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1.
Org Lett ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026228

RESUMO

The first Pd/Cu catalyzed selective C2-alkenylation of pyridines with internal alkynes has been developed via the pyridinium salt activation strategy. Importantly, the configuration of the product alkenylpyridines could be tuned by the choice of the proper N-alkyl group of the pyridinium salts, thus allowing for both the Z- and E-alkenylpyridines synthesized with good regio- and stereoselectivity. A plausible mechanism was proposed based on the Hammett study and KIE experiment.

2.
Ann Rheum Dis ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998865

RESUMO

OBJECTIVES: Autoreactive B cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA), and B cell-depleting therapies using an antibodies, such as rituximab, have been suggested to be effective in RA treatment. However, transient B cell depletion with rituximab is associated with significant safety challenges related to global suppression of the immune system and thus increases the risks of infection and cancer development. To address selective and persistent issues associated with RA therapy, we developed a customised therapeutic strategy employing universal antifluorescein isothiocyanate (FITC) chimeric antigen receptor T cells (CAR-T cells) combined with FITC-labelled antigenic peptide epitopes to eliminate autoreactive B cell subsets recognising these antigens in RA. METHODS: For a proof-of-concept study, four citrullinated peptide epitopes derived from citrullinated autoantigens, namely, citrullinated vimentin, citrullinated type II collagen, citrullinated fibrinogen and tenascin-C, and a cyclocitrulline peptide-1 were selected as ligands for targeting autoreactive B cells; Engineered T cells expressing a fixed anti-FITC CAR were constructed and applied as a universal CAR-T cell system to specifically eliminate these protein-specific autoreactive B cells via recognition of the aforementioned FITC-labelled autoantigenic peptide epitopes. RESULTS: We demonstrated that anti-FITC CAR-T cells could be specifically redirected and kill hybridoma cells generated by immunisation with antigenic peptides, and autoreactive B cell subsets from RA patients via recognition of corresponding FITC-labelled citrullinated peptide epitopes. Additionally, the cytotoxicity of the CAR-T cells was dependent on the presence of the peptides and occurred in a dose-dependent manner. CONCLUSIONS: The approach described here provides a direction for precise, customised approaches to treat RA and can likely be applied to other systemic autoimmune diseases.

4.
Eur J Radiol ; 132: 109324, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33038576

RESUMO

PURPOSE: Neurocognitive impairment is a common complication in cirrhosis and is associated with alterations in static functional network connectivity (FNC) between distinct brain systems. However, accumulating evidence suggests temporal variability in FNC even at rest. This study aimed to explore dynamic FNC (dFNC) differences and to elucidate their association with neurocognitive changes in cirrhotic patients. METHODS: Fifty-four cirrhotic patients and 42 controls underwent resting-state functional magnetic resonance imaging. Psychometric hepatic encephalopathy score (PHES) was used to assess neurocognitive function. Independent component analysis was performed to identify the components of seven intrinsic brain networks, including sensorimotor (SMN), auditory, visual, cognitive control (CCN), default mode (DMN), subcortical (SC), and cerebellar networks. Sliding window correlation approach was employed to calculate dFNC. FNC states were determined by k-means clustering method, and then functional state analysis was conducted to measure dynamic indices. RESULTS: The patients showed decreased dFNC in State 2, involving the connectivity between posterior subsystem of DMN and CCN (represented by bilateral insular cortex), and in State 3, involving the connectivity between SMN (represented by bilateral precentral gyrus) and SC (represented by bilateral putamen and caudate). The patients spent significantly longer time in State 4 that was with weakest FNC across all networks. We observed a significant correlation between PHES and fraction time/mean dwell time in State 4. CONCLUSIONS: Aberrant dFNC may be the underlying mechanism of neurocognitive impairments in cirrhosis. Dynamic FNC analysis may potentially be utilized in investigating cirrhosis-related neuropathological processes.

