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1.
Analyst ; 146(9): 3041-3051, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33949412

RESUMO

As an enzyme-free isothermal amplification strategy, catalytic hairpin assembly (CHA) is a very promising method for cell imaging. However, the practical application of CHA on intracellular miRNA imaging is limited by slow kinetics, insufficient amplification efficiency and strong interference in living cells. Herein, a localized catalytic hairpin assembly-based DNA nanomachine (LCHA nanomachine) was developed for the rapid, efficient and reliable fluorescence resonance energy transformation (FRET) imaging of miRNA-21 in living cells. The nanomachine was simply constructed by a one-step self-assembly process of a stator strand, a pair of hairpin probes from CHA and an AS1411 aptamer. Benefiting from the spatial-confinement effect, a pair of hairpin probes with high collision frequency was rapidly and efficiently assembled using miRNA-21 as the catalyst on a stator strand in every nanomachine. Compared with the free-CHA nanomachine, the LCHA nanomachine shortened the reaction time by 4.5-fold for reaching a plateau and significant improved the sensitivity by 7.6-fold for miRNA-21 detection in vitro. Importantly, the nanomachine was successfully applied for miRNA-21 imaging in living cells. With the assistance of an AS1411 aptamer and stator strand, the pair of hairpin probes with the ratio of 1 : 1 synchronously transported into a co-site of the cytoplasm, which ensures efficient imaging of trace miRNA-21. The signal output of the ratio of 6-carboxy-fluorescein (FAM) to tetramethyl rhodamine (TAMRA) intensities guaranteed reliability through avoiding the interference from different amounts of the nanomachine that enters into cells. Notably, the nanomachine can distinguish the miRNA-21 expression level in different kinds of cancer cells. By virtue of the advantages of simplicity, efficiency and reliability, the proposed strategy provides a powerful method for exploring the functions of miRNA and diagnosis of disease.

4.
J Mater Sci Mater Med ; 32(5): 52, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900464

RESUMO

This study is aimed at comparing and evaluating the biocompatibility and antibacterial activities of mineral trioxide aggregate (MTA) and iRoot BP Plus as novel retro-filling materials. Discs of both materials were prepared and incubated for 72 h to obtain material extracts in medium. Flow cytometry and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were used to assess the rate of apoptosis and proliferation of human periodontal ligament stem cells (hPDLSCs) when exposed to eluates of both materials. The expression levels of alkaline phosphatase, collagen type I, osteocalcin, Runt-related transcription factor-2, and Osterix were tested for evaluating the osteogenic differentiation of hPDLSCs. The antibacterial activities of both materials were compared by the direct contact test. The hPDLSCs stimulated by MTA or iRoot BP Plus eluates showed significantly higher cell viability than that of the control group with no eluates. No significant differences were observed among the percentages of necrotic and apoptotic cells stimulated by MTA and iRoot BP Plus eluates and the control group. The expression of all osteogenic differentiation markers of hPDLSCs in both experimental groups were significantly higher than those of the control group, while the increment values in MTA group were significantly higher than those of the iRoot BP Plus group. The antibacterial activity against Enterococcus faecalis showed no significant difference between MTA and iRoot BP Plus. Therefore, both materials may be suitable for retro-filling applications.

