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1.
Eur J Neurol ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33905575

RESUMO

BACKGROUND: Motoric cognitive risk syndrome (MCR) is characterized by slow walking speed and subjective memory complaints (SMCs). This study investigated the prevalence and potential risk factors of MCR and its association with falls in Chinese community-dwelling older adults. METHODS: The analysis was based on data from the Rugao Longevity and Aging Study (RuLAS). MCR was defined as presence of both SMC and slow walking speed in participants free of major neurocognitive disorders. SMCs were determined according to a positive answer to the question "Do you feel you have more problems with memory than most?" in the 15-item Geriatric Depression Scale. Slow walking speed was defined as ≤1 standard deviation below the mean values for patients' age and sex. Data on falls were derived from a standardized questionnaire. RESULTS: The prevalence of SMC, slow walking speed, and MCR in the RuLAS cohort (N=1592) was 51.9%, 15.6%, and 8.3%, respectively. After adjusting for other covariates, an occupation of farming (OR=2.358; 95% CI: 1.007-5.521, P=0.048), history of cerebrovascular disease (OR=2.215; 95% CI: 1.032-4.752, P=0.041), and hospitalization (OR=2.008; 95% CI: 1.120-3.602, P=0.019) were risk factors for MCR. Binary logistic regression analysis indicated that the risk of falls was increased by MCR (OR=1.547; 95% CI: 1.009-2.371), SMC (OR=1.308; 95% CI: 1.003-1.707), and slow walking speed (OR=1.442; 95% CI: 1.030-2.017). CONCLUSIONS: Early identification of potential risk factors of MCR can prevent the occurrence of adverse health events such as falls in the elderly.

2.
Cell Death Dis ; 12(4): 302, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753726

RESUMO

Expression of kinesin family member 18B (KIF18B), an ATPase with key roles in cell division, is deregulated in many cancers, but its involvement in prostate cancer (PCa) is unclear. Here, we investigated the expression and function of KIF18B in human PCa specimens and cell lines using bioinformatics analyses, immunohistochemical and immunofluorescence microscopy, and RT-qPCR and western blot analyses. KIF18B was overexpressed in PCa specimens compared with paracancerous tissues and was associated with poorer disease-free survival. In vitro, KIF18B knockdown in PCa cell lines promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, while KIF18B overexpression had the opposite effects. In a mouse xenograft model, KIF18B overexpression accelerated and promoted the growth of PCa tumors. Bioinformatics analysis of control and KIF18B-overexpressing PCa cells showed that genes involved in the PI3K-AKT-mTOR signaling pathway were significantly enriched among the differentially expressed genes. Consistent with this observation, we found that KIF18B overexpression activates the PI3K-AKT-mTOR signaling pathway in PCa cells both in vitro and in vivo. Collectively, our results suggest that KIF18B plays a crucial role in PCa via activation of the PI3K-AKT-mTOR signaling pathway, and raise the possibility that KIF18B could have utility as a novel biomarker for PCa.

3.
Inorg Chem ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761240

RESUMO

A mild and environmentally friendly method to synthesize half-sandwich ruthenium complexes through the Wittig reaction between an aldehyde-tagged half-sandwich ruthenium complex and phosphorus ylide mechanochemically is reported herein. The mechanochemical synthesis of valuable half-sandwich ruthenium complexes resulted in a fast reaction, good yield with simple workup, and the avoidance of harsh reaction conditions and organic solvents. The synthesized half-sandwich ruthenium complexes exhibited high catalytic activity for transfer hydrogenation of ketones using 2-propanol as the hydrogen source and solvent. Density functional theory was carried out to propose a mechanism for the transfer hydrogenation process. The modeling suggests the importance of the labile p-cymene ligand in modulating the reactivity of the catalyst.

