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1.
Biochim Biophys Acta Mol Cell Res ; 1868(1): 118858, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32950569

RESUMO

Protein phosphatase 2A (PP2A) complex comprises an extended family of intracellular protein serine/threonine phosphatases, that participate in different signaling transduction pathways. Different functions of PP2As are determined by the variety of regulatory subunits. In this study, CRISPR/Cas9-mediated loss-of-function screen revealed that PPP2R2A downregulation suppressed cell growth in NSCLC cells. AMOTL2 was identified and confirmed as a novel binding partner of PPP2R2A in NSCLC cells by mass spectrometry, CO-IP, GST pull-down and immunofluorescence. Upregulation of AMOTL2 also led to cell proliferation delay in human and mouse lung tumor cells. The proto-oncogene JUN is a key subunit of activator protein-1 (AP-1) transcription factor which plays crucial role in regulating tumorigenesis and its activity is negatively regulated by the phosphorylation at T239. Our results showed that either AMOTL2 upregulation or PPP2R2A downregulation led to great increase in JUN T239 phosphorylation. AMOTL2 bound PPP2R2A in cytoplasm, which reduced nuclear localization of PPP2R2A. In conclusion, AMOTL2 and PPP2R2A act respectively as negative and positive regulator of cell growth in NSCLC cells and function in the AMOTL2-PPP2R2A-JUN axis, in which AMOTL2 inhibits the entry of PPP2R2A into the nucleus to dephosphorylate JUN at T239.

2.
Biosens Bioelectron ; 171: 112737, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080464

RESUMO

Olfaction is a synthetic sense in which odor mixtures elicit emergent perceptions at the expense of perceiving the individual components. The most common result of mixing two odors is masking one component by another. However, there is lack of analytical techniques for measuring the sense of smell, which is mediated by cross-odorant interactions. Here, we propose a biohybrid nose for objective and quantitative evaluation of malodor masking efficiency of perfumed products. This biohybrid nose is constructed by integrating mammalian olfactory epithelium with microelectrode array chip to read out the olfactory information as electrical signal from multiple tissue sites. The intrinsic odor response of olfactory epithelium is found to be represented by widespread spatiotemporal oscillatory activity. The masking efficiency of fragrance is quantified by calculating the relative difference between the malodor and the binary mixture (malodor + fragrance) response patterns. Results indicate that masking efficiency of fragrance is concentration-dependent, whereas completely masking may occurs when fragrance is employed at a concentration 2-3 orders of magnitude higher than malodor. This study demonstrates for the first time that capitalizing on the biological sense of smell to create biohybrid system provides an effective technique to resolve more complex biosensing-related issues such as odor interactions in mixtures.

3.
JAMA Netw Open ; 3(11): e2024385, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33151318

RESUMO

Importance: Secondhand smoke (SHS) exposure is associated with many health conditions in children and adults. Millions of individuals in the US are currently exposed to SHS in their homes. Objective: To investigate whether a federal ban on smoking in public housing settings was associated with a decrease in indoor SHS levels in New York City public housing developments 12 months after the policy's implementation. Design, Setting, and Participants: This cohort study tracked indoor air quality longitudinally from April 2018 to September 2019 and used difference-in-differences analysis to examine SHS exposure before vs after implementation of the 2018 federal smoke-free housing (SFH) policy in 10 New York City Housing Authority (NYCHA) buildings vs 11 matched low-income buildings not subject to the SFH policy (ie, Section 8 buildings). Exposures: Federal SFH policy implementation, beginning July 30, 2018. Main Outcomes and Measures: Comparison of nicotine concentration levels from passive, bisulfate-coated filters before vs 12 months after implementation of the federal SFH policy. Secondary outcomes included changes in particulate matter less than 2.5 µm in diameter, measured with low-cost particle monitors, and counts of cigarette butts in common areas. Results: Air quality was measured repeatedly in a total of 153 NYCHA and 110 Section 8 nonsmoking households as well as in 91 stairwells and hallways. Before the SFH policy implementation, air nicotine was detectable in 19 of 20 stairwells (95.0%) in NYCHA buildings and 15 of 19 stairwells (78.9%) in Section 8 buildings (P = .19) and in 17 of 19 hallways (89.5%) in NYCHA buildings and 14 of 23 hallways (60.9%) in Section 8 buildings (P = .004). Nicotine was detected less frequently inside nonsmoking apartments overall (26 of 263 [9.9%]) but more frequently in NYCHA apartments (20 of 153 [13.1%]) than in Section 8 apartments (6 of 110 [5.5%]) (P = .04). One year after policy implementation, there was no differential change over time in nicotine concentrations measured in stairwells (DID, 0.03 µg/m3; 95% CI, -0.99 to 1.06 µg/m3) or inside nonsmoking households (DID, -0.04 µg/m3; 95% CI, -0.24 to 0.15 µg/m3). Larger decreases in nicotine concentration were found in NYCHA hallways than in Section 8 hallways (DID, -0.43 µg/m3; 95% CI, -1.26 to 0.40 µg/m3). Conclusions and Relevance: The findings suggest that there was no differential change in SHS in NYCHA buildings 12 months after SFH policy implementation. Additional support may be needed to ensure adherence to SFH policies.

