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1.
Materials (Basel) ; 14(6)2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33799448

RESUMO

Directed energy deposition (DED) has been widely used for component repair. In the repair process, the surface defects are machined to a groove or slot and then refilled. The sidewall inclination angle of the groove geometry has been recognized to have a considerable impact on the mechanical properties of repaired parts. The objective of this work was to investigate the feasibility of repairing various V-shaped defects with both experiments and modeling. At first, the repair volume was defined by scanning the defective zone. Then, the repair volume was sliced to generate the repair toolpath. After that, the DED process was used to deposit Ti6Al4V powder on the damaged plates with two different slot geometries. Mechanical properties of the repaired parts were evaluated by microstructure analysis and tensile test. Testing of the repaired parts showed excellent bonding between the deposits and base materials with the triangular slot repair. 3D finite element analysis (FEA) models based on sequentially coupled thermo-mechanical field analysis were developed to simulate the corresponding repair process. Thermal histories of the substrate on the repair sample were measured to calibrate the 3D coupled thermo-mechanical model. The temperature measurements showed very good verification with the predicted temperature results. After that, the validated model was used to predict the residual stresses and distortions in the parts. Predicted deformation and stress results can guide the evaluation of the repair quality.

2.
Eur J Orthod ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33822036

RESUMO

BACKGROUND: Several orthognathic procedures have been applied to correct skeletal anterior open bites (SAOB). Which method is most stable has been debated and no consensus has been reached and there is no conclusive evidence for clinicians to use. OBJECTIVE: To analyse whether maxillary, mandibular, or bimaxillary surgery provides a better stability. MATERIALS AND METHODS: A systematic search was conducted up to December 2020 using PubMed, EMBASE, Medline, Scopus, Web of Science, Cochrane CENTRAL, and Google Scholar. We made direct comparisons among the controlled trials and also made indirect comparisons via subgroup analysis on the aspects of occlusional, skeletal, and dento-alveolar stability to assess the overall stability of each method. RESULTS: Finally 16 cohort studies were identified. At the occlusional level, pooled change in overbite was 0.21 mm in maxillary surgery, 0.37 mm in bimaxillary surgery, and -0.32 mm in mandibular surgery. At the skeletal level, pooled sella-nasion-Point A angle (SNA) was -0.12 degrees in bimaxillary surgery, -0.37 degrees in maxillary surgery and -0.20 degrees in mandibular surgery. The sella-nasion to palatal plane angle (SNPP) relapsed to a statistically significant degree in all samples received single maxillary surgery. Relapse of the sella-nasion-Point B angle (SNB) was 0.47 degrees in mandibular setback, -1.8 degrees in mandibular advancement, and -0.48 degrees in maxillary surgery. The Sella-Nasion to mandibular plane angle (SNMP) relapsed more in procedures involving bilateral sagittal split osteotomy than in other procedures. As for dento-alveolar changes, intrusion of molars and extrusion of incisors took place in most patients. CONCLUSIONS: Bimaxillary surgery produced the most beneficial post-operative increase in overbite, maxillary surgery led to a lesser but still positive overbite change, and mandibular surgery correlated with some extent of relapse. Skeletally, bimaxillary surgery was more stable than maxillary surgery at both SNA and SNPP; SNB was more stable in mandibular setback than advancement; and SNMP was unstable in both mandibular and bimaxillary surgeries versus maxillary surgery with comparable surgical changes. Dento-alveolar compensation helped maintain a positive overbite. REGISTRATION NUMBER: CRD42020198088.

4.
J Integr Plant Biol ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33811744

RESUMO

In plants, clade A type 2C protein phosphatases (PP2CAs) have emerged as major players in abscisic acid (ABA)-regulated stress responses by inhibiting protein kinase activity. However, how different internal and external environmental signals modulate the activity of PP2CAs are not well known. The Transmembrane Kinase (TMK) protein 4 (TMK4), one member of a previously identified receptor kinase subfamily on the plasma membrane that play vital roles in plant cell growth, directly interacts with PP2CAs member (ABA-Insensitive 2, ABI2). tmk4 mutant is hypersensitive to ABA in both ABA-inhibited seed germination and primary root growth, indicating that TMK4 is a negative regulator in ABA signaling pathway. Further analyses indicate that TMK4 phosphorylates ABI2 at three conserved Ser residues, thus enhancing the activity of ABI2. The phosphorylation-mimic ABI2S139DS140DS266D can complement but non-phosphorylated form ABI2S139AS140AS266A cannot complement ABA hypersensitive phenotype of the loss-of- function mutant abi1-2abi2-2. This study provides a previously unidentified mechanism for positively regulating ABI2 by a plasma membrane protein kinase. This article is protected by copyright. All rights reserved.

