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1.
Cancer Lett ; 524: 15-28, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461182

RESUMO

Sunitinib is the first-line drug for treating renal cell carcinoma (RCC), and it functions mainly through inhibition of tumor angiogenesis. However, the patients may become insensitive or develop resistance toward sunitinib treatment, but the underlying mechanisms have not yet been fully elucidated. Herein, it was found that sunitinib could have adverse effects of promoting RCC progression by increasing vascular mimicry (VM) formation of RCC cells. Mechanism dissection revealed that sunitinib can increase the expression of a long non-coding RNA (lncRNA), lncRNA-ECVSR, thereby enhancing the stability of estrogen receptor ß (ERß) mRNA. Subsequently, the increased ERß expression can then function via transcriptional up-regulation of Hif2-α. Notably, sunitinib-increased lncRNA-ECVSR/ERß/Hif2-α signaling resulted in an increased cancer stem cell (CSC) phenotype, thereby promoting VM formation. Furthermore, the sunitinib/lncRNA-ECVSR-increased ERß expression can transcriptionally regulate lncRNA-ECVSR expression via a positive-feedback loop. Supportively, preclinical studies using RCC mouse xenografts demonstrated that combining sunitinib with the small molecule anti-estrogen PHTPP can increase sunitinib efficacy with reduced VM formation. Collectively, the findings of this study may aid in the development of potential biomarker(s) and novel therapies to better monitor and suppress RCC progression.

2.
Phys Rev Lett ; 127(16): 161101, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34723593

RESUMO

Light axion fields, if they exist, can be sourced by neutron stars due to their coupling to nuclear matter, and play a role in binary neutron star mergers. We report on a search for such axions by analyzing the gravitational waves from the binary neutron star inspiral GW170817. We find no evidence of axions in the sampled parameter space. The null result allows us to impose constraints on axions with masses below 10^{-11} eV by excluding the ones with decay constants ranging from 1.6×10^{16} to 10^{18} GeV at a 3σ confidence level. Our analysis provides the first constraints on axions from neutron star inspirals, and rules out a large region in parameter space that has not been probed by the existing experiments.

3.
Heart Lung ; 51: 25-31, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34731694

RESUMO

BACKGROUND: Fixed-dose combination (FDC) of Aclidinium (ACL) and Formoterol (FOR) is a maintenance therapy for patients with stable chronic obstructive pulmonary disease (COPD). Although the effect of combination of long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) is less compared with the statistical sum of the effects of LABA and LAMA alone, the effect of combination of LABA and LAMA is significantly higher than that of either of the two. Thus, the resulting therapeutic effect in pulmonary function, improvement of dyspnea, quality of life, and incidence of adverse events was analyzed to explore the efficacy of FDC and monotherapy of either ACL or FOR in stable COPD patients. METHODS: Methods Chronic obstructive pulmonary disease (COPD), aclidinium or LAMA, formoterol or LABA, randomized controlled trials, or RCT were used as keywords in the search for studies in PubMed, EMBASE, Cochrane Library, Reference List, and Clinicaltrails.gov databases. Studies that evaluated efficacy and side effects of Fixed-dose combination of Aclidinium/Formoterol and Monotherapy of Aclidinium or Formoterol in COPD published between the establishment period of the database and June 2020 were retrieved. Two independent reviewers extracted the data; Revman 5.3 software was used for data analysis with dose efficacy and side effects were presented as mean difference at 95% confidence interval. Notably, ACL 400 mg / FOR 12ug and ACL 400 mg / 6ug were used as subgroup analysis. RESULTS: A total of 6 studies with 7,081 patients were enrolled for analysis. The trough forced expiratory volume in 1 second (FEV1) mean difference (MD) for FDC was 0.01 (95% CI, - 0.01 to 0.03); St George's respiratory COPD specific questionnaire (SGRQ) MD for FDC was - 0.76 (95% CI, - 1.81 to 0.29); transitional dyspnea index (TDI) MD for FDC was 0.33 (95% CI, 0.06 to 0.60) compared to that of ACL. Furthermore, trough FEV1 MD for FDC was 0.05 (95% CI, 0.03 to 0.06); SGRQ MD for FDC was - 1.52 (95% CI, - 2.57 to-0.47); TDI MD for FDC was 0.43 (95% CI, 0.15 to 0.70) compared to that of the FOR. The evidence for each result was accurate and the results were unaffected by the duration of the study. CONCLUSION: The findings of this study showed that, unlike monotherapies, FDC significantly improves lung function, dyspnea, and quality of life. In addition, FDC significantly improves dyspnea compared to ACL alone.

