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1.
Eur J Clin Nutr ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790398

RESUMO

BACKGROUND/OBJECTIVE: To investigate impacts of early postnatal macronutrient intakes on growth and body composition of preterm infants within the first 6 months. SUBJECTS/METHODS: One hundred and thirty-three very preterm (VPT) and/or very low birth weight (VLBW) infants were consecutively included. Enteral and parenteral macronutrient intakes during the first 28 days were recorded and average daily intakes were calculated. Growth was measured at birth, term age, and 6 months of corrected age (CA). Body composition was examined by air displacement plethysmograph at term age and 6 months of CA. Associations of nutrient intakes with growth and body composition over time were analyzed using generalized estimating equation. RESULTS: After adjusting for covariates, higher daily protein, lipid, and energy intake during the first 28 days was associated with higher weight at term age for every 1 g/kg/day increment of protein and lipid intake, and every 10 kcal/kg/day increment of energy intake was associated with 0.50 (95% CI 0.04, 0.96), 0.29 (95% CI 0.07, 0.51), and 0.27 (95% CI 0.10, 0.44) higher weight z-score, respectively. Higher protein intake was associated with lower z-score of fat mass (FM, ß = -1.88, 95% CI -3.53, -0.23) and percentage of body fat (PBF, ß = -2.18, 95% CI -3.98, -0.39) at 6 months of CA, but higher lipid and carbohydrate intake was associated with higher FM and PBF z-scores at 6 months of CA. CONCLUSIONS: Macronutrient intakes during the first month of life have impacts on growth and body composition before 6 months of age. Higher daily protein intake is associated with a better growth and healthier body composition for VPT/VLBW infants.

2.
J Biochem Mol Toxicol ; : e22766, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793019

RESUMO

BACKGROUND AND PURPOSE: Atherosclerosis is a common cardiovascular disease with high morbidity and mortality. It is reported to be related to oscillatory shear stress (OSS)-induced endothelial dysfunction and excessive production of inflammatory factors. Azilsartan, a specific antagonist of the angiotensin II receptor, has been approved for the management of hypertensive subjects with diabetes mellitus type II (DMII). The present study will investigate the effects of azilsartan against OSS-induced endothelial dysfunction and inflammation, as well as the underlying mechanism. MATERIALS AND METHODS: Cell viability was detected using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay were used to determine the expression levels of IL-6, TNF-α, IL-1ß, VCAM-1, and ICAM-1 in human aortic endothelial cells (HAECs). Generation of reactive oxygen species (ROS) was measured using 2'-7'dichlorofluorescin diacetate (DCFH-DA) staining, and the level of reduced glutathione (GSH) was evaluated using a commercial kit. The adhesion of THP-1 monocytes to HAECs was evaluated using calcein-AM staining. The expression level of KLF6 was determined using qRT-PCR and Western blot analysis. RESULTS: According to the result of the MTT assay, 5 and 10 µM azilsartan were considered as the optimized concentrations applied in the present study. The elevated production of IL-6, TNF-α, and IL-1ß, increased levels of ROS, decreased levels of reduced GSH, upregulated VCAM-1, ICAM-1, and E-selectin, and the aggravated adhesion of THP-1 cells to HAECs induced by OSS were all reversed by the introduction of azilsartan. The downregulation of KLF6 induced by OSS was significantly reversed by azilsartan. By knocking down the expression of KLF6, the suppressed adhesion of THP-1 cells to the HAECs, and the downregulation of VCAM-1 and ICAM-1 induced by azilsartan in OSS-stimulated HAECs were greatly reversed. CONCLUSION: The protective effects of azilsartan against OSS-induced endothelial dysfunction and inflammation might be mediated by KLF6.

