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2.
Ecotoxicol Environ Saf ; 225: 112738, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481352

RESUMO

Arsenic is a significant food safety and environmental concern due to its mutagenic and carcinogenic effect on living organism. Soybean (Glycine max [L.] Merrill) is a global staple crop grown intensively in arsenic-contaminated regions of the world (e.g., Southern Province of China). Therefore, the objective of this study was to investigate whether Se-NPs and/or ZnO-NPs could be used as an eco-friendly and efficient amendment to reduce arsenic uptake and toxicity in soybean. Ten-days-old seedling, grown in vermiculite, were transferred to hydroponic media and further grown till V2 growth stage appeared. AsV (25 µM Na2HAsO4) stressed plants were treated with ZnONP (25 µM ZnO) and SeNP (25 µM Se) separately and in combination, which were grown for another 10 d. The result demonstrated that arsenic-treated soybean plants displayed a reduction in photosynthetic efficiency, increased proline and glycine betaine accumulation in tissues, and altered antioxidant activity compared to an untreated control. The application of zinc oxide and selenium nanoparticles, both independently and in tandem, reduced arsenic stress in root and shoot tissues and rescued plant health. This was reflected through increased levels of reduced glutathione content, ascorbic acid, and various photosynthesis- and antioxidant-relevant enzymes. In addition, nanoparticle-treated soybean plants displayed higher expression of defense- and detoxification-related genes compared to controls. Cellular toxicants (i.e., oxidized glutathione, reactive oxygen species, and malondialdehyde) were reduced upon nanoparticle treatment. These data collectively suggest that selenium and zinc oxide nanoparticles may be a solution to ameliorate arsenic toxicity in agricultural soils and crop plants.

3.
Food Chem ; 370: 131030, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34507209

RESUMO

Phytosterols are commonly found in vegetable oils and possess health benefits for humans. While investigating the chemical conversion of stigmasterol at deodorisation temperatures, gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) experiments led to the identification of 5-ethyl-6-methyl-3-heptene-2-one, 3-hydoxy-steroid, 3-ketostigmasterol, and 3,7-diketostigmasterol as by-products. The identification of these compounds assisted in the interpretation of the stigmasterol oligomers characterised by high-pressure size exclusion chromatography (HPSEC). A similar analysis was conducted in stripped corn oil at the deodorisation temperatures. As such, 5-ethyl-6-methyl-3-heptene-2-one, 3-hydoxy-steroid, 3-ketostigmasterol and 3,7-diketostigmasterol were also detected in stripped corn oil, while the contents of 3-hydoxy-steroid and 5-ethyl-6-methyl-3-heptene-2-one were higher than those of 3-ketostigmasterol, as revealed by quantum chemical simulations. In addition, stripped corn oil exhibited the characteristic of preventing stigmasterol degradation below 200 °C, whereas it enhanced the chemical conversion (such as esterification and degradation) of stigmasterol at higher temperatures.

4.
Neuroimmunomodulation ; : 1-20, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34535590

RESUMO

BACKGROUND AND PURPOSE: Increased researches focus into pathophysiological mechanisms of spinal cord injury (SCI), particularly toward the relationship between relevant biomarkers and the degree of SCI and prognosis. Circular ribonucleic acids (circRNAs) possess microRNA (miRNA) binding sites that can play the role of miRNA sponges and thus participate in the expression of parental gene modification. This study focused on rat SCI models and explore the relationship between circRNAs and SCI at a genomic level. METHODS: We first established a rat SCI model and extracted the target spinal cord tissue according to 4 time points. Then investigated the alterations in the circRNA expression by high-throughput whole transcriptome sequencing, analyzed data by gene ontology and the Kyoto Encyclopedia of Genes and Genomes, and constructed the circRNA-miRNA network. RESULTS: A total of 178 circRNAs were dysregulated (89 upregulated/89 downregulated). Differential circRNAs were found to be mainly involved in the composition of specific organelles in the cytoplasm and are mainly involved in the energy transfer process associated with electron transfer (and similar activities). In all the signaling pathways identified in this study, the MAPK, Wnt, and mTOR signaling pathways are intimately associated with the pathophysiological process of rats post-SCI. In this study, 10 circRNAs with obvious dysregulation were selected for prediction, 26 miRNAs with additional interactions were obtained, and a network diagram of circRNAs-miRNAs was constructed. In this manner, one can understand in further detail the pathogenesis of SCI and to provide new strategies for the prevention, diagnosis, and treatment of SCI-related injuries at the genetic level.

