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1.
Genome Res ; 33(10): 1818-1832, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37730437

RESUMO

The subventricular zone (SVZ) is a neurogenic niche that contributes to homeostasis and repair after brain injury. However, the effects of mild traumatic brain injury (mTBI) on the divergence of the regulatory DNA landscape within the SVZ and its link to functional alterations remain unexplored. In this study, we mapped the transcriptome atlas of murine SVZ and its responses to mTBI at the single-cell level. We observed cell-specific gene expression changes following mTBI and unveiled diverse cell-to-cell interaction networks that influence a wide array of cellular processes. Moreover, we report novel neurogenesis lineage trajectories and related key transcription factors, which we validate through loss-of-function experiments. Specifically, we validate the role of Tcf7l1, a cell cycle gene regulator, in promoting neural stem cell differentiation toward the neuronal lineage after mTBI, providing a potential target for regenerative medicine. Overall, our study profiles an SVZ transcriptome reference map, which underlies the differential cellular behavior in response to mTBI. The identified key genes and pathways that may ameliorate brain damage or facilitate neural repair serve as a comprehensive resource for drug discovery in the context of mTBI.


Assuntos
Lesões Encefálicas Traumáticas , Células-Tronco Neurais , Animais , Camundongos , Transcriptoma , Células-Tronco Neurais/metabolismo , Neurônios , Diferenciação Celular , Neurogênese/fisiologia , Lesões Encefálicas Traumáticas/genética , Lesões Encefálicas Traumáticas/metabolismo
2.
Nature ; 565(7737): E3, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30523330

RESUMO

In this Letter, 'released' should have been 'regulated' in the sentence starting: 'Deletion of Atg5 in the host similarly regulated circulating arginine and suppressed tumorigenesis...' This has been corrected online.

3.
Nature ; 563(7732): 569-573, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30429607

RESUMO

Autophagy captures intracellular components and delivers them to lysosomes, where they are degraded and recycled to sustain metabolism and to enable survival during starvation1-5. Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect that manifests as starvation intolerance and gradual loss of white adipose tissue, liver glycogen and muscle mass1. Cancer cells also benefit from autophagy. Deletion of essential autophagy genes impairs the metabolism, proliferation, survival and malignancy of spontaneous tumours in models of autochthonous cancer6,7. Acute, systemic deletion of Atg7 or acute, systemic expression of a dominant-negative ATG4b in mice induces greater regression of KRAS-driven cancers than does tumour-specific autophagy deletion, which suggests that host autophagy promotes tumour growth1,8. Here we show that host-specific deletion of Atg7 impairs the growth of multiple allografted tumours, although not all tumour lines were sensitive to host autophagy status. Loss of autophagy in the host was associated with a reduction in circulating arginine, and the sensitive tumour cell lines were arginine auxotrophs owing to the lack of expression of the enzyme argininosuccinate synthase 1. Serum proteomic analysis identified the arginine-degrading enzyme arginase I (ARG1) in the circulation of Atg7-deficient hosts, and in vivo arginine metabolic tracing demonstrated that serum arginine was degraded to ornithine. ARG1 is predominantly expressed in the liver and can be released from hepatocytes into the circulation. Liver-specific deletion of Atg7 produced circulating ARG1, and reduced both serum arginine and tumour growth. Deletion of Atg5 in the host similarly regulated [corrected] circulating arginine and suppressed tumorigenesis, which demonstrates that this phenotype is specific to autophagy function rather than to deletion of Atg7. Dietary supplementation of Atg7-deficient hosts with arginine partially restored levels of circulating arginine and tumour growth. Thus, defective autophagy in the host leads to the release of ARG1 from the liver and the degradation of circulating arginine, which is essential for tumour growth; this identifies a metabolic vulnerability of cancer.


