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1.
J Cell Physiol ; 235(1): 114-127, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31347175

RESUMO

Myosin phosphatase-Rho interacting protein (p116Rip ) was originally found as a RhoA-binding protein. Subsequent studies by us and others revealed that p116Rip facilitates myosin light chain phosphatase (MLCP) activity through direct and indirect manners. However, it is unclear how p116Rip regulates myosin phosphatase activity in cells. To elucidate the role of p116Rip in cellular contractile processes, we suppressed the expression of p116Rip by RNA interference in human airway smooth muscle cells (HASMCs). We found that knockdown of p116Rip in HASMCs led to increased di-phosphorylated MLC (pMLC), that is phosphorylation at both Ser19 and Thr18. This was because of a change in the interaction between MLCP and myosin, but not an alteration of RhoA/ROCK signaling. Attenuation of Zipper-interacting protein kinase (ZIPK) abolished the increase in di-pMLC, suggesting that ZIPK is involved in this process. Moreover, suppression of p116Rip expression in HASMCs substantially increased the histamine-induced collagen gel contraction. We also found that expression of the p116Rip was decreased in the airway smooth muscle tissue from asthmatic patients compared with that from non-asthmatic patients, suggesting a potential role of p116Rip expression in asthma pathogenesis.

2.
Biomaterials ; 225: 119514, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31569018

RESUMO

Selenoxide elimination reaction has been widely used in the field of organic synthesis. However, few studies have been conducted to apply this reaction in biodegradable nanomedicine. In this work, the selenoxide elimination reaction was used for cancer treatment via producing excess cellular reactive oxygen species (ROS) for the first time. The ß-seleno diesters and porphyrin derivates containing nanoparticle could be responsive to the intracellular ROS and produce acrylates through the elimination reaction. The acrylates would further deplete intracellular GSH in tumor cells and finally improved the anticancer activity in the mice tumor model. Different from traditional ROS-responsive nanomedicine, the elimination product of this reaction could regenerate cytotoxic ROS and specifically disturb the redox balance of tumor cells. This work would provide attractive avenues for the development of therapeutic strategies against cancer via synthesis of well-designed biodegradable polymers.

3.
Biomed Pharmacother ; 120: 109506, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31586904

RESUMO

Myricetin (3, 5, 7, 3', 4', 5'-hexahydroxyflavone) is a natural flavonol compound found in a large variety of plants, including berries, oranges, grapes, herbs, teas, and wine. In the last decade, a convergence of evidence has demonstrated that myricetin has good biological activity as an anti-tumor, anti-inflammatory, and anti-oxidation agent. In studies involving various types of cancer cells, myricetin has been shown to suppress cancer cell invasion and metastasis, to induce cell cycle arrest and apoptosis of cancer cells, and to inhibit their proliferation. These findings have raised interest in myricetin as a potential tumor inhibitor in human patients. In this review, evidence of myricetin's anti-tumor activity and its underlying molecular mechanisms published in the last decade are summarized.

4.
J Hazard Mater ; 384: 121264, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31590082

RESUMO

Promotional effect of Mn(II)/K2FeO4 [Fe(VI)] applying onto Se(IV) removal was determined for the first time, with description of reaction mechanisms. Four different combinations of water treatment agents [K2FeO4 alone, K2FeO4 with Al(III) ions, K2FeO4 with Fe(III) ions, and K2FeO4 with Mn(II) ions] were used for Se removal in spiked deionized water, and K2FeO4 in combination with Mn(II) ions showed great removal efficiency. Over 90% of Se(IV) (200 µg/L) was removed within 2 min by using 1 mg/L of K2FeO4 and 9 mg/L of Mn(II) ions (pH 7.0, 23 °C). XPS analysis identified that in the reaction process, Se(0) formed on the settlement. It was speculated that Se(IV) was oxidized to Se(VI) by K2FeO4, and the Se(VI) species was reduced to insoluble Se(0) by γ-Fe2O3-Mn(II) nanocomplex. Insoluble Se(0) adsorbed on the surface of Fe-Mn particle and coprecipitated, thus removed from aqueous solution. As solution pH varied from 4.0 to 8.0, Se(IV) removal ratio ranged from 89% to 98% in the system. Co-existing ions such as Na+, Ca2+ and SO42- had no intense effect on Se removal, while PO43- and humic acid (HA) inhibited Se removal in Mn(II)/K2FeO4 system. Mn(II)/K2FeO4 was an effective and convenient way for Se(IV) removal from polluted water.

