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1.
Environ Sci Technol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917550

RESUMO

Isoprene (C5H8) is the main non-methane hydrocarbon emitted into the global atmosphere. Despite intense research, atmospheric transformations of isoprene leading to secondary organic aerosol (SOA) are still not fully understood, including its multiphase chemical reactions. Herein, we report on the detailed structural characterization of atmospherically-relevant isoprene-derived organosulfates (OSs) with molecular weights (MW) of 212 (C5H8SO7), which are abundantly present in both ambient fine aerosol (PM2.5) and laboratory-generated isoprene SOA. The results obtained from smog chamber-generated isoprene SOA and aqueous-phase laboratory experiments coupled to the S(IV)-autooxidation chemistry of isoprene, 3-methyl-2(5H)-furanone and 4-methyl-2(5H)-furanone, allowed us for the first time to fully elucidate the isomeric structures of the MW 212 OSs. By application of liquid chromatography interfaced to electrospray ionization high-resolution mass spectrometry (LC/ESI-HR-MS), we firmly confirmed six positional isomers of the MW 212 OSs in PM2.5 collected from different sites in Europe and the United States. Our results also show that despite low solubility of isoprene in water, aqueous-phase or multiphase chemistry can play an important role in the formation of OSs from isoprene. Possible formation mechanisms for the MW 212 OSs are also tentatively proposed.

2.
Health Qual Life Outcomes ; 18(1): 8, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910863

RESUMO

BACKGROUND: Acute leukemia (AL) not only impairs the quality of life (QOL) of patients, but also affects that of their family caregivers (FCs). Studies on QOL of AL patients and their FCs are limited. This study aimed to evaluate the QOL of AL patients and their FCs, and to explore the factors associated with QOL of patients and of FCs. METHODS: A multicenter cross-sectional study was conducted. The QOL of 196 patient-FC dyads was assessed. The Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) was used for patients, and the 36-item Short-Form Health Survey (SF-36) was used for FCs. Independent-samples t-tests or one-way analysis of variance were used to compare QOL subscale scores between groups with different sociodemographic/clinical characteristics. Multiple regression analysis was conducted to identify the factors associated with QOL of AL patients and their FCs. RESULTS: The total FACT-Leu score for AL patients was 76.80 ± 16.44, and the physical component summary (PCS) and mental component summary (MCS) scores for FCs were 64.67 ± 15.44 and 52.50 ± 13.49, respectively. All QOL subscales for patients (t = 12.96-34.73, p < 0.001) and FCs (t = 2.55-14.36, p < 0.05), except role emotional (t = - 0.01, p = 0.993), were lower than those reported in previous studies. Sex, employment, and chemotherapy were significantly associated with total FACT-Leu score in AL patients (p < 0.05). Age, sex, marital status, education, employment, and relationship to patients were significantly associated with SF-36 PCS or MCS (p < 0.05). CONCLUSIONS: AL patients and their FCs both have lower QOL than the population in previous studies. These findings suggest that not only AL patients' physical and mental health but also overall family QOL should be assessed. Interventions supporting patient-FC dyads should be developed to improve their QOL.

3.
Int J Antimicrob Agents ; : 105889, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31923573

RESUMO

Colistin is the last resort against infections caused by multidrug-resistance Gram-negative bacteria (MDR-GNB). Nonetheless, different risk of colistin-associated acute kidney injury (CA-AKI) has been demonstrated without affecting the mortality. The association and its importance had been questioned. To assess the impact of this adverse effect, we conducted a meta-analysis comparing colistin to other antibiotics in treating MDR-GNB infections. Electronic databases of PubMed, Embase and Cochrane library were searched up to Dec 31, 2018 for all cohort studies and randomized controlled trials (RCTs) with two or more arms containing colistin-based antibiotic treatments. Primary endpoint was the incidence of AKI. Secondary endpoint was 30-day all-cause-mortality. A total of 34 studies, including 26 colistin-based therapy versus other antibiotics and 9 colistin monotherapy versus combination therapy, were included. The incidence of CA-AKI was 32.3%. Colistin was associated with 82% higher incidence of AKI than other antibiotics (Odd ratio (OR) = 1.82; 95% confidence interval (CI) 1.13-2.92; p = 0.01). Most of the AKI events were usually mild and reversible without higher mortality rate, nor higher rate of renal replacement therapy. Only 1.0% patients need renal replacement therapy for more than 4 weeks. When compared to monotherapy, the combination therapy was associated with a significant lower incidence of AKI (OR = 1.46; 95% CI 1.10-1.94; p = 0.009), particularly in combination with carbapenem (OR = 1.97; 95% CI 1.30-2.99; p = 0.001). To sum up, CA-AKI might not be an important limit for colistin in MDR-GNB therapy.

