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1.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33649864

RESUMO

Atherosclerosis (AS) is a chronic inflammatory disease of the vascular wall with multiple causes. AS is the primary pathological basis of cardiovascular disease and stroke. Moreover, carotid plaque rupture and thrombus formation are the main causes of ischemic stroke. Therefore, understanding the formation of carotid plaques may help improve the prediction and prevention of cardiovascular and cerebrovascular events. Endothelial cell dysfunction results in re­endothelialization and angiogenesis in atherosclerotic plaques, thus promoting plaque destabilization. The aim of the present study was to evaluate the effect of circular RNA (circRNA) molecules in serum exosomes (serum­Exos) from patients with stable plaque atherosclerosis (SA) and unstable/vulnerable plaque atherosclerosis (UA). Specifically, the effect of circRNA on human umbilical vein endothelial cell (HUVEC) behavior and the mechanisms underlying plaque destabilization in AS were evaluated. Serum­Exos were isolated, then identified using transmission electron microscopy, nanoparticle tracking analysis and western blotting. The serum­Exo­circRNA expression profile of patients with SA or UA was investigated using a circRNA array. The relationship between circRNA­006896 in serum­Exos and biochemical parameters of patients with SA and UA were analyzed using Spearman's correlation. In addition, HUVECs were incubated with serum­Exos for in vitro functional assays. The present study demonstrated that circRNAs expression profiles in SA and UA serum­Exos were significantly different, indicating a potential role for circRNAs in carotid plaque destabilization. The expression of circRNA­0006896 was positively correlated with triglyceride, low­density lipoprotein cholesterol (LDL­C) and C­reactive protein levels, and negatively correlated with albumin levels in patients with UA. However, circRNA­0006896 expression was positively correlated with LDL­C in patients with SA. Using bioinformatic analysis, a competing endogenous RNA (ceRNA) network was selected to study the regulatory roles of circRNA­0006896 in serum­Exos. Additionally, in HUVECs treated with serum­Exos derived from patients with UA, the expression of circRNA­0006896 in HUVECs was upregulated. This was accompanied by decreased expression of microRNA­1264 and SOCS3, increased levels of DNMT1 and phosphorylated STAT3. HUVEC proliferation and migration were significantly increased in the UA group, compared with the mock and SA groups. This finding indicates that the circRNA­0006896­miR-1264­DNMT1 axis plays an important role in carotid plaque destabilization by regulating the behavior of endothelial cells. Moreover, it suggests that circRNA­0006896 may represent a therapeutic target for controlling JNK/STAT3 signaling in HUVECs. Thus, this study may provide insight on potential interventions against vulnerable plaque formation in patients with AS.

2.
Curr Protoc ; 1(3): e69, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33656278

RESUMO

Data-independent-acquisition mass spectrometry (DIA-MS) is a state-of-the-art proteomic technique for high-throughput identification and quantification of peptides and proteins. Interpretation of DIA-MS data relies on the use of a spectral library, which is optimally created from data acquired from the same samples in data-dependent acquisition (DDA) mode. As DIA-MS quantification relies on the spectral libraries, having a high-quality, non-redundant, and comprehensive spectral library is essential. This article describes the major steps for creating a high-quality spectral library using a combination of multiple complementary search engines. We discuss appropriate strategies to control the false discovery rate for the final spectral library as a result of merging multiple searches. © 2021 The Authors Current Protocols © 2021 Wiley Periodicals LLC. Basic Protocol 1: Searching DDA-MS files with multiple search engines Basic Protocol 2: Merging results from multiple search engines Basic Protocol 3: Creating spectral libraries from merged results Alternate Protocol: Using CLI for automating tasks Support Protocol: Creating concatenated FASTA files.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33669356

RESUMO

The effects of microcystin-RR (MC-RR) on water metabolism were studied on Sprague-Dawley (SD) rats and KunMing (KM) mice. In the single dose toxicity test, polydipsia, polyuria, hematuria and proteinuria were found in group of rats receiving a MC-RR dose of 574.7 µg/kg, and could be relieved by dexamethasone (DXM). Gradient damage was observed in kidney and liver in rats with gradient MC-RR doses of 574.7, 287.3, and 143.7 µg/kg. No significant water metabolic changes or kidney injuries were observed in mice treated with MC-RR doses of 210.0, 105.0, and 52.5 µg/kg. In the continuous exposure test, in which mice were administrated with 140.0, 70.0, and 35.0 µg/kg MC-RR for 28 days, mice in the 140.0 µg/kg group presented increasing polydipsia, polyuria, and liver damage. However, no anatomic or histological changes, including related serological and urinary indices, were found in the kidney. In summary, abnormal water metabolism can be induced by MC-RR in rats through kidney injury in single dose exposure; the kidney of SD rats is more sensitive to MC-RR than that of KM mouse; and polydipsia and polyuria in mice exposed to MC-RR for 28 days occurred but could not be attributed to kidney damage.

