Environmental cadmium (Cd) exposure is linked to pulmonary function injury in the general population. But, the association between blood Cd concentration and pulmonary function has not been ...investigated thoroughly in chronic obstructive pulmonary disease (COPD) patients, and the potential mechanisms are unclear.
All eligible 789 COPD patients were enrolled from Anhui COPD cohort. Blood specimens and clinical information were collected. Pulmonary function test was conducted. The subunit of telomerase, telomerase reverse transcriptase (TERT), was determined through enzyme linked immunosorbent assay (ELISA). Blood Cd was measured via inductively coupled-mass spectrometer (ICP-MS).
Blood Cd was negatively and dose-dependently associated with pulmonary function. Each 1-unit increase of blood Cd was associated with 0.861 L decline in FVC, 0.648 L decline in FEV1, 5.938 % decline in FEV1/FVC %, and 22.098 % decline in FEV1 % among COPD patients, respectively. Age, current-smoking, self-cooking and higher smoking amount aggravated Cd-evoked pulmonary function decrease. Additionally, there was an inversely dose-response association between Cd concentration and TERT in COPD patients. Elevated TERT obviously mediated 29.53 %, 37.50 % and 19.48 % of Cd-evoked FVC, FEV1, and FEV1 % declines in COPD patients, respectively.
Blood Cd concentration is strongly associated with the decline of pulmonary function and telomerase activity among COPD patients. Telomere attrition partially mediates Cd-induced pulmonary function decline, suggesting an underlying mechanistic role of telomere attrition in pulmonary function decline from Cd exposure in COPD patients.
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•Blood cadmium is negatively related to lung function in COPD patients.•Smoking COPD patients with higher BMI are prone to Cd-related lung function decline.•Blood cadmium is inversely related to telomerase activity among COPD patients.•Telomerase activity is positively associated with lung function in COPD patients.•Telomerase activity mediates cadmium-evoked lung function decline in COPD patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A new coumarin-based fluorescent probe, containing an allylic esters group, has been designed and synthesized for sensing cysteine in physiological pH. In this fluorescent probe, the coumarin was ...applied as the fluorophore and an allylic esters group was combined as both a fluorescence quencher and a recognition unit. The probe can selectively and sensitively detect cysteine (Cys) over homocysteine, glutathione, and other amino acids, and has a rapid response time of 30 min and a low detection limit of 47.7 nM. In addition, the probe could be applied for cell imaging with low cytotoxicity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Protein posttranslational modification regulates synaptic protein stability, sorting and trafficking, and is involved in emotional disorders. Yet the molecular mechanisms regulating emotional ...disorders remain unelucidated. Here we report unknown roles of protein palmitoylation/nitrosylation crosstalk in regulating anxiety-like behaviors in rats. According to the percentages of open arm duration in the elevated plus maze test, the rats were divided into high-, intermediate- and low-anxiety groups. The palmitoylation and nitrosylation levels were detected by acyl-biotin exchange assay, and we found low palmitoylation and high nitrosylation levels in the basolateral amygdala (BLA) of high-anxiety rats. Furthermore, we observed that 2-bromopalmitate (2-BP), a palmitoylation inhibitor, induced anxiety-like behaviors, accompanied with decreased amplitude and frequency of mEPSCs and mIPSCs in the BLA. Additionally, we also found that inhibiting nNOS activity with 7-nitroindazole (7-NI) in the BLA caused anxiolytic effects and reduced the synaptic transmission. Interestingly, diazepam (DZP) rapidly elevated the protein palmitoylation level and attenuated the protein nitrosylation level in the BLA. Specifically, similar to DZP, the voluntary wheel running exerted DZP-like anxiolytic action, and induced high palmitoylation and low nitrosylation levels in the BLA. Lastly, blocking the protein palmitoylation with 2-BP induced an increase in protein nitrosylation level, and attenuating the nNOS activity by 7-NI elevated the protein palmitoylation level. Collectively, these results show a critical role of protein palmitoylation/nitrosylation crosstalk in orchestrating anxiety behavior in rats, and it may serve as a potential target for anxiolytic intervention.