4.
Exp Cell Res ; : 111815, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31911152

RESUMO

Extracellular vesicular long noncoding RNAs (lncRNAs) to influence recipient cells is emerging as a novel mechanism for disease progression. TC0101441 is a newly identified metastasis-related lncRNA involved in cancer. Since endometriosis exhibits prometastasis behavior similar to those observed in cancer, we aimed to investigate whether TC0101441 is involved in endometriosis and, if so, whether extracellular vesicular TC0101441 contributes to the migration/invasion of endometriotic cyst stromal cells (ECSCs). Clinically, we found that TC0101441 was highly expressed in ectopic endometria than in the eutopic and normal endometria. Serum extracellular vesicular TC0101441 levels were substantially increased in patients at stage III/IV endometriosis in comparison with stage I/II endometriosis and controls. In vitro, using TC0101441-high-expression ECSCs (ECSCs-H) as extracellular vesicles (EVs)-generating cells and TC0101441-low-expression ECSCs (ECSCs-L) as recipient cells, we observed that the PKH67-labeled ECSCs-H-derived EVs were effectively internalized by ECSCs-L. ECSCs-H-derived EVs shuttling TC0101441 were transferred to ECSCs-L, modulating their migratory/invasive abilities partially by regulating certain metastasis-related proteins, which eventually facilitated endometriosis migration/invasion. This study elucidates a potential crosstalk between ECSCs via EVs in endometriotic milieus, suggests a novel mechanism for endometriosis migration/invasion from the perspective of the "extracellular vesicular transfer of lncRNAs" and highlights the potential of circulating extracellular vesicular TC0101441 as a biomarker for endometriosis.

5.
Sci Transl Med ; 12(525)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915304

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is a major health problem without effective therapies. This study assessed the effects of histone deacetylase (HDAC) inhibition on cardiopulmonary structure, function, and metabolism in a large mammalian model of pressure overload recapitulating features of diastolic dysfunction common to human HFpEF. Male domestic short-hair felines (n = 31, aged 2 months) underwent a sham procedure (n = 10) or loose aortic banding (n = 21), resulting in slow-progressive pressure overload. Two months after banding, animals were treated daily with suberoylanilide hydroxamic acid (b + SAHA, 10 mg/kg, n = 8), a Food and Drug Administration-approved pan-HDAC inhibitor, or vehicle (b + veh, n = 8) for 2 months. Echocardiography at 4 months after banding revealed that b + SAHA animals had significantly reduced left ventricular hypertrophy (LVH) (P < 0.0001) and left atrium size (P < 0.0001) versus b + veh animals. Left ventricular (LV) end-diastolic pressure and mean pulmonary arterial pressure were significantly reduced in b + SAHA (P < 0.01) versus b + veh. SAHA increased myofibril relaxation ex vivo, which correlated with in vivo improvements of LV relaxation. Furthermore, SAHA treatment preserved lung structure, compliance, blood oxygenation, and reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar capillary stress failure. Acetylation proteomics revealed that SAHA altered lysine acetylation of mitochondrial metabolic enzymes. These results suggest that acetylation defects in hypertrophic stress can be reversed by HDAC inhibitors, with implications for improving cardiac structure and function in patients.

