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1.
Oxid Med Cell Longev ; 2021: 5876841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603599

RESUMO

Myocardial fibrosis represents the primary pathological change associated with diabetic cardiomyopathy and heart failure, and it leads to decreased myocardial compliance with impaired cardiac diastolic and systolic function. Quercetin, an active ingredient in various medicinal plants, exerts therapeutic effects against cardiovascular diseases. Here, we investigate whether SIRT5- and IDH2-related desuccinylation is involved in the underlying mechanism of myocardial fibrosis in heart failure while exploring related therapeutic drugs for mitochondrial quality surveillance. Mouse models of myocardial fibrosis and heart failure, established by transverse aortic constriction (TAC), were administered with quercetin (50 mg/kg) daily for 4 weeks. HL-1 cells were pretreated with quercetin and treated with high glucose (30 mM) in vitro. Cardiac function, western blotting, quantitative PCR, enzyme-linked immunosorbent assay, and immunofluorescence analysis were employed to analyze mitochondrial quality surveillance, oxidative stress, and inflammatory response in myocardial cells, whereas IDH2 succinylation levels were detected using immunoprecipitation. Myocardial fibrosis and heart failure incidence increased after TAC, with abnormal cardiac ejection function. Following high-glucose treatment, HL-1 cell activity was inhibited, causing excess production of reactive oxygen species and inhibition of mitochondrial respiratory complex I/III activity and mitochondrial antioxidant enzyme activity, as well as increased oxidative stress and inflammatory response, imbalanced mitochondrial quality surveillance and homeostasis, and increased apoptosis. Quercetin inhibited myocardial fibrosis and improved cardiac function by increasing mitochondrial energy metabolism and regulating mitochondrial fusion/fission and mitochondrial biosynthesis while inhibiting the inflammatory response and oxidative stress injury. Additionally, TAC inhibited SIRT5 expression at the mitochondrial level and increased IDH2 succinylation. However, quercetin promoted the desuccinylation of IDH2 by increasing SIRT5 expression. Moreover, treatment with si-SIRT5 abolished the protective effect of quercetin on cell viability. Hence, quercetin may promote the desuccinylation of IDH2 through SIRT5, maintain mitochondrial homeostasis, protect mouse cardiomyocytes under inflammatory conditions, and improve myocardial fibrosis, thereby reducing the incidence of heart failure.

2.
Contrast Media Mol Imaging ; 2021: 2146578, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497480

RESUMO

This exploration aims to investigate the important role of magnetic resonance imaging (MRI) in the diagnosis of ovarian cancer under the ADNEX. From March 2017 to December 2019, 84 patients with ovarian cancer confirmed by pathological operation were selected as the research objects. The consistency of ADNEX, MRI, and ADNEX∗MRI in the diagnosis and staging of ovarian cancer was calculated separately. SPSS 26.0 statistical software was used to compare the accuracy, sensitivity, specificity, and diagnostic value of the two diagnostic methods. The results show that the accuracy and sensitivity of ADNEX are 78.6% and 93.2%, respectively. The accuracy and sensitivity of MRI are 81.2% and 89.4%, respectively. There is no significant difference between the two methods (p < 0.05). The overall consistency rates of ADNEX∗MRI, MRI diagnosis, and ADNEX for ovarian cancer staging are 94.2%, 74%, and 65.4%, respectively. There was a significant difference (p < 0.05). ADNEX∗MRI and MRI diagnosis were compared with each stage of ADNEX. There is a significant difference between the second and fourth stages (p < 0.05), and there is also a significant difference in the fourth stage (p < 0.017). It is concluded that MRI diagnosis of ovarian cancer based on ADNEX is superior to ADNEX and MRI examination alone, which provides a certain reference value for clinical staging of ovarian cancer.

3.
J Colloid Interface Sci ; 607(Pt 1): 769-781, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34536934

RESUMO

In this study, non-noble metal Cd decorated cubic phase CdS (CdS/Cd) thin layer on a millimeter-scale chitosan-Mg(OH)2 xerogel beads (CMB) were elaborately designed and successfully synthesized via facile hydrated electrons (eaq•-) assistant strategy. The in-situ formation of metallic Cd was driven by eaq•- generated from UV/Na2SO3 process. Owing to metallic Cd, CMB@CdS/Cd exhibited better visible-light absorption ability and more efficient separation capability for photo-induced carriers, its hydrogen production efficiency was about threefold improved compared to CMB@CdS. Both characterization methods and density functional theory calculations determined a built-in electric field from metallic Cd to CdS and Ohmic-contact between Cd and CdS, which largely promoted the carriers transfer efficiency. Moreover, the introduction of metallic Cd on the CdS could reduce the ΔGH*, thus greatly boosting the photocatalytic hydrogen production efficiency. This work provides a simple and green approach to construct metallic Cd coupled semiconductor to achieve efficient photocatalytic applications.

