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1.
Int J Infect Dis ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798720

RESUMO

OBJECTIVE: Guidelines from different areas on the use of non-invasive ventilation in COVID-19 have generally been inconsistent. The goals were to appraise the quality and availability of guidelines stated and whether non-invasive ventilation in the early stage of the pandemic is of importance. DESIGN AND METHOD: Databases including PubMed, Web of Science, Cochrane Library, and websites of international organizations and gray databases were searched up to June 23, 2020. We also hand-searched the reference lists of eligible papers. RESULTS: A total of 26 guidelines met the inclusion criteria. Regarding the appraisal by the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, the guidelines' methodological quality was low. Among six domains, Rigour. of Developmentand Editorial Independencewere of the lowest quality. Given the lack of evidence from randomized clinical trials and the great differences between different regions, non-invasive ventilation's recommendations generated a considerable debate at the early stage of COVID-19. CONCLUSIONS: Improving the methodological quality of the guidelines should be a goal in future pandemics. Additionally, more well-designed randomized clinical trials are needed to solve the controversy on the impact of non-invasive ventilation.

2.
J Cardiovasc Pharmacol ; 77(4): 480-490, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33818551

RESUMO

ABSTRACT: Atherosclerosis is a chronic lipid-induced inflammation of the vessel wall. Oxidized low-density lipoprotein was confirmed to drive the onset of atherogenesis. Zinc finger e-box-binding homeobox 1 antisense 1 (ZEB1-AS1) is a long noncoding RNA that is involved in human diseases, including atherosclerosis. In this study, the role of exosomes-mediated ZEB1-AS1 and its underlying mechanisms in atherosclerosis were explored in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). Exosomes were extracted from HUVECs. Quantitative real-time polymerase chain reaction was conducted to measure the expression of ZEB1-AS1, microRNA-590-5p (miR-590-5p), or erythroblastosis virus E26 oncogene homolog 1 (ETS1) in cells or exosomes. Cell proliferation and apoptosis were assessed by MTT assay and flow cytometry analysis, respectively. Western blot was performed to detect apoptosis-related factors, ETS1, and TGF-ß/Smad pathway protein levels. The secretion of inflammatory factors in supernatant was detected by ELISA assay. Oxidative stress damage indicators were used to assess cellular damage. Relationship between miR-590-5p and ZEB1-AS1 or ETS1 was analyzed. Our data indicated that ox-LDL-induced exosomes-mediated ZEB1-AS1 in HUVECs. Ox-LDL treatment resulted in limited proliferation, proapoptosis, inflammation, and oxidative stress damage, whereas knockdown of ZEB1-AS1 could reverse these effects. Mechanically, ZEB1-AS1 sponged miR-590-5p to regulate ETS1 expression. MiR-590-5p knockdown inverted effects above of si-ZEB1-AS1 on HUVECs under ox-LDL exposure. Moreover, ETS1 reversed miR-590-5p-induced effects and activated the TGF-ß/Smad pathway in ox-LDL-treated HUVECs. Taken together, our findings demonstrated that exosomes-mediated ZEB1-AS1 enhanced cell injuries by miR-590-5p/ETS1 axis through the TGF-ß/Smad pathway in ox-LDL-induced HUVECs, suggesting that inhibiting ZEB1-AS1 might be an effective way for atherosclerosis treatment.

