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1.
Prev Chronic Dis ; 17: E11, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027814

RESUMO

We conducted a multicomponent, low-cost, home intervention for children with uncontrolled asthma, the Reducing Ethnic/Racial Asthma Disparities in Youth (READY) study, to evaluate its effect on health outcomes and its return on investment. From 2009 through 2014 the study enrolled 289 children aged 2 to 13 years with uncontrolled asthma and their adult caregivers in Boston and Springfield, Massachusetts. Community health workers (CHWs) led in-home asthma management and environmental trigger remediation education over 5 visits spanning 6 months. Asthma health outcomes and indoor environment data were collected via survey, and health use costs were accessed through Massachusetts Medicaid (MassHealth). Results showed significant improvements in asthma control, health care use, and environmental trigger reduction and a positive return on investment (1.34) for participants who had 2 or more emergency department visits 1 year prior to the first home visit. The CHW asthma home visiting intervention improved trigger management, clinical outcomes, and Medicaid cost savings, demonstrating that asthma home visits improve health quality and reduce costs.

2.
Blood Purif ; : 1-10, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32050204

RESUMO

PURPOSE: Cardiac valve calcification (CVC) is frequently occurred in maintenance hemodialysis (MHD) patients and is associated with cardiovascular and all-cause mortality. This study aimed to evaluate the relationships between risk factors and extent of CVC and further provide the treatment target in MHD patients. METHODS: One hundred and forty-five patients who received MHD ≥3 months were enrolled. CVC was assessed by an echocardiographic, semi-quantitative manner called global cardiac calcium scoring system (GCCS), and demographic, clinical, and laboratory parameters including mineral metabolism markers were collected. RESULTS: The average age of the patients was 50 ± 12 years, and 54.5% were men. The mean GCCS was 1.8 ± 2.4; 57.2% of patients had GCCS ≥1. Age, dialysis vintage, serum alkaline phosphatase (ALP), and intact parathyroid hormone levels were positively correlated with CVC, whereas serum albumin levels were negatively related to CVC, based on univariate analysis. With multivariate linear regression analysis, serum ALP was the only bone-derived biomarker that showed significant correlation with CVC. Serum ALP ≥232 U/L was a robust predictor of CVC and was associated with the likelihood of GCCS ≥1 (OR 3.92, 95% CI 1.37-11.2, p = 0.011). The decision tree model was used to identify ALP ≥232 U/L and age ≥60 years as important determinative variables in the prediction of CVC in MHD patients. CONCLUSION: Serum ALP level is significantly associated with CVC in MHD patients. ALP is suggested to be a promising interventional target for cardiovascular calcification in MHD patients.

3.
J Invest Surg ; : 1-7, 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32064986

RESUMO

Objectives: We investigated whether the totally video-assisted thoracoscopic mitral valve surgery provides superior clinical outcomes and less inflammatory injury reaction compared with conventional sternotomy.Methods: A total of 504 consecutive patients admitted for mitral valve surgery from May 2014 through May 2019 in a single center were retrospectively analyzed according to two distinct procedure approach: the totally video-assisted thoracoscopic approach (group A, n = 127) and standard median sternotomy (group B, n = 377). The primary end point was the durations of cardiopulmonary bypass, aortic cross-clamping, the ventilation time and intensive care unit of stay; the secondary endpoints included inflammation indexes like high sensitivity C-reactive protein, neutrophil-lymphocyte ratio and metabolic injury parameters cardiac Troponin and lactate.Results: There was only one in-hospital death due to diffuse intravascular coagulation in group A, but similar complications such as repair failure, re-thoracotomy and stroke in both groups. The durations of cardiopulmonary bypass and aortic cross-clamping were significantly longer in group A. In contrast, ventilation time and intensive care unit of stay were shortened compared with these in group B. In addition, postoperative equivalent lactate clearance but lower high sensitivity C-reactive protein, neutrophil-lymphocyte ratio and cardiac Troponin level was in group A than those in group B within postoperative 24 hours(P < 0.05).Conclusions: The analysis of present study indicated despite relatively longer cardiopulmonary bypass time, the totally thoracoscopic mitral valve procedure seemed to be favorable with regard to the extent of inflammatory reaction, cardiac injury and postoperative recovery compared with conventional median sternotomy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32014256