4.
Tissue Eng Part C Methods ; 27(8): 481-486, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34376080

RESUMO

Meniscus injury is a health problem that greatly affects people's quality of life. In recent years, the number of diagnosed meniscus injury is increasing year by year. If not treated in time and correctly, it causes severe damages to the cartilage. Owing to the meniscus' limited healing ability, synthetic/tissue-engineered meniscus has emerged as a new treatment modality in recent years. Rabbit models, which have been proved to be a feasible animal model, have been extensively used to study meniscus implantation. However, there is not a unified and minimally invasive surgical method for meniscus implantation in rabbits, and the current surgical methods have unsolved problems, such as long incisions, patella valgus, and cutting of the medial collateral ligament. Therefore, the goal of this study is to provide a minimally invasive and versatile meniscus implantation method. Compared with the control group, our study showed less trauma to the animal model, and we believe that it has the application significance on tissue-engineered meniscus implantation. Impact statement Meniscal injury is a central area of sports medicine research because of the high and increasing global rate. With its profound potential implications for patients' functions and the subsequent development of arthritis, there is a great need for the synthetic/tissue-engineered menisci. Animal meniscus implantation models allow studying meniscus implantation with synthetic/tissue-engineered meniscus, and the rabbit model is a gold method for meniscus implantation in the laboratory. However, there has not yet been a minimally invasive and versatile surgical technique describing this surgery method. This article, therefore, provides a detailed description of the rabbit meniscus implantation method, including step-by-step surgical instructions and accompanying pictures.

5.
Nat Commun ; 12(1): 4721, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354057

RESUMO

G protein-coupled receptors (GPCRs) are the most common proteins targeted by approved drugs. A complete mechanistic elucidation of large-scale conformational transitions underlying the activation mechanisms of GPCRs is of critical importance for therapeutic drug development. Here, we apply a combined computational and experimental framework integrating extensive molecular dynamics simulations, Markov state models, site-directed mutagenesis, and conformational biosensors to investigate the conformational landscape of the angiotensin II (AngII) type 1 receptor (AT1 receptor) - a prototypical class A GPCR-activation. Our findings suggest a synergistic transition mechanism for AT1 receptor activation. A key intermediate state is identified in the activation pathway, which possesses a cryptic binding site within the intracellular region of the receptor. Mutation of this cryptic site prevents activation of the downstream G protein signaling and ß-arrestin-mediated pathways by the endogenous AngII octapeptide agonist, suggesting an allosteric regulatory mechanism. Together, these findings provide a deeper understanding of AT1 receptor activation at an atomic level and suggest avenues for the design of allosteric AT1 receptor modulators with a broad range of applications in GPCR biology, biophysics, and medicinal chemistry.


Assuntos
Receptor Tipo 1 de Angiotensina/química , Receptor Tipo 1 de Angiotensina/metabolismo , Regulação Alostérica , Sítio Alostérico , Sítios de Ligação/genética , Desenho de Fármacos , Humanos , Cadeias de Markov , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Conformação Proteica , Receptor Tipo 1 de Angiotensina/genética , Transdução de Sinais , beta-Arrestinas/metabolismo
6.
Nat Commun ; 12(1): 4452, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294713

RESUMO

Atherosclerosis-associated cardiovascular disease is one of the main causes of death and disability among patients with diabetes mellitus. However, little is known about the impact of S-nitrosylation in diabetes-accelerated atherosclerosis. Here, we show increased levels of S-nitrosylation of guanine nucleotide-binding protein G(i) subunit alpha-2 (SNO-GNAI2) at Cysteine 66 in coronary artery samples from diabetic patients with atherosclerosis, consistently with results from mice. Mechanistically, SNO-GNAI2 acted by coupling with CXCR5 to dephosphorylate the Hippo pathway kinase LATS1, thereby leading to nuclear translocation of YAP and promoting an inflammatory response in endothelial cells. Furthermore, Cys-mutant GNAI2 refractory to S-nitrosylation abrogated GNAI2-CXCR5 coupling, alleviated atherosclerosis in diabetic mice, restored Hippo activity, and reduced endothelial inflammation. In addition, we showed that melatonin treatment restored endothelial function and protected against diabetes-accelerated atherosclerosis by preventing GNAI2 S-nitrosylation. In conclusion, SNO-GNAI2 drives diabetes-accelerated atherosclerosis by coupling with CXCR5 and activating YAP-dependent endothelial inflammation, and reducing SNO-GNAI2 is an efficient strategy for alleviating diabetes-accelerated atherosclerosis.