4.
BMC Pregnancy Childbirth ; 20(1): 673, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160306

RESUMO

BACKGROUND: The effect and extent of abnormal placental perfusion (APP) on the risk of male hypospadias are poorly understood. We compared the prevalence of male hypospadias in the offspring of women with APP and quantify the extent of the APP effect on the anomaly. METHODS: A hospital-based retrospective analysis of births from 2012 to 2016 was conducted in 2018. Women of singleton pregnancy and male infants born to them were included (N = 21,447). A multivariate analysis was performed to compare the prevalence of male hypospadias in infants exposed to APP with those that were not exposed to APP. RESULTS: Compared with the infants of women without APP, infants of women with APP showed an increased risk of male hypospadias (odds ratio, 2.40; 95% confidence interval, 1.09-5.29). The male hypospadias cumulative risk increased with the severity of APP. Infants exposed to severe APP had a significantly higher risk of male hypospadias than those without APP exposure (9.2 versus 1.7 per 1000 infants, P < 0.001). A path analysis indicated that 28.18-46.61% of the risk of hypospadias may be attributed to the effect of APP. CONCLUSIONS: Male hypospadias risk was associated with APP and increased with APP severity, as measured in the second trimester. APP had an important role in the development of the anomaly.

5.
Int Immunopharmacol ; 88: 107021, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33182037

RESUMO

Mammalian Ste20-like kinase 4 (MST4), a new member of the germinal-center kinase STE20 family, was recently demonstrated to be a negative regulator of inflammation. However, whether MST4 participates in the inflammatory response to fungal infection remains unknown. Our study investigated the role and molecular mechanisms of MST4 in mice cornea and corneal epithelial cells exposed to Aspergillus fumigatus (A. fumigatus). Protein level of MST4 was detected in mice corneas and human corneal epithelial cells (HCECs) by Western blot analysis. The MST4 protein level was significantly elevated in mice corneas infected with A. fumigatus and HCECs exposed to A. fumigatus. MST4 expression was also detected in mice corneas by immunofluorescence staining. Furthermore, we found recombinant MST4 inhibited proinflammatory cytokines expressions induced by A. fumigatus at both the mRNA and protein levels in mice corneas and HCECs. To further investigate the mechanism of MST4's anti-inflammatory effect in A. fumigatus keratitis, we verified recombinant MST4 can inhibit curdlan-mediated proinflammatory cytokines production in HCECs. Surprisingly, recombinant MST4 protein downregulated A. fumigatus-induced Dectin-1 expression in both mRNA and protein levels in mice corneas. Recombinant MST4 can inhibit the mRNA expression level of Dectin-1 which was induced by curdlan in HCECs. MST4 can also inhibit the expression of Dectin-1 in mRNA levels increased by Dectin-1 overexpression plasmid in HCECs. Moreover, A. fumigatus or curdlan significantly induced the phosphorylation of Syk, which was consequently suppressed by recombinant MST4. Finally, recombinant MST4 promotes HCECs proliferation, which contribute to cornea wound healing. Taken together, our results provide evidences that MST4 inhibits inflammatory signaling response in A. fumigatus keratitis by downregulating Dectin-1/p-Syk pathway and simultaneously promotes HCECs proliferation.

