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1.
Pharmacol Ther ; : 107696, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33022301

RESUMO

Artemisinin and its derivatives are the most effective antimalarial drugs. Besides anti-malarial activity, artemisinin and its derivatives have displayed wide-spectrum bioactivities such as anti-parasite, anti-tumor, and anti-obesity effects. Obesity is an epidemic worldwide which is a big threat to human health, but there are only a few approved anti-obesity drugs in the world. Also, these drugs are efficient to limited patients partly because their safety and efficacy are questioned. Anti-inflammatory therapies may be valuable in obesity treatment since growing evidence shows chronic metabolic inflammation is implicated in metabolic disease pathogenesis. As artemisinin and its derivatives display effective anti-inflammatory and immunoregulatory properties with less toxicity, it provides an insight for novel drug development in obesity therapeutic strategies via immune-regulatory mechanisms. In this review, the potential of artemisinin and its derivatives to treat various metabolic diseases such as obesity and diabetes is discussed.

2.
Cell Mol Biol (Noisy-le-grand) ; 66(5): 73-79, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33040817

RESUMO

This study aimed to investigate the effect of dexmedetomidine combined with ropivacaine on inflammatory factors in children with axillary brachial plexus block. Ninety patients who underwent upper limb surgery in our hospital from January 2017 to December 2018 were enrolled and divided into groups A and B. Group A (n=40) was treated with ropivacaine as a local anesthetic, and group B (n= 50) was treated with dexmedetomidine combined with ropivacaine as a local anesthetic during surgery. Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Pain Assessment Scale was employed to evaluate the pain behavior of the children. Intravenous blood (3 ml) was taken before surgery (T0), 30 min (T1) and 3 hours after surgery (T2) respectively to detect serum TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6) and IL-1ß (interleukin-1ß) levels using ELISA. The adverse reactions in the two groups were observed, and the MAP (mean arterial pressure) and HR (heart rate) were compared before anesthesia, 30 min and 1 hour after block. The FLACC score of both groups showed a marked upward trend (p< 0.001), with that of group B being significantly lower than group A (p< 0.001). Group B presented a remarkably shorter onset time than group A, and the analgesic time was significantly longer (p< 0.001). The incidence of adverse reactions in group B was significantly lower than that in group A (p< 0.05). MAP and HR dropped significantly 30 min and 1 h after block (p< 0.05). MAP and HR were significantly lower in group B than those in group A 30 min and 60 min after block (p< 0.05). As to serum levels of TNF-α, IL-6, and IL-1ß, both groups presented notably increased ones after block (p< 0.05). The application of dexmedetomidine combined with ropivacaine in upper limb surgery has a faster onset time and longer duration than ropivacaine alone, which is of certain clinical effect.

3.
Food Chem ; 340: 128128, 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-33010646

RESUMO

In this research, a novel signal-on aptasensor for highly sensitive detection of zearalenone (ZEN) was reported based on target-induced amplification strategy. Specifically, chitosan functionalized acetylene black and multi-walled carbon nanotubes (CS@AB-MWCNTs) nanocomposite with large specific surface area and excellent conductivity was synthesized and served as the sensing platform. In addition, carboxylated graphene oxide-labeled ZEN binding aptamer (CGO-ZBA) would specifically recognized with ZEN to detach from the electrode, allowing the electrochemical signal of [Fe(CN)6]3-/4- increased more obviously. Under the optimal conditions, the proposed aptasensor exhibited exceptional detection performances for ZEN with a linear range from 10 fg mL-1 to 1 ng mL-1 and a low limit of detection of 3.64 fg mL-1. Given its great sensitivity, excellent selectivity, satisfactory stability and reproducibility, this method would provide a promising application for ZEN and other biomolecules by replacing the corresponding nucleicacidsequences.

