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1.
Sci Total Environ ; 923: 171349, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38438030

RESUMO

Benzo(a)pyrene as a pervasive environmental contaminant is characterized by its substantial genotoxicity, and epidemiological investigations have established a correlation between benzo(a)pyrene exposure and the susceptibility to human lung cancer. Notably, much research has focused on the link between epigenetic alterations and lung cancer induced by chemicals, although circRNAs are also emerging as relevant contributors to the carcinogenic process of benzo(a)pyrene. In this study, we identified circ_0067716 as being significantly upregulated in response to stress injury and downregulated during malignant transformation induced by benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) in human bronchial epithelial cells. The observed differential expression of circ_0067716 in cells treated with BPDE for varying durations suggests a strong correlation between this circRNA and BPDE exposure. The tissue samples of lung cancer patients also suggest that a lower circ_0067716 expression is associated with BPDE-DNA adduct levels. Remarkably, we demonstrate that EIF4A3, located in the nucleus, interacts with the flanking sequences of circ_0067716 and inhibits its biogenesis. Conversely, circ_0067716 is capable of sequestering EIF4A3 in the cytoplasm, thereby preventing its translocation into the nucleus. EIF4A3 and circ_0067716 can form a double-negative feedback loop that could be affected by BPDE. During the initial phase of BPDE exposure, the expression of circ_0067716 was increased in response to stress injury, resulting in cell apoptosis through the involvement of miR-324-5p/DRAM1/BAX axis. Subsequently, as cellular adaptation progressed, long-term induction due to BPDE exposure led to an elevated EIF4A3 and a reduced circ_0067716 expression, which facilitated the proliferation of cells by stabilizing the PI3K/AKT pathway. Thus, our current study describes the effects of circ_0067716 on the genotoxicity and carcinogenesis induced by benzo(a)pyrene and puts forwards to the possible regulatory mechanism on the occurrence of smoking-related lung cancer, providing a unique insight based on epigenetics.


Assuntos
Neoplasias Pulmonares , MicroRNAs , Humanos , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/metabolismo , Benzo(a)pireno/metabolismo , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/farmacologia , Células Epiteliais , Fator de Iniciação 4A em Eucariotos/metabolismo , Fator de Iniciação 4A em Eucariotos/farmacologia , Retroalimentação , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo
2.
Mol Med ; 30(1): 4, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172666

RESUMO

BACKGROUND: Autophagic defects are involved in Methamphetamine (Meth)-induced neurotoxicity. Syntaxin 17 (Stx17), a member of the SNARE protein family, participating in several stages of autophagy, including autophagosome-late endosome/lysosome fusion. However, the role of Stx17 and potential mechanisms in autophagic defects induced by Meth remain poorly understood. METHODS: To address the mechanism of Meth-induced cognitive impairment, the adenovirus (AV) and adeno-associated virus (AAV) were injected into the hippocampus for stereotaxis to overexpress Stx17 in vivo to examine the cognitive ability via morris water maze and novel object recognition. In molecular level, the synaptic injury and autophagic defects were evaluated. To address the Meth induced neuronal damage, the epidermal growth factor receptor (EGFR) degradation assay was performed to evaluate the degradability of the "cargos" mediated by Meth, and mechanistically, the maturation of the vesicles, including autophagosomes and endosomes, were validated by the Co-IP and the GTP-agarose affinity isolation assays. RESULTS: Overexpression of Stx17 in the hippocampus markedly rescued the Meth-induced cognitive impairment and synaptic loss. For endosomes, Meth exposure upregulated Rab5 expression and its guanine-nucleotide exchange factor (GEF) (immature endosome), with a commensurate decreased active form of Rab7 (Rab7-GTP) and impeded the binding of Rab7 to CCZ1 (mature endosome); for autophagosomes, Meth treatment elicited a dramatic reduction in the overlap between Stx17 and autophagosomes but increased the colocalization of ATG5 and autophagosomes (immature autophagosomes). After Stx17 overexpression, the Rab7-GTP levels in purified late endosomes were substantially increased in parallel with the elevated mature autophagosomes, facilitating cargo (Aß42, p-tau, and EGFR) degradation in the vesicles, which finally ameliorated Meth-induced synaptic loss and memory deficits in mice. CONCLUSION: Stx17 decrease mediated by Meth contributes to vesicle fusion defects which may ascribe to the immature autophagosomes and endosomes, leading to autophagic dysfunction and finalizes neuronal damage and cognitive impairments. Therefore, targeting Stx17 may be a novel therapeutic strategy for Meth-induced neuronal injury.