3.
J Pharm Pharmacol ; 73(3): 322-331, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33793882

RESUMO

OBJECTIVES: Improper usage of acetaminophen (APAP) leads to morbidity and also mortality secondary to liver damage. Ginseng could suppress APAP-induced hepatotoxicity and ginsenoside Rg3 is a kind of major component in ginseng against liver damage. Herein, we intended to estimate the beneficial function and molecular mechanism of Rg3 on APAP-caused hepatotoxicity and identified hepatoprotection. METHODS: A total of 50 C57BL/6J mice were divided into five random groups, and each contains 10 mice as the control, acetaminophen (350 mg/kg) and Rg3 (5, 10 and 20 mg/kg) + acetaminophen (350 mg/kg) groups. These mice were intragastric administration a single dose of acetaminophen by oral treatment behind pre-administered with several doses of ginsenoside Rg3 for six hours. KEY FINDINGS: According to our data, the injection of APAP (350 mg/kg) enhanced the basal levels of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and lactic dehydrogenase. However, these abnormal added were alleviated by Rg3. Moreover, Rg3 treatment obviously relieved APAP-caused inflammation and oxidant in liver tissues. The depletion of glutathione, glutathione peroxidase, total antioxidant capacity and generation of malondialdehyde induced by APAP treatment were reduced by Rg3. By H&E staining, Rg3 effectively reduced APAP-caused apoptosis and inflammatory infiltration. Moreover, Rg3 attenuated APAP-caused hepatic damage in part by regulating the pro-inflammatory and anti-inflammatory cytokines. Moreover, we found that Rg3 could bind to NLRP3 suggesting the anti-inflammatory effects of Rg3 by molecular docking study. CONCLUSIONS: In summary, Rg3 showed hepatic protective function in APAP-induced hepatotoxicity as evidenced by a reduction of the oxidant and the inflammatory reply, relieve of hepatocellular damage, showing potential in Rg3 as a potential therapeutic medicine to prevent hepatic injury.

4.
Micromachines (Basel) ; 12(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808702

RESUMO

In the field of underwater emergency maintenance, submarine pipeline cutting is generally performed by a diamond wire saw. The process, in essence, involves diamond grits distributed on the surface of the beads cutting X56 pipeline steel bit by bit at high speed. To find the effect of the different parameters (cutting speed, coefficient of friction and depth of cut) on cutting force, the finite element (FEA) method and response surface method (RSM) were adopted to obtain cutting force prediction models. The former was based on 64 simulations; the latter was designed according to DoE (Design of Experiments). Confirmation experiments were executed to validate the regression models. The results indicate that most of the prediction errors were within 10%, which were acceptable in engineering. Based on variance analyses of the RSM models, it could be concluded that the depth of the cut played the most important role in determining the cutting force and coefficient the of friction was less influential. Despite making little direct contribution to the cutting force, the cutting speed is not supposed to be high for reducing the coefficient of friction. The cutting force models are instructive in manufacturing the diamond beads by determining the protrusion height of the diamond grits and the future planning of the cutting parameters.

5.
Talanta ; 228: 122268, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773716

RESUMO

Smart nanozymes that can be facile and rapidly produced, while with efficiently bio-regulated activity, are attractive for biosensing applications. Herein, a smart nanozyme, silver hexacyanoferrate (Ag4[Fe(CN)6]), was constructed in situ via the rapid, direct reaction between silver(I) and K4[Fe(CN)6]. And the activity of the nanozyme can be rationally modulated by different enzymatic reactions including the glucose oxidase (GOx, taken as a model oxidoreductase), alkaline phosphatase (ALP), and acetylcholinesterase (AChE). On the basis of which, a multiple function platform for the highly sensitive detection of glucose, ALP and AChE were developed through colorimetry. Corresponding detection limits for the above three targets were found to be as low as 0.32 µM, 3.3 U/L and 0.083 U/L (S/N = 3), respectively. The present study provides a novel nanozyme that can be produced in situ, which rules out the harsh, cumbersome, and time-consuming synthesis/purification procedures. In addition, it establishes a multiple function platform for the amplified detection of versatile targets by the aid of the developed nanozyme, whose detection has the advantages of low cost, ease-of-use, high sensitivity, and good selectivity.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33755783

RESUMO

PURPOSE: Ca2+-activated chloride channel TMEM16A has been found to be overexpressed in many cancers including head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of TMEM16A in oral squamous cell carcinoma (OSCC) remains unclear. Although simvastatin is known to produce anti-tumor effect, the mechanisms by which simvastatin inhibits cancer remain unclear. METHODS: In this study, we explored the role of TMEM16A expression in human OSCC tissues using both TCGA dataset and immunohistochemistry. CCK-8 assay was applied to evaluate cell proliferation. Patch clamp technique was applied to record TMEM16A Cl- currents. RESULTS: We found that high TMEM16A expression is related with large tumor size, lymph node metastasis, and poor clinical outcome in patients with OSCC. In addition, TMEM16A overexpression could promote cell proliferation, and inhibition of TMEM16A channel activities could suppress cell proliferation in OSCC cells. Furthermore, simvastatin could suppress TMEM16A channel activities, and inhibited cell proliferation in OSCC cells via TMEM16A. CONCLUSION: Our findings identify a novel anti-tumor mechanism of simvastatin by targeting TMEM16A. Simvastatin may represent an innovative strategy for treating OSCC with high TMEM16A expression.

