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1.
Artigo em Inglês | MEDLINE | ID: mdl-34333150

RESUMO

BACKGROUND/AIMS: Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. METHODS: 12,995 CHC patients treated with sofosbuvir-based (n=6,802) or non-sofosbuvir-based (n=6,193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF, 3 months after EOT). RESULTS: The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2, P<0.001) and substantially recovered at EOF (88.8 mL/min/1.73 m2) but did not return to pretreatment levels (P<0.001). Notably, a significant decrease in eGFR was observed only in patients with baseline eGFR ≥90 mL/min/1.73 m2 (from 112.9 to 106.4 mL/min/1.73 m2, P<0.001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m2 (from 70.0 to 71.5 mL/min/1.73 m2, P<0.001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR> 90 ml/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 ml/min/1.73 m2; 95% C.I.: -2.24, -1.72, P<0.001). The usage of sofosbuvir was not an independent factor associated with eGFR change. CONCLUSIONS: Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.

2.
Curr Med Chem ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34238143

RESUMO

This review describes how phase-changeable nanoparticles enable highly efficient high-intensity focused ultrasound ablation (HIFU). HIFU is effective in the clinical treatment of solid malignant tumors. However, it has intrinsic disadvantages for treating some deep lesions, such as damage to surrounding normal tissues. When phase-changeable nanoparticles are used in HIFU treatment, they could serve as good synergistic agents because they are transported in the blood and permeated and accumulated effectively in tissues. HIFU's thermal effects can trigger nanoparticles to undergo a special phase transition, thus enhancing HIFU ablation efficiency. Nanoparticles can also carry anticancer agents and release them in the targeted area to achieve chemo-synergistic therapy response. Although the formation of nanoparticles is complicated and HIFU applications are still in an early stage, the potential for their use in synergy with HIFU treatment shows promising results.

3.
Int J Hyperthermia ; 38(1): 1023-1030, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34219596

RESUMO

OBJECTIVE: To compare the clinical outcomes of microwave ablation (MWA) and radiofrequency ablation (RFA) in the treatment of primary hyperparathyroidism (pHPT). METHOD: This retrospective study included 104 pHPT patients treated by MWA or RFA between January 2015 and March 2020 in four centers. The clinical outcomes including effectiveness and complications were compared between the two groups. Ablation cure was defined as the reestablishment of normal values of serum calcium and intact parathyroid hormone (iPTH) at least more than 6 months. Clinical cure was defined as the reestablishment of normal values of serum calcium and iPTH throughout the entire follow-up period. RESULTS: A total of 77 patients underwent MWA (mean age, 55.5 ± 16.4 years) and 27 underwent RFA (mean age, 58.9 ± 15.6 years). During the follow-up (median, 18.7 months in the MWA group; 12 months in the RFA group), no difference was observed between ablation cure rates (88.3% vs. 88.9%, p = 1.000), clinical cure rates (87.0% vs. 82.3%, p = .880), recurrent pHPT (5.2% vs. 3.7%, p = .447), persistent pHPT (11.7% vs. 11.1%, p = 1.000) and complication rate (9.1% vs. 3.7%, p = .677). A maximum diameter less than 0.7 cm was an independent prognostic factor of uncured pHPT in ablation (hazard ratio, 0.1; 95% confidence interval: 0.02, 0.54; p = .007). Major complication - voice change encountered in five patients (6.5%) in the MWA group and in one patient (3.7%) in the RFA group. CONCLUSION: Both RFA and MWA are safe and effective techniques for patients with pHPT, with comparable clinical outcomes.

4.
Phytother Res ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236105

RESUMO

Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1  day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.

5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 585-591, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34323035

RESUMO

Objective: To prepare and evaluate a new formulation of thermosensitive and ion-sensitive in situ gel for nasal administration, using the volatile oil of Bupleuri radix and baicalin, the effective component extracted from Scutellariae radix . Methods: Formulation of in situ nasal gel of Bupleuri radix volatile oil and baicalin was prepared by using poloxamer 407 and deacetylated gellan gum as the gel base, 10% pharmasolve and 2% polysorbate 80 as the solubilizer, and 0.8% triethanolamine as the pH regulator. The physical appearance, phase transition temperature, and baicalin release performance of the prepared gel were examined. The pharmacodynamic evaluation was done with the rat fever model developed with dry yeast and the mouse auricle swelling inflammation model. Results: The phase transition temperature of the gel was optimized to be 36 ℃. The release of baicalin from the gel showed obvious features of sustained release, which accorded well the zero-order kinetics equation. The results of experiments with the rat dry yeast fever model and the mouse xylene auricle swelling inflammation model showed that the gel had significant antipyretic and anti-inflammatory effects that were significantly better than those of the groups treated with the blank gel base and the Bupleuri radix and Scutellariae radix granule. Results from the cilia toxicity test showed that the gel did not have obvious toxic effect on toad palate mucosal cilia. Conclusion: The in situ nasal gel of Bupleuri radix volatile oil and baicalin prepared in the study had a rapid onset time, high efficiency, and prolonged release of active ingredients, thus showing promises for further applicational development.