Assuntos
Autofagossomos , Autofagia , Animais , Camundongos , Autofagossomos/metabolismo , Endossomos/metabolismo , Receptores ErbB/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Guanosina Trifosfato/metabolismo
3.
Ann Vasc Surg ; 99: 117-124, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37972727

RESUMO

BACKGROUND: The aim of this paper was to report our experience in the management of isolated abdominal aortic dissection with endovascular aortic repair and conservative treatment. METHODS: A cohort of 22 consecutive patients with isolated abdominal aortic dissection was treated between January 2016 and December 2021. We reviewed the demographics, clinical features, therapeutic modalities and follow-up results. Retrospective data analysis from patient charts was performed. RESULTS: Twenty-two patients were enrolled in this study from 2 centers. The mean age was 66.2 ± 13.3 years. Hypertension was the primary risk factor. Seventeen (72.7%) patients were asymptomatic, and 18 patients were subrenal artery type (type II). A total of 12 patients had successful endovascular repair (EVAR), and 10 patients underwent conservative treatment. In the group receiving conservative treatment, no patients required EVAR during follow-up, and 4 patients died. However, none of them had aortic causes: 2 patients had cardiac causes, the other 2 had cancer, and the others remained symptom-free. The latest computed tomographic angiography images showed that abdominal aortic dissection still existed, and the extent of the false lumen did not increase significantly. CONCLUSIONS: Both conservative treatment and EVAR are effective treatment options. Appropriate treatment needs to be performed according to different patients' clinical manifestations and doctors' experience.


Assuntos
Aneurisma da Aorta Abdominal , Dissecção Aórtica , Implante de Prótese Vascular , Dissecção da Aorta Abdominal , Procedimentos Endovasculares , Humanos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Implante de Prótese Vascular/efeitos adversos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/etiologia , Estudos Retrospectivos , Fatores de Risco , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos
4.
Exp Ther Med ; 27(1): 36, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38125357

RESUMO

Local ulcerative cutaneous hemorrhage resulting from breast cancer profoundly effects the quality of life of patients, at times even posing a threat to life. While early diagnosis rates of breast cancer have shown improvement, some patients may present at an advanced stage upon consultation. Presently, there is no standardized treatment approach for these patients. In this context, the present study presented two case studies detailing the use of interventional embolization chemotherapy for addressing severe local ulcerative hemorrhage associated with breast cancer. Post-treatment, there was a notable amelioration in the mammary ulceration among the patients, an elevated hemoglobin level compared with baseline and a consequent enhancement in their overall quality of life. These cases may serve as valuable references for the management of such clinical situations.

5.
Opt Express ; 31(13): 21845-21862, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37381272

RESUMO

Revealing the expansion and interaction dynamics of multiple shock waves induced by a nanosecond laser is important for controlling laser surgery. However, the dynamic evolution of shock waves is a complex and ultrafast process, making it difficult to determine the specific laws. In this study, we conducted an experimental investigation into the formation, propagation, and interaction of underwater shock waves that are induced by nanosecond laser pulses. The effective energy carried by the shock wave is quantified by the Sedov-Taylor model fitting with experimental results. Numerical simulations with an analytic model using the distance between adjacent breakdown locations as input and effective energy as fit parameters provide insights into experimentally not accessible shock wave emission and parameters. A semi-empirical model is used to describe the pressure and temperature behind the shock wave taking into account the effective energy. The results of our analysis demonstrate that shock waves exhibit asymmetry in both their transverse and longitudinal velocity and pressure distributions. In addition, we compared the effect of the distance between adjacent excitation positions on the shock wave emission process. Furthermore, utilizing multi-point excitation offers a flexible approach to delve deeper into the physical mechanisms that cause optical tissue damage in nanosecond laser surgery, leading to a better comprehension of the subject.

