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1.
Int J Chron Obstruct Pulmon Dis ; 16: 2721-2733, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621122

RESUMO

Background: Several observational studies have found that statins may materially decrease the risk of chronic obstructive pulmonary disease (COPD) exacerbations. However, most of these studies used a prevalent user, non-user comparison approach, which may lead to overestimation of the clinical benefits of statins. We aimed to explore the risk of COPD exacerbations associated with statins with a new user, active comparison approach to address potential methodological concerns. We selected fibrates, another class of lipid-lowering agents, as the reference group because no evidence suggests that fibrates have an effect on COPD exacerbations. Methods: We identified patients with COPD who initiated statins or fibrates from a nationwide Taiwanese database. Patients were followed from cohort entry to the earliest of the following: hospitalization for COPD exacerbations, death, end of the data, or 180 days after cohort entry. Stratified Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of COPD exacerbations comparing statins with fibrates after variable-ratio propensity score (PS) matching and high-dimensional PS (hd-PS) matching, respectively. Results: We identified a total of 134,909 eligible patients (110,726 initiated statins; 24,183 initiated fibrates); 1979 experienced COPD exacerbations during follow-up. The HRs were 1.10 (95% CI, 0.96 to 1.26) after PS matching and 1.08 (95% CI, 0.94 to 1.24) after hd-PS matching. The results did not differ materially by type of statins and patient characteristic and did not change with longer follow-up durations. Conclusion: This large-scale, population-based cohort study did not show that use of statins was associated with a reduced risk of acute exacerbations in patients with COPD using state-of-the-art pharmacoepidemiologic approaches. The findings emphasize the importance of applying appropriate methodology in exploring statin effectiveness in real-world settings.

2.
BMC Public Health ; 21(1): 1831, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627173

RESUMO

BACKGROUND: In July 1984, Taiwan officially began a nationwide hepatitis B virus (HBV) vaccination program where only infants born to HBsAg-positive mothers were vaccinated free of charge until June 1986. However, from July 1986, all infants were vaccinated against HBV. The impact of the July 1986 HBV vaccination program on first-time blood donors has not been exhaustively studied. We, therefore, determined the risk of HBV among male and female first-time blood donors born before and after the July 1986 HBV vaccination program in Taiwan. METHODS: Initially, we recruited 857,310 first-time blood donors whose data were collected between 2013 and 2018 from 5 blood donation centers in Taiwan. However, we excluded donors with incomplete and outlying data (n = 12,213) and those born between July 1984 and June 1986 (n = 21,054). The final study participants comprised 9118 HBV positive and 814,925 HBV negative individuals. We divided the participants into two birth cohorts (born before and after July 1986) and assumed that those born before July 1986 were not vaccinated at birth while those born after July 1986 were vaccinated. RESULTS: The prevalence of HBV among those born before and after July 1986 was 4.53 and 0.25%, respectively. Individuals born after July 1986 had a lower risk of HBV than those born before July 1986. The adjusted odds ratio (OR), 95% confidence interval (CI) was 0.16, 0.13-0.19. Men had a higher risk of HBV than women (OR = 1.40, 95% CI = 1.34-1.47). The interaction between sex and birth date was significant (p-value = 0.0067). Stratification of participants by birth date revealed a higher risk of HBV in men compared to women in both birth cohorts. The OR, 95% CI was 1.47, 1.40-1.55 for those born before July 1986 but declined to 1.15, 1.02-1.29 for those born after July 1986. CONCLUSIONS: The risk of HBV was lower among those born after than those born before the July 1986 vaccination program. In both cohorts, the risk was high in men relative to women. The seemingly protective effect among those born after July 1986 was higher in women than men.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34669131

