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1.
Zhonghua Yi Xue Za Zhi ; 100(17): 1315-1319, 2020 May 05.
Artigo em Chinês | MEDLINE | ID: mdl-32375439

RESUMO

Objective: To investigate the expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) in patients with chronic heart failure and its modulatory activity on T lymphocytes. Methods: Eighty-six patients with chronic heart failure (CHF group) who were hospitalized in Department of Cardiology, the First Affiliated Hospital of Zhengzhou University between January and October 2018 were enrolled in the study. Meanwhile, thirty-two healthy controls (HC group) who received healthy examination were also selected. Peripheral blood mononuclear cells were isolated, and TIM-3 expression of CD4(+)and CD8(+)T cells was investigated by flow cytometry. CD4(+)and CD8(+)T cells were purified, and were stimulated by anti-TIM-3 antibody. Interferon-γ (IFN-γ), interleukin (IL)-4, IL-10, IL-35, IL-17, and IL-22 expressions in the supernatants of cultured CD4(+)T cells and tumor necrosis factor-α (TNF-α) and IFN-γ expressions in the supernatants of cultured CD8(+) T cells were measured by enzyme-linked immunosorbent assay. mRNA expressions of T-bet, GATA-3, FoxP3, and RORγt in CD4(+)T cells and perforin and granzyme B in CD8(+)T cells were semi-quantified by real-time PCR. Student t test or paired t test was used for comparisons between the two groups. Results: TIM-3(+) CD4(+) T cell percentage significantly increased in CHF group than that of HC group (3.47%±1.06% vs 0.92%±0.27%, P<0.001). TIM-3(+)CD8(+)T cell percentage also notably elevated in CHF group compared to HC group (6.12%±1.91% vs 1.77%±0.63%, P<0.001). CD4(+)T and CD8(+)T cells were dysfunctional in chronic heart failure. The levels of IFN-γ, IL-17, and IL-22 secreted by purified CD4(+) T cells significantly reduced in CHF group, while IL-10 and IL-35 expressions elevated in CHF group (all P<0.05). The relative mRNA expression levels of T-bet and RORγt in CD4(+) T cells remarkably decreased in CHF group than those of HC group (all P<0.01), while relative expression level of FoxP3 mRNA increased in CHF group (1.93±0.88 vs 0.97±0.28, P=0.031). The levels of TNF-α and IFN-γ produced by purified CD8(+)T cells notably reduced in CHF group than those of HC group (all P<0.05), and relative mRNA expression levels of perforin and granzyme B also decreased in CHF group (all P<0.05). The levels of anti-TIM-3 antibody stimulation-produced IFN-γ, IL-17, and IL-22 increased (all P<0.05) but IL-35 secretion reduced [(61±13) ng/ml vs (72±17) ng/ml, P=0.029] by CD4(+)T cells in CHF group. The relative mRNA expression levels of T-bet and RORγt also elevated in response to anti-TIM-3 antibody stimulation (all P<0.05). Anti-TIM-3 antibody stimulation promoted TNF-α and IFN-γ production by CD8(+)T cells in CHF group (all P<0.01). The relative mRNA expression levels of perforin and granzyme B also increased (all P<0.05). Conclusion: TIM-3 was increasingly expressed in T cells from patients with chronic heart failure, and might take part in the regulation of T cell dysfunction in chronic heart failure.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32367566

RESUMO

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease with diverse phenotypes. However, its biological diversity has not been well-characterized in Chinese psoriasis population. OBJECTIVES: To characterize psoriasis biological heterogenicity using gene expression profiles of lesional skin biopsy specimens in a Chinese psoriasis population. METHODS: Lesional tissues and blood samples from Chinese psoriasis patients (n = 40), atopic dermatitis (AD) patients (n = 25) and age-matched healthy controls (n = 19) were investigated by using Real-Time PCR Array, histological evaluation and flow cytometry. Unsupervised hierarchical clustering was performed using gene expression profiles of patients with psoriasis. RESULTS: Two distinct psoriasis clusters were identified. Both clusters indicated high TH 17 activation. One cluster (n = 6 of 40 consecutive psoriasis patients) indicated a strong TH 2 component in skin lesions, with early onset and low peripheral blood eosinophil level. Significantly higher IL-4, IL-13, IL-25, IL-31 and TSLP gene induction typified this cluster of psoriasis patients, even compared with AD patients. Both psoriasis clusters were characterized by neutrophilic microabscess formation. Histologically, the TH 2 high psoriasis cluster indicated a low percentage of perivascular eosinophils. CONCLUSIONS: Two distinct psoriasis clusters were identified. One presented early onset and a low eosinophil level, indicating TH 17 polarization and a strong TH 2 component. These results laid the foundation for further demonstrating the pathogenesis of psoriasis in Chinese population.