5.
Acta Biomater ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32956872

RESUMO

Photodynamic Therapy (PDT) is an effective treatment modality for cancers, with Protoporphyrin IX (PPIX)-based PDT being the most widely used to treat cancers in patients. However, PDT is limited to superficial, thin (few mm in depth) lesions that can be accessed by visible wavelength light. Interstitial light-delivery strategies have been developed to treat deep-seated lesions (i.e. prostate cancer). The most promising of these are X-ray-induced scintillation nanoparticles, which have shown potential benefits for PDT of deep-seated tumors. Herein, the design and use of a new nanoscintillator-based radiation-activated PDT (radioPDT) system is investigated in the treatment of deep-seated tumors. Poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG-PLGA) nanospheres were loaded with a scintillator (LaF3:Ce3+) and photosensitizer (PPIX) to effect radioPDT. UV-Vis spectroscopy and electron microscopy studies demonstrated efficient encapsulation of nanoscintillators and PPIX (>90% efficiency) into the PEG-PLGA nanospheres. The nanoparticles were uniform in size and approximately 100 nm in diameter. They were highly stable and functional for up to 24 h under physiological conditions and demonstrated slow release kinetics. In vitro and in vivo toxicity studies showed no appreciable drug toxicity to human skin fibroblast (GM38), prostate cancer cells (PC3), and to C57/BL mice. Cell uptake studies demonstrated accumulation of the nanoparticles in the cytoplasm of PC3 cells. When activated, fluorescent resonant energy transfer (FRET) was evident via fluorescent spectroscopy and singlet oxygen yield. Determination of stability revealed that the nanoparticles were stable for up to 4 weeks. The nanoparticle production was scaled-up with no change in properties. This nanoparticle represents a unique, optimally designed therapeutic and diagnostic agent (theranostic) agent for radioPDT with characteristics capable of potentially augmenting radiotherapy for deep-seated tumors and integrating into current cancer radiotherapy.

6.
Medicine (Baltimore) ; 99(36): e21653, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32898999

RESUMO

The expression profile and specific roles of microRNAs (miRNAs) in regulation of atrophic bone nonunion are not fully understood. Here, we present evidence that miRNAs are involved in regulation of several osteogenic genes and may contribute to the development of atrophic bone nonunion.The miRNA expression profile of repairing tissues in atrophic bone nonunion patients (group A) and in callus tissues from patients with healed fractures (group B) were quantitatively measured. microRNA microarrays were used to identify differentially expressed miRNAs, and the bioinformatics methods were used to predict the potential target genes. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and dual-luciferase reporter assay were performed in human bone marrow stromal cells (hBMSCs) to validate the microarray results.Nine miRNAs in group A were up-regulated 1.5 times compared to group B, while the other 9 miRNAs in group A were down-regulated 1.5 times. Several target regions of these miRNAs were identified in the osteogenic genes, as well as in the other genes in their families or related regulatory factors. Four miRNAs (hsa-miR-149, hsa-miR-221, hsa-miR-628-3p, and hsa-miR-654-5p) could play important roles in regulating bone nonunion development. hBMSCs transfected with these miRNAs significantly decreased mRNA levels of alkaline phosphatase, liver/bone/kidney (ALPL), platelet derived growth factor subunit A (PDGFA), and bone morphogenetic protein 2 (BMP2). Lower protein expression levels were observed using western blotting, confirming that ALPL, PDGFA, and BMP2 were directly targeted by hsa-miR-149, hsa-miR-221, and hsa-miR-654-5p, respectively.In summary, hsa-miR-149, hsa-miR-221, and hsa-miR-654-5p may play important biological roles by repressing osteogenic target genes ALPL, PDGFA, and BMP2, and, therefore, contributing to progression of atrophic bone nonunion.


