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1.
Chemistry ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196050

RESUMO

Solar-driven photothermal antibacterial devices have attracted a lot of interest due to the fact that solar energy is one of the cleanest sources of energy in the world. However, conventional materials have a narrow absorbance band, resulting in deficient solar harvesting. In addition, lack of knowledge on temperature change in these devices during the photothermal process has also led to a waste of energy. Here, we presented an elegant multi-channel optical device with a multilayer structure to simultaneously address the above-mentioned issues in solar-driven antibacterial devices. In the photothermal channel, semiconductor IrO2 -nanoaggregates exhibited higher solar absorbance and photothermal conversion efficiency compared with nanoparticles. In the luminescence channel, thermal-sensitive Er-doped upconversion nanoparticles were utilized to reflect the microscale temperature in real-time. The bacteria were successfully inactivated during the photothermal effect under solar irradiation with temperature monitoring. This study could provide valuable insight for the development of smart photothermal devices for solar-driven photothermal bacterial inactivation in the future.

2.
Adv Mater ; : e2101316, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34302392

RESUMO

The magnetic Weyl fermion originates from the time reversal symmetry (TRS)-breaking in magnetic crystalline structures, where the topology and magnetism entangle with each other. Therefore, the magnetic Weyl fermion is expected to be effectively tuned by the magnetic field and electrical field, which holds promise for future topologically protected electronics. However, the electrical field control of the magnetic Weyl fermion has rarely been reported, which is prevented by the limited number of identified magnetic Weyl solids. Here, the electric field control of the magnetic Weyl fermion is demonstrated in an epitaxial SrRuO3 (111) thin film. The magnetic Weyl fermion in the SrRuO3 films is indicated by the chiral anomaly induced magnetotransport, and is verified by the observed Weyl nodes in the electronic structures characterized by the angle-resolved photoemission spectroscopy (ARPES) and first-principles calculations. Through the ionic-liquid gating experiment, the effective manipulation of the Weyl fermion by electric field is demonstrated, in terms of the sign-change of the ordinary Hall effect, the nonmonotonic tuning of the anomalous Hall effect, and the observation of the linear magnetoresistance under proper gating voltages. The work may stimulate the searching and tuning of Weyl fermions in other magnetic materials, which are promising in energy-efficient electronics.

3.
Adv Mater ; : e2103672, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34302404

RESUMO

Neuromorphic computing has become an increasingly popular approach for artificial intelligence because it can perform cognitive tasks more efficiently than conventional computers. However, it remains challenging to develop dedicated hardware for artificial neural networks. Here, a simple bilayer spintronic device for hardware implementation of neuromorphic computing is demonstrated. In L11 -CuPt/CoPt bilayer, current-inducted field-free magnetization switching by symmetry-dependent spin-orbit torques shows a unique domain nucleation-dominated magnetization reversal, which is not accessible in conventional bilayers. Gradual domain nucleation creates multiple intermediate magnetization states which form the basis of a sigmoidal neuron. Using the L11 -CuPt/CoPt bilayer as a sigmoidal neuron, the training of a deep learning network to recognize written digits, with a high recognition rate (87.5%) comparable to simulation (87.8%) is further demonstrated. This work offers a new scheme of implementing artificial neural networks by magnetic domain nucleation.

4.
Nat Med ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312556

RESUMO

Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. To prevent relapse with CD19- or CD19lo disease, we tested a bispecific CAR targeting CD19 and/or CD22 (CD19-22.BB.z-CAR) in a phase I clinical trial ( NCT03233854 ) of adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility and safety with a secondary efficacy end point. Primary end points were met; 97% of products met protocol-specified dose and no dose-limiting toxicities occurred during dose escalation. In B-ALL (n = 17), 100% of patients responded with 88% minimal residual disease-negative complete remission (CR); in LBCL (n = 21), 62% of patients responded with 29% CR. Relapses were CD19-/lo in 50% (5 out of 10) of patients with B-ALL and 29% (4 out of 14) of patients with LBCL but were not associated with CD22-/lo disease. CD19/22-CAR products demonstrated reduced cytokine production when stimulated with CD22 versus CD19. Our results further implicate antigen loss as a major cause of CAR T cell resistance, highlight the challenge of engineering multi-specific CAR T cells with equivalent potency across targets and identify cytokine production as an important quality indicator for CAR T cell potency.