Assuntos
Arginina/sangue , Autofagia , Neoplasias/sangue , Neoplasias/patologia , Aloenxertos , Animais , Arginase/sangue , Arginase/metabolismo , Arginina/administração & dosagem , Arginina/farmacologia , Autofagia/genética , Proteína 5 Relacionada à Autofagia/deficiência , Proteína 5 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/deficiência , Proteína 7 Relacionada à Autofagia/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Suplementos Nutricionais , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Fígado/enzimologia , Masculino , Camundongos , Transplante de Neoplasias , Neoplasias/genética , Ornitina/metabolismo
4.
Mol Cancer ; 21(1): 153, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879762

RESUMO

BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Biomarcadores , Neoplasias Encefálicas/metabolismo , Proteínas de Ciclo Celular/genética , Glioma/patologia , Humanos , NF-kappa B , Proteínas Nucleares/genética , Prognóstico
5.
Int J Mol Sci ; 23(3)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35163726

RESUMO

Optogenetics is emerging as an ideal method for controlling cellular activity. It overcomes some notable shortcomings of conventional methods in the elucidation of neural circuits, promotion of neuroregeneration, prevention of cell death and treatment of neurological disorders, although it is not without its own limitations. In this review, we narratively review the latest research on the improvement and existing challenges of optogenetics, with a particular focus on the field of brain injury, aiming at advancing optogenetics in the study of brain injury and collating the issues that remain. Finally, we review the most current examples of research, applying photostimulation in clinical treatment, and we explore the future prospects of these technologies.


Assuntos
Lesões Encefálicas , Doenças do Sistema Nervoso , Encéfalo/fisiologia , Lesões Encefálicas/terapia , Humanos , Optogenética/métodos
6.
BMC Nurs ; 21(1): 333, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36447215

RESUMO

BACKGROUND: Coronary heart disease (CHD) has become a leading cause of morbidity and premature death worldwide. Cardiac rehabilitation (CR) was proved to have substantial benefits for patients with CHD. The CR was divided into three phases. Phase 2 is the important part of CR which involves hospital-based structured and closely monitored exercises and activities. However, CR utilization is low worldwide. The barriers to hospital-based phase 2 CR in China have not been well identified. AIMS: To investigate barriers to hospital-based phase 2 cardiac rehabilitation among coronary heart disease patients in China and to explore the reasons. METHODS: This study employed an explanatory sequential mixed-methods design. The study was conducted in a university hospital in China from July 2021 to December 2021. Quantitative data was collected through the Cardiac Rehabilitation Barrier Scale. Qualitative data was collected through unstructured face-to-face interviews. Data analysis included descriptive statistics and inductive qualitative content analysis. RESULTS: One hundred and sixty patients completed the Cardiac Rehabilitation Barrier Scale and 17 patients participated in unstructured face-to-face interviews. The main barriers identified were distance (3.29 ± 1.565), transportation (2.99 ± 1.503), cost (2.76 ± 1.425), doing exercise at home (2.69 ± 1.509) and time constraints (2.48 ± 1.496). Six themes were identified; logistical factors, social support, misunderstanding of cardiac rehabilitation, program and health system-level factors, impression of CR team and psychological distress. The first four themes confirmed the quantitative results and provide a deeper explanation for the quantitative results. The last two themes were new information that emerged in the qualitative phase. CONCLUSION: This study provides a better understanding of the barriers to hospital-based phase 2 cardiac rehabilitation among coronary heart disease patients in the Chinese context during the Covid-19 pandemic. Innovative programs such as home-based CR, mobile health, and hybrid programs might be considered to overcome some of these barriers. In addition, psychosocial intervention should be included in these programs to mitigate some of the barriers associated with the impression of CR team and psychological distress.

7.
BMC Neurol ; 21(1): 411, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702212

RESUMO

BACKGROUND: Cerebral fat embolism (CFE) is a subtype of fat embolism syndrome which tends to cause ischemic cerebral infarction. Fat embolism in the cerebral venous system have not been reported. We hereby present a rare case of fat embolus formed in the cerebral venous system 10 days after cosmetic surgery, and describe our management of this patient. CASE PRESENTATION: A 26-year-old woman with the disturbance of consciousness and recurrent convulsions of the right upper extremity over a 21-h period was admitted to our hospital. The patient was initially diagnosed with haemorrhagic infarction, and cerebral venous thrombosis (CVT) was suspected based on computed tomography (CT). A diagnosis of CFE was confirmed based on surgical findings. Breast and hip augmentation performed 10 days ago was considered the underlying cause. Drug-induced hypothermia, low molecular weight heparin, atorvastatin, dexamethasone, piperacillin/tazobactam, valproic acid, and mannitol were applied. On hospital day 30, she was discharged with a Montreal Cognitive Assessment score of 25. CONCLUSIONS: Fat embolism can occur in the cerebral venous system, and may mimic CVT symptoms rather than CFE symptoms. Early identification of the nature of the embolus is essential. The use of heparin may prevent secondary thrombus formation, and accelerate fat embolus decomposition.


