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1.
Quant Imaging Med Surg ; 12(4): 2378-2384, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35371957

RESUMO

Background: To investigate the value of intraoperative frozen section examination (IFSE) in multiparametric magnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion prostate biopsy in a major pandemic. Methods: A total of 35 patients were prospectively enrolled in our hospital from March 2020 to January 2021. The mpMRI/TRUS fusion system was used to perform a targeted biopsy, and the collected specimens were examined by IFSE (Observation Group 1). Then, a targeted biopsy was performed again for routine pathological examination (Observation Group 2). Finally, a systemic biopsy was performed, and the obtained specimens were routinely examined (Control Group). The positive rate, single core positive rate, Gleason score, and time to obtain pathological reports were compared between the groups. Results: The positive rate was 48.6% (17/35) in the control group, 48.6% (17/35) in Observation Group 1, and 51.4% (18/35) in Observation Group 2, showing no significant difference (P>0.05). The single core positive rates were 17.8%, 44.6%, and 47.1% in the Control Group, Observation Group 1, and Observation Group 2, respectively. Observation Group 1 and Observation Group 2 were significantly different from the Control Group (P<0.001). No participants in Observation Group 1 had increased or decreased Gleason scores compared with those in Observation Group 2. The time to obtain the pathological report was 0.025±0.014 days and 4.216±1.073 days for Observation Group 1 and Observation Group 2, respectively, showing a significant difference (P<0.001). Conclusions: This study showed that IFSE can not only rapidly obtain the pathological report of an mpMRI/TRUS biopsy, but can also ensure the accuracy of the pathological diagnosis. Trial Registration: CHICTR, Identifier: ChiCTR2000040789. Registered 10 December 2020 - Retrospectively registered, http://www.chictr.org.cn/edit.aspx?pid=63252&htm=4.

2.
Expert Rev Hematol ; : 1-8, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35535679

RESUMO

BACKGROUND: Relapse is the leading cause of death from myeloid malignancies after allogeneic hematopoietic stem cell transplantation (HSCT). Azacitidine has gained attention in recent years in the prophylaxis of relapsed refractory hematologic malignancies. This study evaluated the efficacy of AZA in preventing relapse after HSCT in patients with myeloid malignancies. METHODS: A systematic review and meta-analysis of all available cohort studies were performed regarding the application of AZA for prophylaxis of relapse after HSCT for advanced MDS and AML. Databases were searched for relevant studies. Endpoints included 2-year relapse rate, survival, relapse-related mortality, as well as the incidence of graft-versus-host disease (GVHD). RESULTS: A total of 444 patients from 13 studies were included in this analysis. The pooled estimate of the cumulative incidence of relapse after two years in enrolled patients was 25% (95% confidence interval [CI], 18%-33%). The pooled estimates of 2-year survival probabilities were 65% (95% CI, 50%-79%). The pooled cumulative incidence of relapse-related mortality was 28% (95% CI, 22%-34%). The pooled estimated incidence of acute and chronic GVHD, respectively, were 28% (95% CI, 22%-34%) and 38% (95% CI, 27%-49%). CONCLUSION: AZA administration is efficacious for relapse prevention after HSCT in myeloid malignancies.

3.
Front Immunol ; 13: 843067, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547733

RESUMO

The diagnostic value of procalcitonin and the prognostic role of PCT clearance remain unclear in neutropenic period after allogeneic hematopoietic stem cell transplantation introduction. This study evaluated 219 febrile neutropenic patients (116, retrospectively; 103, prospectively) who underwent allo-HSCT from April 2014 to March 2016. The area under the receiver operator characteristic curve (AUC) of PCT for detecting documented infection (DI) was 0.637, and that of bloodstream infection (BSI) was 0.811. In multivariate analysis, the inability to decrease PCT by more than 80% within 5-7 days after the onset of fever independently predicted poor 100-day survival following allo-HSCT (P = 0.036). Furthermore, the prognostic nomogram combining PCTc and clinical parameters showed a stable predictive performance, supported by the C-index of 0.808 and AUC of 0.813 in the primary cohort, and C-index of 0.691 and AUC of 0.697 in the validation cohort. This study demonstrated the diagnostic role of PCT in documented and bloodstream infection during the neutropenic period after allo-HSCT. PCTc might serve as a predictive indicator of post-HSCT 100-day mortality. A nomogram based on PCTc and several clinical factors effectively predicted the 100-day survival of febrile patients and may help physicians identify high-risk patients in the post-HSCT neutropenic period.