4.
Immunol Cell Biol ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565158

RESUMO

The obligate intracellular bacterium Chlamydia is a genital tract pathogen that can also colonize the gastrointestinal tract for long periods. The long-lasting colonization is dependent on chlamydial spreading from the small intestine to the large intestine. We previously reported that a mutant Chlamydia was able to activate an intestinal barrier for blocking its own spreading to the large intestine. In the current study, we used the mutant Chlamydia colonization model to confirm the intestinal barrier function and further to determine the immunological basis of the barrier with gene-deficient mice. Recombination activating gene 1-/- mice failed to block the mutant Chlamydia spreading, while mice deficient in toll-like receptors, myeloid differentiation primary response 88 or stimulator of interferon genes still blocked the spreading, suggesting that the intestinal barrier function is dependent on lymphocytes that express antigen receptors. Mice deficient in CD4, but not CD8 nor µ chain failed to prevent the chlamydial spreading, indicating a protective role of CD4+ cells in the intestinal barrier. Consistently, adoptive transfer of CD4+ T cells reconstituted the intestinal barrier in CD4-/- mice. More importantly, CD4+ but not CD8+ T cells nor B cells restored the intestinal barrier function in recombination activating gene 1-/- mice. Thus, CD4+ T cells are necessary and sufficient for maintaining the intestinal barrier function, indicating that the spread of an intracellular bacterium from the small intestine to the large intestine is regulated by an immunological barrier. This study has also laid a foundation for further illuminating the mechanisms by which a CD4+ T cell-dependent intestinal barrier regulates bacterial spreading in the gut.

5.
JCI Insight ; 6(3)2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33400692

RESUMO

2'3'-cGAMP is known as a nonclassical second messenger and small immune modulator that possesses potent antitumor and antiviral activities via inducing the stimulator of IFN genes-mediated (STING-mediated) signaling pathway. However, its function in regulating type 2 immune responses remains unknown. Therefore, we sought to determine a role of STING activation by 2'3'-cGAMP in type 2 inflammatory reactions in multiple mouse models of eosinophilic asthma. We discovered that 2'3'-cGAMP administration strongly attenuated type 2 lung immunopathology and airway hyperreactivity induced by IL-33 and a fungal allergen, Aspergillus flavus. Mechanistically, upon the respiratory delivery, 2'3'-cGAMP was mainly internalized by alveolar macrophages, in which it activated the STING/IFN regulatory factor 3/type I IFN signaling axis to induce the production of inhibitory factors containing IFN-α, which blocked the IL-33-mediated activation of group 2 innate lymphoid (ILC2) cells in vivo. We further demonstrated that 2'3'-cGAMP directly suppressed the proliferation and function of both human and mouse ILC2 cells in vitro. Taken together, our findings suggest that STING activation by 2'3'-cGAMP in alveolar macrophages and ILC2 cells can negatively regulate type 2 immune responses, implying that the respiratory delivery of 2'3'-cGAMP might be further developed as an alternative strategy for treating type 2 immunopathologic diseases such as eosinophilic asthma.

6.
BMC Cancer ; 21(1): 79, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468079

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most frequent malignancies; however, the present prognostic factors was deficient. This study aims to explore whether there is a relationship between tumor volume (TV) and oncological outcomes for localized ccRCC. METHODS: Seven hundred forty-nine localized ccRCC patients underwent surgery in our hospital. TV was outlined and calculated using a three-dimensional conformal radiotherapy planning system. We used receiver operating characteristic (ROC) curves to identified optimal cut-off value. Univariable and multivariable Cox regression models were performed to explore the association between TV and oncological outcomes. Kaplan-Meier method and log-rank test were used to estimate survival probabilities and determine the significance, respectively. Time-dependent ROC curve was utilized to assess the prognostic effect. RESULTS: Log rank test showed that higher Fuhrman grade, advanced pT classification and higher TV were associated with shortened OS, cancer-specific survival (CSS), freedom from metastasis (FFM) and freedom from local recurrence (FFLR). multivariable analysis showed higher Fuhrman grade and higher TV were predictors of adverse OS and CSS. The AUC of TV for FFLR was 0.822. The AUC of TV (0.864) for FFM was higher than that of pT classification (0.818) and Fuhrman grade (0.803). For OS and CSS, the AUC of TV was higher than that of Fuhrman grade (0.832 vs. 0.799; 0.829 vs 0.790). CONCLUSIONS: High TV was an independent predictor of poor CSS, OS, FFLR and FFM of localized ccRCC. Compared with pT classification and Fuhrman grade, TV could be a new and better prognostic factor of oncological outcome of localized ccRCC, which might contribute to tailored follow-up or management strategies.

