Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 993
Filtrar
1.
Front Endocrinol (Lausanne) ; 13: 933921, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105407

RESUMO

Background: The association between glioma risk and body mass index (BMI) remains obscure. Methods: This study aimed to assess the association between glioma risk and BMI in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The onset of a total of 269 gliomas was observed during a median follow-up period of 12.04 years. Compared with the normal weight, overweight (HR: 1.05; 95% CI: 0.80, 1.39) and obesity (HR: 0.91; 95% CI: 0.56, 1.39) were not significantly associated with glioma risk. Further analysis showed a nonlinear relationship between glioma risk and BMI in men but not women. The multivariable-adjusted HRs per unit increase in BMI were 0.94 (95% CI: 0.89, 1.00; P = 0.037) in men with BMI >25 kg/m2 and 1.16 (95% CI: 0.98, 1.38; P = 0.075) in men with BMI <25 kg/m2. Conclusion: The present data provide evidence that there may be a nonlinear association between BMI and glioma risk in men. The risk of glioma decreased with increasing BMI among men with BMI >25 kg/m2. Future studies are needed to validate our observation.


Assuntos
Glioma , Neoplasias Ovarianas , Índice de Massa Corporal , Feminino , Glioma/epidemiologia , Glioma/etiologia , Humanos , Masculino , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Estudos Prospectivos
2.
Comput Math Methods Med ; 2022: 6879035, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118840

RESUMO

Objective: This study is aimed at exploring the efficacy of transarterial chemotherapy embolization (TACE)+radiofrequency ablation+sorafenib in the treatment of patients with recurrent liver cancer and at constructing its prediction model. Methods: A total of 60 patients with recurrent liver cancer treated in our hospital from March 2020 to March 2022 were enrolled and divided into two groups according to treatment methods, with 30 patients in each group. Group A adopted TACE+radiofrequency ablation+sorafenib therapy while group B adopted TACE+radiofrequency ablation therapy. Clinical efficacy, complications, and adverse reactions of the two groups were observed. A total of 30 patients with nonrecurrent liver cancer in the same period were enrolled. 60 patients with recurrent liver cancer and 30 patients with nonrecurrent liver cancer were taken as the recurrence group and the nonrecurrence group, respectively. The baseline data and clinical data of the patients were queried by the Hospital Information System. The data included age, gender, Child-Pugh grade, HBV/HCV infection, portal vein tumor thrombus, degree of differentiation, vascular invasion, serum alpha fetal protein (AFP) level, number of tumors, maximum diameter of tumors, and number of nodules. The logistic regression analysis was used to analyze the independent risk factors for liver cancer recurrence. The Hosmer-Lemeshow test was used to analyze the degree of fitting between the prediction model and the standard curve. The ROC curve was used to analyze the predictive value of the model for liver cancer recurrence. Results: The objective effective rate and disease control rate in group A (33.33% and 70.00%) were higher than those in group B (10.00% and 43.33%), and the differences were statistically significant (both P < 0.05). There were no significant differences in the incidence of complications such as embolism syndrome, hand and foot skin reaction, gastrointestinal reaction, hypertension, diaphragmatic injury and bleeding, and biliary leakage and fever between the two groups (all P > 0.05). The proportions of patients in the recurrence group with portal vein tumor thrombus (PVTT), medium and high degree of differentiation, combined with vascular invasion, serum AFP level ≥ 400 ng/dL, multiple tumors, maximum tumor diameter ≥ 5 cm, combined with cirrhosis, and polynodules were all higher than those in the nonrecurrence group; the differences were statistically significant (all P < 0.05). Complication of PVTT, the degree of medium and high differentiation, and the maximum tumor diameter ≥ 5 cm were independent risk factors for recurrence of liver cancer (all P < 0.05). The prediction model of liver cancer recurrence was obtained by multiple regression analysis, P = 1/[1 + e -(-5.441 + 6.154∗PVTT + 3.475∗differentiateddegree + 3.001∗maximumdiameteroftumor)]. The Hosmer-Lemeshow test showed that χ 2 = 1.558 (P = 0.992). According to the ROC curve analysis, the AUC, SE, and 95% CI value of the prediction model for liver cancer recurrence were 0.977, 0.012, and 0.953-1.000, respectively. Conclusion: TACE+radiofrequency ablation+sorafenib is effective in the treatment of recurrent liver cancer, and the prediction model established based on the risk factor has high predictive value for patients with recurrent liver cancer.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas , Trombose , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/efeitos adversos , Quimioembolização Terapêutica/métodos , Doença Crônica , Terapia Combinada , Humanos , Neoplasias Hepáticas/cirurgia , Sorafenibe/uso terapêutico , Trombose/terapia , alfa-Fetoproteínas/uso terapêutico
4.
ACS Omega ; 7(35): 31047-31058, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36092632