6.
Int Immunopharmacol ; 88: 106989, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33182069

RESUMO

Retinal ischemia/reperfusion (I/R) occurs in various vision disabled ocular diseases, involved in acute glaucoma, diabetic retinopathy, ischemic optic neuropathy, hypertensive retinopathy and retinal vascular occlusion. Laquinimod (LQ), a new type of immunosuppressant, has been reported to exert anti-inflammatory effects on autoimmune diseases. This research aims to investigate the protective effect of LQ on I/R damage by focusing on inhibiting dysregulated neuroinflammation and neuronal apoptosis. In our study, mice were treated with LQ after high intraocular pressure (IOP)-induced retinal I/R injury. The data showed that LQ significantly attenuated high IOP-induced retinal ganglion cell (RGC) death and inner plexiform layer (IPL) thinning and inhibited microglial activation. The results of qRT-PCR, flow cytometry and Luminex multiplex assays demonstrated the anti-inflammatory action of LQ in BV2 cells stimulated with lipopolysaccharide (LPS). In addition, primary RGC apoptosis induced by oxygen-glucose deprivation/reperfusion (OGD/R) was also directly suppressed by LQ. Importantly, LQ inhibited the expression of cleaved caspase-8 and the downstream NLRP3 inflammasome and IL-1ß. In conclusion, our findings offer the first evidence that LQ treatment prevents retinal I/R damage. Furthermore, LQ could directly inhibit RGC apoptosis. Caspase-8 activation and subsequent inflammation can also be suppressed by LQ, which suggests that LQ may act through inhibiting the caspase-8 pathway. This study demonstrates a new mechanism of LQ and provides beneficial preclinical data for the clinical application of LQ.

7.
J Cell Physiol ; 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33184860

RESUMO

Morphine, a mu-opioid receptor (MOR) agonist, has been extensively used to treat advanced cancer pain. In particular, in patients with cancer metastasis, both morphine and anticancer drugs are given simultaneously. However, evidence showed that morphine might be a risk factor in promoting the tumor's malignant potential. In this study, we report that treatment with morphine could activate MOR and lead to the promotion of proliferation, migration, and invasion in HCT116 and DLD1 colorectal cancer (CRC) cells with time-concentration dependence. Moreover, morphine can also contribute to cetuximab's drug resistance, a targeted drug widely used to treat advanced CRC by inducing the activation of epidermal growth factor receptor (EGFR). The cell phenotype includes proliferation, migration, invasion, and drug resistance, which may be reversed by MOR knockdown or adding nalmefene, the MOR receptor antagonist. Receptor tyrosine kinase array analysis revealed that morphine selectively induced the transactivation of EGFR. EGFR transactivation resulted in the activation of ERK1/2 and AKT. In conclusion, morphine induces the transactivation of EGFR via MOR. It activates the downstream signal pathway AKT-MTOR and RAS-MAPK, increases proliferation, migration, and invasion, and promotes resistance to EGFR inhibitors in a CRC cell line. Furthermore, we verified that EGFR inhibition by cetuximab strongly reversed the protumoral effects of morphine in vitro and in vivo. Collectively, we provide evidence that morphine-EGFR signaling might be a promising therapeutic target for CRC patients, especially for cetuximab-resistant CRC patients.

8.
Updates Surg ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146887

RESUMO

Although the number of robotic hepatectomy (RH) performed is increasing, few studies have reported its efficacy in comparison with the conventional surgical modalities. The aim of this meta-analysis was to evaluate the perioperative results of RH vs. open hepatectomy (OH) and RH vs. laparoscopic hepatectomy (LH). We systematically searched for English papers published in PubMed (Medline), Embase, and Cochrane library before March 1, 2020. A total of 39 papers and 2999 patients were eventually included. Among the included patients, 1249, 1010, and 740 underwent RH, LH, and OH, respectively. Compared with OH, the operation time was significantly increased but the intraoperative blood loss, blood transfusion rate, incidence of severe complications, and length of postoperative hospitalization were significantly reduced in patients with RH. However, there was no significant difference in the use of Pringle maneuver and overall incidence of complications. Compared with LH, the operation time was significantly increased, and the intraoperative blood loss was also more in RH. However, there were no differences in blood transfusion rate, use of Pringle maneuver, incidence of complications, incidence of severe complications, and length of postoperative hospitalization between the two groups. A longer operation time remains the main shortcoming of RH. However, based on the perioperative clinical efficacy, we conclude that RH is comparable to LH but is better than OH for selected patients.

