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1.
PLoS One ; 15(4): e0232092, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32352995

RESUMO

Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012-2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isolated viruses covering from seven provinces of China. Additionally, we compared with data from representative sequences of 21 strains covering seven more provinces in China and 32 international HAdV-7 strains obtained from GenBank database to determine the phylogenetic, sequence variations, and molecular evolution of HAdV-7. The results indicated that HAdV-7 infection occurred throughout the year, and a high proportion of severe cases (27 cases, 22.1%) exhibited infantile pneumonia. Moreover, phylogenetic analysis showed that all HAdV-7 strains could be divided into two major evolutionary branches, including subtype 1 and subtype 2, and subtype 3 was also formed according to analysis of the penton base gene. Subtypes 1 and 2 co-circulated in China before 2008, and HAdV-7 strains currently circulating in China belonged to subtype 2, which was also the predominant strain circulating worldwide in recent years. Further sequence variation analysis indicated that three genes of HAdV-7 were relatively stable across time and geographic space, particularly for viruses within subtypes, which shared almost the same variation sites. Owing to continuous outbreaks caused by HAdV-7, resulting in increased illness severity and fatality rates in China, the establishment of a national HAdV surveillance system is urgently needed for the development of effective preventive and infection-control interventions for adenovirus respiratory infections in China.

2.
J Mater Chem B ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32373898

RESUMO

Decellularized cartilage scaffold (DCS) is an emerging substitute for cartilage defect application. However, it is hard to preserve an intact structure of such scaffolds derived from terrestrial animals, because of their dense and compact constitution. In contrast, squid (Dosidicus gigas) cranial cartilage, which possesses a relatively loose structure, could be easily decellularized using mild conditions and it retains the original microstructures of extracellular matrix (ECM). Herein, decellularized squid cranial cartilage scaffold (DSCS) was fabricated successfully after substantially removing the cells, which contained abundant ECM components (proteoglycans and type II collagen). Microscopic structure results showed that the DSCS possesses a relatively smooth and dense surface with a favorable interconnected inner porous structure for cell growth. DSCS exhibited excellent biomechanics and hydrophilicity. In vitro experiments indicated that the scaffold extracts were not toxic to cells, and were amenable to chondrocyte migration. Meanwhile, chondrocytes seeded in DSCS could maintain a favorable viability and present a spreading morphology. Furthermore, the in vivo experiments revealed that both cell-free scaffold and cell-laden scaffold exert promotive effects for the regeneration of cartilage in a full-thickness rabbit cartilage defect model. Taken together, these results suggested that DSCS presents a novel and promising cell-free therapeutic choice for cartilage tissue engineering.

3.
Arthritis Rheumatol ; 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32362074

RESUMO

OBJECTIVE: This study was undertaken to uncover the pathophysiologic role of discoidin domain receptor 2 (DDR-2), a putative fibrillar collagen receptor, in inflammation promotion and joint destruction in rheumatoid arthritis (RA). METHODS: In synovial tissue from patients with RA and from mice with collagen antibody-induced arthritis (CAIA) (using Ddr2-/- and DBA/1 mice), gene and protein expression levels of DDR-2, interleukin-15 (IL-15), and Dkk-1 were measured by quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Gene knockdown of DDR2 in human RA fibroblast-like synoviocytes (FLS) was conducted via small interfering RNA. Interaction between the long noncoding RNA H19 and microRNA 103a (miR-103a) was assessed in RA FLS using RNA pulldown assays. Cellular localization of H19 was examined using fluorescence in situ hybridization assays. Chromatin immunoprecipitation and dual luciferase reporter assays were applied to verify H19 transcriptional and posttranscriptional regulation by miR-103a. RESULTS: DDR2 messenger RNA (mRNA) expression was significantly associated with the levels of IL-15 and Dkk-1 mRNA in the synovial tissue of RA patients (r2 = 0.2022-0.3293, all P < 0.05; n = 33) and with the serum levels of IL-15 and Dkk-1 in mice with CAIA (P < 0.05). In human RA FLS, activated DDR-2 induced the expression of H19 through c-Myc. Moreover, H19 directly interacted with and promoted the degradation of miR-103a. CONCLUSION: These results indicate a novel role for activated DDR-2 in RA FLS, showing that DDR-2 is responsible for regulating the expression of IL-15 and Dkk-1 in RA FLS and is involved in the promotion of inflammation and joint destruction during pathophysiologic development of RA. Moreover, DDR-2 inhibition, acting through the H19-miR-103a axis, leads to reductions in the inflammatory reaction and severity of joint destruction in mice with CAIA, suggesting that inhibition of DDR-2 may be a potential therapeutic strategy for RA.