5.
Pregnancy Hypertens ; 24: 100-106, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33773326

RESUMO

OBJECTIVES: The aim of this study was to compare radial arterial catheter-derived pressure with oscillometric blood pressure in women with severe peripartum hypertension undergoing urgent treatment with intravenous nicardipine at a maternal intensive care unit. STUDY DESIGN: We obtained patients' paired values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). All of the measurements were divided into four groups based on the levels of SBP and MAP measured using the oscillometric method. MAIN OUTCOME MEASURES: We assessed agreements of the paired values using the Bland-Altman method. The clinical relevance of differences between the two methods was assessed by error grid analysis. RESULTS: A total of 337 paired SBP and DBP values and 305 paired MAP values were obtained for 89 patients. The values of intra-arterial SBP were higher than those of oscillometric SBP. The values of intra-arterial MAP were higher than those of oscillometric MAP except for the women with MAP ≥ 125 mm Hg. Bland - Altman analysis showed acceptable agreement for DBP and MAP measured by intra-arterial method and oscillometric method. Error grid analysis showed the proportions of measurements in risk zones A to E were 83.22%, 16.46%, 0.32%, 0%, and 0% for SBP, and 97.81%, 2.19%, 0%, 0%, and 0% for MAP, respectively. CONCLUSION: Intra-arterial MAP can be used reliably to monitor the effect of intravenous nicardipine for treating severe hypertension. Intra-arterial SBP may trigger moderate-risk treatment decisions in the women with oscillometric SBP ≤ 160 mm Hg.

6.
Liver Int ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33786995

RESUMO

BACKGROUND: Liver fibrosis is pathologically important in the liver cirrhosis progression. The epithelial-mesenchymal transition (EMT) is crucial for organ fibrosis. Macrophage stimulating protein (MSP) and its receptor tyrosine kinase, RON, promote cellular EMT. However, their role in liver fibrosis is unclear. Here, we clarify the biological profile, potential mechanisms, and therapeutic targets of the MSP-RON pathway in liver fibrosis. MATERIALS AND METHODS: MSP expression and its correlation with clinicopathological characteristics of cirrhosis were evaluated in 57 clinical cases and a control group. The effect of MSP-RON pathway in liver fibrosis were determined in vitro and in vivo. The therapeutic effects of MSP or RON inhibition on liver fibrosis were evaluated in a mouse liver fibrosis model. RESULTS: MSP is upregulated in liver cirrhosis, which was associated with poor patient prognosis. The MSP-RON pathway promoted hepatocytes EMT. MSP-RON-induced EMT depends on the TGF-ß pathway and is regulated by TGF-ß inhibitors. In animal models, an MSP blocking antibody and a small molecule inhibitor of RON, BMS-777607, both inhibited liver fibrosis progression. CONCLUSION: Our study revealed that MSP is an important biomarker in liver cirrhosis progression and can be used to prognose patients. The MSP-RON pathway promotes the EMT of hepatocytes and the progress of fibrosis via a TGF-ß related pathway. Consequently, we identified a new treatment strategy for liver cirrhosis through targeted inhibition of MSP/RON. This research increases the understanding of EMT-modulated liver fibrosis and provides new insights into biomarkers and therapeutic targets of liver fibrosis. (250 words).