5.
Hum Genomics ; 15(1): 24, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892795

RESUMO

OBJECTIVE: The occurrence of osteoarthritis is related to genetic and environmental factors. Among them, the change of chondrocyte gene expression pattern regulated by epigenetic modification is an important participant. This study analyzed the effect of CAMP gene methylation on the level of oxidative stress and inflammation of chondrocytes. METHODS: We analyzed the changes of the transcriptome in the articular cartilage tissue of osteoarthritis (OA) patients from the GSE117999 dataset. The GSE48422 dataset was used to analyze the changes in the methylation level of osteoarthritis cells. Cell Counting Kit-8 (CCK-8) and flow cytometry analysis of short hairpin RNA (shRNA) silencing CAMP gene and 5-µM 5-Aza-2'-Deoxycytidine (AZA) treatment on the proliferation and apoptosis of Human chondrocytes osteoarthritis (HC-OA) cells. The Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was used to detect the level of reactive oxygen species (ROS), and the expression level of inflammatory factors was analyzed by Western Blot. RESULTS: The expression of CAMP in cartilage tissue of OA patients was upregulated, and the level of methylation was downregulated. CAMP was highly expressed in osteoarthritis articular cartilage cells. Silencing CAMP inhibited the proliferation of HC-OA cells and promoted their apoptosis. CAMP gene methylation inhibited ROS levels and tumor necrosis factor-α (TNF-α) expression levels in HC-OA cells, and promoted transforming growth factor beta (TGF-ß) expression. CAMP gene methylation inhibited the proliferation of HC-OA cells and promoted their apoptosis. CONCLUSION: CAMP gene promoter methylation inhibits ROS levels and inflammation and induces chondrocyte apoptosis.

6.
Water Res ; 198: 117145, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33905974

RESUMO

Phytoremediation has been proven to be an alternative in-situ treatment technique for sulfonamide polluted wastewater. However, the fate of sulfonamides in the phytoremediation process of multiple sulfonamides coexistence is unclear. Therefore, the possibility and mechanism of phytoremediation of ten sulfonamides by different wetland plants through hydroponics were investigated in this study. The phytoremediation rates of Σsulfonamides by different wetland plants were from 44.5% to 56.9%. Mass balance analysis showed that rhizosphere biodegradation (90.2% - 92.2%) dominated the phytoremediation of Σsulfonamides, while hydrolysis (7.63% - 8.95%) and plant uptake (0.05% - 0.17%) accounted for a small proportion. It is worth mentioning that the dissipation of the target sulfonamides in the hydroponic system followed the first-order reaction kinetic model, with half-lives of 13.3 d to 53.3 d, which are close to or even lower than that of aerobic biodegradation in river water, sediment, and piggery wastewater. Six of the ten spiked sulfonamides were detected in plant samples demonstrated that the selective uptake of plants under the coexistence of multiple sulfonamides. The distribution of sulfonamides (concentrations and uptake amounts) in plant tissues followed the sequence of root > stem > leaf in this study, but the distribution in stems and leaves needs further study. The uptake and rhizosphere biodegradation of Cyperus papyrus to sulfonamides are optimally resulting that its phytoremediation rate is significantly higher than other plants (p < 0.05), which indicates that plant species is one of the key factors affecting the phytoremediation efficiency of sulfonamides. These findings verify the feasibility of phytoremediation of sulfonamides, and provide new insights into the fate of sulfonamides in the process of phytoremediation.

7.
PLoS Biol ; 19(3): e3001096, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33705388

RESUMO

The regulation of protein synthesis is essential for maintaining cellular homeostasis, especially during stress responses, and its dysregulation could underlie the development of human diseases. The critical step during translation regulation is the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α). Here we report the identification of a direct kinase of eIF2α, microtubule affinity-regulating kinase 2 (MARK2), which phosphorylates eIF2α in response to proteotoxic stress. The activity of MARK2 was confirmed in the cells lacking the 4 previously known eIF2α kinases. MARK2 itself was found to be a substrate of protein kinase C delta (PKCδ), which serves as a sensor for protein misfolding stress through a dynamic interaction with heat shock protein 90 (HSP90). Both MARK2 and PKCδ are activated via phosphorylation in proteotoxicity-associated neurodegenerative mouse models and in human patients with amyotrophic lateral sclerosis (ALS). These results reveal a PKCδ-MARK2-eIF2α cascade that may play a critical role in cellular proteotoxic stress responses and human diseases.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33690794