Assuntos
Aterosclerose/etiologia , Aterosclerose/metabolismo , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Células Cultivadas , Cisteína/química , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/química , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Melatonina/farmacologia , Camundongos , Camundongos Knockout , Mutagênese Sítio-Dirigida , Óxido Nítrico Sintase Tipo II/metabolismo , Compostos Nitrosos/química , Compostos Nitrosos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores CXCR5/deficiência , Receptores CXCR5/genética , Receptores CXCR5/metabolismo , Fatores de Transcrição/metabolismo
7.
J Healthc Eng ; 2021: 6626957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257852

RESUMO

In order to improve the effect of human motion rehabilitation, a design model of human motion rehabilitation based on object-oriented technology is proposed. The entire model design process includes the following steps. First, a visual dynamic tracking model for human motion rehabilitation is established, and then a fuzzy PID (Proportion Integration Differentiation) superheterodyne control method is used to design the bone training control for human motion rehabilitation. The bone tracking control and adaptive training are under the control of object-oriented technology; it is analyzed by collecting human activity data during training. The 6-DOF kinematics problem of human movement rehabilitation is decomposed into the bone training control problem in the subspace. Combining object-oriented technology, visual blur recognition of human sports rehabilitation training, and adopting an adaptive kinematics model to design sports rehabilitation can improve the control convergence and global stability of the human sports rehabilitation process. The simulation results show that the method has a good overall steady state and the sports rehabilitation training effect is obvious.

8.
Environ Sci Pollut Res Int ; 28(32): 43035-43049, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34125384

RESUMO

Urban drainage pipeline systems collect and transport domestic sewage, industrial wastewater, and rainwater. They are important components of urban infrastructure. The quality of drainage facilities directly determines the level of urban development and affects the urban landscape and sanitary environment. In recent years, however, the phenomenon of "attaching importance to construction, despising management and maintenance" has prevailed in China's urban drainage pipeline network. The problems such as structural damage, corrosion, and blockage of the sewage pipelines are becoming increasingly prominent in China, causing a lot of operational challenges such as direct discharge of sewage, backward irrigation of river and lake water, infiltration of external water, and overflow pollution. To comprehensively acquire these information about China's urban drainage pipeline network, this paper reviews current status of construction, operation, management and maintenance, existent problems, and coping strategy of the sewage pipelines. Finally, future directions are also discussed in detail for rational construction and maintenance of sewage pipelines.


Assuntos
Esgotos , Águas Residuárias , Adaptação Psicológica , China , Rios , Esgotos/análise , Águas Residuárias/análise
9.
ACS Sens ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34132539

RESUMO

Methotrexate (MTX), a folate antagonist drug, has been widely used for treating various cancers. Since high-dose MTX treatment can cause unwanted serious side effects, tracking the blood concentration of MTX is essential for safe medication. However, available methods are often complex, time-consuming, and expensive. In this study, a highly selective DNA aptamer was selected for recognizing MTX based on a capture-systematic evolution of ligands by an exponential enrichment (C-SELEX) approach. Taking advantage of our selected MTX aptamer, we further unveil a novel structure-switching fluorescent sensor for the specific and rapid monitoring of MTX with good analytical performances (i.e., a linear detection range of 0.1-2 µM with a low detection limit (LOD) of 0.03 µM in buffer and a linear detection range of 0.5-10 µM with an LOD of 0.18 µM in 50% serum). Compared with conventional methods, this assay has great potential for detecting the blood concentration of MTX in clinical use. By coupling with other sensory techniques, our presented aptamer will potentially inspire the development of various sensors toward the monitoring of MTX.