5.
Am J Pathol ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34242656

RESUMO

Inflammation drives the development and progression of non-alcoholic steatohepatitis (NASH). The present study examined changes in intestinal inflammation during NASH. In male C57BL/6J mice, feeding a methionine- and choline-deficient diet (MCD) resulted in severe hepatic steatosis and inflammation relative to feeding a chow diet (CD). Also, MCD-fed mice revealed characteristics of mucosal and submucosal inflammatory responses and increased CD68-postive cells compared with CD-fed mice. Moreover, intestinal phosphorylation states of c-Jun N-terminal protein kinase (JNK) p46 and mRNA levels of interleukin (IL) 1 beta (IL1B), IL6, tumor necrosis factor alpha (TNF), and monocyte chemoattractant protein-1 were significantly higher and intestinal mRNA levels of IL4 and IL13 were significantly lower in MCD-fed mice compared to their respective levels in CD-fed mice. Surprisingly, upon treatment with MCD-mimicking media, the proinflammatory responses in cultured intestinal epithelial cells (IECs) (CMT-93 cells, a transformed epithelial cell line) did not differ significantly from those in IECs treated with control media. In contrast, in RAW264.7 cells (transformed macrophages), MCD-mimicking media significantly increased the phosphorylation states of JNK p46 and mitogen-activated protein kinases p38 and mRNA levels of IL1B, IL6, IL10, and TNF under either basal or lipopolysaccharide-stimulated conditions. Collectively, these results suggest that increased intestinal inflammation is associated with NASH phenotype. Additionally, elevated proinflammatory responses in macrophages likely contribute to, in large part, increased intestinal inflammation in NASH.

6.
Mol Cancer ; 20(1): 96, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301266

RESUMO

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

7.
Artigo em Chinês | MEDLINE | ID: mdl-34256900

RESUMO

BACKGROUND: Autophagy related genes (ARGs) regulate lysosomal degradation to induce autophagy, and are involved in the occurrence and development of a variety of cancers. The expression of ARGs in tumor tissues has a great prospect in predicting the survival of patients. The aim of this study was to construct a prognostic risk score model for lung adenocarcinoma (LUAD) based on ARGs. METHODS: 5,786 ARGs were obtained from GeneCards database. Gene expression profiles and clinical data of 395 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. All ARGs expression data were extracted, and The ARGs differentially expressed were identified by R software. Survival analysis of differentially expressed ARGs was performed to screen for ARGs with prognostic value, and functional enrichment analysis was performed. The least absolute selection operator (LASSO) regression and Cox regression model were used to construct a prognostic risk scoring model for ARGs. The receiver operating characteristic (ROC) curve was drawn to obtain the optimal cut-off value of risk score. According to the cut-off value, the patients were divided into high-risk group and low-risk group. The area under curve (AUC) and the Kaplan-Meier survival curve was plotted to evaluate the model performance, which was verified in external data sets. Finally, univariate and multivariate Cox regression analysis was applied to evaluate the independent prognostic value of the model, and its clinical relevance was analyzed. RESULTS: Survival analysis, Lasso regression and Cox regression analysis were used to construct a LUAD prognostic risk score model with five ARGs (ADAM12, CAMP, DKK1, STRIP2 and TFAP2A). The survival time of patients with low-risk score in this model was significantly better than that of patients with high-risk score (P<0.001). The model showed good prediction performance for LUAD in both the training set (AUCmax =0.78) and two external validation sets (AUCmax =0.88). Risk score was significantly associated with the prognosis of LUAD patients in univariate and multivariate Cox regression analyses, suggested that risk score could be a potential independent prognostic factor for LUAD. Correlation analysis of clinical characteristic showed that high risk score was closely associated with high T stage, high tumor stage and poor prognosis. CONCLUSIONS: We constructed a LUAD risk score model consisting of five ARGs, which can provide a reference for predicting the prognosis of LUAD patients, and may be used in combination with TNM staging for prognosis prediction of LUAD patients in the future.
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8.
Artigo em Inglês | MEDLINE | ID: mdl-34206436