4.
Sci Rep ; 10(1): 16119, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999343

RESUMO

Obesity is common comorbidity in patients with schizophrenia. Previous studies have reported that homocysteine (Hcy) is increased in schizophrenia. However, no study has reported the association between BMI and Hcy levels in schizophrenia. This cross-sectional naturalistic study aimed to evaluate the relationship between BMI, Hcy and clinical symptoms in Chinese Han patients with chronic schizophrenia. Clinical and anthropometric data as well as plasma Hcy level and glycolipid parameters were collected. Psychopathology was measured with the Positive and Negative Syndrome Scale (PANSS). Our results showed that compared with the low BMI group, the high BMI group had a higher PANSS general psychopathology subscore, higher levels of blood glucose, total cholesterol and high-density lipoprotein (HDL) cholesterol (all p < 0.05). Hcy levels were negatively associated with BMI in patients (p < 0.001). Hcy level, the PANSS general psychopathology subscale, total cholesterol and education (all p < 0.05) were the influencing factors of high BMI. Our study suggest that Hcy level may be associated with BMI in patients with schizophrenia. Moreover, patients with high BMI show more severe clinical symptoms and higher glucose and lipid levels.

6.
Mediators Inflamm ; 2020: 2960517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013197

RESUMO

Insulin resistance has been shown to be the common pathogenesis of many metabolic diseases. Metainflammation is one of the important characteristics of insulin resistance. Macrophage polarization mediates the production and development of metainflammation. Toll-like receptor 4 (TLR4) mediates macrophage activity and is probably the intersection of immunity and metabolism, but the detailed mechanism is probably not fully understood. Activated protein 1 (AP1) signaling pathway is very important in macrophage activation-mediated inflammation. However, it is unclear whether AP1 signaling pathway mediates metabolic inflammation in the liver. We aimed to investigate the effects of macrophage TLR4-AP1 signaling pathway on hepatocyte metabolic inflammation, insulin sensitivity, and lipid deposition, as well as to explore the potential of TLR4-AP1 as new intervention targets of insulin resistance and liver steatosis. TLR4 and AP1 were silenced in the RAW264.7 cells by lentiviral siRNA transfection. In vivo transduction of lentivirus was administered in mice fed with high-fat diet. Insulin sensitivity and inflammation were evaluated in the treated cells or animals. Our results indicated that TLR4/AP-1 siRNA transfection alleviated high-fat diet-induced systemic and hepatic inflammation, obesity, and insulin resistance in mice. Additionally, TLR4/AP-1 siRNA transfection mitigated palmitic acid- (PA-) induced inflammation in RAW264.7 cells and metabolic abnormalities in cocultured AML hepatocytes. Herein, we propose that TLR4-AP1 signaling pathway activation plays a crucial role in high fat- or PA-induced metabolic inflammation and insulin resistance in hepatocytes. Intervention of the TLR4 expression regulates macrophage polarization and metabolic inflammation and further alleviates insulin resistance and lipid deposition in hepatocytes.

7.
Medicine (Baltimore) ; 99(40): e22507, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019451

RESUMO

RATIONALE: In this report, a combination of platelet-rich fibrin (PRF) membrane and semi-open flap technique was used to improve soft tissue regeneration in immediate implant placement in the molar region. PRF, an autologous fibrin matrix, has been widely used for soft tissue wound healing and regeneration. Semi-open flap technique is beneficial to eliminating exudates and relieving the swelling after surgery. PATIENT CONCERNS: Case 1 was a 45-year-old female with a residual crown in the posterior maxillary region that desired a dental implant operation. Case 2 was a 24-year-old male with retained deciduous tooth that requested a restoration of his congenital absent tooth. DIAGNOSES: In case 1, the tooth 16 was diagnosed with a residual crown, while in case 2, a deciduous tooth 75 was a retained deciduous tooth and 35 was congenital absent. INTERVENTIONS: In both cases, immediate implant placement was installed and PRF membranes were made to improve soft tissue augmentation with semi-open flap technique. In case 1, the mixture of an organic bovine bone and blood was filled in the gap between the implant and the socket wall. Subsequently, 2 PRF membranes covered the open wound with semi-open flap. Similarly, in case 2, another 2 PRF membranes were used to improve the soft tissue regeneration, with the same semi-open flap technique as mentioned above. OUTCOMES: In both cases, successfully soft tissue regeneration was obviously observed without postoperative infection. LESSONS: Utilizing the PRF membrane combined with semi-open flap technique can achieve excellent soft tissue augmentation around immediate implant placement in the molar regions.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33051060