Assuntos
Embolia Gordurosa , Embolia Intracraniana , Trombose Intracraniana , Embolia Pulmonar , Adulto , Embolia Gordurosa/diagnóstico por imagem , Embolia Gordurosa/etiologia , Feminino , Heparina , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/etiologia
8.
Endocrine ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622435

RESUMO

PURPOSE: Multiple daily injection (MDI) insulin therapy is an effective method of glycemic control and appropriate assignment to MDI therapy could minimize the risks of hypoglycemia and weight gain. The aim of the present study was to identify factors associated with indication for MDI therapy in type 2 diabetes (T2DM). METHODS: We recruited 360 participants with T2DM that were admitted to the Endocrinology Department of Peking University People's Hospital between August 2017 and July 2018. They first underwent intensive insulin therapy, then were switched to an optimized, simpler insulin treatment that aimed to maintain fasting blood glucose between 4.4 and 7.2 mmol/L, without episodes of hypoglycemia. The baseline characteristics of groups administering either MDI or basal/premix insulin were compared and multivariable logistic regression analysis was used to determine the odds ratios (ORs) for factors associated with MDI therapy. Receiver operating characteristic (ROC) curves were then used to identify independent predictors of MDI insulin regimen efficacy. RESULTS: The mean age of the participants was 57.6 ± 12.9 years, and diabetes duration was 14.2 ± 8.2 years. Two hundred and sixty-seven participants administered basal/premix insulin and 93 underwent MDI therapy, of whom 61.8% and 46.2% were male, respectively (p = 0.01). The duration of diabetes was significantly longer in the MDI group (13.1 ± 7.7 years vs. 17.3 ± 8.7 years; p < 0.01). Fasting plasma glucose (FPG) was higher in the MDI group than in the basal/premix group (8.3 [6.7, 11.3] mmol/L vs. 7.2 [5.7, 9.3] mmol/L; p < 0.01), while the postprandial C-peptide concentration (PCP) was significantly lower in the MDI group (2.6 [1.8, 3.5] ng/mL) compared to the basal/premix group (3.6 [2.5, 6.2] ng/mL, p < 0.01. Multivariable logistic regression analysis suggested that diabetes duration and FPG were positively associated with MDI therapy: OR (95% confidence interval [CI]) 1.06 (1.02, 1.10) and 1.12 (1.02, 1.24), respectively. In addition, PCP was negatively associated with MDI therapy (0.72 [0.60, 0.86]). ROC analysis suggested that a PCP of < 3.1 ng/mL predicted MDI therapy with 59.6% sensitivity and 72.1% specificity. CONCLUSION: The results of our study suggest that longer diabetes duration, higher FPG, and lower PCP were associated with necessity for MDI insulin regimen. These findings should assist with the personalization of insulin treatment.

9.
Front Chem ; 12: 1417763, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887698

RESUMO

Introduction: Facial nerve injury significantly impacts both the physical and psychological] wellbeing of patients. Despite advancements, there are still limitations associated with autografts transplantation. Consequently, there is an urgent need for effective artificial grafts to address these limitations and repair injuries. Recent years have witnessed the recognition of the beneficial effects of chitosan (CS) and graphene in the realm of nerve repair. Dental pulp stem cells (DPSCs) hold great promise due to their high proliferative and multi-directional differentiation capabilities. Methods: In this study, Graphene/CS (G/CST) composite tubes were synthesized and their physical, chemical and biological properties were evaluated, then DPSCs were employed as seed cells and G/CST as a scaffold to investigate their combined effect on promoting facial nerve injury repair. Results and Disscussion: The experimental results indicate that G/CST possesses favorable physical and chemical properties, along with good cyto-compatibility. making it suitable for repairing facial nerve transection injuries. Furthermore, the synergistic application of G/CST and DPSCs significantly enhanced the repair process for a 10 mm facial nerve defect in rabbits, highlighting the efficacy of graphene as a reinforcement material and DPSCs as a functional material in facial nerve injury repair. This approach offers an effective treatment strategy and introduces a novel concept for clinically managing facial nerve injuries.