RESUMO

The COVID-19 pandemic has greatly influenced society in the past few years. Park accessibility and social distancing are considered important under the threat of a long-term epidemic. However, measures that can maintain park accessibility and diminish virus spreading synchronously have been seldom studied before, which may threaten public health in all major urban parks globally. This paper proposed a methodology based on an agent-based model to analyze capacities for parks by simulating park visitor behaviors when they all are social distancing. The model was derived from historical visitor data and realistic visitor behaviors in three park settings. Then, park capacities of varied contact conditions, different park policies, and layout adjustments were analyzed. First, congestions caused by social distancing without proper visitor control are found inside all parks. Second, 85 to 3972 square meters per person is predicted as a safe space in different parks. Third, the current results can be easily adjusted according to various concerns regarding infection distance and rate. Finally, it can be inferred that information provisions are more effective than space design adjustments and mandatory measures. The results can guide park managers and those who plan and design park settings. They are also helpful in improving knowledge of the mechanisms behind visitor behaviors. Moreover, these findings can be tested and verified in a variety of public spaces with many other contact-based illnesses.


Assuntos
COVID-19 , Parques Recreativos , Humanos , Pandemias , Distanciamento Físico , Recreação , SARS-CoV-2 , Análise de Sistemas
9.
BMJ Open ; 11(7): e046442, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215605

RESUMO

INTRODUCTION: Several studies have evaluated the diagnostic values of D-dimer and fibrin degradation product (FDP) for detecting periprosthetic joint infection (PJI), but their conclusions have been inconsistent. More importantly, whether the diagnostic value of these two biomarkers differs depending on whether they are assayed in plasma or serum is unclear. METHODS AND ANALYSIS: This prospective single-centre, parallel comparative study will involve patients planning to undergo revision hip or knee arthroplasty due to an aseptic mechanical failure or PJI. After the patients provide written informed consent, their serum and plasma will be sampled and assayed for D-dimer and FDP. The diagnostic value of these two biomarkers in plasma and serum will be compared with one another and with the value of two traditional inflammatory markers (C reactive protein and erythrocyte sedimentation rate) used to diagnose PJI according to the 2013 International Consensus Meeting criteria. Diagnostic value will be assessed in terms of area under receiver operating characteristic curves, sensitivity, specificity, as well as positive and negative predictive values, all calculated based on the optimal cut-off determined from the Youden index. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of our hospital (approval no. 2020-859). Written informed consent will be obtained from all patients before enrollment. Study findings will be disseminated widely through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038547), and it is ongoing.

10.
Ann Palliat Med ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34263634

RESUMO

BACKGROUND: This study aimed to investigate independent risk factors of postoperative hypoxemia in patients with acute type A aortic dissection (ATAAD). METHODS: A single-center retrospective study was conducted with enrolled 75 ATAAD patients following surgery, which were stratified into three groups on the basis of the postoperative PaO2/FiO2 ratio: severe hypoxemia group (PaO2/FiO2 ratio ≤100 mmHg); moderate hypoxemia group (100 mmHg < PaO2/FiO2 ratio ≤200 mmHg); and non-hypoxemia group (PaO2/FiO2 ratio >200 mmHg). The patient's demography, perioperative laboratory results, operative details, clinical outcomes were collected and analyzed. Univariable and multivariable analyses were performed and logistic regression model was established. RESULTS: The incidence of postoperative severe hypoxemia and hypoxemia was 32% and 52%, respectively. Among the three groups, severe hypoxemia group exhibited a high significance of body mass index (BMI) and preoperative white blood cell (WBC) and main distribution of hypertension; meanwhile, Marfan syndrome was mainly distributed in non-hypoxemia group. On intensive care unit (ICU) admission, severe hypoxemia group exhibited a high significance of Acute Physiology and Chronic Health Evaluation (APACHE II) score of postoperative patients, and more patients would present shock. Moreover, severe hypoxemia group patients had a higher incidence of postoperative acute kidney injury (AKI) and usage of renal replacement therapy, longer length of stay (LOS) of ICU, and shorter 28 days ventilator-free days (VFDs). CONCLUSIONS: The incidence of postoperative hypoxemia was high in ATAAD patients owing to comprehensive high-risk factors. Besides, postoperative complications negatively impacted their clinical outcomes.

