Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.178
Filtrar
2.
Neuroimage ; : 119613, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36075539

RESUMO

How do humans excel at tracking the narrative of a particular speaker with a distracting noisy background? This feat places great demands on the collaboration between speech processing and goal-related regulatory functions. Here, we propose that separate subsystems with different cross-task dynamic activity properties and distinct functional purposes support goal-directed speech listening. We adopted a naturalistic dichotic speech listening paradigm in which listeners were instructed to attend to only one narrative from two competing inputs. Using functional magnetic resonance imaging with inter- and intra-subject correlation techniques, we discovered a dissociation in response consistency in temporal, parietal and frontal brain areas as the task demand varied. Specifically, some areas in the bilateral temporal cortex (SomMotB_Aud and TempPar) and lateral prefrontal cortex (DefaultB_PFCl and ContA_PFCl) always showed consistent activation across subjects and across scan runs, regardless of the task demand. In contrast, some areas in the parietal cortex (DefaultA_pCunPCC and ContC_pCun) responded reliably only when the task goal remained the same. These results suggested two dissociated functional neural networks that were independently validated by performing a data-driven clustering analysis of voxelwise functional connectivity patterns. A subsequent meta-analysis revealed distinct functional profiles for these two brain correlation maps. The different-task correlation map was strongly associated with language-related processes (e.g., listening, speech and sentences), whereas the same-task versus different-task correlation map was linked to self-referencing functions (e.g., default mode, theory of mind and autobiographical topics). Altogether, the three-pronged findings revealed two anatomically and functionally dissociated subsystems supporting goal-directed speech listening.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36076020

RESUMO

Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits including those in Alzheimer's disease. SAP has been observed to be elevated in patients with depression, and higher SAP levels are associated with better response to the antidepressant escitalopram. The mechanisms underlying these clinical observations remain unclear. We examined the effect of SAP on serotonin transporter (SERT) expression and localization using Western blot, confocal microscopy, and positron emission tomography with the radioligand [11C]DASB. We also investigated the effect of SAP on treatment response to escitalopram in mice with the forced swim test (FST), a classical behaviour paradigm to assess antidepressant effects. SAP reduced [11C]DASB binding as an index of SERT levels, consistent with Western blots showing decreased total SAP protein because of increased protein degradation. In conjunction with the global decrease in SERT levels, SAP also promotes VAMP-2 mediated SERT membrane insertion. SAP levels are correlated with behavioural despair and SSRI treatment response in mice with FST. In MDD patients, the SAP and membrane SERT levels are correlated with response to SSRI treatment. SAP has complex effects on SERT levels and localization, thereby modulating the effect of SSRIs, which could partially explain clinical variability in antidepressant treatment response. These results add to our understanding of the mechanism for antidepressant drug action, and with further work could be of clinical utility.

4.
Adv Mater ; : e2206765, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36082582

RESUMO

The limited drug penetration and robust bacteria-mediated drug inactivation in pancreatic cancer result in the failure of chemotherapy. To fight against these issues, a dual-cascade responsive nanoparticle (sNP@G/IR) that can sequentially trigger deep penetration, killing of intratumor bacteria, and controlled release of chemo-drug, is reported. sNP@G/IR consists of a hyaluronic acid (HA) shell and glutathione (GSH) responsive polymer-core (NP@G/IR) that encapsulates gemcitabine (Gem) and photothermal agent (IR1048). The polymer core, as an antibiotic alternative, is tailored to exert the optimal antibacterial activity and selectivity. sNP@G/IR actively homes in tumor due to CD44 targeting of the HA shell, which is subsequently degraded by the hyaluronidase in extracellular matrix. The resultant NP@G/IR in a decreased size and reversed charge facilitates deep tumor penetration. After cellular endocytosis, the exposed guanidine on NP@G/IR kills intracellular bacteria through disrupting cell membranes. Intracellular GSH further triggers the controlled release of cargos. Thus, the protected Gem eventually induces cell apoptosis. Under laser irradiation, the hyperthermia of IR1048 helps further elimination of tumors and bacteria. Moreover, sNP@G/IR activates immune response, thereby reinforcing anticancer capacity. Therefore, this dual-cascade responsive sNP@G/IR eliminates tumor-resident intracellular bacteria and augments drug delivery efficacy, providing a new avenue for improving cancer therapy. This article is protected by copyright. All rights reserved.