5.
J Hand Surg Eur Vol ; : 1753193419878981, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584341

RESUMO

The Wrist and Radius Injury Surgical Trial (WRIST) collaboration is the largest clinical trial ever conducted in hand surgery. We applied data from this study to examine the relationship between functional outcomes and patient satisfaction after treatment of distal radial fractures. Patients aged 60 years and older with isolated distal radial fractures were enrolled at 24 health systems. Grip strength and the arc of wrist motion were measured after treatment. The Michigan Hand Outcomes Questionnaire was used to measure patient satisfaction. Receiver operating characteristic curves were created using patient satisfaction as the reference standard and each functional measure as a predictor. At 12 months after treatment, mean grip strength was 82% of normal and mean arc of motion was 88% of normal. The optimal cut-off points to distinguish satisfaction from dissatisfaction occurred when patients recovered 59% of hand strength and 79% of wrist motion. Continuing therapy to increase functional gains beyond this point unnecessarily utilizes healthcare resources without additional patient-reported gains. Level of evidence: IV.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31589394

RESUMO

Developing new filters for the effective removal of high temperature particulate matter is of great importance but still remains challenging. Herein, we demonstrate a novel and facile strategy for producing hierarchical ceramic foams with three-dimensional interconnected porous architecture via the combination of chemical grafting of pore-forming agent and polyurethane foaming technique. Carbamate groups are directly grafted onto carbon black surface to enhance its dispersion. Abundant micron-sized pores are generated on the cell walls of porous frameworks to form three-dimensional interconnected porous architectures, resulting in the mullite foam with high particulate matter removal efficiency and relatively low pressure drop. The optimized mullite foam exhibits integrated properties of high particulate matter removal efficiency (96.7%), ultralow pressure drop (35 Pa) and outstanding recyclability. Our results open up new opportunities for fabricating efficient particulate matter filters used in high temperature environmental fields.

7.
Cell Death Dis ; 10(10): 774, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601780

RESUMO

Neonatal jaundice is prevalent among newborns and can lead to severe neurological deficits, particularly sensorimotor dysfunction. Previous studies have shown that bilirubin (BIL) enhances the intrinsic excitability of central neurons and this can potentially contribute to their overexcitation, Ca2+ overload, and neurotoxicity. However, the cellular mechanisms underlying elevated neuronal excitability remain unknown. By performing patch-clamp recordings from neonatal neurons in the rat medial vestibular nucleus (MVN), a crucial relay station for locomotor and balance control, we found that BIL (3 µM) drastically increases the spontaneous firing rates by upregulating the current-mediated voltage-gated sodium channels (VGSCs), while shifting their voltage-dependent activation toward more hyperpolarized potentials. Immunofluorescence labeling and western immunoblotting with an anti-NaV1.1 antibody, revealed that BIL elevates the expression of VGSCs by promoting their recruitment to the membrane. Furthermore, we found that this VGSC-trafficking process is Ca2+ dependent because preloading MVN neurons with the Ca2+ buffer BAPTA-AM, or exocytosis inhibitor TAT-NSF700, prevents the effects of BIL, indicating the upregulated activity and density of functional VGSCs as the core mechanism accountable for the BIL-induced overexcitation of neonatal neurons. Most importantly, rectification of such overexcitation with a low dose of VGSC blocker lidocaine significantly attenuates BIL-induced cell death. We suggest that this enhancement of VGSC currents directly contributes to the vulnerability of neonatal brain to hyperbilirubinemia, implicating the activity and trafficking of NaV1.1 channels as a potential target for neuroprotection in cases of severe jaundice.