5.
Br J Haematol ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528239

RESUMO

We performed a double-blind, double-dummy controlled study to compare the efficacy between recombinant human thrombopoietin (rhTPO) and eltrombopag in rapidly increasing the platelet counts in Chinese patients with immune thrombocytopenia (ITP). A total of 96 patients diagnosed with ITP for ≥6 months who had baseline platelet counts of <30 × 109 /l were randomly assigned (1:1 ratio) to receive eltrombopag 25 mg/day or rhTPO 300 u/kg for 2 weeks. Compared with the eltrombopag group, a significantly higher proportion of patients in the rhTPO group achieved platelet counts of ≥50 × 109 /l [75·00% (36/48) vs. 43·75% (21/48), P = 0·003] or complete response (64·58% vs. 25·00%) on day 15. Moreover, a higher proportion of patients in the rhTPO group either had platelet counts that rapidly increased to twice that of baseline and with platelet counts of ≥30 × 109 /l, or reached ≥50 × 109 /l at least once when analysed on day 9, 12, and 15. However, upon discontinuation of the treatment, the platelet counts reduced to the baseline within 1 week in the rhTPO group, but on the fourth week in the eltrombopag group. Adverse events were similar in patients given rhTPO and eltrombopag. To conclude, rhTPO is superior to eltrombopag at 25 mg/day in rapidly increasing platelet counts in patients with ITP (ClinicalTrials.gov Identifier: NCT03771378).

6.
BMJ Open ; 11(9): e045655, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518248

RESUMO

INTRODUCTION: Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder that presents with abdominal pain/discomfort and altered bowel patterns. IBS has multiple potential causes for which conventional medicines have had limited success, resulting in a significant number of patients who do not sensitively respond to pharmacotherapy for a period of 12 months and who develop a continuing symptom profile (described as refractory IBS) and seek help through (non)pharmacological treatments. The aim of this study is to investigate the efficacy and safety of acupuncture therapy for refractory IBS on the basis of conventional treatments. METHODS AND ANALYSIS: A total of 170 eligible patients who meet the Rome IV criteria for refractory IBS will be randomly allocated to receive acupuncture or sham acupuncture. Each patient will receive 12 sessions of acupuncture over 4 weeks and a 4-week follow-up. The primary outcome will be the IBS Symptom Severity Score. Secondary outcomes will include the proportion of participants experiencing adequate relief of global IBS symptoms, the weekly frequency of defecation, the stool properties assessed by the Bristol Grading Scale, the Work and Social Adjustment Scale, the IBS-Quality of Life score, and the Self-Rating Depression Scale and Self-Rating Anxiety Scale anxiety and depression scores. Outcome measures will be collected at baseline, 2 and 4 weeks of the intervention, and 6 and 8 weeks after the intervention. Categorical variables will be compared with Fisher's exact test or the Wilcoxon rank-sum test, and continuous variables will be compared using Student's t-test or the Wilcoxon rank-sum test. ETHICS AND DISSEMINATION: The entire project has been approved by the ethics committees of Beijing University of Chinese Medicine (2020BZYLL0507) and Sichuan Province Regional Institution for Conducting Research on Traditional Chinese Medicine (2020KL-025). The outcomes of the trial will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04276961.