RESUMO

The topic of inflammatory bowel disease (IBD) has attracted more and more attention. Accumulating evidence suggests that exposure to air pollutants is associated with IBD, yet the results are inconsistent and study about daily exposure is few. This study evaluated the association between daily air pollution and IBD in Hefei, China. Daily IBD admission data were obtained from two hospitals in Hefei from January 1, 2019, to December 31, 2019. Daily concentrations of major air pollutants were provided by the Hefei Environmental Protection Bureau. Meteorological data were collected from China Meteorological Data Network. Distributed lag nonlinear model (DLNM) considering both the lag effects of exposure factors and nonlinear relationship of exposure-reaction was used to assess the effect of daily air pollutants exposure on IBD admission. During the study period, totally 886 cases of IBD were recruited, including 313 cases of ulcerative colitis (UC) and 573 cases of Crohn's disease (CD). The findings showed PM2.5, O3, and CO exposure significantly increased the risk of IBD. Mean concentrations of PM2.5, O3, and CO in Hefei were 43.85ug/m3, 100.78ug/m3, and 0.76 mg/m3, respectively. Each increase of 10 mg/m3 in PM2.5/O3 and 0.1 mg/m3 in CO increased the risk of IBD. The strongest effects of these three pollutants on IBD were observed in lag2-lag3 (RR = 1.037, 95% CI: 1.005-1.070%), lag3 (RR = 1.020, 95% CI: 1.002-1.038%), and lag2 (RR = 1.036, 95% CI: 1.003-1.071%), respectively. In warm seasons, PM2.5, O3, and CO had a stronger effect increased the risk of IBD, which were observed in lag2 (RR = 1.104, 95% CI: 1.032-1.181%), lag2 and lag5 (RR = 1.023, 95% CI: 1.002-1.044%; RR = 1.036, 95% CI: 1.004-1.069%), and lag2 (RR = 1.071, 95% CI: 1.012-1.133%), respectively. Air pollutant (PM2.5, O3, and CO) exposure could increase the risk of IBD, while the most susceptibility seasons for the exposure were mainly in warm seasons. The results of this study suggest that air pollutants increase the risk of IBD patients in Hefei, China, providing a basis for developing countries to improve effective prevention of IBD, and a potential opportunity to avoid part of the risk of the onset or recurrence of IBD. This study contributes to the knowledge of the association between air pollution and IBD, but the associations need to be verified by further studies.

4.
Oxid Med Cell Longev ; 2021: 6249509, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552686

RESUMO

Objective: To investigate the association between early perihematomal edema (PHE) expansion and functional outcome in patients with intracerebral hemorrhage (ICH). Methods: Patients with ICH who underwent initial computed tomography (CT) scans within 6 hours after the onset of symptoms and follow-up CT scans within 24 ± 12 hours were included. Absolute PHE increase was defined as the absolute increase in PHE volume from baseline to 24 hours. A receiver-operating characteristic (ROC) curve was generated to determine the cutoff value for early PHE expansion, which was operationally defined as an absolute increase in PHE volume of >6 mL. The outcome of interest was 3-month poor outcome defined as modified Rankin scale score of ≥4. A multivariable logistic regression procedure was used to assess the association between early PHE expansion and outcome after ICH. Results: In 233 patients with ICH, 89 (38.2%) patients had poor outcome at 3-month follow-up. Early PHE expansion was observed in 56 of 233 (24.0%) patients. Patients with early PHE expansion were more likely to have poor functional outcome than those without (43.8% vs. 11.8%, p < 0.001). After adjusting for age, admission systolic blood pressure, admission Glasgow Coma Scale score, baseline ICH volume and the presence of intraventricular hemorrhage, and time from onset to CT, early PHE expansion was associated with poor outcome (adjusted odds ratio, 4.25; 95% confidence interval, 1.70-10.60; p = 0.002). Conclusions: The early PHE expansion was not uncommon in patients with ICH and was correlated with poor outcome following ICH.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34590234