3.
Eur Rev Med Pharmacol Sci ; 24(9): 4963-4970, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32432759

RESUMO

OBJECTIVE: To clarify the role of HOXA-AS2 in the progression of diabetic nephropathy (DN) and the molecular mechanism. MATERIALS AND METHODS: Relative levels of HOXA-AS2 and microRNA-302b-3p (miRNA-302b-3p) in serum and kidney tissues of DN rats induced by STZ administration and controls were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Serum levels of interleukin-1ß (IL-1ß), Transforming Growth Factor-α (TNF-α), creatinine, and BUN, as well as blood glucose in DN rats administrated with vector or pcDNA-HOXA-AS2 lentivirus, were detected. Dual-Luciferase reporter gene assay was conducted to verify the interaction among HOXA-AS2, miRNA-302b-3p, and TIMP3. At last, the regulatory effects of HOXA-AS2/miRNA-302b-3p/TIMP3 axis on levels of IL-1ß and TNF-α, proliferative, and apoptotic rates in podocytes undergoing high-level glucose treatment were explored. RESULTS: HOXA-AS2 was downregulated in STZ-induced DN rats. In vivo overexpression of HOXA-AS2 alleviated kidney injuries in DN rats, manifesting as elevations on serum levels of IL-1ß, TNF-α, creatinine, BUN, and blood glucose. HOXA-AS2/miRNA-302b-3p/TIMP3 axis protected DN-induced inflammatory response, proliferation suppression, and apoptosis in podocytes following the high-glucose treatment. CONCLUSIONS: HOXA-AS2/miRNA-302b-3p/TIMP3 axis protects inflammatory response, proliferation suppression, and apoptosis in podocytes treated with high-level glucose, thus alleviating the deterioration of DN.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32286971

RESUMO

This paper reports a design journey for ScxAl1-xN based dual-mode hybrid quasi-surface and bulk acoustic wave (quasi-SAW/BAW) resonators. Four types of acoustic excitation configurations are proposed in these designs based on ScxAl1-xN/6H-SiC stack architectures. The influence of ScxAl1-xN materials, film thickness, and device configurations on the performance are investigated. After design optimization, the final dual-mode hybrid quasi-SAW/BAW resonators comprise of top electrode, partially etched ScxAl1-xN pillars and bottom electrode which are stacked on a 6H-SiC substrate. The coupled quasi-SAW and BAW excited in the hybrid resonators enhance the resonance for both quasi-Rayleigh and quasi-Sezawa modes which results in a high effective coupling coefficient (Keff2) and phase velocity (v). Simulation results show that the optimized hybrid quasi-SAW/BAW resonator based on Mo/Sc0.4Al0.6N/Mo/6H-SiC configuration with SiO2 filling the grooves has a remarkable Keff2 value of 14.55% and a high v above 7500m/s, which make this kind of dual-mode hybrid quasi-SAW/BAW resonators have great potential in wideband and high frequency applications.