4.
Front Cardiovasc Med ; 9: 860322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548443

RESUMO

Objectives: To investigate the characteristics of patients with primary hypertension who had positive responses to the cold pressor test (CPT). Methods: This cross-sectional study was conducted between November 2018 to November 2019, and the CPT was performed in patients with primary hypertension in 48 hospitals. The demographic characteristics and complications were collected through a questionnaire and physical examinations. A 12-month follow-up was conducted to identify the occurrence of the following events: a) all-cause mortality; b) myocardial infarction; c) stroke; d) hospitalized for heart failure. Results: The CPT was positive in 30.7% of the patients. Compared with the negative CPT group, the positive CPT group was associated with a lower rate of blood pressure control, and was more likely to have a high salt diet, diabetes, hyperuricemia, left ventricular wall thickening, carotid plaques, coronary heart disease and heart failure. A high-salt diet (OR = 1.228, 95%CI: 1.037-1.456) was found to be correlated with the positive result of CPT. Among patients in the positive CPT group, those using diuretics had a significantly higher rate of blood pressure control than those not using diuretics (54.6 vs.42.6%, x2 = 6.756, P = 0.009). After a 12-month follow-up, the incidence of heart failure in the positive CPT group was significantly higher than that in the negative CPT group (7.35 vs.5.01%, x2 = 3.945, P = 0.047). Conclusions: Patients with positive responses to the CPT had lower rates of BP control and a high risk of heart failure, which may be related to their preference for a high-salt diet. The use of diuretics helps to better control blood pressure in those patients.

6.
J Extracell Vesicles ; 11(5): e12223, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35595717

RESUMO

Extracellular vesicles (EVs) are single-membrane vesicles that play an essential role in long-range intercellular communications. EV investigation has been explored largely through cell-culture systems, but it remains unclear how physiological EVs exert homeostatic or pathological functions in vivo. Here, we report that lung EVs promote chemotaxis of neutrophils in bone marrow through delivery of double stranded DNA (dsDNA). We have identified and characterized EVs containing dsDNA collected from both human and murine lung tissues using newly developed approaches. Our analysis of EV proteomics together with single-cell RNA sequencing data reveals that type II alveolar epithelial cells are the main source of the lung EVs. Furthermore, we demonstrate that the lung EVs accumulate in bone marrow and enhance neutrophil recruitment under inflammation conditions. Moreover, lung EV-DNA stimulates neutrophils to release the chemokines CXCL1 and CXCL2 via DNA-TLR9 signalling. Our findings establish a molecular basis of lung EVs in enhancement of host immune response to bacterial infection and provide new insights into understanding of vesicle-mediated systematic communications.


Assuntos
Medula Óssea , Vesículas Extracelulares , Animais , DNA , Humanos , Inflamação , Pulmão , Camundongos , Infiltração de Neutrófilos
7.
Acta Biomater ; 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35580830