6.
Am J Ophthalmol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31926161

RESUMO

PURPOSE: The goal of this study was to determine the volumetric vessel density (VVD) in the intraretinal layers, and its relations with visual function and disability in patients with multiple sclerosis (MS). DESIGN: Cross-sectional study METHODS: Eighty patients with relapsing-remitting MS (RRMS) and 99 age- and gender-matched healthy controls (HC) were recruited. The retinal microvascular network in the macular area was imaged using optical coherence tomography angiography in 123 eyes without a history of optic neuritis (MSNON) and 36 eyes with a history of ON (MSON). The VVD was calculated as the vessel densities in the retinal vascular network (RVN), superficial vascular plexus (SVP) or deep vascular plexus (DVP) of an annulus (0.6 - 2.5 mm diameter), divided by the corresponding tissue volume of the intraretinal layers respectively. RESULTS: The VVD of RVN and DVP in MSNON were significantly higher than in HC (P < .05). The VVD of RVN, SVP, and DVP in MSON were significantly higher than in MSNON and HC (P < .05). The VVD in both RVN and SVP were positively related to EDSS and disease duration, but negatively related to low contrast letter acuity (P < .05). The VVD measurements were also negatively and strongly related to the corresponding tissue volumes (P < .05). CONCLUSIONS: This is the first study to reveal increased retinal VVD in patients with RRMS. The measurements of VVD in the RVN and SVP are related to disability and visual function, which may be developed as image markers for tracking disease progression.

7.
Ultrasonics ; 101: 106001, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31505328

RESUMO

Ultrasound is the first-line tool for screening hepatic steatosis. Statistical distributions can be used to model the backscattered signals for liver characterization. The Nakagami distribution is the most frequently adopted model; however, the homodyned K (HK) distribution has received attention due to its link to physical meaning and improved parameter estimation through X- and U-statistics (termed "XU"). To assess hepatic steatosis, we proposed HK parametric imaging based on the α parameter (a measure of the number of scatterers per resolution cell) calculated using the XU estimator. Using a commercial system equipped with a 7-MHz linear array transducer, phantom experiments were performed to suggest an appropriate window size for α imaging using the sliding window technique, which was further applied to measuring the livers of rats (n = 66) with hepatic steatosis induced by feeding the rats a methionine- and choline-deficient diet. The relationships between the α parameter, the stage of hepatic steatosis, and histological features were verified by the correlation coefficient r, one-way analysis of variance, and regression analysis. The phantom results showed that the window side length corresponding to five times the pulse length supported a reliable α imaging. The α parameter showed a promising performance for grading hepatic steatosis (p < 0.05; r2 = 0.68). Compared with conventional Nakagami imaging, α parametric imaging provided significant information associated with fat droplet size (p < 0.05; r2 = 0.53), enabling further analysis and evaluation of severe hepatic steatosis.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Ultrassonografia/métodos , Animais , Modelos Animais de Doenças , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Imagens de Fantasmas , Ratos , Ratos Wistar
8.
Plast Reconstr Surg ; 145(1): 42e-50e, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31881603

RESUMO

BACKGROUND: With an increase in recent years in the number of people receiving cosmetic facial injection treatments of hyaluronic acid, the incidence of hyaluronic acid embolism has also increased commensurately. Hyaluronic acid embolism leads to serious complications, including blindness, eye and eyelid movement disorders, skin necrosis, and cerebral embolism. However, there is a lack of robust clinical evidence regarding the benefits of treatment for hyaluronic acid embolism by intraarterial thrombolysis therapy. METHODS: This study included 24 patients with a decrease in visual acuity and other complications induced by facial hyaluronic acid injection. Patients underwent emergency intraarterial thrombolysis therapy by injection of hyaluronidase (500 to 1500 units) alone or hyaluronidase (750 to 1500 units) combined with urokinase (100,000 to 250,000 units), followed in both cases by a general symptomatic treatment and nutritional therapy. RESULTS: Ten (42 percent) of 24 patients ultimately had improvements to visual acuity, even when the clinical application of the thrombolytic treatments had passed the recommended window for optimal treatment. In all cases, patients' facial skin necrosis was restored to nearly normal appearance. In addition, the authors found that hyaluronidase combined with urokinase was a more effective therapy than hyaluronidase alone. CONCLUSIONS: The authors' results indicate that intraarterial thrombolysis therapy is beneficial to patients suffering from blindness induced by hyaluronic acid embolism. The therapy was shown to be worthy of clinical application because it alleviated the impairment to patients' vision and was also beneficial in the recovery from other serious complications, including eye movement disorder, eye edema, headaches, and skin necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