7.
Diagn Interv Imaging ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33741266

RESUMO

PURPOSE: To determine the capabilities of MRI-based traditional radiomics and computer-vision (CV) nomogram for predicting lymphovascular space invasion (LVSI) in patients with endometrial carcinoma (EC). MATERIALS AND METHODS: A total of 184 women (mean age, 52.9±9.0 [SD] years; range, 28-82 years) with EC were retrospectively included. Traditional radiomics features and CV features were extracted from preoperative T2-weighted and dynamic contrast-enhanced MR images. Two models (Model 1, the radiomics model; Model 2, adding CV radiomics signature into the Model 1) were built. The performance of the models was evaluated by the area under the curve (AUC) of the receiver operator characteristic (ROC) in the training and test cohorts. A nomogram based on clinicopathological metrics and radiomics signatures was developed. The predictive performance of the nomogram was assessed by AUC of the ROC in the training and test cohorts. RESULTS: For predicting LVSI, the AUC values of Model 1 in the training and test cohorts were 0.79 (95% confidence interval [CI]: 0.702-0.889; accuracy: 65.9%; sensitivity: 88.8%; specificity: 57.8%) and 0.75 (95% CI: 0.585-0.914; accuracy: 69.5%; sensitivity: 85.7%; specificity: 62.5%), respectively. The AUC values of Model 2 in the training and test cohorts were 0.93 (95% CI: 0.875-0.991; accuracy: 94.9%; sensitivity: 91.6%; specificity: 96.0%) and 0.81 (95% CI: 0.666-0.962; accuracy: 71.7%; sensitivity: 92.8%; specificity: 62.5%), respectively. The discriminative ability of Model 2 was significantly improved compared to Model 1 (Net Reclassification Improvement [NRI]=0.21; P=0.04). Based on histologic grade, FIGO stage, Rad-score and CV-score, AUC values of the nomogram to predict LVSI in the training and test cohorts were 0.98 (95% CI: 0.955-1; accuracy: 91.6%; sensitivity: 91.6%; specificity: 96.0%) and 0.92 (95% CI: 0.823-1; accuracy: 91.3%; sensitivity: 78.5%; specificity: 96.8%), respectively. CONCLUSIONS: MRI-based traditional radiomics and computer-vision nomogram are useful for preoperative risk stratification in patients with EC and may facilitate better clinical decision-making.

8.
Aging (Albany NY) ; 13(6): 8421-8439, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33714196

RESUMO

Because of the key role of impaired mitochondria in the progression of acute kidney injury (AKI), it is striking that peroxisome proliferator γ coactivator 1-α (PGC-1α), a transcriptional coactivator of genes involved in mitochondrial biogenesis and autophagy, protects from kidney injury. However, the specific mechanism involved in PGC-1α-mediated autophagy remains elusive. In vivo, along with the severe kidney damage, the expression of PGC-1α was decreased in cisplatin-induced AKI mice. Conversely, PGC-1α activator (ZLN005) administration could alleviate kidney injury. Consistently, in vitro overexpression of PGC-1α or ZLN005 treatment inhibited cell apoptosis and mitochondrial dysfunction induced by cisplatin. Moreover, ZLN005 treatment increased the expression of LC3-II and co-localization between LC3 and mitochondria, suggesting that the mitophagy was activated. Furthermore, PGC-1α-mediated the activation of mitophagy was reliant on the increased expression of TFEB, and the protective effects were abrogated in TFEB-knockdown cells. These data suggest that the activation of PGC-1α could alleviate mitochondrial dysfunction and kidney injury in AKI mice via TFEB-mediated autophagy.