8.
JAMA Netw Open ; 2(10): e1912960, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31603484

RESUMO

Importance: Stenosing tenosynovitis (trigger finger) affects approximately 2% of the population. Given the prevalence of trigger finger and rising health care costs, adherence to the cost-effective and evidence-based treatment algorithm will permit better outcomes and allocation of resources. Objectives: To examine treatment patterns for trigger finger and to determine surgeon-level and patient-level factors that influence adherence to evidence-based treatment. Design, Setting, and Participants: This retrospective population-based cohort study examined deidentified claims for treatment of trigger finger from a national insurance provider using the Clinformatics Data Mart database. Patients were included if they were 18 years or older and treated from January 1, 2002, through December 31, 2016 (excluding a washout period from July 1, 2008, until June 30, 2010), with a new diagnosis of single-digit trigger finger. Data were analyzed from December 21, 2018, through April 28, 2019. Exposures: Cost-effective and evidence-based research published in July 2009 for the treatment of trigger finger. Main Outcomes and Measures: After excluding the 1-year washout period on either side of July 1, 2009, adherence to the recommended treatment algorithm of 2 corticosteroid injections before surgical release of trigger finger was compared with practice before publication of research supporting this cost-effective and evidence-based approach. Results: In this analysis of 83 667 patients with trigger finger, 52 698 (63.0%) were women, and 20 045 (24.0%) had type 1 or 2 diabetes. Mean (SD) age was 61 (13) years. From 2002 to 2016, an overall increasing trend in adherence to the cost-effective and evidence-based approach to treatment was noted, with no significant increase in adherence in the postpublication era (67.5% vs 73.3%; P = .27). Substantial variation in adherence was observed at the surgeon level (intraclass correlation, 33%). Plastic surgeons had no change in adherence over time compared with orthopedic surgeons (odds ratio [OR], 1.00; 95% CI, 0.98-1.02; P = .90), whereas general surgeons had increased adherence (OR, 1.04; 95% CI, 1.02-1.06; P < .001). Higher-volume surgeons were also more adherent to these evidence-based recommendations (OR, 1.59; 95% CI, 1.53-1.65; P < .001). Conclusions and Relevance: This study found substantial surgeon-level variation in adherence to evidence-based treatment of trigger finger. Surgeon specialty and volume were associated with differences in adherence. Efforts to understand surgeon barriers to implementation, regardless of physician specialty, appear to be necessary, and better implementation strategies may permit increased uptake of evidence-based treatment of trigger finger.

9.
Cochrane Database Syst Rev ; 10: CD010693, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596946

RESUMO

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in December 2017. OBJECTIVES: To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA). SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (30 July 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 7), MEDLINE (1949 to 30 July 2019), Embase (1980 to 30 July 2019), CINAHL (1982 to 30 July 2019), AMED (1985 to 30 July 2019), and 11 Chinese databases (30 July 2019). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trials registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies. We did not impose any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events, and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed methodological quality and risk of bias. We evaluated the quality of evidence for each outcome using the GRADE approach. MAIN RESULTS: We identified five RCTs with 5039 participants; two studies had a low risk of bias for all domains. Four studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone. The participants in different studies were heterogeneous.Recurrent strokeThree studies evaluated the number of participants with recurrent stroke (4979 participants, a single study contributing 3876 of these). Peroxisome proliferator-activated receptor gamma agonists probably reduce the recurrence of stroke compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.99; moderate-quality evidence).Adverse eventsEvidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was uncertain due to wide confidence interval and high levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low-quality evidence).Data were available on additional composite outcomes reflecting serious vascular events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) from one study in 984 people. This study provided low-quality evidence that PPAR-γ agonists led to fewer events (data not meta-analysed).Vascular eventsPeroxisome proliferator-activated receptor gamma agonists given over a mean duration of 34.5 months in a single trial of 984 participants may reduce serious vascular events expressed as a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99; low-quality evidence).Other outcomesOne study in 20 people measured insulin sensitivity, and one study in 40 people measured the ubiquitin-proteasome activity in carotid plaques. Our confidence in the improvements observed with PPAR-γ agonists were limited by small sample sizes and risk of bias. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life. AUTHORS' CONCLUSIONS: Peroxisome proliferator-activated receptor gamma agonists probably reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and may improve insulin sensitivity and the stabilisation of carotid plaques. Their effects on adverse events are uncertain. Our conclusions should be interpreted with caution considering the small number and the quality of the included studies. Further well-designed, double-blind RCTs with large samples are required to assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31597428