4.
Acta Biochim Biophys Sin (Shanghai) ; 53(4): 400-409, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33677475

RESUMO

Persistent hypotonic and inflammatory conditions in the joint cavity can lead to the loss of cartilage matrix and cell death, which are the important mechanisms of osteoarthritis (OA) onset. Previous studies have confirmed that the existence of a hypotonic environment is a red flag for inflammation, as hypotonic environment induces the opening of the chloride channel of the cell and promotes chloride ion efflux, which prompts the cell volume to increase. Chloride channels play an important role in the regulation of mineralization and chondrocyte death. Here, we reported that OA chondrocytes showed a significant increase of cell death rate and the imbalance of cartilage matrix catabolism. We found that the distribution of skeleton protein F-actin was disordered. In addition, the volume-sensitive chloride current of OA chondrocytes decreased significantly with the increase of the expression levels of inflammation-related proteins caspase-1, caspase-3, and NLRP3. Moreover, interleukin-1ß (IL-1ß) showed a potential to activate the chloride current of normal chondrocytes. These results indicate that IL-1ß-induced chloride channel opening in chondrocytes may be closely related to the occurrence of OA. This chloride channel opening process may therefore be a potential target for the treatment of OA.

5.
Cancer Res ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574084

RESUMO

Oncogenic protein tyrosine phosphatases have long been viewed as drug targets of interest, and recently developed allosteric inhibitors of SH2 domain-containing phosphatase-2 (SHP2) have entered clinical trials. However, the ability of phosphatases to regulate many targets directly or indirectly and to both promote and antagonize oncogenic signaling may make the efficacy of phosphatase inhibition challenging to predict. Here we explore the consequences of antagonizing SHP2 in glioblastoma, a recalcitrant cancer where SHP2 has been proposed as a useful drug target. Measuring protein phosphorylation and expression in glioblastoma cells across 40 signaling pathway nodes in response to different drugs and for different oxygen tensions revealed that SHP2 antagonism has network-level, context-dependent signaling consequences that affect cell phenotypes (e.g., cell death) in unanticipated ways. To map specific signaling consequences of SHP2 antagonism to phenotypes of interest, a data-driven computational model was constructed based on the paired signaling and phenotype data. Model predictions aided in identifying three signaling processes with implications for treating glioblastoma with SHP2 inhibitors. These included PTEN-dependent DNA damage repair in response to SHP2 inhibition, AKT-mediated bypass resistance in response to chronic SHP2 inhibition, and SHP2 control of hypoxia-inducible factor expression through multiple mitogen-activated protein kinases. Model-generated hypotheses were validated in multiple glioblastoma cell lines, in mouse tumor xenografts, and through analysis of TCGA data. Collectively, these results suggest that in glioblastoma, SHP2 inhibitors antagonize some signaling processes more effectively than existing kinase inhibitors but can also limit the efficacy of other drugs when used in combination.

6.
Public Health Nutr ; : 1-9, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33634772

RESUMO

OBJECTIVE: Previous studies have reported inverse associations between certain healthy lifestyle factors and non-alcoholic fatty liver disease (NAFLD), but limited evidence showed the synergistic effect of those lifestyles. This study examined the relationship of a combination of lifestyles, expressed as Healthy Lifestyle Score (HLS), with NAFLD. DESIGN: A community-based cross-sectional study. Questionnaires and body assessments were used to collect data on the six-item HLS (ranging from 0 to 6, where higher scores indicate better health). The HLS consists of non-smoking (no active or passive smoking), normal BMI (18·5-23·9 kg/m2), physical activity (moderate or vigorous physical activity ≥ 150 min/week), healthy diet pattern, good sleep (no insomnia or <6 months) and no anxiety (Self-rating Anxiety Scale < 50), one point each. NAFLD was diagnosed by ultrasonography. SETTING: Guangzhou, China. PARTICIPANTS: Two thousand nine hundred and eighty-one participants aged 40-75 years. RESULTS: The overall prevalence of NAFLD was 50·8 %. After adjusting for potential covariates, HLS was associated with lower presence of NAFLD. The OR of NAFLD for subjects with higher HLS (3, 4, 5-6 v. 0-1 points) were 0·68 (95 % CI 0·51, 0·91), 0·58 (95 % CI 0·43, 0·78) and 0·35 (95 % CI 0·25, 0·51), respectively (P-values < 0·05). Among the six items, BMI and physical activity were the strongest contributors. Sensitivity analyses showed that the association was more significant after weighting the HLS. The beneficial association remained after excluding any one of the six components or replacing BMI with waist circumference. CONCLUSIONS: Higher HLS was associated with lower presence of NAFLD, suggesting that a healthy lifestyle pattern might be beneficial to liver health.