RESUMO

Diabetes mellitus (DM) is currently a major global health problem, which is associated with the development of cognitive dysfunction. However, although numerous clinical drugs for hyperglycemia have been used at present, safer and more effective therapeutic intervention strategies for diabetic cognitive impairments are still a huge challenge. Recently, several studies have indicated that a novel class of branched palmitic acid esters of hydroxyl stearic acids (PAHSAs) may have anti-diabetes and anti-inflammatory effects in insulin-resistant mice. Herein, whether the 9-PAHSA that one of the PAHSAs can attenuates DM-associated cognitive impairment in a mouse model of type 2 diabetes has been investigated. Our results showed that 9-PAHSA mildly prevented deficits of spatial working memory in Y-maze test while reversed the preference bias toward novel mice in Social choice test. Furthermore, the effect of REST on cognitive impairment of diabetes was explored for the first time. It was found that the expression of REST in diabetic mice increased, and the expression of target protein BDNF (Brain-derived neurotrophic factor) was decreased. After administration of 9-PAHSA, the situation was reversed. In summary, we conclude that exogenous supplement of 9-PAHSA can improve DM-related cognitive impairment to some extent, and the protective effect may be associated with decreased REST/NRSF (repressor element-1 silencing transcription factor/neuron-restrictive silence factor) and upregulated BDNF expression in frontal cortex.

5.
Aging (Albany NY) ; 122020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015217

RESUMO

Tumour regrowth is a key characteristic of clinically non-functioning pituitary adenoma (NFPA). No applicable prognosis evaluation method is available for post-operative patients. We aimed to identify DNA methylation biomarkers that can facilitate prognosis evaluation. Genome-wide DNA methylation and mRNA microarray analyses were performed for tumour samples from 71 NFPA patients. Differentially expressed genes and methylated genes were identified based on the regrowth vs non-regrowth grouping. There were 139 genes that showed alterations in methylation status and expression level, and only 13 genes showed a negative correlation. The progression-free analysis found that FAM90A1, ETS2, STAT6, MYT1L, ING2 and KCNK1 are related to tumour regrowth. A prognosis-prediction model was built based on all 13 genes from integrated analysis, and the 6-gene model achieved the best area under the receiver operating characteristic curves (AUC) of 0.820, compared with 0.785 and 0.568 for the 13-gene and 7-gene models, respectively. Our prognostic biomarkers were validated by pyrosequencing and RT-PCR. FAM90A1 and ING2 was found to be independent prognostic factors of tumour regrowth with univariate Cox regression. The DNA methylation and expression levels of FAM90A1 and ING2 are associated with tumour regrowth, and may serve as biomarkers for predicting the prognosis of patients with NFPA.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32031755

RESUMO

OBJECTIVE: To determine the efficacy and the prognostic value of amplitude-integrated electroencephalography (aEEG) in term and near-term neonates with high risk of neurological sequelae. METHODS: Infants of ≥35 weeks of gestation diagnosed with neonatal encephalopathy or with high risk of brain injury were included. All eligible infants underwent aEEG within 6 h after clinical assessment. The infants were followed up 12 months to evaluate neurological development. RESULTS: A total of 250 infants were eligible, of which 85 had normal aEEG, 81 had mildly abnormal aEEG, and 84 had severely abnormal aEEG. Of these infants, 168 were diagnosed with different neonatal encephalopathies, 27 with congenital or metabolic diseases, and 55 with high risk of brain injury. In all, 22 infants died, 19 were lost to follow-up, and 209 completed the follow-up at 12 months, of which 62 were diagnosed with a neurological disability. Statistical analysis showed that severely abnormal aEEG predicted adverse neurological outcome with a sensitivity of 70.2%, a specificity of 87.1%, a positive predictive value of 75.6%, and a negative predictive value of 83.7%. INTERPRETATION: aEEG can predict adverse outcomes in high-risk neonates and is a useful method for monitoring neonates with high risk of adverse neurological outcomes.