6.
Ecotoxicol Environ Saf ; 258: 114996, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37167740

RESUMO

A growing body of evidence shows that cigarette smoking impairs cognitive performance. The 'Calcium Hypothesis' theory of neuronopathies reveals a critical role of aberrant calcium signaling in compromised cognitive functions. However, the underlying implications of abnormalities in calcium signaling in the neurotoxicity induced by cigarette smoke (CS) have not yet been identified. CACNA2D1, an important auxiliary subunit involved in the composition of voltage-gated calcium channels (VGCCs), was reported to affect the calcium signaling in neurons by facilitating VGCCs-mediated Ca2+ influx. ΔFOSB, an alternatively-spliced product of the Fosb gene, is an activity-dependent transcription factor induced robustly in the brain in response to environmental stimuli such as CS. Interestingly, our preliminary bioinformatics analysis revealed a significant co-expression between ΔFOSB and CACNA2D1 in brain tissues of patients with neurodegenerative diseases characterized by progressive cognitive decline. Therefore, we hypothesized that the activation of the ΔFOSB-CACNA2D1 axis in response to CS exposure might cause dysregulation of calcium homeostasis in hippocampal neurons via VGCCs-mediated Ca2+ influx, thereby contributing to cognitive deficits. To this end, the present study established a CS-induced mouse model of hippocampus-dependent cognitive impairment, in which the activation of the ΔFOSB-CACNA2D1 axis accompanied by severe calcium overload was observed in the mouse hippocampal tissues. More importantly, ΔFOSB knockdown-/overexpression-mediated inactivation/activation of the ΔFOSB-CACNA2D1 axis interdicted/mimicked CS-induced dysregulation of calcium homeostasis followed by severe cellular damage in HT22 mouse hippocampal neurons. Mechanistically speaking, a further ChIP-qPCR assay confirmed the physical interaction between transcription factor ΔFOSB and the Cacna2d1 gene promoter, suggesting a direct transcriptional regulation of the Cacna2d1 gene by ΔFOSB. Overall, our current work aims to deliver a unique insight into the neurotoxic mechanisms induced by CS to explore potential targets for intervention.


Assuntos
Cálcio , Fumar Cigarros , Camundongos , Animais , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Cognição
7.
Eur J Med Chem ; 257: 115492, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37210838

RESUMO

Multiple myeloma (MM) is a hematologic neoplasm of plasma cells that is currently deemed incurable. Despite the introduction of novel immunomodulators and proteasome inhibitors, MM remains a challenging disease with high rates of relapse and refractoriness. The management of refractory and relapsed MM patients remains a formidable task, primarily due to the emergence of multiple drug resistance. Consequently, there is an urgent need for novel therapeutic agents to address this clinical challenge. In recent years, a significant amount of research has been dedicated to the discovery of novel therapeutic agents for the treatment of MM. The clinical utilization of proteasome inhibitor carfilzomib and immunomodulator pomalidomide has been successively introduced. As basic research continues to advance, novel therapeutic agents, including panobinostat, a histone deacetylase inhibitor, and selinexor, a nuclear export inhibitor, have progressed to the clinical trial and application phase. This review aims to furnish a comprehensive survey of the clinical applications and synthetic pathways of select drugs, with the intention of imparting valuable insights for future drug research and development geared towards MM.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Panobinostat/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Inibidores de Proteassoma , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
8.
Biotechnol Genet Eng Rev ; : 1-17, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-36999778

RESUMO

Tumor imaging represents an ideal environment for collecting novel biomarkers from different technologies, as patients with tumors often undergo multiple imaging studies.With the aging of the Chinese population, the number of elderly patients with gastric cancer is also increasing. In the past, patients with gastric cancer in the elderly have been conservative in whether surgical treatment can be performed, and advanced age is regarded as a relative contraindication to the effect of surgical treatment on gastric cancer patients. To investigate the clinical characteristics of patients with upper gastrointestinal hemorrhage complicated by deep vein thrombosis in elderly patients with gastric cancer. One patient with upper gastrointestinal hemorrhage complicated by deep venous thrombosis, and elderly gastric cancer patients admitted to our hospital on 11 October 2020, were selected. After anti-shock symptomatic support, filter placement, prevention and treatment of thrombosis, gastric cancer eradication, anticoagulation, immune regulation, etc. Treatment and long-term follow-up observation. Long-term follow-up showed that the patient's condition was stable, there was no sign of metastasis or recurrence after radical gastrectomy for gastric cancer, and there were no serious pre- and post-operative complications such as upper gastrointestinal bleeding and deep vein thrombosis, and the prognosis was satisfactory. How to choose the appropriate operation timing and method for elderly gastric cancer patients with upper gastrointestinal bleeding and deep vein thrombosis at the same time to maximize benefits, clinical experience in this area is particularly valuable.