7.
Hypertension ; 77(3): 868-881, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33486984

RESUMO

Genome-wide association studies have identified that NPR-C (natriuretic peptide receptor-C) variants are associated with elevation of blood pressure. However, the mechanism underlying the relationship between NPR-C and blood pressure regulation remains elusive. Here, we investigate whether NPR-C regulates Ang II (angiotensin II)-induced hypertension through sodium transporters activity. Wild-type mice responded to continuous Ang II infusion with an increased renal NPR-C expression. Global NPR-C deficiency attenuated Ang II-induced increased blood pressure both in male and female mice associated with more diuretic and natriuretic responses to a saline challenge. Interestingly, Ang II increased both total and phosphorylation of NCC (NaCl cotransporter) abundance involving in activation of WNK4 (with-no-lysine kinase 4)/SPAK (Ste20-related proline/alanine-rich kinase) which was blunted by NPR-C deletion. NCC inhibitor, hydrochlorothiazide, failed to induce natriuresis in NPR-C knockout mice. Moreover, low-salt and high-salt diets-induced changes of total and phosphorylation of NCC expression were normalized by NPR-C deletion. Importantly, tubule-specific deletion of NPR-C also attenuated Ang II-induced elevated blood pressure, total and phosphorylation of NCC expression. Mechanistically, in distal convoluted tubule cells, Ang II dose and time-dependently upregulated WNK4/SPAK/NCC kinase pathway and NPR-C/Gi/PLC/PKC signaling pathway mediated NCC activation. These results demonstrate that NPR-C signaling regulates NCC function contributing to sodium retention-mediated elevated blood pressure, which suggests that NPR-C is a promising candidate for the treatment of sodium retention-related hypertension.

8.
Vascular ; : 1708538120979874, 2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33308107

RESUMO

OBJECTIVE: The present study aims to analyze the outcomes of three cases of pre-fenestration and branch stent-graft endovascular repair of aortic disease with zone 2 aortic lesions. METHODS: From August 2017 to June 2018, three patients with zone 2 aortic lesions underwent thoracic endovascular repair with innominate artery, left common carotid artery, and left subclavian artery recannulation using pre-fenestration and branched stent-grafts to preserve the patency of the aortic arch branches. RESULTS: The technical success rate was 100%. One patient had a proximal type I endoleak with no need for additional treatment. The overall mortality was 0%. All branches were patent. The follow-up period lasted for 2-15 months, with one patient lost to follow-up. There were no conversions to open surgical repair, aortic rupture, paraplegia, or retrograde type A aortic dissection. CONCLUSION: The use of a pre-fenestration and branch stent-graft for the thoracic endovascular repair of zone 2 aortic lesions is a feasible and effective method for aortic arch branch revascularization. The risk of this surgical procedure is high, requiring significant expertise. The procedure should be conducted only in experienced centers. Durability concerns should be assessed in future studies with long-term follow-up.

9.
Chin Med J (Engl) ; 134(4): 379-389, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33323820

RESUMO

ABSTRACT: Increasing evidence suggests that long non-coding RNAs (lncRNAs) are of vital importance for various biological processes, and dysregulation of lncRNAs is frequently associated with various diseases such as psoriasis. LncRNAs modulate gene expression at the transcriptional, post-transcriptional, and translational levels; however, the specific regulatory mechanisms of lncRNAs in psoriasis remain largely unexplored. This review provides an overview of recent studies investigating mechanisms and functions of lncRNAs in psoriasis, especially focusing on the role of lncRNAs in keratinocytes, T cells, and dendritic cells.