RESUMO

Ambient fine particulate matter (PM2.5) is one of the main environmental air pollutants that is closely related to the development of lung cancer, but the mechanisms are unclear. In this study, A549 cells were exposed to ambient PM2.5 to investigate the alterations of biological behaviors, and the possible role of miR-582-3p in the effects was further explored. The findings showed that PM2.5 exposure could significantly enhance the biological behaviors of A549 cells, and promote their epithelial-mesenchymal transition (EMT) transformation, especially at relatively low doses. Over-activation of Wnt/ß-catenin signaling pathway and increased expression of miR-582-3p were also found in A549 cells after PM2.5 exposure. After the knockdown of miR-582-3p in A549 cells, the effects of PM2.5 on malignant biological behavior changes, EMT, and the activation of Wnt/ß-catenin signaling pathway were all significantly alleviated. Furthermore, the inhibition of Wnt/ß-catenin signaling pathway also inhibited the EMT process of A549 cells, which was rescued by the overexpression of miR-582-3p. Therefore, this study showed that ambient PM2.5 can upregulate the expression of miR-582-3p, consequently activate the Wnt/ß-catenin signaling pathway, and thereby enhance EMT transformation and promote the malignant biological behaviors of A549 cells. These findings provide evidence for further research into the mechanisms by which exposure to PM2.5 in the environment promotes lung cancer.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34417698

RESUMO

Effects of prenatal ambient air pollution exposure could increase the risk of adverse pregnancy outcomes, which have been well documented by various studies. However, only very few studies investigated the effects on macrosomia. This study investigated the effects of prenatal air pollution exposure on the risk of macrosomia in a coastal city of China. Data of birth outcomes and air pollution in a coastal city in China between November 1, 2013, and December 31, 2017, were collected. Finally, 58,713 eligible births, including 8159 (13.9%) macrosomia and 50554 (86.1%) normal birth weight (NBW) infants, were included in the analysis. Logistic regression analyses were used to evaluate the effects of prenatal air pollution exposure on macrosomia. In the single-pollutant models, each 10 µg/m3 increase of PM2.5, PM10, and SO2 exposures, during the entire pregnancy or three trimesters, were related to elevated risk of macrosomia (adjusted RR, 95% CI) ranging from 1.018 (1.001, 1.035) to 1.314 (1.188, 1.454). In addition, O3 exposure in the first trimester (adjusted RR =1.034, 95% CI 1.009, 1.059) also increased the macrosomia risk. Prenatal PM2.5, PM10, and SO2 exposure could significantly increase the risk of macrosomia. These findings need to be further verified in more studies with multiple coastal cities included.

8.
J Pharm Biomed Anal ; 204: 114272, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34358813

RESUMO

Increased turnover of extracellular matrix proteins is seen in many different diseases and is an underlying and driving feature of pathogenesis. An increased ratio of formation over degradation of extracellular matrix proteins, such as collagens, leads to accumulation of proteins in the tissues, ultimately impairing organ function. Understanding how this balance is regulated is key to providing deeper insight into high extracellular matrix turnover diseases. Type XXVIII collagen is a novel collagen with limited information available in relation to expression, tissue prevalence and clinical implication. We generated a novel, technically robust ELISA to measure a C-terminal fragment of type XXVIII collagen in plasma and serum (PRO-C28). PRO-C28 was found to be significantly elevated in circulation in patients with heart failure with preserved ejection fraction (HFpEF) and in patients with lung cancer. Additionally, PRO-C28 correlated significantly to NT-proBNP levels in HFpEF patients. PRO-C28 levels were elevated in diseases characterized by high ECM-turnover. This suggests that type XXVIII collagen may play a role in fibroproliferative disorders in the heart and the lungs.


Assuntos
Insuficiência Cardíaca , Neoplasias , Biomarcadores , Insuficiência Cardíaca/diagnóstico , Humanos , Fragmentos de Peptídeos , Volume Sistólico
9.
Angew Chem Int Ed Engl ; 60(42): 22990-22995, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34414652