RESUMO

OBJECTIVE: Facial masks are an essential personal protective measure to fight the COVID-19 pandemic. However, the mask adoption rate in the US is still less than optimal. This study aims to understand the beliefs held by individuals who oppose the use of facial masks, and the evidence that they use to support these beliefs, to inform the development of targeted public health communication strategies. MATERIALS AND METHODS: We analyzed a total of 771,268 US-based tweets between January to October 2020. We developed machine-learning classifiers to identify and categorize relevant tweets, followed by a qualitative content analysis of a subset of the tweets to understand the rationale of those opposed mask wearing. RESULTS: We identified 267,152 tweets that contained personal opinions about wearing facial masks to prevent the spread of COVID-19. While the majority of the tweets supported mask wearing, the proportion of anti-mask tweets stayed constant at about 10% level throughout the study period. Common reasons for opposition included physical discomfort and negative effects, lack of effectiveness, and being unnecessary or inappropriate for certain people or under certain circumstances. The opposing tweets were significantly less likely to cite external sources of information such as public health agencies' websites to support the arguments. DISCUSSION AND CONCLUSION: Combining machine learning and qualitative content analysis is an effective strategy for identifying public attitudes toward mask wearing and the reasons for opposition. The results may inform better communication strategies to improve the public perception of wearing masks and, in particular, to specifically address common anti-mask beliefs.

9.
Zhongguo Zhen Jiu ; 41(1): 99-102, 2021 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-33559452

RESUMO

To explore the implementation path of the ideological and political education according to the characteristics of teaching sections in acupuncture-moxibustion courses. Excavating the traditional Chinese culture and medical ethics contained in acupuncture-moxibustion courses helps strengthening the ideological and political quality of medical students and noble medical ethics, strengthening self-confidence in both professions and culture, and also helps students establishing a correct outlook on life, world and value. The moral education integrated with the professional teaching will helps explore ideological and political education path in acupuncture-moxibustion courses, so as to solidify them into each teaching sections and improve the teaching effect.


Assuntos
Terapia por Acupuntura , Acupuntura , Moxibustão , Humanos , Estudantes
10.
Ann Palliat Med ; 10(1): 810-817, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545803

RESUMO

Pseudomonas aeruginosa (PA) is a common gram-negative bacterium. Imipenem (IMP) is considered to be the most effective clinical drug for the treatment of PA infection. IMP-resistant ceftazidime-susceptible PA is relatively rare in clinical practice; so far, there have been no clinical reports regarding the treatment of IMP-resistant PA with piperacillin/tazobactam alone. This paper will report the case of a severe pneumonia patient with IMP-resistant ceftazidime-susceptible PA infection that was successfully treated with piperacillin/tazobactam monotherapy after initial therapy with biapenem (BIP) according to the drug sensitivity test. The patient was a 75-year-old female, her main symptom was drowsiness. She was admitted to hospital due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and pulmonary encephalopathy. After admission, endotracheal intubation was performed immediately, and the lavage fluid was sent to the laboratory for sputum culturing for several times. BIP was selected for the initial anti-infection regimen, and other symptomatic treatments were performed at the same time. On the day 8, the sputum culture drug sensitivity test results showed PA (sensitive to: piperacillin/tazobactam sodium, ceftazidime, aminoglycoside, and fluoroquinolones; resistant to IMP; and intermediate sensitivity to: cefoperazone-sulbactam and meropenem), so we adjusted the anti-infection regimen as piperacillin/tazobactam sodium. After that, the infection index of the patient declined steadily, and the patient was discharged from hospital after continuous treatment with piperacillin tazobactam until the 24th day. For severe pneumonia patients with IMP-resistant ceftazidime-susceptible PA infection, piperacillin/tazobactam is still an option specially when the MIC of piperacillin/tazobactam is very low.