4.
Pestic Biochem Physiol ; 179: 104970, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802520

RESUMO

The widespread use of herbicides has raised considerable concern with regard to their harmful consequences on plant growth, crop yield and the soil ecological environment. It has been well documented that colonization of rhizobacteria in the plant root system has a positive effect on activation of plant defenses to protect the plant from damage. Using the platform of high-throughput analysis with tandem mass spectrometry and Illumina sequencing, we identified the specific activated rhizobacteria, the key growth stimulating substances and the metabolic pathways involved in seedling stage tolerance to mefenacet stress in rice. The relative abundance of beneficial rhizospheremicrobes such as Acidobacteria and Firmicutes increased with mefenacet treatment, indicating that the rhizosphere recruited some beneficial microbes to resist mefenacet stress. Mefenacet treatment induced alterations in several interlinked metabolic pathways, many of which were related to activation of defense response signaling, especially the indole-3-pyruvate pathway. Indole-3-acetaldehyde and indole-3-ethanol from this pathway may act as flexible storage pools for indole-3-acetic acid (IAA). Our findings also suggest that a significant increase of IAA produced by the enrichment of beneficial rhizospheremicrobes, for example genus Bacillus, alleviated the dwarfing phenomenon observed in hydroponic medium following mefenacet exposure, which may be a key signaling molecule primarily for phytostimulation and phytotolerance in microbe-plant interactions.


Assuntos
Oryza , Rizosfera , Acetanilidas , Benzotiazóis , Raízes de Plantas , Microbiologia do Solo
5.
Opt Express ; 29(24): 40668-40676, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809401

RESUMO

Coherence and steerability are two essential characteristics of quantum systems. For a two-qubit state, the first-order coherence and the maximal violation of linear steering inequality are used to operationally measure the degree of coherence and steerability, respectively. Recently, a complementary relation between first-order coherence and linear steerability has been proposed. In this paper, we report an experimental verification of the complementary relation by preparing biphoton polarization entangled states in an all-optical setup. We propose an operable method for experimental measurement of the first-order coherence and linear steerability and calculate the purity of the initial states by reconstructing the density matrices of them. The experimental results coincide with the theoretical predictions very well, which provides a valuable reference for the application of optical quantum technology.