9.
Vet Microbiol ; 251: 108905, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33186757

RESUMO

Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), is the most important immunosuppressive disease threatening the poultry industry worldwide. Recently, the novel variant IBDV has been emerging in large-scale in Asia including China and is becoming a new threat to the healthy development of the poultry industry, but no ideal vaccine is available. Therefore, it is necessary and urgent to develop a new vaccine against the novel variant IBDV. In this study, based on the skeleton of an attenuated vaccine strain Gt, a reassortment virus strain rGtVarVP2 was constructed for the first time, which could express the main protective antigen VP2 of the novel variant IBDV and replicate well in cell culture. Subsequently, the safety and effectiveness of rGtVarVP2 were further evaluated using animal experiments. The rGtVarVP2 is nonpathogenic to specific-pathogen-free (SPF) chicken. The immunization of rGtVarVP2 could induce the specific neutralizing antibodies against the novel variant IBDV. The challenge protection tests further confirmed the effectiveness of the IBDV reassortment virus rGtVarVP2. No atrophy and obvious lesions were observed in the immunization group while the bursae of non-immunization control group were severely destroyed after challenge, which showed that rGtVarVP2 could provide complete protection against the novel variant IBDV. These data indicate that the vaccine candidate (rGtVarVP2 strain) is safe and effective, which is of great significance for comprehensive control of IBD and healthy breeding.

10.
Emerg Microbes Infect ; : 1-8, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33215979

RESUMO

Toxoplasmosis is a foodborne parasitic disease. Toxoplasma gondii oocysts in the environment are a threat to humans and animals. White spoonbills could serve as a sentinel animal for T. gondii contamination in the environment because of their food intake from soil or water. This study is aimed to evaluate the prevalence of T. gondii in white spoonbills and isolate viable T. gondii from white spoonbills. In 28.6% (2/7) of white spoonbills, T. gondii antibodies were found in heart juice by the modified agglutination test (cut-off: 1:4). T. gondii DNA was detected in tissues of 42.9% (3/7) white spoonbills. One viable T. gondii strain, named TgSpoonbillCHn1, was isolated from the myocardium of a white spoonbill by bioassay in mice. DNA extracted from TgSpoonbillCHn1 tachyzoites was characterized by PCR-restriction fragment length polymorphism with ten markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) and the virulence genes ROP5 and ROP18. The results revealed that it was ToxoDB#2 (Type III). The ROP18/ROP5 genotype combination predicts that this strain is avirulent for mice, which is supported by the infection experiments in mice. This is the first report of the isolation of viable T. gondii strain from white spoonbil. The prevalence of T. gondii in white spoonbills may be indicative of environmental contamination of oocysts. This report provides direct evidence of white spoonbill as an intermediate host of T. gondii.

11.
Mol Reprod Dev ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216405

RESUMO

Psychological stress can affect female reproduction by deteriorating oocyte quality, but the molecular mechanism is unclear. In this study, we used the chronic unpredictable stress model to study the effect of psychological stress on mouse oocyte competence during preimplantation stage, and RNA sequencing in single oocytes to analyze differential gene expression at the transcription level. Stress changed the serum levels of glucocorticoids and reduced oocyte developmental potential, depending on the strength of the stress. Strong stress (two stressors per day) reduced the fertilization rate and induced significant apoptosis in blastocysts. Moderate stress (one stressor per day) reduced the cleavage rate and blastocyst formation rate. Weak stress (one stressor every 2 days) did not have any significant negative effect on the fertilization, cleavage, and blastocyst formation. Hatching rate was not affected by stress, but stress retarded the development of the expanded blastocysts and inhibited the embryo development at early stages. Transcriptome analysis revealed that stress disturbed the expression of cell cycle regulators and apoptotic genes. The hub genes identified through protein-protein interaction analysis include Msln, Ceacam12, Psg16, Psg17, and Psg23, which are all carcinoembryonic or related genes involved in cell adhesion, proliferation, and migration. Thus, stress was inhibitory on fertilization and early embryo development in mice.