9.
Eur J Pharmacol ; 868: 172881, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31866405

RESUMO

Psoriasis is a chronic, inflammatory skin disease with high incidence and high rates of relapse, for which no satisfactory treatments are currently available. Yes-associated protein (YAP) is highly expressed in psoriasis and may regulate the proliferation and apoptosis of keratinocytes. Danshen is a traditional Chinese medicine, commonly used in the treatment of psoriasis. Danshensu is the most abundant water-soluble component of Danshen, but its therapeutic mechanism is still unclear. In this study, MTT was used to detect the effects of different danshensu concentrations (0.125, 0.25, 0.5 mmol/l) on the proliferation of an M5-based psoriasis cell model. The effects of danshensu on cell cycle and apoptosis were detected by flow cytometry. Cyclins and apoptosis-related proteins were evaluated by Western blot. Danshensu (20, 40, 80 mg/kg/day) was administered intraperitoneally to the imiquimod (IMQ) psoriasis mouse model. After 7 days, the expression of YAP in the lesions was detected by immunohistochemistry and Western blot. We found that danshensu reduced the expression of YAP in the M5 psoriasis cell model, inhibited cell proliferation, induced cell cycle arrest in G0/G1 phase, and promoted cell apoptosis. All these effects were partly reverted by YAP overexpression. The skin lesions of IMQ mice were thinned and the scales reduced after intragastric administration of danshensu, which also resulted in dose-dependent inhibition of YAP expression. We concluded that danshensu prevents abnormal epidermis proliferation in psoriasis possibly by modulating YAP expression. Our work can provide a theoretical basis for the clinical application of Danshen in the treatment of psoriasis.

10.
J Mol Cell Cardiol ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31836543

RESUMO

Succinylation is a post-translational modification of protein lysine residues with succinyl groups derived from succinyl CoA. Succinylation is considered a significant post-translational modification with the potential to impact protein function which is highly conserved across numerous species. The role of succinylation in the heart, especially in heart failure and myofibril mechanics, remains largely unexplored. Mechanical parameters were measured in myofibrils isolated from failing hearts of ischemic cardiomyopathy patients and non-failing donor controls. We employed mass spectrometry to quantify differential protein expression in myofibrils from failing ischemic cardiomyopathy hearts compared to non-failing hearts. In addition, we combined peptide enrichment by immunoprecipitation with liquid chromatography tandem mass spectrometry to quantitatively analyze succinylated lysine residues in these myofibrils. Several key parameters of sarcomeric mechanical interactions were altered in myofibrils isolated from failing ischemic cardiomyopathy hearts, including lower resting tension and a faster rate of activation. Of the 100 differentially expressed proteins, 46 showed increased expression in ischemic heart failure, while 54 demonstrated decreased expression in ischemic heart failure. Our quantitative succinylome analysis identified a total of 572 unique succinylated lysine sites located on 181 proteins, with 307 significantly changed succinylation events. We found that 297 succinyl-Lys demonstrated decreased succinylation on 104 proteins, while 10 residues demonstrated increased succinylation on 4 proteins. Investigating succinyl CoA generation, enzyme activity assays demonstrated that α-ketoglutarate dehydrogenase and succinate dehydrogenase activities were significantly decreased in ischemic heart failure. An activity assay for succinyl CoA synthetase demonstrated a significant increase in ischemic heart failure. Taken together, our findings support the hypothesis that succinyl CoA production is decreased and succinyl CoA turnover is increased in ischemic heart failure, potentially resulting in an overall decrease in the mitochondrial succinyl CoA pool, which may contribute to decreased myofibril protein succinylation in heart failure.