8.
Thorac Cancer ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33787090

RESUMO

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

9.
Huan Jing Ke Xue ; 42(4): 1626-1635, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742797

RESUMO

In order to reveal the chemical composition characteristics and pollution sources of fine particulate matter (PM2.5) in autumn and winter in Yuncheng, PM2.5 samples were continuously collected using a four-channel small-flow particulate sampler from October 15, 2018 to March 15, 2019. The study prediminantly analyzed the chemical components of water-soluble ions, elemental carbon, organic carbon, and metal elements. Additionally, the chemical mass reconstruction method of particulate matter and the positive matrix factorization model (PMF) were combined for an in-depth discussion. During the sample period, the PM2.5 mass concentrations range was 29.37-370.11 µg·m-3, and 101 days during the sampling period exhibited concentrations that were higher than the secondary standard in China's Ambient Air Quality Standards (GB 3095-2012), with an exceeding rate of 70.63%. These results indicate that the air pollution in Yuncheng in autumn and winter is serious. According to the air quality index (AQI), the collected samples are classified as clean, light-moderate pollution, and heavy-severe pollution. Water-soluble ions, OC, EC and metal elements account for 40%, 19%, 5%, and 7% on clean days, 46%, 18%, 4%, and 5% on days with light-moderate pollution, and 46%, 21%, 4%, and 4% on days with heavy-severe pollution, respectively. Secondary ions NO3-, SO42-, and NH4+ are the primary components of water-soluble ions, accounting for 81% (clean days), 87% (light-moderate pollution), and 87% (heavy-severe pollution) of the total ion concentration, respectively. The OC/EC ratios during the sampling period were 3.78 (clean days), 4.02 (light-moderate pollution), and 5.37 (heavy-severe pollution). With the intensification of pollution, the pollution of secondary organic aerosols in the atmosphere becomes increasingly serious. In addition, as the air pollution increased, the concentration of Fe and Cr elements gradually decreased, while the concentration of other metal elements showed an overall upward trend. The results of the chemical mass reconstruction demonstrate that among the different pollution levels of atmospheric PM2.5 in Yuncheng, the mass percentages of secondary inorganic salt, sea salt, heavy metals, mineral dust, construction dust, organic matter, and elemental carbon were 36%, 2%, 2%, 8%, 1%, 33%, and 5% (clean days), 41%, 1%, 1%, 5%, 0.01%, 31%, and 5% (light-moderate pollution), and 41%, 1%, 1%, 4%, 0.004%, 34%, and 4% (heavy-severe pollution). The proportion of secondary inorganic ions increased and mineral dust decreased with the deterioration of air quality. The PMF analysis results suggest that secondary related sources, coal combustion sources, vehicle exhaust sources, biomass burning, and secondary organic matter are the predominant sources of PM2.5 during serious air pollution in Yuncheng.

10.
Chest ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33745993

RESUMO

BACKGROUND: Visceral pleural invasion (VPI) with PL1 or PL2 increases the T classification from T1 to T2 in non-small cell lung cancers (NSCLCs) 3 cm or less. We proposed a modified T classification based on VPI to guide adjuvant therapy. RESEARCH QUESTION: Is it reasonable to upstage PL1-positive cases from T1 to T2 for NSCLCs 3 cm or less? STUDY DESIGN AND METHODS: In total, 1,055 resected NSCLC patients were retrospectively included. Tumor sections were re-stained with hematoxylin and eosin stain and Vitoria blue's elastic stain for the elastic layer. Disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Subgroup analysis and a Cox proportional hazards model were used to further determine the impact of VPI on survival. RESULTS: The extent of VPI was diagnosed as PL0 in 824 patients, PL1 in 133 patients, and PL2 in 98 patients. The 5-year DFS rates of patients with PL0, PL1, and PL2 were 62.6%, 60.2%, and 28.8% (P<0.01), respectively, while the corresponding 5-year OS rates were 78.6%, 74.4%, and 50.0% (P<0.01). As predicted, the DFS and OS of PL2 patients were much worse than those of PL0 (P<0.01) and PL1 (P<0.01) patients. However, both the DFS and OS of PL0 and PL1 patients were comparable (DFS, P=0.198; OS, P=0.150). For node-negative cases, the DFS and OS of PL0 and PL1 patients were also comparable (DFS, P=0.468; OS, P=0.388), but PL2 patients again had much worse DFS and OS than PL0 (P<0.01) and PL1 (P<0.01) patients. Multivariable analyses suggested that PL2, together with node positivity and poor cell differentiation, was an independent adverse prognostic factor. INTERPRETATION: In NSCLCs 3 cm or less, tumors with PL1 should remain defined as T1, not T2. Overtreatment by adjuvant chemotherapy in node-negative NSCLCs 3 cm or less might be avoided in PL1 cases.