11.
Neurosci Lett ; 747: 135679, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33524475

RESUMO

Vestibular hair cells (HCs) are mechanoreceptors for the detection of head movement. Vestibular HCs of adult mammals never completely regenerate after damage, resulting in vestibular dysfunction. Overexpression of Atoh1 is effective for inducing HC regeneration. However, method of clinical feasibility and improvement of regenerative extent are both in need. Here we used an adeno-associated virus (AAV) serotype 8 vector of two different titers to overexpress Atoh1 in the injured utricles of adult mice. One month after virus inoculation, abundant myosin VIIa-positive cells and immature stereocilia were observed. Quantitative analyses revealed that Atoh1 overexpression replenished vestibular HCs in a dose-dependent manner. Vectors of a higher titer increased the number of myosin VIIa-positive cells compared to those of lower titer. Moreover, only Atoh1 overexpression in the higher titer group enhanced stereocilium regeneration, which is an important step in the maturation of regenerated HCs. Although the current treatment failed to initiate functional recovery of the animals, our results prompt further improvements in the recovery of vestibular dysfunction by AAV.

12.
Water Res ; 193: 116870, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33545438

RESUMO

Research on decentralized wastewaters deserves special focus due to the potential abundance of emerging organic pollutants including pharmaceutical and personal care products (PPCPs), which might pose serious threats to the local water bodies and even to human health. Constructed wetland (CW) is a common decentralized wastewater treatment technology, with a certain ability to eliminate PPCPs. Nonetheless, PPCPs removal in common CWs is frequently challenging, besides, the removal mechanism remains elusive. Based on our previous study, tidal flow constructed wetlands (TFCWs) is effective in nitrogen removal. Here, 3 TFCWs with different modifications (baffle, plants, both baffle and plants) were constructed to treat raw domestic sewage and specifically to evaluate the removal efficiencies and mechanism of PPCPs. 24 PPCPs including 7 antibiotics, 8 steroid hormones and 9 biocides were detected in the level of 1.10 ± 0.29 ng/L-799 ± 10.6 ng/L in the influents. Consequently, we found that modification with both baffle and plants significantly influenced the removal of PPCPs. Moreover, the highest removal rates of biocides (97.1 ± 0.29%), steroid hormones (99.8 ± 0.02%), and antibiotics (90.2 ± 1.60%) were achieved via both baffles and plants in TFCWs. Based on the mass balance analysis, microbial degradation dominated the removal of PPCPs with a percentage higher than 85.7%, followed by substrate adsorption (5.22 × 10-2-14.3%) and plant uptake (1.66 × 10-3-0.44%). Further, 16S rDNA sequencing analysis revealed that the presence of baffle and plants improve the removal efficiency of PPCPs by means of enhancing microbial diversity and changing dominant microorganisms. Moreover, Thaumarchaeota was potentially the key microorganism in the phylum level for PPCPs elimination by TFCWs through LEfSe (linear discriminant analysis (LDA) effect size) analysis. These findings provide new insights into the removal of PPCPs in CWs.


Assuntos
Cosméticos , Preparações Farmacêuticas , Poluentes Químicos da Água , Humanos , Eliminação de Resíduos Líquidos , Águas Residuárias/análise , Poluentes Químicos da Água/análise , Áreas Alagadas
13.
Hepatology ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33609283

RESUMO

Myofibroblasts play a pivotal role in the development and progression of hepatocellular carcinoma (HCC). Here, we aimed to explore the role and mechanism of myofibroblast Musashi RNA binding protein 2 (MSI2) in HCC progression. Myofibroblast infiltration and collagen deposition were detected and assessed in the tissues from 117 HCC patients. Transgenic mice (Msi2ΔCol1a1 ) with floxed Msi2 allele and Col1a1-CreER were constructed to generate a myofibroblast-specific Msi2 knockout model. Mouse HCC cells were orthotopically transplanted into the Msi2ΔCol1a1 or the control mice (Msi2F/F ). We found that the deposition of collagen fibers, the main product of myofibroblasts, predicted a poor prognosis for HCC; meanwhile, we detected high MSI2 expression in the peritumoral infiltrated myofibroblasts. Conditional deletion of Msi2 in myofibroblasts significantly inhibited the growth of orthotopically implanted HCC, reduced both intrahepatic and lung metastasis, and prolonged the overall survival of tumor-bearing mice (P = 0.002). In vitro analysis demonstrated that myofibroblasts promoted cell proliferation, invasion, and epithelial-mesenchymal transformation of HCC cells, whereas Msi2 deletion in myofibroblasts reversed these effects. Mechanically, Msi2 knockout decreased myofibroblast-derived IL6 and IL11 secretion by inhibiting the ERK1/2 pathway, and thus attenuated the cancer stem cell promoting effect of myofibroblasts. Interestingly, we found that the simultaneous knockout of Msi2 in myofibroblasts and knockdown of Msi2 in HCC cells could not further attenuate the implanted HCC progression. CONCLUSION: Myofibroblast-specific Msi2 knockout abrogated the tumor-promoting function of myofibroblasts and inhibited HCC progression in mouse models. Targeting myofibroblast MSI2 expression may thus prove to be a therapeutic strategy for HCC treatment in the future.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33625562

