose possible crosstalk with regard to the physiological outcome. The stress-centric perspective allows us to highlight the crucial roles of peptides in regulating the dynamics of stress physiology. Inspired by historic and recent findings, we review how peptides initiate complex molecular interactions to coordinate biotic and abiotic stress responses in plants.

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