6.
Se Pu ; 39(12): 1314-1323, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34812003

RESUMO

Rice is an important cereal that is consumed as both an energy and protein source by a large proportion of the population worldwide. However, clinical studies have found that rice grains are responsible for cases of severe asthma, eczema, and atopic dermatitis in some adult patients. Several allergenic proteins have been identified and biochemically and immunochemically characterized from rice grains. These include α-amylase/trypsin inhibitors, glyoxalase Ⅰ, and α-globulin. In this study, we proposed an approach for the simultaneous quantification of three allergenic proteins in rice and its products, based on a stable isotope-labeled signature peptide standard and liquid chromatography-tandem mass spectrometry. Samples of rice and products were extracted by a salt solution, hydrolyzed by Lys-C and Trypsin, and purified by C18-SD. The linear ion trap-high resolution mass spectrometry (LTQ-Orbitrap) and Protein Discovery software were used to acquire and identify allergenic proteins in rice samples. In present study, three proteins including seed allergenic protein RAG2, glyoxalase Ⅰ, and 19 kDa globulin were identified. To establish a stable quantitative detection method, the signature peptides selected from the identified enzymatic hydrolysis peptides must have greater abundance and higher specificity as characteristic peptides. Three corresponding signature peptides in rice were screened based on the principles of previous study, and were validated through comparisons of the basic local alignment search tool (BLAST) with the NCBI and UniProt databases. The three signature peptides were successively eluted by liquid chromatography and separated on a Poroshell column. They were then detected by positive electrospray ionization (ESI+) in multiple reaction monitoring mode and quantified by an isotope dilution method. To achieve an improvement in the detection sensitivity and specificity, mass spectrometry parameters, such as the collision energy of three ion pairs of each peptide, were optimized. Three recombinant allergenic proteins and the winged stable isotope-labeled signature peptide standard were synthesized. These were then used to compare the effects of different enzymatic conditions, including hydrolysis solvents containing sodium dodecyl sulfate (SDS) with different contents, as well as the enzymes and their amounts, on the digestion efficiency. The data showed that the digestion efficiency of the three proteins could be improved to 65.7%-97.3% when 1 g/L of the SDS-containing hydrolysis solvent, and the combined digestion strategy of Lys-C and Trypsin, were adopted in the enzymatic process. These results indicate the following inferences: a small amount of SDS (1 g/L) in the enzymatic hydrolysis system is beneficial to complete protein denaturation, a Lys-C and Trypsin combined digestion strategy can complement the shortcomings of the two enzymes and improve the digestion efficiency, and the recoveries of the three proteins was not significantly increased by increasing the amount of enzyme when the ratio of protein to enzyme reached more than 20∶1. The method displayed good linearity in the range of 1-200 nmol/L with the correlation coefficients greater than 0.9972. The limits of detection and limits of quantification of the three proteins were 3 mg/kg and 10 mg/kg, respectively. The average recoveries of the three proteins spiked at three levels in different matrices ranging between 80.6%-103.7%, with the intra-day and inter-day precision less than 11.5%. Due to its high stability, excellent sensitivity, and simple operation, this method presents a wide range of application prospects in the analysis of the three allergenic proteins in different rice and rice food products.


Assuntos
Oryza , Cromatografia Líquida de Alta Pressão , Humanos , Isótopos , Peptídeos , Espectrometria de Massas em Tandem
7.
Signal Transduct Target Ther ; 6(1): 405, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795208

RESUMO

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

8.
Nat Commun ; 12(1): 6727, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795303

RESUMO

In transition metal compounds, due to the interplay of charge, spin, lattice and orbital degrees of freedom, many intertwined orders exist with close energies. One of the commonly observed states is the so-called nematic electron state, which breaks the in-plane rotational symmetry. This nematic state appears in cuprates, iron-based superconductor, etc. Nematicity may coexist, affect, cooperate or compete with other orders. Here we show the anisotropic in-plane electronic state and superconductivity in a recently discovered kagome metal CsV3Sb5 by measuring c-axis resistivity with the in-plane rotation of magnetic field. We observe a twofold symmetry of superconductivity in the superconducting state and a unique in-plane nematic electronic state in normal state when rotating the in-plane magnetic field. Interestingly these two orders are orthogonal to each other in terms of the field direction of the minimum resistivity. Our results shed new light in understanding non-trivial physical properties of CsV3Sb5.

9.
Front Neurol ; 12: 761636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795634

RESUMO

Background: Congenital myopathy constitutes a heterogeneous group of orphan diseases that are mainly classified on the basis of muscle biopsy findings. This study aims to estimate the prevalence of congenital myopathy through a systematic review and meta-analysis of the literature. Methods: The PubMed, MEDLINE, Web of Science, and Cochrane Library databases were searched for original research articles published in English prior to July 30, 2021. The quality of the included studies was assessed by a checklist adapted from STrengthening the Reporting of OBservational studies in Epidemiology (STROBE). To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using the random effects model. Heterogeneity was assessed using the Cochrane Q statistic as well as the I 2 statistic. Results: A total of 11 studies were included in the systematic review and meta-analysis. Of the 11 studies included, 10 (90.9%) were considered medium-quality, one (9.1%) was considered low-quality, and no study was assessed as having a high overall quality. The pooled prevalence of congenital myopathy in the all-age population was 1.50 (95% CI, 0.93-2.06) per 100,000, while the prevalence in the child population was 2.73 (95% CI, 1.34-4.12) per 100,000. In the pediatric population, the prevalence among males was 2.92 (95% CI, -1.70 to 7.55) per 100,000, while the prevalence among females was 2.47 (95% CI, -1.67 to 6.61) per 100,000. The prevalence estimates of the all-age population per 100,000 were 0.20 (95% CI 0.10-0.35) for nemaline myopathy, 0.37 (95% CI 0.21-0.53) for core myopathy, 0.08 (95% CI -0.01 to 0.18) for centronuclear myopathy, 0.23 (95% CI 0.04-0.42) for congenital fiber-type disproportion myopathy, and 0.34 (95% CI, 0.24-0.44) for unspecified congenital myopathies. In addition, the prevalence estimates of the pediatric population per 100,000 were 0.22 (95% CI 0.03-0.40) for nemaline myopathy, 0.46 (95% CI 0.03-0.90) for core myopathy, 0.44 (95% CI 0.03-0.84) for centronuclear myopathy, 0.25 (95% CI -0.05 to 0.54) for congenital fiber-type disproportion myopathy, and 2.63 (95% CI 1.64-3.62) for unspecified congenital myopathies. Conclusions: Accurate estimates of the prevalence of congenital myopathy are fundamental to supporting public health decision-making. The high heterogeneity and the lack of high-quality studies highlight the need to conduct higher-quality studies on orphan diseases.