4.
Vaccine ; 38(22): 3832-3838, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32280040

RESUMO

Measles incidence has decreased dramatically in China due to the implement of measles-containing vaccine (MCV). However, a measles epidemic caused resurgence recently, even among vaccinated individuals. To evaluate the effectiveness of current immunization programs and discuss initiatives for the next step in measles elimination in mainland China, the characteristics of 121,969 laboratory-confirmed measles cases reported in the measles surveillance system (MSS) during 2014-2018 were analyzed according to the vaccination status of the cases in this study. Children under 2 years of age without MCV vaccination (44,424, 36.42% of all cases) and adults over 20 years of age with an unknown vaccination history (37,564, 30.80% of all cases) accounted for the majority of measles cases from 2014 to 2018. 42,425 (34.78%) of the 77,384 cases with available vaccination information were categorized as programmatically preventable. 38,840 (91.55%) of the 42,425 cases were aged ≥8 months without the MCV vaccination history. 34,959 (28.66%) cases were categorized as programmatically non-preventable, of whom 22,611 (64.68%) were too young to receive their first MCV dose, 6857 (19.61%) received their first dose and were too young to receive their second dose, 5491 (15.71%) received at least two doses of MCV. 15,933 (13.06%) of the 121,969 cases had a history of MCV vaccination. Measles virus infection in cases with an MCV vaccination history mainly occurred within the first month after MCV vaccination, especially in those who received a one-dose measles vaccination. MCV vaccination could reduce the frequencies of clinical symptoms and complications of measles cases. Our study confirmed that the current measles immunization programs used in mainland China is effective in reducing the measles incidence in China. Unvaccinated infants/children aged 8-23 months and high risk susceptible adults over 20 years of age with unknown vaccination histories should be the focus groups of measles immunization activities in China in the future.

5.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(2): 139-144, 2020 Apr 01.
Artigo em Chinês | MEDLINE | ID: mdl-32314885

RESUMO

OBJECTIVE: This study aimed to observe the metastatic behavior of head and neck squamous cell carcinoma cells after knocking down heat shock protein (Hsp) 27. METHODS: The experiment was divided into three groups: the lentivirus vector plasmid of pLenti-shRNA-Hsp27 was transfected into UM-SCC-22B cells as experimental group (shHsp27 group), routine culture of UM-SCC-22B cells as blank control (ctrl group), UM-SCC-22B cells transfection of pLenti-shRNA-ctrl lentivirus vector as negative control (shctrl group). Through real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay to detect the mRNA expression of Hsp27 in three groups. MTS assay was performed to detect cell-proliferation changes, wounding healing assay was performed to detect cell-migration changes, and Matrigel Transwell invasion assay was performed to detect cell-invasion changes. RESULTS: The expression of Hsp27 in shHsp27 group decreased signifi-cantly; MTS assay showed that UM-SCC-22B before and after Hsp27 knockdown had similar proliferation rates after being cultured for 24 or 48 h. Compared with the ctrl group, the shHsp27 group decreased the metastatic behavior by 4.38-fold in migration and 2.03-fold in cell invasion. CONCLUSIONS: Stably transfected lentivirus vector plasmid of pLenti-shRNA-Hsp27 can efficiently decrease Hsp27 expression and reduce the metastasis ability of UM-SCC-22B.