7.
Exp Cell Res ; : 111880, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32017930

RESUMO

This study aims to clarify the role and molecular mechanism of dynamin-related protein 1 (Drp1)-mediated mitochondrial homeostasis in high glucose (HG)-induced endometrial cancer (EC). Normal endometrium and tumor tissues of EC patients with normal and HG levels were collected, and Drp1 and p-Drp1 expression levels were detected by immunohistochemistry. Human EC cells were cultured with different glucose concentrations, and Drp1 and p-Drp1 expression levels were evaluated by Western blotting. Cell models of control and siDrp1 groups under normal and HG conditions were established, and subsequent functional experiments were conducted. Histology and in vitro experiments showed that the HG environment increased Drp1 activation, which could lead to mitochondrial dysfunction. Moreover, the imbalance of mitochondrial homeostasis mediated by Drp1 resulted in cell dysfunction, including altered glucose metabolism and increased epithelial-mesenchymal transition (EMT), migration and invasion. All these changes caused by HG could be partially alleviated by Drp1 knockdown. This study revealed that Drp1 was involved in the progression of EC associated with HG, and Drp1 might be a new potential therapeutic target for EC patients with diabetes.

8.
J Oleo Sci ; 69(2): 115-122, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023578

RESUMO

A new difunctional Zn(II) coordination polymer (CP) with the chemical formula of [Zn(TBTA) (L)1.5]n (1) has been synthesized hydrothermally from tetrabromoterephthalic acid (H2TBTA) and 4,4'-bis(imidazole-1-yl)-biphenyl (L) ligands. Furthermore, due to its strong intense emission and open N donor sites, complex 1 could be used as a light-emitting sensor to determine 2,4,6-trinitrophenol (TNP) which has high selectivity and sensitivity. Furthermore, the anti-bacterial effect of the compound against P. gingivalis in vitro was evaluated by measuring the P. gingivalis growth curves after compound treatment. And the RT-PCR assay was performed to detect the relative expression of ragA and ragB, which are important for the P. gingivalis growth. The potential anti-infectious mechanism was further studied by using molecular docking technique.

9.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(1): 101-103, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32037775

RESUMO

This article reports a case of an orthodontic adolescent patient without a right inferior incisor. The right lower canine was used as the abutment. The single-retainer all-ceramic resin-bonded fixed partial denture was used to restore the complete dentition. Thus, the missing space was filled, and the function and aesthetics were restored.


Assuntos
Prótese Adesiva , Adolescente , Cerâmica , Planejamento de Dentadura , Prótese Parcial Fixa , Estética Dentária , Humanos , Incisivo
10.
Angle Orthod ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045299

RESUMO

OBJECTIVES: To evaluate changes in dimensions and volume of upper airway before and after mini-implant assisted rapid maxillary expansion (MARME) and observe correlations between changes of upper airway and vertical skeletal pattern in young adults. MATERIALS AND METHODS: In this retrospective study, 22 patients (mean age, 22.6 ± 4.5 years; 4 male 18 female) with transverse discrepancy underwent MARME. Cone beam computed tomography was taken before and 3 months after expansion. Vertical and horizontal dimensions and volume of the nasal cavity, nasopharyngeal, retropalatal, retroglossal and hypopharyngeal airway were compared before and after MARME. Correlations between changed volume and dimensions were explored, as well as the vertical skeletal pattern. RESULTS: Nasal osseous width, maxillary width, volume of the nasal cavity and nasopharynx increased significantly (P < .05). Enlarged nasopharyngeal volume correlated with increased nasal width at the PNS plane (P < .05). There were no correlations between expanded volume and maxillary width. No measurements except nasal cavity volume had a correlation with Sum angle. Increased maxillary width correlated negatively with hard palate thickness (P < .05). CONCLUSIONS: (1) MARME caused an increase in volume of the nasal cavity and nasopharynx, with expansion of nasal osseous width and maxillary width. (2) Enlarged nasal width at the PNS plane contributed to the increase in nasopharynx volume. Enlarged maxillary width showed no direct relation with increased volume. (3) In this study, it was unclear about the association between changes of the upper airway and vertical skeletal pattern because of complex structures. (4) Palate thickness affected skeletal expansion of the maxilla in MARME.

11.
Hum Reprod Update ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045470

RESUMO

BACKGROUND: Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine. OBJECTIVE AND RATIONALE: The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included. SEARCH METHODS: Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217). OUTCOMES: Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls). WIDER IMPLICATIONS: For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses.