10.
Int J Mol Med ; 48(1)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33955518

RESUMO

Women experience cognitive decline as they age due to the decrease in estrogen levels following menopause. Currently, effective pharmaceutical treatments for age­related cognitive decline are lacking; however, several Traditional Chinese medicines have shown promising effects. Lycium barbarum polysaccharides (LBPs) were found to exert a wide variety of biological activities, including anti­inflammatory, antioxidant and anti­aging effects. However, to the best of our knowledge, the neuroprotective actions of LBP on cognitive impairment induced by decreased levels of estrogen have not yet been determined. To evaluate the effects of LBP on learning and memory impairment in an animal model of menopause, 45 female ICR mice were randomly divided into the following three groups: i) Sham; ii) ovariectomy (OVX); and iii) OVX + LBP treatment. The results of open­field and novel object recognition tests revealed that mice in the OVX group had learning and memory impairments, and lacked the ability to recognize and remember new objects. Notably, these deficits were attenuated following LBP treatment. Immunohistochemical staining confirmed the protective effects of LBP on hippocampal neurons following OVX. To further investigate the underlying mechanism of OVX in mice, mRNA sequencing of the hippocampal tissue was performed, which revealed that the Toll­like receptor 4 (TLR4) inflammatory signaling pathway was significantly upregulated in the OVX group. Moreover, reverse transcription­quantitative PCR and immunohistochemical staining demonstrated that OVX induced hippocampal injury, upregulated the expression levels of TLR4, myeloid differentiation factor 88 and NF­κB, and increased the expression of TNF­α, IL­6 and IL­1ß inflammatory factors. Conversely, LBP treatment downregulated the expression levels of mRNAs and proteins associated with the TLR4/NF­κB signaling pathway, decreased the inflammatory response and reduced neuronal injury in mice that underwent OVX. In conclusion, the findings of the present study indicated that oral LBP treatment may alleviate OVX­induced cognitive impairments by downregulating the expression levels of mRNAs and proteins associated with the TLR4/NF­κB signaling pathway, thereby reducing neuroinflammation and damage to the hippocampal neurons. Thus, LBP may represent a potential agent for the prevention of learning and memory impairments in patients with accelerated aging caused by estrogen deficiency.

11.
Cell Death Dis ; 12(5): 470, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976108

RESUMO

Endothelial-to-mesenchymal transition (EndMT) has been shown to contribute to cardiac fibrosis and heart failure (HF). Recent studies have demonstrated that EndMT is regulated by autophagy, and we previously showed suppression of excessive autophagy and alleviation of cardiac fibrosis in HF mice with inactivated receptor for advanced glycation end products (RAGE). Thus, we investigated whether reduced cardiac fibrosis due to RAGE knockout occurred by inhibiting EndMT mediated by excessive autophagy. We found a decrease in endothelial cells (CD31+/VE-Cadherin+) and an increase in cells co-expressing CD31 and α-smooth muscle actin (α-SMA, myofibroblast marker) at 8 weeks in heart tissue of mice subjected to transverse aortic constriction (TAC), which implied EndMT. Knockout RAGE decreased EndMT accompanied by decreased expression of autophagy-related proteins (LC3BII/I and Beclin 1), and alleviated cardiac fibrosis and improved cardiac function in TAC mice. Moreover, 3-methyladenine (3-MA) and chloroquine (CQ), inhibitors of autophagy, attenuated EndMT, and cardiac fibrosis in TAC mice. Importantly, EndMT induced by AGEs could be blocked by autophagy inhibitor in vivo and in vitro. These results suggested that AGEs/RAGE-autophagy-EndMT axis involved in the development of cardiac fibrosis and knockout RAGE ameliorated cardiac fibrosis through decreasing EndMT regulated by autophagy, which could be a promising therapeutic strategy for HF.


Assuntos
Autofagia/genética , Transição Epitelial-Mesenquimal/genética , Fibrose/fisiopatologia , Cardiopatias/fisiopatologia , Insuficiência Cardíaca/genética , Receptor para Produtos Finais de Glicação Avançada/genética , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos
12.
J Knee Surg ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33932945

