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1.
Phys Rev Lett ; 128(25): 250401, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35802432

RESUMO

First proposed by Mayers and Yao, self-testing provides a certification method to infer the underlying physics of quantum experiments in a black-box scenario. Numerous demonstrations have been reported to self-test various types of entangled states. However, all the multiparticle self-testing experiments reported so far suffer from both detection and locality loopholes. Here, we report the first experimental realization of multiparticle entanglement self-testing closing the locality loophole in a photonic system, and the detection loophole in a superconducting system, respectively. We certify three-party and four-party GHZ states with at least 0.84(1) and 0.86(3) fidelities in a device-independent way. These results can be viewed as a meaningful advance in multiparticle loophole-free self-testing, and also significant progress on the foundations of quantum entanglement certification.

2.
Int Immunopharmacol ; 110: 108991, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35792272

RESUMO

BACKGROUND: Effective treatment methods for rheumatoid arthritis (RA) are still lacking. Previous studies have shown that icariin exerts a significant therapeutic effect on RA; however, the molecular mechanism requires further analysis. METHODS: qRT-PCR and western blot were performed to examine the gene or protein levels, respecctively. The proinflammatory cytokine levels were determined utilizing ELISA and western blot assays. Cell proliferation and apoptosis were quantified using CCK-8, EdU and flow cytometry assays, respectively. A RA mouse model was established to observe histopathological changes. RESULTS: Both icariin treatment and TRIB1 overexpression inhibited proliferation and inflammatory responses but promoted the apoptosis of TNF-α-treated RA-FLSs. Icariin treatment increased TRIB1 expression by promoting Nrf2 expression, thus blocking TLR2/NF-κB signalling. In addition, functional rescue experiments suggested that TRIB1 knockdown strikingly restrained the biological effects of icariin on TNF-α-treated RA-FLSs. Moreover, in vivo experimental results revealed that icariin restored inflammation and deterioration in RA mice by upregulating TRIB1. CONCLUSIONS: Based on these results, icariin repressed TNF-α-induced inflammatory responses and survival in RA-FLSs by regulating the TRIB1/TLR2/NF-kB pathway, implying that icariin may be a promising candidate drug for RA treatment.


Assuntos
Artrite Reumatoide , Sinoviócitos , Animais , Apoptose/genética , Artrite Reumatoide/metabolismo , Proliferação de Células , Células Cultivadas , Fibroblastos , Flavonoides , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
3.
Front Genet ; 13: 878607, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646080

RESUMO

Objective: We identify and explore the candidate susceptibility genes for cirrhosis and their underlying biological mechanism. Methods: We downloaded the genome-wide association studies summary data of 901 cirrhosis cases and 451,363 controls and integrated them with reference models of five potential tissues from the Genotype-Tissue Expression (GTEx) Project, including whole blood, liver, pancreas, spleen, and thyroid, to identify genes whose expression is predicted to be associated with cirrhosis. Then, we downloaded gene expression data of individuals with hepatocellular carcinoma from TCGA database to conduct differential expression analysis to validate these identified genes and explored their possible role in driving cirrhosis via functional enrichment and gene set enrichment analysis (GSEA). Results: We identified 10 significant genes (SKIV2L, JPH4, UQCC2, RP11-91I8.3, MAU2, ERAP1, PUS3, ZNF677, ARHGAP40, and SHANK3) associated with cirrhosis at a Bonferroni-corrected threshold of p < 0.01, among which two (SKIV2L and JPH4) were identified in the liver and five (SKIV2L, JPH4, MAU2, SHANK3, and UQCC2) were validated by differential expression analysis at an FDR-corrected threshold of p < 0.01. The enrichment analysis showed that the degradation process of RNA, which is enriched by 58 genes, is significantly under-enriched in liver cancer tissues (p = 0.0268). Conclusion: We have identified several candidate genes for cirrhosis in multiple tissues and performed differential genetic analysis using the liver cancer database to verify the significant genes. We found that the genes SKIV2L and JPH4 identified in the liver are of particular concern. Finally, through enrichment analysis, we speculate that the process of mRNA transcription and RNA degradation may play a role in cirrhosis.