10.
Sci Total Environ ; 749: 141682, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-33370886

RESUMO

The coexistence of denitrification and bacterial sulfate reduction (BSR) processes is commonly observed in natural water systems. However, its formation mechanism remains unclear at a basin scale due to the difficulty of precise identification of these processes. To address this issue, we investigated the spatial-temporal variations in water chemistry and isotopic compositions (e.g., δ13CDIC, δ15NNO3, δ18ONO3, δ34SSO4, and δ18OSO4) in cascade reservoirs (artificial dam lakes) of the Jialing River, SW China in 2016. The results showed that the denitrification and BSR processes coexisted in the studied reservoirs, which was supported by the positive correlation between δ15NNO3 and δ18ONO3 and between δ34SSO4 and δ18OSO4, and by the decreasing concentrations of NO3- and SO42-. Moreover, covariation of Δ13CDIC, Δ15NNO3, and Δ34SSO4 indicated the dominance of heterotrophic denitrification (HD) in the reservoir waters along with the occurrence of bacterial sulfide oxidation (BSO). In addition to SO42- and NO3-, the coexistence of HD and BSR processes were also controlled by the dissolved organic carbon (DOC) in winter and dissolved oxygen (DO) contents in other seasons. Overall, the cumulative effect of cascade reservoirs caused δ15NNO3 and δ34SSO4 to display an upward trend from upstream to downstream in the Jialing River, while δ13CDIC showed an opposite downward trend, which implying that cascade reservoirs may be in favor of the coexistence of the HD and BSR processes. This study therefore concludes that the multi-isotope approach could be a useful technique to ascertain the coexistence mechanism of HD and BSR processes in reservoir water systems.

11.
J Clin Ultrasound ; : e22966, 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33377230

RESUMO

There are few studies in the literature about arrhythmogenic cardiomyopathy complicated with right atrial thrombus. We report a case of right atrial thrombus complicating a right-sided arrhythmogenic cardiomyopathy detected by echocardiography. Electrocardiography showed typical Epsilon waves, and the diagnosis was further confirmed by cardiac magnetic resonance imaging.

12.
Aquat Toxicol ; 229: 105678, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33197688

RESUMO

The rotifer, Brachionus plicatilis, is a widely used model species in marine ecotoxicology for evaluating pollutions, toxins, and harmful algae. In this paper, the marine ecotoxicology of Brachionus plicatilis was reviewed, including toxicity measurements of harmful algae species and environmental stresses. In addition, marine pollution involving pesticides, heavy metals, drugs, petroleum, and petrochemicals were addressed. Methods for measuring toxicity were also discussed. The standard acute lethal assay and the chronic population dynamics test were indicated as common methods of toxicity evaluating using B. plicatilis. Research on other biomarkers, such as behaviour, enzyme activity, or gene expression, are also reported here, with potential applications for fast detection or the scientific exploration of underlying molecular mechanisms. It is suggested that the methods selected should reflect the experimental purpose. Additionally, series assays should be conducted for comprehensive evaluation of ecotoxicity as well as to elucidate the correct mechanisms. Genetic methods, such as transcriptomics, were suggested as useful tools for exploring the toxicity mechanism using the rotifer B. plicatilis.

13.
J Virol ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208452

RESUMO

Mites are notorious for being vectors transmitting infectious pathogens and source of allergens causing allergic conditions in animals and humans. However, despite their huge impact on public health, the virome of mites remains unknown. Here we characterized the virus diversity and abundance of 14 species of medically important mites based on total RNA sequencing data sets generated in this study as well as those deposited in the Sequence Read Archive (SRA) database. A total of 47 genetically distinct viruses were identified and classified into 17 virus families or virus super-groups, and the viral sequences accounted for as much as 29.67% of total non-rRNA transcriptome in one mite library. The most commonly identified viruses are members of Picornavirales, among which we revealed more than one type of viruses that are evolutionarily related to dicistronic viruses but contain a single open reading frame, thus likely representing a recent example of host (i.e., mite)-related parallel evolution from dicistronic to monocistronic genomic form within the family Dicistroviridae To our best knowledge, this is the first time to perform comprehensive and systematic screening of RNA virome in medically important mites including house dust mites (HDM). Overall, the RNA virome identified here provides not only significant insights into the diversity and evolution of RNA viruses in mites, but also a solid knowledge base for studying their roles in human diseases.IMPORTANCE Mites are important group of arthropods that are associated with a variety of human diseases including scrub typhus and asthma. However, it remains unclear whether or not mites carry viruses that might play a role in human infections or allergic disease. In this study, we used a total transcriptomics approach to characterize and compare the complete RNA virome within mites that are relevant to human health and diseases. Specifically, our data revealed a large diversity, a high abundance, and a flexible genomic evolution for these viruses. Although most of the viruses identified here are unknown to associate with human infectious disease, the abundant presence of viral RNAs may play an immunomodulatory role in the development of allergic reactions such as asthma during environmental exposure to mite allergens, and therefore provide important insights into the mite-induced allergy and preparation of mite allergen vaccines.