12.
Aging (Albany NY) ; 122020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206628

RESUMO

Heart failure (HF) affects over 26 million people worldwide, yet the pathologies of this complex syndrome have not been completely understood. Here, we investigated the involvement of deacetylase Sirtuin 1 (Sirt1) in HF and its downstream signaling pathways. A HF model was induced by the ligation of the left coronary artery in rats, where factors associated with left ventricular echocardiography, heart hemodynamics and ventricular mass indexes were recorded. Collagen volume fraction in heart tissues was determined by Masson's trichrome staining. Cell models of HF were also established (H2O2, 30 min) in cardiomyocytes harvested from suckling rats. HF rats presented with downregulated expressions of Sirt1, brain-derived neurotrophic factor (BDNF) and exhibited upregulated expressions of NF-κB p65 and miR-155. Repressed Sirt1 expression increased acetylation of NF-κB p65, resulting in the elevation of NF-κB p65 expression. NF-κB p65 silencing improved heart functions, decreased ventricular mass and reduced apoptosis in cardiomyocytes. MiR-155 inhibition upregulated its target gene BDNF, thereby reducing cardiomyocyte apoptosis. Sirt1 overexpression upregulated BDNF, improved heart function, and reduced apoptosis in cardiomyocytes. In conclusion, Sirt1 alleviates HF in rats through the NF-κB p65/miR-155/BDNF signaling cascade.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33174357

RESUMO

Tin halide perovskites are rising as promising materials for lead-free perovskite solar cells (PSCs). However, the crystallization rate of tin halide perovskites is much faster than the lead-based analogs, leading to more rampant trap states and much lower power conversion efficiencies. Here, we disclose a key finding to modulate the crystallization kinetics of FASnI 3 (FA: formamidinium) through a non-classical nucleation mechanism based on pre-nucleation clusters (PNCs). By introducing piperazine dihydriodide to tune the colloidal chemistry of the FASnI 3 perovskite precursor solution, stable clusters could be readily formed in the solution before nucleation. These pre-nucleation clusters act as intermediate phase and thus can reduce the energy barrier for the perovskite nucleation. The precursor solution enriched with such intermediate PNCs could be readily converted to a high-quality perovskite film with a much lower defect density. This PNCs-based method has led to a conspicuous photovoltaic performance improvement for FASnI 3 -based PSCs, delivering an impressive efficiency of 11.39% plus improved stability.

14.
J Ultrasound Med ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174632

RESUMO

OBJECTIVES: Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, raising widespread public health concerns. Our team treated hospitalized patients with COVID-19 in Wuhan, where the outbreak first began, and we suspected that SARS-CoV-2 may cause testicular infection in male patients. We conducted this study to explore that observation. METHODS: We enrolled male patients with a confirmed diagnosis of COVID-19 and performed a bedside ultrasound (US) examination of the scrotum, focused on findings of acute inflammation such as tunica albuginea thickening, enlargement and heterogeneous echogenicity of the testis, epididymis, or both, an abscess, scrotal wall edema, and hydrocele. Then we compared the proportions of observed epididymo-orchitis in patients from different age groups and COVID-19 severity groups. RESULTS: A total of 142 patients with COVID-19 were enrolled in our study, and 32 (22.5%) patients had acute orchitis, epididymitis, or epididymo-orchitis on scrotal US imaging, according to the diagnosis criteria. The observed risk of acute scrotal infection increased with age, with the incidence reaching 53.3% in men older than 80 years. We also observed that men with severe COVID-19 had a significantly higher possibility of epididymo-orchitis compared to the nonsevere COVID-19 group (P = .037). CONCLUSIONS: This study shows US imaging evidence that SARS-CoV-2 may cause infection of the testis or epididymis, and the risk is worthy of the attention of clinicians.