4.
Int J Ophthalmol ; 14(10): 1501-1507, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34667725

RESUMO

AIM: To observe and compare the statistical significance of superficial and deep vascular leakage in the pathological changes of the diabetic rats retina after the Evans blue (EB) perfusion, and utilize the modified whole-retina spreading method to make the slides while protecting the periphery of the retina. METHODS: The Sprague-Dawley (SD) rats were randomly divided into 6 groups. Each group named as the normal groups for 4, 8, and 12wk and the diabetic groups for 4, 8, and 12wk. The EB was injected into the cardiovascular system of the rats at the different time points. The retina of each group was obtained for observation. RESULTS: The superficial vascular leakage was found in all 6 groups. The size of leakage area of superficial retinal blood vessels was (0.54±0.23)%, (0.65±0.11)%, and (0.58±0.10)% in normal group. No notable leakage was found in the deep blood vessels [(0.03±0.04)%, (0.03±0.05)%, and (0.03±0.05)%]. The deep retinal vascular leakage was found in the peripheral retina of diabetic rats. The size of leakage area of superficial retinal blood vessels in diabetic group were (0.53±0.22)%, (0.69±0.16)%, and (0.52±0.11)%. The leakage areas of deep blood vessels were (0.54±0.50)%, (1.42±0.16)%, and (1.80±0.07)% at 4, 8, and 12wk, respectively. There was a statistically difference of the leakage area between the 8th week and the 4th week of diabetes group (P=0.003). The statistically significant difference between the diabetes and the control groups was noted at 4wk and 8wk (P<0.001). CONCLUSION: The main retinal pathological changes of early-stage diabetic rats are the vascular leakage of the periphery of deep retina. Diabetic rats modeled after 8wk have semi-quantitative statistical difference compared with the normal rats, thus early intervention treatment research can start at this time point.

5.
Front Aging Neurosci ; 13: 723405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35126085

RESUMO

BACKGROUND: Psychotic symptoms are common in Parkinson's disease (PD). However, the clinical characteristics of PD psychosis (PDP) have been rarely reported in Chinese PD patients. We aimed to categorize PDP in a PD cohort and its relationship to other clinical characteristics. METHODS: A total of 149 Chinese PD patients were consecutively enrolled, and idiopathic PD patients were recruited in the study. The symptoms of PDP were assessed with the enhanced Scale for the Assessment of Positive Symptoms in PD. Then, the patients were classified into a PD-control group, isolated minor hallucination (MH) group, and complex MH group, and clinical and demographic data of different groups were compared. RESULTS: Parkinson's disease psychosis was present in 40.3% (60/149) of our patients. The most common PDPs were MHs, present in 32.9% (49 of 149) of the cohort. Compared to patients without MHs, patients with MHs were older, had a longer disease duration, a higher levodopa equivalent daily dose, more severe motor symptoms, dyskinesia, a higher rate of rapid eye movement sleep behavior disorders, frontal lobe function impairments, and a higher percentage of cognitive impairment. Logistic regression analysis showed that advanced Hoehn-Yahr stage [odds ratio (OR): 2.697, p = 0.007)] and frontal lobe function impairment (OR: 0.684, p = 0.003) were independent risk factors for MHs. CONCLUSION: MHs were frequent non-motor symptoms in PD patients. It was associated with increased motor and non-motor symptom burdens and reduced quality of life. MHs have been called "minor," but they have major clinical and prognostic implications and need early screening.

6.
Front Med (Lausanne) ; 8: 770362, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35004738

RESUMO

Aims: To examine the prevalence of primary epiretinal membranes (ERMs) and associated systemic factors. Methods: The cross-sectional, community-based Tongren Health Care Study enrolled participants who received regular health examinations in the Beijing Tongren Hospital from 2017 to 2019. Using fundus photographs, retinal specialists assessed the presence of ERMs and their systemic associations. Results: Primary ERMs were detected in 841/22820 individuals, with a prevalence of 3.7% [95% confidence intervals (CI): 3.4-3.9%] in the total study population (mean age: 44.5 ± 13.8 years) and 6.5% (95% CI: 6.1-7.0%) in individuals aged 40+ years. In multivariable analysis, a higher ERMs prevalence was associated with older age [odds ratio (OR): 1.10; P < 0.001], higher serum cholesterol concentration (OR: 1.14; P = 0.003) and higher serum sodium concentration (SSC) (OR: 1.12; P < 0.001). In women, a higher SSC, even within the normal range, was associated with an increased risk of ERMs (OR: 1.19; P < 0.001). Female participants with an SSC of 144-145mmol/L as compared with those with an SSC of 135-137 mmol/L had a 5-fold increased odds of having ERMs (All women: OR: 5.33; P < 0.001; Women aged 40+years: OR: 4.63; P < 0.001). Conclusion: Besides older age and higher serum cholesterol concentration, a higher SSC, even if within the normal range, was independently associated with a higher ERM prevalence in women.