5.
Eur Rev Med Pharmacol Sci ; 24(6): 2836-2842, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32271401

RESUMO

OBJECTIVE: To explore the influence of osteopontin (OPN) on the chondrocyte proliferation in osteoarthritis (OA) rats. MATERIALS AND METHODS: A total of 30 Sprague-Dawley rats were divided in the control group (n=10), model group (n=10), and OPN knockdown group (n=10). No treatment was performed in the control group, while OA rats were administrated with control adenovirus in the model group and OPN knockdown adenovirus in the OPN knockdown group. After sampling, the degree of OA was evaluated via hematoxylin-eosin (HE) staining, and the mRNA expression of OPN was detected. Moreover, the expression of the proliferation-associated protein cyclin D1 was detected using immunohistochemistry. The chondrocytes were isolated from the normal rats, cultured, and transfected with OPN overexpression vector or si-OPN. Methyl thiazolyl tetrazolium (MTT) assay was adopted to determine the proliferative capacity of chondrocytes, and Caspase3 activity was measured to evaluate the changes in the apoptotic capacity of chondrocytes. Meanwhile, Western blotting was performed to verify the influences of OPN on the pathways on chondrocyte proliferation. RESULTS: After the OA model was established, the expression level of OPN significantly increased. According to HE staining results, OPN knockdown effectively inhibited the onset of OA. Compared with that in the control group, the expression level of cyclin D1 in the model group was raised. However, upregulated cyclin D1 in OA rats was repressed in OPN knockdown group. OPN overexpression promoted the proliferation of chondrocytes, but suppressed their apoptosis, while OPN knockdown had the opposite effects. Besides, OPN overexpression upregulated nuclear factor-κB (NF-κB), and NF-κB knockdown eliminated the regulatory effects of OPN on proliferation and apoptosis of chondrocytes. CONCLUSIONS: OPN promotes the expression of NF-κB signals to accelerate chondrocyte proliferation, thereby inducing OA in rats.

6.
Eur Rev Med Pharmacol Sci ; 24(6): 3215-3222, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32271439

RESUMO

OBJECTIVE: To study the protective effect of micro ribonucleic acid (miR)-146 against kidney injury in diabetic nephropathy (DN) rats through the nuclear factor-κB (NF-κB) signaling pathway. MATERIALS AND METHODS: In this experiment, 30 adult Sprague-Dawley rats with 5-6 weeks old and weighing 20-30 g were selected and randomly divided into control group (n=10), model group (n=10), and miR-146 Mimic group (n=10, DN rat model + miR-146 Mimic). The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) in the three groups were detected using the full-automatic biochemical analyzer. The protein expression levels of phosphorylated-inhibitor of NF-κB (p-IκB), p-P65, P65, and Tubulin were detected via Western blotting. The messenger RNA (mRNA) of P65 was determined using quantitative Polymerase Chain Reaction (qPCR). Positive expression of p-IκB in tissues was determined using immunohistochemistry. Moreover, the contents of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected using the enzyme-linked immunosorbent assay (ELISA) kits. Finally, the apoptosis was detected through Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) dual-fluorescence labeling. RESULTS: The serum levels of Cr and BUN were significantly higher in the model group than those in the control group (p<0.01), while they were significantly lower in miR-146 Mimic group than those in the model group (p<0.05). The levels of p-IκB and p-P65/P65 significantly increased in the model group compared with those in the control group (p<0.01), while they remarkably declined in the miR-146 Mimic group compared with those in the model group (p<0.05). The results of qPCR showed that the mRNA level of P65 had no significant difference among the three groups (p>0.05). The immunohistochemical assay showed that the positive expression of p-IκB in tissues was consistent with those of the protein level as Western blotting revealed. The rats in the model group had evidently increased levels of TNF-α, IL-1ß, and IL-6 compared with the control group (p<0.01), while miR-146 Mimic group had evidently decreased levels of them compared with the model group (p<0.01). Finally, apoptosis was enhanced in the model group compared with that in the control group, while it was remarkably inhibited in the miR-146 Mimic group. CONCLUSIONS: MiR-146 can inhibit the NF-κB signaling pathway, lower the levels of TNF-α, IL-1ß, and IL-6, and reduce the apoptosis, thereby exerting a protective effect against kidney injury in DN.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32304745

RESUMO

OBJECTIVE: In December 2019, coronavirus disease (COVID-19) emerged in Wuhan. However, the characteristics and risk factors associated with disease severity, unimprovement and mortality are unclear and our objective is to throw some light on these. METHODS: All consecutive patients diagnosed with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 11 to February 6, 2020, were enrolled in this retrospective cohort study. RESULTS: A total of 663 COVID-19 patients were included in this study. Among these, 247 (37.3%) had at least one kind of chronic disease; 0.5% of the patients (n = 3) were diagnosed with mild COVID-19, while 37.8% (251/663), 47.5% (315/663), and 14.2% (94/663) were in moderate, severe, and critical conditions, respectively. In our hospital, during follow-up 251 of 663 patients (37.9%) improved and 25 patients died, a mortality rate of 3.77%. Older patients (>60 years old) and those with chronic diseases were prone to have a severe to critical COVID-19 condition, to show unimprovement, and to die (p <0.001, <0.001). Multivariate logistic regression analysis identified being male (OR = 0.486, 95%CI 0.311-0.758; p 0.001), having a severe COVID-19 condition (OR = 0.129, 95%CI 0.082-0.201; p <0.001), expectoration (OR = 1.796, 95%CI 1.062-3.036; p 0.029), muscle ache (OR = 0.309, 95%CI 0.153-0.626; p 0.001), and decreased albumin (OR = 1.929, 95%CI 1.199-3.104; p 0.007) as being associated with unimprovement in COVID-19 patients. CONCLUSION: Male sex, a severe COVID-19 condition, expectoration, muscle ache, and decreased albumin were independent risk factors which influence the improvement of COVID-19 patients.

