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1.
J Exp Clin Cancer Res ; 40(1): 373, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823564

RESUMO

BACKGROUND: Gallbladder cancer (GBC) is known for its high malignancy and multidrug resistance. Previously, we uncovered that impaired integrity and stability of the elongator complex leads to GBC chemotherapy resistance, but whether its restoration can be an efficient therapeutic strategy for GBC remains unknown. METHODS: RT-qPCR, MS-qPCR and ChIP-qPCR were used to evaluate the direct association between ELP5 transcription and DNA methylation in tumour and non-tumour tissues of GBC. EMSA, chromatin accessibility assays, and luciferase assays were utilized to analysis the DNA methylation in interfering PAX5-DNA interactions. The functional experiments in vitro and in vivo were performed to investigate the effects of DNA demethylating agent decitabine (DAC) on the transcription activation of elongator complex and the enhanced sensitivity of gemcitabine in GBC cells. Tissue microarray contains GBC tumour tissues was used to evaluate the association between the expression of ELP5, DNMT3A and PAX5. RESULTS: We demonstrated that transcriptional repression of ELP5 in GBC was highly correlated with hypermethylation of the promoter. Mechanistically, epigenetic analysis revealed that DNA methyltransferase DNMT3A-catalysed hypermethylation blocked transcription factor PAX5 activation of ELP5 by disrupting PAX5-DNA interaction, resulting in repressed ELP5 transcription. Pharmacologically, the DNA demethylating agent DAC eliminated the hypermethylated CpG dinucleotides in the ELP5 promoter and then facilitated PAX5 binding and reactivated ELP5 transcription, leading to the enhanced function of the elongator complex. To target this mechanism, we employed a sequential combination therapy of DAC and gemcitabine to sensitize GBC cells to gemcitabine-therapy through epigenetic activation of the elongator complex. CONCLUSIONS: Our findings suggest that ELP5 expression in GBC is controlled by DNA methylation-sensitive induction of PAX5. The sequential combination therapy of DAC and gemcitabine could be an efficient therapeutic strategy to overcome chemotherapy resistance in GBC.

2.
Front Oncol ; 11: 761700, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712617

RESUMO

A core transcriptional regulatory circuit (CRC) is a group of interconnected auto-regulating transcription factors (TFs) that form loops and can be identified by super-enhancers (SEs). Studies have indicated that CRCs play an important role in defining cellular identity and determining cellular fate. Additionally, core TFs in CRCs are regulators of cell-type-specific transcriptional regulation. However, a global view of CRC properties across various cancer types has not been generated. Thus, we integrated paired cancer ATAC-seq and H3K27ac ChIP-seq data for specific cell lines to develop the Cancer CRC (http://bio.liclab.net/Cancer_crc/index.html). This platform documented 94,108 cancer CRCs, including 325 core TFs. The cancer CRC also provided the "SE active core TFs analysis" and "TF enrichment analysis" tools to identify potentially key TFs in cancer. In addition, we performed a comprehensive analysis of core TFs in various cancer types to reveal conserved and cancer-specific TFs.

3.
Biomed Res Int ; 2021: 6672899, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513995

RESUMO

Background: Slow transit constipation (STC) is characterized by persistent, infrequent, or incomplete defecation. Systematic analyses of mRNA, lncRNA, and circRNA expression profiling in STC provide insights to understand the molecular mechanisms of STC pathogenesis. The present study is aimed at observing the interaction of mRNAs, lncRNAs, and circRNAs by RNA sequencing in vivo of STC. Methods: A rat model of STC was induced by loperamide. The expression profiles of both mRNAs and miRNAs were performed by RNA sequencing. Enrichment analyses of anomalous expressed mRNAs, lncRNAs, and circRNAs were performed in order to identify the related biological functions and pathologic pathways through the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: In total, 26435 mRNAs, 5703 lncRNAs, and 7708 circRNAs differentially expressed were identified between the two groups. The analyses of GO and KEGG show that (1) upregulated genes were enriched in a positive regulation of GTPase activity, cell migration, and protein binding and lipid binding and (2) GO annotations revealed that most trans-target mRNAs are involved in the regulation process of immune signal together with the proliferation and differentiation of immune cells. Additionally, the protein-protein interaction (PPI) network of differentially expressed (DE) mRNAs was constructed. Interestingly, all of the core lncRNAs and their coexpression mRNAs in this network are downregulated. Moreover, downregulated circRNAs have a set of target mRNAs related to immunoreaction, which was consistent with the overall tendency. Conclusion: Our investigation enriches the STC transcriptome database and provides a preliminary exploration of novel candidate genes and avenues expression profiles in vivo. The dysregulation of mRNAs, lncRNAs, and circRNAs might contribute to the pathological processes during STC.