Assuntos
Osso e Ossos/metabolismo , Fraturas do Fêmur/genética , Fraturas do Úmero/genética , MicroRNAs/metabolismo , Fraturas da Tíbia/genética , Adulto , Criança , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Regulação para Cima
7.
Eur J Radiol ; 131: 109252, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32949859

RESUMO

PURPOSE: To conduct the first investigation on thalamic metabolic alterations in minimal hepatic encephalopathy (MHE) and elucidate their association with intrinsic neural activity change and cognitive dysfunction. METHODS: Thirty-eight cirrhotic patients [18 with MHE, 20 without MHE (NHE)] and 21 healthy controls (HC) were included, all of whom underwent 1H-magnetic resonance spectroscopy, resting-state functional magnetic resonance imaging (fMRI), as well as cognitive assessment based on the Psychometric Hepatic Encephalopathy Score (PHES). Metabolite ratios in the thalamus were measured, including N-acetyl aspartate (NAA)/creatine (Cr), glutamate plus glutamine (Glx)/Cr, choline (Cho)/Cr, and myo-inositol (mI)/Cr. Intrinsic neural activity was evaluated based on frequency-specific amplitude of low-frequency fluctuations (ALFF) using fMRI signals. RESULTS: MHE patients showed an increase in Glx/Cr and a decrease in Cho/Cr and mI/Cr, compared with HC. These changes were aggravated from NHE to MHE. Cho/Cr and mI/Cr were positively correlated with regional ALFF derived from the frequency-specific band (0.01-0.027 Hz) and PHES. Receiver operating characteristic curve analysis showed that Cho/Cr and mI/Cr measurements exhibited moderate discrimination ability between NHE and MHE. CONCLUSION: Our findings provide evidence that MHE is associated with disturbed metabolism in the thalamus, which may contribute to the altered neural activity and underlie the mechanisms of cognitive impairments. MRS measurements in the thalamus could serve as the potential biomarker for diagnosing MHE among cirrhotic patients.

8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(4): 570-572, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895114

RESUMO

This article reports a patient who suffered from Wolffian adnexal tumor.We also briefly elucidate the pathogenesis,clinicopathological features,diagnosis,differentiation,and treatment of Wolffian adnexal tumor,with an attempt to increase the awareness of the disease and reduce misdiagnosis.


Assuntos
Adenoma , Doenças dos Anexos , Feminino , Humanos , Imuno-Histoquímica , Ductos Mesonéfricos
9.
Aging (Albany NY) ; 12(18): 18436-18452, 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32979259

RESUMO

Tendon-derived stem cells (TSCs) play a primary role in tendon physiology, pathology, as well as tendon repair and regeneration after injury. TSCs are often exposed to mechanical loading-related cellular stresses such as oxidative stress, resulting in loss of stemness and multipotent differentiation potential. Cytoprotective autophagy has previously been identified as an important mechanism to protect human TSCs (hTSCs) from oxidative stress induced impairments. In this study, we found that high-mobility AT-hook 2 (HMGA2) overexpression protects hTSCs against H2O2-induced loss of stemness through autophagy activation. Evidentially, H2O2 treatment increases the expression of Nudt21, a protein critical to polyadenylation site selection in alternative polyadenylation (APA) of mRNA transcripts. This leads to increased cleavage and polyadenylation of HMGA2 3'-UTR at the distal site, resulting in increased HMGA2 silencing by the microRNA let-7 and reduced HMGA2 expression. In conclusion, Nudt21-regulated APA of HMGA2 3'-UTR and subsequent HMGA2 downregulation mediates oxidative stress induced hTSC impairments.