9.
BMC Pregnancy Childbirth ; 21(1): 207, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33711956

RESUMO

BACKGROUND: Along with progress in embryo cryopreservation, especially the vitrification, freeze all strategy has become more acceptable than ever. Some studies have found comparable or higher live birth rate with frozen embryo transfer (FET) than with fresh embryo transfer(ET)in gonadotropin releasing hormone antagonist (GnRH-ant) protocol. However from our literature research, there have been no reports about live birth rate comparison between fresh ET and FET with gonadotropin releasing hormone agonist (GnRH-a) long protocol. The aim of this study is to retrospectively investigate whether patients benefit from freeze all strategy in GnRH-a protocol using real-world data. METHODS: This is a retrospective cohort study, in which women undergoing fresh ET or FET with GnRH-a long protocol at Chongqing Reproductive and Genetics Institute from January 2016 to December 2018 were evaluated. The primary outcome was live birth rate. The secondary outcomes were implantation rate, clinical pregnancy rate, pregnancy loss and ectopic pregnancy rate. RESULTS: A total of 7,814 patients met inclusion criteria, implementing 5,216 fresh ET cycles and 2,598 FET cycles, respectively. The demographic characteristics of the patients were significantly different between fresh ET and FET groups, except BMI. After controlling for a broad range of potential confounders including age, infertility duration, BMI, AMH, number of oocytes retrieved and of available embryos, multivariate logistic regression analysis demonstrated that there was no significant difference in clinical pregnancy rate, ectopic pregnancy rate and pregnancy loss rate between two groups (all P > 0.05). However, the implantation rate and live birth rate in fresh ET group were significantly higher than FET group (P < 0.001 and P = 0.012, respectively). CONCLUSIONS: Under GnRH-a long protocol, compared to FET, fresh ET was associated with higher implantation rate and live birth rate in infertile patients that underwent in vitro fertilization (IVF). The freeze all strategy should be individualized and made with caution especially with GnRH-a long protocol.

10.
Cancer Sci ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33728806

RESUMO

The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of COVID-19 deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID-19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis were conducted to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C-index and time-dependent AUC. Internal validation was assessed by the validation cohort. Risk stratification based on the model was performed. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, , CT baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C-reactive protein, aspartate aminotransferase, direct bilirubin, urea and d-dimer) were significantly associated with symptomatic deterioration. The C-index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. T-AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low-risk (total points≤ 9.98) and high-risk (total points> 9.98) group. The Kaplan-Meier C-DFS curves presented the significant discrimination between the two risk groups in both training and validation cohort. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer.

11.
J Phys Chem A ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33754720

RESUMO

In the troposphere, the knowledge about nitrous acid (HONO) sources is incomplete. The missing source of sulfate and fine particles cannot be explained during haze events. Air quality models cannot predict high levels of secondary fine-particle pollution. Despite extensive studies, one challenging issue in atmospheric chemistry is identifying the source of HONO. Here, we present direct ab initio molecular dynamics simulation evidence and typical air pollution events of the formation of gaseous HONO, nitrogen dioxide/hydrogen sulfite (HOS(O)2-NO2 or NO2-HSO3) from nitrogen dioxide (NO2), sulfur dioxide (SO2), water (H2O), and ammonia (NH3) molecules in a proportion of 2:1:3:3. The reactions show a new mechanism for the formation of HONO and NO2-HSO3 in the troposphere, especially when the concentration of NO2, SO2, H2O, and NH3 is high (e.g., 2:1:3:3 or higher) in the air. Contrary to the proportion NO2, SO2, H2O, and NH3 equaling to 1:1:3:1 and 1:1:3:2, the proportion (2:1:3:3) enables barrierless reactions and weak interactions between molecules via the formation of HONO, NO2-HSO3, and NH3/H2O. In addition, field observations are carried out, and the measured data are summarized. Correlation analysis supported the conversion of NO2 to HONO during observational studies. The weak interactions promote proton transfer, resulting in the generation of HONO, NO2-HSO3, and NH3/H2O pairs.