RESUMO

Zinc (Zn)-based composites have received extensive attention as promising biodegradable materials due to their unique combination of moderate biodegradability, biocompatibility, and functionality. Nevertheless, the low mechanical strength of as-cast Zn-based composites impedes their practical clinical application. Here we reported the mechanical properties, corrosion behavior, wear properties, and cytotoxicity of in situ synthesized biodegradable Zn-xMg2Ge (x = 1, 3, and 5 wt.%) composites for bone-implant applications. The mechanical properties of Zn-xMg2Ge composites were effectively improved by alloying and hot-rolling due to particle reinforcement of the Mg2Ge intermetallic phase and dynamic recrystallization. The hot-rolled (HR) Zn-3Mg2Ge composite exhibited the best mechanical properties, including a yield strength of 162.3 MPa, an ultimate tensile strength of 264.3 MPa, an elongation of 10.9%, and a Brinell hardness of 83.9 HB. With an increase in Mg2Ge content, the corrosion and degradation rates of the HR Zn-xMg2Ge composites gradually increased, while their wear rate decreased and then increased in Hanks' solution. The diluted extract (12.5% concentration) of the HR Zn-3Mg2Ge composite showed the highest cell viability compared to the other HR composites and their as-cast pure Zn counterparts. Overall, the HR Zn-3Mg2Ge composite can be considered a promising biodegradable Zn-based composite for bone-implant applications. STATEMENT OF SIGNIFICANCE: This paper reports the mechanical properties, corrosion behavior, wear properties, and cytotoxicity of in situ synthesized biodegradable Zn-xMg2Ge (x = 1, 3, and 5 wt.%) composites for bone-implant applications. Our findings demonstrated that the mechanical properties of Zn-xMg2Ge composites were effectively improved by alloying and hot-rolling due to Mg2Ge particle reinforcement and dynamic recrystallization. The hot-rolled Zn-3Mg2Ge composite showed superior cytocompatibility, satisfying corrosion and degradation rates, and the best mechanical properties including a yield strength of 162.3 MPa, an ultimate tensile strength of 264.3 MPa, and an elongation of 10.9%.

8.
Chem Commun (Camb) ; 58(42): 6200-6203, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35506738

RESUMO

Highly enantioselective palladium-catalyzed dearomative reductive Heck reaction and domino Heck-Suzuki reaction of 2-CF3-indoles have been developed. Using Pd(OAc)2/(R)-Synphos as the catalyst and Et3SiH as a hydride source, a variety of indolines bearing a 2-trifluoromethyl quaternary stereocenter were obtained via a dearomative reductive Heck reaction. Alternatively, using Pd(dba)2/phosphoramidite as the catalyst and Ar4BNa as a coupling partner, structurally diverse indolines containing two vicinal carbon stereocenters were afforded through the domino dearomative Heck-Suzuki reaction.

9.
Theriogenology ; 187: 119-126, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35567989

RESUMO

RNA-seq technology can be used for the detection of miRNA transcripts in tissues and cells at specific periods and under specific treatment conditions, which can easily and effectively screen out differential transcripts. The purpose of this study was to compare miRNA expression in porcine cumulus cells before and after oocyte maturation, and to investigate the mechanism whereby cumulus cells may influence oocyte maturation. To that aim, cumulus cells surrounding GV- and MII-stage oocytes were isolated, and their differences in miRNA expression were examined using miRNA-seq. 143 differentially expressed miRNAs were identified, among which miR-101 was selected and further verified by qPCR. Moreover, miR-101 was found to target HAS2 through target gene prediction, luciferase-based co-transfection and cumulus cells transfection. Transfection of COCs with miR-101 mimics or inhibitor revealed that the miR-101 could inhibit oocyte IVM by regulating the expanding of CCSs, but had no effect on the embryo development competence. These findings demonstrated that miR-101 regulated oocyte maturation in vitro via targeting HAS2 in porcine cumulus cells.