RESUMO

The purpose of this study was to (1) compare the efficacy of root repair versus partial meniscectomy and observation for patients with meniscus root tears; (2) compare osteoarthritis (OA) progression and functional outcomes in patients with isolated repair and with adjuvant surgery; and (3) evaluate OA progression and functional outcomes after pullout repair or all-inside repair of meniscus root tears. We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane Library up to September 1, 2020, to identify studies that evaluated the efficacy of root repair versus partial meniscectomy and observation in patients with meniscus root tears. Random-effects meta-analysis was used to pool data. A total of nine studies were included in the meta-analysis, with 485 patients comprising 238 in the root repair group, 113 in the partial meniscectomy group, and 134 in the observation group. The mean age of the patients ranged from 46.1 to 64.8 years. Compared with partial meniscectomy, root repair was associated with significantly lower postoperative Kellgren-Lawrence (K-L) grade (mean difference [MD]: -0.62, 95% confidence interval [CI]: -1.00 to -0.23) and progression to arthroplasty rate (odds ratio [OR]: 0.15, 95% CI: 0.04-0.60) at final follow-up. Compared with observation, root repair was associated with significantly lower arthroplasty rate (OR: 0.07, 95% CI: 0.01-0.44) and better International Knee Documentation Committee (IKDC) score (MD: 8.07, 95% CI: 0.72-15.41) at final follow-up. Moreover, significantly lower postoperative K-L grade and progression to arthroplasty rate, as well as higher IKDC and Lysholm scores were seen in favor of root repair in patients with isolated meniscus root tears. Additionally, significantly lower OA progression and higher function scores were found in favor of root repair when the tears were repaired with pullout technique. Current evidence indicates that root repair with pullout technique may be a better choice than partial meniscectomy and observation for patients with isolated meniscus root tears as measured by OA progression, progression to arthroplasty, as well as functional outcomes.

13.
Water Sci Technol ; 83(9): 2063-2074, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33989176

RESUMO

The corrosion and odor in concrete sewers are mainly related to the sulfide production, which is, under certain circumstances, directly proportional to the hydraulic retention time (HRT) of the sewer. To reduce the corrosion and control the odor in concrete sewers, it is necessary to model the production of sulfide in the concrete sewers with different HRTs. However, previous researches were mostly carried out in simulated Perspex-made sewers, and the obtained theoretical formulas based on the Monod equation were impractical because of the complexity. An actual concrete pipe with domestic sewage was employed in this study to obtain a simple but practical model, which can be applied to quantitively describe the sulfide production according to the HRT of the sewer and the chemical oxygen demand (COD) of the sewage. The empirical equation obtained was rs = (0.045 × lnHRT + 0.071) × ([COD] - b)0.6, the coefficient is a logarithmic function of the HRT, and the sulfide production rate and COD have a power relationship. Based on the data of COD and HRT obtained in the realistic sewer, the production of sulfide in the sewer can be predicted for better maintaining sewers through sulfide control.


Assuntos
Sulfeto de Hidrogênio , Esgotos , Corrosão , Sulfeto de Hidrogênio/análise , Odorantes , Sulfetos
14.
J Ethnopharmacol ; 274: 114078, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33798659

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xinyang tablet (XYT) has been traditionally used in the treatment of cardiovascular diseases (CVDs). Our previous study indicated that XYT exhibited protective effects in heart failure (HF). AIM OF THE STUDY: The aim of the present study was to determine the protective effects of XYT in pressure overload induced HF and to elucidate its underlying mechanisms of action. MATERIALS AND METHODS: We analyzed XYT content using high-performance liquid chromatography (HPLC.). Mice were subjected to transverse aortic constriction (TAC) to generate pressure overload-induced cardiac remodeling and were then orally administered XYT or URMC-099 for 1 week after the operation. HL1 mouse cardiomyoblasts were induced by lipopolysaccharides (LPS) to trigger pyroptosis and were then treated with XYT or URMC-099. We used echocardiography (ECG), hematoxylin and eosin (H&E) staining, Masson's trichrome staining and a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay to evaluate the effects of XYT. Messenger ribonucleic acid (mRNA) levels of collagen metabolism biomarkers and inflammation-related factors were detected. We determined protein levels of inflammation- and pyroptosis-related signaling pathway members via Western blot (WB). Caspase-1 activity was measured in cell lysate using a Caspase-1 Activity Assay Kit. Subsequently, to define the candidate ingredients in XYT that regulate mixed-lineage kinase-3 (MLK3), we used molecular docking (MD) to predict and evaluate binding affinity with MLK3. Finally, we screened 24 active potential compounds that regulate MLK3 via MD. RESULTS: ECG, H&E staining, Masson's trichrome staining and TUNEL assay results showed that XYT remarkably improved heart function, amelorated myocardial fibrosis and inhibited apoptosis in vivo. Moreover, it reduced expression of proteins or mRNAs related to collagen metabolism, including collagen type 1 (COL1), fibronectin (FN), alpha smooth-muscle actin (α-SMA), and matrix metalloproteinases-2 and -9 (MMP-2, MMP-9). XYT also inhibited inflammation and the induction of pyroptosis at an early stage, as well as attenuated inflammation and pyroptosis levels in vitro. CONCLUSION: Our data indicated that XYT exerted protective effects against pressure overload induced myocardial fibrosis (MF), which might be associated with the induction of pyroptosis-mediated MLK3 signaling.