Assuntos
Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas de Choque Térmico HSP27 , Humanos , RNA Interferente Pequeno , Transfecção
6.
Food Funct ; 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32347846

RESUMO

In this paper, glycyrrhizic acid (GZA) was extracted from the stem of licorice by enzymatic hydrolysis, separated and purified by silica gel column chromatography, its purity was determined by high performance liquid chromatography (HPLC), and the structure was identified by Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. The hypoglycemic activity of GZA was measured by α-glucosidase inhibition in vitro and the establishment of a T2DM diabetic mouse model in vivo. The experimental results showed that the extraction rate and purity of GZA were 92.4% and 93.53%, respectively, and the IR spectrum and NMR spectrum were consistent with the standard and literature, respectively. The IC50 value of GZA for α-glucosidase inhibition was 1.88 mmol L-1, which was close to the positive control (acarbose). In addition, GZA could reduce the fasting blood glucose of T2DM mice by increasing insulin sensitivity, increasing glucose tolerance, significantly decreasing serum triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) contents, and increasing high density lipoprotein cholesterol (HDL-C) content. At the same time, it could also repair damaged organs to some extent. Therefore, GZA has broad application prospects in the treatment of T2DM.

7.
J BUON ; 25(1): 308-313, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32277647

RESUMO

PURPOSE: Studies have shown that Phloretin exerts anticancer effects on several types of cancer cells. Nonetheless, the anticancer effects of Phloretin have not been fully explored against the human gastric cancer cells. Therefore, this study was undertaken to evaluate the anticancer effects of Phloretin against the human gastric cancer cells. METHODS: Cell proliferation was evaluated by WST-1 assay while cell cycle analysis was carried out by flow cytometry. The effects on cell migration and invasion were evaluated by wound healing assay and transwell assays, respectively. Electron microscopy and western blot methods were used to study effects on autophagy and ERK1/2/MAPK signalling pathway. RESULTS: The results showed that Phloretin inhibited the proliferation rate of the human SNU-1 gastric cancer cells and showed an IC50 of 18 µM. However, Phloretin showed very high IC50 (80 µM) against the normal GES-1 normal gastric cells. Electron microscopy showed that Phloretin triggered autophagy in the SNU-1 gastric cancer cells which was accompanied by enhancement in the expression of LC3B II and Beclin 1. Cell cycle analysis showed that Phloretin caused accumulation of the SNU-1 cells in the G0/G1 phase of the cell cycle triggering G0/G1 cell cycle arrest. The G0/G1 arrest of SNU-1 cells was also associated with depletion of cyclin D1 and D2 expression. Wound healing and transwell assays showed that Phloretin suppressed the migration of the SNU-1 gastric cancer cells, suggestive of the anti-metastatic potential of this molecule. Finally, this molecule also blocked the ERK1/2/MAPK signalling pathway in SNU-1 cells in a concentration-dependent manner. CONCLUSIONS: Phloretin may prove beneficial as a promising drug candidate for gastric cancer treatment provided further studies are carried out on it, especially toxicological studies.

8.
BMC Pulm Med ; 20(1): 94, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32303211

RESUMO

BACKGROUND: Malignant melanoma (MM) generally presents as a primary neoplasm of the skin, and most MM cases of the respiratory system are metastatic. Primary MM of the lung (PMML) is quite rare, and its diagnosis is relatively difficult. CASE PRESENTATION: We report the case of a 57-year-old male patient with PMML who denied any history of tumours. His initial complaint was frequent coughs with bloody sputum for 4 days. Chest radiography demonstrated a high-density shadow in the lower lobe of the right lung, which was suspected to be a large space-occupying lesion on subsequent computed tomography (CT) and to be a hypermetabolic tumour by positron emission tomography-CT. To confirm the diagnosis, exploratory surgery was performed. Finally, we confirmed the diagnosis of PMML. CONCLUSIONS: PMML is extremely rare and easily misdiagnosed as lung cancer. Because of its morphological and immunophenotypic variations, the diagnosis of PMML remains difficult. This case report discusses the diagnosis and case management of a patient while referring to the existing literature.