RESUMO

High-energy-density lithium (Li) metal batteries suffer from a short lifespan owing to apparently ceaseless inactive Li accumulation, which is accompanied by the consumption of electrolyte and active Li reservoir, seriously deteriorating the cyclability of batteries. Herein, a triiodide/iodide (I3 - /I- ) redox couple initiated by stannic iodide (SnI4 ) is demonstrated to reclaim inactive Li. The reduction of I3 - converts inactive Li into soluble LiI, which then diffuses to the cathode side. The oxidation of LiI by the delithiated cathode transforms cathode into the lithiation state and regenerates I3 - , reclaiming Li ion from inactive Li. The regenerated I3 - engages the further redox reactions. Furthermore, the formation of Sn mitigates the corrosion of I3 - on active Li reservoir sacrificially. In working Li | LiNi0.5 Co0.2 Mn0.3 O2 batteries, the accumulated inactive Li is significantly reclaimed by the reversible I3 - /I- redox couple, improving the lifespan of batteries by twice. This work initiates a creative solution to reclaim inactive Li for prolonging the lifespan of practical Li metal batteries.

10.
JMIR Mhealth Uhealth ; 9(8): e24555, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398796

RESUMO

BACKGROUND: Self-management of ambulatory cancer pain is full of challenges. Motivated by the need for better pain management, we developed a WeChat-supported platform, Medication Housekeeper (MediHK), to enhance communication, optimize outcomes, and promote self-management in the home setting. OBJECTIVE: We conducted a randomized controlled trial to assess whether the joint physician-pharmacist team through MediHK would provide better self-management of ambulatory patients with cancer pain. METHODS: Patients were randomly assigned to either an intervention group or control group. During the 4-week study period, the pharmacist would send 24-hour pain diaries daily, adverse drug reaction (ADR) forms every 3 days, and the Brief Pain Inventory form every 15 days to patients in the intervention group via MediHK. If a patient needed a change in drug/dosage or treatment of an ADR after the comprehensive review, the pharmacist would propose pharmacological interventions to the attending physician, who was then responsible for prescribing or adjusting pain medications. If no adjustments were needed, the pharmacist provided appropriate targeted education based on knowledge deficits. Patients in the control group received conventional care and did not receive reminders to fill out the forms. However, if the control group patients filled out a form via MediHK, the pain management team would review and respond in the same way as for the intervention group. The primary outcomes included pain intensity and pain interference in daily life. Secondary outcomes included patient-reported outcome measures, medication adherence, ADRs, and rehospitalization rates. RESULTS: A total of 100 patients were included, with 51 (51%) in the intervention group and 49 (49%) in the control group. The worst pain scores, least pain scores, and average pain scores in the intervention group and the control group were statistically different, with median values of 4 (IQR 3-7) vs 7 (IQR 6-8; P=.001), 1 (IQR 0-2) vs 2 (IQR 1-3; P=.02), and 2 (IQR 2-4) vs 4 (IQR 3-5; P=.001), respectively, at the end of the study. The pain interference on patients' general activity, mood, relationships with others, and interests was reduced, but the difference was not statistically significant compared with the control group (Ps=.10-.76). The medication adherence rate increased from 43% to 63% in the intervention group, compared with an increase of 33% to 51% in the control group (P<.001). The overall number of ADRs increased at 4 weeks, and more ADRs were monitored in the intervention group (P=.003). Rehospitalization rates were similar between the 2 groups. CONCLUSIONS: The joint physician-pharmacist team operating through MediHK improved pain management. This study supports the feasibility of integrating the internet into the self-management of cancer pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900023075; https://www.chictr.org.cn/showproj.aspx?proj=36901.