RESUMO

PURPOSE: To investigate the relationship between leakage index on ultra-widefield fluorescence angiography (UWFFA) in different regions of retina and its correlation with cystoid macular edema (CME) in central retinal vein occlusion (CRVO) eyes. METHODS: Patients with naïve non-ischemic CRVO that had undergone UWFFA were identified. UWFFA images in the late phase were used to analyze the leakage index, which was performed by a semi-automatic method using ImageJ. The UWFFA images were subdivided into four regions by concentric circles centered on the macula for analysis. Optical coherence tomography (OCT) images were used to identify the presence of CME and obtain central macular thickness (CMT). RESULTS: A total of 57 eyes from 57 CRVO patients were analyzed in this study, including 43 eyes with CME and 14 eyes without CME. The leakage index in panretinal, peri-macular area (PMA), and near-peripheral area (NPA) was significantly different between eyes with CME and eyes without CME. Leakage index of PMA, NPA, mid-peripheral area (MPA), and panretinal area was significantly correlated with CMT, particularly the PMA. CONCLUSIONS: The distribution of leakage is different between patients with CME and patients without CME. The contribution of leakage index in different regions to CME was different, most predominant in PMA and NPA, and the closer to the center of the macula, the stronger the correlation between leakage index and CMT. A linear correlation was observed between CMT and the leakage index of panretinal area and all regions except far-peripheral area (FPA).

15.
Sci Total Environ ; 772: 145516, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33571766

RESUMO

Mining activities are known to generate a large amount of mine tailings and acid mine drainage which contain varieties of heavy metals. Heavy metals play an important role in co-selection for bacterial antibiotic resistance. However, the characteristics of antibiotic resistance genes (ARGs) in mining-affected water environments are still unclear. Here we investigated the pollution of metals, profiles of ARGs, mobile genetic elements (MGEs) and microbial community in mining-affected surface water and groundwater. The results showed that in the tested water samples, the concentrations of Zn and Mn were the highest, and Ni was the lowest. Higher abundances of ARGs with great proportion of sulfonamides, chloramphenicols and tetracyclines resistance genes were found in mining-affected water when compared with those without mining activities. Additionally, there were positive correlations between heavy metals (especially Ni, Zn and Mn) and these ARGs. Linear regression analysis suggested that MGEs were positively correlated with ARGs. In addition, total phosphorus was correlated with ARGs (p < 0.05). The microbial community was different between the mining-affected water and the reference (p < 0.05). Proteobacteria, Bacteroidetes and Actinobacteria were dominant phyla in the surface water and groundwater. Network analysis showed that many ARGs were significantly associated with these dominant bacteria, which suggested they might be potential hosts for these ARGs. These findings provide a clear evidence that the mining activities in the study area had a significant impact on surface water and groundwater to different degrees.