9.
Alzheimers Dement ; 16(5): 779-788, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32270572

RESUMO

INTRODUCTION: Metabolomics provide a promising tool to understand the pathogenesis and to identify novel biomarkers of dementia. This study aimed to determine circulating metabolites associated with incident dementia in a Chinese cohort, and whether a selected metabolite panel could predict dementia. METHODS: Thirty-eight metabolites in baseline serum were profiled by nuclear magnetic resonance in 1440 dementia-free participants followed 5 years in the Shanghai Aging Study. RESULTS: Higher serum levels of glutamine and O-acetyl-glycoproteins were associated with increased risk of dementia, whereas glutamate, tyrosine, acetate, glycine, and phenylalanine were negatively related to incident dementia. A panel of five metabolites selected by least absolute shrinkage and selection operator within cross-validation regression analysis could predict incident dementia with an area under the receiver-operating characteristic curve of 0.72. DISCUSSION: We identified seven candidate serum metabolic biomarkers for dementia. These findings and the underlying biological mechanisms need to be further replicated and elucidated in future studies.

10.
Biosci Rep ; 40(5)2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32319512

RESUMO

Precartilaginous stem cells (PCSCs) are adult stem cells that can initiate chondrocytes and bone development. In the present study, we explored whether miR-132/212 was involved in the proliferation of PCSCs via Hedgehog signaling pathway. PCSCs were isolated and purified with the fibroblast growth factor receptor-3 (FGFR-3) antibody. Cell viability, DNA synthesis and apoptosis were measured using MTT, BrdU and flow cytometric analysis. The mRNA and protein expression were detected by real-time PCR and Western blot, respectively. The target gene for miR-132/212 was validated by luciferase reporter assay. Results showed that transfection with miR-132/212 mimic significantly increased cell viability and DNA synthesis, and inhibited apoptosis of PCSCs. By contrast, miR-132/212 inhibitor could suppress growth and promote apoptosis of PCSCs. Luciferase reporter assays indicated that transfection of miR-132/212 led to a marked reduction of luciferase activity, but had no effect on PTCH1 3'-UTR mutated fragment, suggesting that Patched1 (PTCH1) is a target of miR-132/212. Furthermore, treatment with miR-132/212 mimics obviously increased the protein expression of Indian hedgehog (Ihh) and parathyroid hormone related protein (PTHrP), which was decreased after treatment with Hedgehog signaling inhibitor, cyclopamine. We also found that inhibition of Ihh/PTHrP signaling by cyclopamine significantly suppressed growth and DNA synthesis, and induced apoptosis in PCSCs. These findings demonstrate that miR-132/212 promotes growth and inhibits apoptosis in PCSCs by regulating PTCH1-mediated Ihh/PTHrP pathway, suggesting that miR-132/212 cluster might serve as a novel target for bone diseases.

11.
Int J Biol Macromol ; 155: 560-571, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32224177

RESUMO

GIBP, a homogeneous polysaccharide extracted from Glycyrrhiza inflata Batalin with a molecular weight 1.96 × 103 kDa, had a triple helix structure, smooth and sheet-like structure. Comprehensive analysis showed that the main chain of GIBP was composed of α-D-1,4 linked glucose, branch points were composed of α-D-1,3,6 and α-D-1,2,3,6 linked glucoses, and side chains were composed of α-D-1,3 and ß-D-1,6 linked galactose, ß-L-1,2 linked arabinose, α-D-1,3 and ß-D-1,3 mannose. The scavenging abilities of GIBP (3 mg/mL) against DPPH radical, OH radical, O2- radical and ABTS were 50.75 ± 0.13% and 52.32 ± 0.13, 25.84 ± 0.35% and 44.57 ± 0.15% and it also demonstrated an obvious dose-effect relationship. The inhibitory activity of α-glucosidase showed that the inhibitory effect of GIBP was enhanced with the increase of concentration. When the concentration reached 6 mg/mL, the inhibition rate of α-glucosidase activity reached 64.77%. And the ka, kd and KD were 6.472 × 104 1/Ms., 2.934 × 10-3 1/s and 4.534 × 10-8 M.