10.
Sci Total Environ ; 860: 160115, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36368399

RESUMO

Automobile repair is regarded as a typical domestic source of VOCs in China characterized by numerous sites, wide dispersion and intermittent VOCs emissions. It is of great importance to study and control VOCs from such activities. In this research, emission characteristics, risk assessment and scale effective control of VOCs from automobile repair in Beijing were studied. Results showed that coating spraying and baking were the main processes of VOCs and the major species determined were mostly oxygen-containing VOCs and aromatic hydrocarbons in the case of solvent-based coating usage. Meanwhile, alkanes were determined and accounted for 40 % of total VOCs emissions during the water-based coating spraying and baking. Generally, the total determined VOCs during the automobile repair processes were 1.06-1.27 mg/m3 and 2.93-53.46 mg/m3 for the usage of water-based and solvent-based paint, respectively. Health risk assessments indicated that the residents in the region about 30 m high within a radius of 20 m around the automobile repair plants might suffer from both serious non-carcinogenic and carcinogenic risk threats in the case of solvent-based coating usage in that the values of total hazard index (HI) represented by dichloropropane and acrolein were higher than 1 and the value of lifetime cancer risk (LCR) represented by dichloroethane was higher than 10-5. Besides, those in the region about 30 m high and within a wider radius of 340 m might suffer from carcinogenic risk threat with a certain probability (LCR > 10-6) no matter either solvent-based or water-based coatings were used. As for the scale control of VOCs from automobile repair, independent adsorption by activated carbon combined with mobile regeneration by catalytic combustion was also proposed as an efficient way.


Assuntos
Poluentes Atmosféricos , Neoplasias , Ozônio , Compostos Orgânicos Voláteis , Humanos , Pequim , Poluentes Atmosféricos/análise , Automóveis , Compostos Orgânicos Voláteis/análise , China , Solventes , Carcinógenos , Medição de Risco , Água , Carcinogênese , Monitoramento Ambiental , Ozônio/análise
11.
Sci Data ; 10(1): 638, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730716

RESUMO

As a significant type of traumatic brain injury (TBI), blast-induced traumatic brain injury (bTBI) frequently results in severe neurological and psychological impairments. Due to its unique mechanistic and clinical features, bTBI presents diagnostic and therapeutic challenges compared to other TBI forms. The hippocampus, an important site for secondary injury of bTBI, serves as a key niche for neural regeneration and repair post-injury, and is closely associated with the neurological outcomes of bTBI patients. Nonetheless, the pathophysiological alterations of hippocampus underpinning bTBI remain enigmatic, and a corresponding transcriptomic dataset for research reference is yet to be established. In this investigation, the single-nucleus RNA sequencing (snRNA-seq) technique was employed to sequence individual hippocampal nuclei of mice from bTBI and sham group. Upon stringent quality control, gene expression data from 17,278 nuclei were obtained, with the dataset's reliability substantiated through various analytical methods. This dataset holds considerable potential for exploring secondary hippocampal injury and neurogenesis mechanisms following bTBI, with important reference value for the identification of specific diagnostic and therapeutic targets for bTBI.


Assuntos
Lesões Encefálicas Traumáticas , Transcriptoma , Animais , Camundongos , Lesões Encefálicas Traumáticas/genética , Perfilação da Expressão Gênica , Hipocampo , Reprodutibilidade dos Testes
12.
Acta Biomater ; 167: 473-488, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37271248