11.
Ther Adv Med Oncol ; 11: 1758835919889002, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839809

RESUMO

Background: Stereotactic ablative radiotherapy (SABR) can deliver tumoricidal doses and achieve long-term control in early hepatocellular carcinoma (HCC). However, limited studies have investigated the safety and effectiveness of SABR in patients with advanced diseases that is unsuitable for transarterial chemoembolization (TACE). Methods: In this observational study, we reviewed the medical records of patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease treated with linear accelerator-based SABR between 2008 and 2016. Their tumors were either refractory to TACE or TACE was contraindicated. Overall survival (OS), in-field progression-free survival (IFPFS), and out-field progression-free survival were calculated using Kaplan-Meier analysis. The Cox regression model was used to examine the effects of variables. Treatment-related toxicities were scored according to the Common Terminology Criteria for Adverse Events (version 4.03) and whether patients developed radiation-induced liver disease (RILD) after SABR. Results: This study included 32 patients. The mean maximal tumor diameter and tumor volumes were 4.7 cm and 135.9 ml, respectively. Patients received linear accelerator-based SABR with a median prescribed dose of 48 Gy (30-60 Gy) in three to six fractions. Based on the assessment of treatment response by using the Response Evaluation Criteria in Solid Tumors (version 1.1), 19% of patients achieved a complete response and 53% achieved a partial response. After a median follow-up of 18.1 months (4.0-65.9 months), 10, 19, and 9 patients experienced in-field failure, out-field hepatic recurrence, and extrahepatic metastases, respectively. The estimated 2-year OS and IFPFS rates were 54.4% and 62.7%, respectively. In a multivariate analysis, a pretreatment Cancer of the Liver Italian Program (CLIP) score of ⩾2 (p = 0.01) was a prognostic factor for shorter OS, and a biologically effective dose (BED) of < 85 Gy10 (p = 0.011) and a Child-Pugh score of ⩾6 (p = 0.014) were prognostic factors for inferior IFPFS. In this study five and eight patients developed classic and nonclassic RILD, respectively. Conclusions: SABR can serve as a salvage treatment for patients with HCC with BCLC stage C disease unsuitable for TACE, in particular, in those with a baseline CLIP score of ⩽1. A BED10 of ⩾85 Gy is an appropriate prescribed dose for tumor control. Because out-field relapse is the major cause of treatment failure, SABR in combination with novel systemic modalities should be investigated in future studies.

12.
J Exp Clin Cancer Res ; 38(1): 483, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805977

RESUMO

BACKGROUND: The dysfunction of type I interferon (IFN) signaling is an important mechanism of immune escape and metastasis in tumors. Increased NOS1 expression has been detected in melanoma, which correlated with dysfunctional IFN signaling and poor response to immunotherapy, but the specific mechanism has not been determined. In this study, we investigated the regulation of NOS1 on the interferon response and clarified the relevant molecular mechanisms. METHODS: After stable transfection of A375 cells with NOS1 expression plasmids, the transcription and expression of IFNα-stimulated genes (ISGs) were assessed using pISRE luciferase reporter gene analysis, RT-PCR, and western blotting, respectively. The effect of NOS1 on lung metastasis was assessed in melanoma mouse models. A biotin-switch assay was performed to detect the S-nitrosylation of HDAC2 by NOS1. ChIP-qPCR was conducted to measure the binding of HDAC2, H4K16ac, H4K5ac, H3ac, and RNA polymerase II in the promoters of ISGs after IFNα stimulation. This effect was further evaluated by altering the expression level of HDAC2 or by transfecting the HDAC2-C262A/C274A site mutant plasmids into cells. The coimmunoprecipitation assay was performed to detect the interaction of HDAC2 with STAT1 and STAT2. Loss-of-function and gain-of-function approaches were used to examine the effect of HDAC2-C262A/C274A on lung metastasis. Tumor infiltrating lymphocytes were analyzed by flow cytometry. RESULTS: HDAC2 is recruited to the promoter of ISGs and deacetylates H4K16 for the optimal expression of ISGs in response to IFNα treatment. Overexpression of NOS1 in melanoma cells decreases IFNα-responsiveness and induces the S-nitrosylation of HDAC2-C262/C274. This modification decreases the binding of HDAC2 with STAT1, thereby reducing the recruitment of HDAC2 to the ISG promoter and the deacetylation of H4K16. Moreover, expression of a mutant form of HDAC2, which cannot be nitrosylated, reverses the inhibition of ISG expression by NOS1 in vitro and decreases NOS1-induced lung metastasis and inhibition of tumor infiltrating lymphocytes in a melanoma mouse model. CONCLUSIONS: This study provides evidence that NOS1 induces dysfunctional IFN signaling to promote lung metastasis in melanoma, highlighting NOS1-induced S-nitrosylation of HDAC2 in the regulation of IFN signaling via histone modification.