5.
Biomed Chromatogr ; : e5501, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36082703

RESUMO

Anlotinib is a novel small molecule multitarget tyrosine kinase inhibitor (TKI) for the treatment of several cancers. We developed and validated a highly sensitive, rapid and stable high-performance liquid chromatography-mass spectrometry (LC-MS/MS) method for the determination of anlotinib in human plasma with anlotinib-d5 as a stable isotopically labeled internal standard (SIL-IS). To explore the feasibility of therapeutic drug monitoring (TDM) in the treatment of tumors with anlotinib, human plasma samples were prepared by protein precipitation (PPT). The mobile phase consisted of A (5.0 mM NH4 AC aqueous solution containing 0.1% formic acid) and B (100% methanol containing 0.1% formic acid). A gradient mobile phase system was adopted for chromatographic separation using a BEH C18 (2.1 mm× 50 mm, 1.7 µm). A positive ion pattern was chosen for quantification under multiple reaction monitoring. The ion pairs were detected at m/z 408.2→339.1 and m/z 413.4→344.3 for anlotinib and anlotinib-d5 (SIL-IS), respectively. The total run time was 5.0 min. The calibration curve was found to be linear within a plasma concentration range of 2-400 ng·mL-1 .The precision and accuracy, matrix effect, extraction recovery and stability were all validated and met the requirements of international guidelines. The proposed methods were successfully applied to support TDM breast and thyroid Cancer patients receiving anlotinib for therapy. Clinical data showed that in the 12 mg dose group, the mean plasma concentrations of anlotinib in breast cancer (BC)patients and thyroid cancer (TC) patients were 87.1 and 118.8ng·mL-1 , respectively. The data demonstrate that the peak concentration of anlotinib it may be related to the different tumor types of patients.

6.
Sci Rep ; 12(1): 15101, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068260

RESUMO

A computational method, dubbed simplified unit-cell micromechanics model, is generalized and applied to establish the effective nonlinear responses of three-phase magnetoelectric composites that are composed of two distinct magnetostrictive and piezoelectric phases embedded in elastic polymer matrices. The nature of nonlinear constitutive behavior of each constituent is expected to significantly influence the overall responses of the composites. To obtain the effective nonlinear responses, a mathematical linearization is first introduced to perform the constitutive linearization for the nonlinear materials, and the resulting constitutive equations are then unified and nested into the micromechanics model followed by iterations in order to minimize errors from the linearization process. For the purpose of comparison, we also reformulate the well-established Mori-Tanaka micromechanics model insofar as its mathematical structure is aligned with that of the simplified unit-cell model. Numerical results are first validated against limited experimental measurements available in literature. Parametric studies are then conducted in order to reveal the effect of phase constitutive laws, volume fractions, and geometries on the overall nonlinear responses of there-phase magnetoelectric composites. The contributions of this work complement those of earlier studies that prevalently devoted to two-phase magnetoelectric composites and linear magneto-electro-elastic coupled responses only.