10.
PLoS One ; 15(9): e0239617, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991614

RESUMO

Cadmium (Cd) is a toxic metal occurring in the environment naturally. Almond mushroom (Agaricus brasiliensis) is a well-known cultivated edible and medicinal mushroom. In the past few decades, Cd accumulation in A.brasiliensis has received increasing attention. However, the molecular mechanisms of Cd-accumulation in A. brasiliensis are still unclear. In this paper, a comparative transcriptome of two A.brasiliensis strains with contrasting Cd accumulation and tolerance was performed to identify Cd-responsive genes possibly responsible for low Cd-accumulation and high Cd-tolerance. Using low Cd-accumulating and Cd-tolerant (J77) and high Cd-accumulating and Cd-sensitive (J1) A.brasiliensis strains, we investigated 0, 2 and 5 mg L-1 Cd-effects on mycelium growth, Cd-accumulation and transcriptome revealed by RNA-Seq. A total of 57,884 unigenes were obtained. Far less Cd-responsive genes were identified in J77 mycelia than those in J1 mycelia (e.g., ABC transporters, ZIP Zn transporter, Glutathione S-transferase and Cation efflux (CE) family). The higher Cd-accumulation in J1 mycelia might be due to Cd-induced upregulation of ZIP Zn transporter. Cd impaired cell wall, cell cycle, DNA replication and repair, thus decreasing J1 mycelium growth. Cd-stimulated production of sulfur-containing compounds, polysaccharides, organic acids, trehalose, ATP and NADPH, and sequestration of Cd might be adaptive responses of J1 mycelia to the increased Cd-accumulation. DNA replication and repair had better stability under 2 mg L-1 Cd, but greater positive modifications under 5 mg L-1 Cd. Better stability of DNA replication and repair, better cell wall and cell cycle stability might account for the higher Cd-tolerance of J77 mycelia. Our findings provide a comprehensive set of DEGs influenced by Cd stress; and shed light on molecular mechanism of A.brasiliensis Cd accumulation and Cd tolerance.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32936696

RESUMO

Myoblast differentiation is a crucial process for myogenesis. Mitochondria function as an energy-providing machine that is critical to this process, and mitochondrial dysfunction can prevent myoblasts from fusing into myotubes. However, the molecular mechanisms underlying the dynamic regulation of mitochondrial networks remain poorly understood. In the present study, we found that the PTEN induced kinase 1(PINK1) /Parkin (an E3 ubiquitin-protein ligase) pathway is activated at the early stage of myoblast differentiation. Moreover, downregulation of mitofusin 2 (Mfn2) and increased dynamin-related protein 1 (Drp1) resulted in loosely formed mitochondria during this period. Furthermore, selective knockdown of the mitochondrial matrix protein Lon proteinase-1 (LonP1) at the early stage of myoblast differentiation induced mitochondrial depolarization and suppressed the PINK1/Parkin pathway and reduced Mfn2 and Drp1 levels, which blocked mitochondrial remodeling and myoblast differentiation. Overall, these data suggest that LonP1 plays an essential role in maintaining the normal myoblast differentiation process, which partly by regulating PINK1/Parkin mediated mitochondrial remodeling.

12.
J Colloid Interface Sci ; 581(Pt B): 964-978, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32956914

RESUMO

Supported copper oxides with well-dispersed metal species, small size, tunable valence and high stability are highly desirable in catalysis. Herein, novel copper oxide (CuOx) catalysts supported on defect-rich mesoporous alumina microspheres are developed using a spray-drying-assisted evaporation induced self-assembly method. The catalysts possess a special structure composed of a mesoporous outer layer, a mesoporous-nanosphere-stacked under layer and a hollow cavity. Because of this special structure and the defective nature of the alumina support, the CuOx catalysts are ultrasmall in size (1 ~ 3 nm), bivalent with a very high Cu+/Cu2+ ratio (0.7), and highly stable against sintering and oxidation at high temperatures (up to 800 °C), while the wet impregnation method results in CuOx catalysts with much larger sizes (~15 nm) and lower the Cu+/Cu2+ ratios (~0.29). The catalyst formation mechanism through the spray drying method is proposed and discussed. The catalysts show remarkable performance in catalytic ozonation of phenol wastewaters. With high-concentration phenol (250 ppm) as the model organic pollutant, the optimized catalyst delivers promising catalytic performance with 100% phenol removal and 53% TOC removal in 60 min, and a high cyclic stability. Superoxide anion free radicals (⋅O2-), singlet oxygen (1O2) and hydroxyl radicals (⋅OH) are the predominant reactive species. A detailed structure-performance study reveals the surface hydroxyl groups and Cu+/Cu2+ redox couples play cooperatively to accelerate O3 decomposition generating reactive radicals. The plausible catalytic O3 decomposition mechanism is proposed and discussed with supportive evidences.