9.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36769161

RESUMO

Pancreatic cancer (PC) is one of the most aggressive malignancies. A combination of targeted therapies could increase the therapeutic efficacy in tumors with heterogeneous target expression. Overexpression of the human epidermal growth factor receptor type 3 (HER3) and the epithelial cell adhesion molecule (EpCAM) in up to 40% and 30% of PCs, respectively, is associated with poor prognosis and highlights the relevance of these targets. Designed ankyrin repeat protein (DARPin) Ec1 fused with the low immunogenic bacterial toxin LoPE provides specific and potent cytotoxicity against EpCAM-expressing cancer cells. Here, we investigated whether the co-targeting of HER3 using the monoclonal antibody seribantumab (MM-121) and of EpCAM using Ec1-LoPE would improve the therapeutic efficacy in comparison to the individual agents. Radiolabeled 99mTc(CO)3-Ec1-LoPE showed specific binding with rapid internalization in EpCAM-expressing PC cells. MM-121 did not interfere with the binding of Ec1-LoPE to EpCAM. Evaluation of cytotoxicity indicated synergism between Ec1-LoPE and MM-121 in vitro. An experimental therapy study using Ec1-LoPE and MM-121 in mice bearing EpCAM- and HER3-expressing BxPC3 xenografts demonstrated the feasibility of the therapy. Further development of the co-targeting approach using HER3 and EpCAM could therefore be justified.


Assuntos
Proteínas de Repetição de Anquirina Projetadas , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Molécula de Adesão da Célula Epitelial , Xenoenxertos , Estudos de Viabilidade , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Modelos Animais de Doenças , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Pancreáticas
10.
Ann Vasc Surg ; 89: 338-352, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36343863

RESUMO

BACKGROUND: The aim of this study was to evaluate the safety, applicability, and outcomes of the endovascular aneurysm repair (EVAR) technique for patients in mainland China with abdominal aortic aneurysm (AAA) by performing a systematic review. METHODS: We conducted a systematic search using the PubMed, Embase, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases to identify Chinese studies on the management of AAAs using the EVAR technique published in English between January 2000 and December 2020. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The included studies investigated the clinical outcomes and postprocedural complications of using EVAR techniques. RESULTS: Sixteen studies reported a total of 3,024 AAA patients. The follow-up period ranged from 1 to 133 months. The mean follow-up time was 38.5 months, the mean age was 69.2 years, and the mean aneurysm diameter was 56.1 mm. The pooled technical success rate was 95% (95% confidence interval [CI]: 92-96%). The endoleak rate was 7% (95% CI: 6-8%). The rate of endoleak requiring reintervention was 3% (95% CI: 3-4%). The 30-day morbidity rate was 9% (95% CI: 6-14%). The 30-day mortality rate was 2% (95% CI: 1-3%). The follow-up mortality was 5% (95% CI: 3-8%). CONCLUSIONS: The results of the study showed that using the EVAR technique for treating patients in mainland China with AAAs produced encouraging mid-term outcomes. Long-term outcomes should be examined in future research.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Endoleak , Resultado do Tratamento , Implante de Prótese Vascular/efeitos adversos , Fatores de Risco , Estudos Retrospectivos
11.
Biochem Pharmacol ; 206: 115344, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36372331