11.
Fish Physiol Biochem ; 47(5): 1597-1610, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34417918

RESUMO

Foxo1, a member of Foxo transcription factor family, is involved in a number of physiological processes including metabolism, cell cycle progression, aging, and apoptosis. In the ovarian granulosa cell of mouse, Foxo1 is implicated to inhibit the expression of Cyp19a1, a gene encoding the aromatase that converts androgens into estrogens. Currently, the information about the expression and physiological relevance of Foxo1 homologues in the ovary of teleosts is scarce. In the present study, cDNAs encoding two forms of Foxo1, Foxo1a and Foxo1b, were isolated from the orange-spotted grouper. Phylogenetic analysis indicated that the orange-spotted groupers Foxo1a and Foxo1b were closely related to the counterparts of the ricefield eel. RT-PCR analysis showed that the orange-spotted groupers foxo1a and foxo1b were expressed in a wide range of tissues, with high levels detected in the brain regions, liver, and intestine. Quantitative real-time PCR analysis showed similar expression profiles for cyp19a1a, foxo1a, and foxo1b in the ovary during development from the primary growth to mature stages, with peak values detected at the vitellogenic stage. In situ hybridization detected mRNA of foxo1a, foxo1b, and cyp19a1a in granulosa cells surrounding vitellogenic oocytes. In vitro transfection showed that both Foxo1a and Foxo1b upregulated the orange-spotted grouper cyp19a1a promoter activities, possibly through the conserved Foxo binding site. Collectively, these results suggest that both Foxo1a and Foxo1b may be involved in the regulation of the ovarian functions in the orange-spotted grouper and the physiological roles of Foxo1 homologues in the ovary may be diversified in vertebrates.

12.
Environ Res ; 202: 111654, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34252430

RESUMO

Preterm birth (PTB), a major public health impact, has been shown to be associated with prenatal air pollution exposure, but the results are still inconsistent. This meta-analysis was performed to quantitatively evaluate the correlation between maternal air pollutant exposure and PTB, and provide evidence of higher grade to help improving the pregnancy outcomes. Databases including Web of Science and PubMed were searched to retrieve eligible studies published up to October 2020. The quality of the articles was assessed by the Newcastle-Ottawa Quality Score (NOS), after which the pooled estimate of the effect was calculated. The robustness of the joint estimates was confirmed by sensitivity analysis of excluded studies one by one, and the sources of heterogeneity were discussed by stratification analysis. Egger's and Begg's tests were performed to examine publication bias. Sixty studies that met the eligible criteria were finally included in this study. The findings showed combined relative risks of 1.032-1.070 for PTB, 0.859-1.081 for moderate PTB, 1.119-1.194 for very PTB and 1.128-1.259 for extremely PTB when mothers were exposed to PM2.5, PM10, NO2, O3, SO2, CO and NOx during pregnancy, while the sensitive windows varied for different air pollutants. Notably, PM2.5 exposure in only the 2nd trimester, NO2 exposure in only the 3rd trimester, and O3 exposure in all three trimesters were positively associated with PTB, while NO2 exposure in the 1st trimester was negatively associated with PTB. In addition, exposure of PM2.5 and PM10 in the 2nd trimester was positively associated with moderate PTB, and in the 1st and 2nd trimesters were positively associated with very PTB. These findings demonstrated that PM2.5, PM10, O3, NO2 were associated with PTB (including moderate PTB, very PTB, and/or extremely PTB), while NOx was not, and the relationship between CO and SO2 and PTB was not stable.

13.
Environ Res ; 202: 111743, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34331927

RESUMO

BACKGROUND: Exposure to air pollutants is associated with adverse pregnancy outcomes. But evidence on the effects of preconceptional air pollution exposure on the risk of termination of pregnancy (TOP) caused by pregnancy losses and congenital malformations is lacking. METHODS: The distributed lag nonlinear model (DLNM) was used to evaluate the impact of short-term air pollutants exposure on the risk of TOP. Stratified analyses by age (<35 years old, ≥ 35 years old) and season (warm season, cold season) were further conducted. Relative risk (RR) and 95 % confidential interval (95 % CI) were calculated for per interquartile range (IQR) increment in air pollutants during the study period. RESULTS: PM2.5, PM10, and O3 exposure were significantly associated with elevated risk of TOP. The risk of TOP was associated with PM2.5 exposure from lag11 to lag15 in the single-pollutant model, and the strongest association was observed at lag13 (RR = 1.021, 95%CI:1.002-1.040). PM10 exposure from lag10 to lag15 was associated with increased TOP risk, with the corresponding peak association being at lag13 (RR = 1.020, 95%CI: 1.004-1.037). For O3, the single-day lag association appeared to be statistically significant from lag26 to lag27, with the highest RR of TOP cases being at lag27 (RR = 1.044, 95%CI: 1.005-1.084). Similar results were observed for pregnancy losses (PL). However, no significantly association between air pollution exposure and the risk of congenital malformations (CM) was found in this study. Stratified analyses showed that pregnant women with more advanced ages were more susceptible to PM2.5, PM10, and O3 exposure. The effect of PM2.5 exposure was statistically significant in cold season subgroups. CONCLUSION: The findings suggest that exposure to PM2.5, PM10, and O3 before pregnancy are associated with the risk of TOP in Lu'an, China, reflecting the significance of preconceptional environmental exposure in the development of adverse pregnancy outcomes.