15.
Cell Immunol ; 361: 104282, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33453507

RESUMO

Changes in immunoglobulin G (IgG) glycan structures are currently believed to closely related to the emergence of cancer. In this review, we summarize the current body of evidence suggesting that differences in serum IgG glycosylation patterns correspond to changes in multiple types of cancer. Modifications include IgG terminal N-link galactosylation, IgG core fucosylation, IgG terminal sialylation, and IgG terminal bisecting N-acetylglucosamine. IgG N-glycomic alterations represent promising novel biomarkers for non-invasive-cancer diagnosis, prognosis, and progression monitoring; they are characterized by high sensitivity and specificity, compensating for previously identified glycobiomarkers.


Assuntos
Biomarcadores Tumorais/imunologia , Imunoglobulina G/imunologia , Neoplasias/imunologia , Detecção Precoce de Câncer/métodos , Glicosilação , Humanos , Fragmentos Fc das Imunoglobulinas , Imunoglobulina G/metabolismo , Polissacarídeos/imunologia , Polissacarídeos/metabolismo , Prognóstico
16.
Eur J Clin Pharmacol ; 77(1): 71-77, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32803289

RESUMO

PURPOSE: To evaluate the role of diltiazem on tacrolimus sparing in pediatric primary nephrotic syndrome (PNS) and its relation to CYP3A4, CYP3A5, ABCB1, and SLCO1B3 polymorphisms. METHODS: The PNS children treated with tacrolimus and with steady-state trough concentration (C0) were retrospectively collected. The impacts of diltiazem on tacrolimus dose-adjusted C0 (C0/D), target concentration achievement, and required dose were evaluated. Meanwhile, the relationship between the polymorphisms (including CYP3A4*1G, CYP3A5*3, ABCB1-C3435T, and SCLO1B3) and dose-sparing effect were investigated. RESULTS: A total of 71 children with 535 concentrations, including 16 children with concomitant diltiazem, were involved. Significantly increased C0/D (94.0 vs 83.8 ng/mL per mg/kg, p = 0.038) and lower required daily dose of tacrolimus (0.056 vs 0.064 mg/kg, p = 0.003) were observed in patients co-administered with diltiazem. Subpopulation carrying CYP3A4*1G, CYP3A5*1, ABCB1-3435TT, or SLCO1B3-699AA was presented with enhanced increment in tacrolimus C0/D by 38.8-102.9%. CONCLUSION: Moderate effect of diltiazem on tacrolimus sparing, which might relate to the polymorphisms of CYP3A4, CYP3A5, ABCB1, and SLCO1B3, was documented.

17.
J Clin Neurophysiol ; 38(3): 192-197, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32011355

RESUMO

PURPOSE: Previous studies have proved that the people with subthreshold depression (SD) had negative cognitive bias in conscious level. However, it still remains a point of controversy whether they have impairment in unconscious level. The present study aimed to explore whether the implicit emotional processing differed between people with SD and healthy controls (HCs) and the details by analyzing the event-related potentials. METHODS: We recruited 35 SD participants and 35 age- and sex-matched HCs to collect event-related potential data. A visual oddball task was used to investigate implicit emotional processing with three types of emotional pictures (positive, negative, and neutral as stimuli). The N2 and P3 components were used to compare the neurocognitive differences of implicit emotional processing between two groups. RESULTS: Compared with the HC group, the SD participants showed no significant differences in the amplitudes or latencies of the N2 component for any kind of emotional stimuli but smaller P3 amplitudes for all kinds of emotional stimuli. The P3 latencies for positive stimuli were slower than the negative ones in the SD group but not in the HC group. The SD group showed slower P3 latencies than the HC group only for positive stimuli. There was a positive correlation between Center for Epidemiological Survey, Depression Scale score and average N2 and P3 amplitudes. CONCLUSIONS: The SD people demonstrate implicit cognitive processing impairments, and the impairments of emotional cognitive processing in SD may exist mainly in evaluative stage and primarily for positive stimuli.