RESUMO

Exploring the highly efficient catalysts for electrochemical hydrogen evolution reaction (HER) is highly demanded in the sustainable production of hydrogen. MoS2 is recognized as the potential candidate catalyst for HER, but its active site is mainly located at the edges, which is extremely limited. Here, we have investigated the catalytic performance of HER in the MoS2 basal planes during the structural transition from 2H to 1T' phase. Different kinds of 2H/1T' structural interfaces are considered and the adsorbed H free energies (∆GH) on these surfaces were calculated. The active site for H adsorption is on top of S atoms at the 2H/1T' phase boundary. The zigzag 2H/1T' interfaces exhibit optimal performance for Volmer reaction with the ∆GH very close to zero. And the Volmer-Heyrovsky reaction is dominantly preferred to the Volmer-Tafel reaction. Our study provides a new picture to boost up the active sites of basal plane for HER on MoS2, and this electrocatalytic mechanism is also applicable for the other transition metal dichalcogenides materials.

11.
Chem Commun (Camb) ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31576840

RESUMO

A range of ionic solvatochromic dye (SD) transducers for use in ion-selective emulsified optical sensors are introduced and characterized. They share the same chromophore group, (E)-4-(4-(dimethylamino)styryl)pyridinium, but vary in their lipophilicities by grafted alkyl or ethoxy groups. The calibration curve is found to shift by a total of 2.7 orders of magnitude with the lipophilicity of the SD.

12.
Nanoscale ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31576895

RESUMO

Introducing magnetism in two-dimensional materials is of particular importance for both fundamental research and practical applications in nanoscale spintronics. Herein, we report the lifting of valley degeneracy in a MoS2 monolayer via magnetic proximity coupling to an insulating antiferromagnetic Cr2O3 substrate and the gate-voltage tunability of the MoS2/Cr2O3 heterojunction on the basis of first-principles calculations. Our calculations suggest that there is a large Zeeman splitting of 23.4 meV in the MoS2 monolayer due to strong spin-orbit coupling, corresponding to a magnetic exchange field of 100 T. Both spin and valley indices flip when the magnetic ordering of Cr2O3 is reversed. More interestingly, the charge transfer, magnetic moment, band gap and Schottky barrier of the heterojunction can be tuned continually by applying an external out-of-plane gate voltage, resulting in variable valley Zeeman splitting ranging from 11.3 to 34.5 meV. These findings demonstrate great potential applications of the Cr2O3/MoS2 heterojunction in nanoscale spintronics.