RESUMO

Ovarian cancer is a gynecological cancer that has the highest mortality rate and is often resistant to conventional treatments. Therefore, development of new therapies is essential. Metformin (MET), which is the priority drug for treatment of type 2 diabetes, has received increasing attention because of its anti-tumor effects. Here, we examined combined anti-tumor effects of MET and RG7388, the only MDM2 (mouse double minute 2 homolog) antagonist that has entered phase III clinical trials, on ovarian cancer cell lines. We examined effects on proliferation by Cell Counting Kit-8 (CCK-8) and colony formation assays, and effects on apoptosis by flow cytometric analysis and Hoechst staining. Western blotting was used to measure protein expression in cells and tissues treated with MET and/or RG7388. Flow cytometry was used to measure reactive oxygen species (ROS). We also examined the effects of MET and/or RG7388 on inhibition of A2780 cell growth in vivo. The combination of MET and RG7388 significantly increased growth inhibition, apoptosis, and ROS of A2780 and SKOV3 cells compared with either agent alone. Additionally, in vitro and in vivo results showed that MET and/or RG7388 inhibited the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and their combination had a stronger effect. Our findings suggest that the combination of MET and RG7388 enhances growth inhibition and apoptosis induction of ovarian cancer cells through the PI3K/AKT/mTOR pathway and accumulation of intracellular ROS.

9.
Braz J Med Biol Res ; 53(11): e10009, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32965322

RESUMO

The epidermis, the outermost layer of the skin, is the first barrier that comes into contact with the external environment. It plays an important role in resisting the invasion of harmful substances and microbial infections. The skin changes with age and external environmental factors. This study aimed to investigate epidermal stem cells during the process of aging. This study enrolled 9 volunteers with benign pigmented nevus for clinical dermatologic surgery. The phenotypes associated with skin aging changes such as skin wrinkles and elasticity of the unexposed/healthy parts near benign pigmented skin were measured, and epidermal stem cells from this region were isolated for transcriptome sequencing. The results showed that epidermal stem cells could be obtained by magnetic activated cell sorting (MACS) with high purity. Results of the transcriptome sequencing revealed that aquaporin (AQP)5 significantly decreased in the epidermal stem cells with age, and further functional experiments revealed that AQP5 could promote the proliferation and dedifferentiation of HaCaT, but did not influence cell apoptosis. In summary, AQP5 regulated the proliferation and differentiation of epidermal stem cells in skin aging, and it may play an important role in the balance of proliferation and differentiation. However, further studies are needed to determine the mechanism by which AQP5 regulates the proliferation and differentiation of epidermal skin cells in aging.

10.
Anticancer Drugs ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32932277

RESUMO

A growing number of evidence has revealed that aberrantly expressed long noncoding RNAs (lncRNAs) are involved in the development of a variety of malignancies, including colorectal cancer (CRC). However, the clinical relevance of most lncRNAs and their potential biological functions in CRC remains poorly understood. The aim of this study was to identify the key lncRNAs related to patient prognosis as well as their biological function and underlying mechanism in CRC. Therefore, five independent datasets containing CRC and normal tissue RNA sequencing, microarray data and the corresponding clinical data from The Cancer Genome Atlas and Gene Expression Omnibus were screened. Hundreds of significantly differentially expressed lncRNAs in CRC were determined, and Kaplan-Meier analyses revealed that some of these lncRNAs were related to the overall survival and progression-free survival of patients with CRC, such as RP11-108K3.2, FOXD3-AS1, H19 and AP001469.9. Among these dysregulated lncRNAs, LINC02163 and FEZF1-AS1 were significantly upregulated in CRC tissues, suggesting that they may have oncogenic roles in CRC. Furthermore, loss of function assays revealed that downregulation of LINC02163 and FEZF1-AS1 impaired CRC cell proliferation. In addition, RNA Immunoprecipitation and Chromatin Immunoprecipitation assays determined that FEZF1-AS1 regulates CRC cell growth via interacting with LSD1 and repressing KLF2 expression. Collectively, hundreds of dysregulated lncRNAs and their associated biological roles identified in this study may provide potentially useful biomarkers and therapeutic targets for CRC.