8.
Artigo em Chinês | MEDLINE | ID: mdl-32268695

RESUMO

Objective: To explore the feasibility of retroauricular robotic thyroidectomy and introduce the experience and lessons. Methods: From May 2018 to December 2018, 5 consecutive cases underwent gasless retroauricular robotic thyroidectomy by using Davinci Si system at Beijing United Family Hospital, including 1 male and 4 females, aged from 18 to 37 years old. And they were retrospectively reviewed and analyzed. Among them, one case was a recurrence of cervical lympy nodes after total thyroidectomy for thyroid cancer. Results: Among 5 patients (mean age 32.4 years, mean tumor size 1.3 cm), one patient underwent unilateral thyroid lobectomies, 3 patients did total thyroidectomy and 4 patients did neck dissection. All patients had papillary thyroid carcinomas (PTC). The average time for unilateral retroauricular robotic thyroidectomy was 375 min. Intraoperative conversion to open surgery happened in one patient. Postoperative vocal cord paralysis and hypocalcemia developed in one of the patients. Conclusion: Retroauricular robotic thyroidectomy is feasible for selected patients and would be a potential alternative approach in remote-access approaches for thyroid surgery.

9.
Breast Cancer Res Treat ; 181(2): 411-421, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32253683

RESUMO

BACKGROUND: Advances in breast cancer research are making treatment options increasingly effective and reducing mortality. Body composition is an example of a prognostic tool that can help personalize breast cancer treatments and further increase their effectiveness. In this study, we examine the association of several body composition measures with comorbidities, physical function, and quality of life. METHODS: This study is a cross-sectional analysis of 99 women with early breast cancer scheduled for chemotherapy. Univariate regression models were used to identify significant associations of body composition metrics with patient demographics, clinical characteristics, measures of physical function, and patient-reported outcomes (PRO)s. Multivariable modeling was used to evaluate associations adjusted for age. RESULTS: Median age was 58 (range 24-83), 27% were non-white, and, 47% were obese (≥ 30 kg/m2). Increasing age was associated with lower Skeletal Muscle Density (SMD) (p = 0.0001), lower Skeletal Muscle Gauge (SMG) (p = 0.0005), and higher Visceral Adipose Tissue (VAT) (p < 0.0001). In patients with a prolonged Timed Up and Go tests (> 14 s), mean VAT was 57.87 higher (p = 0.004), SMD 5.70 lower (p = 0.04), and SMG 325.4 lower (p = 0.02). For each point of higher performance on the Short Physical Performance Battery (SPPB), VAT decreased 12.24 (p = 0.002) and SMD rose 1.22 (p = 0.02). In multivariable analysis adjusting for age, the association of TUG > 14 with higher VAT remained significant (p = 0.02). CONCLUSIONS: Suboptimal body composition prior to treatment is associated poor physical function and may be an indicator of clinical importance.

10.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(5): 486-490, 2020 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-32171191