3.
Med Sci Monit ; 27: e928863, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33642564

RESUMO

BACKGROUND Accurate risk assessment and prospective stratification are of great importance for treatment of acute coronary syndrome (ACS). However, the optimal risk evaluation systems for predicting different type of ACS adverse events in Chinese population have not been established. MATERIAL AND METHODS Our data were derived from the Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) Project, a multicenter registry program. We incorporated data on 44 750 patients in the study. We compared the performance of the following 4 different risk score systems with regard to prediction of in-hospital adverse events: the Global Registry for Acute Coronary Events (GRACE) risk score system; the age, creatinine and ejection fraction (ACEF) risk score system, and its modified version (AGEF), and the Canada Acute Coronary Syndrome (C-ACS) risk assessment system. RESULTS Admission AGEF risk score was a better prognosis index of potential for in-hospital mortality for patients with ST segment elevation myocardial infarction (STEMI) than GRACE risk score (AUC: 0.845 vs 0.819, P=0.012), ACEF (AUC: 0.845 vs 0.827, P=0.014), C-ACS (AUC: 0.845 vs 0.767, P<0.001). In patients with non-ST segment-elevation acute coronary syndrome (NSTE-ACS), there was no statistically significant difference between the GRACE risk scale and AGEF (AUC: 0.853 vs 0.832, P=0.140) for in-hospital death. CONCLUSIONS AGEF risk score showed a non-inferior utility compared with the other 3 scoring systems in estimating in-hospital mortality in ACS patients.

4.
Zhongguo Zhen Jiu ; 41(2): 217-20, 2021 Feb 12.
Artigo em Chinês | MEDLINE | ID: mdl-33788474

RESUMO

Given that the biomechanical theory cannot well explain the therapeutic effect of fan-ashi point (a special site that may relieve pain by pressing), the skeletal muscle tension is adopted and it is attempted to interpret the mechanism of the curative effect and the effect onset of fan-ashi point. It is viewed that the longitudinal tension conduction and transverse tension conduction pathways of skeletal muscle are the material basis of the effect onset of fan-ashi point. Hence, acupuncture at fan-ashi point may alter the longitudinal or transverse tension conduction of skeletal muscle to relieve muscle and tendon pain.


Assuntos
Terapia por Acupuntura , Acupuntura , Dor Musculoesquelética , Pontos de Acupuntura , Humanos , Músculo Esquelético
5.
Technol Health Care ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33682770

RESUMO

BACKGROUND: Malignant lymphoma is a type of tumor that originated from the lymphohematopoietic system, with complex etiology, diverse pathological morphology, and classification. It takes a lot of time and energy for doctors to accurately determine the type of lymphoma by observing pathological images. OBJECTIVE: At present, an automatic classification technology is urgently needed to assist doctors in analyzing the type of lymphoma. METHODS: In this paper, by comparing the training results of the BP neural network and BP neural network optimized by genetic algorithm (GA-BP), adopts a deep residual neural network model (ResNet-50), with 374 lymphoma pathology images as the experimental data set. After preprocessing the dataset by image flipping, color transformation, and other data enhancement methods, the data set is input into the ResNet-50 network model, and finally classified by the softmax layer. RESULTS: The training results showed that the classification accuracy was 98.63%. By comparing the classification effect of GA-BP and BP neural network, the accuracy of the network model proposed in this paper is improved. CONCLUSIONS: The network model can provide an objective basis for doctors to diagnose lymphoma types.

6.
Aging (Albany NY) ; 13(5): 6236-6246, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33640878

RESUMO

BACKGROUND: The immune responses, hyper-inflammation or immunosuppression, may be closely related to COVID-19 progression. We aimed to evaluate the changes of frequency of CD14+HLA-DRlo/neg MDSCs, a population of cells with potent immunosuppressive capacity, in COVID-19 patients. METHODS: The levels of CD14+HLA-DRlo/neg MDSCs were determined by flow cytometry in 27 COVID-19 patients, and their association with clinical characteristics and laboratory data were analyzed. RESULTS: The frequency of CD14+HLA-DRlo/neg MDSCs was elevated in COVID-19 patients, particularly severe patients. A follow-up comparison revealed a decline of CD14+HLA-DRlo/neg MDSCs percentages in most patients 1 day after testing negative for SARS-CoV-2 nucleic acid, but the levels of CD14+HLA-DRlo/neg MDSCs were still greater than 50.0% in 3 ICU patients 4-10 days after negative SARS-CoV-2 results. Elevated frequency of CD14+HLA-DRlo/neg MDSCs was positively correlated with oropharyngeal viral loads and length of hospital stay, while negatively correlated with lymphocyte counts and serum albumin. Moreover, strong correlations were observed between the frequency of CD14+HLA-DRlo/neg MDSCs and T cell subsets, NK cell counts, and B cell percentages. The frequency of CD14+HLA-DRlo/neg MDSCs could be used as a predictor of COVID-19 severity. CONCLUSIONS: A high frequency of CD14+HLA-DRlo/neg MDSCs, especially in severe patients, may indicate an immunoparalysis status and could be a predictor of disease severity and prognosis.