11.
Curr Med Res Opin ; : 1-7, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32945707

RESUMO

BACKGROUND: Since December 2019, the cumulative number of coronavirus disease 2019 (COVID-19) deaths worldwide has reached 1,013,100 and continues to increase as of writing. Of these deaths, more than 90% are people aged 60 and older. Therefore, there is a need for an easy-to-use clinically predictive tool for predicting mortality risk in older individuals with COVID-19. OBJECTIVE: To explore an easy-to-use clinically predictive tool that may be utilized in predicting mortality risk in older patients with COVID-19. METHODS: A retrospective analysis of 118 older patients with COVID-19 admitted to the Union Dongxihu Hospital, Huazhong University of Science and Technology, Wuhan, China from 12 January to 26 February 2020. The main results of epidemiological, demographic, clinical and laboratory tests on admission were collected and compared between dying and discharged patients. RESULTS: No difference in major symptoms was observed between dying and discharged patients. Among the results of laboratory tests, neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase, albumin, urea nitrogen and D-dimer (NLAUD) show greater differences and have better regression coefficients (ß) when using hierarchical comparisons in a multivariate logistic regression model. Predictors of mortality based on better regression coefficients (ß) included NLR (OR = 31.2, 95% CI 6.7-144.5, p < .0001), lactate dehydrogenase (OR = 73.4, 95% CI 11.8-456.8, p < .0001), albumin (OR < 0.1, 95% CI <0.1-0.2, p < .0001), urea nitrogen (OR = 12.0, 95% CI 3.0-48.4, p = .0005), and D-dimer (OR = 13.6, 95% CI 3.4-54.9, p = .0003). According to the above indicators, a predictive NLAUD score was calculated on the basis of a multivariate logistic regression model to predict mortality. This model showed a sensitivity of 0.889, specificity of 0.984 and a better predictive ability than CURB-65 (AUROC = 0.955 vs. 0.703, p < .001). Bootstrap validation generated the similar sensitivity and specificity. CONCLUSIONS: We designed an easy-to-use clinically predictive tool for early identification and stratified treatment of older patients with severe COVID-19.

12.
Pancreas ; 49(9): 1220-1224, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32898006

RESUMO

OBJECTIVES: Splanchnic venous thrombosis (SVT) is a relevant complication in patients with acute necrotizing pancreatitis. So far, no specific treatment for preventing development of SVT exists, and the effect of systemic anticoagulation (SAC) is unclear. METHODS: Patients with acute necrotizing pancreatitis admitted to our center within 7 days from onset of abdominal pain were screened. In the historic group, during which period, most patients received no SAC. Patients in the study group received SAC therapy considering the risk of deep vein thrombosis and SVT. The primary outcome measure was the incidence of SVT. RESULTS: Splenic vein was involved in 71% of all 84 SVT patients. Compared with the historic cohort, patients who received SAC experienced lower incidence of SVT (P < 0.001), especially for splenic venous thrombosis (P = 0.002). Patients in the study group also showed lower mortality (P = 0.04) and incidence of new-onset organ failure (P = 0.03). The incidence of bleeding shows no statistical significance between 2 groups. CONCLUSIONS: Application of SAC seems to reduce the incidence of SVT and improve clinical outcomes without increasing the risk of bleeding. Randomized clinical trials are needed to confirm our findings.