13.
Surg Endosc ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792690

RESUMO

BACKGROUND: The feasibility of endoscopic dissection for gastric gastrointestinal stromal tumor (gGIST) between 2 and 5 cm in size has been demonstrated. However, its impact on short-term and long-term outcomes, compared with laparoscopic resection, is unknown. The purpose of this study was to compare short-term and long-term outcomes between laparoscopic resection and endoscopic dissection for 2-5-cm gGIST. METHODS: A case-matched study was performed using the propensity score. To overcome selection bias, we performed a 1:1 match using six covariates, including age, sex, BMI, ASA score, tumor size, and tumor location. Short-term and long-term outcomes between laparoscopic resection and endoscopic dissection were compared. RESULTS: A total of 210 patients with 2-5-cm gGIST were enrolled between 2006 and 2017 in our gastrointestinal center. According to the intention-to-treat approach, 165 patients underwent laparoscopic resection, and 45 patients underwent endoscopic dissection. After the propensity score, 45 pairs were balanced and analyzed. There was no significant difference in the baseline characteristics between the laparoscopic and endoscopic groups after matching. The rate of complications was significantly higher in the endoscopic group compared with the laparoscopic group (P < 0.001). Perforations occurred in 16 patients in the endoscopic group (16/45, 35.6%). The postoperative hospital stay was significantly longer in the endoscopic group compared with the laparoscopic group (P < 0.001). There was no significant difference between the two groups in disease-free survival or overall survival. CONCLUSION: Laparoscopic resection is better than endoscopic dissection for 2-5-cm gGIST because of the lower complication rate and shorter hospital stay.

14.
Sci Total Environ ; : 135732, 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31818575

RESUMO

In this study, we assessed the toxicological potencies of particulate matter (PM) emissions from a modern vehicle equipped with a gasoline direct injection (GDI) engine when operated on eight different fuels with varying aromatic hydrocarbon and ethanol contents. Testing was conducted over the LA92 driving cycle using a chassis dynamometer with a constant volume sampling system, where particles were collected onto Teflon filters. The extracted PM constituents were analyzed for their oxidative potential using the dithiothreitol (DTT) chemical assay and exposure-induced gene expression in human airway epithelial cells (BEAS-2B). Different trends of DTT activities were seen when testing PM samples in 100% aqueous buffer solutions versus elevated fraction of methanol in aqueous buffers (50:50), indicating the effect of solubility of organic PM constituents on the measured oxidative potential. Higher aromatics content in fuels corresponded to higher DTT activities in PM. Exposure to PM exhaust upregulated the expression of HMOX-1, but downregulated the expression of IL-6, TNF-α, CCL5 and NOS2 in BEAS-2B cells. The principal component regression analysis revealed different patterns of correlations. Aromatics content contributed to more significant PAH-mediated IL-6 downregulation, whereas ethanol content was associated with decreased downregulation of IL-6. Our findings highlighted the key role of fuel composition in modulating the toxicological responses to GDI PM emissions.