Assuntos
Medicamentos de Ervas Chinesas , Óleos Voláteis , Administração Intranasal , Animais , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides , Camundongos , Óleos Voláteis/farmacologia , Ratos
6.
J Hazard Mater ; 417: 126009, 2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-34229376

RESUMO

In this study, various HCl-supported hydrochar made from root powder of long-root Eichhornia crassipes were applied to adsorb aqueous sulfachloropyridazine (SCP). Adsorption capacity (qe µg g-1) was positively correlated with combined severity-CS. With CS increasing, carbonization degree, hydrophobicity, porosity and isoelectric point of hydrochar increased, but content of polar functional groups decreased. Hydrophobic interaction was important for SCP adsorption. A 24 × 36 peak area table was generated from 24 FT-IR absorbance spectra computed by peak detection algorithm. Afterwards, correlation analysis between qe µg g-1 and FT-IR peak area were conducted, indicating that wavenumbers at 555.4, 1227.47, 1374.51, 1604.5, 2901.4/2919.2 and 3514.63 cm-1 were helpful for SCP adsorption. Further, multivariate linear regression analyses showed that aromatic skeleton and phenolic hydroxyl were the two biggest contributors. Electrostatic attraction did not exist during the SCP adsorption process. Under strong acid condition, protonated amino groups in cationic SCP acting as a hydrogen donator interacted with electron-rich functional groups onto hydrochar by Hydrogen interaction. Under weak acid condition, neutral SCP served as an π electron donor to bond with hydrochar by π-π electron donator-acceptor interaction. This work could guide the functional groups modification strategy of hydrochar to make better use of it in water purification field.


Assuntos
Sulfacloropiridazina , Poluentes Químicos da Água , Purificação da Água , Adsorção , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análise
7.
Clin Mol Hepatol ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34255961

RESUMO

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. The safety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval (CI): 82.5%-94.2%), 94.1% (95% CI: 87.8%-97.3%), and 100% (96 of 96 patients; 95% CI: 96.2%-100%). No patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥ 15 was associated with an improved MELD score of ≥ 3 (odds ratio (OR): 4.13, 95% CI: 1.16-14.71; p = 0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate (eGFR) declines than patients with CKD stage 2 (-0.42 mL/min/1.73m2/month; p = 0.01) or stage 3 (-0.56 mL/min/1.73m2/month; p < 0.001). Conclusions: SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.

8.
Toxicol Mech Methods ; : 1-40, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225584

RESUMO

Pulmonary fibrosis induced by silica dust is an irreversible, chronic, and fibroproliferative lung disease with no effective treatment at present. BMSCs-derived exosomes (BMSCs-Exo) possess similar functions to their parent cells. In this study, we investigated the therapeutic potential and underlying molecular mechanism for BMSCs-Exo in the treatment of silica-induced pulmonary fibrosis. The rat model of experimental silicosis pulmonary fibrosis was induced with 1.0mL of one-off infusing silica suspension using the non-exposed intratracheal instillation (50 mg/mL/rat). In vivo transplantation of BMSCs-Exo effectively alleviated silica-induced pulmonary fibrosis, including a reduction in collagen accumulation, inhibition of TGF-ß1, and decreased HYP content. Treatment of BMSCs-Exo increased the expression of epithelial marker proteins including E-cadherin (E-cad) and cytokeratin19 (CK19) and reduced the expression of fibrosis marker proteins including α-Smooth muscle actin (α-SMA) after exposure to silica suspension. Furthermore, we found that BMSCs-Exo inhibited the expression of Wnt/ß-catenin pathway components (P-GSK3ß, ß-catenin, Cyclin D1) in pulmonary fibrosis tissue. BMSCs-Exo is involved in the alleviation of silica-induced pulmonary fibrosis by reducing the level of profibrotic factor TGF-ß1 and inhibiting the progression of epithelial-mesenchymal transition (EMT). Additionally, attenuation of the Wnt/ß-catenin signaling pathway closely related to EMT may be one of the mechanisms involved in anti-fibrotic effects of exosomes.