7.
Int J Mol Med ; 47(2): 511-522, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33416097

RESUMO

Acute kidney injury (AKI) is characterized by an abrupt deterioration of renal function. Formononetin (FOR) protects against cisplatin (CIS)­induced AKI, and it has various potential pharmacological and biological effects, including anti­inflammatory, antioxidative and anti­apoptotic effects. The current study investigated the role of FOR in CIS­induced AKI. Rats were treated with CIS to establish an AKI model, followed by treatment with FOR. HK­2 cells were treated with CIS, FOR, GW6471 [a peroxisome proliferator­activated receptor α (PPARα) antagonist], eupatilin (a PPARα agonist) and nuclear factor erythroid 2­related factor 2 (Nrf2) small interfering RNA (siNrf2), and cell proliferation and apoptosis were determined by MTT and flow cytometry assays. The mRNA and proteins levels of PPARα, Nrf2, heme oxygenase­1 (HO­1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were measured by reverse transcription­quantitative PCR and western blotting. The results demonstrated that FOR attenuated the histopathological changes, the levels of blood urea nitrogen, creatinine, TNF­α and IL­1ß, and the MDA content and MPO activity, whereas it enhanced CAT activity in the AKI rat model. Furthermore, FOR and eupatilin promoted cell viability and CAT activity, and increased the levels of PPARα, Nrf2 and HO­1 and NQO1, but suppressed apoptosis and MPO activity, and reduced the levels of MDA, TNF­α and IL­1ß in CIS­treated HK­2 cells. Notably, the aforementioned effects were reversed by GW6471 treatment or siNrf2 transfection. In conclusion, FOR protects against CIS­induced AKI via activation of the PPARα/Nrf2/HO­1/NQO1 pathway.

8.
BMC Med Educ ; 21(1): 70, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478500

RESUMO

BACKGROUND: The Comprehensive Osteopathic Medical Licensing Examination of the United States Level 1 (COMLEX 1) is important for medical students to be able to graduate. There is a glaring need to identify students who are at a significant risk of performing poorly on COMLEX 1 as early as possible so that extra assistance can be provided to those students. Our goal is to produce a reliable predictive model to identify students who are at risk of scoring lower than 500 on COMLEX 1 at the earliest possible time. METHODS: Academic data from medical students who matriculated at Rocky Vista University College of Osteopathic Medicine between 2011 and 2017 were obtained. Odds ratios were used to assess the predictors for scoring lower than 500 on COMLEX 1. Correlation with COMLEX 1 scores was assessed with Pearson correlation coefficient. The predictive models were developed by multiple logistic regression, backward logistic regression, and logistic regression with average scores in courses in the first three semesters, and were based on performances on the Medical College Admissions Test (MCAT) before admission, as well as students' performances in preclinical courses during the first three semesters. The models were generated in about 82% of the student performance data and were then validated in the remaining 18% of the data. RESULTS: Odds ratios showed that MCAT scores and final grades in each course in the first three semesters were significant in predicting a score lower than 500 on COMLEX 1. Performances in third-semester courses including Renal System II, Cardiovascular System II, and Respiratory System II were most important in prediction. The three predictive models had sensitivities of 65.8 -71%, and specificities of 83.2 - 88.2% in predicting a score lower than 500 on COMLEX 1. CONCLUSIONS: Lower MCAT scores and lower grades in the first three semesters of medical school predict scoring lower than 500 on COMLEX 1. Students who are identified at risk by our models will have a 65.8 -71% chance of actually scoring lower than 500 on COMLEX 1. Those students will have enough time to receive assistance before taking COMLEX 1.