RESUMO

Gas explosion is one of the main causes of casualties in coal mines. Studying the propagation law of shock wave of mine gas explosion can reduce the economic loss and personnel injury caused by mine gas explosion. To solve the difficulty in the research of shock wave propagation of gas explosion in the mine scale, the segmented relay simulation method of shock wave propagation of gas explosion in a coal mine was put forward, the related key problems were studied, and the results were successfully applied in Yangchangwan No. 2 Mine. The results show the following: (1) When the length of the forked roadway exceeds 50 m, the length of the forked roadway has little effect on the shock wave overpressure in the main roadway. When the length of the forked roadway is short, the closure of the forked roadway has a great influence on the change curve of the shock wave overpressure in the main roadway. Therefore, the length of the bifurcation roadway should not be less than 50 m in numerical simulation. (2) The angle of the bifurcated roadway has a great influence on the shock wave propagation of explosion in the main roadway. With the increase in the angle of the bifurcated roadway, the overpressure in the main roadway tends to increase at first and then decrease, and the peak overpressure is the highest when the angle of the bifurcated roadway is 90°. (3) The influence range of the roadway pressure-outlet boundary is about 5 m, and the dynamic parameter monitoring point should be set at about 10 m away from the pressure outlet; dynamic boundary monitoring parameters should include static pressure, dynamic pressure, and temperature. (4) When the gas explosion occurs in the heading face, the shock wave will cause great damage to the adjacent heading face. When the shock wave reaches the head-on and upper corner of the heading face, it will be reflected violently, which will cause the local overpressure to rise obviously. The peak overpressure and gas accumulation length conform to the logarithmic function.

5.
Nano Lett ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098785

RESUMO

Organic-inorganic hybrid perovskites (OIHPs) with superior optoelectronic properties have emerged as revolutionary semiconductor materials for diverse applications. A fundamental understanding of the interplay between the microscopic molecular-level structure and the macroscopic optoelectronic properties is essential to boost device performance toward theoretical limits. Here, we reveal the critical role of CH3NH3+ (MA) in the regulation of the physicochemical and optoelectronic properties of a MAPbI3 film irradiated by an electron beam at 130 K. The order-to-disorder transformation of the MA cation not only leads to a notably enhanced photoluminescence emission but also results in the suppression of the orthorhombic phase down to 85 K. Taking advantage of the regulation of MA cation dynamics, we demonstrate a perovskite photodetector with 100% photocurrent enhancement and long-term stability exceeding one month. Our study provides a powerful tool for regulating the optoelectronic properties and stabilities of perovskites and highlights potential opportunities related to the organic cation in OIHPs.