Assuntos
Antibacterianos , Água Subterrânea , Antibacterianos/análise , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Água
16.
Neurorehabil Neural Repair ; 35(2): 145-157, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33410385

RESUMO

Background. Little is known about the induction of functional and brain structural reorganization in hemiplegic cerebral palsy (HCP) by constraint-induced movement therapy (CIMT). Objective. We aimed to explore the specific molecular mechanism of functional and structural plasticity related to CIMT in HCP. Methods. The mice were divided into a control group and HCP groups with different interventions (unconstraint-induced movement therapy [UNCIMT], CIMT or siRNA-Nogo-A [SN] treatment): the HCP, HCP+UNCIMT, HCP+CIMT, HCP+SN, and HCP+SN+CIMT groups. Rotarod and front-limb suspension tests, immunohistochemistry, Golgi-Cox staining, transmission electron microscopy, and Western blot analyses were applied to measure motor function, neurons and neurofilament density, dendrites/axon areas, myelin integrity, and Nogo-A/NgR/RhoA/ROCK expression in the motor cortex. Results. The mice in the HCP+CIMT group had better motor function, greater neurons and neurofilament density, dendrites/axon areas, myelin integrity, and lower Nogo-A/NgR/RhoA/ROCK expression in the motor cortex than the HCP and HCP+UNCIMT groups (P < .05). Moreover, the expression of Nogo-A/NgR/RhoA/ROCK, the improvement of neural remodeling and motor function of mice in the HCP+SN group were similar to those in the HCP+CIMT group (P > .05). The neural remodeling and motor function of the HCP+SN+CIMT group were significantly greater than those in the HCP+SN and HCP+CIMT groups (P < .05). Motor function were positively correlated with the density of neurons (r = 0.450 and 0.309, respectively; P < .05) and neurofilament (r = 0.717 and 0.567, respectively; P < .05). Conclusions. CIMT might promote the remodeling of neurons, neurofilament, dendrites/axon areas, and myelin in the motor cortex by partially inhibiting the Nogo-A/NgR/RhoA/ROCK pathway, thereby promoting the improvement of motor function in HCP mice.

17.
J Cell Mol Med ; 25(3): 1568-1582, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410581

RESUMO

The pro-inflammatory and pro-fibrotic liver microenvironment facilitates hepatocarcinogenesis. However, the effects and mechanisms by which the hepatic fibroinflammatory microenvironment modulates intrahepatic hepatocellular carcinoma (HCC) progression and its response to systematic therapy remain largely unexplored. We established a syngeneic orthotopic HCC mouse model with a series of persistent liver injury induced by CCl4 gavage, which mimic the dynamic effect of hepatic pathology microenvironment on intrahepatic HCC growth and metastasis. Non-invasive bioluminescence imaging was applied to follow tumour progression over time. The effect of the liver microenvironment modulated by hepatic injury on sorafenib resistance was investigated in vivo and in vitro. We found that the persistent liver injury facilitated HCC growth and metastasis, which was positively correlated with the degree of liver inflammation rather than the extent of liver fibrosis. The inflammatory cytokines in liver tissue were clearly increased after liver injury. The two indicated cytokines, tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), both promoted intrahepatic HCC progression via STAT3 activation. In addition, the hepatic inflammatory microenvironment contributed to sorafenib resistance through the anti-apoptotic protein mediated by STAT3, and STAT3 inhibitor S3I-201 significantly improved sorafenib efficacy impaired by liver inflammation. Clinically, the increased inflammation of liver tissues was accompanied with the up-regulated STAT3 activation in HCC. Above all, we concluded that the hepatic inflammatory microenvironment promotes intrahepatic HCC growth, metastasis and sorafenib resistance through activation of STAT3.