Assuntos
/imunologia , Antígenos HLA-DR/imunologia , Receptores de Lipopolissacarídeos/imunologia , Células Supressoras Mieloides/patologia , /imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , /patologia , Feminino , Antígenos HLA-DR/análise , Humanos , Tolerância Imunológica , Receptores de Lipopolissacarídeos/análise , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Prognóstico , /isolamento & purificação
7.
Neurobiol Dis ; 153: 105313, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33636388

RESUMO

Vacuolar protein sorting protein 35 (VPS35) is a core component of the retromer complex involved in regulating protein trafficking and retrieval. Recently, a missense mutation, Asp620Asn (D620N), in VPS35 (PARK17) has been identified as a pathogenic mutation for late-onset autosomal dominant Parkinson's disease (PD). Although PD is characterized by a range of motor symptoms associated with loss of dopaminergic neurons in the substantial nigra, non-motor symptoms such as impaired hippocampal neurogenesis were observed in both PD patients and animal models of PD caused by multiple PD-linked pathogenic genes such as alpha-synuclein and leucine-rich repeat kinase 2 (LRRK2). However, the role of the VPS35 D620N mutation in adult hippocampal neurogenesis remains unknown. Here, we showed that the VPS35 D620N mutation impaired hippocampal neurogenesis in adult transgenic mice expressing the VPS35 D620N gene. Specifically, we showed a reduction in the neural stem cell pool and neural proliferation and differentiation, retarded migration, and impaired neurite outgrowth in 3-month-old VPS35 D620N mutant mice. Moreover, we found that the VPS35 D620N mutant hyperphosphorylates amyloid precursor protein (APP) at Thr668and interacts with APP. Notably, by crossing the VPS35 D620N mutant mice with APP knockout (KO) mice, we showed that loss of APP function rescues VPS35 D620N-inhibited neurogenesis, neural migration, and maturation. Our study provides important evidence that APP is involved in the VPS35 D620N mutation in regulating adult neurogenesis, which sheds light on the pathogenic mechanisms in PD.

8.
Environ Int ; 150: 106435, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33601224

RESUMO

BACKGROUND: Air pollution is a major environmental hazard to human health and a leading cause of morbidity for asthma worldwide. OBJECTIVES: To assess the current evidence on short-term effects (from several hours to 7 days) of exposure to ozone (O3), nitrogen dioxide (NO2), and sulphur dioxide (SO2) on asthma exacerbations, defined as emergency room visits (ERVs) and hospital admissions (HAs). METHODS: We searched PubMed/MEDLINE, EMBASE and other electronic databases to retrieve studies that investigated the risk of asthma-related ERVs and HAs associated with short-term exposure to O3, NO2, or SO2. We evaluated the risks of bias (RoB) for individual studies and the certainty of evidence for each pollutant in the overall analysis. A subgroup analysis was performed, stratified by sex, age, and type of asthma exacerbation. We conducted sensitivity analysis by excluding the studies with high RoB and based on the E-value. Publication bias was examined with the Egger's test and with funnel plots. RESULTS: Our literature search retrieved 9,059 articles, and finally 67 studies were included, from which 48 studies included the data on children, 21 on adults, 14 on the elderly, and 31 on the general population. Forty-three studies included data on asthma ERVs, and 25 on asthma HAs. The pooled relative risk (RR) per 10 µg/m3 increase of ambient concentrations was 1.008 (95%CI: 1.005, 1.011) for maximum 8-hour daily or average 24-hour O3, 1.014 (95%CI: 1.008, 1.020) for average 24-hour NO2, 1.010 (95%CI: 1.001, 1.020) for 24-hour SO2, 1.017 (95%CI: 0.973, 1.063) for maximum 1-hour daily O3, 0.999 (95%CI: 0.966, 1.033) for 1-hour NO2, and 1.003 (95%CI: 0.992, 1.014) for 1-hour SO2. Heterogeneity was observed in all pollutants except for 8-hour or 24-hour O3 and 24-hour NO2. In general, we found no significant differences between subgroups that can explain this heterogeneity. Sensitivity analysis based on the RoB showed certain differences in NO2 and SO2 when considering the outcome or confounding domains, but the analysis using the E-value showed that no unmeasured confounders were expected. There was no major evidence of publication bias. Based on the adaptation of the Grading of Recommendations Assessment, Development and Evaluation, the certainty of evidence was high for 8-hour or 24-hour O3 and 24-hour NO2, moderate for 24-hour SO2, 1-hour O3, and 1-hour SO2, and low for 1-hour NO2. CONCLUSION: Short-term exposure to daily O3, NO2, and SO2 was associated with an increased risk of asthma exacerbation in terms of asthma-associated ERVs and HAs.