9.
Phys Rev Lett ; 127(2): 020602, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34296924

RESUMO

We experimentally study the ergodic dynamics of a 1D array of 12 superconducting qubits with a transverse field, and identify the regimes of strong and weak thermalization with different initial states. We observe convergence of the local observable to its thermal expectation value in the strong-thermalizaion regime. For weak thermalization, the dynamics of local observable exhibits an oscillation around the thermal value, which can only be attained by the time average. We also demonstrate that the entanglement entropy and concurrence can characterize the regimes of strong and weak thermalization. Our work provides an essential step toward a generic understanding of thermalization in quantum systems.

10.
Cell Death Dis ; 12(8): 712, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34272359

RESUMO

Melatonin has been reported to have tumor-suppressive effects via comprehensive molecular mechanisms, and long non-coding RNAs (lncRNAs) may participate in this process. However, the mechanism by which melatonin affects the function of lncRNAs in triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is still unknown. Therefore, we aimed to investigate the differentially expressed mRNAs and lncRNAs in melatonin-treated TNBC cells and the interaction mechanisms. Microarray analyses were performed to identify differentially expressed mRNAs and lncRNAs in TNBC cell lines after melatonin treatment. To explore the functions and underlying mechanisms of the mRNAs and lncRNAs candidates, a series of in vitro experiments were conducted, including CCK-8, Transwell, colony formation, luciferase reporter gene, and RNA immunoprecipitation (RIP) assays, and mouse xenograft models were established. We found that after melatonin treatment, FUNDC1 and lnc049808 downregulated in TNBC cell lines. Knockdown of FUNDC1 and lnc049808 inhibited TNBC cell proliferation, invasion, and metastasis. Moreover, lnc049808 and FUNDC1 acted as competing endogenous RNAs (ceRNAs) for binding to miR-101. These findings indicated that melatonin inhibited TNBC progression through the lnc049808-FUNDC1 pathway and melatonin could be used as a potential therapeutic agent for TNBC.

11.
Sensors (Basel) ; 21(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201656

RESUMO

Computer numerical control (CNC) is a machine used in the manufacturing industry to produce components quickly for the engineering field or the desired shape. In the milling process carried out by CNC machines, sometimes vibrations occur that cause unwanted cracks or damage, which if left unchecked, will cause more severe damage. For this reason, this study describes how to monitor and analyze the sound produced by CNC during the milling process. This study uses six sound sample videos from YouTube, and there are two modes: (1) the operating mode is three different shapes with XY, XZ, and XYZ axes, and the second (2) is based on material differences. Namely, wood, Styrofoam, and plastic. The sound generated from all samples of the CNC milling processes will be detected using a sound detection program that has been designed in the LabVIEW using a simple microphone. The resulting sound frequency will be analyzed using the fast Fourier transform (FFT) process in spectral measurements, which will produce the amplitude and frequency of the detected sound in real time in the form of a graph. All frequency results that have been obtained from the sound detection monitoring tool in the CNC milling machine will be imported into the K-means clustering algorithm where the different frequencies between the resonant frequency and noise will be classified. Based on the experiments conducted, the sound detection program can detect sounds with a significant level of sensitivity.


Assuntos
Algoritmos , Som , Análise por Conglomerados , Análise de Fourier
12.
Pharmacol Res ; 171: 105755, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34229049