RESUMO

Owing to the advantages of the in situ production of toxic agents through catalytic reactions, nanocatalytic therapy has arisen as a highly potential strategy for cancer therapeutics in recent years. However, the insufficient amount of endogenous hydrogen peroxide (H2O2) in the tumor microenvironment commonly limits their catalytic efficacy. Here, we employed carbon vesicle nanoparticles (CV NPs) with high near-infrared (NIR, 808 nm) photothermal conversion efficiency as carriers. Ultrafine platinum iron alloy nanoparticles (PtFe NPs) were grown in situ on the CV NPs, where the highly porous nature of the resultant CV@PtFe NPs was employed to encapsulate a drug, ß-lapachone (La), and phase-change material (PCM). As a multifunctional nanocatalyst CV@PtFe/(La-PCM) NPs can exhibit a NIR-triggered photothermal effect and activate cellular heat shock response, which upregulates the downstream NQO1 via HSP70/NQO1 axis to facilitate bio-reduction of the concurrently melted and released La. Moreover, sufficient oxygen (O2) is supplied by CV@PtFe/(La-PCM) NPs catalyzed at the tumor site to reinforce the La cyclic reaction with abundant H2O2 generation. This promotes the bimetallic PtFe-based nanocatalysis, which breaks H2O2 down into highly toxic hydroxyl radicals (•OH) for catalytic therapy. Our results show that this multifunctional nanocatalyst can be used as a versatile synergistic therapeutic agent with NIR-enhanced nanocatalytic tumor therapy by tumor-specific H2O2 amplification and mild-temperature photothermal therapy, which holds promising potential for targeted cancer treatment. STATEMENT OF SIGNIFICANCE: We present a multifunctional nanoplatform with mild-temperature responsive nanocatalyst for controlled drug release and enhanced catalytic therapy. This work aimed at not only reduce the damage to normal tissues caused by photothermal therapy, but also improves the efficiency of nanocatalytic therapy by stimulating endogenous H2O2 production through photothermal heat. In vitro and in vivo confirmed that CV@PtFe/(La-PCM) NPs exhibited powerful and overall antitumor effects. This formulation may provide an alternative strategy for the development of the mild- photothermal enhanced nanocatalytic therapy effect in solid tumor.


Assuntos
Nanopartículas , Neoplasias , Humanos , Liberação Controlada de Fármacos , Peróxido de Hidrogênio/farmacologia , Temperatura , Linhagem Celular Tumoral , Nanopartículas/uso terapêutico , Catálise , Microambiente Tumoral
13.
Sci Data ; 10(1): 13, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604452

RESUMO

Explosive blast-related traumatic brain injuries (bTBI) are common in war zones and urban terrorist attacks. These bTBIs often result in complex neuropathologic damage and neurologic complications. However, there is still a lack of specific strategies for diagnosing and/or treating bTBIs. The sub-ventricular zone (SVZ), which undergoes adult neurogenesis, is critical for the neurological maintenance and repair after brain injury. However, the cellular responses and mechanisms that trigger and modulate these activities in the pathophysiological processes following bTBI remain poorly understood. Here we employ single-nucleus RNA-sequencing (snRNA-seq) of the SVZ from mice subjected to a bTBI. This data-set, including 15272 cells (7778 bTBI and 7494 control) representing all SVZ cell types and is ideally suited for exploring the mechanisms underlying the pathogenesis of bTBIs. Additionally, it can serve as a reference for future studies regarding the diagnosis and treatment of bTBIs.


Assuntos
Traumatismos por Explosões , Lesões Encefálicas Traumáticas , Lesões Encefálicas , Animais , Camundongos , Traumatismos por Explosões/complicações , Traumatismos por Explosões/patologia , Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Lesões Encefálicas Traumáticas/complicações
14.
Artigo em Inglês | MEDLINE | ID: mdl-36999178

RESUMO

BACKGROUND: A significant part of blast injury is accompanied by hemorrhagic shock (BS), while research on its fluid resuscitation strategies have not been reported. Although blood products are usually recommended in most resuscitation cases, they are less available in certain conditions. To this end, here, we focused on a widely used and more accessible fluid type- crystalloid fluid, in BS treatment. METHODS: We conducted studies in rats comparing the therapeutic effects of 3 different crystalloid solutions at different time points after BS, and explored the underlying mechanisms. Generally, the survival rates gradually dropped along with the time when fluid resuscitation was given. RESULTS: Among different types of solution, the hypertonic saline (HS) group showed the highest survival rates. The lactated Ringer's solution (LR) only displayed lifesaving effect at 0.5h resuscitation time point. Moreover, it is worth noting that the survival rates of the normal saline (NS) group at all the time points were lower than the non-treatment control. Mechanism study in rats indicated that the therapeutic differences may be caused by varied degrees of pulmonary edema and inflammatory responses under different crystalloid fluid resuscitation. CONCLUSIONS: In conclusion, we assessed the effects and investigated the mechanisms of different crystalloid fluid resuscitation strategies for BS for the first time, which potentially contributes to the establishment of guidance for crystalloid fluid resuscitation of BS patients.