6.
Int J Mol Sci ; 23(18)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36142671

RESUMO

ATP citrate lyase (ACLY) is a key enzyme in glucolipid metabolism and its aberrantly high expression is closely associated with various cancers, hyperlipemia and atherosclerotic cardiovascular diseases. Prospects of ACLY inhibitors as treatments of these diseases are excellent. To date, flavonoids have not been extensively reported as ACLY inhibitors. In our study, 138 flavonoids were screened and 21 of them were subjected to concentration-response curves. A remarkable structure-activity relationship (SAR) trend was found: ortho-dihydroxyphenyl and a conjugated system maintained by a pyrone ring were critical for inhibitory activity. Among these flavonoids, herbacetin had a typical structure and showed a non-aggregated state in solution and a high inhibition potency (IC50 = 0.50 ± 0.08 µM), and therefore was selected as a representative for the ligand-protein interaction study. In thermal shift assays, herbacetin improved the thermal stability of ACLY, suggesting a direct interaction with ACLY. Kinetic studies determined that herbacetin was a noncompetitive inhibitor of ACLY, as illustrated by molecular docking and dynamics simulation. Together, this work demonstrated flavonoids as novel and potent ACLY inhibitors with a remarkable SAR trend, which may help design high-potency ACLY inhibitors. In-depth studies of herbacetin deepened our understanding of the interactions between flavonoids and ACLY.

7.
Langmuir ; 38(37): 11337-11345, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36063092

RESUMO

When metakaolin (MK) is alkalized with an alkaline activator, it depolymerizes under the action of the alkali. However, the process of MK alkalinization is still unrevealed. Here, we supplied a molecular insight into the process of MK alkalinization through reaction molecular dynamics (MD) simulation. The structure, dynamics, and process of MK alkalinization are systematically investigated. The results showed that the layered structure of MK was destroyed and the silicates in MK were dissolved by sodium hydroxide solution during the alkalinization reaction of MK. The aluminates in MK are not dissolved, indicating that aluminates are more stable than silicates. Moreover, the equilibrium structures of MK with H2O and MK with NaOH solution show that only when both sodium hydroxide and water are involved in the alkalinization reaction, the silicates in MK undergo depolymerization. Also, the observed final state of MK alkalinization can be recognized as the precursor of alkali-activated materials (AAMs).

8.
Biol Psychiatry ; 2022 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-36137824

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder with significant heterogeneity. Different AD phenotypes may be associated with specific brain network changes. Uncovering disease heterogeneity by using functional networks could provide insights into precise diagnoses. METHODS: We investigated the subtypes of AD using nonnegative matrix factorization clustering on the previously identified 216 resting-state functional connectivities that differed between AD and normal control subjects. We conducted the analysis using a discovery dataset (n = 809) and a validated dataset (n = 291). Next, we grouped individuals with mild cognitive impairment according to the model obtained in the AD groups. Finally, the clinical measures and brain structural characteristics were compared among the subtypes to assess their relationship with differences in the functional network. RESULTS: Individuals with AD were clustered into 4 subtypes reproducibly, which included those with 1) diffuse and mild functional connectivity disruption (subtype 1), 2) predominantly decreased connectivity in the default mode network accompanied by an increase in the prefrontal circuit (subtype 2), 3) predominantly decreased connectivity in the anterior cingulate cortex accompanied by an increase in prefrontal cortex connectivity (subtype 3), and 4) predominantly decreased connectivity in the basal ganglia accompanied by an increase in prefrontal cortex connectivity (subtype 4). In addition to these differences in functional connectivity, differences between the AD subtypes were found in cognition, structural measures, and cognitive decline patterns. CONCLUSIONS: These comprehensive results offer new insights that may advance precision medicine for AD and facilitate strategies for future clinical trials.