8.
Hum Vaccin Immunother ; : 1-6, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491888

RESUMO

OBJECTIVES: To summarize reports to the national adverse event following immunization surveillance system (NAEFISS) following inactivated quadrivalent influenza vaccine (QIV) in Zhejiang province from 2018 to 2020. METHODS: We analyzed adverse events following immunization (AEFI) reports following QIV, with a comparison, with the AEFI reports following inactivated trivalent influenza vaccine (TIV). Reporting rates of AEFI were calculated by age, severity of AEFI, categories of AEFI, and reaction categories. The data mining algorithm used in this study was reporting odds ratio (ROR). A value of ROR­1.96SE >1 (standard error [SE]) was considered as positive signal. These reporting rates between vaccine types were compared through chi-square tests. RESULTS: NAEFISS received 514 AEFI reports following QIV and 536 reports following TIV, with a reporting rate of 13.66/100,000 100,000 doses/100,000 doses (χ2 = 7.11, P> .05). Of the 514 reports following QIV, 410 were vaccine product-related reactions and 51 were severe AEFI. Fever/redness/induration was the most frequent clinical diagnosis of the QIV AEFI, with a reporting rate of 12.42/100,000 doses in the age group of 3-17 years, and 12.44/100,000 doses in the age group of ≥18 years. The positive signal of QIV AEFI was observed for the allergic rash and asthma/wheezing. CONCLUSION: The present analysis did not identify any new/unexpected safety concerns. We suggested that NAEFISS continue to monitor the safety of QIV.

9.
Lupus ; : 9612033211040366, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34482739

RESUMO

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

10.
Dis Markers ; 2021: 9965343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497677

RESUMO

Background: The role of IgG subclass in idiopathic membranous nephropathy (IMN) was unclarified. Recent study found IgG subtype switches from IgG1 to IgG4 in the early pathological stage in IMN. The profile of IgG subclass in phospholipase A2 receptor- (PLA2R-) related and PLA2R-unrelated IMN was unrevealed. Our study is aimed at testifying whether IgG subclass switch existed in PLA2R-related and PLA2R-unrelated IMN, respectively. Methods: Our study retrospectively enrolled 157 Chinese patients with biopsy-confirmed IMN between September 2017 and November 2019. We measured glomerular PLA2R antigen and serum anti-PLA2R antibody to classify the patients into PLA2R-related (n = 132) and PLA2R-unrelated (n = 25) subgroup. We evaluated glomerular IgG subclass by immunofluorescence (IF) predominance. Our study defined IgG subclass deposition as predominant if the IF score was higher than the other three and ≥1 +, or as codominant if the IF intensity was equal to any other and ≥1 +. We explored the relationship between IF predominance of glomerular IgG subtype and electron microscopic (EM) stages of IMN. Results: We did not find statistical difference of predominant or codominant rate (pre/co-rate) among EM stages in any subclass (P > 0.05). Pre/co-rate of IgG3 linearly associated with EM stage in total and PLA2R-related subgroup (P = 0.044, P = 0.013). PLA2R-related subgroup showed higher IgG4 intensity (2.1 ± 0.6 vs. 1.6 ± 0.7, P = 0.001) and pre/co-rate of IgG4 in stage 1 (97% vs. 57%, P = 0.015) than PLA2R-unrelated group. We found no difference of IgG subclass pre/co-rate in different EM stages or linear association between pre/co-rate of IgG1, IgG2, IgG4, and EM stages (P > 0.05). Conclusions: Pre/co-rate of IgG3 declined with EM stage in total and PLA2R-related subgroup. We did not find IgG subclass switches from IgG1 to IgG4 in either IMN patients or subgroups.