9.
Surg Endosc ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398574

RESUMO

BACKGROUND AND AIMS: POEM is a rescue endoscopic therapy for patients who had previously failed surgical or endoscopic treatment. However, data regarding its effectiveness after failed pneumatic dilation (PD) and its long-term effects are limited. We aimed to retrospectively investigate the long-term outcomes in patients who had undergone POEM after failed PD. METHODS: Data from 66 achalasia patients with a 2-year follow-up period were analyzed. Intraprocedural events were compared between the first POEM group (patients without prior-endoscopic intervention) and prior PD group (patients who had pre-POEM PD). Symptom evaluation, HRM and 24 h-pH DeMeester scores between the two groups were performed at 2 years after the POEM procedure. Muscularis externa samples were obtained from the lower esophagus using POEM to assess the muscle fibrosis with Azan-Mallory staining. RESULTS: POEM was successfully performed for all achalasia patients. During the 2-year follow-up period, the success rate of POEM was 96.15% (25/26) for patients with prior PD and 95% (38/40) with primary POEM. For patients with type II achalasia and who underwent prior PD, the post-procedure DeMeester score was higher compared to patients who underwent POEM only (P < 0.05). A larger number of patients who underwent primary POEM (27.50%, 11/40) complained of mild heartburn compared to patients who underwent POEM after PD (7.69%, 2/26) (P < 0.05). With regards to fibrosis, the majority of patients who underwent POEM only were classified as F-1 (45.00%, 18/40), while the majority of patients who underwent prior PD were classified as F-2 (42.3%, 11/26). The degree of fibrosis was significantly different between the two groups (P < 0.05). Both surgical time and prior PD were correlated with the degree of fibrosis (P < 0.05). CONCLUSIONS: Despite the technical challenges, pre-POEM endoscopic treatment does not impact the safety and efficacy of POEM in achalasia patients. Longer follow-up studies using larger cohorts are needed to determine long-term outcomes and complications of POEM.

10.
Ann Surg ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33491975

RESUMO

OBJECTIVE: To compare the short-term outcomes, surgery burden, and technical performance of robotic total gastrectomy (RTG) and laparoscopic total gastrectomy (LTG) for gastric cancer (GC). SUMMARY BACKGROUND DATA: The impact of robotic systems on total gastrectomy remains obscure. METHODS: This prospective study included 50 patients with advanced proximal GC underwent RTG combined with spleen-preserving splenic hilar lymphadenectomy between March 2018 and February 2020. Patients who underwent LTG in the FUGES-002, http://links.lww.com/SLA/C929 study were enrolled to compare the outcomes between RTG and LTG. RESULTS: After propensity score matching, 48 patients in the RTG group and 96 patients in the LTG group were included in the analysis. The RTG group had a lower volume of intraoperative blood loss than the LTG group (38.7 vs. 66.4 mL, P = 0.042). Significantly more extraperigastric lymph nodes were retrieved in the RTG group than in the LTG group (20.2 vs. 17.5, P = 0.039). The average number of errors was lower in the RTG group than in the LTG group (43.2 vs. 53.8 times/case, P < 0.001). The RTG group had a higher technical skill score (30.2 vs. 28.4, P < 0.001) and a lower surgery task load index (33.2 vs. 39.8, P < 0.001) than the LTG group. No significant difference was found in terms of postoperative morbidity between the two groups (14.6% vs. 16.7%, P = 0.748). CONCLUSIONS: In complex TG for GC, compared with traditional laparoscopic surgery, robotic surgery provides a technically superior operative environment and reduces surgeon workload at high-volume specialized institutions.

12.
Sci Total Environ ; 754: 142070, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920390

RESUMO

Degradation and metabolism of chlorfluazuron and flonicamid from tea garden to cup were simultaneously investigated by a modified QuEChERS method coupled with UPLC-MS/MS quantification. The dissipation half-lives of chlorfluazuron, flonicamid, and total flonicamid (the sum of flonicamid and its metabolites TFNG, TFNA, and TFNA-AM) in fresh tea leaves during tea growth were 6.0 d, 4.8 d, and 8.1 d, respectively. TFNG and TFNA were generated during tea growth. After tea processing, the residues of chlorfluazuron, flonicamid, and its metabolites in black tea were higher than those in green tea. The average processing factors of chlorfluazuron, flonicamid, and total flonicamid in black tea were 2.54, 3.02, and 2.87, respectively, while in green tea they were 2.40, 2.93, and 2.79, respectively. TFNG, TFNA, and TFNA-AM were formed rapidly during the drying step. Considering the influence of water content at various processing steps, the average loss rates of chlorfluazuron, flonicamid, and total flonicamid residue from fresh tea leaves to black tea were 16.7%, 33.8%, and 20.7%, respectively, and 29.6%, 14.0% and 18.2%, respectively, in the case of green tea. The highest leaching rates of chlorfluazuron, flonicamid, and total flonicamid during tea brewing were 6.8%, 97.0%, and 97.4%, respectively, in black tea infusion, and 6.0%, 98.9%, and 98.6%, respectively, in green tea infusion. The metabolites, especially TFNG, had a higher leaching rate during tea brewing. The migration of chlorfluazuron from fresh leaves to tea infusion was low, and the migration of flonicamid was high. The RQc and RQa of chlorfluazuron and total flonicamid were less than 1. This result indicates that the potential dietary intake risk of chlorfluazuron from tea is negligible. However, the risk of total flonicamid intake is three times higher than that of chlorfluazuron. There is a potential risk of intake of flonicamid and its metabolites in tea for human consumption.