11.
Prenat Diagn ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33720417

RESUMO

OBJECTIVE: Twin-twin transfusion syndrome (TTTS) causes perinatal mortality and morbidity in monochorionic twins. The early recognition of and interventional therapy for TTTS is associated with a more favorable overall prognosis. However, the prediction by the use of ultrasound in the first trimester has relatively poor sensitivity and specificity. This study aimed to identify metabolic biomarkers to aid in ultrasound screening of TTTS. METHODS: Maternal plasma was prospectively collected between 11 and 15 weeks of gestation in apparently uncomplicated monochorionic-diamniotic twin pregnancies. This cohort was divided into: (i) patients who were subsequently diagnosed with TTTS by using ultrasound; (ii) uncomplicated matched controls. Metabolome was profiled by using gas chromatography-mass spectrometry. RESULTS: The levels of fatty acids, organic acids, oxaloacetic acid, and beta-alanine were significantly lower in the TTTS maternal plasma at 11-15 weeks of gestation, and methionine and glycine were also higher (p < 0.05, FDR<0.12). Generally, in TTTS pregnancies, the metabolisms of amino acid, carbohydrate, cofactors, vitamins, and purine were "down-regulated"; whereas bile secretion and pyrimidine metabolism were "upregulated." CONCLUSIONS: The metabolomics scanning of early gestation maternal plasma may identify those pregnancies that subsequently develop TTTS; in particular, downregulated fatty acid levels may be biologically plausible to be implicated in the pathogenesis of TTTS.

12.
BMC Psychiatry ; 21(1): 144, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691663

RESUMO

BACKGROUND: It is still unknown whether the "Somatic symptom disorders (SSD) and related disorders" module of the Structured Clinical Interview for DSM-5, research version (SCID-5-RV), is valid in China. This study aimed to assess the SCID-5-RV for SSD in general hospital outpatient clinics in China. METHODS: This multicentre cross-sectional study was conducted in the outpatient clinics of nine tertiary hospitals in Beijing, Jincheng, Shanghai, Wuhan, and Chengdu between May 2016 and March 2017. The "SSD and related disorders" module of the SCID-5-RV was translated, reversed-translated, revised, and used by trained clinical researchers to make a diagnosis of SSD. Several standardized questionnaires measuring somatic symptom severity, emotional distress, and quality of life were compared with the SCID-5-RV. RESULTS: A total of 699 patients were recruited, and 236 were diagnosed with SSD. Of these patients, 46 had mild SSD, 78 had moderate SSD, 100 had severe SSD, and 12 were excluded due to incomplete data. The SCID-5-RV for SSD was highly correlated with somatic symptom severity, emotional distress, and quality of life (all P < 0.001) and could distinguish nonsevere forms of SSD from severe ones. CONCLUSIONS: This study suggests that SCID-5-RV for SSD can distinguish SSD from non-SSD patients and severe cases from nonsevere cases. It has good discriminative validity and reflects the DSM-5 diagnostic approach that emphasizes excessive emotional, thinking, and behavioural responses related to symptoms.

13.
J Nat Prod ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33666437

RESUMO

Five new aconitine-type C19-diterpenoid alkaloids, apetalrines A-E (1-5), were isolated from Aconitum apetalum. Their structures were determined by analysis of 1D and 2D NMR, IR, and HRESIMS data. Semisynthesis of apetalrine B (2) from its parent compound aconorine was achieved to confirm the structure proposed. Twenty derivatives of 2 (11a-11l, 12a, 12b, 12d, 12e, 12j, 12k, 12m, 12n) were synthesized via a unified approach relying on simple coupling reactions. The evaluation of neuroprotective effects of compounds (1-5, 11b, 11c, 11f-11i, 12a, 12b, 12d, 12e, 12k, 12m, 12n) with low cytotoxicity revealed compound 2 to exhibit good neuroprotective effects in H2O2-treated SH-SY5Y cells at a concentration of 50 µM. A series of studies using flow cytometry, staining, and Western blotting on 2 indicated that its neuroprotective effects may arise from inhibiting cell apoptosis.