10.
Front Immunol ; 13: 858590, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371098

RESUMO

Background/Aims: Chimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B-cell acute lymphoblastic leukemia (ALL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here aimed to identify the independent factors of CAR-T treatment response and construct the models for predicting the complete remission (CR) and minimal residual disease (MRD)-negative CR in r/r B-ALL patients after CAR-T cell infusion. Methods: Univariate and multivariate logistic regression analyses were conducted to identify the independent factors of CR and MRD-negative CR. The predictive models for the probability of remission were constructed based on the identified independent factors. Discrimination and calibration of the established models were assessed by receiver operating characteristic (ROC) curves and calibration plots, respectively. The predictive models were further integrated and validated in the internal series. Moreover, the prognostic value of the integration risk model was also confirmed. Results: The predictive model for CR was formulated by the number of white blood cells (WBC), central neural system (CNS) leukemia, TP53 mutation, bone marrow blasts, and CAR-T cell generation while the model for MRD-negative CR was formulated by disease status, bone marrow blasts, and infusion strategy. The ROC curves and calibration plots of the two models displayed great discrimination and calibration ability. Patients and infusions were divided into different risk groups according to the integration model. High-risk groups showed significant lower CR and MRD-negative CR rates in both the training and validation sets (p < 0.01). Furthermore, low-risk patients exhibited improved overall survival (OS) (log-rank p < 0.01), higher 6-month event-free survival (EFS) rate (p < 0.01), and lower relapse rate after the allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T cell infusion (p = 0.06). Conclusions: We have established predictive models for treatment response estimation of CAR-T therapy. Our models also provided new clinical insights for the accurate diagnosis and targeted treatment of r/r B-ALL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Receptores de Antígenos Quiméricos/genética
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 593-599, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35396002

RESUMO

AbstractObjective: To investigate the role and mechanism of circulating follicular helper T cells (cTfh), extrafollicular helper T cells, B cells and their subsets in chronic graft-versus-host disease (cGVHD) after transplantation. METHODS: Peripheral blood of cGVHD 64 patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Soochow University from 2016 to 2019 were collected. The percentage of cTfh cells, extrafollicular helper T cells, B cells and subsets were detected by flow cytometry. The healthy donors were detected as control. Percentage of each cell subpopulation between the two groups were compared by the two-tailed Students' T test. RESULTS: The percentage of circulating follicular helper T cells (cTfh, CD4+CXCR5+) was markedly decreased in patients with cGVHD as compared with that in the healthy donors (0.53%±0.10% vs 3.91%±0.60%, P<0.001). The percentage of extrafollicular helper T cells (CD44hiCD62LloPSGL-1loCD4+T) of the patients in cGVHD and the healthy donors were 8.86%±0.45% and 5.38%±0.79% (P=0.003). A significant change in B cell subsets was found in the patients with cGVHD. The two types of antigen-stimulate CD27+ B cell: the percentages of pre-GC B cells (CD19+IgD+CD38hiCD27+) and plasmablast/plasma cells (PB/PC, CD19+IgD-CD38hiCD27+) of patients with cGVHD were 20.91%±2.70% and 41.05%±5.00%, respectively, which were significantly higher than those in healthy donors (P=0.005, P=0.014). Meanwhile, the percentage of unstimulated CD27- B cells in patients with cGVHD was significantly reduced, especially the naive B cells (CD19+IgD+CD38loCD27-, 12.59%±2.63%, P=0.025). There was a positive correlation between the percentage of extrafollicular helper T cells and plasmablast/ plasma cells (PB/PC) in cGVHD patients (r=0.43). CONCLUSION: Compared with healthy donor, cTfh cells, extrafollicular helper T cells and B cell subsets in the peripheral blood of patients with cGVHD after transplantation changed in varying degress.