11.
Sci Rep ; 11(1): 14636, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282208

RESUMO

Finding effective and objective biomarkers to inform the diagnosis of schizophrenia is of great importance yet remains challenging. Relatively little work has been conducted on multi-biological data for the diagnosis of schizophrenia. In this cross-sectional study, we extracted multiple features from three types of biological data, including gut microbiota data, blood data, and electroencephalogram data. Then, an integrated framework of machine learning consisting of five classifiers, three feature selection algorithms, and four cross validation methods was used to discriminate patients with schizophrenia from healthy controls. Our results show that the support vector machine classifier without feature selection using the input features of multi-biological data achieved the best performance, with an accuracy of 91.7% and an AUC of 96.5% (p < 0.05). These results indicate that multi-biological data showed better discriminative capacity for patients with schizophrenia than single biological data. The top 5% discriminative features selected from the optimal model include the gut microbiota features (Lactobacillus, Haemophilus, and Prevotella), the blood features (superoxide dismutase level, monocyte-lymphocyte ratio, and neutrophil count), and the electroencephalogram features (nodal local efficiency, nodal efficiency, and nodal shortest path length in the temporal and frontal-parietal brain areas). The proposed integrated framework may be helpful for understanding the pathophysiology of schizophrenia and developing biomarkers for schizophrenia using multi-biological data.

12.
Nat Commun ; 12(1): 4445, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290245

RESUMO

Immune checkpoint inhibitors demonstrate clinical activity in many tumor types, however, only a fraction of patients benefit. Combining CD137 agonists with these inhibitors increases anti-tumor activity preclinically, but attempts to translate these observations to the clinic have been hampered by systemic toxicity. Here we describe a human CD137xPD-L1 bispecific antibody, MCLA-145, identified through functional screening of agonist- and immune checkpoint inhibitor arm combinations. MCLA-145 potently activates T cells at sub-nanomolar concentrations, even under suppressive conditions, and enhances T cell priming, differentiation and memory recall responses. In vivo, MCLA-145 anti-tumor activity is superior to immune checkpoint inhibitor comparators and linked to recruitment and intra-tumor expansion of CD8 + T cells. No graft-versus-host-disease is observed in contrast to other antibodies inhibiting the PD-1 and PD-L1 pathway. Non-human primates treated with 100 mg/kg/week of MCLA-145 show no adverse effects. The conditional activation of CD137 signaling by MCLA-145, triggered by neighboring cells expressing >5000 copies of PD-L1, may provide both safety and potency advantages.

13.
PLoS One ; 16(7): e0254891, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34293043

RESUMO

The geographical variation of maternal dietary patterns related to birth outcomes is important for improving the health of mothers and children; however, it is currently unknown. Thus, the objective of the study was to investigate geographical variations of maternal dietary pattern during pregnancy, and evaluate the spatial varying association of maternal dietary patterns in pregnancy with abnormal birth weight. A population-based cross-sectional study was conducted in Shaanxi province in Northwest China in 2013 to evaluate the relationship between abnormal birth weight and dietary pattern using the Geographically Weighted Logistic Regression (GWLR). Three dietary patterns during pregnancy were extracted through factor analysis, explaining approximately 45.8% of the variability of food intake. Approximately 81.6% of mothers with higher scores on the equilibrium pattern was more unlikely to have small for gestational age (SGA) infants, with the lower OR observed in Central and South Shaanxi. The snacks pattern was positively associated with low birth weight (LBW) for 23.2% of participants, with the highest OR in Central Shaanxi. Among about 80.0% of participants with higher scores on the snacks pattern living in South and Central Shaanxi, there was a higher risk for SGA. The OR values tend to descend from South to North Shaanxi. The OR values of the negative association between prudent pattern and LBW decreased from South to North Shaanxi among approximately 59.3% of participants. The prudent pattern was also negatively associated with the increasing risk of fetal macrosomia among 19.2% of participants living mainly in South Shaanxi. The association of maternal dietary patterns during pregnancy with abnormal birth weight varied geographically across Shaanxi province. The findings emphasize the importance of geographical distribution to improve the dietary patterns among disadvantaged pregnant women.