13.
Int J Clin Pract ; : e13704, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32931059

RESUMO

AIMS: The relationship between ferritin levels and survival in adult hemophagocytic lymphohistiocytosis (HLH) has been evaluated in previous studies. However, Admission-to-discharge percentage ferritin reduction (named as ferritin index) level in adult patients with HLH has never been evaluated to predict 6-month survival. METHODS: The demographic, laboratory and clinical information of 102 newly diagnosed adult HLH patients were collected. Regression analysis, receiver operating curve and Kaplan-Meier curves were analysed to explore the performance of ferritin levels. RESULTS: Ferritin index and discharge ferritin level were significantly different between survivour and non-survivour group (all P < .001). Ferritin index had the highest area under the curve (AUC) for predicting the survival (AUC = 0.802, P < .001) followed by discharge ferritin (AUC = 0.746, P < .001). Kaplan-Meier analysis showed a significant difference in survival according to optimum cutoff values of ferritin index ≥ 10.19% (P < .001) or discharge ferritin ≤ 1056.1 µg/L (P < .001). Multivariate analysis confirmed that ferritin index and discharge ferritin are independent predictors of 6-month survival (ferritin index: odds ratio (HR) 6.237, 95% confidence interval (CI) 2.075-18.774, P = .001; discharge ferritin: HR 6.024, 95% CI 1.894-19.231, P = .002). In addition, the combination of a ferritin index ≥ 10.19% and discharge ferritin ≤ 1056.1 µg/L had a significantly higher 6-month survival (P < .001). CONCLUSION: Ferritin index is a better predictor of 6-month survival than admission and discharges ferritin levels in adult patients with HLH.

14.
J Mol Cell Cardiol ; 149: 41-53, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32950539

RESUMO

OBJECTIVE: Reportedly, nestin was re-expressed in proliferative synthetic-type pulmonary artery smooth muscle cells (PASMCs) and obligatory for PASMC proliferation in pulmonary arterial hypertension (PAH). Accordingly, nestin is increased in pulmonary vascular lesions of congenital heart disease (CHD)-associated PAH patients. We tested the hypothesis whether nestin was re-expressed in proliferative synthetic-type PASMCs and associated with pulmonary vascular remodeling in CHD-PAH. MATERIALS AND METHODS: Nestin expression was tested using lung tissues from CHD-PAH patients and monocrotaline (MCT) plus aortocaval (AV) shunt-induced PAH rats, human PASMCs (HPASMCs), and pulmonary artery endothelial cells (PAECs) and PASMCs from MCT-AV-induced PAH rats. The role and possible mechanism of nestin on HPASMC proliferation, apoptosis, cell cycle and migration were investigated by assays of CCK-8, EdU, TUNEL, flow cytometry, transwell chamber and immunoblotting assays. RESULTS: Nestin was solely expressed in proliferative synthetic-type PASMCs, but rarely detected in PAECs. Nestin was barely detected in normal pulmonary arterioles and occlusive pulmonary vascular lesions. Its expression was robustly increased in developing pulmonary vasculature, but returned to normal levels at the late stage of pulmonary vascular remodeling in lung tissues from CHD-PAH patients and MCT-AV-induced PAH rats. Besides, nestin peaks were consistent with the histological features in lung tissues of MCT-AV-induced PAH rats. Moreover, nestin overexpression effectively promoted HPASMC phenotypic transformation, proliferation, apoptosis resistance and migration via enhancing Wnt/ß-catenin activation. CONCLUSIONS: These data indicated that nestin was re-expressed in proliferative synthetic-type PASMCs and might represent a potential marker of pulmonary vascular remodeling in CHD-PAH.

15.
Ann Noninvasive Electrocardiol ; : e12797, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32896950

RESUMO

In patients with preserved ejection fraction or right bundle branch block (RBBB) pattern requiring a high percentage of ventricular pacing, His-bundle pacing (HBP) might be an alternative to biventricular pacing, although the high threshold occasionally occurs. We provided a case of the intrinsic RBBB correction by capturing intra-Hisian left bundle branch (LBB) or distal His-bundle with different output settings. LBB pacing had the advantage of a much lower threshold while remained most synchrony as HBP. LBB pacing might be a promisingly safe and effective procedure for patients with high-grade atrioventricular (AV) block and RBBB pattern.