9.
Matrix Biol ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33548399

RESUMO

Autophagy is a fundamental cellular process discovered as a response to nutrient deprivation. It provides the cellular and molecular machinery for catabolism of cellular constituents, generating energy and providing building blocks for continued survival. However, autophagy does much more than provide an entry into catabolic pathways, it provides a mechanism for intracellular quality control, removing damaged organelles and misfolded proteins, processes critical for cellular health. Autophagy serves as a counterpoint to cell growth and anabolic events, activated when growth is not possible or is suppressed. Hence, there is an inherent antagonism between autophagy and growth. Heparan sulfate modified proteins are important co-receptors that generally promote growth factor activity and are therefore positioned within signaling networks that inhibit, or negatively regulate autophagy levels. This review summarizes evidence that heparan sulfate modified proteins provide an evolutionarily conserved inhibitory modulation of autophagy that can have profound effects on cell physiology and organismal responses to stress.

10.
Sci Rep ; 11(1): 4530, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33633208

RESUMO

Immune profiling is becoming a vital tool for identifying predictive and prognostic markers for translational studies. The study of the tumor microenvironment (TME) in paraffin tumor tissues such as malignant pleural mesothelioma (MPM) could yield insights to actionable targets to improve patient outcome. Here, we optimized and tested a new immune-profiling method to characterize immune cell phenotypes in paraffin tissues and explore the co-localization and spatial distribution between the immune cells within the TME and the stromal or tumor compartments. Tonsil tissues and tissue microarray (TMA) were used to optimize an automated nine-color multiplex immunofluorescence (mIF) panel to study the TME using eight antibodies: PD-L1, PD-1, CD3, CD8, Foxp3, CD68, KI67, and pancytokeratin. To explore the potential role of the cells into the TME with this mIF panel we applied this panel in twelve MPM cases to assess the multiple cell phenotypes obtained from the image analysis and well as their spatial distribution in this cohort. We successful optimized and applied an automated nine-color mIF panel to explore a small set of MPM cases. Image analysis showed a high degree of cell phenotype diversity with immunosuppression patterns in the TME of the MPM cases. Mapping the geographic cell phenotype distribution in the TME, we were able to identify two distinct, complex immune landscapes characterized by specific patterns of cellular distribution as well as cell phenotype interactions with malignant cells. Successful we showed the optimization and reproducibility of our mIF panel and their incorporation for comprehensive TME immune profiling into translational studies that could refine our ability to correlate immunologic phenotypes with specific patterns of cells distribution and distance analysis. Overall, this will improve our ability to understand the behavior of cells within the TME and predict new treatment strategies to improve patient outcome.