15.
Nutrition ; 109: 111992, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36871445

RESUMO

Ferroptosis, a newly characterized form of programmed cell death that results from lipid peroxidation and mitochondrial dysfunction, has been demonstrated to be involved in the pathogenesis of traumatic brain injury (TBI). Scientific evidence has shown that intermittent fasting (IF) reduces both the lipid peroxidation and the mitochondrial dysfunction, raising the question of whether IF affects the ferroptosis induced by TBI. Here, based on an established TBI animal model, we examine the effects of IF on the activation of ferroptosis pathway as well as related outcomes. We uncovered that a 1-mo IF elevated the protective Gpx4 and Hspb1 expression, and partly abolished the increase of Nfe2l2, Slc7a11, Alox8, Steap3, and Nox2 in the cortex, which were induced by TBI. Furthermore, the characteristic cellular damage induced by ferroptosis was alleviated by IF, as revealed by Perls' Prussian blue staining, Nissl staining, and transmission electron microscope examination. Consistently, we examined the outcomes of mice subjected to TBI and found an improved cognitive function of the IF mice. In sum, our study demonstrated, to our knowledge for the first time, that a 1-mo IF regimen partly ameliorates ferroptosis in the cortex of mice subjected to TBI, which potentially contributes to a lessening of cognitive impairment.


Assuntos
Lesões Encefálicas Traumáticas , Disfunção Cognitiva , Ferroptose , Camundongos , Animais , Jejum Intermitente , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Neurônios/metabolismo
16.
Mol Biol Rep ; 39(1): 1-4, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22033829

RESUMO

We aimed to investigate whether interleukin-10 (IL-10) -1082 G/G genotype is associated with lower mortality of acute respiratory distress syndrome (ARDS) in a Chinese population. A hospital-based case-control study was conducted in 314 cases of ARDS and 210 controls who were admitted to an intensive care unit with sepsis, trauma, aspiration or massive transfusions. Cases were followed for 30-day mortality. The -1082G/G genotype was associated with lower development of ARDS (OR=0.51; 95% CI 0.34-0.76; P=0.001). Among patients with ARDS, the -1082G/G genotype was associated with lower 30-day mortality (OR=0.44; 95% CI 0.25-0.76; P=0.003). In conclusion, IL-10-1082 G/G genotype is associated with lower development and mortality of ARDS in a Chinese population.


Assuntos
Interleucina-10/genética , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/mortalidade , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Primers do DNA/genética , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
17.
Oral Oncol ; 124: 105466, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34348839

RESUMO

Sarcomatoid carcinoma of maxillary sinus tumor is extremely rare in head and neck tumors and has poor prognosis and frequently occurs to relapse locally after surgery. We first reported a case of locally advanced undifferentiated sarcomatoid carcinoma of right maxillary sinus with PDCD6-TERT fusion gene. The patient with a previous history of moderate alcohol drinking and smoking. The patient underwent surgical treatment. The tumor tissue using NGS analysis, no other driver gene mutations, and the PD-L1 IHC was negative. He received TPF regimen induction chemotherapy combined with anti-PD1 inhibitor and radiotherapy. The effect of treatment was good.


Assuntos
Carcinoma , Neoplasias de Cabeça e Pescoço , Neoplasias do Seio Maxilar , Telomerase , Proteínas Reguladoras de Apoptose , Proteínas de Ligação ao Cálcio , Humanos , Masculino , Seio Maxilar , Neoplasias do Seio Maxilar/diagnóstico por imagem , Neoplasias do Seio Maxilar/genética , Neoplasias do Seio Maxilar/cirurgia , Recidiva Local de Neoplasia
18.
Pharmaceuticals (Basel) ; 15(12)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36558933