RESUMO

Objective: To understand the viral genomic characteristics of a 2019-novel coronavirus (2019-nCoV) strain in the first COVID-19 patient found in Hangzhou, China. Methods: Viral RNA was extracted in throat swab and sputum sample of the patient and was performed real-time reverse transcription PCR detection and obtained viral genome by high-throughput sequencing method. Phylogenetic analysis was conducted using 29 2019-nCoV genomes and 30 ß-coronavirus genomes deposited in NCBI GenBank. Fifteen genomes from Wuhan were grouped by mutation sites and others were identified by Wuhan's or specific mutation sites. Results: A 29 833 bp length genome of the first 2019-nCoV strain in Hangzhou was obtained, covering full length of the coding regions of coronavirus. Phylogenetic analysis showed that the genome was closest to the genome of a bat SARS-like coronavirus strain RaTG13 with an identity of 96.11% (28 666/29 826). Among the genes between two genomes, E genes were highly conserved (99.56%), while S genes had lowest identity (92.87%). The genome sequence similarities among 29 strains from China (Hangzhou, Wuhan, and Shenzhen), Japan, USA, and Finland, were all more than 99.9%; however, some single nucleotide polymorphisms were identified in some strains. Conclusion: The genome of Hangzhou 2019-nCoV strain was very close to the genomes of strains from other cities in China and overseas collected at early epidemic phase. The 2019-nCoV genome sequencing method used in this paper provides an useful tool for monitoring variation of viral genes.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/virologia , Genoma Viral , Pneumonia Viral/virologia , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia
11.
Ann Oncol ; 31(4): 507-516, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32139298

RESUMO

BACKGROUND: Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab [anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody]. PATIENTS AND METHODS: Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25-75 mg p.o. twice a day; continuous or intermittent), savolitinib (600-800 mg p.o. once a day), or durvalumab (3-10 mg/kg intravenous every 2 weeks). RESULTS: At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n = 36), savolitinib (n = 18), or durvalumab (n = 23). Most common adverse events (any grade), occurring in ≥20% of patients across dose groups, were: selumetinib arm-diarrhea (75%), rash (58%), nausea (47%); savolitinib arm-nausea (67%), rash (56%), vomiting (50%); durvalumab arm-rash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n = 1), 50 mg (n = 1), and 75 mg (n = 4) continuous-dose groups, savolitinib 600 mg (n = 1) and 800 mg dose groups (n = 2), and durvalumab 10 mg/kg (n = 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively. CONCLUSION: Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated. CLINICAL TRIALS NUMBER: NCT02143466.

12.
Eur Rev Med Pharmacol Sci ; 24(5): 2256-2263, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32196576

RESUMO

OBJECTIVE: Ovarian cancer (OC) is still the third leading cause of death in reproductive system malignancies. In OC, the biological function of microRNA-202-5p (miR-202-5p) is unknown. Our current research mainly focuses on miR-202-5p in the OC progression. PATIENTS AND METHODS: MiR-202-5p was determined to be down-regulated in OC by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay and colony formation assay were recruited to access the ability of miR-202-5p on cell proliferation. Cell migration and invasion were determined by transwell assay and Matrigel assay. Dual-Luciferase reporter assay was recruited, and it validated that HOXB2 was a downstream target of miR-202-5p. Epithelial-mesenchymal transition (EMT) hallmark genes and HOXB2 expression level were examined by Western blotting. RESULTS: MiR-202-5p was down-expressed in OC. Receiver operating characteristic (ROC) curve indicated that miR-202-5p was positively related to HOXB2. MiR-202-5p over-expression led to a higher 5-year survival rate. Up-regulated miR-202-5p inhibited cell proliferation and metastasis in vitro. HOXB2 was a downstream target of miR-202-5p. CONCLUSIONS: We verified that miR-202-5p suppressed cell proliferation, migration, and invasion in OC via regulating HOXB2. Our findings provide new insights into the underlying mechanism of OC progression and may be useful in finding biomarkers and therapeutic targets of OC.

13.
Biochim Biophys Acta Biomembr ; : 183241, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32126227

RESUMO

The presence of an asymmetric distribution of lipids in biological membranes was first described ca. 50 years ago. While various studies had reported the role of loss of lipid asymmetry on signaling processes, its effect on membrane physical properties and membrane-protein interactions lacks further understanding. The recent description of new technologies for the preparation of asymmetric model membranes has helped to fill part of this gap. However, the major effort so far has been on plasma membrane models. Here we describe the preparation of liposomes mimicking the mitochondria outer membrane (MOM) in regard to its lipid composition and asymmetry. By employing the methyl-ß-cyclodextrin-catalyzed lipid exchange technology and accurate quantification of lipid asymmetry with head group-specific probes we showed the successful preparation of a MOM model bearing a physiologically relevant lipid composition and asymmetry. In addition, by a direct comparison with its lipid symmetrical counterpart it is shown that asymmetric models were more resistant to tBid-promoted Bax-permeabilization, suggesting a role played by MOM lipid asymmetry on the mitochondria pathway of apoptosis. The barrier imposed by lipid asymmetry on membrane permeabilization was in part due to a decrease in the concentration of membrane-bound proteins, which was likely a consequence of the two mutually-dependent properties; i.e., the lower electrostatic surface potential and the higher molecular packing imposed by lipid asymmetry. It is proposed that MOM lipid asymmetry imparts different physical properties on the membrane and might add an additional component of regulation in intricate mitochondrial processes.