11.
Sci Rep ; 11(1): 4769, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637790

RESUMO

Salvia miltiorrhiza is one of the most widely used traditional medicines. Natural antisense transcripts (NATs) are a class of long noncoding RNAs that can regulate gene expression. Here, we identified 812 NATs, including 168 cis-NATs and 644 trans-NATs from twelve root, flower, and leaf samples of S. miltiorrhiza using RNA-seq. The expression profiles for 41 of 50 NATs and their sense transcripts (STs) obtained from RNA-Seq were validated using qRT-PCR. The expression profiles of 17 NATs positively correlated with their STs. GO and KEGG pathway analyses mapped the STs for cis-NATs to pathways for biosynthesis of secondary metabolites. We characterized four NATs in detail, including NAT0001, NAT0002, NAT0004, and NAT00023. Their STs are kaurene synthase-like 1 and the homologs of UDP-glucose flavonoid 3-O-glucosyltransferase 6, UDP-glycosyltransferase 90A1, and beta-glucosidase 40, respectively. The first gene is involved in the biosynthesis of bioactive tanshinones, the next two are involved in anthocyanin biosynthesis, whereas the last is involved in phenylpropanoid biosynthesis. Besides, we found seven STs that are potential targets of miRNAs. And we found two miRNAs including miR156a and miR7208, might originate from NATs, NAT0112 and NAT0086. The results suggest that S. miltiorrhiza NATs might interact with STs, produce miRNAs, and be regulated by miRNAs. They potentially play significant regulatory roles in the biosynthesis of bioactive compounds.

12.
Parasitology ; : 1-9, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33536085

RESUMO

Toxoplasma gondii can infect almost all warm-blooded vertebrates with pathogensis being largely influenced by the host immune status. As important epidemiological hosts, rodents are globally distributed and are also commonly found infected with haemoflagellates, such as those in the genus Trypanosoma. We here address whether and how co-infection with trypanosomes can influence T. gondii infection in laboratory models. Rats of five strains, co-infected with T. lewisi and mice of four strains, co-infected with T. musculi, were found to be more or less susceptible to T. gondii infection, respectively, with corresponding increased or decreased brain cyst burdens. Downregulation of iNOS expression and decreased NO production or reverse were observed in the peritoneal macrophages of rats or mice, infected with trypanosomes, respectively. Trypanosoma lewisi and T. musculi can modulate host immune responses, either by enhancement or suppression and influence the outcome of Toxoplasma infection.

13.
Int J Infect Dis ; 104: 415-422, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33450372

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. METHODS: A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG-); (2) IgG-positive but IgM-negative (IgG+IgM-); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/-); (5) IgG-positive without IgM information (IgG+IgM+/-); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). RESULTS: Sixty-eight studies were included. Pooled sensitivities for IgM+IgG-, IgG+IgM-, IgM+IgG+, IgM+IgG+/-, IgG+IgM+/-, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. DISCUSSION: These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.

14.
Med Res Rev ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33393116

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global crisis. As of November 9, COVID-19 has already spread to more than 190 countries with 50,000,000 infections and 1,250,000 deaths. Effective therapeutics and drugs are in high demand. The structure of SARS-CoV-2 is highly conserved with those of SARS-CoV and Middle East respiratory syndrome-CoV. Enzymes, including RdRp, Mpro /3CLpro , and PLpro , which play important roles in viral transcription and replication, have been regarded as key targets for therapies against coronaviruses, including SARS-CoV-2. The identification of readily available drugs for repositioning in COVID-19 therapy is a relatively rapid approach for clinical treatment, and a series of approved or candidate drugs have been proven to be efficient against COVID-19 in preclinical or clinical studies. This review summarizes recent progress in the development of drugs against SARS-CoV-2 and the targets involved.

15.
J Texture Stud ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33438754

RESUMO

This study aimed to evaluate the effects of fat content on the textural and in vivo buccal breakdown properties of soy yogurt (SY) at different pH (5.4, 5.0, and 4.6). The microbial analysis, textural and rheological properties, and interfacial protein composition of all the samples were monitored. Microbial results suggested that the increased fat content in SY-5.0 and SY-4.6 resulted in significantly high viable cell counts of lactic acid bacteria (LAB). Textural studies demonstrated that the presence of a low fat content (1-3%) significantly reduced the hardness, springiness, and gumminess of the sample, but this effect was negligible with the addition of fat content (4-5%). The apparent viscosity and thixotropy of the SY-4.6 sample increased as the fat content increased. in vivo buccal digestion showed that a high fat content (2-4%) reduced the number of chews and chewing durations, which might be correlated with high oil droplet release (%) after mastication.