7.
Pharmazie ; 75(10): 500-504, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33305725

RESUMO

The etiology of osteoarthritis (OA) has been discussed widely, but the molecular mechanisms beneath OA aggravation have not yet been investigated in detail. This study focused on the role of lncRNA RMRP (RMRP) on OA progression. We found that the expression of RMRP was significantly increased in cartilage tissues of patients with OA. CCK-8 and colony formation assays showed that RMRP knockdown promoted proliferation of chondrocytes treated with IL-1ß. Flow cytometry and caspase-3 activity analysis indicated that RMRP silence inhibited apoptosis of chondrocytes treated with IL-1ß. Moreover, luciferase reporter, RNA pull-down and RIP assays showed that RMRP competing with miR-206. Additionally, CDK9 acted as a direct target of miR-206. Moreover, rescue assays indicated that miR-206 inhibitor or pcDNA-CDK9 reversed the effects of RMRP suppression on the proliferation and apoptosis of chondrocytes. Taken together, our results indicated that RMRP knockdown could promote proliferation and inhibit apoptosis in OA chondrocytes via the miR-206/CDK9 axis.


Assuntos
Condrócitos/patologia , MicroRNAs/genética , Osteoartrite/patologia , RNA Longo não Codificante/genética , Apoptose/genética , Cartilagem/patologia , Linhagem Celular , Proliferação de Células/genética , Quinase 9 Dependente de Ciclina/genética , Progressão da Doença , Técnicas de Silenciamento de Genes , Humanos , Interleucina-1beta/administração & dosagem , Osteoartrite/genética
8.
Autoimmunity ; 53(8): 450-458, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33084415

RESUMO

Rheumatoid arthritis (RA) is considered to be a chronic autoimmune disease, pathogenesis of RA is complex and effective treatments for RA is still lacking. Previous studies found that microRNAs (miRNAs) play important roles in the pathogenesis of RA, and miR-223-3p is considered to be one of the possible biomarkers of RA. Recent studies have revealed that icariin alleviates RA in murine models, but the underlying mechanism needs to be further investigated. MiR-223-3p expression levels in fibroblast-like synoviocyte (RA-FLS) and patients with RA were quantified by qRT-PCR, cell proliferation was analyzed by CCK-8 and BrdU assay. Cell apoptosis was assessed by flow cytometry and western blotting. TNF-α, IL-1ß and IL-6 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Dual luminescence-based reporter gene assay was conducted to confirm the possible interaction between miR-223-3p and NLRP3. Icariin inhibits proliferation and inflammation cytokines secretion, promotes apoptosis of RA-FLS cells and upregulated the expression of miR-223-3p. MiR-223-3p targets to 3'-UTR of NRLP3 and regulates its expression. MiR-223-3p inhibitor reversed the effect of icariin on RA-FLS cells function. Additionally, anti-RA activity of icariin was restored by NLRP3 inhibitor MCC950 in miR-223-3p knockdown RA-FLS cells. Icariin inhibits proliferation and inflammation, promotes apoptosis of RA-FLS cells by regulating miR-223-3p/NLRP3 signalling, which may serve as a potential therapeutic target to alleviate RA.


Assuntos
Artrite Reumatoide/etiologia , Artrite Reumatoide/metabolismo , Flavonoides/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Artrite Reumatoide/patologia , Doenças Autoimunes/etiologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Autoimunidade , Modelos Animais de Doenças , Suscetibilidade a Doenças , Humanos , Camundongos
9.
Int J Ophthalmol ; 13(9): 1467-1476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32953588

RESUMO

AIM: To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy (NPDR) in the Kailuan area of Tangshan, Hebei Province, China. METHODS: In this non-interventional, retrospective study, 683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study. Based on the undilated ultra-wide field (200°; UWF) images and partial dilated digital fundus images, the diabetic retinopathy (DR) of the surveyed population was graded. Interobserver agreement was estimated by using Cohen's Kappa statistics. The main outcome indicators included gender, age, weight, height, body mass index, blood pressure, circumferences of neck, waist and hip, current smoking, levels of fasting plasma glucose (FPG), hypersensitive C-reactive protein, creatinine, and cholesterol, etc. According to different lesions' locations of patients with mild NPDR, logistic regression models were used to estimate the odds ratios (ORs) and their 95%CIs of each risk factor. RESULTS: The study group of 683 patients included 570 males and 113 females. The mean age of the patients was 62.18±9.41y. Compared with dilated fundus examinations, there was fair agreement with the level of DR identified on UWF images in 63.91% of eyes (k=0.369, 95%CI, 0.00-0.00). Detected by UWF images, there were 98 patients with mild NPDR having peripheral retinal lesions, 35 patients with mild NPDR having posterior lesions, 44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area, and 336 patients with non obvious DR. Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance (OR, 1.124; 95%CI, 1.044-1.211), and with posterior lesions were FPG (OR, 1.052; 95%CI, 1.007-1.099). CONCLUSION: UWF is an effectiveness means of DR screening. Moreover, it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR. The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found. And the influencing factors in mild NPDR are differing by different lesions' locations.