RESUMO

Diabetic retinopathy (DR) is one of the common complications in diabetic patients. Nowadays, VEGF pathway is subject to extensive research. However, about 27% of the patients have a poor visual outcome, with 50% still having edema after two years' treatment of diabetic macular edema (DME) with ranibizumab. Docosahexaenoic acid (DHA), the primary ω-3 long-chain polyunsaturated fatty acid (LC-PUFA), reduces abnormal neovascularization and alleviates neovascular eye diseases. A study reported that fish oil reduced the incidence of retinopathy of prematurity (ROP) by about 27.5% in preterm infants. Although ω-3 LC-PUFAs protects against pathological retinal neovascularization, the treatment effectiveness is low. It is interesting to investigate why DHA therapy fails in some patients. In human vitreous humor samples, we found that the ratio of DHA and DHA-derived metabolites to total fatty acids was higher in vitreous humor from DR patients than that from macular hole patients; however, the ratio of DHA metabolites to DHA and DHA-derived metabolites was lower in the diabetic vitreous humor. The expression of Mfsd2a, the LPC-DHA transporter, was reduced in the oxygen-induced retinopathy (OIR) model and streptozotocin (STZ) model. In vitro, Mfsd2a overexpression inhibited endothelial cell proliferation, migration and vesicular transcytosis. Moreover, Mfsd2a overexpression in combination with the DHA diet obviously reduced abnormal retinal neovascularization and vascular leakage, which is more effective than Mfsd2a overexpression alone. These results suggest that DHA therapy failure in some DR patients is linked to low expression of Mfsd2a, and the combination of Mfsd2a overexpression and DHA therapy may be an effective treatment.

13.
Sensors (Basel) ; 21(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34300564

RESUMO

Intra-abdominal pressure (IAP) is defined as the steady-state pressure within the abdominal cavity. Elevated IAP has been implicated in many medical complications. This article reviews the current state-of-the-art in innovative sensors for the measurement of IAP. A systematic review was conducted on studies on the development and application of IAP sensors. Publications from 2010 to 2021 were identified by performing structured searches in databases, review articles, and major textbooks. Sixteen studies were eligible for the final systematic review. Of the 16 articles that describe the measurement of IAP, there were 5 in vitro studies (31.3%), 7 in vivo studies (43.7%), and 4 human trials (25.0%). In addition, with the advancement of wireless communication technology, an increasing number of wireless sensing systems have been developed. Among the studies in this review, five presented wireless sensing systems (31.3%) to monitor IAP. In this systematic review, we present recent developments in different types of intra-abdominal pressure sensors and discuss their inherent advantages due to their small size, remote monitoring, and multiplexing.


Assuntos
Cavidade Abdominal , Humanos , Monitorização Fisiológica , Tecnologia sem Fio
14.
Ying Yong Sheng Tai Xue Bao ; 32(7): 2355-2362, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34313052

RESUMO

Stand density is a critical factor impacting the diversity of understory plants. We analyzed the diversity of understory plants and soil seed banks, as well as their relationship by setting up three planting densities in a Pinus massoniana plantation, including low density (1575 trees·hm-2, D1), medium (2474 trees·hm-2, D2), and high (3550 trees·hm-2, D3). It aimed to provide a scientific basis for the implementation of the multi-objective sustainable development of plantations. The results showed that there were 70 species of herbs and shrubs belonging to 42 families and 62 genera. D1 was dominated by heliophiles, whereas both the D2 and D3 were dominated by shade-tolerant species. The Margalef (M), Shannon (H), Simpson (D), Pielou (Jsw), and Altalo (Al) indices of the herbs and shrubs exhibited a downward trend with increasing stand den-sity. In the herb layer, D1 and D3 showed significant difference in H, D, Jsw and Al. There were significant differences of Jsw and Al in the shrub layer among the three stand densities, but no diffe-rence of H and D. H, D, Jsw and Al in the soil seed bank first decreased and then increased with increasing stand density, with species richness and diversity being the highest in D1. The similarity coefficient of Jaccard and Sorensen among different stand densities was low. In the herb layer, M was positively correlated with Jsw. The correlations between stand density and H, D, Jsw and Al were greater in the shrub layer than in the herb layer. There was significant negative correlation between stand density and Jsw both in the shrub and herb layers. The stand density of 1575 trees·hm-2 was comparatively beneficial for the development of understory, plant diversity, and sustainability of P. massoniana plantation.


Assuntos
Pinus , China , Humanos , Banco de Sementes , Solo , Árvores
15.
Sci Total Environ ; 794: 148744, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34323757