13.
Psychosom Med ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32947582

RESUMO

OBJECTIVE: The death of a parent during childhood is a severe life event with potentially long-term consequences. Earlier studies have shown an increased risk of cardiovascular diseases (CVD) after the death of a spouse, child or sibling. Whether parental death during childhood is associated with an increased risk of incident CVD is unknown and was investigated in this study. METHODS: We studied 48,992 men born 1949-51 and enlisted for military conscription in 1969-70. We obtained information on death of a parent during childhood, CVD up to 2008 and covariates by linking the questionnaire and the clinical examination data from conscription with nationwide socioeconomic and health registers. RESULTS: Men who lost a parent during childhood had an increased risk of ischemic heart disease (IHD) [adjusted hazard ratio (HR) and 95% confidence interval (CI): 1.30 (1.13-1.49)], but not of stroke during the 39-year follow-up [adjusted HR (95% CI): 0.87 (0.66-1.15)]. Maternal death was associated with IHD both when the loss was due to cardiovascular [adjusted HR (95% CI): 2.04 (1.02-4.08)] and unnatural causes [adjusted HR (95% CI): 2.50 (1.42-4.42)]; in case of paternal death an increased IHD risk was observed only when the loss was due to cardiovascular causes [adjusted HR (95% CI): 1.82(1.37-2.42)]. There were no substantial differences in CVD according to the child's age at the loss. CONCLUSIONS: Parental death during childhood was associated with an increased risk of IHD in men. If these associations are confirmed in future studies, the long-term effects of childhood bereavement may warrant attention.

14.
Clin Rheumatol ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32939568

RESUMO

INTRODUCTION/OBJECTIVES: Behcet's disease (BD) is a systemic and chronic inflammatory vasculitis with unknown etiology. Diagnosis is determined by evaluating several clinical criteria, but the lack of specific laboratory diagnostic markers makes the diagnosis of BD more difficult. Therefore, the aim of this study was to determine the changes in hematological parameters in BD patients to investigate their relationship with BD clinical features. METHOD: A total of 48 BD patients and 96 healthy controls were included in this study. The severity of each BD patient was associated to a severity score according to the entire spectrum of disease manifestations. Several laboratory tests were assessed, and the difference in their results between BD patients and healthy controls was evaluated. Correlation analysis was performed to reveal the interaction of these parameters. RESULTS: C-reactive protein (CRP), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), neutrophil count, platelet count, and plateletcrit significantly increased in BD patients compared with healthy controls (P < 0.05). CRP was higher in patients with skin lesions, MCH and MCHC were lower in patients with vascular involvement, and the neutrophil count was higher in patients with skin lesions and genital ulcers. In addition, higher CRP and lower MCH and MCHC were associated with a severe condition. Besides, MCH and MCHC were negatively correlated with the platelet count, plateletcrit, and neutrophil count. CONCLUSIONS: This study revealed that MCH and MCHC are valuable parameters for BD. Their levels help assess the disease severity and indicate the vascular involvement in BD. Key Points • This is the first study reporting MCH and MCHC as important biomarkers in BD. • BD patients with vascular involvement and thrombosis potential have lower levels of MCH and MCHC. • MCH and MCHC are negatively correlated with platelet count, plateletcrit, and neutrophil count. • Lower MCH and MCHC are associated with a severe condition.