15.
Nat Sci Sleep ; 11: 357-366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819689

RESUMO

Purpose: Chronic intermittent hypoxia (CIH) contributes to the increased risk of cardiovascular diseases in obstructive sleep apnea (OSA). We previously reported the anti-apoptotic effects of estradiol (E2) on IH-exposed human umbilical vein endothelial cells (HUVECs). Herein, we employed a proteomic analysis to elucidate the mechanisms of the protective effects of E2 under IH exposure. Methods: HUVECs were divided into three groups: control, IH, and IH+E2 group. Isobaric tags for relative and absolute quantification (iTRAQ) were performed to compare protein profiles among the groups. Some of the identified proteins were validated by Western blotting. Results: A total of 185 proteins were differentially expressed in the IH+E2 group compared to the IH group. Bioinformatics analysis indicated that the effects of E2 may be linked to the regulation of cellular stress response. Among the differentially expressed proteins, we identified that serine-protein kinase ataxia telangiectasia mutated (ATM) and its downstream target, cellular inhibitor of apoptosis protein 1 (c-IAP1), were up-regulated by E2. We also observed that E2 decreased the level of cleaved caspase-3 and inhibited cell apoptosis in IH-exposed HUVECs. The inhibition of ATM abolished the anti-apoptotic effect of E2. Conclusion: The ATM-c-IAP1 pathway is involved in the cardioprotective effects of E2 in HUVECs exposed to IH.

16.
Sci Rep ; 9(1): 18783, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827106

RESUMO

Dialysis-induced hemodynamic instability has been associated with increased risk of cardiovascular (CV) mortality. However, the control mechanisms beneath the dynamic BP changes and cardiac function during hemodialysis and subsequent CV events are not known. We hypothesize that the impaired hemodynamic control can be prognostic indicators for subsequent CV events in end stage renal diseaes (ESRD) patients. To explore the association of hemodynamic parameters and CV events in hemodialysis patients, we enrolled ESRD patients who received chronic hemodialysis without documented atherosclerotic cardiovascular disease and hemodynamic parameters were continuously obtained from the impedance cardiography during hemodialysis. A total of 35 patients were enrolled. 16 patients developed hospitalized CV events. The statistical properties [coefficient of variance (standard deviation / mean value; CoV)] of hourly beat-to-beat dynamics of hemodynamic parameters were calculated. The CoV of stroke volume (SV) and cardiac index (CI) between the 1st and 2nd hour of dialysis were significantly increased in patients without CV events compared to those with CV events. Higher CoV of SVdiff and CIdiff were significantly correlated with longer CV event-free survival, and the area under the receiver operating characteristic (ROC) curve showed fair overall discriminative power (0.783 and 0.796, respectively). The responses of hemodynamic control mechanisms can be independent predictive indexes for lower hospitalized CV events, which implies that these patients who have better autonomic control systems may have better CV outcomes.

17.
Microb Cell Fact ; 18(1): 207, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783868

RESUMO

BACKGROUND: The methylotrophic yeast Pichia pastoris is well-known for the production of a broad spectrum of functional types of heterologous proteins including enzymes, antigens, engineered antibody fragments, and next gen protein scaffolds and many transcription factors are utilized to address the burden caused by the high expression of heterologous proteins. In this article, a novel P. pastoris transcription factor currently annotated as Fhl1p, an activator of ribosome biosynthesis processing, was investigated for promoting the expression of the recombinant proteins. RESULTS: The function of Fhl1p of P. pastoris for improving the expression of recombinant proteins was verified in strains expressing phytase, pectinase and mRFP, showing that the productivity was increased by 20-35%. RNA-Seq was used to study the Fhl1p regulation mechanism in detail, confirming Fhl1p involved in the regulation of rRNA processing genes, ribosomal small/large subunit biogenesis genes, Golgi vesicle transport genes, etc., which contributed to boosting the expression of foreign proteins. The overexpressed Fhl1p strain exhibited increases in the polysome and monosome levels, showing improved translation activities. CONCLUSION: This study illustrated that the transcription factor Fhl1p could effectively enhance recombinant protein expression in P. pastoris. Furthermore, we provided the evidence that overexpressed Fhl1p was related to more active translation state.