14.
J Am Geriatr Soc ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33683703

RESUMO

BACKGROUND/OBJECTIVES: Psychotropic and opioid medications are routinely prescribed for symptom management in hospice, but national estimates of prescribing are lacking. Changes in Medicare hospice payment in 2014 provide the first opportunity to examine psychotropic and opioid prescribing among hospice beneficiaries, and the factors associated with use of specific medication classes. DESIGN: Cross-sectional analysis of a 20% sample of traditional and managed Medicare with Part D enrolled in hospice, 2014-2016. SETTING: Beneficiaries enrolled in the Medicare hospice benefit. PARTICIPANTS: Medicare beneficiaries ≥65 newly enrolled in hospice between July 1, 2014 and December 31, 2016 (N = 554,022). MAIN OUTCOME: Prevalence of psychotropic and opioid medication prescribing by class and factors associated with prescribing. RESULTS: 70.3% of hospice beneficiaries were prescribed a psychotropic and 63.3% were prescribed an opioid. The most common psychotropic classes prescribed were: benzodiazepines (60.6%), antipsychotics (38.3%), antidepressants (18.4%), and antiepileptics (10.2%). Lorazepam (56.4%), morphine (52.8%), and haloperidol (28.6%) were received by the most beneficiaries. Prevalence of any psychotropic and opioid prescription was highest among beneficiaries who were female (76.7%), non-Hispanic white (76.6%), and those with cancer (78.9%). Compared to white beneficiaries, non-Hispanic black beneficiaries were less likely to receive nearly every class of medication, with significantly lower odds of receiving opioids (64.1% vs 57.9%; AOR 0.75, 95% CI 0.72-0.77) and benzodiazepines (61.6% vs 52.2%; AOR 0.66, 95% CI 0.64-0.68). Differences were seen across hospice diagnosis; those with cancer were more likely to receive opioids, benzodiazepines, and antipsychotics but less likely to receive antidepressants and antiepileptics. CONCLUSIONS: Psychotropic and opioid medications are frequently prescribed in hospice. Observed variations in prescribing across race and ethnicity may reflect disparities in prescribing as well as patient preferences for care. Further work is important to understand factors driving prescribing given limited studies surrounding medication prescribing in hospice.

15.
Acad Radiol ; 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33653656

RESUMO

OBJECTIVE: This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with modified FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as an alternative treatment option in advanced hepatocellular carcinoma (HCC) patients with failed or unsuitability for transarterial chemoembolization (TACE). MATERIALS AND METHODS: From September 2018 to January 2020, 87 advanced HCC patients who progressed on TACE or were not eligible for TACE received HAIC treatment with modified FOLFOX. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1, and adverse events graded according to CTCAE 5.0. Based on prognostic factors determined by multivariate analysis, a nomogram was developed to predict patient survival. RESULTS: The median OS and PFS were 9.0 months (95%CI 7.6-10.4) and 3.7 months (95%CI 3.1-4.3), respectively. The objective response rate was 13.8%, with a disease control rate of 48.3%. Grade 3 adverse events were observed, such as infection (9.2%), thrombocytopenia (5.7%), hyperbilirubinemia (3.4%), abdominal pain (2.3%) and alanine aminotransferase increase (2.3%). Albumin, AST, and extrahepatic metastasis were incorporated to construct a new nomogram that could stratify patients into three prognostic subgroups, including low-, intermediate-, and high-risk groups, with significant differences in 9-month OS rates (71%, 42% and 6%, respectively; p< 0.001). The nomogram was better than the Okuda, AJCC, and CLIP staging systems for OS prediction. CONCLUSION: These findings support the feasibility of HAIC with modified FOLFOX as an alternative treatment strategy for advanced HCC when TACE is ineffective or unsuitable.