11.
Opt Express ; 29(17): 26822-26830, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615109

RESUMO

Quantum entanglement, quantum steering and Bell nonlocality, as significant quantum resources in the field of quantum information science, can achieve variously valuable quantum information tasks. Among of them, quantum entanglement and Bell nonlocality are the weakest and strongest nonlocal correlations, respectively. One can capture the quantum steering and Bell nonlocality via violating steering inequality and Bell inequality, respectively. In general, the detections of quantum steering and Bell nonlocality are strictly harder than entanglement detection. Here, based on steering inequality test and quantum state tomography, we attain various nonlocal correlations and experimentally demonstrate that the estimations of quantum steering and Bell nonlocality can be realized according to the quantum entanglement of the prepared two-photon test states. The estimated efficiency of quantum steering is stronger than the one of Bell nonlocality in this scenario, i.e., more steerable two-photon test states can be verified through quantum entanglement. In addition, quantum steering and Bell nonlocality are bounded by the corresponding upper and lower bounds, and these bounds cannot be punctured by all prepared two-photon states in experiment. These results are conducive to understand the relations among these nonlocal correlations.

12.
Opt Express ; 29(20): 31337-31347, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615228

RESUMO

The high absorption confined-doped ytterbium fiber with 40/250 µm core/inner-cladding diameter is proposed and fabricated, where the relative doping ratio of 0.75 is selected according to the simulation analysis. By employing this fiber in a tandem-pumped fiber amplifier, an output power of 6.2 kW with an optical-to-optical efficiency of ∼82.22% is realized. Benefiting from the large-mode-area confined-doped fiber design, the beam quality of the output laser is well maintained during the power scaling process with the beam quality factor of ∼1.7 of the seed laser to ∼ 1.89 at the output power of 5.07 kW, and the signal-to-noise ratio of the output spectrum reaches ∼40 dB under the maximum output power. In the fiber amplifier based on the 40/250 µm fully-doped ytterbium fiber, the beam quality factor constantly degrades with the increasing output power, reaching 2.56 at 2.45 kW. Moreover, the transverse mode instability threshold of the confined-doped fiber amplifier is ∼4.74 kW, which is improved by ∼170% compared with its fully-doped fiber amplifier counterpart.

13.
Front Immunol ; 12: 733418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603311

RESUMO

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and abnormal fatigability due to the antibodies against postsynaptic receptors. Despite the individual discrepancy, patients with MG share common muscle weakness, autoimmune dysfunction, and immunosuppressive treatment, which predispose them to infections that can trigger or exacerbate MG. Vaccination, as a mainstay of prophylaxis, is a major management strategy. However, the past years have seen growth in vaccine hesitancy, owing to safety and efficacy concerns. Ironically, vaccines, serving as an essential and effective means of defense, may induce similar immune cross-reactivity to what they are meant to prevent. Herein, we outline the progress in vaccination, review the current status, and postulate the clinical association among MG, vaccination, and immunosuppression. We also address safety and efficacy concerns of vaccination in MG, in relation to COVID-19. Since only a handful of studies have reported vaccination in individuals with MG, we further review the current clinical studies and guidelines in rheumatic diseases. Overall, our reviews offer a reference to guide future vaccine clinical decision-making and improve the management of MG patients.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Miastenia Gravis/imunologia , Miastenia Gravis/patologia , SARS-CoV-2/imunologia , Autoimunidade/imunologia , Humanos , Tolerância Imunológica/imunologia , Vacinas contra Influenza/imunologia , Risco , Vacinação/efeitos adversos
14.
Arch Toxicol ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34642769