7.
Pest Manag Sci ; 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36054776

RESUMO

BACKGROUND: The molting hormone 20-hydroxyecdysone (20E) plays a key role in insect development, metamorphosis, and reproduction. Previous studies have shown that ecdysteroid metabolism is regulated by a series of CYP genes in most of the insect species. However, the roles of these CYP genes in a Coleopteran beetle, Aethina tumida (Small Hive Beetle, SHB) have not yet been explored. RESULTS: In the current study, we identified seven CYP genes (six Halloween genes and one AtCYP18A1 gene) related to 20E metabolism. RT-qPCR showed that AtCYP307A1 and AtCYP307B1 were primarily expressed in the embryonic stage and in the cephalothorax of larvae. RNA interference (RNAi) screening revealed that suppression of AtCYP307A1 expression caused a lethal phenotype during the larval-pupal metamorphosis. Furthermore, hematoxylin-eosin staining of the integument showed that the RNAi of AtCYP307A1 inhibited the apolysis and degradation of the old cuticle. In addition, silencing of AtCYP307A1 resulted in significant down-regulation of 20E titers and the expression levels of 20E signaling pathway genes. Finally, the AtCYP307A1 RNAi phenotype was rescued by topical application of 20E. CONCLUSION: Our studies suggest that AtCYP307A1 involved in 20E synthesis is indispensable during the larval-pupal metamorphosis of beetles, which could serve as a putative insecticide target for pest control. This article is protected by copyright. All rights reserved.

8.
Am J Hematol ; 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36054234

RESUMO

Cytomegalovirus (CMV) infection remains a major cause of mortality after hematopoietic stem cell transplantation (HSCT). Current treatments, including anti-viral drugs and adoptive cell therapy with CMV-specific cytotoxic T lymphocytes (CTLs),only show limited benefits in patients. T-cell receptor (TCR)-T cell therapy offers a promising option to treat CMV infections. Here, using tetramer-based screening and single-cell TCR cloning technologies, we identified various CMV antigen-specific TCRs from healthy donors, and generated TCR-T cells targeting multiple pp65 epitopes corresponding to three major HLA-A alleles. The TCR-T cells showed efficient cytotoxicity towards epitope-expressing target cells in vitro. After transfer into immune-deficient mice bearing pp65+ HLA+ tumor cells, TCR-T cells induced dramatic tumor regression and exhibited long-term persistence. In a phase I clinical trial (NCT04153279), CMV TCR-T cells were applied to treat patients with CMV reactivation after HSCT. Except one patient who withdrew at early treatment stage, all other 6 patients were well-tolerated and achieved complete response (CR), no more than grade 2 cytokine release syndrome (CRS) and other adverse events were observed. CMV TCR-T cells persisted up to 3 months. Among them, 2 patients have survived for more than one year. This study demonstrates the great potential in the treatment and prevention of CMV infection following HSCT or other organ transplantation. This article is protected by copyright. All rights reserved.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36063256

RESUMO

This study explored the relationship between temperament-i.e., negative affectivity (NA) and effortful control (EC)-and depression in preadolescents, considering emotion regulation (ER) strategies as mediating mechanisms in this relationship. We examined data from 535 children aged 8-12 years (M ± SD = 10.01 ± 1.42) who completed self-report measures related to NA, EC, ER strategies, depressive symptoms, and depressive mood. The results demonstrated that NA was significantly positively related to both depressive symptoms and depressive mood, while EC was significantly negatively related to both depressive symptoms and depressive mood. The structural equation model of latent variable analysis showed that cognitive reappraisal mediated the relationship between NA and depressive symptoms and depressive mood. Moreover, cognitive reappraisal was also identified as a mediator of the association between EC and depressive symptoms and depressive mood. However, expressive suppression only mediated the relationship between NA and depressive symptoms. Interventions aimed at ER strategies would be an effective program for preadolescents with depression and further improve preadolescents' social-emotional development.