RESUMO

Tobacco remains the most common environmental carcinogen leading to the occurrence and development of lung cancer. Nicotine, a tumor promoter in cigarette smoke, has been shown to induce epithelial-mesenchymal transition (EMT), a cellular program required for the invasion and metastasis in tumor cells. Specificity Protein 1 (SP1) is a well-characterized transcription factor that can regulate the EMT process via transcriptionally activating E-cadherin expression. Protein Phosphatase 1 Regulatory Subunit 13 Like (PPP1R13L) is a newly identified oncoprotein previously reported to inhibit the transcriptional activity of SP1 via a direct protein-protein interaction. To reveal the underlying implication of the interconnections between PPP1R13L and SP1 in the nicotine-induced EMT process, the present study established an EMT cell model of lung cancer using 1 µM of nicotine, a dose close to human exposure, in which an alternate fluctuation in the expression of PPP1R13L and SP1 was captured. Subsequently, the direct inhibition of SP1 by PPP1R13L was demonstrated to be a critical mechanism underlying the involvement of PPP1R13L in the nicotine-induced EMT process. More interestingly, SP1 was further shown to transcriptionally activate PPP1R13L expression in a feedback manner. In addition, PPP1R13L and SP1 expression was found to be closely associated with the clinicopathological characteristics of lung cancer patients. Here we proposed a novel feedback regulation mechanism, in which SP1 may transcriptionally activate the PPP1R13L gene expression in the early stage of lung cancer to promote tumor growth, while the accumulation of PPP1R13L drives tumor invasion and metastasis by direct repression of SP1. Thus, this unique feedback loop between PPP1R13L and SP1 may play a vital role in chemical carcinogenesis and serve as a potential intervention target for lung cancer progression attributable to cigarette smoking.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Transição Epitelial-Mesenquimal , Nicotina/toxicidade , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo , Retroalimentação , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão/genética , Fatores de Transcrição/metabolismo , Proteínas Oncogênicas/metabolismo , Linhagem Celular Tumoral , Fator de Transcrição Sp1 , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Proteínas Repressoras/metabolismo
12.
J Cell Mol Med ; 26(21): 5439-5451, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36181289

RESUMO

Platinum-based chemotherapy is regarded as a preferential curative-intent option for non-small cell lung cancer (NSCLC), while the acquired drug resistance has become a major obstacle that limits its clinical application. Since the repair efficiency of tumour cells to platinum-DNA adducts plays a crucial role in chemotherapy resistance, we aimed to explore whether several meaningful polymorphisms of DNA repair genes were associated with the benefits of platinum-based chemotherapy in NSCLC patients. Firstly, six single nucleotide polymorphisms (SNPs) located in the 3'untranslated region (3'UTR) of three DNA repair genes were detected in 246 NSCLC patients receiving platinum-based chemotherapy and analysed the correlation of these candidate SNPs with the overall survival. Cox proportional hazard model showed that NSCLC patients carrying ERCC1 rs3212986 AA genotype had a shorter overall survival compared to those with CC. Mechanistically, we performed tumour chemosensitivity assay to observe the convincing linkage of rs3212986 polymorphism with ERCC1 expression and cisplatin sensitivity. The subsequent in vitro experiments identified that rs3212986 polymorphism altered the post-transcriptional regulation of ERCC1 via affecting the binding of miR-15a, and further changed the sensitivity to platinum analogue. It reminded that patients carrying ERCC1 rs3212986 CC homozygote were expected to respond better to platinum-based chemotherapy due to a lower expression of ERCC1. Compared with previous studies, our current comprehensive study suggested that rs3212986, a 3'UTR polymorphism in ERCC1, might have clinical relevance in predicting the prognosis of NSCLC patients receiving platinum-based chemotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Regiões 3' não Traduzidas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Platina/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética
13.
Front Surg ; 9: 963399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017519

RESUMO

Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by the calcification and ossification of ligaments and tendons. Progressive dysphagia caused by DISH-related anterior cervical osteophytes and deteriorating dysphagia caused by DISH combined with neurological dysfunction resulting from the posterior longitudinal ligament is rare. The initial diagnosis is misleading and patients often consult several specialists before spine surgeons. This study aims to provide a comprehensive review of the literature on this challenging pathological association. We also present a case illustration where a 53-year-old man presented with progressive dysphagia and foreign body sensation in the pharynx, accompanied by a neurological numbness defect in the right upper limb. Radiography and computed tomography confirmed the existence of osteophytes at the anterior edge of the C4-C7 pyramid and ossification of the posterior longitudinal ligament, in which the giant coracoid osteophyte could be seen at the anterior edge of the C4-C5 pyramid. The anterior cervical osteophyte was removed, and decompression and fusion were performed. The symptoms were relieved postoperatively. No recurrence of symptoms was found during the six-month follow-up. Spine surgeons should consider progressive dysphagia caused by DISH-related osteophytes at the anterior edge of the cervical spine as it is easily misdiagnosed and often missed on the first evaluation. When combined with ossification of the posterior longitudinal ligament, following cervical osteophyte resection it is necessary to consider stabilizing the corresponding segments via fusion.