9.
Nanomaterials (Basel) ; 12(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36080062

RESUMO

Degradation of organic pollutants, especially organic dyes and antibiotics, by semiconductor photocatalysts is an efficient strategy for wastewater treatment. TiO2 nanomaterials are considered to be promising photocatalysts due to their high chemical stability, high efficiency and availability. Anatase TiO2 generally has superior photocatalytic activity to the rutile phase. However, the anatase phase can be irreversibly transformed to rutile phase when calcined at an elevated temperature. Methods to improve the stability of anatase are especially important for the TiO2 gas sensors working at high temperatures. The addition of strong acids can effectively suppress this transformation process. However, these strong acids are relatively expensive, corrosive and environmentally unfriendly. Herein, oxalic acid (OA) as a natural acid was used to control the hydrolysis process of tetrabutyl titanate (TBOT), leading to controllable crystalline phase transformation and reduced crystalline size of TiO2 on the nanoscale. What is more, the photocatalytic degradation performances were enhanced continuously when the molar ratio of OA to TBOT increased. The degradation reaction rate constants of CT650-R25 were about 10 times that of CT650-R0. The mechanism study shows that the enhanced photocatalytic activity can be attributed to the improved dispersibility, increased specific surface area and reduced recombination rates of photo-induced charge carriers and decreased energy bands as the concentration of OA increased. Thus, this work provides a simple, mild and effective method for controlling the crystalline forms of nano-TiO2 with enhanced photocatalytic performance towards waste water treatment.

10.
J Mol Neurosci ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048344

RESUMO

Intracerebral hemorrhage causes high mortality and morbidity, but its therapy methods are limited. In the present study, pulsed electromagnetic field (PEMF) was demonstrated to have beneficial effects on an intracerebral hemorrhage (ICH) model. This study explored the effects and underlying mechanisms of PEMF in a mouse model of ICH and cultured BV2 cells. PEMF was applied 4 hours after collagenase-induced ICH at day 0 and 4 hours per day for seven consecutive days. The expression levels of proinflammatory factors were assessed by ELISA kits and western blotting. Hematoma volume was measured by histological analysis. The effects of PEMF on phagocytosis of the erythrocytes were observed in cultured BV2 cells and ICH mouse models. Seven days after ICH, the hematoma volume was significantly reduced in PEMF-treated animals compared to nontreated mice. We found that PEMF decreased the hematoma volume and the expression levels of proinflammatory factors after ICH. Moreover, PEMF enhanced the erythrophagocytosis of microglia via CD36. Furthermore, we found that downregulation CD36 with Genistein blocked the effects of PEMF-induced hematoma clearance and anti-inflammations effects. Thus, the PEMF-mediated promotion of neurological functions may at least partly involve anti-inflammatory processes and hematoma clearance. These results suggest that PEMF treatment promoted the hematoma clearance and alleviated the inflammation after ICH.

12.
Transl Pediatr ; 11(7): 1267-1273, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35958006

RESUMO

Background: The neuroblastoma (NB) is a highly malignant tumor of the ectoderm of sympathetic nerve cells and one of the most common malignant tumors in children, which can occur in any part of the sympathetic nerve plexus distribution, however it is less common in the kidney. Case Description: Here we present a case of a 4-year-old boy who came to our hospital for medical help because of "abdominal distension for 1 day". Abdominal computed tomography (CT) revealed a huge retroperitoneal soft tissue mass with unclear boundaries with kidneys and adrenal glands, and low-density cystic necrosis areas were seen in the tumor. Contrast-enhanced scan showed that the mass showed mild heterogeneous enhancement. Based on these findings in the patient, he was initially considered to have Wilms tumor, but was finally pathologically confirmed as renal NB. The purpose of this article is to provide the clinicopathological features and CT manifestations of renal NB, and to discuss its differential diagnosis with other renal tumors, in order to better provide clinicians with a better understanding of the rare solid tumor. The renal NB is usually a large lobulated soft tissue mass with unclear boundary and incomplete capsule, which is prone to hemorrhage, necrosis, cystic degeneration and calcification. On CT, the mass is usually isodensity or slightly hypodense, and the cystic degeneration and necrosis area is hypodense, and on contrast-enhanced scan, it can be mildly to significantly enhanced, but the cystic degeneration and necrosis area have no enhancement. Conclusions: The CT findings of our case were atypical and overlapped with those of Wilms, so our case suggests that renal NB should be considered as one of the differential diagnoses of Wilms, the most common malignancy of the kidney in children.