18.
Sci Rep ; 11(1): 1329, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446724

RESUMO

Higher mortality in asthmatics has been shown previously. However, evidence on different asthma phenotypes on long-term mortality risk is limited. The aim was to evaluate the impact of asthma phenotypes on mortality in general population. Data from the National Health and Nutrition Examination Survey from 2001-2002 to 2013-2014 linked mortality files through December 31, 2015, were used (N = 37,015). Cox proportional hazards regression was used to estimate the risk of all-cause and cause-specific mortality adjusting for sociodemographic characteristics, smoking, body mass index, and chronic conditions. During the mean follow-up time of 7.5 years, 4326 participants died from a variety of causes. Current asthma, but not former asthma was associated with increased all-cause mortality (current asthma: HR = 1.37; 95% CI 1.20-1.58; Former asthma: HR = 0.93; 95% CI 0.73-1.18); as well as mortality from cardiovascular disease (HRCurrent = 1.41; 95% CI 1.08-1.85) and chronic lower respiratory diseases (HRCurrent = 3.17; 95% CI 1.96-5.14). In addition, we found that the HR for cardiovascular disease (CVD) mortality was slightly greater in people with childhood-onset asthma than those with adult-onset asthma. The HR for chronic lower respiratory diseases (CLRD) mortality was greater in people with adult-onset asthma than those with childhood-onset asthma. However, the differences were not statistically significant. Our study suggested that current asthma but not former asthma was associated with increased all-cause, CLRD and CVD mortality. Future well-designed studies with larger sample are required to demonstrate the association and clarify the potential mechanisms involved.

19.
Free Radic Biol Med ; 163: 125-134, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347985

RESUMO

Mitochondrial unfolded protein response (UPRmt) is a mitochondria stress response, which the transcriptional activation programs of mitochondrial chaperone proteins and proteases are initiated to maintain proteostasis in mitochondria. Additionally, the activation of UPRmt delays aging and extends lifespan by maintaining mitochondrial proteostasis. Growing evidences suggests that UPRmt plays an important role in diverse human diseases, especially ageing-related diseases. Therefore, this review focuses on the role of UPRmt in ageing and ageing-related neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease. The activation of UPRmt and the high expression of UPRmt components contribute to longevity extension. The activation of UPRmt may ameliorate Alzheimer's disease, Parkinson's disease and Huntington's disease. Besides, UPRmt is also involved in the occurrence and development of cancers and heart diseases. UPRmt contributes to the growth, invasive and metastasis of cancers. UPRmt has paradoxical roles in heart diseases. UPRmt not only protects against heart damage, but may sometimes aggravates the development of heart diseases. Considering the pleiotropic actions of UPRmt system, targeting UPRmt pathway may be a potent therapeutic avenue for neurodegenerative diseases, cancers and heart diseases.

20.
J Transl Med ; 18(1): 462, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33287854

RESUMO

BACKGROUND: Sepsis is a significant cause of mortality in-hospital, especially in ICU patients. Early prediction of sepsis is essential, as prompt and appropriate treatment can improve survival outcomes. Machine learning methods are flexible prediction algorithms with potential advantages over conventional regression and scoring system. The aims of this study were to develop a machine learning approach using XGboost to predict the 30-days mortality for MIMIC-III Patients with sepsis-3 and to determine whether such model performs better than traditional prediction models. METHODS: Using the MIMIC-III v1.4, we identified patients with sepsis-3. The data was split into two groups based on death or survival within 30 days and variables, selected based on clinical significance and availability by stepwise analysis, were displayed and compared between groups. Three predictive models including conventional logistic regression model, SAPS-II score prediction model and XGBoost algorithm model were constructed by R software. Then, the performances of the three models were tested and compared by AUCs of the receiver operating characteristic curves and decision curve analysis. At last, nomogram and clinical impact curve were used to validate the model. RESULTS: A total of 4559 sepsis-3 patients are included in the study, in which, 889 patients were death and 3670 survival within 30 days, respectively. According to the results of AUCs (0.819 [95% CI 0.800-0.838], 0.797 [95% CI 0.781-0.813] and 0.857 [95% CI 0.839-0.876]) and decision curve analysis for the three models, the XGboost model performs best. The risk nomogram and clinical impact curve verify that the XGboost model possesses significant predictive value. CONCLUSIONS: Using machine learning technique by XGboost, more significant prediction model can be built. This XGboost model may prove clinically useful and assist clinicians in tailoring precise management and therapy for the patients with sepsis-3.

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