Assuntos
Constipação Intestinal/genética , Transcriptoma/genética , Animais , Diferenciação Celular/genética , Constipação Intestinal/patologia , Modelos Animais de Doenças , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Redes Reguladoras de Genes/genética , Loperamida/farmacologia , Masculino , MicroRNAs/genética , Mapas de Interação de Proteínas/genética , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Análise de Sequência de RNA/métodos
4.
Foods ; 10(9)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34574217

RESUMO

The Maillard reaction between the lactose and milk proteins unavoidably occurs during the thermal treatment of milk. Although the impact of this reaction on protein nutrition and safety has been well-studied, whether a lactose glycation of milk proteins of the Maillard-type might affect the rats in their growth and intestinal morphology needs an investigation. In this study, caseinate and lactose-glycated caseinate were digested using pepsin and trypsin. Afterward, the resultant caseinate digest and glycated caseinate digest (lactose content of 13.5 g/kg of protein) at 100, 200, and 400 mg/kg body weight (BW)/d were assessed for their effects on the female weaned Wistar rats in terms of daily body weight gain, intestinal morphology, digestive and brush-border enzyme activities, as well as serum chemical indices. The results showed that glycated caseinate digest always showed a weaker effect on rat than caseinate digest either at the 0-7 or 0-28 d feeding stage, and more importantly, at the highest dose of 400 mg/kg BW/d, it caused obvious adverse effect on the rats, reflected by lower values of these indices. Compared with caseinate digest, glycated caseinate digest in the rats caused 0.9-15.4% and 10.6-49.7% decreases in average daily gain of BW and small intestinal length, 1.1-21.5% and 2.3-33.3% decreases in villus height and the ratio of villus height to crypt depth of the small intestine, or 0.3-57.6% and 0.2-55.7% decreases in digestive and critical brush-border enzyme activities, respectively. In addition, when the rats were fed with glycated caseinate digest, some serum indices related to oxidative stress status were enhanced dose-dependently. Lactose glycation of the Maillard-type is thus considered as a negative event of the Maillard reaction on milk proteins because this reaction might impair protein benefits to the body.

5.
Neurosurg Focus ; 51(3): E9, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34469867

RESUMO

OBJECTIVE: This prospective study was designed to confirm the role of atorvastatin in collateral circulation formation induced by encephaloduroarteriosynangiosis (EDAS) in patients with moyamoya disease (MMD). METHODS: Patients who were diagnosed with MMD at the Department of Neurosurgery in the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China, between June 2017 and May 2018 were included. Blood samples were obtained from an antecubital vein and were analyzed using flow cytometry. Endothelial progenitor cells (EPCs) were defined as CD34brCD133+CD45dimKDR+. All patients included in the study underwent EDAS. Patients voluntarily chose whether to undergo atorvastatin treatment after EDAS. The correlation between atorvastatin and good postoperative collateral circulation was evaluated. RESULTS: A total of 106 patients with MMD were included in this study. Fifty-three patients (50%) received atorvastatin treatment. The baseline characteristics did not display statistically significant differences between the atorvastatin-treated and non-atorvastatin groups. Seventy-eight (42.9%) of the 182 hemispheres investigated postoperatively were classified as grade A collateral circulation, 47 (25.8%) as grade B, and 57 (31.3%) as grade C. Multivariate analysis revealed that only atorvastatin was significantly correlated with good collateral circulation after EDAS (p = 0.041). CONCLUSIONS: The results of this prospective clinical trial have indicated that atorvastatin administered at 20 mg daily is safe and effective for the formation of postoperative collateral induced by EDAS.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Atorvastatina/uso terapêutico , Circulação Colateral , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
6.
Cell Biosci ; 11(1): 177, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583752