Assuntos
Doença Enxerto-Hospedeiro , Linfócitos B , Humanos , Imunoglobulina D , Células T Auxiliares Foliculares , Linfócitos T Auxiliares-Indutores
12.
Mol Genet Genomic Med ; : e1958, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35426266

RESUMO

BACKGROUND: Genetic testing of UGT1A1 was used to facilitate the diagnosis of Gilbert syndrome, and analyze the distribution features of pathogenic variants in the Chinese population. METHODS: DNA was extracted from whole blood samples of patients with unconjugated hyperbilirubinemia, and sequencing of the UGT1A1 gene was performed after PCR amplification. After alignment with reference sequences, the known pathogenic variants were identified, the variant spectrum was analyzed, and the pathogenicity of novel variants was predicted using online mutation prediction tools. RESULTS: A total of 117 patients were confirmed with Gilbert syndrome by UGT1A1 genetic diagnosis, where the most common pathogenic variants included promoter A(TA)7 TAA insertion and p.Gly71Arg missense variant. Following novel variants were also identified: p.Ala61Gly, p.Tyr67Phe, p.Leu166Alafs*16, p.Arg240Lys, p.Ser306Phe, p.Arg341Gln, and p.Glu424* variants. CONCLUSIONS: Genetic testing of UGT1A1 in clinical practices could facilitate confirming Gilbert syndrome and performing differential diagnosis. The pathogenic variant spectrum in the Chinese population was similar to other Asian populations. The novel pathogenic variants identified in this study require further investigation.

13.
Blood Adv ; 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35390147

RESUMO

Hemophilia A and B are hereditary coagulation defects resulting in unstable blood clotting and recurrent bleeding. Current factor replacement therapies have major limitations such as the short half-life of the factors and development of inhibitors. Alternative approaches to rebalance the hemostasis by inhibiting the anticoagulant pathways have recently gained considerable interest. In this study, we tested the therapeutic potential of a monoclonal antibody, HAPC1573, that selectively blocks the anticoagulant activity of human activated protein C (APC). We generated F8-/- or F9-/- hemophilia mice expressing human protein C by genetically replacing the murine Proc gene with the human PROC. The resulting PROC+/+;F8-/- or PROC+/+;F9-/- mice had bleeding characteristics similar to their corresponding F8-/- or F9-/- mice. Pretreating the PROC+/+;F8-/- mice with HAPC1573 shortened the tail bleeding time. HAPC1573 pretreatment significantly reduced mortality and alleviated joint swelling, similar to those treated with either FVIII or FIX, of either PROC+/+;F8-/- or PROC+/+;F9-/- mice in a needle-puncture-induced knee joint bleeding model. Additionally, we found that HAPC1573 significantly improved the thrombin generation of PROC+/+;F8-/- mice but not F8-/- mice, indicating that HAPC1573 enhanced the coagulant activity of hemophilia mice by modulating human APC in vivo. We further documented that HAPC1573 inhibited the APC anticoagulant activity to improve the clotting time of human plasma deficient of FVIII, FIX, FXI, FVII, VWF, FV, or FX. These results demonstrate that selectively blocking the anticoagulant activity of human APC may be an effective therapeutic and/or prophylactic approach for bleeding disorders lacking FVIII, FIX, or other clotting factors.

14.
Adv Sci (Weinh) ; : e2201702, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35470590

RESUMO

Organic ferroelectrics, as a type of crystalline compound, are generally solution processing. However, for most crystalline compounds, the changing of solvent would not influence the crystalline phase, let alone their physical performance. Here, the solvent selective effect occurs in the iodinated adamantanone ferroelectrics. By changing the solvent with different polarities, the ferroelectric crystals can be induced in two different phases, which is unprecedented to the knowledge. More strikingly, this solvent-induced transformation could realize the physical performance optimization in the orthorhombic phase (orth-I-OA, obtained from ethanol) with a stronger second harmonic generation (SHG) response, greater piezoelectric coefficient d33 of 5 pC N-1 , and larger spontaneous polarization (Ps ) of 3.43 µC cm-2 than those of monoclinic one (mono-I-OA, obtained from ethyl acetate). Such an intriguing phenomenon might be closely related to solvent polarity. Based on the quantitative and qualitative analyses, the similar interaction energies of these two phases suggest that their transformation could be easily realized via changing the solvent. This work provides new insights into the chemical design and performance optimization of organic ferroelectrics.