11.
mBio ; : e0159921, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488453

RESUMO

Cellular immunity may be involved in organ damage and rehabilitation in patients with coronavirus disease 2019 (COVID-19). We aimed to delineate immunological features of COVID-19 patients with pulmonary sequelae (PS) 1 year after discharge. Fifty COVID-19 survivors were recruited and classified according to radiological characteristics, including 24 patients with PS and 26 patients without PS. Phenotypic and functional characteristics of immune cells were evaluated by multiparametric flow cytometry. Patients with PS had an increased proportion of natural killer (NK) cells and a lower percentage of B cells than patients without PS. Phenotypic and functional features of T cells in patients with PS were predominated by the accumulation of CD4-positive (CD4+) T cells secreting interleukin 17A (IL-17A), short-lived effector-like CD8+ T cells (CD27-negative [CD27-] CD62L-), and senescent T cells with excessive secretion of granzyme B/perforin/interferon gamma (IFN-γ). NK cells were characterized by the excessive secretion of granzyme B and perforin and the downregulation of NKP30 and NKP46; highly activated NKT and γδ T cells exhibited NKP30 and TIM-3 upregulation and NKB1 downregulation in patients with PS. However, immunosuppressive cells were comparable between the two groups. The interrelationship of immune cells in COVID-19 was intrinsically identified, whereby T cells secreting IL-2, IL-4, and IL-17A were enriched among CD28+ and CD57- cells and cells secreting perforin/granzyme B/IFN-γ/tumor necrosis factor alpha (TNF-α)-expressed markers of terminal differentiation. CD57+ NK cells, CD4+Perforin+ T cells, and CD8+ CD27+ CD62L+ T cells were identified as the independent predictors for residual lesions. Overall, our findings unveil the profound imbalance of immune landscape that may correlate with organ damage and rehabilitation in COVID-19. IMPORTANCE A considerable proportion of COVID-19 survivors have residual lung lesions such as ground-glass opacity and fiber streak shadow. To determine the relationship between host immunity and residual lung lesions, we performed an extensive analysis of immune responses in convalescent patients with COVID-19 1 year after discharge. We found significant differences in immunological characteristics between patients with pulmonary sequelae and patients without pulmonary sequelae 1 year after discharge. Our study highlights the profound imbalance of immune landscape in the COVID-19 patients with pulmonary sequelae, characterized by the robust activation of cytotoxic T cells, NK cells, and γδ T cells, as well as the deficiencies of immunosuppressive cells. Importantly, CD57+ NK cells, CD4+Perforin+ T cells, and CD8+ CD27+ CD62L+ T cells were identified as the independent predictors for residual lesions.

12.
Adv Sci (Weinh) ; : e2102539, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34473423

RESUMO

The stress-response strategy is one of the nature's greatest developments, enabling animals and plants to respond quickly to environmental stimuli. One example is the stress-response strategy of the Venus flytrap, which enables such a delicate plant to perceive and prey on insects at an imperceptible speed by their soft terminal lobes. Here, inspired by this unique stress-response strategy, a soft gripper that aims at the challenges of high-speed dynamic grasping tasks is presented. The gripper, called high-speed soft gripper (HSG), is based on two basic design concepts. One is a snap-through instability that enables the HSG to sense the mechanical stimuli and actuating instantly. The other one is the spider-inspired pneumatic-powered control system that makes the trigger process repeatable and controllable. Utilizing the stress-response strategy, the HSG can accomplish high-speed sensing and grasping and handle a dynamic grasping task like catching a thrown baseball. Whereas soft machines typically exhibit slow locomotion speed and low manipulation strength for the intrinsic limitations of soft materials, the exploration of the stress-response strategy in this study can help pave the way for designing a new generation of practical high-speed soft robots.