Assuntos
Espectrometria de Massas em Tandem , Chá , Cromatografia Líquida , Humanos , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas , Medição de Risco
13.
J Sci Food Agric ; 101(1): 194-204, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32623719

RESUMO

BACKGROUND: Picoxystrobin is a new osmotic and systemic broad-spectrum methoxyacrylate fungicide with a good control effect on tea anthracnose, so it has been proposed to spray picoxystrobin before the occurrence and onset of tea anthracnose during tea bud growth in order to protect them. However, there are few reports about the residue analysis method, field dissipation, terminal residue and risk assessment of picoxystrobin in tea. And there is no scientific and reasonable maximum residue limit of picoxystrobin in green tea. RESULTS: A rapid and sensitive analysis method for picoxystrobin residue in fresh tea leaf, green tea, tea infusion and soil was established by UPLC-MS/MS. The spiked recoveries of picoxystrobin ranged from 73.1% to 111.0%, with relative standard deviations from 1.8% to 9.2%. The limits of quantitation were 20 µg kg-1 in green tea, 8 µg kg-1 in fresh tea leaves and soil and 0.16 µg kg-1 in tea infusion. The dissipation half-lives of picoxystrobin in fresh tea leaf and soil were 2.7-6.8 and 2.5-14.4 days, respectively. And the maximum residue of picoxystrobin in green tea was 15.28 mg kg-1 with PHI at 10 days for terminal test. The total leaching rate of picoxystrobin during green tea brewing was lower than 35.8%. CONCLUSIONS: According to safety evaluation, the RQc and RQa values of picoxystrobin in tea after 5 to 14 days for the last application were significantly lower than 1. Therefore, the maximum residue limit value of picoxystrobin in tea that we suggest to set at 20 mg kg-1 can ensure the safety of tea for human drinking. © 2020 Society of Chemical Industry.


Assuntos
Camellia sinensis/crescimento & desenvolvimento , Fungicidas Industriais/análise , Resíduos de Praguicidas/química , Estrobilurinas/química , Camellia sinensis/química , Cromatografia Líquida de Alta Pressão , Qualidade de Produtos para o Consumidor , Culinária , Contaminação de Alimentos/análise , Meia-Vida , Humanos , Espectrometria de Massas , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento
14.
Mol Ther ; 29(4): 1585-1601, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33333291

RESUMO

Suicide gene therapies provide a unique ability to target cancer cells selectively, often based on modification of viral tropism or transcriptional regulation of therapeutic gene expression. We designed a novel suicide gene therapy approach wherein the gene product (herpes simplex virus thymidine kinase or yeast cytosine deaminase) is phosphorylated and stabilized in expression by the extracellular signal-regulated kinase (ERK), which is overactive in numerous cancers with elevated expression or mutation of receptor tyrosine kinases or the GTPase RAS. In contrast to transcriptional strategies for selectivity, regulation of protein stability by ERK allows for high copy expression via constitutive viral promoters, while maintaining tumor selectivity in contexts of elevated ERK activity. Thus, our approach turns a signaling pathway often coopted by cancer cells for survival into a lethal disadvantage in the presence of a chimeric protein and prodrug, as highlighted by a series of in vitro and in vivo examples explored here.