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Palmitoylation deficiency in the BLA led to anxiety-like behavior in rat.Decreasing protein nitrosylation level induced anxiolytic effects.Diazepam regulated palmitoylation/nitrosylation crosstalk in the BLA.Running mediated anxiolytic action by palmitoylation/nitrosylation crosstalk.Palmitoylation negatively regulated nitrosylation in vitro.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background and Aims: Coronavirus disease 2019 (COVID-19) is a new respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (commonly known as SARS-CoV-2) with multiple ...organ injuries. The aim of this study was to analyze COVID-19-associated liver dysfunction (LD), its association with the risk of death and prognosis after discharge. Methods: Three-hundred and fifty-five COVID-19 patients were recruited. Clinical data were collected from electronic medical records. LD was evaluated and its prognosis was tracked. The association between LD and the risk of death was analyzed. Results: Of the 355 COVID-19 patients, 211 had mild disease, 88 had severe disease, and 51 had critically ill disease. On admission, 223 (62.8%) patients presented with hypoproteinemia, 151(42.5%) with cholestasis, and 101 (28.5%) with hepatocellular injury. As expected, LD was more common in critically ill patients. By multivariate logistic regression, male sex, older age and lymphopenia were three important independent risk factors predicting LD among COVID-19 patients. Risk of death analysis showed that the fatality rate was higher in patients with hypoproteinemia than in those without hypoproteinemia (relative risk=9.471, p<0.01). Moreover, the fatality rate was higher in patients with cholestasis than those without cholestasis (relative risk=2.182, p<0.05). Follow-up observation found that more than one hepatic functional index of two-third patients remained abnormal at 14 days after discharge. Conclusions: LD at early disease stage elevates the risk of death of COVID-19 patients. COVID-19-associated LD does not recover completely by 14 days after discharge.Background and Aims: Coronavirus disease 2019 (COVID-19) is a new respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (commonly known as SARS-CoV-2) with multiple organ injuries. The aim of this study was to analyze COVID-19-associated liver dysfunction (LD), its association with the risk of death and prognosis after discharge. Methods: Three-hundred and fifty-five COVID-19 patients were recruited. Clinical data were collected from electronic medical records. LD was evaluated and its prognosis was tracked. The association between LD and the risk of death was analyzed. Results: Of the 355 COVID-19 patients, 211 had mild disease, 88 had severe disease, and 51 had critically ill disease. On admission, 223 (62.8%) patients presented with hypoproteinemia, 151(42.5%) with cholestasis, and 101 (28.5%) with hepatocellular injury. As expected, LD was more common in critically ill patients. By multivariate logistic regression, male sex, older age and lymphopenia were three important independent risk factors predicting LD among COVID-19 patients. Risk of death analysis showed that the fatality rate was higher in patients with hypoproteinemia than in those without hypoproteinemia (relative risk=9.471, p<0.01). Moreover, the fatality rate was higher in patients with cholestasis than those without cholestasis (relative risk=2.182, p<0.05). Follow-up observation found that more than one hepatic functional index of two-third patients remained abnormal at 14 days after discharge. Conclusions: LD at early disease stage elevates the risk of death of COVID-19 patients. COVID-19-associated LD does not recover completely by 14 days after discharge.