13.
J Control Release ; 338: 694-704, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34509585

RESUMO

Self-amplifying RNA (SaRNA) is a burgeoning platform that exploits the replication machinery of alphaviruses such as Venezuelan equine encephalitis (VEE) virus or Sindbis virus (SIN). SaRNA has been used for development of human vaccines, but has not been evaluated for porcine vaccine development. Porcine reproductive and respiratory syndrome virus (PRRSV) causes tremendous economic losses to the worldwide pork industry, but current vaccines trigger delayed neutralizing antibody response and confer only partial protection. Here we first compared two SaRNA systems based on VEE and SIN, and demonstrated that in vitro transcribed VEE-based SaRNA conferred prolonged reporter gene expression and RNA amplification in pig cells with low cytotoxicity, but SIN-based SaRNA imparted evident cytotoxicity and limited gene expression in pig cells. Transfection of VEE-based SaRNA that encodes the major PRRSV antigen dNGP5 (SaRNA-dNGP5) conferred persistent expression for at least 28 days in pig cells. We next complexed SaRNA-dNGP5 with the polyaspartamide block copolymer PEG-PAsp(TEP) to form polyplex nanomicelle with high packaging efficiency and narrow size distribution. The polyplex nanomicelle enabled sustained dNGP5 expression and secretion in vitro. Compared with the commercial PRRS vaccine, nanomicelle delivery of SaRNA-dNGP5 into animal models accelerated the induction of potent neutralizing antibodies with minimal side effects, and elicited stronger IL-4 and IFN-γ responses against homologous and heterologous PRRSV. These properties tackle the problems of current vaccines and implicate the potential of SaRNA-dNGP5 nanomicelle as an effective PRRS vaccine.

14.
Exp Cell Res ; : 112832, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536391

RESUMO

The autophagy/apoptosis interaction has always been a focus of study in pathogenicity models. Neuritin is a neurotrophic factor that is highly expressed primarily in the central nervous system. Our previous study revealed that it protects against apoptosis in cortical neurons subjected to oxygen-glucose deprivation (OGD)/reoxygenation (OGD/R), and later animal experiments revealed that it can increase the expression of the autophagy-related protein LC3. Whether this neuroprotective effect is closely related to autophagy is still unclear. In this study, we hypothesized that neuritin can promote autophagic flux to protect nerve cells after OGD/R. To verify this hypothesis, we induced OGD/R in primary cortical neurons and assessed cell viability by the CCK8 and LDH assays. Cell apoptosis was assessed by Annexin V-FITC/PI, staining, and the contents and mRNA abundances of the autophagy-related proteins LC3 and p62, the apoptotic protein Caspase3 were quantified by Western blotting and RT-PCR. Autophagic flux was assessed by immunofluorescence after RFP-GFP-LC3 virus transfection, and ultrastructural changes in autophagosomes were observed by transmission electron microscopy (TEM). The results showed that cell viability was decreased, apoptosis was increased and autophagy was enhanced after OGD/R. Neuritin significantly increased cell viability, decreased apoptosis, further increased the expression of the autophagic flux-related protein LC3, further decreased p62 expression, and significantly increased the autophagosome number and autophagosome to lysosome ratio. Bafilomycin A1 (BafA1) is a late autophagy inhibitor, aggravated cell damage and apoptosis and counteracted the enhancement of autophagy activation and protective effects of neuritin. In conclusion, neuritin may promote the completion of autophagic flux by ameliorating neuronal damage after OGD/R.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34468890

RESUMO

PURPOSE: The relationship between height and incident atrial fibrillation (AF) has recently been demonstrated. We aimed to evaluate the impact of height on outcomes of ablation in patients with drug-refractory symptomatic paroxysmal AF (PAF). METHODS: A total of 689 patients (470 males; age, 53.0 ± 11.7 years) with symptomatic paroxysmal AF receiving index catheter ablation (CA) between 2003 and 2013 were enrolled in this study. The baseline characteristics, ablation, and follow-up results were evaluated. The patients were categorized according to the quartiles of height for each sex. RESULTS: Patients in the lower quartiles of height had a lower incidence of AF recurrence (log-rank p = 0.022). Height in female patients was strongly associated with AF recurrence (p = 0.027) after an index ablation in the 6.33 ± 4.32 years of follow-up. Female patients > 159 cm in height had a higher likelihood of AF recurrence after index CA (HR = 2.01, 95% CI: 1.24-3.25, p = 0.005) than that in those below this height. In computed tomography (CT) scan, the superoinferior diameter of the left atrium (LA) correlated with body height in females, but not in male patients. CONCLUSIONS: Height is associated with AF recurrence after the index CA of PAF in female patients. In Asian populations, women above height 159 cm are twice as likely to have AF recurrence post-ablation as shorter women.