14.
J Chem Neuroanat ; 121: 102088, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35283255

RESUMO

Aging is the primary cause of neurodegenerative diseases, which are mainly characterized by cognitive decline and neuropsychiatric symptoms. Corn embryo, an important component of corn kernels, contains plenty of essential nutrients and bioactive compounds. However, corn embryo is often removed in the process of refining corn. To reveal potential biological benefits of corn embryo, the present study investigated the intervention effects of corn embryo on age-related cognitive decline and neuropsychiatric symptoms. Ninety male Wistar rats were randomly divided into six groups: Control, Corn embryo, Aging model, Low-, Medium- and High-dose intervention group. Aging models induced by an intraperitoneal injection of 60 mg/kg D-galactose plus a gavage of 200 mg/kg aluminum chloride were intervened with a gavage of 0.3, 0.6 or 1 g/kg corn embryo while the Control and Corn embryo groups received saline and 0.6 g/kg corn embryo respectively. Morris water maze and open field test were performed to assess cognitive abilities and anxiety-like behaviors. Brain biochemical parameters including the malondialdehyde, glutathione, glutathione sulfhydryl transferase and γ-glutamylcysteine synthetase were detected to evaluate oxidative stress levels. The mRNA expression of brain-derived neurotrophic factor was determined to estimate neurotrophic factor levels. Besides, histopathological alterations were visualized by hematoxylin-eosin staining and neuronal apoptosis levels were measured by the immunohistochemical staining of Bax and Bcl-2. Ultimately, the mimetic aging rats showed significant cognitive impairment (n = 15, P < 0.01) and anxiety-like behaviors (n = 15, P < 0.01), increased oxidative stress (n = 5, P < 0.001), neurodegeneration (n = 5, P < 0.001) and apoptosis (n = 5, P < 0.01) and reduced neurotrophic factors (n = 5, P = 0.074) in the brain. However, corn embryo effectively prevented the above undesirable neurobehavioral alterations via attenuating oxidative stress (n = 5, P < 0.01), neurodegeneration (n = 5, P < 0.001) and apoptosis (n = 5, P < 0.01) and increasing the levels of neurotrophic factors (n = 5, P < 0.001), suggesting its strong neuroprotective effects.


Assuntos
Disfunção Cognitiva , Fármacos Neuroprotetores , Envelhecimento , Animais , Ansiedade , Apoptose , Disfunção Cognitiva/tratamento farmacológico , Galactose/efeitos adversos , Galactose/metabolismo , Glutationa/metabolismo , Hipocampo/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Ratos , Ratos Wistar , Zea mays/metabolismo
15.
Chem Biol Interact ; 349: 109683, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34610339

RESUMO

Previous studies have shown that PPP1R13L as an inhibitor of apoptosis protease TP53 can lead to abnormal cell proliferation and carcinogenesis, however, the function of PPP1R13L was complicated and the interaction between TP53 and PPP1R13L needs to be further explored. In the present study, a malignant transformation model of human bronchial epithelial cells induced by benzo (a) pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) was established to observe the regulatory patterns between TP53 and PPP1R13L during carcinogenesis. In vitro experiments including CRISPR-Cas9 editing, RNA silence, Co-Immunoprecipitation and Chromatin Immunoprecipitation were applied to discuss their interactive effects. Additionally, TCGA data profile and our clinical samples of lung cancer were also used to analyze their relationship at the transcriptome level. Interestingly, we found that the mRNA and protein level of TP53 and PPP1R13L fluctuated as a wave in BPDE-induced malignant transformation under wild-type TP53 genetic background. Our results have also demonstrated that PPP1R13L acts as an inhibitor of TP53, while TP53 can regulate PPP1R13L via binding a possible enhancer of the first intron of PPP1R13L gene. Likewise, TCGA data and clinical samples have identified that in the case of TP53 mutation, TP53 expression was negatively correlated with PPP1R13L, while in the case of TP53 wild-type, TP53 expression was not correlated with PPP1R13L. It suggested that there existed a negative feedback of wild-type TP53 to PPP1R13L, which reminded a unique implication during chemical carcinogenesis.