16.
Allergy Asthma Proc ; 42(1): e40-e46, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33404400

RESUMO

Background: House-dust mites (HDM) allergen is one of the most important allergens in southern China; however, studies on the Dermatophagoides pteronyssinus components are relatively lacking. Objective: This study analyzed the molecular components of D. pteronyssinus in patients with allergic asthma (AS) and/or allergic rhinitis (AR) sensitized to D. pteronyssinus, and aimed to improve HDM immunotherapy in southern China. Methods: Allergen component-resolved diagnosis detection technology was used to detect the serum levels of specific immunoglobulin E (sIgE) to D. pteronyssinus allergen components (Der p 1, 2, 3, 5, 7, 10, and 23) in patients who were sensitized to D. pteronyssinus and with AR (n = 106), AS (n = 144), or AR combined with AS (n = 134). Results: The highest positive rates of D. pteronyssinus components were Der p 1 (94.8%), followed by Der p 2 (77.6%), Der p 23 (62.5%), Der p 7 (34.6%), Der p 5 (17.7%), Der p 10 (12.2%), and Der p 3 (2.6%). Patients with AR+AS had the highest positive rates to Der p 2 (85.8%), Der p 23 (62.7%), Der p 7 (40.3%), Der p 5 (25.0%), and Der p 10 (16.4%). Der p 1 had the highest positive rate in patients with AR (95.3%). The Der p 3 positive rate in patients with AS (6.0%) was higher than that in patients with AR (0.0%, χ² = 6.872, p < 0.05) and patients with AR+AS (0.7%, χ² = 6.063, p < 0.05) Among the patients with AR+AS, 19.1% were co-sensitized to Der p 1, Der p 2, Der p 23, and Der p 7. Interestingly, only one patient with AR was exclusively sensitized to Der p 23. An optimal scale analysis showed that Der p 5, Der p 23, and Der p 7 had strong connection (Cronbach α = 93.7%). Conclusion: Der p 1 and Der p 2 were the main sensitization components of D. pteronyssinus, and patients with AS+AR had the highest positive rate for five of seven D. pteronyssinus allergen components. This research can provide suggestions for personalized HDM-specific immunotherapy in southern China.

17.
Lung Cancer ; 152: 58-65, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33352384

RESUMO

INTRODUCTION: The relationship between Body-Mass-Index (BMI) and lung cancer prognosis is heterogeneous. We evaluated the impact of sex, smoking and race on the relationship between BMI and overall survival (OS) in non-small-cell-lung-cancer (NSCLC). METHODS: Data from 16 individual ILCCO studies were pooled to assess interactions between BMI and the following factors on OS: self-reported race, smoking status and sex, using Cox models (adjusted hazard ratios; aHR) with interaction terms and adjusted penalized smoothing spline plots in stratified analyses. RESULTS: Among 20,937 NSCLC patients with BMI values, females = 47 %; never-smokers = 14 %; White-patients = 76 %. BMI showed differential survival according to race whereby compared to normal-BMI patients, being underweight was associated with poor survival among white patients (OS, aHR = 1.66) but not among black patients (aHR = 1.06; pinteraction = 0.02). Comparing overweight/obese to normal weight patients, Black NSCLC patients who were overweight/obese also had relatively better OS (pinteraction = 0.06) when compared to White-patients. BMI was least associated with survival in Asian-patients and never-smokers. The outcomes of female ever-smokers at the extremes of BMI were associated with worse outcomes in both the underweight (pinteraction<0.001) and obese categories (pinteraction = 0.004) relative to the normal-BMI category, when compared to male ever-smokers. CONCLUSION: Underweight and obese female ever-smokers were associated with worse outcomes in White-patients. These BMI associations were not observed in Asian-patients and never-smokers. Black-patients had more favorable outcomes in the extremes of BMI when compared to White-patients. Body composition in Black-patients, and NSCLC subtypes more commonly seen in Asian-patients and never-smokers, may account for differences in these BMI-OS relationships.