16.
BMC Cardiovasc Disord ; 21(1): 387, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372779

RESUMO

BACKGROUND: Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear. METHODS: Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25-30 W, force-time integral = 400 g s, n = 40) or with HPSD (power control: 40-50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed. RESULTS: 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P < 0.01). In the conventional group, most type A lesions were at the right pulmonary vein (RPV) posterior wall (50.2%) whereas in the HPSD group, most type A lesions were at the RPV anterior wall (44.0%) (P = 0.04). The procedure time and ablation time were significantly shorter in the HPSD group than that in the conventional group (91.0 ± 12.1 vs. 124 ± 14.2 min, P = 0.03; 30.7 ± 19.2 vs. 57.8 ± 21 min, P = 0.02, respectively). At a mean follow-up period of 11 ± 1.4 months, there were 13 and 7 patients with recurrence in conventional and HPSD group respectively (P = 0.03). CONCLUSION: Optimal ablation lesion characteristics and distribution after conventional and HPSD ablation differed significantly. HPSD ablation had shorter ablation time and lower recurrence rate than did conventional ablation.

17.
Neurobiol Aging ; 106: 292-303, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34340010

RESUMO

Increasing evidence has placed inflammation and immune dysfunction at the center of the pathogenesis of Alzheimer's disease (AD). The mitochondrial protein translocator protein (18 kDa) (TSPO) is highly upregulated in microglia and astrocytes in response to inflammatory stimulation. However, the biological action of TSPO in the pathogenesis of AD has not been determined to date. In this study, we showed that TSPO expression was upregulated in brain tissues from AD patients and AD model mice. APP/PS1 mice lacking TSPO generated significantly higher levels of Aß1-40 and Aß1-42 peptides and more Aß plaques, as well as enhanced microglial activation, in the brain. TSPO-deficient microglia cultured in vitro showed a significant decrease in the ability to phagocytose Aß peptides or latex beads and generated more proinflammatory cytokines (TNF-α and IL-1ß) in response to Aß peptides. Our findings suggest that TSPO has protective functions against neuroinflammation and Aß pathogenesis in AD. TSPO may be a potential drug target for the development of drugs that have therapeutic or preventive effects in neuroinflammatory diseases.

18.
Ecotoxicol Environ Saf ; 224: 112678, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34419641

RESUMO

PM2.5 exposure is considered harmful to central nerve system, while the specific biochemical mechanism underlying is still unrevealed. Neuronal apoptosis is believed the crucial event in pathogenesis of neurodegenerative diseases, but evidence supporting neuronal apoptosis as the mechanism for PM2.5 exposure induced neuronal injury is insufficient. S-adenosylmethionine decarboxylase 1 (AMD1) and its related spermidine synthesis have been shown to associate with cellular apoptosis, but its role in PM2.5 exposure induced neuronal apoptosis was rarely reported. The current study was aimed to better understand contribution of AMD1 activity and spermidine in PM2.5 exposure induced neuronal apoptosis. Sixteen C57BL/6 male mice were randomly divided and kept into ambient PM2.5 chamber or filtered air chamber for 6 months to establish the mouse model of whole-body ambient PM2.5 chronic exposure. In parallel, PC12 cells and primary hippocampal neurons were applied for various concentrations of PM2.5 treatment (0, 25, 50, 100, 200, and 400 µg/mL) to explore the possible cellular and molecular mechanism which may be critically involved in the process. Results showed that PM2.5 exposure triggered neuronal apoptosis with increased expression of Bax/Bcl-2 and cleaved caspase-3. PM2.5 exposure reduced AMD1 expression and spermidine synthesis. AMD1 inhibition could mimic PM2.5 exposure induced neuronal apoptosis. Spermidine supplementation rescued against neurotoxicity and inhibited PM2.5 induced apoptosis via impaired depolarization of mitochondrial membrane potential and reduced mitochondrial apoptosis related proteins. In summary, our work demonstrated that exposure to PM2.5 led to neuronal apoptosis, which may be the key event in the process of air pollution induced neurodegenerative diseases. AMD1 and spermidine associated with neuronal apoptosis induced by PM2.5 exposure, which was at least partially dependent on mitochondria mediated pathway.