15.
Genome Biol ; 21(1): 302, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33317623

RESUMO

BACKGROUND: Tumor-specific genomic aberrations are routinely determined by high-throughput genomic measurements. It remains unclear how complex genome alterations affect molecular networks through changing protein levels and consequently biochemical states of tumor tissues. RESULTS: Here, we investigate the propagation of genomic effects along the axis of gene expression during prostate cancer progression. We quantify genomic, transcriptomic, and proteomic alterations based on 105 prostate samples, consisting of benign prostatic hyperplasia regions and malignant tumors, from 39 prostate cancer patients. Our analysis reveals the convergent effects of distinct copy number alterations impacting on common downstream proteins, which are important for establishing the tumor phenotype. We devise a network-based approach that integrates perturbations across different molecular layers, which identifies a sub-network consisting of nine genes whose joint activity positively correlates with increasingly aggressive tumor phenotypes and is predictive of recurrence-free survival. Further, our data reveal a wide spectrum of intra-patient network effects, ranging from similar to very distinct alterations on different molecular layers. CONCLUSIONS: This study uncovers molecular networks with considerable convergent alterations across tumor sites and patients. It also exposes a diversity of network effects: we could not identify a single sub-network that is perturbed in all high-grade tumor regions.

16.
Zhonghua Nan Ke Xue ; 26(9): 838-843, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33377710

RESUMO

Radical prostatectomy is a standard surgical strategy for prostate cancer though with a few postoperative complications such as urinary incontinence, erectile dysfunction and vesicle urethral anastomotic stricture. Post-prostatectomy incontinence, as a common complication seriously affecting the patient's quality of life, is mainly diagnosed according to the clinical symptoms and the results of urodynamic and imaging examinations. Patients with post-prostatectomy incontinence may undergo corresponding anatomic and functional changes, which can be clearly and directly observed in imaging examination. This review focuses on the advances in the imaging studies of post-prostatectomy urinary incontinence from the perspectives of MRI, ultrasound and cystourethrography.


Assuntos
Prostatectomia/efeitos adversos , Incontinência Urinária , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Incontinência Urinária/diagnóstico por imagem , Incontinência Urinária/etiologia , Urodinâmica
17.
Scand J Immunol ; : e13003, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33247440

RESUMO

It was reported that the expression of Toll like receptor (TLR) 9 may be related to Th2-type allergic inflammation including allergic rhinitis (AR). However, little is known about the expression of TLR9 in the basophils in AR. In the present study, the expression of TLR9 was examined by flow cytometry analysis, and the expression of TLR9 mRNA in KU812 was determined by quantitative real-time PCR. The results showed that the percentage of TLR9+ CCR3+ cells in blood granulocytes increased by 46% in patients with AR, but not in peripheral blood mononuclear cells (PBMCs). Allergens namely Dermatophagoide allergen extract (DAE) and Platanus pollen allergen extract (PPAE) upregulated the expression of TLR9 in CCR3+ granulocytes by 76% and 84%, respectively. DAE and PPAE also enhanced the proportions of TLR9+ CD123+ HLA-DR- cells and TLR9+ CCR3+ CD123+ HLA-DR- cells in granulocytes and PBMCs of patients with AR. In order to investigate the actions of allergens on basophils, KU812 cells were used. It was observed that all KU812 cells expressed TLR9, and the expression intensity of TLR9 in a single KU812 cell was elevated by CpG. IL-37, IL-31, IL-33, Artemisia sieversiana wild allergen extract (ASWAE), DAE, OVA, and Der p 1 induced an increase in the expression of TLR9 mRNA and IL-6 production in KU812 cells. It was shown that the percentage of TLR9-expressing basophils increased in the blood of ovalbumin (OVA)-sensitised mice. In conclusion, an increased expression of TLR9 and the production of IL-6 in basophils implicate that the contribution of basophils to AR is likely via TLR9.

18.
FASEB J ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191543

RESUMO

Autophagy, a cellular stress response to starvation and bacterial infection, is executed by double-membrane-bound organelles called autophagosomes. Autophagosomes transfer cytosolic material to acidified lysosomes for degradation following soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE)-dependent fusion processes. Many of the autophagy-related disorders stem from defective end-step proteolysis inside lysosomes. The role of epithelial cystic fibrosis (CF) transmembrane conductance regulator (CFTR) chloride channel has been argued to be critical for efficient lysosomal clearance; however, its context to autophagic clearance and the underlying mechanism is poorly defined. Here, we report that syntaxin17 (Stx17), an autophagic SNARE protein interacts with CFTR under nutritional stress and bacterial infection and incorporates it into mature autophagosomes to mediate an efficient lysosomal clearance. Lack of CFTR function and Stx17 and loss of CFTR-Stx17 interaction impairs bacterial clearance. We discover a specialized role of the Stx17-CFTR protein complex that is critical to prevent defective autophagy as has been the reported scenario in CF airway epithelial cells, infectious diseases, and lysosomal clearance disorders.

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