16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(4): 452-458, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895096

RESUMO

Objective To understand the family sex education for young children in rural areas of Sichuan province and analyze the influencing factors. Methods A multi-stage random sampling method was used to select 2246 parents of kindergarten children from rural areas in Sichuan province for a questionnaire-based survey.The Chi-square test and Logistic regression model were used for data analysis. Results It was found 1132(52.33%)parents had implemented family sex education for young children and 1031(47.67%)had not.Young children having asked sex-related questions(OR=1.536,95%CI=1.257-1.878),parents thinking that early childhood sex education is necessary(OR=3.691,95%CI=2.029-6.717),and parents having the intention to know early childhood sex education(OR=1.700,95%CI=1.274-2.269),and kindergarten having implemented early childhood sex education(OR=3.316,95%CI=2.515-4.372)were promoting factors for parents to conduct early childhood sex education,whereas a total annual household income at the middle level(OR=0.664,95%CI=0.456-0.968)was a hindering factor for parents to conduct early childhood sex education. Conclusions Parents of young children in rural areas of Sichuan province have poor awareness of sex education,and the proportion of parents who have never conducted sex education for children is high.The total annual income of the family,whether the children have asked about sex-related questions,parents' attitude towards early childhood sex education,and whether the kindergarten has conducted the early childhood sex education are important factors that influence the level of children's family sex education.


Assuntos
Educação Sexual , Criança , China , Humanos , Modelos Logísticos , Pais , Inquéritos e Questionários
17.
Virulence ; 11(1): 1250-1256, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32921249

RESUMO

The cause of some patients with negative RT-PCR results experienced turn-positive after treatment remains unclear. In addition, understanding the correlation between changes in clinical data in the course of COVID-19 and treatment outcomes is of great importance in determining the prognosis of COVID-19. To perform cause analysis of RT-PCR turn-positive and the effective screening factors related to treatment outcome in COVID-19. Clinical data, including clinical manifestations, laboratory tests, radiography results, treatment methods and outcomes, were retrospectively collected and analyzed from January to March 2020 in Renmin Hospitals of Wuhan University. 116 COVID-19 patients (40 in recurrent group, 29 in recovered group and 47 in unrecovered group) were recruited. In the recurrent group, white blood cell, Neutrophils, prothrombin time, activated partial thromboplastin time, CD3, CD4, CD8, ratio of CD4/CD8, IgG and C4 complement were of significant difference among the baseline, negative and turn-positive time points. CD19 and CT scan results were found notable difference between recurrent group and recovered group. Odds from CD3, CD4, CD8, CD19, IgM, C3 complement, C4 complement and CT scan results validated associations with clinical outcomes of COVID-19. The so-called recurrence in some COVID-19 patients may be due to the false-negative of nucleic acid test results from nasopharyngeal swabs. Levels of CD3, CD4, CD8, CD19, IgM, C3 complement, C4 complement and CT results were significantly correlated with the outcome of COVID-19. The cellular immunity test could be beneficial to further screen the reliability of RT-PCR test on the basis of CT images.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/epidemiologia , Reações Falso-Negativas , Feminino , Humanos , Imunidade Celular , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Virulência
18.
Molecules ; 25(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977419

RESUMO

Neuroinflammation is a feature common to neurodegenerative diseases, such as Parkinson's disease (PD), which might be responsive to therapeutic intervention. Rotenone has been widely used to establish PD models by inducing mitochondrial dysfunction and inflammation. Our previous studies have reported that pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor, could prevent mitochondrial dysfunction in rotenone induced PD models by regulating mitochondrial functions. In the present study, we aimed to investigate the effect of PQQ on neuroinflammation and the mechanism involved. BV2 microglia cells were pre-treated with PQQ followed by rotenone incubation. The data showed that PQQ did not affect the cell viability of BV2 cells treated with rotenone, while the conditioned medium (CM) of BV2 cells pre-treated with PQQ significantly increased cell viability of SH-SY5Y cells. In rotenone-treated BV2 cells, PQQ dose-dependently decreased lactate dehydrogenase (LDH) release and suppressed the up-regulation of pro-inflammation factors, such as interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) in the cultured media, as well as nitric oxide (NO) release induced by rotenone. PQQ pretreatment also increased the ratio of LC3-II/LC3-I and expression of Atg5 in BV2 cells stimulated with rotenone. Additionally, the autophagosome observed by transmission electron microscopy (TEM) and co-localization of mitochondria with lysosomes indicated that mitophagy was induced by PQQ in rotenone-injured BV2 cells, and the PINK1/parkin mediated mitophagy pathway was regulated by PQQ. Further, autophagy inhibitor, 3-methyladenine (3-MA), partially abolished the neuroprotective effect of PQQ and attenuated the inhibition of inflammation with PQQ pretreatment. Taken together, our data extend our understanding of the neuroprotective effect of PQQ against rotenone-induced injury and provide evidence that autophagy enhancement might be a novel therapeutic strategy for PD treatment.