12.
Stem Cells ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739541

RESUMO

Mesenchymal stem cells (MSCs) have fueled ample translation for treatment of immune-mediated diseases. Our previous study had demonstrated that MSCs could elicit macrophages (Mϕ) into anti-inflammatory phenotypes, and alleviate kidney injury in diabetic nephropathy mice via improving mitochondrial function of Mϕ, yet the specific mechanism was unclear. Recent evidence indicated that MSCs communicated with their microenvironment through exchanges of mitochondria. By a co-culture system consisting of MSCs and Mϕ, we showed that MSCs-derived mitochondria (MSCs-Mito) were transferred into Mϕ, and the mitochondrial functions were improved, which contributed to M2 polarization. Furthermore, we found that MSCs-Mito transfer activated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis. In addition, PGC-1α interacted with TFEB in high glucose (HG)-induced Mϕ, leading to the elevated lysosome-autophagy, which was essential to removal of damaged mitochondria. As a result, in Mϕ the mitochondrial bioenergy and capacity to combat inflammatory response were enhanced. Whereas, the immune-regulatory activity of MSCs-Mito was significantly blocked in PGC-1α knockdown Mϕ. More importantly, MSCs-Mito transfer could be observed in DN mice, and the adoptive transfer of MSCs-Mito educated Mϕ (MϕMito ) inhibited the inflammatory response and alleviated kidney injury. While the kidney-protective effects of MϕMito were abolished when the MSCs-Mito was impaired with rotenone (Rot), and the similar results were also observed when MϕMito were transfected with sipgc-1α before administration. Collectively, these findings suggested that MSCs elicited Mϕ into anti-inflammatory phenotype and ameliorated kidney injury through mitochondrial transfer in DN mice, and the effects were relied on PGC-1α-mediated mitochondrial biogenesis and PGC-1α/TFEB-mediated lysosome-autophagy. © AlphaMed Press 2021 SIGNIFICANCE STATEMENT: Our previous study had demonstrated that MSCs elicited Mϕ into M2 phenotype via improving mitochondrial function of Mϕ, yet the specific mechanism remained to be elucidated. The current study was the first to assess the potential role of mitochondrial transfer from MSCs to Mϕ and further explore the underlying mechanisms. We found that mitochondrial transfer from MSCs to Mϕ restricted inflammation and alleviated kidney injury in diabetic nephropathy mice via PGC-1α-mediated mitochondrial biogenesis and PGC-1α/TFEB-mediated autophagy. While shedding light on this new immune-regulatory mechanism, our findings offer strategies to improve cell-based therapies or eventual cell-free therapeutic approaches for inflammation-related diseases.

13.
Nat Prod Res ; : 1-7, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33715538

RESUMO

Four new resorcinol derivatives, namely (-)/(+)-xylarinig A (1), as well as xylarinigs B (2) and C (3), were isolated from the ethyl acetate extracts of the solid fermentation of Xylaria nigripes. Their structures were established by comprehensive spectroscopic analysis combined with electronic circular dichroism (ECD) calculations. Compound 1 is an optical mixture, and was resoluted into optical pure enatiomers (+)-1 and (-)-1 by chiral HPLC. The neuroprotective effects of 1-3 against the damage of PC12 cells induced by oxygen and glucose deprivation (OGD) were evaluated.

14.
Int J Mol Sci ; 22(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670592

RESUMO

In this study, we investigated the effects of blue light exposure on nucleotide-binding oligomerization domain 2 (NOD2) expression on the mouse ocular surface and evaluated the role of NOD2 activation in light-induced cell death. Mice were divided into wild-type (WT), NOD2-knock out (KO), WT + blue light (WT + BL), and NOD2-KO + blue light (NOD2-KO + BL) groups, and the mice in the WT+BL and NOD2-KO + BL groups were exposed to blue light for 10 days. After 10 days of blue light exposure, increased reactive oxygen species and malondialdehyde were observed in the WT + BL and NOD2-KO + BL groups, and the WT + BL group showed a higher expression of NOD2 and autophagy related 16 like 1. Although both WT+BL and NOD2-KO + BL groups showed an increase in the expression of light chain 3-II, NOD2-KO + BL mice had a significantly lower p62 expression than WT + BL mice. In addition, NOD2-KO+BL mice had significantly lower corneal epithelial damage and apoptosis than WT + BL mice. In conclusion, blue light exposure can induce impaired autophagy by activation of NOD2 on the ocular surface. In addition, the reactive oxygen species (ROS)-NOD2-autophagy related 16 like 1 (ATG16L) signaling pathway may be involved in the blue-light-induced autophagy responses, resulting in corneal epithelial apoptosis.