10.
Invest Ophthalmol Vis Sci ; 61(11): 37, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32955561

RESUMO

Purpose: To investigate the prevalence of epiretinal membranes (ERMs) and their risk factors in a Chinese population. Methods: The community-based Kailuan Eye Study included 14,440 participants (9835 male, 4605 female) with a mean age of 54.0 ± 13.3 years (range, 20-110 years). They underwent a systemic and ophthalmologic examination. ERMs were diagnosed on fundus photographs. Results: Retinal photographs assessable for the presence of ERMs were available for 13,295 (92.0%) individuals (9094 male) with a mean age of 53.6 ± 13.3 years (range, 20-110 years). ERMs were found in 1013 participants (1489 eyes) with a prevalence of 7.6% (95% confidence interval [CI], 7.1%-8.1%). Secondary ERMs caused by intraocular reasons were found 46 (4.5%) individuals (69 [4.6%] eyes). A higher prevalence of any ERMs (and of primary ERMs) was associated with older age (odds ratio [OR]: 1.08; 95% CI:1.07-1.10), higher body mass index (OR: 1.05; 95% CI: 1.00-1.11), higher prevalence of smoking (OR:1.43; 95% CI: 1.01-2.03), higher serum concentration of glucose (OR: 1.08; 95% CI: 1.04-1.13), and lower serum concentration of uric acid (OR: 0.99; 95% CI: 0.99-1.00). Visual acuity was significantly (P = 0.002) lower in eyes with premacular fibroses than in eyes with cellophane macular reflexes. Conclusions: In our cross-sectional community-based study, the prevalence of all ERMs was 7.6%. Among the group of participants with ERMs, secondary ERMs caused by intraocular reasons were detected in 46 (4.5%) individuals (69 [4.6%] eyes). A higher prevalence of any ERM and of primary ERMs was associated with older age, higher body mass index, higher prevalence of smoking, a higher serum concentration of glucose, and a lower serum concentration of uric acid.


Assuntos
Membrana Epirretiniana/epidemiologia , Vigilância da População , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Membrana Epirretiniana/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
11.
J Biochem Mol Toxicol ; 34(12): e22600, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32815255

RESUMO

The impact of resveratrol (RSV) on radiation (RAD)-induced brain injury in rats' brains was investigated. A total of 40 male Wistar Albino rats were randomly divided into four groups (control, RAD, RAD + RSV, and RSV groups, with 10 rats in each group). The results revealed a significant decrease in catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities, as well as glutathione (GSH) content. Further, a significant elevation in malondialdehyde, nitric oxide, interleukin-1-beta (IL-1ß), IL-6, and transforming growth factor-ß1 levels were observed. Furthermore, decreased B-cell lymphoma 2 (Bcl-2), increased Bcl-2-associated X, and tumor necrosis factor-α genes expression, decreased nuclear factor erythroid-related factor 2, heme oxygenase-1, and increased nuclear factor-κB protein levels were noticed. Also, an apoptosis marker, caspase-3-positive cells, was seen in the hippocampus. Those effects were observed in the RAD group of rats. The treatment of RSV displayed a significant amendment of the studied parameters in the brain tissues of the RAD group of animals. This effect is interrelated to the ability of RSV to scavenge the free radicals, enhance the activity of the antioxidant enzymes, increase GSH contents, and downregulate the inflammatory responses and apoptosis markers in the brain tissues of RAD animals. In conclusion, this study demonstrated that the potent antioxidant, anti-inflammatory, and antiapoptotic activities of RSV can improve the antioxidant status and suppress the inflammatory responses and apoptosis in the brain tissues of RAD animals.