13.
Food Sci Nutr ; 10(8): 2620-2630, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35959255

RESUMO

Utilization of the biological macromolecule Dendrobium officinale polysaccharide (DOP) as a functional ingredient is limited by its high intrinsic viscosity and molecular weight. The goal of the present study was to improve rheological properties of DOP by ultrasonic treatment. Such a treatment resulted in the degradation of DOP and consequent reduction of rheological properties. Among DOP samples treated with ultrasonication at low (L), medium (M), and high (H) power intensities (25, 50, 75 w/cm2), M-DOP displayed the highest reactive oxygen species (ROS) and reactive nitrogen species (RNS) radical scavenging activity in vitro. In a mouse D-galactose (D-Gal)-induced aging model, M-DOP significantly increased activities of antioxidant enzymes and reduced levels of pro-inflammatory cytokines in liver. Real-time polymerase chain reaction (RT-PCR) analysis indicated that M-DOP upregulated messenger RNA (mRNA) expression of anti-inflammatory/antioxidant proteins such as Nrf2 (nuclear factor erythroid 2-related factor), hemeoxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase (NQO1) in liver. In summary, M-DOP displayed a strong radical scavenging activity in vitro, and ameliorated liver injury in the mouse aging model through the promotion of Nrf2/HO-1/NQO1 signaling pathway.

14.
Bioresour Technol ; 362: 127843, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36031136

RESUMO

In the present study, a biochemical strategy for improving propionic acid production from kitchen waste acidification by bioaugmentation with Propionibacterium acidipropionici (P. acidipropionici) was investigated. When the inoculum of P. acidipropionici was 30% (w/w) of the seeding sludge, the propionic acid production increased by 79.57%. Further, bioaugmentation improved the relative abundance of Firmicute and Actinobacteria. The results of metagenomic analysis further reveal that the ATP-binding cassette (ABC) transporters and all related pathways of Propanoate metabolism (ko00640) were enriched when P. acidipropionici was added. For Propanoate metabolism, most functional genes involved in the conversion from Glycolysis / Gluconeogenesis (ko00010) to Propanoyl-CoA and conversion from Propanoyl-CoA to propionic acid were enhanced after bioaugmentation with P. acidipropionici, thereby promoting propionic acid production. As such, bioaugmentation with P. acidipropionici was effective in the anaerobic acidification of kitchen waste for propionic acid production.


Assuntos
Propionatos , Propionibacterium , Anaerobiose , Coenzima A/metabolismo , Concentração de Íons de Hidrogênio , Metagenômica , Propionatos/metabolismo , Propionibacteriaceae , Propionibacterium/genética , Propionibacterium/metabolismo
15.
Front Med (Lausanne) ; 9: 967531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991641

RESUMO

Plasma cell myeloma (PCM) is a malignant clonal disease of abnormal proliferation of plasma cells, which is the second most common hematological malignancy after leukemia. PCM often diffuses and involves the bones of the whole body, especially the spinal column, ribs, skull, pelvis, and other axial bones and flat bones. Herein, we present a 55-year-old man who came to the hospital seeking medical help for low-back pain and numbness in his lower limbs. Computed tomography (CT) was performed because the clinician suspected that the patient had a herniated disc, and the results showed that the 7th thoracic vertebrae and the 3rd lumbar vertebrae showed a low density of bone destruction with "honeycombing" changes. Magnetic resonance imaging (MRI) showed that the corresponding lesions presented long T1 and long T2 signals, and the lesions were significantly enhanced in contrast-enhanced T1WI sequences, and fluoro18-labeled deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed mild radioactive uptake in the lesions. Based on these imaging findings, the patient was considered for a diagnosis of hemangiomas, and surgery was performed because the affected vertebra was pressing on the spinal cord. However, intraoperative frozen section examination showed that the patient had plasma cell myeloma. Our case study suggests that PCM involving a single thoracic and lumbar spine is rare and should be considered as one of the imaging differential diagnoses of hemangiomas. Moreover, the diagnosis of PCM is difficult when the number of lesions is small, especially when the plasma cell ratio is within the normal reference range in laboratory tests.