10.
Food Funct ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36093635

RESUMO

Background: The association between the ratio of fiber to carbohydrate (F : C-R) and cancer mortality is not currently well-known. We prospectively evaluated for the first time the aforementioned topic among ovarian cancer (OC) patients. Methods: A total of 703 newly diagnosed OC patients aged 18-79 years were included. Pre-diagnosis diet intake details were collected with a validated food frequency questionnaire. Deaths were ascertained until March 31, 2021, based on medical records and the cancer registry. Cox proportional hazard models were used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) between pre-diagnostic fiber, carbohydrate, and F : C-R intake and OC mortality. Restricted cubic splines were used to analyze the potential nonlinear relationship between F : C-R and OC mortality. Results: During the follow-up period (median: 37.2 months; interquartile: 24.7-50.2 months), we observed 130 (18.49%) OC patients died. The pre-diagnosis higher fiber intake (comparing the highest with the lowest tertile of intake: HR = 0.56, 95% CI = 0.35-0.92; HR per 1 SD increment: 0.78, 95% CI = 0.64-0.96; P trend < 0.05) and higher F : C-R intake (comparing the highest with the lowest tertile of intake: HR = 0.51, 95% CI = 0.31-0.85; HR per 1-SD increment: 0.73; 95% CI = 0.59-0.91; P trend < 0.05) were significantly associated with lower mortality for OC patients, but no evidence of the association between pre-diagnosis carbohydrate intake and OC mortality was observed. We found no evidence of a nonlinear relationship between F : C-R and OC mortality. Significant inverse associations were also observed for subgroup analyses stratified by age at diagnosis, menopausal status, residual lesions, histological type, FIGO stage, and body mass index, although not all associations showed statistical significance. Conclusion: Pre-diagnosis high fiber intake and high F : C-R diet intake were associated with a decreased risk of OC mortality.

11.
Front Plant Sci ; 13: 1000348, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119591

RESUMO

Cotton is an important natural fiber crop worldwide. Cotton fiber cell is regarded as an ideal material for studying the growth and development of plant cells. Sphingolipids are important components of biomembrane and bioactive molecules which participate in many processes such as plant growth, development regulation, stimulus sensing, and stress response. However, the functions of sphingolipids in the cotton fiber development are still unclear. In the present study, we identified a cotton ceramide synthase gene, GhCS1, which is predominantly expressed in fiber cell. The GhCS1 is located in the endoplasmic reticulum and has the conserved domains of ceramide synthase. Overexpression of GhCS1 gene inhibited both vegetative and reproductive growth in cotton. Importantly, the fiber cell initiation and elongation were severely inhibited when compared with control. Comparison of the sphingolipid profile in the 0-DPA (days past anthesis) ovule (with fiber cell) between control and transgenic cotton plants showed that the content of sphingosines (Sph) decreased significantly in transgenic ovules, whereas the content of phyto-sphingosines (Phyto-Sph) had no change. Meanwhile, the content of ceramide containing Sph and very-long-chain fatty acid (VLCFA) increased significantly in transgenic ovules, while ceramide containing Phyto-Sph and long-chain fatty acids (LCFA)/VLCFA significantly decreased. These results indicated that GhCS1 was a functional ceramide synthase, which preferentially used Sph and VLCFA as substrates and was different from the Arabidopsis ceramide synthase AtLOH1/AtLOH3, which preferentially used Phyto-Sph and VLCFA as substrates, and also different from AtLOH2, which preferentially used Sph and LCFA as substrates. It is suggested that GhCS1 might be a new ceramide synthase gene in the plant, play some roles in the development of fiber cells and cotton plants.

12.
Front Pediatr ; 10: 933693, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090579

RESUMO

Kabuki syndrome (KS) is a rare genetic disorder characterized by dysmorphic facial features, skeletal abnormalities, and intellectual disability. KMT2D and KDM6A were identified as the main causative genes. To our knowledge, there exist no cases of KS, which were reported with pneumorrhagia. In this study, a 10-month-old male was diagnosed to have KS with typical facial features, skeletal anomalies, and serious postnatal growth retardation. Whole exome sequencing of the trio family revealed the presence of a de novo KMT2D missense variant (c.15143G > A, p. R5048H). The child was presented to the pediatric emergency department several times because of cough, hypoxemia, and anemia. After performing chest CT and fiberoptic bronchoscopy, we found that the child had a pulmonary hemorrhage. During research on the cause of pulmonary hemorrhage, the patient's anti-GBM antibodies gradually became positive, and the urine microalbumin level was elevated at the age of 12-month-old. After glucocorticoids and immunosuppressant therapy, the patient became much better. But he had recurrent pulmonary hemorrhage at the age of 16 months. Therefore, the patient underwent digital subtraction angiography (DSA). However, the DSA showed three abnormal bronchial arteries. This single case expands the phenotypes of patients with KS and Goodpasture's syndrome, which were found to have a de novo KMT2D missense variant.