RESUMO

Background: Due to the blood-brain barrier and limited antibiotic choices, polymyxin is currently the first-line agent for the treatment of central nervous system infections (CNSIs) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin sulfate, as a polymyxin E different from CMS, is used in Chinese clinics, and there are limited reports on its use in the treatment of CNSIs. Case Presentation: This case describes a 76-year-old man who underwent complex neurosurgery for cervical spinal stenosis. Postoperatively, the patient developed a fever and a poorly healed surgical wound. Numerous blood routine tests, inflammatory markers, pathogenic tests of cervical secretions, cerebrospinal fluid (CSF), and sputum were sent for diagnosis. After empirical antimicrobial treatments failed, the CSF and wound pus cultured carbapenem-resistant Klebsiella pneumoniae. The regimen was adjusted to colistin sulfate intravenously and intrathecal injection combined with tigecycline. In addition, the management of infection foci, including continuous lumbar pool drain, cervical 3-5 internal fixation removal with cervical 1-6 spine dilation, CSF leak repair, and right thigh broad fasciotomy, were performed. After treatment, the patient was discharged with multiple sets of negative CSF cultures and the infection under control. Conclusions: For CNSIs caused by MDR-GNB, the selection of colistin sulfate for intravenous and topical combination treatment is a viable choice.

19.
J Colloid Interface Sci ; 623: 267-276, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35588634

RESUMO

Generally, it is important to ameliorate the co-catalyst used in photocatalytic hydrogen evolution reactions (PHERs) to achieve efficient transfer and separation of photogenerated carriers, decrease the surface reaction energy barrier, and hence improve the photocatalytic activity. In this study, N-doped graphite carbon (GC) was introduced in situ to MoO2 to ensure the presence of well-dispersed active sites, lower the overpotential of hydrogen evolution, and further achieve high conductivity. Then, the MoO2/GC composite obtained was used as a co-catalyst of ZnIn2S4 (ZIS) in a PHER, resulting in a great improvement in the photocatalytic activity. Given the metallicity and large work function of MoO2/GC, a Schottky interface can form between MoO2/GC and ZIS, which accelerates the transmission of photogenerated electrons. As a result, the separation efficiency of photogenerated carriers improves, whereas the surface overpotential of PHERs clearly decreases for ZIS. This study proposes a new idea for exploiting efficient co-catalysts and promotes the wide and heavy use of carbon materials in the field of solar energy conversion.

20.
Nutrition ; 97: 111621, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35255397

RESUMO

OBJECTIVES: Interventions for preventing cognitive dysfunction after traumatic brain injury (TBI) are limited. Given that adult hippocampal neurogenesis after brain injury contributes to cognitive recovery, and hippocampal neurogenesis is potentially affected by nutritional factors, the aim of this study was to examine whether fasting could promote hippocampal neurogenesis and thus ameliorate the cognitive defects after TBI. METHODS: The present study used 8- to 10-wk-old C57 BL/6 N mice weighing 23 g, half males and half females. The mice were randomly assigned to each group, with 10 to 18 mice per group. All mice were housed in an approved animal facility with a 12-h light/dark cycle. In the metabolic study (food intake, body weight, blood glucose, triacylglycerol, total cholesterol, and ß-hydroxybutyric acid ), 54 mice (male:female = 1:1) were randomized to the ad libitum (AL) group (n = 18) and the intermittent fasting (IF) group (n = 36). In the neurogenesis study, 45 mice (male:female = 1:1) were randomized to AL (n  = 18), IF (n  = 9), IF + scramble (n  = 9), and the IF + neuropeptide Y (NPY)_siRNA (n  = 9) groups. In the Morris water maze test, 48 mice (male:female = 1:1) were randomized to AL (n  = 12), IF (n  = 12), IF + scramble (n  = 12), and the IF + NPY_siRNA (n  = 12) groups. RESULTS: We showed that a 1-mo-long IF regimen enhanced the proliferation of neural stem cells in the subgranular zone of the hippocampus 3 d after TBI, in addition to improving the cognitive performance in the Morris water maze test. Furthermore, an increase in the hippocampal NPY expression was detected in the IF group after the injury, compared with the mice fed AL, and local knockdown of NPY in vivo attenuated the effects of IF on TBI. CONCLUSIONS: These findings suggest that IF promotes hippocampal neurogenesis after TBI by a mechanism that involves enhancement of NPY expression, to alleviate cognitive dysfunction caused by injury.


Assuntos
Lesões Encefálicas Traumáticas , Neuropeptídeo Y , Animais , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/terapia , Jejum , Feminino , Hipocampo , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese , Neurônios/metabolismo , Neuropeptídeo Y/metabolismo , Neuropeptídeo Y/farmacologia , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/farmacologia
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