18.
Trials ; 20(1): 675, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801563

RESUMO

BACKGROUND: Biannual, mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. Subgroup analysis suggested that the strongest effects were in the youngest children, leading to the hypothesis that targeting younger age groups might be an effective strategy to prevent mortality. We present the methods of two randomized controlled trials designed to evaluate mass and targeted azithromycin distribution for the prevention of child mortality in Burkina Faso, West Africa. METHODS/DESIGN: The Child Health with Azithromycin Treatment (CHAT) study consists of two nested, randomized controlled trials. In the first, communities are randomized in a 1:1 fashion to biannual, mass azithromycin distribution or placebo. The primary outcome is under-5 all-cause mortality measured at the community level. In the second, children attending primary healthcare facilities during the first 5-12 weeks of life for a healthy child visit (e.g., for vaccination) are randomized in a 1:1 fashion to a single orally administered dose of azithromycin or placebo. The primary outcome is all-cause mortality measured at 6 months of age. The trial commenced enrollment in August 2019. DISCUSSION: This study is expected to provide evidence on two health systems delivery approaches (mass and targeted treatment) for azithromycin to prevent all-cause child mortality. The results will inform global and national policies related to azithromycin for the prevention of child mortality. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03676764. Registered on 19 September 2018; prospectively registered pre results.

19.
Brain Struct Funct ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31858236

RESUMO

Making reasonable decisions related to financial and health scenarios is a crucial capacity that can be difficult for older adults to maintain as they age, yet few studies examine neurocognitive factors that are generalizable to different types of everyday decision-making capacity. Here we propose an innovative approach, based on individual risk-taking preference, to identify neural profiles that may help predict older adults' everyday decision-making capacity. Using performance and cognitive arousal information from two gambling tasks, we identified three decision-making preference groups: ambiguity problem-solvers (A), risk-seekers (R), and a control group without strong risk-taking preferences (C). Comparisons of the number of connections within white matter tracts between A vs. C and R vs. C groups resulted in features consistent with the theory of dual neural functional systems involved in decision-making. Unique tracts from the A vs. C contrast were primarily centered in dorsal frontal regions/reflective system; unique tracts from the R vs. C contrast were centered in the ventral frontal regions/impulsive system; and shared tracts from both contrasts were centered in the basal ganglia, coordinating the switch between the two types of decision-making preference. Number of connections from the tracts differentiating A vs. C significantly predicted financial and health/safety decision-making capacity, and the association remained significant after controlling for multiple socioeconomic and cognitive factors. The connectome identified may provide insight into a generic white matter mechanism related to everyday decision-making capacity in older age.

20.
Sci Total Environ ; 705: 135837, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31846818

RESUMO

As an emerging environmental pollutant, microplastics (MPs) are increasingly viewed as a serious health concern to terrestrial and aquatic ecosystems. However, previous toxicological studies examining MPs on freshwater and terrestrial organisms provide contradictory results, possibly due to few investigations at environmentally relevant concentrations. Here, the nematode Caenorhabditis elegans (C. elegans), a model organisms with both aquatic and terrestrial free-living forms, was employed to investigate the effects of 1 and 5 µm MPs (107-1010 particles/m2) on the intake, lifespan, defecation rhythm, defecation-related neurons and transcriptional expression of related genes (skn-1, mkk-4, pmk-1, cpr-1 and itr-1). We demonstrated that the percentage of MP-contaminated nematodes increased with increasing exposure concentrations and duration. The lifespan of nematodes in the lower concentration exposure groups (2.4 × 107 and 2.4 × 108 particles/m2) decreased more prominently than that of higher concentration groups (2.4 × 109 and 2.4 × 1010 particles/m2) after a 72-h exposure period. Concomitantly, expression of the skn-1 gene, involved in detoxification and lifespan regulation, was significantly altered at lower MP concentrations. Physiologically, the defecation rhythm after a 72-h exposure period was most strongly affected by 1 µm MPs at 2.4 × 108 particles/m2. The significant up-regulation of related genes by 1 µm MPs appears responsible for the shortened defecation interval. Results of this study identified a potential toxicity threat to C. elegans from exposure to MPs at environmentally relevant concentrations and provide novel evidence for MP risks to freshwater and terrestrial organisms. Capsule. After exposure to 1 and 5 µm MPs (107-1010 particles/m2), the lifespan of C. elegans decreased more rapidly at lower concentrations.

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