Assuntos
Benzo(a)pireno/toxicidade , Brônquios/citologia , Transformação Celular Neoplásica , Elementos Facilitadores Genéticos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Repressoras/genética , Proteína Supressora de Tumor p53/genética , Linhagem Celular Transformada , Humanos
16.
Ann Vasc Surg ; 76: 472-480, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33508460

RESUMO

BACKGROUND: The aim of this study was to evaluate the safety, applicability and outcomes of the endovascular in situ fenestration (ISF) technique for patients with aortic arch pathologies by performing a systematic review. METHODS: We conducted a systematic search using the PubMed, Embase, and Cochrane databases to identify English language articles between January 2004 and March 2019 on the management of aortic arch pathologies using an in situ fenestration technique. Two independent observers selected studies for inclusion in the study, assessed the methodological quality of the included studies, and extracted the data. The studies included all investigated the clinical outcomes and postprocedural complications of using ISF techniques. RESULTS: Seven studies reported on a total of 117 aortic arch pathologies patients. Including 52 dissection patients, 47 aneurysm patients, 18 intramural hematomas and penetrating ulcers patients. Needle fenestration and laser fenestration were performed in 62 and 45 patients respectively, and the rest 10 patients received radiofrequency fenestration. The follow-up period ranged from 1 to 55 months. The pooled technical success rates were 94% (95% confidence interval [CI]: 79-98%). The stroke rate was 6% (95% CI: 3-13%). The 30-day MAE was 11% (95% CI: 6-18%). CONCLUSION: The results of the study showed that using the in-situ fenestration technique for treating patients with aortic arch pathologies produced encouraging mid-outcomes. Long-term outcomes remain undefined.


Assuntos
Aorta Torácica/cirurgia , Doenças da Aorta/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Fatores de Tempo , Resultado do Tratamento
17.
Chemosphere ; 248: 126024, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32004891

RESUMO

Root uptake, translocation, and subcellular distribution of six pesticides (dinotefuran, thiamethoxam, imidacloprid, imazethapyr, propiconazole, and chlorpyrifos) with Kow ranging from -0.549 to 4.7 were investigated in wheat to study transportation and accumulation of pesticides. The root bioconcentration factor (RCF) of pesticides decreased with water solubility (R2 = 0.6121) and increased with hydrophobicity (when the pH-adjusted log Kow > 2, R2 = 0.925), respectively. The translocation of neutral pesticides from roots to shoots increased positively with water solubility (R2 > 0.6484) but decreased with hydrophobicity (R2 > 0.8039). The subcellular fraction concentration factor (SFCF) increased linearly with hydrophobicity of the tested pesticides (R2 > 0.958). The log RCF was positively correlated with log SFCF in root cell walls (R2 = 0.9894) and organelles (R2 = 0.9786). Transportation of the pesticides from roots to stems and stems to leaves was adversely affected by the log SFCF of cell walls and organelles of roots (R2 > 0.7997) and stems (R2 > 0.6666), respectively. Hydrophobicity-dependent SFCF is a factor governing accumulation of pesticides in roots after uptake and their subsequent upward translocation.


Assuntos
Praguicidas/farmacocinética , Triticum/efeitos dos fármacos , Triticum/metabolismo , Transporte Biológico , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Praguicidas/química , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/metabolismo , Solubilidade , Triticum/citologia , Triticum/crescimento & desenvolvimento
18.
J Phys Chem A ; 123(23): 4891-4899, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31117587

RESUMO

Understanding the interactions between water and Fe-based clusters is necessary to unravel the micromechanics of the surface hydrophilic property and the corrosion process of iron-related materials. Herein, a theoretical study is conducted of water adsorption and dissociation on icosahedral Fe13 and Fe12X (X = Ti, V, Cr, Mn, Co, Ni) clusters. It is found that the doping atoms have significant influence on the geometric structures, magnetic moments, and electronic states of Fe12X clusters. The center-doped clusters X@Fe12 show higher stability than the shell-doped X-Fe12; Ni@Fe12 exhibits lower activation energy for the dissociation of H2O than all the others; Ti@Fe12 strikes a weak bonding energy and high activation energy for water dissociation. Also, a water dimer finds a decreased energy barrier for O-H dissociation, and the electronic states and metal-water interactions can be altered by the support effect. This information is helpful to those working on water chemistry, anticorrosion wading devices, and high-standard potable water utilization.