18.
Int J Pharm ; 594: 120183, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33340596

RESUMO

Lymph node metastases in cancer patients are associated with high aggressiveness, poor prognosis, and short survival time. The chemokine receptor 4 (CXCR4)/stroma derived factor 1α (CXCL12) biological axis plays a critical role in the spread of cancer cells. Designing effective delivery systems that can successfully deliver CXCR4 antagonists to lymph nodes, which are rich in CXCR4-overexpressing cancer cells, for controlling cancer metastasis remain challenging. In this study, we demonstrated that such a challenge may be alleviated by developing nanometer-sized polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles for the co-delivery of the CXCR4 antagonistic peptide E5 and doxorubicin (M-E5-Dox). This nanomicelle platform enables the preferential accumulation of cargos into lymph nodes and thus can better inhibit cancer metastasis and enhance antitumor efficacy than either free drugs or single drug-loaded micelles in breast cancer-bearing mouse models. Hence, M-E5-Dox is expected to be a potential therapeutic agent that would improve the clinical benefits of breast cancer therapy and treatment of various CXCR4-overexpressing malignancies.

19.
Mol Brain ; 13(1): 164, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33261640

RESUMO

Vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex that mediates the retrograde transport of cargo proteins from endosomes to the trans-Golgi network. Mutations such as D620N in the VPS35 gene have been identified in patients with autosomal dominant Parkinson's disease (PD). However, it remains poorly understood whether and how VPS35 deficiency or mutation contributes to PD pathogenesis; specifically, the studies that have examined VPS35 thus far have differed in results and methodologies. We generated a VPS35 D620N mouse model using a Rosa26-based transgene expression platform to allow expression in a spatial manner, so as to better address these discrepancies. Here, aged (20-months-old) mice were first subjected to behavioral tests. Subsequently, DAB staining analysis of substantia nigra (SN) dopaminergic neurons with the marker for tyrosine hydroxylase (TH) was performed. Next, HPLC was used to determine dopamine levels, along with levels of its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum. Western blotting was also performed to study the levels of key proteins associated with PD. Lastly, autoradiography (ARG) evaluation of [3H]FE-PE2I binding to the striatal dopamine transporter DAT was carried out. We found that VPS35 D620N Tg mice displayed a significantly higher dopamine level than NTg counterparts. All results were then compared with that of current VPS35 studies to shed light on the disease pathogenesis. Our model allows future studies to explicitly control spatial expression of the transgene which would generate a more reliable PD phenotype.

20.
Dis Markers ; 2020: 8833438, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33273988

RESUMO

Background: Appreciable findings have pointed out pivotal roles of N 6-methyladenosine (m6A) machinery in cancer onset and progression. However, limited efforts have been directed towards relevant research in the prostate cancer area. Methods: A PubMed search was conducted to acquire components of the mRNA m6A machinery. Multiomics integration was performed to systematically investigate the mRNA m6A machinery in primary prostate cancer. Furthermore, RNA interference assays of two prognostic m6A readers EIF3D and HNRNPA2B1 were conducted to explore m6A dependence of their functions in prostate cancer cell proliferation and migration. Results: A total of 41 mRNA m6A regulators have been identified to date. A small degree of copy number aberrations and an extremely low frequency of somatic mutations were observed in the regulators across prostate tumors. Enrichment of CpG sites and extensive changes of DNA methylation in the m6A machinery were also found. Impact of copy number variation on m6A regulator expression was stronger than that of DNA methylation disturbance. Furthermore, our study identified a set of m6A regulators related to clinical features and/or survival which were largely m6A-binding proteins. The translation initiation factor subunit EIF3D and the splicing factor HNRNPA2B1 can be independent prognostic factors which may contribute to retardation and promotion of cancer progression, respectively, through affecting cancer-related processes such as cell cycle. Moreover, in vitro assays demonstrated that m6A impacted the EIF3D and HNRNPA2B1 roles in proliferation and migration of prostate cancer cells. Conclusions: Our report systematically described molecular features of the mRNA m6A machinery and their potential roles in primary prostate cancer. Knowledge gained from this work may pave the way for further studies on the m6A system in prostate cancer.

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