13.
Sleep ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31585012

RESUMO

STUDY OBJECTIVES: Both periodic limb movements during sleep (PLMS) and arousals are associated with sympathetic nervous system activation and may be arrhythmogenic. We hypothesize a temporal relationship exists between individual PLMS, particularly with arousal, and nonsustained ventricular tachycardia (NSVT) events. METHODS: A bidirectional time-stratified case-crossover design was used to assess temporal associations between PLMS and NSVT during sleep in 49 Osteoporotic Fractures in Men Sleep Study participants with NSVT in a community-based cohort (n = 2,911). Sleep time was divided into approximate 30-min segments. For each NSVT (n = 141), we selected a preceding 30-s hazard period and three randomly chosen 30-s control periods from sleep within the same segment and evaluated for PLMS, respiratory events, minimum saturation, and arousals. Odds ratios and 95% confidence intervals-OR (95% CI)-were determined by conditional logistic regression; covariates included EEG arousals, minimum saturation, and respiratory events in the same hazard/control period. RESULTS: Participants with NSVT were 79.5 ± 6.2 years with a PLMS index of 32.1 (IQR: 10.1, 61.4) and apnea-hypopnea index of 17.1 (IQR: 9.4, 26.1). PLMS without arousal were not significantly associated with NSVT (OR = 0.80, 95% CI: 0.41-1.59). PLMS with arousal were associated with NSVT in unadjusted analyses (OR = 2.50, 95% CI: 1.11-5.65) and after adjustment (OR = 2.31, 95% CI: 1.02-5.25). Arousals associated with PLMS were associated with NSVT in unadjusted (OR = 2.84, 95% CI: 1.23-6.56) and adjusted analyses (OR = 2.61, 95% CI: 1.13-6.05). CONCLUSIONS: PLMS with (but not without) arousals are temporally associated with a greater than twofold higher odds of subsequent NSVT episodes. PLMS-related arousals may be physiologically important ventricular arrhythmia triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00070681.

14.
J Med Genet ; 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31586943

RESUMO

BACKGROUND: Protein disulfide isomerase (PDI) proteins are part of the thioredoxin protein superfamily. PDIs are involved in the formation and rearrangement of disulfide bonds between cysteine residues during protein folding in the endoplasmic reticulum and are implicated in stress response pathways. METHODS: Eight children from four consanguineous families residing in distinct geographies within the Middle East and Central Asia were recruited for study. All probands showed structurally similar microcephaly with lissencephaly (microlissencephaly) brain malformations. DNA samples from each family underwent whole exome sequencing, assessment for repeat expansions and confirmatory segregation analysis. RESULTS: An identical homozygous variant in TMX2 (c.500G>A), encoding thioredoxin-related transmembrane protein 2, segregated with disease in all four families. This variant changed the last coding base of exon 6, and impacted mRNA stability. All patients presented with microlissencephaly, global developmental delay, intellectual disability and epilepsy. While TMX2 is an activator of cellular C9ORF72 repeat expansion toxicity, patients showed no evidence of C9ORF72 repeat expansions. CONCLUSION: The TMX2 c.500G>A allele associates with recessive microlissencephaly, and patients show no evidence of C9ORF72 expansions. TMX2 is the first PDI implicated in a recessive disease, suggesting a protein isomerisation defect in microlissencephaly.

15.
J Invest Surg ; : 1-8, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31588822

RESUMO

Purpose: Practical training models can be a viable and effective educational tool that allows surgeons to acquire specific surgical techniques or skills. However, a suitable animal training model for reconstruction after a pancreaticoduodenectomy (PD) has not yet been reported. Therefore, we explored the feasibility and safety of establishing an animal training model for digestive tract reconstruction after a simulated PD using mongrel dogs. Methods: We used the anatomical similarity between the canine and human digestive tract to simulate the digestive tract reconstruction after pancreatoduodenectomy. A hepatobiliary surgeon performed simulated PD digestive reconstructions on 6 mongrel canines. Pancreaticojejunostomy (PJ), biliary-enteric anastomosis (BEA), and jejuno-jejunal anastomosis (JJ) were performed sequentially. The survival rate, surgical operation time, complications, body weight changes, gross specimen, and pathological examination of the anastomotic region were observed 30 days after surgery. Results: The survival rate 30 days after surgery was 100%. Total mean operative time was 230.5 ± 39.7 min. The operative time for PJ, BEA, and JJ was calculated as 21.5 ± 7 min, 21.7 ± 8.7 min, and 13.2 ± 1.8 min, respectively. An incision infection occurred in 1 case (16.7%); there was 1 case of ascites (16.7%), and 1 case of vomiting (16.7%). The total protein and total bilirubin indicators of the 6 dogs and the serum amylase index of 5 dogs 30 days postoperatively were within the normal range. The 6th dog's serum amylase was approximately double the normal value, possibly due to pancreatitis. Observing the gross specimen, the mucosa of the anastomosis was intact and smooth. Masson staining showed that the bile duct and jejunum anastomosis, the pancreas, and jejunum of the 6 canines were all integrated with rich collagen. Conclusion: Establishing an animal model for digestive tract reconstruction after a simulated PD in canines is feasible and safe.