RESUMO

A total of 51 water and 43 sediment samples were collected from the locations surrounding the two e-waste dismantling zones in Taizhou, the Fengjiang resource recycling industrial zone (FJ, shut down in 2017) and the Taizhou resource recycling base (TZ, newly constructed in recent years). The concentrations of polybrominated diphenyl ethers (PBDEs) ranged from 1.7 to 44 ng/L in water and from not detected (nd) to 7100 ng/g in sediment. Novel brominated flame retardants (NBFRs) ranged from 0.29 to 1.6 ng/L in water, and from nd to 5300 ng/g in sediment. The levels of PBDEs and NBFRs in the water were comparable between FJ and TZ, while their concentrations were higher in the sediment from FJ than those from TZ. The levels of BDE-28, BDE-153, pentabromotoluene (PBT), pentabromobenzene (PBB), ∑PBDEs and ∑BFRs in the water from FJ or TZ were found to be significantly negatively associated with the distance from the zone center. However, in the sediments from FJ and TZ, the BFRs levels did not decrease from the center to the outer regions. BDE-209 and decabromodiphenyl ethane (DBDPE) were predominant in the sediments and the ratio of DBDPE/BDE-209 were as high as 5.6 (mean: 0.97). The mass burden of PBDEs, BDE-209, DBDPE, 1,2-bis(2,4,6-tribromophenoxy) ethane (BTBPE), and HBB in the riverine sediments in Luqiao District was 829, 787, 363, 85, and 61 kg, respectively. The ecological risk assessment revealed that BDE-99 posed an unacceptable risk to aquatic life at 86% of the locations. The hazard quotients for penta-BDE, BDE-209, and HBB exceeded one for 30%, 28%, and 2.3% of the sediment samples, respectively.

16.
Int J Mol Sci ; 22(14)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34299149

RESUMO

In the last decades, a kind of small non-coding RNA molecules, called as microRNAs, has been applied as negative regulators in various types of cancer treatment through down-regulation of their targets. More recent studies exert that microRNAs play a critical role in the EMT process of cancer, promoting or inhibiting EMT progression. Interestingly, accumulating evidence suggests that pure compounds from natural plants could modulate deregulated microRNAs to inhibit EMT, resulting in the inhibition of cancer development. This small essay is on the purpose of demonstrating the significance and function of microRNAs in the EMT process as oncogenes and tumor suppressor genes according to studies mainly conducted in the last four years, providing evidence of efficient target therapy. The review also summarizes the drug candidates with the ability to restrain EMT in cancer through microRNA regulation.


Assuntos
Antineoplásicos/farmacologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , MicroRNAs/antagonistas & inibidores , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Animais , Humanos , MicroRNAs/genética , Neoplasias/genética , Neoplasias/patologia , Transdução de Sinais
17.
Virus Genes ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312741

RESUMO

In this study, we developed a real-time quantitative polymerase chain reaction (qPCR) assay based on a dual-labeled hydrolysis probe to simultaneously detect both duck circovirus (DuCV) 1 and DuCV-2. The reproducibility, sensitivity and specificity of the primer set and probe were evaluated using other duck pathogens. The detection limit was 20 copies per µL. The intra-assay coefficients of variation (CVs) were ≤ 0.73% and the inter-assay CVs were ≤ 1.89%. No cross-reaction occurred with other duck pathogens. In addition, the qPCR assay was successfully applied to the simultaneous detection of DuCV-1 and DuCV-2 in clinical field samples. Therefore, this assay will be useful for laboratory diagnosis and epidemiological field studies of DuCV.

18.
J Immunother Cancer ; 9(7)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34326168

RESUMO

BACKGROUND: Tryptophan catabolites suppress immunity. Therefore, blocking tryptophan catabolism with indoleamine 2,3-dioxygenase (IDO) inhibitors is pursued as an anticancer strategy. METHODS: The intracellular level of tryptophan and kynurenine was detected by mass spectrum analysis. The effect of tryptophan and IDO inhibitors on cell surface programmed cell death protein 1 (PD-1) level were measured by flow cytometry. A set of biochemical analyses were used to figure out the underlying mechanism. In vitro co-culture system, syngeneic mouse models, immunofluorescent staining, and flow cytometry analysis were employed to investigate the role of tryptophan and IDO inhibitor in regulating the cytotoxicity of CD8+ T cells. RESULTS: Here, we reported that IDO inhibitors activated CD8+ T cells also by accumulating tryptophan that downregulated PD-1. Tryptophan and IDO inhibitors administration, both increased intracellular tryptophan, and tryptophanyl-tRNA synthetase (WARS) overexpression decreased Jurkat and mice CD8+ T cell surface PD-1. Mechanistically, WARS tryptophanylated lysine 1136 of and activated E3 ligase TRIP12 to degrade NFATc1, a PD-1 transcription activator. SIRT1 de-tryptophanylated TRIP12 and reversed the effects of tryptophan and WARS on PD-1. Tryptophan or IDO inhibitors potentiated CD8+ T cells to induce apoptosis of co-cultured cancer cells, increased cancer-infiltrating CD8+ T cells and slowed down tumor growth of lung cancer in mice. CONCLUSIONS: Our results revealed the immune-activating efficacy of tryptophan, and suggested tryptophan supplemental may benefit IDO inhibitors and PD-1 blockade during anticancer treatments.