19.
Ann Vasc Surg ; 56: 303-316, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30287293

RESUMO

BACKGROUND: Iliac branch devices (IBDs) have been increasingly reported for treating aortoiliac aneurysms. However, there are still concerns regarding this device. The aim of this study was to evaluate the safety and outcomes of IBDs in treating aortoiliac aneurysms by performing a systematic review and meta-analysis. METHODS: The Medline, EMBASE, and Cochrane databases were systematically searched to identify studies on the management of aortoiliac aneurysms using IBDs. Studies were reviewed and selected using defined criteria by 2 independent investigators who abstracted data on the study characteristics, study quality, and outcomes. The extracted data were presented as a rate and converted through arcsine transformations. Individual studies were evaluated and analyzed for 7 outcomes, including technical success rate, 30-day mortality, 30-day patency, follow-up patency, endoleak rate, buttock claudication, and IBD-associated reintervention. The heterogeneity of the studies was determined using the chi-squared distribution-based Q test and quantified by I2 statistics. Meta-analyses were performed using both a random effects model and fixed effects model. RESULTS: Twenty-two studies with a total of 1064 patients met the inclusion criteria and were selected for analysis. The pooled technical success rate of IBD was 93% (95% confidence interval [CI]: 91-95%). After patients were treated with the IBD, the 30-day mortality rate was 2% (95% CI, 1-4%), 30-day patency rate was 93% (95% CI, 91-94%), follow-up patency was 86% (95% CI, 84-88%), endoleak rate was 12% (95% CI, 8-17%), buttock claudication rate was 6% (95% CI, 5-8%), and IBD-associated reintervention rate was 11% (95% CI, 8-14%). CONCLUSIONS: Our study demonstrates that treating aortoiliac aneurysm with IBD produces satisfactory outcomes in midterm follow-up.


Assuntos
Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Aneurisma Ilíaco/cirurgia , Stents , Idoso , Idoso de 80 Anos ou mais , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Aneurisma Ilíaco/diagnóstico por imagem , Aneurisma Ilíaco/mortalidade , Aneurisma Ilíaco/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular
20.
BMC Complement Altern Med ; 18(1): 46, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29391009

RESUMO

BACKGROUND: Guang-Pheretima, which is originated from Pheretima aspergillum, has been documented in academic Chinese herbal studies for nearly 2000 years for its prominent treating effects of various inflammatory diseases such as asthma, cough and fever. However, the anti-inflammatory activity and mechanism of Guang-Pheretima has been rarely reported. Hence, we investigated the inhibitory effect and the underlying mechanism of Guang-Pheretima aqueous extracts on inflammatory response in RAW 264.7 cells. METHOD: RAW 264.7 macrophages were pretreated with various concentrations of Guang-Pheretima decoction (GPD) or protein-free Guang-Pheretima decoction (PF-GPD) and subsequently stimulated with lipopolysaccharide (LPS) to trigger the inflammatory response. Productions of nitric oxide (NO) were determined by Griess reaction, and prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6 were measured by enzyme-linked immunosorbent assays (ELISA). The protein expressions and messenger ribonucleic acid (mRNA) amounts of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were analyzed by Western Blot and Real-Time polymerase chain reaction (PCR), respectively. Finally, the translocation of nuclear factor (NF)-κB was observed by Western Blot. RESULTS: GPD of the experimental concentrations showed no anti-inflammatory activity. In contrast, PF-GPD at concentrations of 40-320 µg/mL significantly inhibited NF-κB activation and reduced the production of inflammatory mediators, such as NO, PGE2, TNF-α, as well as the related key synthases including iNOS and COX-2. Moreover, PF-GPD markedly suppressed the release of inflammatory cytokines, such as IL-1ß and IL-6. CONCLUSION: These results demonstrate the excellent anti-inflammatory properties of PF-GPD, and suggest that Guang-Pheretima may be used to treat and prevent certain inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Produtos Biológicos/farmacologia , Macrófagos/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Produtos Biológicos/química , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/análise , Citocinas/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , Camundongos , Oligoquetos/química , Células RAW 264.7
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