16.
Nanotechnology ; 31(2): 025601, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31518998

RESUMO

In this study, a novel photocatalyst composed of N-doped TiO2 (N-TiO2) and (Ca, Y)F2:Yb3+, Tm3+ was prepared by simple dealloying followed by a hydrothermal method. The composite exhibits a homogeneous nanoporous structure consisting of large quantities of the spindle-like N-doped TiO2 nanorods, on which the (Ca, Y)F2:Yb3+, Tm3+ particles with a diameter of around 5 nm are uniformly dispersed. In addition, morphology and property of the N-TiO2 can be controlled by adjusting the dealloying period. Results show that a short immersion time leads to a small size, large surface area and low band gap. As a result, the N-TiO2/(Ca, Y)F2:Yb3+, Tm3+ composite after dealloying for 48 h (TiO2-48-C) exhibits higher degradation rates (65.6% for 10 h irradiation by 980 nm NIR) than others after dealloying for 60 h (TiO2-60-C) and 72 h (TiO2-72-C), indicating its excellent potential for practical applications.

17.
Biomater Sci ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31482868

RESUMO

Chemotherapy is one of the most common and effective ways for the clinical treatment of tumors, but tumor cells develop resistance toward drugs after a long period of chemotherapy. Interestingly, the gene expression of resistant cells usually generates increased sialic acid and raises the negative potential of the cell membranes, which is potentially useful to design novel theranostic models. In this work, we demonstrate multidrug resistant tumors-aimed theranostics by the virtue of the strong electrostatic attraction between resistant cells and nanomaterials. Human oral epithelial carcinoma vincristine-resistant tumor (KBV) and human oral epithelial carcinoma tumor (KB) were employed and compared as the tumor models. Polyethylene glycol-coated and Cu(ii) and vincristine codoped polyaniline nanoshuttles (VCR-PEG-CuPani NSs), which possessed multifunctions, positive charges, and blood circulation half-life of 6.26 ± 0.16 h, were employed as the nanomaterials for performing the tumor theranostics. Because of the stronger electrostatic attraction with KBV than that with KB, VCR-PEG-CuPani NSs showed higher enrichment of 8.05 ± 0.39% ID g-1 for KBV and a lower value of 6.02 ± 0.22% ID g-1 for KB. The higher accumulation of VCR-PEG-CuPani NSs in KBV tumors further improved the efficacy of tumor theranostics, such as those using magnetic resonance imaging, chemotherapy, and photothermal therapy.

18.
Cell Mol Immunol ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511643

RESUMO

Interleukin-17A (IL-17A)-producing helper T (Th17) cells are a subset of CD4+ T cells that play important pathological roles in autoimmune diseases. Although the intrinsic pathways of Th17 cell differentiation have been well described, how instructive signals derived from the innate immune system trigger the Th17 response and inflammation remains poorly understood. Here, we report that mice deficient in REGγ, a proteasome activator belonging to the 11S family, exhibit significantly deteriorated autoimmune neuroinflammation in an experimental autoimmune encephalomyelitis (EAE) model with augmented Th17 cell polarization in vivo. The results of the adoptive transfer of CD4+ T cells or dendritic cells (DCs) suggest that this phenotype is driven by DCs rather than T cells. Furthermore, REGγ deficiency promotes the expression of integrin αvß8 on DCs, which activates the maturation of TGF-ß1 to enhance Th17 cell development. Mechanistically, this process is mediated by the REGγ-proteasome-dependent degradation of IRF8, a transcription factor for αvß8. Collectively, our findings delineate a previously unknown mechanism by which REGγ-mediated protein degradation in DCs controls the differentiation of Th17 cells and the onset of an experimental autoimmune disease.