Assuntos
Depressão/fisiopatologia , Depressão/psicologia , Emoções/fisiologia , Eletroencefalografia , Feminino , Humanos , Masculino , Estudantes , Adulto Jovem
18.
Brain Res ; 1750: 147143, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33068632

RESUMO

BACKGROUND: This study aims to identify how the large-scale brain dynamic functional connectivity (dFC) differs between mood states in bipolar disorder (BD). The authors analyzed dFC in subjects with BD in depressed and euthymic states using resting-state functional magnetic resonance imaging (rsfMRI) data, and compared these states to healthy controls (HCs). METHOD: 20 subjects with BD in a depressive episode, 23 euthymic BD subjects, and 31 matched HCs underwent rsfMRI scans. Using an existing parcellation of the whole brain, we measured dFC between brain regions and identified the different patterns of brain network connections between groups. RESULTS: In the analysis of whole brain dFC, the connectivity between the left Superior Temporal Gyrus (STG) in the somatomotor network (SMN), the right Middle Temporal Gyrus (MTG) in the default mode network (DMN) and the bilateral Postcentral Gyrus (PoG) in the DMN of depressed BD was greater than that of euthymic BD, while there was no significant difference between euthymic BD and HCs in these brain regions. Euthymic BD patients had abnormalities in the frontal-striatal-thalamic (FST) circuit compared to HCs. CONCLUSIONS: Differences in dFC within and between DMN and SMN can be used to distinguish depressed and euthymic states in bipolar patients. The hyperconnectivity within and between DMN and SMN may be a state feature of depressed BD. The abnormal connectivity of the FST circuit can help identify euthymic BD from HCs.

19.
Materials (Basel) ; 13(23)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297522

RESUMO

Acidic aggregates have the merits of high strength and good abrasion resistance capacity. However, its poor adhesion with asphalt binder constrains its application in pavement construction. Among these, the granite aggregate is the typical one. Therefore, this study modified granite aggregates' surface to improve their adhesion property with the asphalt binder. Specifically, the silane coupling agent (SCA) KH-560 was adopted to achieve the modification purpose. Subsequently, asphalt mixtures with modified and unmodified granite, basalt, and limestone were subjected to the boiling test, immersion test, and freeze-thaw splitting test to estimate the asphalt adhesion property. Moreover, a molecular dynamic simulation was employed to characterize the asphalt-aggregate interface from the molecular scale. The radius distribution function (RDF) and interaction energy were used as the primary indicators. The results showed that the SCA could efficiently improve the adhesion between asphalt and granite aggregates, comparable with the alkaline aggregates. In terms of the molecular scale, the incorporation of SCA could significantly increase the concentration distribution of asphalt molecules on the aggregate surface. Meanwhile, the interaction energy was correspondingly increased due to the considerable growth of non-bond interaction.

20.
J Biol Chem ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303626

RESUMO

The adhesion GPCR ADGRG2, also known as GPR64, is a critical regulator of male fertility that maintains ion/pH homeostasis and CFTR coupling. The molecular basis of ADGRG2 function is poorly understood, in part due to the fact that no endogenous ligands for ADGRG2 have been reported, thus limiting the tools available to interrogate ADGRG2 activity. It has been shown that ADGRG2 can be activated by a peptide, termed p15, derived from its own N-terminal region known as the Stachel sequence. However, the low affinity of p15 limits its utility for ADGRG2 characterization. In the current study, we used alanine scanning mutagenesis to examine the critical residues responsible for p15-induced ADGRG2 activity. We next designed systematic strategies to optimize the peptide agonist of ADGRG2, using natural and unnatural amino acid substitutions. We obtained an optimized ADGRG2 Stachel peptide T1V/F3Phe(4-Me) (VPM-p15) that activated ADGRG2 with significantly improved (>2 orders of magnitude) affinity. We then characterized the residues in ADGRG2 that were important for ADGRG2 activation in response to VPM-p15 engagement, finding that the toggle switch W6.53 and residues of ECL2 region of ADGRG2 are key determinants for VPM-p15 interactions and VPM-p15 induced Gs or arrestin signaling. Our study not only provides a useful tool to investigate the function of ADGRG2, but also offers new insights to guide further optimization of Stachel peptides to activate adhesion GPCR members.

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