16.
Cell Prolif ; : e13023, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33759281

RESUMO

BACKGROUND: Vascular smooth muscle cells (VSMC) switch to macrophage-like cells after cholesterol loading, and this change may play an important role in atherogenesis. Muscleblind-like splicing regulator 1 (MBNL1) is a well-known splicing factor that has been implicated in many cellular processes. However, the role of MBNL1 in VSMC macrophage-like transdifferentiation is largely unknown. In this study, we aim to characterize the role of MBNL1-induced gene splicing during atherogenesis. METHODS: The expression of MBNL1 and Abelson interactor 1 (Abi1) splice variants (Abi1-e10 and Abi1-Δe10) was compared between artery tissues from healthy donors and atherosclerosis patients. Regulatory mechanisms of MBNL1-induced Abi1 gene splicing were studied, and the signal pathways mediated by Abi1 splice variants were investigated in VSMC. RESULTS: Loss of MBNL1 was found in the macrophage-like VSMC (VSMC-M) in artery wall from atherosclerosis patients. In vitro and in vivo evidence confirmed that Abi1 is one of the MBNL1 target genes. Loss of MBNL1 significantly induces the Abi1-Δe10 isoform expression. Compared to the known actin organization activities of the Abi1 gene, we discovered a novel action of Abi1-Δe10, whereby Abi1-Δe10 activates Rac1 independent of upstream stimulation and triggers the Rac1-NOX1-ROS pathway, which results in increased expression of transcription factor Kruppel-like factor 4 (KLF4). While Abi1-Δe10 inhibits contractile VSMC biomarkers expression and cell contraction, it stimulates VSMC proliferation, migration and macrophage-like transdifferentiation. CONCLUSION: Loss-of-function of MBNL1 activates VSMC-M transdifferentiation to promote atherogenesis through regulating Abi1 RNA splicing.

17.
Ecotoxicol Environ Saf ; 214: 112110, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33677379

RESUMO

BACKGROUND: Previous studies have shown that multiple imbalances of metal ions in the brain are closely associated with the neurodegenerative disorders. Our studies have shown that long-term working exposure to aluminum induces increased plasma aluminum levels and causes cognitive impairment in workers at aluminum factories. OBJECTIVE: To explore the levels of nine metals in plasma and the effect on cognitive function among in-service workers. METHODS: In this cross-sectional study, cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), which included seven subitems: executive/visuospatial abilities; naming; attention and calculation; language; abstract; recall; and orientation. The plasma levels of nine kinds of metals were measured by inductively coupled plasma-mass spectrometry (ICP-MS). A multivariate generalized linear regression model and Bayesian kernel machine regression (BKMR) were selected to estimate the relationship between metal plasma level and MoCA scores with adjustment for confounders. RESULTS: One hundred and eighty-seven workers participated in this study. In the multivariable generalized linear model, among these nine metals studied, five were related to the MoCA score: aluminum, lithium, cobalt, zinc and chromium. In the BKMR model, a significantly negative correlation between the plasma aluminum, lithium and the total MoCA score was observed. Moreover, for subitems on the MoCA scale, the plasma levels of lithium, aluminum, and zinc had a significant correlation with the executive/visuospatial abilities, naming, and orientation abilities, respectively. The log-transformation concentrations of plasma aluminum and lithium were negatively correlated with the executive/visuospatial abilities and naming abilities, respectively. The log-transformation plasma zinc concentration was positively correlated with orientation abilities. CONCLUSION: Based on the results, we determined that increased aluminum and lithium and decreased zinc levels in plasma were associated with the incidence of mild cognitive impairment (MCI) in workers at a Chinese aluminum plant.


Assuntos
Poluentes Ocupacionais do Ar/sangue , Disfunção Cognitiva/epidemiologia , Metais/sangue , Adulto , China/epidemiologia , Cognição , Disfunção Cognitiva/sangue , Estudos Transversais , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Metalurgia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto Jovem
18.
Cells ; 10(2)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530465