14.
BMC Pulm Med ; 21(1): 229, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256754

RESUMO

BACKGROUND: Ferroptosis is a newly discovered form of cell death characterized by iron-dependent lipid peroxidation. This study aims to investigate the potential correlation between ferroptosis and the prognosis of lung adenocarcinoma (LUAD). METHODS: RNA-seq data were collected from the LUAD dataset of The Cancer Genome Atlas (TCGA) database. Based on ferroptosis-related genes, differentially expressed genes (DEGs) between LUAD and paracancerous specimens were identified. The univariate Cox regression analysis was performed to screen key genes associated with the prognosis of LUAD. LUAD patients were divided into the training set and validation set. Then, we screened out key genes and built a prognostic prediction model involving 5 genes using the least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation and the multivariate Cox regression analysis. After dividing LUAD patients based on the median level of risk score as cut-off value, the generated prognostic prediction model was validated in the validation set. Moreover, we analyzed the somatic mutations, and estimated the scores of immune infiltration in the high-risk and low-risk groups. Functional enrichment analysis of DEGs was performed as well. RESULTS: High-risk scores indicated the worse prognosis of LUAD. The maximum area under curve (AUC) of the training set and the validation set in this study was 0.7 and 0.69, respectively. Moreover, we integrated the age, gender, and tumor stage to construct the composite nomogram. The charts indicated that the AUC of LUAD cases with the survival time of 1, 3 and 5 years was 0.698, 0.71 and 0.73, respectively. In addition, the mutation frequency of LUAD patients in the high-risk group was significantly higher than that in the low-risk group. Simultaneously, DEGs were mainly enriched in ferroptosis-related pathways by analyzing the functional results. CONCLUSIONS: This study constructs a novel LUAD prognosis prediction model involving 5 ferroptosis-related genes, which can be used as a promising tool for decision-making of clinical therapeutic strategies of LUAD.

15.
Br J Cancer ; 125(6): 865-876, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34274945

RESUMO

BACKGROUND: Many molecular alterations are shared by embryonic liver development and hepatocellular carcinoma (HCC). Identifying the common molecular events would provide a novel prognostic biomarker and therapeutic target for HCC. METHODS: Expression levels and clinical relevancies of SLC38A4 and HMGCS2 were investigated by qRT-PCR, western blot, TCGA and GEO datasets. The biological roles of SLC38A4 were investigated by functional assays. The downstream signalling pathway of SLC38A4 was investigated by qRT-PCR, western blot, immunofluorescence, luciferase reporter assay, TCGA and GEO datasets. RESULTS: SLC38A4 silencing was identified as an oncofetal molecular event. DNA hypermethylation contributed to the downregulations of Slc38a4/SLC38A4 in the foetal liver and HCC. Low expression of SLC38A4 was associated with poor prognosis of HCC patients. Functional assays demonstrated that SLC38A4 depletion promoted HCC cellular proliferation, stemness and migration, and inhibited HCC cellular apoptosis in vitro, and further repressed HCC tumorigenesis in vivo. HMGCS2 was identified as a critical downstream target of SLC38A4. SLC38A4 increased HMGCS2 expression via upregulating AXIN1 and repressing Wnt/ß-catenin/MYC axis. Functional rescue assays showed that HMGCS2 overexpression reversed the oncogenic roles of SLC38A4 depletion in HCC. CONCLUSIONS: SLC38A4 downregulation was identified as a novel oncofetal event, and SLC38A4 was identified as a novel tumour suppressor in HCC.