14.
Commun Biol ; 4(1): 905, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294876

RESUMO

Natural Killer (NK) cell dysfunction is associated with poorer clinical outcome in cancer patients. What regulates NK cell dysfunction in tumor microenvironment is not well understood. Here, we demonstrate that the human tumor-derived NKG2D ligand soluble MIC (sMIC) reprograms NK cell to secrete pro-tumorigenic cytokines with diminished cytotoxicity and polyfunctional potential. Antibody clearing sMIC restores NK cell to a normal cytotoxic effector functional state. We discovered that sMIC selectively activates the CBM-signalosome inflammatory pathways in NK cells. Conversely, tumor cell membrane-bound MIC (mMIC) stimulates NK cell cytotoxicity through activating PLC2γ2/SLP-76/Vav1 pathway. Ultimately, antibody targeting sMIC effectuated the in vivo anti-tumor effect of adoptively transferred NK cells. Our findings uncover an unrecognized mechanism that could instruct NK cell to a dysfunctional state in response to cues in the tumor microenvironment. Our findings provide a rationale for co-targeting sMIC to enhance the efficacy of the ongoing NK cell-based cancer immunotherapy.

15.
Cell ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34297923

RESUMO

Retinal ganglion cells (RGCs) are the sole output neurons that transmit visual information from the retina to the brain. Diverse insults and pathological states cause degeneration of RGC somas and axons leading to irreversible vision loss. A fundamental question is whether manipulation of a key regulator of RGC survival can protect RGCs from diverse insults and pathological states, and ultimately preserve vision. Here, we report that CaMKII-CREB signaling is compromised after excitotoxic injury to RGC somas or optic nerve injury to RGC axons, and reactivation of this pathway robustly protects RGCs from both injuries. CaMKII activity also promotes RGC survival in the normal retina. Further, reactivation of CaMKII protects RGCs in two glaucoma models where RGCs degenerate from elevated intraocular pressure or genetic deficiency. Last, CaMKII reactivation protects long-distance RGC axon projections in vivo and preserves visual function, from the retina to the visual cortex, and visually guided behavior.

16.
Adv Healthc Mater ; : e2101043, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319657

RESUMO

The incidence of inflammatory bowel diseases (IBD), including Crohn's diseases and ulcerative colitis, is increasing by time and showing a trend of younger age. Precise diagnosis and effective treatments for IBD have attracted growing attention in recent years. However, diagnosing and locating inflammatory lesions remain a great challenge for IBD. In this study, assisted by a kind of aggregation-induced emission (AIE) nanoprobes (BPN-BBTD nanoparticles [NPs]), the second near-infrared (NIR-II) fluorescence imaging is first utilized to accurately trace inflammatory lesions, monitor inflammation severity and detect the response to the drug intervention in IBD mouse models. Through the advantages of high signal-to-background ratio (SBR) and sharp spatial resolution of bio-imaging in NIR-II region, the NIR-II fluorescence imaging-guided surgery can help to achieve a complete resection of severe inflammatory bowls and a secure surgical anastomosis. In addition, with the help of NIR-II fluorescence wide-field microscopy, the distribution of BPN-BBTD NPs can be directly detected in tissue level and found to be mainly accumulated in mucosa and submucosa layers. This study highlights that AIE NPs-assisted NIR-II fluorescence imaging hold a great potential value for future diagnosis and imaging-guided surgery in IBD.

17.
HPB (Oxford) ; 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34217591

RESUMO

BACKGROUND: To evaluate the event rate of major adverse kidney events within 30 days (MAKE30) in acute pancreatitis (AP) and its potential risk factors. METHODS: A retrospective analysis of a tertiary center data on all AP patients admitted within 72 h after onset of abdominal pain between June 2015 and June 2019 was conducted. MAKE30 - a composite of death, new renal replacement therapy (RRT), or persistent renal dysfunction (PRD) - and its individual components were retrieved at discharge or 30 days. Logistic regression analysis was used to assess the risk factors for MAKE30. RESULTS: 295 patients were enrolled and 16% experienced MAKE30. For individual components, the incidence was 3% for death, 15% for new RRT, and 5% for PRD. In multivariate logistic regression analysis, hyperchloremia at admission [OR = 8.38 (1.07-65.64); P = 0.043] and SOFA score [OR 1.63 (1.18-2.26); P = 0.003] were independent risk factors in predicting MAKE30. Further analysis showed that patients with hyperchloremia had more requirements of RRT (57% vs. 10%, P < 0.001), more PRD (14% vs. 4%, P = 0.034). CONCLUSION: MAKE30 is a common event in AP patients. Hyperchloremia and SOFA score at admission were two independent risk factors for MAKE30.