19.
Cell Biol Toxicol ; 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31522336

RESUMO

BACKGROUND: The mouse lung telocyte cell line (TCSV40) recently established provides further opportunities to learn TC biology and functions. The present study aims at investigating regulatory roles of phosphoinositide 3-kinase (PI3K) isoforms in TC proliferation and movement and in TGFß1-induced sensitivity and response of lung TCs to PI3K inhibitors. MATERIALS AND METHODS: Network and molecular interactions of genes coding PI3K family or TGFß family proteins in mouse primary TCs were defined. Mouse lung TCSV40 proliferation, apoptosis, cell cycle, and dynamical bio-behaviors were measured with or without TGFß1 stimulation or PI3K catalytic isoform protein (PI3K/mTOR, PI3Kα/δ/ß, PI3K p110δ, or pan-PI3K) inhibitions. RESULTS: The present study showed the difference of network characteristics and interactions of genes coding PI3K isoform proteins or TGFß family proteins in primary lung telocytes from mouse lungs compared to those of other cells residing in the lung. TGFß1 had diverse effects on TC proliferation with altered TC number in G2 or S phase, independent upon the administered dose of TGFß1. PI3Kα/δ/ß, PI3K/mTOR, and PI3K p110δ were involved in TC proliferation, of which PI3Kα/δ/ß was more sensitive. The effects of pan-PI3K inhibitor indicate that more PI3K isoforms were stimulated by the administering of external TGFß1 and contributed to TGFß1-induced TC proliferation. PI3K p110δ upregulated TC proliferation and movement dynamically without TGFß1, and downregulated TC proliferation with TGFß1 stimulation, but not TC movement. PI3Kα/δ/ß and PI3K/mTOR were more active in TGFß1-induced S phase accumulation and had similar dynamic effects to PI3K p110δ. Gene expression of PI3K isoforms in TCs was upregulated after TGFß1 stimulation. The expression of PIK3CA coding p110-α or PIK3CG coding p110-γ were up- or downregulated in TCs without TGFß1, respectively, when PI3K/mTOR, PI3Kα/δ/ß, PI3K p110δ, or pan-PI3K were inhibited. TGFß1 upregulated the expression of PIK3CA and PIK3CB, while downregulated the expression of PIK3CD and PIK3CG. CONCLUSION: Our data imply that TGFß1 plays divergent roles in the expression of PI3K isoform genes in lung TCs and can alter the sensitivity and response of lung TCs to PI3K inhibitors.

20.
Medicine (Baltimore) ; 98(36): e17044, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490396

RESUMO

RATIONALE: A single atrium is a rare congenital heart disease (CHD) involving zero atrial septal traces and preserved intact ventricular septum and atrioventricular valves, requiring careful surgical intervention. However, developing to Eisenmenger syndrome (ES) makes the surgery complicated. Based on bidirectional cardiac shunting, vegetation easily develops in case of bacterial infection. PATIENT CONCERN AND DIAGNOSES: We reported a 35-year-old woman with a single atrium, patent ductus arteriosus, pulmonary hypertension, and ES who developed infective endocarditis on her left ventricular outflow tract and complicated cerebral abscess and who underwent challenged medical treatment. INTERVENTION: Infection was successfully controlled after 4-time change in antibiotics over 4 months. However, surgery is complicated for her. OUTCOMES: The patient presented a relatively good outcome during follow-up for >6 months. LESSONS: This case report suggests that patients with complex CHD should accept surgery therapy earlier before developing ES. It is imperative to avoid invasive interventions to prevent infectious endocarditis.


Assuntos
Abscesso Encefálico/complicações , Permeabilidade do Canal Arterial/complicações , Complexo de Eisenmenger/complicações , Endocardite/complicações , Átrios do Coração/anormalidades , Adulto , Antibacterianos/uso terapêutico , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/tratamento farmacológico , Endocardite/diagnóstico por imagem , Endocardite/tratamento farmacológico , Feminino , Humanos
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