16.
Cell Death Dis ; 12(6): 594, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103476

RESUMO

Aging is one of the most prominent risk factors for heart failure. Myeloid-derived suppressor cells (MDSCs) accumulate in aged tissue and have been confirmed to be associated with various aging-related diseases. However, the role of MDSCs in the aging heart remains unknown. Through RNA-seq and biochemical approaches, we found that granulocytic MDSCs (G-MDSCs) accumulated significantly in the aging heart compared with monocytic MDSCs (M-MDSCs). Therefore, we explored the effects of G-MDSCs on the aging heart. We found that the adoptive transfer of G-MDSCs of aging mice to young hearts resulted in cardiac diastolic dysfunction by inducing cardiac fibrosis, similar to that in aging hearts. S100A8/A9 derived from G-MDSCs induced inflammatory phenotypes and increased the osteopontin (OPN) level in fibroblasts. The upregulation of fibroblast growth factor 2 (FGF2) expression in fibroblasts mediated by G-MDSCs promoted antisenescence and antiapoptotic phenotypes of fibroblasts. SOX9 is the downstream gene of FGF2 and is required for FGF2-mediated and G-MDSC-mediated profibrotic effects. Interestingly, both FGF2 levels and SOX9 levels were upregulated in fibroblasts but not in G-MDSCs and were independent of S100A8/9. Therefore, a novel FGF2-SOX9 signaling axis that regulates fibroblast self-renewal and antiapoptotic phenotypes was identified. Our study revealed the mechanism by which G-MDSCs promote cardiac fibrosis via the secretion of S100A8/A9 and the regulation of FGF2-SOX9 signaling in fibroblasts during aging.

17.
Medicine (Baltimore) ; 100(25): e26396, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160422

RESUMO

BACKGROUND: Cardiovascular diseases have become a prominent threat to public health and quality of life. In recent years, some studies have reported that ivabradine can improve the cardiac function and prognosis of patients with acute myocardial infarction (AMI). Therefore, we perform a protocol for systematic review and meta-analysis to evaluate the efficacy of ivabradine for treating AMI. METHODS: This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols. We will search PubMed, Cochrane Library, Embase, Web of Science, and Medline databases for relevant studies. In addition, we will also collect 4 databases of China: China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database. Risk of bias will be assessed using the Cochrane Handbook risk of bias assessment tool version (V.5.1.0). We will use STATA 16.0 software (Stata Corporation, College Station, TX) to perform data analysis. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: We hypothesized that ivabradine can reduce the resting heart rate and improve heart function in patients with AMI.


Assuntos
Ivabradina/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Metanálise como Assunto , Infarto do Miocárdio/fisiopatologia , Descanso/fisiologia , Volume Sistólico/efeitos dos fármacos , Revisões Sistemáticas como Assunto , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
18.
Blood ; 138(14): 1211-1224, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34115843

RESUMO

Megakaryocytes (MKs), the platelet progenitor cells, play important roles in hematopoietic stem cell (HSC) maintenance and immunity. However, it is not known whether these diverse programs are executed by a single population or by distinct subsets of cells. Here, we manually isolated primary CD41+ MKs from the bone marrow (BM) of mice and human donors based on ploidy (2N-32N) and performed single-cell RNA sequencing analysis. We found that cellular heterogeneity existed within 3 distinct subpopulations that possess gene signatures related to platelet generation, HSC niche interaction, and inflammatory responses. In situ immunostaining of mouse BM demonstrated that platelet generation and the HSC niche-related MKs were in close physical proximity to blood vessels and HSCs, respectively. Proplatelets, which could give rise to platelets under blood shear forces, were predominantly formed on a platelet generation subset. Remarkably, the inflammatory responses subpopulation, consisting generally of low-ploidy LSP1+ and CD53+ MKs (≤8N), represented ∼5% of total MKs in the BM. These MKs could specifically respond to pathogenic infections in mice. Rapid expansion of this population was accompanied by strong upregulation of a preexisting PU.1- and IRF-8-associated monocytic-like transcriptional program involved in pathogen recognition and clearance as well as antigen presentation. Consistently, isolated primary CD53+ cells were capable of engulfing and digesting bacteria and stimulating T cells in vitro. Together, our findings uncover new molecular, spatial, and functional heterogeneity within MKs in vivo and demonstrate the existence of a specialized MK subpopulation that may act as a new type of immune cell.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34092592