RESUMO

Bone-muscle crosstalk plays an important role in skeletal biomechanical function, the progression of numerous pathological conditions, and the modulation of local and distant cellular environments. Previous work has revealed that the deletion of connexin (Cx) 43 in osteoblasts, and consequently, osteocytes, indirectly compromises skeletal muscle formation and function. However, the respective roles of Cx43-formed gap junction channels (GJs) and hemichannels (HCs) in the bone-muscle crosstalk are poorly understood. To this end, we used two Cx43 osteocyte-specific transgenic mouse models expressing dominant negative mutants, Δ130-136 (GJs and HCs functions are inhibited), and R76W (only GJs function is blocked), to determine the effect of these two types of Cx43 channels on neighboring skeletal muscle. Blockage of osteocyte Cx43 GJs and HCs in Δ130-136 mice decreased fast-twitch muscle mass with reduced muscle protein synthesis and increased muscle protein degradation. Both R76W and Δ130-136 mice exhibited decreased muscle contractile force accompanied by a fast-to-slow fiber transition in typically fast-twitch muscles. In vitro results further showed that myotube formation of C2C12 myoblasts was inhibited after treatment with the primary osteocyte conditioned media (PO CM) from R76W and Δ130-136 mice. Additionally, prostaglandin E2 (PGE2) level was significantly reduced in both the circulation and PO CM of the transgenic mice. Interestingly, the injection of PGE2 to the transgenic mice rescued fast-twitch muscle mass and function; however, this had little effect on protein synthesis and degradation. These findings indicate a channel-specific response: inhibition of osteocytic Cx43 HCs decreases fast-twitch skeletal muscle mass alongside reduced protein synthesis and increased protein degradation. In contrast, blockage of Cx43 GJs results in decreased fast-twitch skeletal muscle contractile force and myogenesis, with PGE2 partially accounting for the measured differences.

19.
BMC Gastroenterol ; 21(1): 59, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568088

RESUMO

BACKGROUND: To explore the postoperative prognosis of esophageal squamous cell carcinoma (ESCC) patients with stage IB/IIA, using a prognostic score (PS). METHODS: Stage IB/IIA ESCC patients who underwent esophagectomy from 1999 to 2010 were included. We retrospectively recruited 153 patients and extracted their medical records. Moreover, we analyzed the programmed death ligand-1 (PD-L1) expression of their paraffin tissue. The cohort were randomly divided into a training group (N = 123) and a validation group (N = 30). We selected overall survival (OS) as observed endpoint. Prognostic factors with a multivariable two-sided P < 0.05 met standard of covariate inclusion. RESULTS: Univariable and multivariable analyses identified pTNM stage, the number of lymph nodes (NLNs) and PD-L1 expression as independent OS predictors. Primary prognostic score which comprised above three covariates adversely related with OS in two cohorts. PS discrimination of OS was comparable between the training and internal validation cohorts (C-index = 0.774 and 0.801, respectively). In addition, the PS system had an advantage over pTNM stage in the identification of high-risk patients (C-index = 0.774 vs. C-index = 0.570, P < 0.001). Based on PS cutoff, training and validation datasets generated low-risk and high-risk groups with different OS. Our three-factor PS predicted OS (low-risk subgroup vs. high-risk subgroup 60-month OS, 74% vs. 23% for training cohort and 83% vs. 45% for validation cohort). CONCLUSION: Our study suggested a PS for significant clinical stratification of IB/IIA ESCC to screen out subgroups with poor prognosis.

20.
Curr Med Sci ; 41(1): 158-166, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582921

RESUMO

Myocardial fiber deformation measurements have been reported to be associated with adverse outcomes in patients with acute heart failure and those with myocardial infarction. However, few studies have addressed the prognostic value of global circumferential strain (GCS) in dilated cardiomyopathy (DCM) patients with severely impaired systolic function. This study aimed to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived GCS in DCM patients with severely reduced ejection. Consecutive DCM patients with severely reduced ejection fraction (EF <35%) who underwent CMR were included. GCS was calculated from CMR cine images. The clinical endpoint was a composite of all-cause mortality, heart transplantation, implantable cardioverter defibrillator (ICD) implantation and aborted sudden cardiac death (SCD). A total of 129 patients with a mean EF of 15.33% (11.36%-22.27%) were included. During a median follow-up of 518 days, endpoint events occurred in 50 patients. Patients with GCS ≥ the median (-5.17%) had significantly reduced event-free survival as compared with those with GCS < the median (P<0.01). GCS was independently associated with adverse events after adjusting for clinical and imaging risk factors including extent of late gadolinium enhancement (LGE) (P<0.05). Adding GCS into the model including the extent of LGE resulted in significant improvements in the C-statistic (from 0.706 to 0.742; P<0.05) with a continuous net reclassification improvement (NRI) of 29.71%. It was concluded that GCS derived from CMR could be useful for risk stratification in DCM patients with severely reduced EF, which may increase common imaging risk factors including LGE.

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