19.
Environ Pollut ; 267: 115539, 2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32892021

RESUMO

Antibiotic pollution from family animal farms is often neglected, but the waste from these farms usually caused more harm to the surroundings because arbitrary discharge without effective disposal. The pollution status and ecological risks of 45 veterinary antibiotics on 33 family animal farms in Dali city, Erhai Lake basin of China, were firstly delivered. The results showed that antibiotic contamination was prevalent in different environmental mediums (feed, manure, wastewater and soil) on these family farms. Manure had highest antibiotic levels among all the environmental mediums. Tetracyclines (TCs) usually had higher concentrations (ND-404.95 mg/kg) than the other classes, among which chlorotetracycline (CTC) was the dominant type. Among different animal species, target 13 pig farms had the highest antibiotic concentrations, the most total types and unique types of antibiotics, which were followed by target 11 chicken farms then target 9 cattle farms. The antibiotic densities of animal waste were calculated by per animal, which showed that pig waste presented high density; and family chicken farms were characterized by quinolone antibiotics (QAs) and macrolide antibiotics (MAs) pollution. For the antibiotic ecological risks in effluent water, oxytetracycline (OTC), CTC, ofloxacin (OFL), enrofloxacin (ENR), ciprofloxacin (CIP) and sulfamethoxazole (SMX2) exhibited much more toxic effects on algae. OTC and doxycycline (DXC) posed high risk for invertebrate; while no antibiotic caused high ecological risk for fish. Some antibiotics were quantitatively detected in the soil but no antibiotic posed obvious ecological risks on soils. However, the interaction of synergistic or antagonistic effects between different antibiotics should be brought to the forefront. This study gave some information of antibiotic pollution on family livestock farms, which indicated that animal waste from family farms was indeed an important pollution source of antibiotics for the environment.

20.
Helicobacter ; : e12755, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914914

RESUMO

OBJECTIVE: This study aims to evaluate the efficacy and safety of three bismuth-based quadruple regimens for eradication of Helicobacter pylori (H pylori) infection in a large number of H pylori-positive patients with or without previous eradication therapy. METHODS: Consecutive adult patients with H pylori infection, regardless of previous eradication therapy, were eligible for the present study. Three bismuth-based quadruple regimens were selected according to the past history of antibiotics use: (A) esomeprazole, amoxicillin, clarithromycin, and colloidal bismuth tartrate; (B) esomeprazole, amoxicillin, furazolidone, and colloidal bismuth tartrate; and (C) esomeprazole, doxycycline, furazolidone, and colloidal bismuth tartrate. All patients received a 14-day course of treatment, and 13 C/14 C urea breath test was utilized at four weeks after the completion of treatment to determine the H pylori eradication. Then, the eradication rates were calculated in terms of intention-to-treat (ITT) and per-protocol (PP) analyses. Adverse events (AEs) were recorded during the treatment. RESULTS: Overall, 1,226 patients were recruited, and 331, 57, and 838 patients were allocated to receive regimens A, B, and C, respectively. The H pylori eradication rates were 84.0%, 82.5%, and 82.9% (ITT) and 94.6%, 92.2%, and 93.7% (PP), respectively, in regimens A, B, and C. However, there was no significant difference among these three regimens. The incidence of AEs was 4.6% for all patients during the study, that is, 3.3%, 10.5%, and 4.7% for regimens A, B, and C, respectively. All AEs were mild and recovered at the follow-up visit. CONCLUSION: All three bismuth-based quadruple regimens based on the previous antibiotic use can achieve satisfactory eradication rates for H pylori infection and are safe.

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