12.
J Infect ; 2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32283143

RESUMO

Lopinavir/ritonavir and arbidol have been previously used to treat acute respiratory syndrome- coronavirus 2 (SARS-CoV-2) replication in clinical practice; nevertheless, their effectiveness remains controversial. In this study, we evaluated the antiviral effects and safety of lopinavir/ritonavir and arbidol in patients with the 2019-nCoV disease (COVID-19). Fifty patients with laboratory-confirmed COVID-19 were divided into two groups: including lopinavir/ritonavir group (34 cases) and arbidol group (16 cases). Lopinavir/ritonavir group received 400 mg/100mg of Lopinavir/ritonavir, twice a day for a week, while the arbidol group was given 0.2 g arbidol, three times a day. Data from these patients were retrospectively analyzed. The cycle threshold values of open reading frame 1ab and nucleocapsid genes by RT-PCR assay were monitored during antiviral therapy. None of the patients developed severe pneumonia or ARDS. There was no difference in fever duration between the two groups (P=0.61). On day 14 after the admission, no viral load was detected in arbidol group, but the viral load was found in 15(44.1%) patients treated with lopinavir/ritonavir. Patients in the arbidol group had a shorter duration of positive RNA test compared to those in the lopinavir/ritonavir group (P<0.01). Moreover, no apparent side effects were found in both groups. In conclusion, our data indicate that arbidol monotherapy may be superior to lopinavir/ritonavir in treating COVID-19.

13.
Antimicrob Agents Chemother ; 64(6)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32253210

RESUMO

Linezolid is the first synthetic oxazolidone agent to treat infections caused by Gram-positive pathogens. Infected patients with liver dysfunction (LD) are more likely to suffer from adverse reactions, such as thrombocytopenia, when standard-dose linezolid is used than patients with LD who did not use linezolid. Currently, pharmacokinetics data of linezolid in patients with LD are limited. This study aimed to characterize pharmacokinetics parameters of linezolid in patients with LD, identify the factors influencing the pharmacokinetics, and propose an optimal dosage regimen. We conducted a prospective study and established a population pharmacokinetics model with the Phoenix NLME software. The final model was evaluated by goodness-of-fit plots, bootstrap analysis, and prediction corrected-visual predictive check. A total of 163 concentration samples from 45 patients with LD were adequately described by a one-compartment model with first-order elimination along with prothrombin activity (PTA) and creatinine clearance as significant covariates. Linezolid clearance (CL) was 2.68 liters/h (95% confidence interval [CI], 2.34 to 3.03 liters/h); the volume of distribution (V) was 58.34 liters (95% CI, 48.00 to 68.68 liters). Model-based simulation indicated that the conventional dose was at risk for overexposure in patients with LD or severe renal dysfunction; reduced dosage (300 mg/12 h) would be appropriate to achieve safe (minimum steady-state concentration [C min,ss] at 2 to 8 µg/ml) and effective targets (the ratio of area under the concentration-time curve from 0 to 24 h [AUC0-24] at steady state to MIC, 80 to 100). In addition, for patients with severe LD (PTA, ≤20%), the dosage (400 mg/24 h) was sufficient at an MIC of ≤2 µg/ml. This study recommended therapeutic drug monitoring for patients with LD. (This study has been registered in the Chinese Clinical Trial Registry under no. ChiCTR1900022118.).

14.
J Asian Nat Prod Res ; : 1-8, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32131631

RESUMO

Two new chlorophenolic glucosides curculigines P (1) and Q (2), together with seven known compounds (3-9), were isolated from the dried rhizomes of Curculigo orchioides. Their structures were determined by spectroscopic methods including 1 D, 2 D NMR and MS. All the isolated compounds were evaluated on 5α-reductase activity by a HaCaT-based bioassay. Compounds 1-9 showed varying degrees of inhibiting activity against 5α-reductase, while compound 1 indicated the most potent inhibitory effect.