RESUMO

Mitochondrial perturbation is a key event in chemical-induced organ toxicities that is incompletely understood. Here, we studied how electron transport chain (ETC) complex I, II, or III (CI, CII and CIII) inhibitors affect mitochondrial functionality, stress response activation, and cell viability using a combination of high-content imaging and TempO-Seq in HepG2 hepatocyte cells. CI and CIII inhibitors perturbed mitochondrial membrane potential (MMP) and mitochondrial and cellular ATP levels in a concentration- and time-dependent fashion and, under conditions preventing a switch to glycolysis attenuated cell viability, whereas CII inhibitors had no effect. TempO-Seq analysis of changes in mRNA expression pointed to a shared cellular response to CI and CIII inhibition. First, to define specific ETC inhibition responses, a gene set responsive toward ETC inhibition (and not to genotoxic, oxidative, or endoplasmic reticulum stress) was identified using targeted TempO-Seq in HepG2. Silencing of one of these genes, NOS3, exacerbated the impact of CI and CIII inhibitors on cell viability, indicating its functional implication in cellular responses to mitochondrial stress. Then by monitoring dynamic responses to ETC inhibition using a HepG2 GFP reporter panel for different classes of stress response pathways and applying pathway and gene network analysis to TempO-Seq data, we looked for downstream cellular events of ETC inhibition and identified the amino acid response (AAR) as being triggered in HepG2 by ETC inhibition. Through in silico approaches we provide evidence indicating that a similar AAR is associated with exposure to mitochondrial toxicants in primary human hepatocytes. Altogether, we (i) unravel quantitative, time- and concentration-resolved cellular responses to mitochondrial perturbation, (ii) identify a gene set associated with adaptation to exposure to active ETC inhibitors, and (iii) show that ER stress and an AAR accompany ETC inhibition in HepG2 and primary hepatocytes.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34627716

RESUMO

Index finger dorsal island flaps were frequently utilized by hand surgeons to reconstruct thumb defects. However, the blood supply of the traditional index finger dorsal island flap comes from the first dorsal metacarpal artery, which has a smaller diameter, more anatomical variation, and can be injured in conjunction with thumb injuries. Therefore, we design an alternative index finger dorsal island flap based on the second dorsal metacarpal artery to treat thumb skin defects. From August 2015 to October 2018, we used the index finger dorsal island flaps with the second dorsal metacarpal artery to treat 11 patients with thumb skin defects. All the flaps and skin grafts survived completely without complications. At the last follow-up, the mean 2PD of the flap was 6.4 mm (45.5% for excellent, 54.5% for good), the mean ROM of the injured thumbs was 115.9° (72.7% for excellent, 27.3% for good), and the mean cosmetics score was 8.6. Our results demonstrate that the index finger dorsal island flap with the second dorsal metacarpal artery is suitable for the reconstruction of thumb skin defects. The flap has an excellent survival rate and good coverage with satisfactory results and represents a promising treatment for the selected patients. Level of Evidence: Therapeutic, level IV.

16.
Neurol Sci ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34677704

RESUMO

BACKGROUND: The incidence of myasthenia gravis (MG) is increasing, and its characteristics in elderly patients are believed to differ from those in younger patients. However, only a few studies have focused on elderly patients with MG. OBJECTIVE: To review the characteristics of MG in elderly patients and evaluate whether older age is an independent factor associated with achieving minimal manifestation status (MMS). METHODS: This retrospective cohort study included 367 patients (319 non-elderly and 48 elderly patients) with MG enrolled at Xiangya Hospital from September 1, 2016, to December 31, 2018. We collected demographic data and information regarding comorbidities, antibody status, Myasthenia Gravis Foundation of America classification, affected muscle groups, thymoma, and treatment. MMS was defined as the primary outcome. RESULTS: Comorbidities were more common in elderly than in younger patients with MG. Anti-acetylcholine receptor antibody was the dominant subtype, whereas anti-muscle-specific tyrosine kinase antibody was rare and detected only in non-elderly patients. Elderly patients were more likely than younger patients to have generalized MG, but the frequency of thymoma was lower (28.5% vs. 10.4%, p = 0.0078). MMS or better was achieved in 154 (48.3%) and 13 (27.1%) non-elderly and elderly patients, respectively. Older age did not appear to be an independent factor associated with MMS (hazard ratio = 0.625; 95% confidence interval, 0.345-1.131). CONCLUSIONS: Older age was not an independent factor for a worse prognosis in patients with MG. The treatment of elderly patients with MG should be individually tailored.