14.
ACS Appl Mater Interfaces ; 12(9): 10503-10514, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32031779

RESUMO

The growing global concerns to public health from human exposure to perfluorooctanesulfonate (PFOS) require rapid, sensitive, in situ detection where current, state-of-the-art techniques are yet to adequately meet sensitivity standards of the real world. This work presents, for the first time, a synergistic approach for the targeted affinity-based capture of PFOS using a porous sorbent probe that enhances detection sensitivity by embedding it on a microfluidic platform. This novel sorbent-containing platform functions as an electrochemical sensor to directly measure PFOS concentration through a proportional change in electrical current (increase in impedance). The extremely high surface area and pore volume of mesoporous metal-organic framework (MOF) Cr-MIL-101 is used as the probe for targeted PFOS capture based on the affinity of the chromium center toward both the fluorine tail groups as well as the sulfonate functionalities as demonstrated by spectroscopic (NMR and XPS) and microscopic (TEM) studies. Answering the need for an ultrasensitive PFOS detection technique, we are embedding the MOF capture probes inside a microfluidic channel, sandwiched between interdigitated microelectrodes (IDµE). The nanoporous geometry, along with interdigitated microelectrodes, increases the signal-to-noise ratio tremendously. Further, the ability of the capture probes to interact with the PFOS at the molecular level and effectively transduce that response electrochemically has allowed us achieve a significant increase in sensitivity. The PFOS detection limit of 0.5 ng/L is unprecedented for in situ analytical PFOS sensors and comparable to quantification limits achieved using state-of-the-art ex situ techniques.

15.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(3): 239-244, 2020 Mar 06.
Artigo em Chinês | MEDLINE | ID: mdl-32064856

RESUMO

In December 2019, novel coronavirus pneumonia epidemic occurred in Wuhan, Hubei Province, and spread rapidly across the country. In the early stages of the epidemic, China adopted the containment strategy and implemented a series of core measures around this strategic point, including social mobilization, strengthening case isolation and close contacts tracking management, blocking epidemic areas and traffic control to reduce personnel movements and increase social distance, environmental measures and personal protection, with a view to controlling the epidemic as soon as possible in limited areas such as Wuhan. This article summarizes the background, key points and core measures in the country and provinces. It sent prospects for future prevention and control strategies.


Assuntos
Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , China , Busca de Comunicante , Humanos , Quarentena
16.
Nat Cell Biol ; 22(2): 200-212, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32015435

RESUMO

PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs essential for fertility. In adult mouse testes, most piRNAs are derived from long single-stranded RNAs lacking annotated open reading frames (ORFs). The mechanisms underlying how piRNA sequences are defined during the cleavages of piRNA precursors remain elusive. Here, we show that 80S ribosomes translate the 5'-proximal short ORFs (uORFs) of piRNA precursors. The MOV10L1/Armitage RNA helicase then facilitates the translocation of ribosomes into the uORF downstream regions (UDRs). The ribosome-bound UDRs are targeted by piRNA processing machinery, with the processed ribosome-protected regions becoming piRNAs. The dual modes of interaction between ribosomes and piRNA precursors underlie the distinct piRNA biogenesis requirements at uORFs and UDRs. Ribosomes also mediate piRNA processing in roosters and green lizards, implying that this mechanism is evolutionarily conserved in amniotes. Our results uncover a function for ribosomes on non-coding regions of RNAs and reveal the mechanisms underlying how piRNAs are defined.