15.
J Gene Med ; : e3183, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32159255

RESUMO

BACKGROUND: MiR-1249 was demonstrated to be dysregulated and related to prognosis in cancers. It has been reported to be significantly down-regulated in colon adenocarcinoma (COAD). The present study aimed to explore the clinical value and biological roles of miR-1249 in the progression of COAD. METHODS: miRWalk was applied to predict potential targets of miR-1249. We investigated the expression patterns of miR-1249 and its potential target Four-Jointed Box Kinase 1 (FJX1) in COAD samples from The Cancer Genome Atlas (TCGA) or ONCOMINE database. Kaplan-Meier with a log-rank test was used to reveal the relationship between overall survival (OS) and miR-1249/FJX1. The predictive ability of miR-1249/FJX1 was investigated using univariate and multivariate Cox regression models. CCK-8 and Transwell assays were performed to determine whether miR-1249 was connected with cell viability, migration and invasion. A luciferase reporter assay was applied to verify the association of miR-1249 and FJX1 as its predicted target gene. RESULTS: We predicted and confirmed FJX1 to be a target gene of miR-1249. MiR-1249 was down-regulated in COAD samples and cell lines. Univariate and multivariate analysis showed that the expression of FJX1 could be regarded as independent predictor for COAD. Moreover, miR-1249 and FJX1 were respectively the indicators of favorable and poor OS. MiR-1249 over-expression repressed cell growth, migration and invasion. Overexpression of FJX1 in cells treated with miR-1249 mimic abolished the inhibitory effect of miR-1249 on cell growth, migration and invasion. CONCLUSIONS: miR-1249 exerts a suppressive effect on cell proliferation, migration and invasion in COAD, which is possibly achieved via modulating FJX1.

16.
Epilepsy Behav ; 106: 107025, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32199345

RESUMO

OBJECTIVE: The aim of this study was to evaluate and compare the performance of the Chinese version of the Neurological Disorder Depression Inventory for Epilepsy (CNDDI-E) with that of the depression subscale of the Hospital Anxiety and Depression Scale (C-HADS-D) as screening tools for depression in the same patients with epilepsy (PWE). METHODS: A total of 213 consecutive PWE were evaluated. Receiver operating characteristic (ROC) analysis was performed using the C-NDDI-E and C-HADS-D as predictors and the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI) as the gold standard. RESULTS: The area under the curve (AUC) for the C-NDDI-E was 0.870, and the optimal cutoff score was >11 (sensitivity 85.71%, specificity 79.78%); for the C-HADS-D, the AUC was 0.804, and the optimal cutoff score was >5 (sensitivity 85.71%, specificity 62.36%). The AUC for the C-NDDI-E was larger than the AUC for the C-HADS-D, but the comparison of the AUCs revealed no significant differences (P = 0.1444). CONCLUSION: Our findings indicate that the C-NDDI-E and C-HADS-D have high validity and support the use of these screening tools for depression in PWE. Moreover, the C-NDDI-E is a better screening scale for diagnosing depression than the C-HADS-D according to the results of this study.

17.
Biochem Biophys Res Commun ; 525(3): 733-739, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32143825

RESUMO

Cigarette smoke is one of major risk factors in the pathogenesis of chronic obstructive pulmonary disease (COPD). It is generally believed that cigarette smoke induces mitochondrial damage in the alveolar epithelial cells to contribute to COPD. However, the exact molecular mechanism remains unknown for the mitochondrial damage. In this study, cigarette smoke extract (CSE) was found to induce the mitochondrial membrane permeability (MMP), which promoted proton leakage leading to the reduction in mitochondrial potential and ATP production. ANT in the mitochondrial inner membrane was activated by CSE for the alteration of MMP. The activation was observed without an alteration in the protein level of ANT. Inhibition of the ANT activity with ADP or bongkrekic acid prevented the MMP alteration and potential drop upon CSE exposure. The ANT activation was observed with a rise in ROS production, inhibition of the mitochondrial respiration, decrease in the complex III protein and rise in mitophagy activity. The results suggest that ANT may mediate the toxic effect of cigarette smoke on mitochondria and control of ANT activity is a potential strategy in intervention of the toxicity.