13.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(7): 759-761, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36100417

RESUMO

With the widespread application of extracorporeal membrane oxygenation (ECMO) technology, ECMO centers have been established in most regions of China, and the demand for ECMO transport is also increasing. Critically ill patients with ECMO carry many catheters. ECMO devices and accessories are cumbersome and numerous, requiring a large amount of manpower to assist in the transfer. At present, most of ECMO transport equipment are vertical carts provided by equipment suppliers, which cannot accommodate all ancillary equipment and are difficult to be loaded into ambulances for transportation. Therefore, critically ill patients face many risks if they need to be transported inter-hospital. A specific vehicle for ECMO patients was designed by the medical staff of the department of critical care medicine of Zhujiang Hospital of Southern Medical University, which integrates the ECMO host, oxygenator, centrifugal pump, portable ventilator, coagulation instrument, injection pump, monitor, oxygen cylinder, and etc., to greatly facilitate the transportionation. This invention obtained the National Utility Model Patent of China (ZL 2019 2 1201261.4). The new ECMO transport vehicle can facilitate the interhospital transport of critically ill patients, reduce the occurrence of accidents, shorten the transport time and reduce the number of transport personnel, and has a good clinical application value.


Assuntos
Oxigenação por Membrana Extracorpórea , Ambulâncias , Estado Terminal , Humanos , Transferência de Pacientes , Estudos Retrospectivos
14.
Am J Hum Genet ; 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36067766

RESUMO

MTSS2, also known as MTSS1L, binds to plasma membranes and modulates their bending. MTSS2 is highly expressed in the central nervous system (CNS) and appears to be involved in activity-dependent synaptic plasticity. Variants in MTSS2 have not yet been associated with a human phenotype in OMIM. Here we report five individuals with the same heterozygous de novo variant in MTSS2 (GenBank: NM_138383.2: c.2011C>T [p.Arg671Trp]) identified by exome sequencing. The individuals present with global developmental delay, mild intellectual disability, ophthalmological anomalies, microcephaly or relative microcephaly, and shared mild facial dysmorphisms. Immunoblots of fibroblasts from two affected individuals revealed that the variant does not significantly alter MTSS2 levels. We modeled the variant in Drosophila and showed that the fly ortholog missing-in-metastasis (mim) was widely expressed in most neurons and a subset of glia of the CNS. Loss of mim led to a reduction in lifespan, impaired locomotor behavior, and reduced synaptic transmission in adult flies. Expression of the human MTSS2 reference cDNA rescued the mim loss-of-function (LoF) phenotypes, whereas the c.2011C>T variant had decreased rescue ability compared to the reference, suggesting it is a partial LoF allele. However, elevated expression of the variant, but not the reference MTSS2 cDNA, led to similar defects as observed by mim LoF, suggesting that the variant is toxic and may act as a dominant-negative allele when expressed in flies. In summary, our findings support that mim is important for appropriate neural function, and that the MTSS2 c.2011C>T variant causes a syndromic form of intellectual disability.

15.
Oncol Rep ; 48(4)2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36082823

RESUMO

Cell division cycle 45 (CDC45) is an essential protein required for the initiation of DNA replication. In the present study, the role of CDC45 across 33 cancers was systematically investigated. It was observed that the expression of CDC45 was significantly upregulated in most cancers, exhibiting a marked negative correlation with the overall survival. Next, there was no significant difference in prognosis between the genomically altered and unaltered groups with respect to clinical outcomes. A decreased level of CDC45 at the DNA promoter region was also identified in several cancers. Furthermore, CDC45 expression was associated with the levels of tumor­infiltrating immune cells in some specific cancer types. In addition, CDC45 was associated with m6A methylation, and CDC45 expression was primarily positively correlated with 'writers' and 'readers' in various cancers, particularly HNRNPC, RBM15 and YTHDC1. Gene enrichment analysis was also performed. In addition, the AUC of each cancer with respect to its 1­, 3­, and 5­year survival rates were explored. Finally, CCK­8 assays, EdU assays and cell cycle analysis were conducted. In conclusion, the present study demonstrated that CDC45 may be a potential biomarker and target for cancer treatment.