15.
Heart Fail Rev ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33713009

RESUMO

Heart failure (HF) often coexists with insulin resistance (IR), and the incidence of HF in type 2 diabetes mellitus (T2DM) patients is significantly higher. The reciprocal relationship between HF and IR has long been recognized, and the integration complicates the therapy of both. A number of mechanisms ascribe to the progression of cardiac IR, in which the main factors are the shift of myocardial substrate metabolism. Studies have found that SGLT2 inhibitors, an anti-diabetic drug, can improve the cardiac prognosis of patients with T2DM, which may be at least partially due to the relief of cardiac IR. Basic and clinical studies have revealed the important role of cardiac IR in the pathogenesis and progression of HF, and studies suggest that energy metabolism plays an important role in the pathogenesis of cardiac IR and HF. SGLT2 inhibitors mediated cardiovascular benefits through various mechanisms such as improving substrate utilization and improving myocardial energy. The regulation of SGLT2 inhibitors on cardiac energy status including carbohydrates, fatty acids (FA), amino acids and ketones, ATP transfer to the cytoplasm, and mitochondrial functional status have received extensive attention in HF, but its specific mechanism of action is still unclear. Therefore, this article reviews the relationship between IR and HF from the perspective of energy metabolism; subsequently, targeting energy metabolism discusses the pivotal role of SGLT2 inhibitors in improving cardiac IR and HF based on basic and clinical research evidences, and sought to clarify the molecular mechanism involved. (Fig. 1).

16.
Phytochemistry ; 186: 112729, 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33721798

RESUMO

Five pairs of undescribed naphthalenone derivative enantiomers, xylarinaps A-E, including one pair of indole naphthalenones and four pairs of naphthalene-naphthalenone dimers, were isolated from the ethyl acetate extracts of the solid fermentation of Xylaria nigripes, which has been used as a traditional Chinese medicinal fungus for the treatment of insomnia, trauma, and depression. The structures of these enantiomers were elucidated based on comprehensive spectroscopic analysis, including NMR and HRESIMS. Their absolute configurations were assigned by the experimental and calculated ECD data. The neuroprotective effects of all the compounds against damage to PC12 cells by oxygen and glucose deprivation (OGD) were evaluated by an in vitro bioassay. The results revealed that xylarinaps A, B, D, and E significantly enhanced cell viability, decreased the levels of malondialdehyde (MDA), increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as further markedly inhibiting apoptosis, which indicated that these results could be the mode of action of their neuroprotective effect.

17.
J Stroke Cerebrovasc Dis ; 30(5): 105688, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33690028

RESUMO

OBJECTIVES: Acute kidney injury (AKI) following intracerebral hemorrhage (ICH) is an intractable medical complication and an independent predictor of short-term mortality. However, the correlation between AKI and long-term mortality has not been fully investigated. The aim of the present study was to determine the relationship between AKI following ICH and long-term mortality in a 10-year (2010-2019) retrospective cohort. MATERIALS AND METHODS: A total of 1449 ICH patients were screened and enrolled at the Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Medical University) from January 2010 to December 2016. The endpoint for follow-up was May 31, 2019. The estimated all-cause mortality was determined using Cox proportional hazard regression models. RESULTS: Among 1449 ICH patients, 136 (9.4%) suffered from AKI, and the duration of follow-up was a median of 5.1 years (IQR 3.2-7.2). The results indicated that the risk factors for AKI without preexisting chronic kidney disease (CKD) in the multivariable analysis were age (p = 0.002), nephrotoxic antibiotics (p = 0.000), diabetes mellitus (p = 0.005), sepsis (p = 0.000), antiplatelet therapy (p = 0.002), infratentorial hemorrhage (p = 0.000) and ICH volume (p = 0.003). Age (p = 0.008), ACEIs/ARBs (p = 0.010), nephrotoxic antibiotics (p = 0.014), coronary artery disease (p = 0.009), diabetes mellitus (p = 0.014), hypertension (p = 0.000) and anticoagulant therapy (p = 0.000) were independent predictors of AKI with preexisting CKD. Meanwhile, the data demonstrated that the estimated all-cause mortality was significantly higher in ICH patients with AKI without preexisting CKD (HR 4.208, 95% CI 2.946-6.011; p = 0.000) and in ICH patients with AKI with preexisting CKD (HR 2.470, 95% CI 1.747-3.492; p = 0.000) than in those without AKI. CONCLUSIONS: AKI is a long-term independent predictor of mortality in ICH patients. Thus, renal function needs to be routinely determined in ICH patients during clinical practice.