15.
Clin Psychol Rev ; 83: 101932, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33176244

RESUMO

To evaluate the global prevalence of antenatal depression and clarify its potential associated factors, we conducted two systematic reviews and meta-analyses, where appropriate. PubMed, Web of Science, and Embase were used to identify studies published up to Feb 28, 2019. The pooled prevalence of any antenatal depression across 173 studies with 182 reports was 20.7% (95% CI 19.4-21.9%, P = 0.000, I2 = 98.4%), and the pooled prevalence of major antenatal depression across 72 studies with 79 reports was 15.0% (95% CI 13.6-16.3%, P = 0.000, I2 = 97.8%). The prevalence of antenatal depression was higher in low- or lower-middle-income countries, and in studies using self-report instruments or conducted after the year 2010. History of depression, lack of social support, single/separated/divorced status, unplanned pregnancy, unemployment, experience of violence, and smoking before or during pregnancy were significantly associated with antenatal depression. The results of our study indicated that a significant number of pregnant women experience depression and verified some factors that are related to this disorder. As countermeasures, it is important to develop effective risk assessment strategies as well as prevention and intervention strategies for antenatal depression based on its associated factors.

16.
Sci Rep ; 10(1): 16679, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028902

RESUMO

Skeletal muscle and the neuromuscular junction are the earliest sites to manifest pathological changes in amyotrophic lateral sclerosis (ALS). Based on prior studies, we have identified a molecular signature in muscle that develops early in ALS and parallels disease progression. This signature represents an intersection of signaling pathways including Smads, TGF-ß, and vitamin D. Here, we show that the Wnt antagonist, Frizzled Related Protein (FRZB), was increased in ALS muscle samples and to a variable extent other denervating disease but only minimally in acquired myopathies. In the SOD1G93A mouse, FRZB was upregulated in the early stages of disease (between 40 and 60 days) until end-stage. By immunohistochemistry, FRZB was predominantly localized to endomysial connective tissue and to a lesser extent muscle membrane. There was a significant increase in immunoreactivity surrounding atrophied myofibers. Because FRZB is a Wnt antagonist, we assessed ß-catenin, the canonical transducer of Wnt signaling, and found increased levels mainly at the muscle membrane. In summary, we show that FRZB is part of a molecular signature of muscle denervation that may reflect disease progression in ALS. Our findings open up avenues for future investigation as to what roles FRZB and Wnt signaling might be playing in muscle denervation/reinnervation.

17.
Arthritis Res Ther ; 22(1): 255, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097076

RESUMO

OBJECTIVE: The aim of this study was to investigate the role of serum IgE levels in the clinical features and outcomes of IgG4-related disease (IgG4-RD). METHODS: We retrospectively enrolled 459 newly diagnosed IgG4-RD patients with serum IgE examined at baseline from 2012 to 2019 and compared the clinical features between group A (serum IgE level ≤ 60 KU/L) and group B (serum IgE level > 60 KU/L). Subsequently, 312 patients who had been followed up for ≥ 1 year were further selected to evaluate the correlation between serum IgE level and disease outcome. RESULTS: At baseline, the serum IgE level was positively correlated with the serum IgG4 level (r = 0.1779, P = 0.0001), eosinophil count (r = 0.3004, P < 0.0001), and serum IgG level (r = 0.2189, P < 0.0001) in IgG4-RD patients. Compared with group A, group B had more patients with allergic diseases (P = 0.004), more organ involvement (P = 0.003), and higher IgG4-RD responder index scores (P = 0.002). During follow-up, group A patients had a higher remission induction rate than group B patients (88.4% vs. 73.6%, P = 0.035), while group B patients had a higher relapse rate than group A patients (29.0% vs. 16.2%, P = 0.039). Multivariate analysis found that a serum IgE level > 125 KU/L at baseline was a risk factor for disease relapse (hazard ratio [HR], 1.894 [95% confidence interval (CI) 1.022-3.508]; P = 0.042). Cox regression analysis showed that elevation of the eosinophil count was a risk factor for relapse in both group A and group B patients (HR, 8.504 [95% CI 1.071-42.511]; P = 0.009; and HR, 2.078 [95% CI 1.277-3.380]; P = 0.003, respectively), and the involvement of the lacrimal gland (HR, 1.756 [95% CI 1.108-2.782]; P = 0.017), submandibular gland (HR, 1.654 [95% CI 1.037-2.639]; P = 0.035), and kidney (HR, 3.413 [95% CI 1.076-10.831]; P = 0.037) were also risk factors for relapse in group B patients. CONCLUSION: IgG4-RD patients with high serum IgE levels at baseline were more likely to have higher disease activity, and baseline high IgE levels were associated with disease relapse.