15.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3584-3593, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893547

RESUMO

Gastric cancer is a disease with high mortality, which threatens the health of people for a long time. At present, the main treatment methods are surgery and chemotherapy, but these methods have great harm to the human body. However, it is found that the active ingredients of traditional Chinese medicine have an obvious therapeutic effect in the adjuvant treatment of the tumor. Therefore, the active ingredients of traditional Chinese medicine have become a research hotspot in the anti-tumor field. In recent years, many related researchers have been particularly active in studying the in vitro activity and mechanism of active ingredients of traditional Chinese medicine on human gastric cancer cells. In this paper, the Chinese herbal medicine extracts, polysaccharides, alkaloids, saponins, flavones, terpenes, quinones, volatile oils, esters, phenols, protein components and other active ingredients of Chinese medicine were used as the starting points to investigate the anti-gastric cancer mechanism, such as inhibiting cell proliferation and inducing apoptosis of cancer cells, inhibiting cell invasion and migration; inhibiting over-expression of vascular endothelial growth factor(VEGF); interfering with cell mitosis; and regulating cell signaling pathways. Their in vitro inhibitory activity and mechanism for gastric cancer cells were described in this study, providing a theoretical reference for the development and application of anti-gastric cancer drugs.


Assuntos
Medicamentos de Ervas Chinesas , Saponinas , Neoplasias Gástricas , Humanos , Medicina Tradicional Chinesa , Fator A de Crescimento do Endotélio Vascular
16.
J Food Biochem ; : e13467, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32935377

RESUMO

Octopus protein hydrolysate has been reported to increase milk yield and milk protein production. In this paper, the utilization and underlying mechanisms of bioactive peptide fractions from octopus protein hydrolysate on ß-casein expression in mouse mammary epithelial cells (HC11) were investigated. Fraction OPH3-1 significantly stimulated cell proliferation and ß-casein synthesis in HC11 cells, which was purified by ultra-filtration and gel-filtration chromatography. The MWs of the peptides from OPH3-1 ranged from 525-2,578 Da and consisted of 7-26 amino acid residues. Most of the peptides demonstrated the typical characteristics of milk protein synthesis promotion, especially MGLAGPR, MGDVLNF, EAPLMHV, and TEAPLMHV. Additionally, the mRNA abundances of mTOR, S6K1, 4EBP1, JAK2, and STAT5 were significantly enhanced by OPH3-1, which was consistent with the increased ß-casein expression. These results suggest that the OPH3-1 peptides can promote the proliferation of mammary epithelial cells and increase ß-casein synthesis. PRACTICAL APPLICATIONS: Breastfeeding mothers are generally recommended to take octopus soup as a daily diet to promote lactation. The peptides fraction OPH3-1 from the enzymatic hydrolysate of Octopus vulgaris which was revealed to significantly stimulate mammary epithelial cell proliferation and ß-casein synthesis was obtained. This study suggests that octopus peptides can be used as nutritional supplements to increase the quantity and quality of milk production.

17.
Soft Robot ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32976080

RESUMO

The compliant nature of soft fingers allows for safe and dexterous manipulation of objects by humans in an unstructured environment. A soft prosthetic finger design with tactile sensing capabilities for texture discrimination and subsequent sensory stimulation has the potential to create a more natural experience for an amputee. In this work, a pneumatically actuated soft biomimetic finger is integrated with a textile neuromorphic tactile sensor array for a texture discrimination task. The tactile sensor outputs were converted into neuromorphic spike trains, which emulate the firing pattern of biological mechanoreceptors. Spike-based features from each taxel compressed the information and were then used as inputs for the support vector machine classifier to differentiate the textures. Our soft biomimetic finger with neuromorphic encoding was able to achieve an average overall classification accuracy of 99.57% over 16 independent parameters when tested on 13 standardized textured surfaces. The 16 parameters were the combination of 4 angles of flexion of the soft finger and 4 speeds of palpation. To aid in the perception of more natural objects and their manipulation, subjects were provided with transcutaneous electrical nerve stimulation to convey a subset of four textures with varied textural information. Three able-bodied subjects successfully distinguished two or three textures with the applied stimuli. This work paves the way for a more human-like prosthesis through a soft biomimetic finger with texture discrimination capabilities using neuromorphic techniques that provide sensory feedback; furthermore, texture feedback has the potential to enhance user experience when interacting with their surroundings.