14.
Sci Total Environ ; : 143416, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33246731

RESUMO

High levels of dissolved arsenic (As) have been reported in many rivers running though the Tibetan Plateau (TP), the "Water Tower of Asia". However, the source, spatiotemporal variations, and geochemical behavior of dissolved As in these rivers remain poorly understood. In this study, hot spring, river water, and suspended particulate material samples collected from the Yarlung Tsangpo River (YTR) (upper reaches of the Brahmaputra River) system in 2017 and 2018 were analyzed. Spatial results shown that the upper reaches of YTR (Zone I) have comparatively high levels of dissolved As ([As]dissolved: mean 31.7 µg/L; 4.7-81.6 µg/L; n = 16), while the tributaries of the lower reaches (Zone II) have relatively low levels (mean 0.54 µg/L; 0.11-1.3 µg/L; n = 7). Seasonal results shown that the high [As]dissolved (6.1-22.4 µg/L) were found in September to June and low [As]dissolved (1.4-3.7 µg/L) were observed in July to August. Geothermal water is suspected as the main source of the elevated As levels in YTR due to the extremely high [As]dissolved in hot springs (1.13-9.76 mg/L) and abundance of geothermal systems throughout TP. However, the seasonal results suggested that weathering of As-containing rocks and minerals is also a key factor affecting the [As]dissolved in the river water in July to August (wet-season). Natural attenuation of As in main channel is dominated by dilution process due to the lower As concentrations in tributaries, but mostly occurred by both dilution and adsorption (or co-precipitation) processes in tributaries. This work highlights that the weathering process may have an important contribution to the dissolved As in the river waters in wet-season, and the geochemical behavior of As is largely transported conservatively in the main channel and relative non-conservatively in the tributaries in YTR system.

15.
Front Oncol ; 10: 1547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32923401

RESUMO

Objective: To explore the risk factors for postoperatively pathological lymph node metastasis in patients with clinical T2N0M0 stage prostate cancer (PCa). Methods: We retrospectively analyzed clinicopathological data of 316 patients with clinical T2 stage PCa and preoperative negative lymph nodes [LN(-)] indicated by imaging (cT2N0M0) between January 2014 and May 2019. Multivariate logistic regression analysis was performed to determine risk factors for postoperatively pathological pLN(+) in patients with cT2N0M0 stage PCa. Spearman correlation analysis was used to explore the relationship between tumor burden and Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score. Results: A total of 45 patients (14.2%) were confirmed by postoperative pathology to have LN metastasis. Univariate analysis indicated that total prostate-specific antigen (tPSA), PI-RADS v2 score, postoperative Gleason grade group (GGG), intraductal carcinoma of the prostate (IDC-P), clinical T2 substaging, and postoperative pathological tumor burden were risk factors for pLN(+) in all patients. Multivariate analysis showed that tPSA and postoperative GGG were risk factors for pLN(+) in all patients. Univariate analysis revealed that tPSA, PIRADS v2 score, clinical T2 substaging, IDC-P, postoperative pathological tumor burden, and postoperative GGG were risk factors for pLN(+) in patients with GGG ≥ 3. Multivariate analysis suggested that tPSA, PI-RADS v2 score, clinical T2 substaging, postoperative pathological tumor burden, and GGG were risk factors for pLN (+) in patients with GGG ≥ 3. Spearman correlation analysis showed that PI-RADS v2 score was positively correlated with clinical T2 substaging and postoperative pathological tumor burden. Conclusion: There was a high risk of LN metastasis in patients with cT2 PCa if they had high preoperative tPSA or high postoperative GGG. Patients with cT2 PCa and GGG ≥ 3 had a high risk of LN metastasis if they had high PI-RADS v2 score, high preoperative clinical stage or high postoperative pathological tumor burden. PI-RADS v2 score predicted tumor burden well in patients with GGG ≥ 3.