12.
Acta Pharmacol Sin ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32047261

RESUMO

Norditerpenoids and dinorditerpenoids represent diterpenoids widely distributed in the genus Podocarpus with notable chemical structures and biological activities. We previously reported that nagilactone E (NLE), a dinorditerpenoid isolated from Podocarpus nagi, possessed anticancer effects against lung cancer cells in vitro. In this study we investigated the in vivo effect of NLE against lung cancer as well as the underlying mechanisms. We administered NLE (10 mg·kg-1·d-1, ip) to CB-17/SCID mice bearing human lung cancer cell line A549 xenograft for 3 weeks. We found that NLE administration significantly suppressed the tumor growth without obvious adverse effects. Thereafter, RNA sequencing (RNA-seq) analysis was performed to study the mechanisms of NLE. The effects of NLE on A549 cells have been illustrated by GO and pathway enrichment analyses. CMap dataset analysis supported NLE to be a potential protein synthesis inhibitor. The inhibitory effect of NLE on synthesis of total de novo protein was confirmed in Click-iT assay. Using the pcDNA3-RLUC-POLIRES-FLUC luciferase assay we further demonstrated that NLE inhibited both cap-dependent and cap-independent translation. Finally, molecular docking revealed the low-energy binding conformations of NLE and its potential target RIOK2. In conclusion, NLE is a protein synthesis inhibitor with anticancer activity.

13.
Medicine (Baltimore) ; 99(5): e18608, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000366

RESUMO

BACKGROUND: The number of dementia patients in the world is large, and the number of dementia patients will continue to rise in the future, which will bring a heavy social and economic burden. No interventions have been found to cure dementia. Medication can delay the progression of the disease and impose an economic burden. Some non-drug therapies often require the care of the caregiver. Probiotics, prebiotics, and synbiotics may intervene in dementia through microbiota-gut-brain axis (MGBA). However, their effectiveness and safety are still obscure and deserve further investigation. The purpose of this study is to assess the effect and safety of probiotics, prebiotics, and synbiotics in treating dementia. METHODS: We will summarize and meta-analyze randomized controlled trials (RCTs) of probiotics, prebiotics, and synbiotics for the treatment of dementia. RCTs comparing probiotics, prebiotics, and synbiotics with blank control, placebo or conventional therapies will be included. RCTs comparing probiotics, prebiotics, and synbiotics plus conventional therapies with conventional therapies alone will also be included. The following electronic databases will be searched: PubMed, Cochrane Library, EMBASE, CNKI, CBM, VIP, and WAN FANG DATA. The methodological quality of RCTs will be assessed using the Cochrane risk assessment tool. All trials included will be analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software will be used for publication bias analysis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) pro-GDT web solution will be used for evidence evaluation. RESULTS: This review will evaluate the effects of probiotics, prebiotics, and synbiotics on cognitive function, behavioral and psychological symptoms of dementia, quality of life (QOL), functional performance in activities of daily living, and compliance with the intervention and safety in patients with dementia. CONCLUSIONS: This review will provide clear evidence to assess the effectiveness and safety of probiotics, prebiotics, and synbiotics for dementia.OSF registration number: DOI 10.17605/OSF.IO/2Q3AK.


Assuntos
Demência/dietoterapia , Prebióticos , Probióticos/uso terapêutico , Humanos , Revisão Sistemática como Assunto
14.
Artigo em Inglês | MEDLINE | ID: mdl-32011801

RESUMO

The enantioselective photoreaction appears to be a long-standing challenge, considering that photodimerization of the simple nonalternant acenaphthylene (ACE) is known for 100 years but asymmetric cycloaddition of its 1-subsituted derivatives is unknown yet. Here, we report a supramolecular photochirogenic approach to utilize homochiral and photoactive Δ/Λ-[Pd6(RuL3)8]28+ metal-organic cage (Δ/Λ-MOC-16) as an effective supramolecular reactor to achieve enantioselective exited-state photocatalysis of 1-Br-ACE. By virtue of molecular cage confinement effect for preorganization of substrates, stereochemical control of triplet-state, and nanospace transfer of energy and chirality, cycloaddition of ACE gives highly conformation selective anti over syn stereoisomers, while cycloaddition of unsymmetric 1-Br-ACE results in exclusive control of regio-, stereo- and enantioselective product with effective enantiodifferination of a pair of anti heat-to-head stereoisomers. The enzyme mimicking photocatalysis is verified by catalytic turnover, rate enhancement and competing-guest inhibition experiments, and photocatalytic selectivity and triplet energy-transfer in molecular confined nanospace are clarified by theoretical modulations. We hope this work provides a confined nanospace engineering approach for single MOC supramolecular nanoreactor coupling photo and stereo factors to expand the burgeoning field of enantioselective photocatalysis.