18.
Ann Hematol ; 99(11): 2659-2670, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32734550

RESUMO

Cytomegalovirus (CMV) can cause end-organ diseases including pneumonia, gastroenteritis, retinitis, and encephalitis in hematopoietic stem cell transplantation recipients. Potential differences among different CMV diseases remain uncertain. This study aimed to compare the clinical characteristics, risk factors, and mortality among different CMV diseases. A retrospective nested case-control study was performed based on a cohort of 3862 patients who underwent haploidentical hematopoietic stem cell transplantation at a single-center. CMV diseases occurred in 113 (2.92%) of 3862 haplo-HSCT recipients, including probable CMV pneumonia (CMVP, n = 34), proven CMV gastroenteritis (CMVG, n = 34), CMV retinitis (CMVR, n = 31), probable CMV encephalitis (CMVE, n = 7), and disseminated CMV disease (Di-CMVD, n = 7). Most (91.2%) cases of CMVG developed within 100 days, while most (90.3%) cases of CMVR were late onset. Refractory CMV infection and CMV viral load at different levels were associated with an increased risk of CMVP, CMVG, and CMVR. Compared with patients without CMV diseases, significantly higher non-relapse mortality at 1 year after transplantation was observed in patients with CMVP and CMVR, rather than CMVG. Patients with CMVP, Di-CMVD, and CMVE had higher overall mortality after diagnosis than that of patients with CMVG and CMVR (61.7%, 57.1%, 40.0% vs 27.7%, 18.6%, P = 0.001). In conclusion, the onset time, viral dynamics, and mortality differ among different CMV diseases. The mortality of CMV diseases remains high, especially for CMVP, Di-CMVD, and CMVE.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/terapia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
19.
J Hazard Mater ; 401: 123412, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32763702

RESUMO

Potential adverse effects of nanoplastics (NPs) on marine organisms have received increased attention in recent years. In contrast, few data are available on terrestrial plants, especially on the mechanisms for transport of NPs in plants and phytotoxicity (at both phenotypic and molecular levels) of plants induced by NPs. To address this knowledge gap, we conducted a microcosm study in which hydroponically-cultured rice (Oryza sativa L.) seedlings were exposed to polystyrene (PS)-NPs at 0, 10, 50, and 100 mg L-1 for 16 d and examined for morphological and physiological phenotypes and transcriptomics. Laser confocal scanning micrographs confirmed PS-NPs were uptaken by rice roots, greatly benefitted from the transport activity of aquaporin in rice roots. The significant enhancement (p < 0.05) of antioxidant enzyme activities reflected the oxidative stress response of rice roots upon exposure to PS-NPs. Treatment by PS-NPs decreased root length and increased lateral root numbers. Carbon metabolism was activated (e.g., increased carbon and soluble sugar contents) whereas jasmonic acid and lignin biosynthesis were inhibited. The present study demonstrated the likelihood for transport of PS-NPs in rice roots and induced phytotoxicity by PS-NPs, which should inspire further investigations into the potential human health risks from rice consumption.

20.
Clin Immunol ; 219: 108549, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32739412

RESUMO

Behçet's disease (BD) patients have abnormal FcγR polymorphisms, the implication of which remains elusive. We examined FcγRIIb expression on neutrophils, monocytes, B cells, natural killer cells, dendritic cells and T cells, and FcγRI and FcγRIII expression on monocytes in BD patients and healthy controls using flow cytometry. We further stimulated monocytes with IgG and (or) lipopolysaccharide (LPS) and measured IL-6 and TNF-α production by enzyme-linked immunosorbent assay. We found that BD monocytes expressed a lower level of FcγRIIb and a higher level of FcγRIII, which were correlated with erythrocyte sedimentation rate and C-reactive protein and were rescued after treatment. Furthermore, LPS- and IgG-stimulated BD monocytes produced higher levels of IL-6 and TNF-α than HC monocytes. In summary, we found that BD monocytes downregulated FcγRIIb expression and upregulated FcγRIII expression, which were correlated with disease activity and potentially contributed to monocyte hyperactivation in BD.

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