Assuntos
Mitocôndrias/genética , Precursores de RNA/genética , RNA Interferente Pequeno/genética , Ribossomos/genética , Testículo/metabolismo , Animais , Galinhas , Biologia Computacional/métodos , Lagartos , Masculino , Camundongos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Fases de Leitura Aberta , Estágio Paquíteno , Fosfolipase D/genética , Fosfolipase D/metabolismo , Ligação Proteica , Biossíntese de Proteínas , Proteínas/genética , Proteínas/metabolismo , RNA Helicases/genética , RNA Helicases/metabolismo , Precursores de RNA/metabolismo , RNA Interferente Pequeno/biossíntese , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ribossomos/metabolismo , Testículo/citologia , Canal de Ânion 1 Dependente de Voltagem/genética , Canal de Ânion 1 Dependente de Voltagem/metabolismo
17.
Zhonghua Wai Ke Za Zhi ; 58(2): 110-113, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32074809

RESUMO

Objectives: To examine the effect of VAE and open surgery on the postoperativelocal recurrence of benign phyllodes tumors of breast and to investigate the clinical efficacy of VAE in the treatment of benign phyllodes tumors. Methods: The clinical data of 128 patients with benign phyllodes tumors of breast admitted to the Guangdong Women and Children Hospital from January 2013 to January 2018 were retrospectively analyzed. All patients were female, aged (37.7±9.1) years (range: 16 to 56 years). Eighty patients underwent ultrasound-guided VAE (minimally invasive group) and 48 patients underwent open surgery (open group). The t-test, χ(2) test or Fisher exact probability method were used to compare the clinical characteristics of the two groups of patients. Logistic regression was used to analyze the prognostic factors of postoperative local recurrence. Results: The maximum diameter of tumor in the minimally invasive group was smaller than that in the open group ((20.6±7.4) mm vs. (42.0±2.0) mm, t=-7.173, P=0.000). The follow-up time was (36.4±1.8) months (range: 12 to 71 months). There were 7 cases of local recurrences during the follow-up period. The local recurrence rates in the minimally invasive and open groups were 5.0% (4/80) and 6.3% (3/48). The results of multivariate analysis showed that the maximum tumor diameter of 25 mm was an independent prognosis factor for postoperativelocal recurrence (OR=0.122, 95%CI: 0.016 to 0.901, P=0.039). While surgical procedure, age, menopausal status and history of fibroadenomas in the ipsilateral breast is not an independent prognostic factor for postoperative local recurrence. In the minimally invasive surgery group, the local recurrence rates were 2.9% (2/69) and 2/11 in patients with tumor maximum diameters<25 mm and ≥25 mm, respectively. Conclusions: Local recurrence of breast benign phyllodes tumors is closely related to the tumor size. For patients with tumor diameter<25 mm, the postoperative local recurrence rate of VAE is low, which can be used in clinical practice. Intraoperative complete resection to achieve a negative surgical margin should be guaranteed to avoid local recurrence.


Assuntos
Neoplasias da Mama , Tumor Filoide , Adolescente , Adulto , Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tumor Filoide/diagnóstico por imagem , Tumor Filoide/cirurgia , Estudos Retrospectivos , Ultrassonografia de Intervenção , Vácuo , Adulto Jovem
18.
Zhonghua Gan Zang Bing Za Zhi ; 28(1): 64-68, 2020 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-32023702