15.
Curr Med Chem ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894740

RESUMO

Protein kinase inhibitors (PKIs) and histone deacetylase inhibitors (HDACIs) are two important classes of anticancer agents and have provided a variety of small molecule drugs for the treatment of various types of human cancers. However, malignant tumors are of a multifactorial nature that can hardly be "cured" by targeting a single target, and treatment of cancers hence requires modulation of multiple biological targets to restore the physiological balance and generate sufficient therapeutic efficacy. Multi-target drugs have attracted great interest because of their advantages in the treatment of complex cancers by simultaneously targeting multiple signaling pathways and possibly leading to synergistic effects. Synergistic effects have been observed in the combination of kinase inhibitors, such as imatinib, dasatinib, or sorafenib, with an array of HDACIs including vorinostat, romidepsin, or panobinostat. A considerable number of multi-target agents based on PKIs and HDACIs have been developed. In this review, we summarize the recent literature on the development of multi-target kinase-HDAC inhibitors and provide our view on the challenges and future directions on this topic.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31972732

RESUMO

OBJECTIVE: To determine the effects of bovine lactoferrin (bLF) on cell viability, proliferation, and the protective roles in intestinal epithelial cells-6 (IEC-6) treated by lipopolysaccharide (LPS). METHODS: Cell viability and proliferation of IEC-6 were detected by MTT and Brdu assay separately. Cell cycle distribution was analyzed by flow cytometry. Inflammatory cytokines were analysed by real-time PCR and ELISA. Western blot was utilized to measure the level of MAPK and NF-κß nuclear translocation. RESULTS: Dose dependent effects of bLF on cell viability and proliferation were observed in IEC-6 cells (both P < 0.05), especially at a dose of 100 µg/ml. The percentage of cells in the G2 and S phase was significantly higher than those of the control group (8.17 ±â€Š0.49% versus 4.72 ±â€Š0.55%, p < 0.01 and 12.75 ±â€Š0.33% versus 9.48 ±â€Š0.33%, p < 0.01 respectively). The mRNA level of IL-1ß, IL-6 and TNF-α was decreased by co-stimulation of bLF and LPS compared with the LPS treatments alone in IEC-6 cells (all P < 0.001). The secretion of IL-6 and TNF-α were also decreased by co-stimulation of bLF and LPS (both P < 0.01). Bovine lactoferrin treatment at dose of 100 µg/ml could inhibit the activation of MAPK/NF-κß signal pathway induced by LPS (both P < 0.001). CONCLUSION: Bovine lactoferrin could promote the cell viability and proliferation, and have anti-inflammatory effects via inhibition of the activation of MAPK and NF-κß nuclear translocation. Supplementation of formula with bLF may be beneficial in preventing NEC in preterm infants.

17.
Environ Sci Technol ; 54(4): 2210-2217, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31994391

RESUMO

Fishery activities are an important source of microplastic pollution in coastal areas but have received little attention. The Beibu Gulf, a traditional fishing ground of China and the China-Indo Peninsula, was selected in this study, and the focus was on the impacts of fishery activities on the horizontal distribution of microplastics in sediment. The results showed that the dominant contaminants (polypropylene fibers and polyethylene fibers) might originate from the abrasion of fishing gear and contributed to 61.6% of the total abundance of microplastics in surface sediment. The abundance of polypropylene fibers and polyethylene fibers exhibited a strong correlation (R2 = 0.8586, p = 0.015) with values of fishery yields of different districts, which highlighted the effects of different fishery activities on microplastic contamination in marine sediment. Microplastics could be "hidden" in deep sediment to a depth of 60 cm. The estimated storage of microplastics in deep sediment (185 tons) was 5 times that in surface sediment. The assessment of microplastic storage worldwide might be underestimated because most previous studies only examined surface sediment. The abundance distribution and size distribution of microplastics in the sediment core suggested long-term burial of microplastics in deep sediment. Bioturbation might be responsible for the vertical transport of microplastics, leading to "fresh microplastics" preservation in "old sediment".