18.
Life Sci ; : 118957, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33524421

RESUMO

The main pathological feature of atherosclerosis is lipid metabolism disorder and inflammation. Macrophages, as the most important immune cells in the body, run through the beginning and end of disease development. After macrophages overtake the atherosclerosis-susceptible area apolipoprotein low-density lipoprotein ox-LDL, they transform into foam cells that adhere to blood vessels and recruit a large number of pro-inflammatory factors to initiate the disease. Promoting the outflow of lipids in foam cells and alleviating inflammation have become the basic ideas for the study of atherosclerosis treatment strategies. The polarization of macrophages refers to the estimation of the activation of macrophages at a specific point in space and time. Determining the proportion of different macrophage phenotypes in the plaque can help identify delay or prevent disease development. However, the abnormal polarization of macrophages and the accumulation of lipid also affect the growth state of cells to some extent, thus aggravate the influence on plaque area and stability. Besides, overactive or deficient autophagy of macrophages may also lead to cell death and participate in lipid metabolism and inflammation regression. In this paper, the role of macrophages in atherosclerosis was discussed from three aspects: polarization, death, and autophagy.

19.
Liver Int ; 41(4): 777-787, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33555112

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD), whose pathogenesis remains unelucidated, has become an increasingly prevalent disease globally requiring novel treatment strategies. This study aims to explore the role of leukocyte cell-derived chemotaxin 2 (LECT2), one of the known hepatokines, in the development of NAFLD. METHODS: The serum LECT2 level was evaluated in patients with NAFLD and male C57BL/6 mice fed a high-fat diet (HFD) for 8 weeks. Tail intravenous injection of adeno-associated virus that contained Lect2 short hairpin RNA or Lect2 overexpression plasmid was administered to mice to inhibit or increase hepatic Lect2 expression. Hepatic steatosis was evaluated by histological staining with haematoxylin and eosin and Oil Red O, and also by quantitative hepatic triglyceride measurements. RNA-seq was performed to discover the specific targets of LECT2 on NAFLD. RESULTS: Serum and hepatic LECT2 levels were elevated in NAFLD patients and HFD-fed mice. Inhibition of hepatic Lect2 expression alleviated HFD-induced hepatic steatosis and inflammation, whereas hepatic overexpression of Lect2 aggravated HFD-induced hepatic steatosis and inflammation. RNA-seq and bioinformatical analysis suggested that the signal transducers and activators of transcription-1 (STAT-1) pathway might play an indispensable role in the interaction between LECT2 and NAFLD. A STAT-1 inhibitor could reverse the accumulation of hepatic lipids caused by Lect2 overexpression. CONCLUSION: LECT2 expression is significantly elevated in NAFLD. LECT2 induces the occurrence and development of NAFLD through the STAT-1 pathway. LECT2 may be a potential therapeutic target for NAFLD.

20.
J Cell Mol Med ; 25(6): 2976-2993, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33591626

RESUMO

The aim of this study was to investigate how mesenchymal stromal cells (MSCs) modulate metabolic balance and attenuate hepatic lipotoxicity in the context of non-alcoholic fatty liver disease (NAFLD). In vivo, male SD rats were fed with high-fat diet (HFD) to develop NAFLD; then, they were treated twice by intravenous injections of rat bone marrow MSCs. In vitro, HepG2 cells were cocultured with MSCs by transwell and exposed to palmitic acid (PA) for 24 hours. The endoplasmic reticulum (ER) stressor thapsigargin and sarco/ER Ca2+ -ATPase (SERCA2)-specific siRNA were used to explore the regulation of ER stress by MSCs. We found that MSC administration improved hepatic steatosis, restored systemic hepatic lipid and glucose homeostasis, and inhibited hepatic ER stress in HFD-fed rats. In hepatocytes, MSCs effectively alleviated the cellular lipotoxicity. Particularly, MSCs remarkably ameliorated the ER stress and intracellular calcium homeostasis induced by either PA or thapsigargin in HepG2 cells. Additionally, long-term HFD or PA stimulation would activate pyroptosis in hepatocytes, which may contribute to the cell death and liver dysfunction during the process of NAFLD, and MSC treatment effectively ameliorates these deleterious effects. SERCA2 silencing obviously abolished the ability of MSCs against the PA-induced lipotoxicity. Conclusively, our study demonstrated that MSCs were able to ameliorate liver lipotoxicity and metabolic disturbance in the context of NAFLD, in which the regulation of ER stress and the calcium homeostasis via SERCA has played a key role.

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