Assuntos
Proteínas de Ciclo Celular , Neoplasias , Carcinogênese/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , DNA , Replicação do DNA/genética , Humanos , Neoplasias/genética , Oncogenes
16.
Front Nutr ; 9: 974367, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091246

RESUMO

Background: Phytosterol is a bioactive compound existing in all plant foods, which might have anticancer properties. The aim of this study was to first assess the impact of the pre-diagnosis phytosterol intake on overall survival (OS) of patients with ovarian cancer (OC). Materials and methods: This ambispective cohort study recruited 703 newly diagnosed OC patients to investigate the aforementioned associations. Dietary intake was assessed using a validated 111-item food frequency questionnaire. Deaths were ascertained until March 31, 2021, through active follow-up and medical records. Cox proportional hazards regression models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During the median follow-up of 37.17 months, 130 deaths occurred. The median age at diagnosis of 703 OC patients was 53.00 (interquartile: 48.00-60.00) years. Of these, almost half patients (48.08%) were diagnosed in advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III-IV). Additionally, more than half patients were serous carcinoma (68.14%), poorly differentiated (85.21%), and no residual lesions (78.66%). Patients consumed the highest tertile of dietary campesterol (HR = 0.54, 95% CI = 0.31-0.94, P trend < 0.05), stigmasterol (HR = 0.60, 95% CI = 0.37-0.98), and ß-sitosterol (HR = 0.63, 95% CI = 0.40-0.99) were significantly associated with better OS compared with those with the lowest tertile of intake. The curvilinear associations were observed between total phytosterols and ß-sitosterol intake and OC survival (P non-linear < 0.05). Significant associations were generally consistent across different subgroups stratified by demographical, clinical, and immunohistochemical characteristics. Moreover, there were significant interactions between phytosterol intake and age at diagnosis, body mass index, as well as expressions of Wilms' tumor-1 and Progestogen Receptor (all P interaction < 0.05). Conclusion: Pre-diagnosis higher campesterol, stigmasterol, and ß-sitosterol intake were associated with better survival among OC patients.

17.
Front Pharmacol ; 13: 959497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091804

RESUMO

Serum creatinine is an endogenous biomarker to estimate glomerular filtration rate (GFR) and is commonly used to assess renal function in clinical practice. Acetaminophen (APAP), the most available analgesic and antipyretic medication, is recommended as the drug of choice for pain control in patients with renal diseases. However, an overdose of APAP can lead to severe acute liver injury, which is also the most common cause of acute liver failure in western countries. The role of creatinine in APAP-induced liver injury is unclear and should be further explored. Herein, clinical data on patients with drug-induced liver injury revealed that the creatinine concentration between 82-442 µmol/L for female and 98-442 µmol/L for male is positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST). While there was no correlation between creatinine and ALT and AST when creatinine concentration is over 442 µmol/L. In addition, mice were administrated with creatinine intraperitoneally for 1 week before APAP injection to investigated the pathophysiological role of creatinine in APAP-induced acute liver injury. The results showed that creatinine administration aggravated hepatic necrosis and elevated serum lactate dehydrogenase (LDH) and ALT levels in mice upon APAP injection. The mechanism study demonstrated that creatinine could increase the production of reactive oxygen activation (ROS) and the activation of c-Jun N-terminal kinase (JNK). Furthermore, the liver injury was alleviated and the difference between APAP-treated mice and APAP combined with creatinine-treated mice was blunted after using specific ROS and JNK inhibitors. Significantly, creatinine stimulation aggravates APAP-induced cell death in HepaRG cells with the same mechanism. In summary, this study proposed that creatinine is closely related with liver function of drug-induced liver injury and exacerbates APAP-induced hepatocyte death by promoting ROS production and JNK activation, thus providing new insight into the usage of APAP in patients with kidney problems.