16.
Heliyon ; 8(8): e10060, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35992010

RESUMO

Based on a high-pressure servo static and dynamic true triaxial test machine (tawz-500/300), uniaxial and true triaxial tests of AC-25C asphalt mixtures under different heat moisture coupling treatments were performed, and the triaxial compressive strength value was determined by mathematical treatment. The test results show that in the range of 20-60 °C, the uniaxial and triaxial compressive strength of the AC-25C asphalt mixture decreases with increasing drying and soaking environment temperature. In the temperature range of 20-40 °C, the drying temperature sensitivity and soaking temperature sensitivity of the asphalt mixture with compressive strength and failure strain value as indices are the maximum. The increase in the intermediate principal stress can improve the triaxial compressive strength, and the increase reaches the maximum when the environmental treatment temperature is 40 °C. The maximum stress ratio is in the range of σ2/σ3 = 0.25 to σ2/σ3 = 0.5. The failure forms of uniaxial tension and triaxial tension are mainly caused by tensile stress. The influence of temperature, humidity and stress ratio on triaxial failure strength is analysed. The relationship between the failure strength and temperature coefficient k is established using a variety of failure criteria, which can provide an experimental and theoretical basis for the mechanical analysis of asphalt mixtures under complex stress states.

17.
J Adv Res ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35933090

RESUMO

INTRODUCTION: Polyploidy is a major force in plant evolution and the domestication of cultivated crops. OBJECTIVES: The study aimed to explore the relationship and underlying mechanism between three-dimensional (3D) chromatin organization and gene transcription upon rice genome duplication. METHODS: The 3D chromatin structures between diploid (2C) and autotetraploid (4C) rice were compared using high-throughput chromosome conformation capture (Hi-C) analysis. The study combined genetics, transcriptomics, whole-genome bisulfite sequencing (WGBS-seq) and 3D genomics approaches to uncover the mechanism for DNA methylation in modulating gene transcription through 3D chromatin architectures upon rice genome duplication. RESULTS: We found that 4C rice presents weakened intra-chromosomal interactions compared to its 2C progenitor in some chromosomes. In addition, we found that changes of 3D chromatin organizations including chromatin compartments, topologically associating domains (TADs), and loops, are uncorrelated with gene transcription. Moreover, DNA methylations in the regulatory sequences of genes in compartment A/B switched regions and TAD boundaries are unrelated to their expression. Importantly, although there was no significant difference in the methylation levels in transposable elements (TEs) in differentially expressed gene (DEG) and non-DEG promoters between 2C and 4C rice, we found that the hypermethylated TEs across genes in compartment A/B switched regions and TAD boundaries may suppress the expression of these genes. CONCLUSION: The study proposed that the rice genome doubling might modulate TE methylation to buffer the effects of chromatin architecture on gene transcription in compartment A/B switched regions and TAD boundaries, resulting in the disconnection between 3D chromatin structure alteration and gene transcription upon rice genome duplication.

18.
Br J Haematol ; 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35974424

RESUMO

Normal early erythropoiesis depends on the precise regulation of protein expression and phosphorylation modification. Dysregulation of protein levels or modification contributes to erythroid disorders. To date, the dynamics of protein phosphorylation profiling across human erythroid development is not fully understood. Here, we characterized quantitative proteomic and phosphoproteomic profiling by tandem mass-tagging technology. We systemically built phospho-expression profiling and expression clusters of 11 414 phosphopeptides for human early erythropoiesis. The standardization methods for multitier integrative analyses revealed multiple functional modules of phosphoproteins (e.g., regulation of the G2/M transition) and active phosphorylated signalling (e.g., cell cycle-related pathways). Our further analysis revealed that CDK family members were the main kinases that phosphorylate substrates in erythroid progenitors and identified that CDK9 played an important role in the proliferation of erythroid progenitors. Collectively, our phosphoproteomic profiling, integrative network analysis and functional studies define landscapes of the phosphoproteome and reveal signalling pathways that are involved in human early erythropoiesis. This study will serve as a valuable resource for further investigations of phosphatase and kinase functions in human erythropoiesis and erythroid-related diseases.