19.
Int Immunopharmacol ; 99: 108016, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34385029

RESUMO

OBJECTIVE: The purpose of this study was to explore the relationship between pretreatment cytokine status and overall survival and establish a prognostic nomogram incorporating cytokines in newly diagnosed multiple myeloma (NDMM) patients. METHODS: A total of 121 patients with NDMM from the Wuhan Union Hospital were included in our study. Patient serum levels of cytokines, including macrophage inflammatory protein 1 alpha (MIP-1α), migration inhibitory factor (MIF), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor-α (VEGF-α), monocyte chemoattractant protein-1 (MCP-1) and soluble interleukins IL-17A, IL-6, IL-21 and IL-10 were assessed before treatment. Based on the results of the multivariate Cox proportional hazards model, we developed a prognostic nomogram. We used the concordance index (C-index) and a calibration curve to measure the predictive performance of the nomogram. RESULTS: Three important variables (lactate dehydrogenase, MIP-1α and creatinine) were incorporated in the nomogram using multivariate Cox analysis. The 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 83.8% and 21.8% in the low-risk group of the nomogram and 17.4% and 8.4% in the high-risk group, respectively. The C-index of the nomogram for OS prediction was 0.80 (95% CI: 0.68-0.92), showing superiority over the predictive power of the Durie-Salmon staging system (C-index = 0.58; 95% CI: 0.49-0.67), International Staging System (C-index = 0.70; 95% CI: 0.61-0.79) and Revised-International Staging System (C-index = 0.71; 95% CI: 0.63-0.80). The calibration curve showed that the nomogram accurately predicted the 1-year, 2-year and 3-year OS of NDMM patients. CONCLUSION: The established nomogram provides accurate and individualized OS risk estimation for NDMM patients.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34449092

RESUMO

BACKGROUND: Atrial fibrillation (AF) prevalence increases with age. Aging affects the substrate properties of the left atrium (LA) and the outcomes of catheter ablation for treating AF. We investigated the AF trigger distribution and catheter ablation outcomes in patients of different ages with AF. METHODS: 1585 patients with AF (1181 paroxysmal and 404 non- paroxysmal AF) who had undergone catheter ablation were enrolled. The patients were divided into young (20-40 year-old, n = 175), middle-aged (41-64 year-old, n = 1134), and old (≥ 65 year-old, n = 276) groups. Electrophysiological characteristics and AF trigger sites were recorded. RESULT: The incidence of AF with only non-pulmonary vein (non-PV) foci was higher in the young group than in the other groups (8.6% vs. 3.6% vs. 3.3%, p < 0.01). Non-PV foci were more commonly located in the superior vena cava (SVC) in the young group than in the other groups (13.1% vs. 7.8% vs. 6.5%, p = 0.03). The left atrium (LA) mean voltage was higher and the incidence of very late recurrence after AF ablation was lower in the young group than in the other groups. However, the final AF recurrence rate after multiple procedures and complication rates were similar among all the groups at a mean follow-up of 5.6 years. CONCLUSION: The young patients with AF had a higher incidence of only non-PV foci, mostly located in SVC, than the middle-aged and old patients. Our study highlights the importance of identifying the non-PV foci in catheter ablation of young patients with AF.

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