18.
Toxins (Basel) ; 12(3)2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32182799

RESUMO

Ribosome-inactivating proteins (RIPs) are N-glycosidases, which depurinate a specific adenine residue in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. This loop is important for anchoring elongation factor (EF-G for prokaryote or eEF2 for eukaryote) in mRNA translocation. Translation is inhibited after the attack. RIPs therefore may have been applied for anti-cancer, and anti-virus and other therapeutic applications. The main obstacles of treatment with RIPs include short plasma half-life, non-selective cytotoxicity and antigenicity. This review focuses on the strategies used to improve the pharmacological properties of RIPs on human immunodeficiency virus (HIV) and cancers. Coupling with polyethylene glycol (PEG) increases plasma time and reduces antigenicity. RIPs conjugated with antibodies to form immunotoxins increase the selective toxicity to target cells. The prospects for future development on the engineering of RIPs for improving their pharmacological properties are also discussed.

19.
Int J Infect Dis ; 94: 68-71, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32179140

RESUMO

OBJECTIVES: To compare the clinical characteristics and the dynamics of viral load between imported and non-imported patients with COVID-19. DESIGN AND METHODS: Data from 51 laboratory-confirmed patients were retrospectively analyzed. RESULTS: The incubation period in the tertiary group was longer than that in the imported and secondary groups (both p < 0.05). Fever was the most common symptom at the onset of illness (73.33%, 58.82%, and 68.42%, respectively), and half of the patients had a low-grade temperature (<38.0 °C) with a short duration of fever (<7 days). CT scans showed that most patients in the three groups had bilateral pneumonia (80.00%, 76.47%, and 73.68%, respectively). Ct values detected in the tertiary patients were similar to those for the imported and secondary groups at the time of admission (both p > 0.05). For the tertiary group, the viral load was undetectable in half of the patients (52.63%) on day 7, and in all patients on day 14. For one third of the patients in the imported and secondary groups, the viral load remained positive on day 14 after the admission. CONCLUSIONS: COVID-19 can present as pneumonia with a low onset of symptoms, and the infectivity of SARS-CoV2 may gradually decrease in tertiary patients.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Carga Viral , Adulto , Idoso , Infecções por Coronavirus/complicações , Feminino , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Estudos Retrospectivos , Testes Sorológicos
20.
Aging (Albany NY) ; 12(3): 2814-2824, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045885

RESUMO

Gait disturbance is considered to be a significant clinical manifestation of cerebral small vessel disease (CSVD). We aimed to investigate the association between different imaging markers of CSVD or total CSVD burden and gait disturbance in a community-dwelling population. In the cross-sectional Taizhou Imaging Study (TIS), 314 participants free of neurological disorders underwent MRI scanning and gait assessment with quantitative wearable devices as well as clinical rating scales. In linear regression, after adjustment for demographics and vascular risks, total CSVD burden was associated with prolonged 3-m walking (ß=0.118, P=0.035), shorter stride length (ß=-0.106, P=0.042), and poorer Timed-Up-and-Go (TUG) performance (ß=0.146, P=0.009). Lacunes were positively associated with 3-m walking (ß=0.118, P=0.037) and duration of TUG test (ß=0.112, P=0.047). White matter hyperintensities and cerebral microbleeds were associated with prolonged stride time (ß=0.134, P=0.024) and increased stance phase time percentage (ß=0.115, P=0.038), respectively. Logistic regression revealed that participants with high CSVD burden or more lacunes were more likely to have an impaired gait velocity and an impaired TUG test. These results suggest that total CSVD burden and CSVD imaging markers are associated with gait disturbance among community-dwelling elderly people. Different CSVD imaging markers may cause gait disturbance through different pathways.

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