15.
Chem Commun (Camb) ; 58(33): 5148-5151, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35383794

RESUMO

We discovered that [(histamine)(18-crown-6)2][BF4]2 is a high-temperature host-guest inclusion complex that presents decent piezoelectric properties (d33 = 5 pC/N), undergoes a phase transition at 406 K, and also possesses potential ferroelectricity. This work provides a new idea for constructing host-guest inclusion piezoelectrics.


Assuntos
Éteres de Coroa , Histamina , Transição de Fase , Temperatura
16.
Theriogenology ; 186: 12-20, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35421774

RESUMO

To investigate the proteomic differences between the capacitated and non-capacitated sperm of the Yanbian yellow cattle, semen was collected from three Yanbian yellow cattle, aged 3-5 years, pooled, and divided into capacitated and non-capacitated groups (n = 9) to be analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and liquid chromatography-mass spectrometry. Gene ontology enrichment, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interactions were used for bioinformatics analysis. The results showed that 598 were described as differentially expressed proteins during sperm capacitation. In the capacitated sperm, 89 proteins were up-regulated, and 509 proteins were downregulated, compared to the non-capacitated sperm. Western blot analysis confirmed that the expression of the Heat Shock 70-kDa Protein 5 (HSPA5) proteins was down-regulated. After HSPA5 inhibition, the level of tyrosine phosphorylation decreased, and the cleaved caspase 3 increased. The results showed that HSPA5 could regulate sperm capacitation and slow down apoptosis. Thus, providing a basis for studying the changes in protein expression during sperm capacitation, which can help identify the marker proteins potentially related to sperm capacitation. Hence, this study can deepen our understanding of the molecular processes involved in the sperm capacitation in Yanbian yellow cattle and provide a framework for future research.

17.
Appl Opt ; 61(12): 3455-3462, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35471442

RESUMO

The captan residues in apple juice were detected by fluorescence spectrometry, and the content level of captan was predicted based on a genetic algorithm and support vector machines (GA-SVMs). According to the captan concentration in apple juice, the experimental samples were divided into four levels, including no excess, slight excess, moderate excess, and severe excess. A GA was used to select the characteristic wavelength and optimize SVM parameters, and SVM was applied to train the classification model. 50 characteristic wavelength points were selected from the original fluorescence spectra, which contained 401 wavelength points, and the classification accuracy of the training set and test set is 99.02% and 100%, respectively, which is higher than the traditional PLS method. The results show that a GA can effectively select the feature wavelengths, and an SVM model can accurately predict the content level of captan residues. A fast and non-destructive analysis method, combined with a GA and SVM based on fluorescence spectroscopy, was realized.


Assuntos
Malus , Máquina de Vetores de Suporte , Algoritmos , Captana , Malus/química , Espectrometria de Fluorescência
18.
Thromb Haemost ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477177

RESUMO

Hypoxia-inducible factors-1α (HIF-1α) involves in redox reaction. Considering the role of reactive oxygen species (ROS) in platelet function, whether it regulates platelet function remains unclear. Using an inhibitor of HIF prolyl hydroxylase IOX-2, we intend to investigate its effect on platelet function. Human platelets were treated with IOX-2 (0, 10, 25, and 50 M) followed by analysis of platelet aggregation, granule secretion, receptor expression, platelet spreading or clot retraction. Additionally, IOX-2 (10 mg/kg) was injected intraperitoneally into mice to measure tail bleeding time and arterial thrombosis. IOX-2 significantly inhibited collagen-related peptide (CRP, 0.25 µg/ml) or thrombin (0.03 U/ml)-induced platelet aggregation and ATP release dose dependently without affecting P-selectin expression and the surface levels of glycoprotein (GP)Ib, GPVI or IIb3. In addition, IOX-2-treated platelets presented significantly decreased spreading on fibrinogen or collagen and clot retraction. Moreover, IOX-2 administration into mice significantly impaired the in vivo hemostatic function of platelets and arterial thrombus formation without affecting the number of circulating platelets and coagulation factor (FVIII and FIX). Further, IOX-2 significantly upregulated HIF-1 in platelets, decreased ROS generation and downregulated NOX1 expression. Finally, IOX-2 increased the phosphorylation level of VASP (Ser157/239), and inhibited the phosphorylation of p38 (Thr180/Tyr182), ERK1/2 (Thr202/Tyr204), AKT (Thr308/Ser473) and PKC (Thr505) in CRP- or thrombin-stimulated platelets. In conclusion, inhibition of HIF prolyl hydroxylase modulates platelet function and arterial thrombus formation, possibly through upregulation of HIF-1α expression and subsequent inhibition of ROS generation, indicating that HIF-1α might be a novel target for the treatment of thrombotic disorders.