Assuntos
Apoptose/efeitos dos fármacos , Lesões Encefálicas/etiologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Resveratrol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Lesões Encefálicas/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Wistar
12.
Int J Ophthalmol ; 12(8): 1243-1249, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456913

RESUMO

AIM: To investigate the expression of TWIK-related arachidonic acid-stimulated K+ channel (TRAAK) in retinal degeneration mice (rd1) and further evaluate how TRAAK affect photoreceptor cell apoptosis. METHODS: The rd1 mice were distributed into blank (no treatment), control (1.4% DMSO, intraperitoneal injection) and riluzole groups (4 mg/kg·d, intraperitoneal injection) from postnatal 7d to 10, 14 and 18d; C57 group (no treatment), as age-matched wild-type control. The thickness of the outer nuclear layer (ONL) of retina was detected by paraffin section hematoxylin and eosin staining. The expression of TRAAK and the apoptosis of the ONL cells were detected by immunostaining, Western blotting, and real-time polymerase chain reaction. RESULTS: The channel agonist riluzole activated TRAAK and delayed the apoptosis of photoreceptor cells in ONL layer of rd1 mice. Both at mRNA and protein levels, after riluzole treatment, TRAAK expression was significantly upregulated, when compared with the control and blank group. Then we detected a series of apoptosis related mRNA and protein. The anti-apoptotic factor Bcl-2 downregulated and the pro-apoptotic factors Bax and cleaved-caspase-3 upregulated significantly. CONCLUSION: Riluzole elevates the expression of TRAAK and inhibits the development of apoptosis. Activation of TRAAK may have some potential effects to put off photoreceptor apoptosis.

13.
Int J Ophthalmol ; 12(6): 924-929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236347

RESUMO

AIM: To examine the expression of Twik-related K+ channel 1 (TREK-1), Twik-related K+ channel 2 (TREK-2), and Twik-related arachidonic acid-stimulated K+ channel (TRAAK) in the retina of adult rd1 mice and to detect the protective roles of TREK-TRAAK two-pore-domain K+ (K2P) channels against retinal degeneration. METHODS: Twenty-eight-day-old C57BL/6J mice and 28-day-old rd1 mice were used in this study. Retinal protein, retinal RNA, and embedded eyeballs were prepared from these two groups of mice. Real-time quantitative polymerase chain reaction and Western blot analyses were used to assess the gene transcription and protein levels, respectively. Retinal structures were observed using hematoxylin and eosin (H&E) staining. Immunohistochemistry was utilized to observe the retinal localization of TREK-TRAAK channels. Current changes in retinal ganglion cells (RGCs) after activation of TREK-TRAAK channels were examined using a patch-clamp technique. RESULTS: Compared with C57BL/6J mice, rd1 mice exhibited significantly higher retinal mRNA and protein expression levels of TREK-1, TREK-2, and TRAAK channels. In both groups, immunohistochemistry showed expression of TREK-TRAAK channels in retinal layers. After addition of the TREK-TRAAK channel agonist arachidonic acid (AA), whole-cell voltage step evoked currents were significantly higher in RGCs from rd1 mice than in RGCs from control C57BL/6J mice, suggesting that TREK-TRAAK channels were opened in RGCs from rd1 mice. CONCLUSION: TREK-TRAAK K2P channels' expression is increased in adult rd1 mice. AA induced the opening of TREK-TRAAK K2P channels in adult rd1 mice and may thus counterbalance depolarization of RGCs and protect the retina from excitotoxicity. TREK-TRAAK channels may play a protective role against retinal degeneration.