RESUMO

BACKGROUND: Although recent molecular analyses have improved our knowledge regarding gastric cancer (GC) biology, the molecular mechanisms that confer metastatic potential to GC remain poorly understood. In this study, we intend to explore the function and characterize the underlying mechanism of long noncoding RNA RNF144A-AS1 in GC metastasis and outgrowth. METHODS: The expression of RNF144A-AS1, miR-30c-2-3p, and Lysyl oxidase (LOX) was detected by quantitative real-time PCR assay. Fluorescence in situ hybridization and subcellular fractionation assay determined the cellular localization of RNF144A-AS1. Cell counting kit 8 assay, transwell assay, and tube formation assay were performed to detect the effect on cell proliferation, migration, invasion, and angiogenesis, respectively. Animal models were also applied to verify the effect on tumor metastasis, outgrowth, and angiogenesis. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay explored the interactions among RNF144A-AS1, miR-30c-2-3p, and LOX. Gene regulation was further validated by knockdown of Dicer or mutating the miRNA binding sites on RNF144A-AS1 and LOX 3'UTR. Cells were treated with recombinant human TGF-ß1 (Transforming Growth Factor ß1) to explore the effect of TGF-ß1 on RNF144A-AS1. Western blot and immunohistochemistry were used to detect protein expression. RESULTS: The expression of RNF144A-AS1 was significantly upregulated in GC tissues and was associated with poor prognosis and later-stage diseases. Hypoxia stimulated the expression of RNF144A-AS1 in a HIF-1α-independent manner. Additionally, RNF144A-AS1 was also induced by TGF-ß1. Loss and gain of function assays revealed that RNF144A-AS1 promoted tumor metastasis, angiogenesis, and proliferation. Mechanism exploration indicated RNF144A-AS1 served as a microRNA decoy of miR-30c-2-3p to release LOX. Gene Set Enrichment Analysis further suggested LOX and RNF144A-AS1 were enriched in the same gene sets, emphasizing the internal mechanism connection between these two genes. CONCLUSIONS: TGF-ß1- and hypoxia-inducible RNF144A-AS1 promoted tumor metastasis, angiogenesis, and proliferation through targeting the miR-30c-2-3p/LOX axis in GC, highlighting the value of the RNF144A-AS1/miR-30c-2-3p/LOX axis in therapeutic interventions of GC.

7.
Polymers (Basel) ; 13(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34451133

RESUMO

Fiber-reinforced polymer (FRP) materials are increasingly used in automotive industrial fields to achieve lightweight. In order to study the influence of high temperature and high humidity on the bonding structure between different materials, this paper selects basalt fiber-reinforced resin composite materials (BFRP) and aluminum alloy (Al), and uses Araldite® 2012 and Araldite® 2014, two adhesives, to make single lap joints (SLJs). The aging test was carried out for 0 (unaged), 10, 20, and 30 days under the environment of 80 °C/95% relative humidity (RH) and 80 °C/pure water. In this work, simple Fickian law was used to simulate the hygroscopic change law of dumbbell specimens of two adhesives and BFRP in a pure water environment. It was discovered that Araldite® 2012 is most affected by moisture, but the time to reach the maximum water absorption in Araldite® 2014 was shorter than in Araldite® 2012. The failure strength of the joint was obtained through a quasi-static tensile experiment, and it was found that the Araldite® 2014 adhesive joint first increased and then decreased in a high temperature environment. The strength increased by 11.63% after 20 days of aging under an 80 °C/95%RH environment, and increased by 16.66% after 10 days of aging under an 80 °C/pure water environment, which indicates that post-curing reaction occurred. The strength of Araldite® 2012 joints showed a downward trend. After 30 days of aging, it reduced by 40.38% under an 80 °C/95%RH environment and 41.11% under an 80 °C/pure water environment. By observing the load-displacement curve, it was found that, as time increased, the slope of the curve decreased, indicating that the stiffness of the bonded joint decreased with time. The failure modes of the joints were analyzed by macroscopic images and microscopic SEM methods, and the results showed that the surface failure transitions from a mixed failure to a complete tear failure over time. The failure of the basalt fiber/resin interface was because the interaction between the epoxy resin in the adhesive and the epoxy resin in BFRP was greater than the force between the basalt fiber layer and the epoxy resin layer in the BFRP sheet.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34408782