19.
Int J Biol Macromol ; 208: 1072-1081, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35381286

RESUMO

As a major microtubule-associated protein, tau is involved in the assembly of microtubules in the central nervous system. However, under pathological conditions tau assembles into amyloid filaments. Liquid droplets formed by liquid-liquid phase separation (LLPS) are a recently identified assembly state of tau and may have a major effect on the physiological function of tau and the formation of tau aggregates. 14-3-3 proteins are ubiquitously expressed in various tissues and regulate a wide variety of biological processes. In this work, we demonstrate that 14-3-3ζ is recruited into tau droplets and regulates tau LLPS by in vitro assays. While the mobility of tau molecules inside the droplets is not affected in the presence of 14-3-3ζ, the amount and size of droplets can vary significantly. Mechanistic studies reveal that 14-3-3ζ regulates tau LLPS by electrostatic interactions and hydrophobic interactions with the proline-rich domain and the microtubule-binding domain of tau. Surprisingly, the disordered C-terminal tail rather than the amphipathic binding groove of 14-3-3ζ plays a key role. Our findings not only provide a novel dimension to understand the interactions between 14-3-3 proteins and tau, but also suggest that 14-3-3 proteins may play an important role in regulating the LLPS of their binding partners.


Assuntos
Proteínas 14-3-3 , Proteínas tau , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Amiloide/metabolismo , Humanos , Simulação de Dinâmica Molecular , Agregação Patológica de Proteínas/metabolismo , Proteínas tau/química
20.
Nutrients ; 14(7)2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35405931

RESUMO

This study aimed to investigate the effect of the oral processing of vegetables induced by texture modification on acute postprandial glycemic response (GR) and insulin response (IR) when co-ingested and ingested prior to a rice meal. In a randomized crossover trial, 14 healthy female subjects consumed (1) co-ingestion of soft broccoli and rice (SR); (2) co-ingestion of hard broccoli and rice (HR); (3) soft broccoli prior to rice (S+R); (4) hard broccoli prior to rice (H+R); (5) rice (R). Postprandial GR and IR was compared between test meals over a period of 180-min, and the oral processing behaviors were measured for each test food samples. Hard broccoli was observed to have a higher mastication time and chews than soft broccoli. All the broccoli meals resulted in reduced incremental peak glucose (IPG) and an increased incremental area under the insulin curve in 180 min (iAUC0-180) compared with R. The S+R curbed the IPG by 40% with comparable HOMA-IR AUC0-180 compared with R, while the H+R elevated the HOMA-IR AUC0-180 by 62% more than that of R. In conclusion, the soft broccoli intake prior to a rice meal effectively attenuated postprandial GR, without lowering insulin sensitivity as its hard counterpart did.


Assuntos
Brassica , Resistência à Insulina , Oryza , Glicemia , Estudos Cross-Over , Carboidratos da Dieta , Feminino , Índice Glicêmico , Humanos , Insulina , Refeições , Período Pós-Prandial/fisiologia , Verduras
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