17.
J Dermatol Sci ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34674925

RESUMO

BACKGROUND: Oncostatin M (OSM), an interleukin-6 (IL-6) family proinflammatory cytokine, plays a critical role in inflammatory skin diseases, but its mechanism of action is not well understood. OBJECTIVE: To demonstrate the mechanism of OSM induced pyropotosis in normal human epidermal keratinocytes (NHEKs) and immortalized human keratinocytes (HaCaT cells). METHODS: NHEKs and HaCaT cells were treated with OSM. Knockout of OSM receptor (OSMR) with CRISPR/Cas9 system, knockdown of GSDME with small interfering RNA and primary keratinocytes from Osmr-/- and Gsdme-/- mice were used to study the effect of OSMR and GSDME. After treatment of OSM, NHEKs and HaCaT cells were irradiated with UVB. The mRNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and RNA sequencing, protein level was detected by Western Blotting, Elisa and immunofluorescence. Cell death was examined by lactate dehydrogenase (LDH) releasing. RESULTS: Here we found that OSM induced pyropotosis in NHEKs and HaCaT cells, but knockout of OSMR abolished pyropotosis. RNA sequencing revealed an upregulation of several key genes involved in NLRP3 inflammasome activation following OSM treatment, among which NLRP3, GSDME, and IL-1ß were confirmed by qRT-PCR and Western Blotting. Knockdown of GSDME alleviated OSM-induced pyropotosis. Pretreatment of OSM boosted UVB-induced pyroptosis and inflammation in NHEKs and HaCaT cells, and this priming function was lost in keratinocytes of Osmr-/- and Gsdme-/- mice. Similar results were obtained in a 3-dimensional culture of human epidermis. CONCLUSION: OSM functions as a priming cytokine to enhance UVB-induced inflammation in keratinocytes, providing insight into the pathogenesis of inflammatory skin diseases.

18.
EC Psychol Psychiatr ; 10(10): 4-16, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34622247

RESUMO

Background: Domestic violence is increasing in China. To explore the effective intervention, we intervened three large independent Chinese communities with different approaches over an eight-year period from 2005 to 2012, with a fourth independent community as a peer control. Methods: The intervention approaches included the psychological intervention with traditional Chinese culture characteristics, the social governance and the poverty relief. The statistical analysis was performed in 2017. Results: We found that while the prevalence of domestic violence kept growing in the control community, it significantly declined in the other three target communities. Among these intervention approaches, the social governance was the most effective, whereas it resulted in the lowest happiness index. Conclusion: This continuous, long-period, prospective and large-scale study showed that these approaches could significantly reduce domestic violence.

19.
Front Immunol ; 12: 748566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630427

RESUMO

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in acute immune responses. In severe cases, a low level of IgG sialylation contributes to the ADCC-regulated enhancement of inflammatory cytokines. The decreases in sialylation and galactosylation play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway. IgG N-glycosylation underlines the complex clinical phenotypes of SARS-CoV-2 infection.


Assuntos
COVID-19/metabolismo , Imunoglobulina G/metabolismo , SARS-CoV-2/fisiologia , Adulto , Citotoxicidade Celular Dependente de Anticorpos , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Lectina de Ligação a Manose da Via do Complemento , Feminino , Glicosilação , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
20.
Front Cell Infect Microbiol ; 11: 708088, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692558

RESUMO

Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.


Assuntos
Doenças das Artérias Carótidas , Microbioma Gastrointestinal , Biomarcadores , Clostridiales , Humanos , Metaboloma , Metabolômica
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