16.
Environ Sci Pollut Res Int ; 27(36): 45018-45030, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32772286

RESUMO

Traceability offers significant information about the quality and safety of Chinese Angelica, a medicine and food homologous substance. In this study, a systematic four-step strategy, including sample collection, specific metal element fingerprinting, multivariate statistical analysis, and benefit-risk assessment, was developed for the first time to identify Chinese Angelica based on geographical origins. Fifteen metals in fifty-six Chinese Angelica samples originated from three provinces were analyzed. The multivariate statistical analysis model established, involving hierarchical cluster analysis (HCA), principal component analysis (PCA), and self-organizing map clustering analysis was able to identify the origins of samples. Furthermore, benefit-risk assessment models were created by combinational calculation of chemical daily intake (CDI), hazard index (HI), and cancer risk (CR) levels to evaluate the potential risks of Chinese Angelica using as traditional Chinese medicine (TCM) and food, respectively. Our systematic strategy was well convinced to accurately and effectively differentiate Chinese Angelica based on geographical origins.


Assuntos
Angelica , Medicina Tradicional Chinesa , Metais , Análise de Componente Principal , Medição de Risco
17.
J Thorac Dis ; 12(7): 3622-3630, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32802441

RESUMO

Background: The accuracy of clinical N staging of esophageal squamous cell carcinoma is suboptimal. As an important station of lymph node metastasis, station C201 (right recurrent laryngeal nerve nodes) has rarely been evaluated alone. We aimed to explore an effective way to evaluate the right recurrent laryngeal nerve nodes in thoracic esophageal squamous cell carcinoma. Methods: We retrospectively analyzed 628 thoracic esophageal squamous cell carcinoma patients who underwent radical resection without neoadjuvant therapy from two Chinese cancer centers. The diameter of the short axis of the largest right recurrent laryngeal nerve node (DC201) was measured on contrast-enhanced multi-slice computed tomography (MSCT). Right recurrent laryngeal nerve nodes were examined by postoperative pathologic results. The receiver operating characteristic (ROC) curve was generated to assess the diagnostic capabilities of DC201 to determine the right recurrent laryngeal nerve nodes status. Results: ROC curve analysis revealed that the optimal cut-off point of DC201 was 6 mm, with an area under curve (AUC), sensitivity, specificity, and Youden index of 0.896, 71.9%, 88.8%, and 0.607 respectively. When the cut-off point of DC201 was set to 10 mm, sensitivity, specificity and the Youden index were 14.1%, 99.6% and 0.137 respectively. Among 128 patients with right recurrent laryngeal nerve node metastasis, 71 and 108 patients had the largest right recurrent laryngeal nerve node located above the suprasternal notch level and in the tracheoesophageal groove respectively. Conclusions: When DC201 ≥6.0 mm instead of DC201 ≥10 mm was used to dictate the right recurrent laryngeal nerve nodes metastasis, contrast-enhanced MSCT could evaluate the status of right recurrent laryngeal nerve nodes with high sensitivity and specificity. The largest right recurrent laryngeal nerve nodes were mainly located in the tracheoesophageal groove and/or above the suprasternal notch.