RESUMO

BACKGROUND: Most studies use platelet-rich plasma (PRP) requiring multiple intraarticular injections for knee osteoarthritis (OA). OBJECTIVE: To investigate the efficacy of a single intraarticular PRP injection for patients with early knee OA and consider subgroup analyses of radiographic severity and age, respectively. METHODS: Forty-one patients with knee OA (Kellgren-Lawrence grade 1-2) received a single PRP injection into the target knee and were assessed at baseline and 1, 3, and 6 months postinjection. The primary outcome was the mean change from baseline in the visual analog scale (VAS) pain (0-100 mm) at 6 months postinjection. Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lequesne index, single leg stance test (SLS), use of rescue analgesics and patients' satisfaction. RESULTS: Thirty-eight patients completed the study. The mean pain VAS decreased significantly from 45.6 ± 13.0 mm at baseline to 16.9 ± 13.4 mm, 14.0 ± 13.1 mm and 15.5 ± 14.0 mm at 1, 3 and 6-month follow-ups (p< 0.001 for all). Significant improvements in WOMAC, Lequesne index, SLS and consumption of analgesics from baseline (p< 0.001 for all) were noted at each follow-up. Patients' satisfaction was high. No serious adverse events occurred. Subgroup analyses revealed that patients with grade 1 OA showed significantly greater VAS pain reduction at 3 months (p= 0.006) and 6 months (p= 0.005) than patients with grade 2 OA. The older-age group (age > 60) showed significantly greater improvements in VAS pain, WOMAC function subscale scores and total scores at 6-month postinjection, compared with the younger age-group (age ≤ 60). The younger-age group reported better satisfaction at 1 and 3-month postinjection. CONCLUSIONS: One injection of PRP improved pain and function for 6 months for patients with early knee OA. This study supports putting the one-injection regimen into clinical practice. Further research is needed for more definite conclusions.

20.
Cardiovasc Res ; 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34100920

RESUMO

AIMS: The goal of our study was to investigate the heterogeneity of cardiac macrophages (CMφs) in mice with transverse aortic constriction (TAC) via single-cell sequencing and identify a subset of macrophages associated with heart injury. METHODS AND RESULTS: We selected all CMφs from CD45+ cells using single-cell mRNA sequencing data. Through dimension reduction, clustering and enrichment analyses, CD72hi CMφs were identified as a subset of proinflammatory macrophages. The pseudotime trajectory and ChIP-Seq analyses identified Rel as the key transcription factor that induces CD72hi CMφ differentiation. Rel KD and Rel-/- bone marrow chimera mice subjected to TAC showed features of mitigated cardiac injury, including decreased levels of cytokines and ROS, which prohibited cardiomyocyte death. The transfer of adoptive Rel-overexpressing monocytes and CD72hi CMφ injection directly aggravated heart injury in the TAC model. The CD72hi macrophages also exerted proinflammatory and cardiac injury effects associated with myocardial infarction (MI). In humans, patients with heart failure exhibit increased CD72hi CMφ levels following dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM). CONCLUSION: Bone marrow-derived, Rel-mediated CD72hi macrophages play a proinflammatory role, induce cardiac injury and, thus, may serve as a therapeutic target for multiple cardiovascular diseases. TRANSLATIONAL PERSPECTIVE: Heart failure (HF) imposes an enormous clinical and economic burden worldwide and presents limited therapeutic approaches. Given the close association between inflammation and adverse outcomes, proinflammatory immune cells are considered potential therapeutic targets for HF treatment. The present studies identified a specific macrophage subset associated with myocardial injury, which may provide an alternative approach for treating cardiovascular diseases.

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