19.
Hepatol Int ; 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35972640

RESUMO

BACKGROUND: Although the diagnostic value of plasma heat-shock protein 90α (HSP90α) in hepatocellular carcinoma (HCC) has been previously reported, the causal effect of the plasma HSP90α levels on HCC prognosis remains largely unclear. To this extent, we sought to assess whether the plasma HSP90α acts as a prognostic factor for HCC patients. METHODS: A total of 2150 HCC patients were included in this retrospective study between August 2016 and July 2021. Plasma HSP90α levels were tested within a week before treatment and their association with prognosis was assessed. RESULTS: An optimal cutoff value of 143.5 for the HSP90α based on the overall survival (OS) was determined using the X-tile software. HCC patients with HSP90α < 143.5 ng/mL (low HSP90α) before and after propensity score matching (PSM) indicated longer median OS (mOS) relative to those with HSP90α ≥ 143.5 ng/mL (high HSP90α) (37.0 vs. 9.0 months, p < 0.001; 19.2 vs. 9.6 months, p < 0.001; respectively). In addition, the high HSP90α plasma level is an independent poor prognostic factor for OS in HCC patients. In our subgroup analysis, including the supportive care group, surgery group, transarterial chemoembolization (TACE) group, adjuvant TACE group, an immune checkpoint inhibitor (ICI) plus targeted therapy group, and TACE plus ICI group, the high HSP90α group demonstrated better OS compared to the low HSP90α group. Moreover, in the supportive care, TACE, ICI plus targeted therapy, TACE plus ICI groups, and high HSP90α levels were also an independent poor prognostic factors for OS. CONCLUSIONS: Our study confirmed that the plasma HSP90α level can be used as a prognostic biomarker for HCC.

20.
Acta Pharmacol Sin ; 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042291

RESUMO

Sirtuin3 (SIRT3), a class III histone deacetylase, is implicated in various cardiovascular diseases as a novel therapeutic target. SIRT3 has been proven to be cardioprotective in a model of Ang II-induced cardiac hypertrophy. However, a few small-molecule compounds targeting deacetylases could activate SIRT3. In this study, we generated a novel SIRT3 activator, 3-(2-bromo-4-hydroxyphenyl)-7-hydroxy-2H-chromen-2-one (SZC-6), through structural optimization of the first SIRT3 agonist C12. We demonstrated that SZC-6 directly bound to SIRT3 with Kd value of 15 µM, and increased SIRT3 deacetylation activity with EC50 value of 23.2 ± 3.3 µM. In neonatal rat cardiomyocytes (NRCMs), pretreatment with SZC-6 (10, 20, 40 µM) dose-dependently attenuated isoproterenol (ISO)-induced hypertrophic responses. Administration of SZC-6 (20, 40 and 60 mg·kg-1·d-1, s.c.) for 2 weeks starting from one week prior ISO treatment dose-dependently reversed ISO-induced impairment of diastolic and systolic cardiac function in wild-type mice, but not in SIRT3 knockdown mice. We showed that SZC-6 (10, 20, 40 µM) dose-dependently inhibited cardiac fibroblast proliferation and differentiation into myofibroblasts, which was abolished in SIRT3-knockdown mice. We further revealed that activation of SIRT3 by SZC-6 increased ATP production and rate of mitochondrial oxygen consumption, and reduced ROS, improving mitochondrial function in ISO-treated NRCMs. We also found that SZC-6 dose-dependently enhanced LKB1 phosphorylation, thereby promoting AMPK activation to inhibit Drp1-dependent mitochondrial fragmentation. Taken together, these results demonstrate that SZC-6 is a novel SIRT3 agonist with potential value in the treatment of cardiac hypertrophy partly through activation of the LKB1-AMPK pathway.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...