18.
Pathol Res Pract ; 216(10): 153109, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853947

RESUMO

OBJECTIVE: To identify hub genes and pathways involved in castrate-resistant prostate cancer (CRPC). METHODS: The gene expression profiles of GSE70768 were downloaded from Gene Expression Omnibus (GEO) datasets. A total of 13 CRPC samples and 110 tumor samples were identified. The differentially expressed genes (DEGs) were identified, and the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis was performed. Protein-protein interaction (PPI) network module analysis was constructed and performed in Cytoscape software. Weighted correlation network analysis (WGCNA) was conducted to determine hub genes involved in the development and progression of CRPC. The gene expression profiles of GSE80609 were used for validation. RESULTS: A total of 1738 DEGs were identified, consisting of 962 significantly down-regulated DEGs and 776 significantly upregulated DEGs for the subsequent analysis. GO term enrichment analysis suggested that DEGs were mainly enriched in the extracellular matrix organization, extracellular exosome, extracellular matrix, and extracellular space. KEGG pathway analysis found DEGs significantly enriched in the focal adhesion pathway. PPI network demonstrated that the top 10 hub genes were ALB, ACACB, KLK3, CDH1, IL10, ALDH1A3, KLK2, ALDH3B2, HBA1, COL1A1. Also, WGCNA identified the top 5 hub genes in the turquoise module, including MBD4, BLZF1, PIP5K2B, ZNF486, LRRC37B2. Plus, the Venn diagram demonstrated that HBA1 was the key gene in both GSE70768 and GSE80609 datasets. CONCLUSIONS: These newly identified genes and pathways could help urologists understand the differences in the mechanism between CRPC and PCa. Besides, it might be promising targets for the treatment of CRPC.

19.
PLoS One ; 15(7): e0236744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730309

RESUMO

Repeated exposures to environmental allergens in susceptible individuals drive the development of type 2 inflammatory conditions such as asthma, which have been traditionally considered to be mainly mediated by Th2 cells. However, emerging evidence suggest that a new innate cell type, group 2 innate lymphoid cells (ILC2), plays a central role in initiating and amplifying a type 2 response, even in the absence of adaptive immunity. At present, the regulatory mechanisms for controlling ILC2 activation remain poorly understood. Here we report that respiratory delivery of immunogenic extracellular RNA (exRNAs) derived from RNA- and DNA-virus infected cells, was able to activate a protective response against acute type 2 lung immunopathology and airway hyperresponsiveness (AHR) induced by IL-33 and a fungal allergen, A. flavus, in mice. Mechanistically, we found that the innate immune responses triggered by exRNAs had a potent suppressive effect in vivo on the proliferation and function of ILC2 without the involvement of adaptive immunity. We further provided the loss-of-function genetic evidence that the TLR3- and MAVS-mediated signaling axis is essential for the inhibitory effects of exRNAs in mouse lungs. Thus, our results indicate that the host detection of extracellular immunostimulatory RNAs generated during respiratory viral infections have an important function in the regulation of ILC2-driven acute lung inflammation.


Assuntos
Armadilhas Extracelulares/imunologia , Imunidade Inata/imunologia , Linfócitos/imunologia , Pneumonia/imunologia , RNA/imunologia , Hipersensibilidade Respiratória/imunologia , Imunidade Adaptativa , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Citocinas/metabolismo , Armadilhas Extracelulares/metabolismo , Interleucina-33/imunologia , Interleucina-33/metabolismo , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/metabolismo , Pneumonia/patologia , RNA/metabolismo , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Transdução de Sinais , Células Th2/imunologia , Células Th2/metabolismo , Receptor 3 Toll-Like/fisiologia
20.
J Asian Nat Prod Res ; : 1-8, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32657145

RESUMO

7ß,8ß-epoxy-(22E,24R)-24-methylcholesta-4,22-diene-3,6-dione (1), a new steroid, along with five known analogues (2-6), was isolated from the deep sea-derived fungus, Aspergillus penicillioides SD-311. Strikingly, 1 possessed a rare 7,8-epoxidation moiety. Meanwhile, this is the first time to report natural products from this fungus species. The structures were established by extensive spectroscopic analysis. The absolute configuration was determined by X-ray diffraction experiments. Compound 1 showed antibacterial activity against Vibrio anguillarum with MIC value of 32.0 µg/mL, while 2 displayed inhibitions against Edwardsiella tarda and Micrococcus luteus with MIC values both of 16 µg/mL.

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