14.
Cell Cycle ; 18(6-7): 670-681, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30829553

RESUMO

Acute interstitial pneumonia (AIP) is an idiopathic pulmonary disease featuring rapid progressive dyspnea and respiratory failure. These symptoms typically develop within several days or weeks in patients without any pre-existing lung disease or external chest disease. Thymocyte differentiation antigen-1 (THY1) has been reported to have an effect on lung fibroblast proliferation and fibrogenic signaling. In this study, the mechanism of THY1 in AIP in influencing pulmonary fibrosis in terms of lung fibroblast proliferation and apoptosis was examined. An AIP mouse model with the pathological changes of lung tissues observed was established to identify the role of THY1 in the pathogenesis of AIP. The expression of THY1, a key regulator of the WNT pathway ß-catenin and fibroblasts markers MMP-2, Occludin, α-SMA and Vimentin were determined. Lung fibroblasts of mice were isolated, in which THY1 expression was altered to identify roles THY1 plays in cell viability and apoptosis. A TOP/TOPflash assay was utilized to determine the activation of WNT pathway. Decrement of pulmonary fibrosis was achieved through THY1 up-regulation. The expression of MMP-2, Occludin, α-SMA, Vimentin and ß-catenin, and the extent of ß-catenin phosphorylation, significantly decreased, thereby indicating that THY1 overexpression inactivated WNT. Cell proliferation was inhibited and apoptosis was accelerated in lung fibroblasts transfected with vector carrying overexpressed THY1. Altogether, this study defines the potential role of THY1 in remission of AIP, via the upregulation of THY1, which renders the WNT pathway inactive. This inactivation of the WNT signaling pathway could alleviate pulmonary fibrosis by reducing lung fibroblast proliferation in AIP. Abbreviations: AIP: Acute interstitial pneumonia; ILDs: interstitial lung diseases; DAD: diffuse alveolar damage; SPF: specific-pathogen-free; NC: negative control; HCMV: human cytomegalovirus; HE: Hematoxylin-eosin; RIPA: radio-immunoprecipitation assay; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; BSA: bovine serum albumin; HRP: horseradish peroxidase; ECL: electrochemiluminescence; FBS: fetal bovine serum; DMSO: dimethyl sulfoxide; OD: optical density.


Assuntos
Apoptose/fisiologia , Fibroblastos/metabolismo , Doenças Pulmonares Intersticiais/metabolismo , Fibrose Pulmonar/metabolismo , Antígenos Thy-1/metabolismo , Regulação para Cima/fisiologia , Via de Sinalização Wnt/fisiologia , Actinas/metabolismo , Animais , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Fibroblastos/patologia , Pulmão/metabolismo , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Ocludina/metabolismo , Fibrose Pulmonar/patologia , Ativação Transcricional/fisiologia , Vimentina/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
15.
J Med Virol ; 91(6): 1097-1103, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30633820

RESUMO

AIMS: To investigate the association between two RIG-I-like receptor gene polymorphisms and hepatitis C virus (HCV) infection in Chinese Han population. METHODS: The current study genotyped two selected SNPs (IFIH1 rs3747517 and DDX58 rs9695310) using TaqMan allelic discrimination assay to assess their association with the susceptibility and clinical outcome of HCV infection among 3065 participants (1545 non-HCV infection individuals, 568 spontaneous HCV clearance cases, and 952 persistent infection patients). RESULTS: IFIH1 rs3747517 (dominant model: Adjusted odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.07-1.68; P = 0.009) and DDX58 rs9695310 (dominant model: Adjusted OR = 1.43, 95% CI = 1.15-1.78; P = 0.001) were associated with chronic hepatitis C (CHC). And the risk of CHC increased when people were carrying more unfavorable rs3747517-GA/AA and rs9695310-GC/CC genotypes from zero to two with the chronic rates of 56.72%, 59.38%, and 69.01%, respectively (Ptrend < 0.001). CONCLUSION: Genetic variations at IFIH1 rs3747517 and DDX58 rs9695310 were independent predictors of chronic hepatitis C in Chinese Han population.


Assuntos
Proteína DEAD-box 58/genética , Predisposição Genética para Doença , Hepatite C Crônica/etnologia , Hepatite C Crônica/genética , Helicase IFIH1 Induzida por Interferon/genética , Adulto , Idoso , Alelos , /estatística & dados numéricos , Estudos de Casos e Controles , China , Feminino , Variação Genética , Genótipo , Hepacivirus , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Receptores Imunológicos
16.
Zhonghua Nan Ke Xue ; 24(6): 529-532, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30173459

RESUMO

Objective: To make a preliminary investigation on the safety and efficacy of focused low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of erectile dysfunction (ED). METHODS: We treated 32 ED patients by focused LI-ESWT with the device of Medispec's ED1000. Before and at 4 and 12 weeks after treatment, we evaluated the erectile function of the patients using the International Index of Erectile Function-erectile function domain (IIEF-EF), Erection Hardness Score (EHS), Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), and Global Assessment Questionnaire questions 1 and 2 (GAQ1 and GAQ2), and recorded the incidence rate of adverse events. RESULTS: The patients averaged 30.69 years of age. Compared with the baseline, the mean IIEF-EF score of the patients was significantly increased at 4 and 12 weeks after LI-ESWT (14.94 vs 20.97 and 21.47, P <0.01), and so were the EHS (1.75 vs 2.66 and 2.56, P <0.01) and the "Yes" answers to SEP2 (21.88% vs 68.75% and 71.88%), SEP3 (0 vs 43.75% and 56.25%), GAQ1 (NA vs 81.25% and 71.88%) and GAQ2 (NA vs 65.63% and 68.75%). The total effectiveness rates at 4 weeks and 12 weeks were 75% and 71.88% respectively. One of the patients felt penile shaft pain with mild ecchymosis after LI-ESWT but was recovered without special treatment a week later. CONCLUSIONS: LI-ESWT can significantly improve the erectile function of ED patients with no obvious adverse effects within 12 weeks after treatment.