18.
Chem Biol Interact ; : 109569, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34197824

RESUMO

As one of the most important members of Phthalate esters (PAEs), di-(2-ethylhexyl) phthalate (DEHP) is widely used in plastics and known as a male reproductive toxicant. Many studies have shown that soybean isoflavones (SI) can rescue the testicular injury caused by DEHP, but the underlying mechanism is unknown. Because methylation is one of the most important mechanisms for maintaining normal biological functions, we studied whether methylation is involved in testicular injury induced by DEHP and whether SI could counter testicular impairment in peripubertal male Sprague Dawley rats. Compared with the control group, we found that the mRNA levels of testicular Sod2, Gpx1, and Igf-1 significantly decreased in the 900 mg/kg DEHP group (DEHP' group) (P < 0.01); however, in the DEHP + SI group, the mRNA levels of the genes obviously increased compared with the DEHP' group (P < 0.01). Simultaneously, the methylation level changes of testicular Sod2, Gpx1, and Igf-1 were similar to the mRNA levels (P < 0.01). Therefore, DEHP may affect testis and leydig cells via inducing methylation of Sod2, Gpx1, and Igf-1, and SI may rescue the impairments at the methylation level. In summary, SI is supposed to be used in DEHP-induced testicular injury treatment.

19.
Biosci Trends ; 2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34248133

RESUMO

Circulating inflammatory factors affect osteoblast and osteoclast formation and activity in osteoporosis. Estrogen affects the migration of Th17 cells via the C-C chemokine receptor type 6 (CCR6) and C-C chemokine ligand 20 (CCL20) signaling pathways to modulate bone metabolism; however, it is unclear whether and how CCR6 modulates bone homeostasis. In the present study, CCR6 knockout (CCR6-/-) mice were selected to investigate the effects of CCR6 in the regulation of homeostasis of osteoblasts and osteoclasts. Primary osteoblasts were isolated from the calvarium of newborn CCR6-/- or wild-type mice, followed by osteoblastic differentiation culture in vitro. CCR6 deletion reduced osteoblast activity in terms of alkaline phosphatase (ALP) activity and inhibited osteoblast mineralization according to the results of Alizarin Red S staining, whereas it did not affect the proliferation of osteoblasts. CCR6 deletion inhibited Osterix mRNA expression in osteoblasts during the late stage of mineralization in vitro, while it did not affect mRNA expression levels of runt-related transcription factor 2 (Runx2) and Collagen-1. The ratio of osteoprotegerin (OPG) /receptor activator of nuclear factor κ-Β ligand (RANKL) mRNA level in osteoblasts was decreased by CCR6 deficiency in the culture treated with 1,25(OH)2D3/PGE2, while there was no effect observed in the normal culture environment. The results provide novel insights, such as that CCR6 deletion suppresses osteoblast differentiation by downregulating the expression levels of the transcription factor Osterix, and indirectly promotes osteoclast production by increasing transcription of RANKL. This may be one of the mechanisms via which CCR6 deletion regulates bone metabolism.

20.
Ren Fail ; 43(1): 1155-1162, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34266358

RESUMO

BACKGROUND: Acute kidney injury (AKI) is one of the most common complications after cardiac surgery. However, effective biomarker used for early diagnosis of AKI has not been identified. Platelet-leukocyte aggregates (PLAs) participate in inflammation and coagulation, leading to vascular lesions and tissue destruction. We designed a prospective study to assess whether PLAs can serve as a good biomarker for early diagnosis of AKI after cardiac surgery. METHODS: Patients with rheumatic heart disease scheduled to undergo valve replacement surgery were enrolled. Blood samples were collected at five timepoints as follows: (a) At baseline. (b) At the end of extracorporeal circulation. (c) Arrival at intensive care unit (ICU). (d) Four-hours after the admission to ICU. (e) Twenty hours after the admission to ICU. After collection, the samples were immediately used for PLAs measurement by flow cytometry. RESULTS: A total of 244 patients were registered, and 15 of them were diagnosed with AKI according to the serum creatinine of KDIGO guidelines. The PLAs levels in AKI group were significantly increased 20 h after surgery (two-way repeated measure analysis of variance, p < 0.01) compared with that at baseline. Patients whose preoperative PLAs were higher than 6.8% showed increased risk of developing AKI (multivariate logistic regression; p = 0.01; adjusted odds ratio, 1.05; 95% confidence interval, 1.01-1.09). CONCLUSION: PLAs is an independent risk factor for AKI after valve replacement among patients with rheumatic heart disease.

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