18.
Front Psychol ; 13: 975335, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092052

RESUMO

Previous research has extended the stress literature by exploring the relationship between family incivility and cyberbullying perpetration, yet relatively less attention has been paid to underlying psychological mechanisms between that relationship among university students. According to the Frustration-Aggression Theory, this study examined the relationships of family incivility, cyberbullying perpetration, negative emotions and neuroticism among Chinese university students. Data were collected from 814 university students (females, N = 423; Mage = 19.96 years, SD = 3.09). The results examined the mechanism through which family incivility was significantly related to cyberbullying perpetration through the mediation of negative emotions, suggesting a strong link of stressful life events to online aggression. In addition, high levels of neuroticism moderated the relationship between family incivility and cyberbullying perpetration, as well as that between family incivility and negative emotions. The study revealed the chronic and potential impact of family incivility, underlined the interaction between stressful life events and online aggression, and put forward the intervention strategies of cyberbullying among university students.

19.
Front Cardiovasc Med ; 9: 992185, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093155

RESUMO

It is arduous to determine clinical solutions for Andersen-Tawil syndrome (ATS) in patients intolerant of ß-blocker. Here, we present the case of a 7-year-old boy with periodic paralysis and dysmorphic features who experienced syncope four times during exercise. His ECG revealed enlarged U waves and QU-prolongation associated with ATS-specific U wave patterns, frequent PVCs, and non-sustained bidirectional or polymorphic ventricular tachycardia. The genetic test showed a de novo missense R218W mutation of KCNJ2. With the diagnosis of ATS and intolerance of ß-blocker, the patient was prescribed oral medications of mexiletine 450 mg/day without severe adverse effects. The repeat ECG showed decreased PVC burden from 38 to 3% and absence of ventricular tachycardia. He remained symptom-free during over 2 years of outpatient follow-up. This case demonstrates a new anti-arrhythmic therapy with mexiletine for prevention of life-threatening cardiac events in patients with ATS who are intolerant of ß-blocker treatment.

20.
Transl Cancer Res ; 11(8): 2660-2670, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36093558

RESUMO

Background: Polypyrimidine tract binding protein 1 (PTBP1) is a member of heterogeneous nuclear ribonucleoprotein (hnRNP) family and has recently been reported to contribute to development and progression of various tumors. However, the clinicopathological significance and prognostic value of PTBP1 in gastric cancer have not been sufficiently elucidated. Methods: Bioinformatic analysis of The Cancer Genome Atlas (TCGA) data were employed to analyze the expression of PTBP1 mRNA and its prognostic value in gastric cancer. The expression type of PTBP1 in gastric cancer cells was further confirmed through reverse transcription polymerase chain reaction (RT-PCR) and western blot assay. Then, the association between PTBP1 protein expression and clinicopathological features was analyzed based on immunohistochemical staining results in gastric cancer tissue microarray including 311 cases. The prognostic value of PTBP1 protein was explored through univariate and multivariate analyses. Additionally, cell count and transwell assay were performed to detect the biological role of PTBP1 in gastric cancer cells in vitro. Results: PTBP1 was highly expressed in gastric cancer cells and tissues at mRNA and protein level. High expression of PTBP1 was closely related to several clinicopathological features, including gender, age at surgery, histological type, TNM stage and lymph node metastasis. Moreover, high expression PTBP1 predicts poor prognosis, and may be an independent prognostic factor for overall survival in gastric cancer patients. Knockdown of PTBP1 substantially suppressed the proliferation, migration and invasion of gastric cancer cells in vitro. Conclusions: PTBP1 is up-regulated and predicts poor prognosis in gastric cancer. PTBP1 may serve as a biomarker of poor prognosis and a novel target in treating gastric cancer.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...