Assuntos
Disfunção Erétil/terapia , Tratamento por Ondas de Choque Extracorpóreas/métodos , Adulto , Método Duplo-Cego , Equimose/etiologia , Tratamento por Ondas de Choque Extracorpóreas/efeitos adversos , Humanos , Masculino , Dor Processual , Ereção Peniana/fisiologia , Inquéritos e Questionários , Resultado do Tratamento
17.
Zhonghua Nan Ke Xue ; 24(4): 340-344, 2018 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30168955

RESUMO

Objective: To investigate the clinical effect of low-intensity extracorporeal shockwave therapy (LI-ESWT) on Peyronie's disease. METHODS: From October 2016 to December 2017, we treated 32 cases of Peyronie's disease by LI-ESWT, with the therapeutic index of 0.09 mJ/mm2 and a pulse frequency of 120 beats/min. Each plaque was approached from two angles, each angle with a shockwave output of 900 times, and the larger ones from three points, each with an output of 600 times in addition to 300 times from the distal and proximal ends of the plaque, respectively. All the patients received 12 courses of treatment (2 courses a week) with a break of 3 weeks between the 1st and 2nd 6 courses. Then we observed the plague size and penile curvature of the patients, obtained their scores on the Visual Analogue Scale (VAS) and International Index of Erectile Function 5 (IIEF-5), and recorded their adverse reactions. RESULTS: The plagues were softened or diminished in different degrees in 9 of the 32 cases and erectile pain was alleviated in 15 cases after treatment. Penile curvature at erection, however, showed no significant improvement. The IIEF-5 scores were increased in 18 of the patients complicated with varied degrees of erectile dysfunction after LI-ESWT. No obvious complications were observed in any of the patients. CONCLUSIONS: Low-intensity extracorporeal shockwave therapy has a certain effect on Peyronie's disease by relieving plague-induced pain and improving the patient's penile erection and quality of life.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas/métodos , Induração Peniana/terapia , Disfunção Erétil , Humanos , Litotripsia , Masculino , Manejo da Dor , Ereção Peniana , Induração Peniana/patologia , Pênis/patologia , Qualidade de Vida , Índice Terapêutico , Resultado do Tratamento , Escala Visual Analógica
18.
Zhonghua Nan Ke Xue ; 24(1): 62-66, 2018.
Artigo em Chinês | MEDLINE | ID: mdl-30157363

RESUMO

Objective: To explore the clinicopathological characteristics, diagnosis and treatment of penile verrucous carcinoma (VC). METHODS: We retrospectively analyzed the clinical data about 18 penile VC patients at the mean age of 52 (35-66) years. The tumors were cauliflower-like, measuring 2.5-8.7 cm in diameter, all with mucopurulentive discharge. A giant tumor invaded the perineum in 1 case, which had a history of surgical excision of penile condyloma acuminatum. The lesions invaded the glans penis in 2 cases, the shafts in 4 (all with a history of phimosis or redundant prepuce), and the whole penis in 11. Partial penectomy was performed for 2 cases with the proximal coronary sulcus involved and another 2 with the condylomata located in the glans penis and measuring <3.5 cm in diameter. Radical surgery was done for 2 cases of glans VC >3.5 cm in diameter, 11 cases with the whole penis involved, and 1 case with the perineum invaded. RESULTS: Postoperative pathology showed well-differentiated tumor cells, negative surgical margins, papillary epithelia with hyperkeratosis and hyperplasia, and lymphocyte infiltration in the surrounding interstitial tissue in all the cases. Neither recurrence nor metastasis was found during the 1 to 8 years of follow-up. CONCLUSIONS: Penile VC is a special type of squamous cell carcinoma with little invasiveness and rare regional lymph node or distant metastasis, for the treatment of which partial penectomy or radical surgery confers good prognosis.