Background. S100A4 is a member of the S100 calcium-binding protein family and is increased in patients with chronic obstructive pulmonary disease (COPD). Sphingosine-1-phosphate (S1P) is a naturally ...occurring bioactive sphingolipid, which regulates the adhesion between the cells and the extracellular matrix and affects cell migration and differentiation. The goal of this study was to analyze the correlations among S100A4, S1P, and pulmonary function among COPD patients. Methods. All 139 serum samples and 15 lung specimens were collected in COPD patients and control subjects. S100A4 and S1P were detected in two groups. The markers of fibrosis and epithelial-mesenchymal transition (EMT) were measured in the lungs of COPD patients and control subjects. Results. The protein expression of S100A4 was higher in the lungs and serum of COPD patients than control cases. Additionally, serum S100A4 was inversely associated with pulmonary function among COPD patients. Meanwhile, collagen deposition and EMT nuclear transcription factors were elevated in the lungs of COPD patients. Moreover, the protein expression of S1P was increased in the serum of COPD patients. Serum S1P was gradually increased along with pulmonary function decline in COPD patients. Further correlation analysis revealed that serum S1P was negatively associated with pulmonary function in COPD patients. Furthermore, there was a positive correlation between S1P and S100A4 in COPD patients. Conclusions. These results provide evidence that the elevation of S100A4 and S1P may be involved in the onset and progression of COPD.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Air pollution exposure has been associated with hypertension, but limited studies have examined the associations in diabetic patients. We aimed to examine the associations of exposure to air ...pollution with blood pressure in diabetic patients. We identified patients who were previously diagnosed as type-2 diabetes mellitus from hospital records from January 2013 to May 2017. We used generalized linear models to estimate adverse effects of air pollution on systolic/diastolic blood pressure in diabetic patients. A total of 40,125 patients were enrolled in this study. An IQR increase in PM2.5, PM10, NO2, SO2, and O3 exposure was associated with an increased risk of higher systolic blood pressure level (β = 0.628 for PM2.5, β = 0.758 for PM10, β = 0.766 for NO2, β = 0.516 for SO2, β = 0.482 for O3, all P value < 0.05). Significant associations were observed for some air pollutants and SBP among patients with fasting blood glucose (FBG) ≥ 7.0 mmol/L, normal weight, and younger age. Little evidence was available for the associations between particulate matter (PM) or O3 exposure and diastolic blood pressure in present study. In our study, diabetic patients were at increased risk of higher blood pressure when exposed to higher residential PM, NO2 and SO2. Individuals with lower BMI, younger age, and FBG ≥ 7.0 mmol/L were more susceptible to the adverse effects of ambient air pollution.
•Air pollution has important impact on blood pressure in Diabetic patients in China.•Higher blood pressure occurred in DM patients when exposed to PM, NO2 and SO2.•Lower BMI, younger age, and FBG ≥ 7.0 mmol/L were more susceptible to air pollution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Oxidative stress is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). 8-Hydroxy-2′-deoxyguanosine (8-OHdG) is recognized as a biomarker of oxidative stress and ...is implicated in several pulmonary diseases. Nonetheless, the role of 8-OHdG remains unclear in COPD patients. This research aimed to evaluate the correlations between serum 8-OHdG on admission and the severity and prognosis of hospitalized COPD patients with acute exacerbation.
Methods
A total of 150 COPD hospitalized patients and 150 healthy individuals were recruited. Serum 8-OHdG was measured by ELISA and the length of hospital stay was calculated. The number of acute exacerbations of COPD was tracked within 1 year after this hospitalization.
Results
The levels of serum 8-OHdG were elevated in COPD patients compared with the control group. Serum 8-OHdG was gradually elevated with decreased pulmonary function in COPD patients. Furthermore, Pearson linear association found that the levels of serum 8-OHdG were inversely correlated with pulmonary function and positively correlated with inflammatory cytokines in COPD patients. In addition, logistic regression analysis revealed that serum 8-OHdG elevation was a risk factor for pulmonary function decline in COPD patients. The length of hospital stay was tracked at this time. Higher serum 8-OHdG on admission increased the length of hospital stay among COPD patients.
Conclusion
Serum 8-OHdG on admission is positively correlated with the severity and adverse prognosis among COPD patients, suggesting that 8-OHdG may be involved in the pathogenesis of COPD. Serum 8-OHdG may be a biomarker to predict the progression of COPD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To examine the association between air pollution and neonatal congenital heart disease (CHD), and evaluate the cumulative burden of CHD attributed to above certain level for ambient air pollution ...exposure.
We identified newborns who were diagnosed as CHD by echocardiography in Network Platform for Congenital Heart Disease (NPCHD) from January 2019 to December 2020 in 11 cities eastern China. The exposure lag response relationship between air pollutants (PM2.5, PM10, SO2, NO2, CO, and O3) concentration and CHDs was calculated by the distributed lag nonlinear model (DLNM). We further calculated the cumulative risk ratios (CRRs) of each air pollutant above reference concentrations on CHDs.