18.
Ecotoxicol Environ Saf ; 206: 111388, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33007543

RESUMO

Black carbon (BC) and heavy metal lead (Pb), as typical components of atmospheric PM2.5, have been shown to cause a variety of adverse health effects. However, co-exposure to BC and Pb may induce pulmonary damage by aggravating toxicity via an unknown mechanism. This study aimed to investigate the combined toxicity of carboxylated black carbon (c-BC) and lead acetate (Pb) on human bronchial epithelial cells (BEAS-2B) at the no-observed-adverse-effect level (NOAEL). Cells were exposed to c-BC (6.25 µg/mL) and Pb (4 µg/mL) alone or their combination, and their combined toxicity was investigated by focusing on cell viability, oxidative stress, DNA damage, mitochondrial membrane potential (MMP), apoptosis, and cellular inflammation. Factorial analyses were also used to determine the potential interactions between c-BC and Pb. The results suggested that the combination of c-BC and Pb could significantly increase the production of reactive oxygen species (ROS), malondialdehyde (MDA), and lactate dehydrogenase leakage (LDH) and decrease the activities of glutathione (GSH) and superoxide dismutase (SOD). The excessive oxidative stress could increase the levels of inflammatory cytokine IL-6 and TNF-α, and induce oxidative DNA damage and dissipation of MMP. Moreover, the results also suggested that the combined group could enhance the cellular apoptotic rate and the activation of apoptotic markers like caspase-3, caspase-8, and caspase-9. The factorial analysis further demonstrated that synergistic interaction was responsible for the combined toxicity of c-BC and Pb co-exposure. Most noticeably, the co-exposure of c-BC and Pb could induce some unexpected toxicity, even beyond the known toxicities of the individual compounds in BEAS-2B cells at the NOAEL.

19.
FASEB J ; 34(12): 16414-16431, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070372

RESUMO

Polyphyllin I (PPI) is a natural phytochemical drug isolated from plants which can inhibit the proliferation of cancer cells. One of the PPI tumor-inhibitory effects is through downregulating the expression of Cancerous Inhibitor of PP2A (CIP2A), the latter, is found upregulated in Alzheimer's disease (AD) brains and participates in the development of AD. In this study, we explored the application of PPI in experimental AD treatment in CIP2A-overexpressed cells and 3XTg-AD mice. In CIP2A-overexpressed HEK293 cells or primary neurons, PPI effectively reduced CIP2A level, activated PP2A, and decreased the phosphorylation of tau/APP and the level of Aß. Furthermore, synaptic protein levels were restored by PPI in primary neurons overexpressing CIP2A. Animal experiments in 3XTg-AD mice revealed that PPI treatment resulted in decreased CIP2A expression and PP2A re-activation. With the modification of CIP2A-PP2A signaling, the hyperphosphorylation of tau/APP and Aß overproduction were prevented, and the cognitive impairments of 3XTg-AD mice were rescued. In summary, PPI ameliorated AD-like pathology and cognitive impairment through modulating CIP2A-PP2A signaling pathway. It may be a potential drug candidate for the treatment of AD.

20.
Hum Brain Mapp ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33112483

RESUMO

How native and non-native languages are represented in the brain is one of the most important questions in neurolinguistics. Much research has found that the similarity in neural activity of native and non-native languages are influenced by factors such as age of acquisition, language proficiency, and language exposure in the non-native language. Nevertheless, it is still unclear how the similarity between native and non-native languages in orthographic transparency, a key factor that affects the cognitive and neural mechanisms of phonological access, modulates the cross-language similarity in neural activation and which brain regions show the modulatory effects of language distance in orthographic transparency. To address these questions, the present study used representational similarity analysis (RSA) to precisely estimate the neural pattern similarity between native language and two non-native languages in Uyghur-Chinese-English trilinguals, whose third language (i.e., English) was more similar to the native language (i.e., Uyghur) in orthography than to their second language (i.e., Chinese). Behavioral results revealed that subjects responded faster to words in the non-native language with more similar orthography to their native language in the word naming task. More importantly, RSA revealed greater neural pattern similarity between Uyghur and English than between Uyghur and Chinese in select brain areas for phonological processing, especially in the left hemisphere. Further analysis confirmed that those brain regions represented phonological information. These results provide direct neuroimaging evidence for the modulatory effect of language distance in orthographic transparency on cross-language pattern similarity between native and non-native languages during word reading.

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