19.
Respir Res ; 22(1): 203, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34243776

RESUMO

BACKGROUND: Thousands of Coronavirus Disease 2019 (COVID-19) patients have been discharged from hospitals Persistent follow-up studies are required to evaluate the prevalence of post-COVID-19 fibrosis. METHODS: This study involves 462 laboratory-confirmed patients with COVID-19 who were admitted to Shenzhen Third People's Hospital from January 11, 2020 to April 26, 2020. A total of 457 patients underwent thin-section chest CT scans during the hospitalization or after discharge to identify the pulmonary lesion. A total of 287 patients were followed up from 90 to 150 days after the onset of the disease, and lung function tests were conducted about three months after the onset. The risk factors affecting the persistence of pulmonary fibrosis were identified through regression analysis and the prediction model of the persistence of pulmonary fibrosis was established. RESULTS: Parenchymal bands, irregular interfaces, reticulation and traction bronchiectasis were the most common CT features in all COVID-19 patients. During the 0-30, 31-60, 61-90, 91-120 and > 120 days after onset, 86.87%, 74.40%, 79.56%, 68.12% and 62.03% patients developed with pulmonary fibrosis and 4.53%, 19.61%, 18.02%, 38.30% and 48.98% patients reversed pulmonary fibrosis, respectively. It was observed that Age, BMI, Fever, and Highest PCT were predictive factors for sustaining fibrosis even after 90 days from onset. A predictive model of the persistence with pulmonary fibrosis was developed based-on the Logistic Regression method with an accuracy, PPV, NPV, Sensitivity and Specificity of the model of 76%, 71%, 79%, 67%, and 82%, respectively. More than half of the COVID-19 patients revealed abnormal conditions in lung function after 90 days from onset, and the ratio of abnormal lung function did not differ on a statistically significant level between the fibrotic and non-fibrotic groups. CONCLUSIONS: Persistent pulmonary fibrosis was more likely to develop in patients with older age, higher BMI, severe/critical condition, fever, a longer viral clearance time, pre-existing disease and delayed hospitalization. Fibrosis developed in COVID-19 patients could be reversed in about a third of the patients after 120 days from onset. The pulmonary function of less than half of COVID-19 patients could turn to normal condition after three months from onset. An effective prediction model with an average area under the curve (AUC) of 0.84 was established to predict the persistence of pulmonary fibrosis in COVID-19 patients for early diagnosis.


Assuntos
COVID-19/virologia , Pulmão/virologia , Alta do Paciente , Fibrose Pulmonar/virologia , SARS-CoV-2/patogenicidade , Adolescente , Adulto , COVID-19/complicações , COVID-19/diagnóstico , China , Feminino , Interações Hospedeiro-Patógeno , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/fisiopatologia , Testes de Função Respiratória , Fatores de Tempo , Tomografia Computadorizada por Raios X , Adulto Jovem
20.
J Hazard Mater ; 420: 126490, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34252661

RESUMO

Recognition and excretion of metal ions play an important role in the diagnosis and treatment of various diseases and poisoning. Although copper (Cu) is a cofactor of many key enzymes in the human body, its accumulation caused by genetic ATP7B mutation or environmental pollution can lead to hepatotoxicity, renal failure, Wilson's disease, inflammation, and even Parkinson's disease (PD) and Alzheimer's disease (AD). Therefore, in this work, a difluoroboron curcumin derivative (DF-Cur) was used for the specific recognition of copper ions (Cu2+). DF-Cur could be further used to as a rapid diagnostic agent for the copper detection in cells and zebrafish at the nanomolar level. DF-Cur could significantly reduce the toxic damage caused by high Cu2+ dose. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis indicated that DF-Cur could promote the excretion of copper ions in the urine and bile and reduce the accumulation of copper ions in vivo. In addition, DF-Cur could selectively detect cholesterol in the blood and adipose tissue in vivo by fluorescent staining. These results demonstrated that this molecule might represent a new and promising diagnostic and therapeutic agent to combat diseases related to copper ions accumulation.

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