18.
Antiviral Res ; 174: 104705, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926181

RESUMO

Monocyte chemotactic protein-induced protein 1 (MCPIP1) is an inflammatory regulator in immune response. Recently, MCPIP1 has also been identified as a host antiviral factor against certain virus infection including human immunodeficiency virus, dengue virus and hepatitis C virus. However, whether MCPIP1 could restrict the replication of hepatitis B virus (HBV), a DNA pararetrovirus belonging to Hepadnaviridae family, has not been investigated. In this study, we found that MCPIP1 expression was up-regulated in mouse livers upon acute HBV replication and in HBV-replicated hepatoma cells or HBV-stimulated macrophages. Enforced MCPIP1 expression by hydrodynamic DNA injection in vivo significantly inhibited HBV replication in the mouse livers. Then in vitro studies by overexpression or knockdown assays in cell-lines identified the direct antiviral effect of MCPIP1 on HBV replication. RNA immunoprecipitation and decay assay further suggested that MCPIP1 potently restricted HBV replication through directly binding viral RNA and degrading RNA via its RNase activity, but not deubiquitinase activity. Moreover, we further verified that MCPIP1 negatively regulated HBV-induced proinflammatory cytokines, such as IL-1ß, TNF-α and IL-6 in macrophages. Taken together, our data expand MCPIP1's range of viral targets to DNA virus and also demonstrate the negative regulatory role of MCPIP1 in suppressing virus-induced inflammatory response, suggesting MCPIP1 as a potential therapeutic target for treating HBV-related diseases via inducing a host defense against HBV and reducing inflammatory injury meanwhile.

19.
Cells ; 9(1)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952347

RESUMO

PDCD4 (programmed cell death 4) is a tumor suppressor that plays a crucial role in multiple cellular functions, such as the control of protein synthesis and transcriptional control of some genes, the inhibition of cancer invasion and metastasis. The expression of this protein is controlled by synthesis, such as via transcription and translation, and degradation by the ubiquitin-proteasome system. The mitogens, known as tumor promotors, EGF (epidermal growth factor) and TPA (12-O-tetradecanoylphorbol-13-acetate) stimulate the degradation of PDCD4 protein. However, the whole picture of PDCD4 degradation mechanisms is still unclear, we therefore investigated the relationship between PDCD4 and autophagy. The proteasome inhibitor MG132 and the autophagy inhibitor bafilomycin A1 were found to upregulate the PDCD4 levels. PDCD4 protein levels increased synergistically in the presence of both inhibitors. Knockdown of p62/SQSTM1 (sequestosome-1), a polyubiquitin binding partner, also upregulated the PDCD4 levels. P62 and LC3 (microtubule-associated protein 1A/1B-light chain 3)-II were co-immunoprecipitated by an anti-PDCD4 antibody. Colocalization particles of PDCD4, p62 and the autophagosome marker LC3 were observed and the colocalization areas increased in the presence of autophagy and/or proteasome inhibitor(s) in Huh7 cells. In ATG (autophagy related) 5-deficient Huh7 cells in which autophagy was impaired, the PDCD4 levels were increased at the basal levels and upregulated in the presence of autophagy inhibitors. Based on the above findings, we concluded that after phosphorylation in the degron and ubiquitination, PDCD4 is degraded by both the proteasome and autophagy systems.

20.
J Autoimmun ; : 102404, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31952907

RESUMO

The chromatin modifier enhancer of zeste homolog 2 (EZH2) methylates lysine 27 of histone H3 (H3K27) and regulates T cell differentiation. However, the potential role of EZH2 in the pathogenesis of rheumatoid arthritis (RA) remains elusive. We analyzed EZH2 expression in PBMC, CD4+ T cells, CD19+ B cell, and CD14+ monocytes from active treatment-naïve RA patients and healthy controls (HC). We also suppressed EZH2 expression using EZH2 inhibitor GSK126 and measured CD4+ T cell differentiation, proliferation and apoptosis. We further examined TGFß-SMAD and RUNX1 signaling pathways in EZH2-suppressed CD4+ T cells. Finally, we explored the regulation mechanism of EZH2 by RA synovial fluid and fibroblast-like synoviocyte (FLS) by neutralizing key proinflammatory cytokines. EZH2 expression is lower in PBMC and CD4+ T cells from RA patients than those from HC. EZH2 inhibition suppressed regulatory T cells (Tregs) differentiation and FOXP3 transcription, and downregulated RUNX1 and upregulated SMAD7 expression in CD4+ T cells. RA synovial fluid and fibroblast-like synoviocytes suppressed EZH2 expression in CD4+ T cells, which was partially neutralized by anti-IL17 antibody. Taken together, EZH2 in CD4+ T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4+ T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4+ T cells. Defective EZH2 in CD4+ T cells might contribute to Treg deficiency in RA.

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