Assuntos
Carcinoma Verrucoso/patologia , Neoplasias Penianas/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma Verrucoso/cirurgia , Condiloma Acuminado/patologia , Condiloma Acuminado/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Penianas/cirurgia , Pênis/patologia , Pênis/cirurgia , Fimose/patologia , Estudos Retrospectivos
19.
Am J Transl Res ; 10(6): 1620-1632, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018705

RESUMO

BACKGROUND: This study is to investigate the effect of Egr1 on the mineralization and accumulation of chondrocyte extracellular matrix. METHODS: The femoral heads of patients of various heights were collected. Egr1 knockout mice were used. Their limb lengtha nd body weight were assessed. The bone characteristics were detected by micro-CT scan and histological staining. Immature murine articular chondrocytes (iMACs) were isolated. Gross morphology was observed by histological staining. Relevant mRNA and protein expression were detected by qRT-PCR and Western blot, respectively. the related proteins were observed by immunohistochemical staining and immunofluorescence assay. Chromatin immunoprecipitation and reporter gene assay were also used. TUNEL was used to detect apoptosis. RESULTS: It was found that shorter patients had reduced Egr1 expression levels in the hypertrophic cartilage zone of the femoral head. In addition, Egr1 knockout mice exhibited reduced body size. Micro-CT analysis showed that these mice also had reduced bone volume. Safranin-O staining showed that the extracellular matrix of these mice exhibited a relatively limited degree of mineralization, and TUNEL staining showed reduced cell apoptosis levels. After transfecting the iMACs with dominant-negative Egr1 adenoviruses to inhibit Egr1, the enzymes of Adamst4, Adamst5, Mmp3 and Mmp13 were significantly upregulated. ChIP and luciferase assays revealed that Egr1 might regulate the chondrocyte extracellular matrix by the PPARγ/RUNX2 signaling pathways. CONCLUSION: Egr1 has an important regulatory effect on the dynamic equilibrium of the chondrocyte extracellular matrix, which may be achieved through the PPARγ/RUNX2 signaling pathways.

20.
Biochem Biophys Res Commun ; 499(2): 128-135, 2018 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-29501491

RESUMO

Hypertension is a multifactorial chronic inflammatory disease that leads to cardiac remodeling. A-kinase anchor protein 12 (AKAP12) is a scaffolding protein that has multiple functions in various biological events, including the regulation of vessel integrity and differentiation of neural barriers in blood. However, the role of AKAP12 in angiotensin II (Ang II)-induced cardiac injury remains unclear. In the present study, Ang II infusion reduced AKAP12 expressions in the hearts of wild-type (WT) mice, and AKAP12 knockout (KO) enhanced the infiltration of inflammatory cells. In addition, AKAP12 deletion accelerated Ang II-induced cardiac histologic alterations and dysfunction. Further, AKAP12-/- aggravated heart failure by promoting the inflammation, oxidative stress, cellular apoptosis, and autophagy induced by Ang II. Furthermore, AKAP12 KO elevated Ang II-induced cardiac fibrosis, as indicated by the following: (1) Masson trichrome staining showed that Ang II infusion markedly increased fibrotic areas of the WT mouse heart, which was greatly accelerated in AKAP12-/- mice; (2) immunohistochemistry analysis showed increased expression of transforming growth factor ß1 (TGF-ß1) and α-smooth muscle actin (α-SMA) in the AKAP12-/- mouse heart; (3) reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) analysis showed increased expression of fibrosis-related molecules in the AKAP12-deficient mouse heart; and (4) Western blot analysis indicated significantly higher upregulation of p-SMAD2/3 in the AKAP12-/- mouse heart. In vitro, AKAP12 knockdown in HL-1 cells was responsible for TGF-ß1-induced inflammation, the generation of reactive oxygen species (ROS), apoptosis, autophagy, and fibrosis. Furthermore, overexpression of AKAP12 reduced fibrosis triggered by TGF-ß1 in cells. Overall, our study suggests that fibrosis induced by Ang II may be alleviated by AKAP12 expression through inactivation of the TGF-ß1 pathway.


Assuntos
Proteínas de Ancoragem à Quinase A/antagonistas & inibidores , Proteínas de Ciclo Celular/antagonistas & inibidores , Traumatismos Cardíacos/metabolismo , Traumatismos Cardíacos/patologia , Miocárdio/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Proteínas de Ancoragem à Quinase A/deficiência , Proteínas de Ancoragem à Quinase A/metabolismo , Angiotensina II , Animais , Proteínas de Ciclo Celular/deficiência , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Progressão da Doença , Fibrose , Técnicas de Silenciamento de Genes , Traumatismos Cardíacos/induzido quimicamente , Camundongos Endogâmicos C57BL , Camundongos Knockout
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