A total of 5904 CHDs from 983, 523 newborns were enrolled in this study. A 10 μg/m3 increase in PM2.5, PM10, SO2, NO2, CO and O3 exposure was associated with an increased risk of higher CHD incident RR = 1.025, 95% CI: 1.016–1.038 for PM2.5 in the third trimester, RR = 1.001, 95% CI: 1.000–1.002 for PM10 in the third trimester, 1.020, 95%CI: 1.004–1.036 for NO2 in the third trimester, RR = 1.001, 95%CI: 1.000–1.002 for O3 in the first trimester, all P value < 0.05). Cumulative effect curves of PM2.5, PM10, SO2, NO2, CO, and O3 were observed as sub-linear with a maximum of 1.876 (95%CI:1.220–2.886), 1.973 (95%CI:1.477,2.637), 2.169 (95%CI:1.347–3.493), 2.902 (95%CI:1.859–4.530), 1.398 (95%CI:1.080–1.809), 2.691 (95%CI:1.705–4.248), respectively. Significant associations were observed for air pollutants and CHDs in cities with higher average education years and babies concepted in cold season.
Our findings could provide growing evidence regarding the adverse health effects of air pollution on CHD, thereby strengthening the hypothesis that air pollutants have harmful impacts on cardiac development. Further studies are needed to verify the associations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective. To examine the use of a viscoelastic agent instead of air in the vitreous cavity during surgery for scleral buckling. Methods. This was a retrospective cohort study of patients who ...underwent scleral buckling surgery for bulging rhegmatogenous retinal detachment (RRD) at Ningbo Eye Hospital from 07/2016 to 12/2019. The patients were grouped into drainage, air injection, cryotherapy and explant (DACE) and drainage, viscoelastic injection, cryotherapy, and explant (DVCE) groups, which were comparatively assessed. Results. There were 25 and 22 patients in the DVCE and DACE groups, respectively. The surgery was significantly shorter with DVCE than DACE (P<0.05), with less intraoperative external pressure adjustment (P<0.05). BCVA was lower in the DVCE group at 1 week compared with the DACE group (P<0.05). Successful retinal reattachment was observed in 92.0% and 81.8% of the DVCE and DACE groups, respectively (P<0.05). Cases requiring laser replenishing after the operation were less in the DVCE group compared with the DACE group (P<0.05). There were no differences in complications and intraocular pressure between the two groups (all P<0.05). Conclusion. DVCE has better operative characteristics and faster vision recovery than DACE, with similar outcomes.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Infantile liver failure syndrome type 1 (ILFS1, OMIM #615,438), caused by leucyl-tRNA synthase 1 (LARS1, OMIM *151,350) deficiency, is a rare autosomal-recessive disorder. The clinical ...manifestations, molecular-genetic features, and prognosis of LARS1 disease remain largely elusive. Three new instances of ILFS1 with confirmed variants in LARS1, encoding LARS1, were identified. Disease characteristics were summarized together with those of 33 reported cases. Kaplan-Meier analysis was performed to assess prognostic factors in ILFS1 patients. The 3 new ILFS1 patients harbored 6 novel variants in LARS1. Among the 36 known patients, 12 died or underwent liver transplantation. The main clinical features of ILFS1 were intrauterine growth restriction (31/32 patients in whom this finding was specifically described), failure to thrive (30/31), hypoalbuminemia (32/32), microcytic anemia (32/33), acute liver failure (24/34), neurodevelopmental delay (25/30), seizures (22/29), and muscular hypotonia (13/27). No significant correlations were observed between genotype and either presence of liver failure or clinical severity of disease. Kaplan-Meier analysis indicated that age of onset < 3mo (p = 0.0015, hazard ratio = 12.29, 95% confidence interval CI = 3.74-40.3), like liver failure (p = 0.0343, hazard ratio = 6.57, 95% CI = 1.96-22.0), conferred poor prognosis. Early age of presentation, like liver failure, confers poor prognosis in ILFS1. Genotype-phenotype correlations remain to be established.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK