Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.333
Filtrar
1.
Front Endocrinol (Lausanne) ; 13: 849076, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35518930

RESUMO

Purpose: As an important public health problem, osteoporosis (OP) in China is also in an upward trend year by year. As a standard method for diagnosing OP, dual-energy X-ray absorptiometry (DXA) cannot analyze the pathological process but only see the results. It is difficult to evaluate the early diagnosis of OP. Our study was carried out through a serum metabolomic study of OP in Chinese postmenopausal women on untargeted gas chromatography (GC)/liquid chromatography (LC)-mass spectrometry (MS) to find possible diagnostic markers. Materials and Methods: 50 Chinese postmenopausal women with osteoporosis and 50 age-matched women were selected as normal controls. We first used untargeted GC/LC-MS to analyze the serum of these participants and then combined it with a large number of multivariate statistical analyses to analyze the data. Finally, based on a multidimensional analysis of the metabolites, the most critical metabolites were considered to be biomarkers of OP in postmenopausal women. Further, biomarkers identified relevant metabolic pathways, followed by a map of metabolic pathways found in the database. Results: We found that there may be metabolic pathway disorders like glucose metabolism, lipid metabolism, and amino acid metabolism in postmenopausal women with OP. 18 differential metabolites are considered to be potential biomarkers of OP in postmenopausal women which are a major factor in metabolism and bone physiological function. Conclusion: These findings can be applied to clinical work through further validation studies. It also shows that metabonomic analysis has great potential in the application of early diagnosis and recurrence monitoring in postmenopausal OP women.


Assuntos
Osteoporose Pós-Menopausa , Osteoporose , Biomarcadores , Cromatografia Líquida , Feminino , Humanos , Osteoporose/metabolismo , Osteoporose Pós-Menopausa/diagnóstico , Espectrometria de Massas em Tandem/métodos
2.
Asian J Androl ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35532558

RESUMO

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35567772

RESUMO

The authors aimed to explore the association between visit-to-visit blood pressure variability (BPV) in pregnant women and adverse neonatal outcomes. The study included 52 891 pregnant women. BPV was calculated as standard deviation (SD) and coefficient of variation (CV) of systolic blood pressure (SBP) or diastolic blood pressure (DBP). All participants were divided into four groups by the quartiles of BPV. When comparing the highest quartiles to the lowest quartiles of DBP SD in all participants, the fully adjusted ORs were 1.19 (95% CI 1.11-1.27, p for trend < .001) for fetal distress, 1.32 (95% CI 1.14-1.54, p for trend < .001) for small for gestational age, 1.32 (95% CI 1.06-1.63, p for trend = .003) for 1-min Apgar score ≤ 7. When comparing the highest quartiles to the lowest quartiles of DBP CV, ORs were 1.22 (95% CI 1.14-1.30, p for trend < .001) for fetal distress, 1.38 (95% CI 1.17-1.61, p for trend < .001) for small for gestational age, 1.43 (95% CI 1.14-1.79, p for trend < .001) for 1-min Apgar score ≤ 7. ORs for preterm birth and 5-min Apgar score ≤ 7 were not statistically significant. However, in participants with gestational hypertension or preeclampsia, ORs for preterm birth were 2.80 (95% CI 1.99-3.94, p for trend < .001) in DBP SD and 3.25 (95% CI 2.24-4.72, p for trend < .001) in DBP CV when extreme quartiles were compared. In conclusion, higher visit-to-visit BPV was associated with adverse neonatal outcomes.

4.
Neural Regen Res ; 17(11): 2537-2543, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35535908

RESUMO

Obstructive sleep apnea can worsen the prognosis of subarachnoid hemorrhage. However, the underlying mechanism remains unclear. In this study, we established a mouse model of subarachnoid hemorrhage using the endovascular perforation method and exposed the mice to intermittent hypoxia for 8 hours daily for 2 consecutive days to simulate sleep apnea. We found that sleep apnea aggravated brain edema, increased hippocampal neuron apoptosis, and worsened neurological function in this mouse model of subarachnoid hemorrhage. Then, we established an in vitro HT-22 cell model of hemin-induced subarachnoid hemorrhage/intermittent hypoxia and found that the cells died, and lactate dehydrogenase release increased, after 48 hours. We further investigated the underlying mechanism and found that sleep apnea increased the expression of hippocampal neuroinflammatory factors interleukin-1ß, interleukin-18, interleukin-6, nuclear factor κB, pyroptosis-related protein caspase-1, pro-caspase-1, and NLRP3, promoted the proliferation of astrocytes, and increased the expression of hypoxia-inducible factor 1α and apoptosis-associated speck-like protein containing a CARD, which are the key proteins in the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway. We also found that knockdown of hypoxia-inducible factor 1α expression in vitro greatly reduced the damage to HY22 cells. These findings suggest that sleep apnea aggravates early brain injury after subarachnoid hemorrhage by aggravating neuroinflammation and pyroptosis, at least in part through the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.

5.
Chem Biodivers ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35560497

RESUMO

Three new compounds named Cynansteroid A ( 1 ), Cynansteroid B ( 2 ) and Cynansteroid C ( 3 ), together with nine known C 21 -steroidal pregnane sapogenins ( 4 - 12 ) were isolated from the hydrolytic extract of the roots of Cynanchum auriculatum . Cynansteroid A-C ( 1 - 3 ) structures were ascertained via the detailed analysis of the HR-ESI-MS, 1D and 2D NMR, and the calculated and experimental ECD data of Cynansteroid B ( 2 ). Compound 11 displayed moderate inhibitory activity toward Verticillium dahliae Kleb (IC 50 = 37.15 µ M), furthermore,  compounds 11 and 12 showed significant inhibitory activity against Phomopsis sp (IC 50 = 16.49 µ M and 17.62 µ M, respectively).

6.
Comput Math Methods Med ; 2022: 1863129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547565

RESUMO

Objective: To explore the effect of the comfortable intervention-based nursing mode under the quality nursing intervention combined with Internet mobile health on the quality of life (QOL) and psychological status of patients with acute cerebral infarction (ACI). Methods: 90 ACI patients treated in our hospital (June 2019-June 2020) were chosen and equally split into the experimental group (EG) and control group (CG) according to the order of admission. CG received routine nursing, while EG received the comfortable intervention-based nursing mode under the quality nursing intervention combined with Internet mobile health to compare the clinical indexes between the two groups. Results: Compared with CG, EG after intervention achieved obviously higher SS-QOL, ESCA, and GCQ scores (P < 0.001), and lower MSSNS and NIHSS scores (P < 0.001). Conclusion: The application of the comfortable intervention-based nursing mode under the quality nursing intervention combined with Internet mobile health effectively improves QOL and alleviates the negative emotions of patients. Compared with routine nursing, this model has higher application value, and further research of the joint intervention will help build better a solution for patients.

7.
Front Med (Lausanne) ; 9: 877186, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572962

RESUMO

The manufacturer's instructions for the venereal disease research laboratory (VDRL) antigen test for diagnosing neurosyphilis describe testing of serum samples and do not include procedures for cerebrospinal fluid (CSF) testing. This study compared the CSF-VDRL test with 10 µL of antigen (CSF-VDRL-10) according to the American Public Health Association to the CSF-VDRL test with 17 µL of antigen (CSF-VDRL-17) according to the VDRL serum procedure. A total of 121 neurosyphilis patients and 86 syphilis/non-neurosyphilis patients were included. The sensitivities of the CSF-VDRL-10 and CSF-VDRL-17 tests were comparable for neurosyphilis diagnosis. The positive rate of the CSF-VDRL-17 test was higher than that of the CSF-VDRL-10 test. In all, 78.3% of the quantitative CSF-VDRL-17 results were consistent with those of the CSF-VDRL-10 test, 18.4% exhibited one-titer higher results than those of the CSF-VDRL-10 test, and 3.4% had positive CSF-VDRL-17 results but negative CSF-VDRL-10 results. The CSF-VDRL test with 17 µL of antigen was more sensitive, and it is worth performing longitudinal studies to understand its practical implications.

8.
Front Endocrinol (Lausanne) ; 13: 864908, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573994

RESUMO

Background: To evaluate the safety and efficacy of daily somatropin (Jintropin®), a recombinant human growth hormone, in prepubertal children with ISS in China. Methods: This study was a multicenter, randomized, controlled, open-label, phase 3 study. All subjects were randomized 3:1 to daily somatropin 0.05 mg/kg/day or no treatment for 52 weeks. A total of 481 subjects with a mean baseline age of 5.8 years were enrolled in the study. The primary endpoint was change in (△) height standard deviation score (HT-SDS) for chronological age (CA). Secondary endpoints included △height from baseline; △bone age (BA)/CA; △height velocity (HV) and △insulin-like growth factor 1 (IGF-1 SDS). Results: △HT-SDS at week 52 was 1.04 ± 0.31 in the treatment group and 0.20 ± 0.33 in the control group (P < 0.001). At week 52, statistical significance was observed in the treatment group compared with control for △height (10.19 ± 1.47 cm vs. 5.85 ± 1.80 cm; P < 0.001), △BA/CA (0.04 ± 0.09 vs. 0.004 ± 0.01; P < 0.001), △HV (5.17 ± 3.70 cm/year vs. 0.75 ± 4.34 cm/year; P < 0.001), and △IGF-1 SDS (2.31 ± 1.20 vs. 0.22 ± 0.98; P < 0.001). The frequencies of treatment-emergent adverse events (TEAEs) were similar for the treatment and the control groups (89.8% vs. 82.4%); most TEAEs were mild to moderate in severity and 23 AEs were considered study-drug related. Conclusions: Daily subcutaneous administration of somatropin at 0.05 mg/kg/day for 52 weeks demonstrated improvement in growth outcomes and was well tolerated with a favorable safety profile. Trial Registration: ClinicalTrials.gov (identifier: NCT03635580). URL: https://clinicaltrials.gov/ct2/show/NCT03635580.

9.
Fish Shellfish Immunol ; 125: 109-119, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35500876

RESUMO

Spiroplasma eriocheiris, the pathogen of Eriocheir sinensis tremor disease (TD), has bring a huge economic loss to China aquaculture. The hemocytes of crab as the first target cells of S. eriocheiris, but the interactive relationship between the E. sinensis and this pathogen not particularly clear. The present study is the first time to analysis the role of protein ubiquitination in the process of E. sinensis hemocytes response S. eriocheiris infection. By applying label-free quantitative liquid chromatography with tandem mass spectrometry proteomics, 950 lysine ubiquitination sites and 803 ubiquitination peptides on 458 proteins were identified, of which 48 ubiquitination sites on 40 proteins were quantified as significantly changed after the S. eriocheiris infection. Bioinformatics analysis of ubiquitination different proteins suggested many biological process and pathways were participated in the interaction between S. eriocheiris and host cell, such as ubiquitin system, endocytosis, prophenoloxidase system (proPO system), cell apoptosis, glycolysis. Our study can enhance our understanding of interaction between the crab and S. eriocheiris, and also provides basis to study the role of protein ubiquitination in other crustacean innate immune system.

10.
Cell Death Dis ; 13(4): 312, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35387981

RESUMO

Increasing research has uncovered the involvement of long noncoding RNAs (lncRNAs) in the progression of multiple cancers including lung adenocarcinoma (LUAD). RT-qPCR and western blot were done to measure RNAs and proteins. Functional assays assessed LUAD cell biological behaviors under knockdown or overexpression of LINC01468, SIX5, SERBP1 or SERPINE1, and the specific function of those genes in regulating LUAD progression was evaluated via animal experiments. Supported by bioinformatics analysis, the interaction among genes was verified via mechanism assays. Upregulation of LINC01468 in LUAD tissues and cells as well as its association with poor clinical outcome was predicted. LINC01468, transcriptionally activated by SIX5, could strengthen proliferative, migratory and invasive abilities of LUAD cells. The oncogenic role of LINC01468 was further validated via animal experiments. SIX5 was a positive transcription regulator of LINC01468 and could exacerbate LUAD cell malignant behaviors. LINC01468 could recruit SERBP1 to enhance SERPINE1 mRNA stability and interact with USP5 to affect PAI1 protein ubiquitination. The oncogenic role of SERBP1 and SERPINE1 was also confirmed. Rescue experiments finally verified LINC01468 modulated proliferation, migration and invasion of LUAD cells via upregulation of SERPINE1. Our observations could contribute to deeper understanding of LUAD.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Pulmão/metabolismo , Neoplasias Pulmonares/patologia , Estabilidade de RNA/genética
11.
Medicine (Baltimore) ; 101(10): e27984, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35451377

RESUMO

RATIONALE: Central retinal artery occlusion and branch retinal artery occlusion (BRAO) result in partial or complete retinal ischemia and sudden loss of vision; to date there is no effective therapy for central retinal artery occlusion and BRAO. Transluminal Nd:YAG laser embolysis (TYE) could represent a therapeutic approach for retinal vascular occlusive diseases. PATIENT CONCERNS: We report 2 cases with BRAO, 1 with inferor-temporal and 1 with superor hemiretinal BRAO. All the patients complained of a history of sudden blurry vision and impaired visual field and had a visible embolus within the intravascular, all of them treated with TYE, the laser applications being delivered directly to the embolus. DIAGNOSIS: The diagnosis was based on the results from color retinography, optical coherence tomography and visual field testing. Fundus fluorescein angiography clearly indicated the location of retinal artery occlusion. INTERVENTIONS: The patients' symptoms could not be relieved after dilating the blood vessels in the eye, lowering intraocular pressure, massaging the eyeball, and inhaling oxygen. Informed consent was obtained from the patient for TYE and the patients were referred for this procedure. OUTCOMES: Upon the successful competition of the TYE procedure the embolus was removed completely, restoring the blood flow in the intraocular vessels and improving significantly the patients' visual acuity. LESSONS: World-wide experience with TYE is still limited, but the technique seems feasible for the treatment of RAO caused by visible emboli on the optic disc surface and the posterior pole of the fundus oculi.


Assuntos
Lasers de Estado Sólido , Oclusão da Artéria Retiniana , Artéria Retiniana , Angiofluoresceinografia , Fundo de Olho , Humanos , Lasers de Estado Sólido/uso terapêutico , Oclusão da Artéria Retiniana/diagnóstico , Acuidade Visual
12.
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.

13.
STAR Protoc ; 3(2): 101308, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35463469

RESUMO

Human colonic organoids derived from biopsy or autopsy tissues are a vital tool to study mucosal homeostasis, model colonic diseases, and develop therapeutics. Rapid and reliable generation of knockout organoid lines from multiple donors enables analysis of specific gene functions. Here, we report protocols to produce colonic organoid knockout lines within 1 to 2 weeks using lentiviral delivery of CRISPR-Cas9, achieving knockout efficiency of 90% or greater. These lines are suitable for multi-lineage differentiation and downstream analysis. For complete details on the use and execution of this protocol, please refer to Gu et al. (2022).


Assuntos
Colo , Organoides , Biópsia , Humanos
14.
Medicine (Baltimore) ; 101(7): e28914, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35363213

RESUMO

BACKGROUND: : Recombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies for patients with acute ischemic stroke. However, wake-up stroke (WUS) is typically excluded from intravenous thrombolytic therapy because of the unclear time of symptom onset. Therefore, we aimed to assess the efficacy and safety of rt-PA intravenous thrombolysis in patients with WUS by meta-analysis. METHODS: : We completed a systematic literature search of PubMed, Embase, the Cochrane Library, and SinoMed and included relevant studies of WUS patients covering rt-PA thrombolysis and nonthrombolysis (published from January 1, 2000, to February 28, 2021, with no language restrictions). The primary outcomes included safety outcomes and functional outcomes. Safety outcomes were measured according to the incidence of symptomatic intracranial hemorrhage and mortality within 90 days. The efficacy outcomes were measured based on 90-day modified Rankin Scale scores. We assessed pooled data using either a random-effects model (when P < .10, I2 > 50%) or a fixed-effects model (when P > .10, I2 < 50%). RESULTS: : A total of 913 patients from 9 studies were included in the meta-analysis. All patients had ischemic stroke confirmed by computed tomography or magnetic resonance imaging. The incidence of modified Rankin Scale 0 to 2 was significantly higher in the rt-PA thrombolysis group compared with the nonthrombolysis group. And rt-PA thrombolytic WUS patients did not differ significantly from nonthrombolytic WUS patients in terms of 90-day mortality. However, the incidence of Symptomatic intracranial hemorrhage was also significantly higher in the rt-PA thrombolysis group than that in the nonthrombolysis group. CONCLUSIONS: : Patients with WUS who received rt-PA thrombolysis had a significant positive effect within 90 days. In addition, although there was no significant increase in mortality, we need to be aware of the risk of intracranial hemorrhage transformation associated with rt-PA thrombolysis despite no obvious increase in mortality. The safety of rt-PA intravenous thrombolysis should be closely monitored in patients with WUS.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Fibrinolíticos/efeitos adversos , Humanos , Acidente Vascular Cerebral/etiologia , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/efeitos adversos
15.
BMC Pediatr ; 22(1): 206, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35418062

RESUMO

BACKGROUND: Precision treatment of pediatric diabetic ketoacidosis (DKA) has been the focus of research for decades. Whether the timing of the initiation of dietary intake contributes to DKA correction is ignored. METHODS: We conducted a retrospective study to investigate the effects of the timing of the initiation of dietary intake on DKA correction in Children's Hospital of Nanjing Medical University, a tertiary children's hospital, from June 2017 to December 2020. Individual basic characteristic and clinical information of all DKA cases (n = 183) were collected. Multiple linear regression, logistic regression model and random forest (RF) model were used to assess the effect of the timing of the initiation of dietary intake on DKA correction. RESULTS: The mean age of the children diagnosed with DKA was 6.95 (SD 3.82) years. The median DKA correction time and the timing of the initiation of dietary intake was 41.72 h and 3.13 h, respectively. There were 62.3% (n = 114) patients corrected DKA at the end of the 48-h rehydration therapy. For each hour delay in starting dietary intake, child's DKA correction was prolonged by 0.5 (95% CI 1.05, 1.11, P < 0.001) hours and the adjusted odds of DKA over 48 h was increased by 8% (OR = 1.08, 95% CI: 1.05, 1.11, P < 0.001) after adjustment for potential confounders. The RF model based on the timing of the initiation of dietary intake and child's weight and systolic pressure achieved the highest AUC of 0.789. CONCLUSION: Pediatricians should pay attention to the effect of the timing of the initiation of dietary intake, a controllable factor, on DKA correction.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Criança , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/terapia , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/etiologia , Cetoacidose Diabética/terapia , Ingestão de Alimentos , Hospitais Pediátricos , Humanos , Estudos Retrospectivos
16.
Oncogene ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35487975

RESUMO

Although it is well-established that p53-mediated tumor suppression mainly acts through its ability in transcriptional regulation, the molecular mechanisms of this regulation are not completely understood. Among a number of regulatory modes, acetylation of p53 attracts great interests. p53 was one of the first non-histone proteins found to be functionally regulated by acetylation and deacetylation, and subsequent work has established that reversible acetylation is a general mechanism for regulation of non-histone proteins. Unlike other types of posttranslational modifications occurred during stress responses, the role of p53 acetylation has been recently validated in vivo by using the knock-in mice with both acetylation-defective and acetylation-mimicking p53 mutants. Here, we review the role of acetylation in p53-mediated activities, with a focus on which specific acetylation sites are critical for p53-dependent transcription regulation during tumor suppression and how acetylation of p53 recruits specific "readers" to execute its promoter-specific regulation of different targets. We also discuss the role of p53 acetylation in differentially regulating its classic activities in cell cycle arrest, senescence and apoptosis as well as newly identified unconventional functions such as cell metabolism and ferroptosis.

17.
Front Mol Biosci ; 9: 761272, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402514

RESUMO

Purpose: This study was performed to investigate the regional cerebral blood flow (CBF) and CBF connectivity in the chemotherapy-induced cognitive impairment of patients with lung cancer by using arterial spin labeling. Methods: Pseudocontinuous arterial spin labeling perfusion magnetic resonance imaging and neuropsychological tests were performed for 21 patients with non-small cell lung cancer who had received chemotherapy CT (+) and 25 non-small cell lung cancer patients who need chemotherapy but did not yet received CT (-). The CT (+) group previously received platinum-based therapy for 3 months to 6 months (the time from their first chemotherapy to the MRI scan). Group comparisons were performed in the regional normalized CBF and CBF connectivity, and the relationship between the regional normalized CBF and cognitive impairment were detected. Results: The CT (+) group exhibited higher CBF in the left insula, right caudate, right superior occipital gyrus, left superior temporal gyrus (STG), and right middle frontal gyrus (MFG). MoCA scores as well as the memory scores were negatively correlated with the increased CBF in the right MFG (r = -0.492, p = 0.023; r = -0.497, p = 0.022). Alterations in the CBF connectivity were detected only in the CT (+) group between the following: right MFG and the right precentral gyrus; the right caudate and the right lingual gyrus; right caudate and right precuneus; left STG and the bilateral MFG; and the left STG and the right middle cingulum. Conclusion: These findings indicated that chemotherapy is associated with abnormalities in the CBF and connectivity alterations, which may contribute to the cognitive impairment in patients with lung cancer.

19.
Angew Chem Int Ed Engl ; : e202203778, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488103

RESUMO

Inorganic cesium lead iodide perovskite CsPbI3 is attracting great attention as a light absorber for single or multi-junction photovoltaics due to its outstanding thermal stability and proper band gap. However, the device performance of CsPbI3 -based perovskite solar cells (PSCs) is limited by the unsatisfactory crystal quality and thus severe non-radiative recombination. Here, vacuum-assisted thermal annealing (VATA) is demonstrated as an effective approach for controlling the morphology and crystallinity of the CsPbI3 perovskite films formed from the precursors of PbI2 , CsI, and dimethylammonium iodide (DMAI). By this method, a large-area and high-quality CsPbI3 film is obtained, exhibiting a much reduced trap-state density with prolonged charge lifetime. Consequently, the solar cell efficiency is raised from 17.26 to 20.06 %, along with enhanced stability. The VATA would be an effective approach for fabricating high-performance thin-film CsPbI3 perovskite optoelectronics.

20.
Oxid Med Cell Longev ; 2022: 7856290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464758

RESUMO

Objectives: This study is aimed at investigating the role of PIWIL1/piRNA in the development of preeclampsia. Methods: High-throughput sequencing was performed in 5 preeclampsia and 5 normal placentas to get a piRNA expression profile. WGCNA network was constructed to find hub piRNAs. Through target gene prediction and protein interaction network analysis, we found the potential relationship between the key genes and PIWIL1. Subsequently, we detected the expression of PIWIL1 in 35 preeclampsia and 29 normal placental tissues. Overexpression and inhibition of PIWIL1 in HTR-8/SVneo trophoblast cells were achieved by transfecting an overexpression vector and siRNAs, respectively. Cell proliferation, apoptosis, and invasion were assessed using CCK-8, flow cytometric, and transwell assays, respectively. Results: It was found that a total of three piRNAs were upregulated in preeclampsia (pir-hsa-1256314, uniq_271431, and uniq_277797). And two target genes with the highest connectivity (FXR1 and DDX6) both pointed to PIWIL1. PIWIL1 expression was significantly lower in preeclampsia. In vitro studies linked PIWIL1 expression to trophoblast overgrowth. Overexpression of PIWIL1 remarkably promoted cell proliferation and invasion and inhibited apoptosis of HTR-8/SVneo cells and vice versa. Conclusions: PIWIL1/piRNA may be involved in the pathogenesis of preeclampsia by inhibiting the proliferation and invasion and promoting the apoptosis of placental trophoblasts. This study was registered with the China Clinical Trials Registry (http://www.clinicaltrials.gov): registration number ChiCTR1900027479.


Assuntos
Pré-Eclâmpsia , Trofoblastos , Apoptose/genética , Proteínas Argonauta/genética , Proteínas Argonauta/metabolismo , Movimento Celular , Proliferação de Células/genética , Feminino , Humanos , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/metabolismo , Trofoblastos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...