RESUMO

Objective: To investigate the effects of metformin on mitochondrial pathway of apoptosis and oxidative stress in cell model of nonalcoholic fatty liver disease. Methods: An in vitro cell model of nonalcoholic fatty liver disease was established using 0.6 mmol/L oleic acid to induce lipid accumulation in HepG2 cells. HepG2 cells were divided into control (Con) group, oleic acid (OA) group, and metformin-low (1mmol/L) and high (10mmol/L) dose group. Oil Red O stain was used to detect intracellular lipid droplet distribution. The levels of alanine aminotransferase and aspartate aminotransferase in the culture supernatant were detected by assay kits. DCFH-DA method was used to detect the reactive oxygen species of HepG2 cells. Double staining flow cytometry was used to detect the apoptosis rate of HepG2 cells. Western blot was used to detect caspase-3, B-lymphocyte lymphoma-related protein, B-cell lymphoma 2, and cytochrome c protein. One-way analysis of variance was used to compare the data between groups. Results: Oleic acid-induced HepG2 cells were significantly increased with lipid droplets. Low and high-dose metformin had reduced intracellular lipid droplets accumulation. The effect of metformin in the high-dose group was more significant than that in the low-dose group. Aspartate aminotransferase and alanine aminotransferase in HepG2 cells of OA group were significantly increased, which were (43.41 ± 7.11) U/L and (29.56 ± 4.11) U/L, respectively. The intracellular aspartate aminotransferase and alanine aminotransferase were decreased significantly after the treatment with low and high-dose metformin, which were (32.44 ± 4.08)U/L, (19.31 ± 3.03) U/L, (26.00 ± 3.11) U/L and (15.11 ± 4.11) U/L, respectively and the differences were statistically significant (P < 0.05). DCFH-DA test results showed that the fluorescence intensity of reactive oxygen species in the oleic acid group was 41.21% ± 4.23%, while the fluorescence intensity of reactive oxygen species in the low and high-dose metformin groups were reduced to 27.44% ± 3.91%, and 17.55% ± 5.11%, respectively and the differences between the groups were statistically significant (P < 0.05). The results of flow cytometry analysis showed that the cell apoptosis rate of the OA group was significantly higher than that of the Con group (12.12% ± 0.72% vs. 3.04% ± 0.57%, P < 0.05).The apoptosis rate of HepG2 cells was significantly reduced after metformin treatment at low and high doses (8.71% ± 0.71%, 5.71% ± 0.61%, P < 0.05). Western blot results showed that compared with the Con group, the expressions of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 were increased in the OA group, while the B-cell lymphoma 2 were decreased (P < 0.05). The expression of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 protein in HepG2 cells was decreased after treatment with low and high-dose metformin, while B-cell lymphoma 2 was increased (P < 0.05). Conclusion: Metformin can effectively alleviate steatosis and improve the HepG2 function in cell model of nonalcoholic fatty liver disease. The mechanism of metformin may be related to the reduction of oxidative stress injury, the regulation of protein expression related to mitochondrial apoptosis pathway and the inhibition of cell apoptosis.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo , Apoptose , Células Hep G2 , Humanos , Metformina , Mitocôndrias
19.
Eur Rev Med Pharmacol Sci ; 24(3): 1524-1536, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32096202

RESUMO

OBJECTIVE: To investigate the roles and underlying mechanisms of melatonin in oxygen-glucose deprivation/reoxygenation (OGD/R)-insulted SH SY5Y cells. MATERIALS AND METHODS: SH SY5Y cells were cultured for OGD/R stimulation. Cell viability and cytotoxicity were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, lactate dehydrogenase (LDH), and Hoechst 33258/propidium iodide (PI) staining assays. The mRNA levels of high mobility group box-1 (HMGB1), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS) were analyzed by quantitative Real Time-PCR assays. Nitric oxide (NO) production was assessed by Griess reagent. Reactive oxygen species (ROS) production was detected by fluorescent probe. Malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were examined by commercial kits. Cell apoptosis was analyzed by flow cytometry and caspase-3 activity. The protein levels were detected by Western blot. RESULTS: Melatonin enhanced the viability and reduced the death and LDH release of OGD/R exposed SH SY5Y cells. Melatonin repressed the HMGB1, TNF-α, and iNOS mRNA expression, NO production, and nuclear factor κB (NF-κB) activation in OGD/R challenged SH SY5Y cells. Melatonin reduced the ROS, MDA, 4-HNE, and 8-OHdG contents but further enhanced the levels of the nuclear factor E2-related factor-2 (Nrf2) and heme oxygenase (HO-1). Melatonin-increased viability and melatonin-decreased LDH release were also mediated by the blockage of NF-κB or reversed by Nrf2 or HO-1 knockdown. Melatonin exerted antiapoptotic effect on OGD/R treated SH SY5Y cells partly by activating Akt signaling. OGD/R challenged SH SY5Y cell autophagy was also repressed by melatonin, as evidenced by the decreased levels of LC-II and beclin-1 and the increased phosphorylation of mammalian target of rapamycin (mTOR), p70 ribosomal protein S6 kinase (p70S6K), and eukaryotic initiation factor 4E binding protein 1 (4E-BP-1). CONCLUSIONS: Melatonin protected SH SY5Y cells from OGD/R induced oxidative stress, inflammation, apoptosis, and autophagy by blocking NF-κB signaling and activating Nrf2/HO-1, Akt, and mTOR/p70S6K/4E-BP-1 pathways, thereby indicating that melatonin is a potential and novel therapeutic drug for ischemic stroke.

20.
Nat Cell Biol ; 22(3): 353, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32066908

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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