RESUMO

Background: The flower of Abelmoschus manihot (AM) has been widely used in the treatment of chronic inflammatory diseases, including ulcerative colitis. This paper aimed to confirm the therapeutic effect of AM on ulcerative colitis (UC) and explore its mechanism. Methods: Mouse models were induced by 2.5% dextran sulfate sodium (DSS) and treated with AM. UC signs, symptoms, colon macroscopic lesion scores, and disease activity index (DAI) scores were observed. Colon levels of interleukin- (IL-) 6, IL-1ß, IL-18, IL-17, tumor necrosis factor- (TNF-) α, and IL-10 were quantified by ELISA. The colon protein expression levels of NLRP3, ASC, caspase 1 p10, ß-arrestin1, ZO-1, occludin-1, and claudin-1 were examined by immunohistochemistry and western blotting. The mRNA levels of IL-1ß, IL-18, NLRP3, ASC, and caspase 1 p10 in the colon were determined by real-time quantitative polymerase chain reaction (qPCR). Results: After treatment with AM, the mortality of mice, pathological damage to the colon, splenomegaly, and the spleen coefficient were decreased. AM reduced the levels of proinflammatory cytokines (IL-6, IL-1ß, IL-18, IL-17, and TNF-α) and increased the level of IL-10. The mRNA expression levels of NLRP3, ASC, and caspase 1 in colon tissue were decreased by AM in a dose-dependent manner. In addition, AM also reduced the protein expression of NLRP3, ASC, caspase 1 p10, IL-1ß, IL-18, and ß-arrestin1 in the colon tissue of model mice. Western blot analysis confirmed that AM increased the expression of occludin-1, claudin-1, and ZO-1 in a dose-dependent manner. Conclusion: This study shows that AM has a significant therapeutic effect on mice with UC, and the mechanism may be related to the inhibition of the ß-arrestin1/NLRP3 inflammasome signaling pathway and the protection of intestinal barrier function.

9.
Pathol Oncol Res ; 27: 1609846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305476

RESUMO

A variety of pathogenic microorganisms promote tumor occurrence and development through long-term colonization in the body. Fusobacterium nucleatum (F. nucleatum) is abundant in precancerous esophageal lesions and is closely related to the malignant progression of esophageal squamous cell carcinoma (ESCC). The invasion of exogenous microorganisms can reshape the immune microenvironment, make the immune system incapacitated, and assist tumor cells in immune escape. A variety of pathogenic microorganisms induce the recruitment of regulatory T cell (Tregs) to allow tumor cells to escape immune surveillance and provide favorable conditions for their own long-term colonization. Tregs are one of the major obstacles to tumor immunotherapy and have a significant positive correlation with the occurrence and development of many kinds of tumors. Because F. nucleatum can instantly enter cells and colonize for a long time, we speculated that F. nucleatum infection could facilitate the immune escape of tumor cells through enrichment of Tregs and promote the malignant progression of ESCC. In this study, we found a significant concordance between F. nucleatum infection and Tregs infiltration. Therefore, we propose the view that chronic infection of F. nucleatum may provide favorable conditions for long-term colonization of itself by recruiting Tregs and suppressing the immune response. At the same time, the massive enrichment of Treg may also weaken the immune response and assist in the long-term colonization of F. nucleatum. We analyzed the correlation between F. nucleatum infection with the clinicopathological characteristics and survival prognosis of the patients. F. nucleatum infection was found to be closely related to sex, smoking, drinking, degree of differentiation, depth of invasion, lymph node metastasis, and clinical stage. The degree of differentiation, depth of infiltration, lymph node metastasis, clinical stage, and F. nucleatum infection are independent risk factors affecting ESCC prognosis. Additionally, the survival rate and median survival time were significantly shortened in the F. nucleatum infection positive group. Therefore, we propose that long-term smoking and alcohol consumption cause poor oral and esophageal environments, thereby significantly increasing the risk of F. nucleatum infection. In turn, F. nucleatum infection and colonization may weaken the antitumor immune response through Treg enrichment and further assist in self-colonization, promoting the malignant progression of ESCC.

10.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(7): 818-822, 2021 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-34308587

RESUMO

Objective: To investigate the effectiveness of limited open reduction via "door-shaft method" and internal fixation with locking plate for two- and three-part fractures of the proximal humerus. Methods: The clinical data of 64 patients with proximal humeral fractures who were admitted between January 2013 and December 2016 and met the selection criteria were retrospectively analyzed. There were 23 males and 41 females, with an average age of 68.0 years (range, 50-89 years). The injuries were caused by falling in 57 cases, traffic accident in 5 cases, and falling from height in 2 cases. The interval between injury and operation was 1-7 days (mean, 2.1 days). According to Neer classification, there were 28 cases of two-part fractures and 36 cases of three-part fractures. According to the angulation direction of the proximal humeral neck shaft angle, there were 21 cases of adduction fractures and 43 cases of abduction fractures. The fractures were treated with limited open reduction via "door-shaft method" and proximal humerus internal locking systems for internal fixation. The operation time, intraoperative blood loss, number of fluoroscopy, hospital stay, and complications were recorded. The fracture healing was reviewed by X-ray film and the healing time was recorded. The shoulder joint function was evaluated by Neer score standard. Results: The operation time was 45-127 minutes, with an average of 82.3 minutes. The intraoperative blood loss was 30-125 mL, with an average of 62.7 mL. Intraoperative fluoroscopy was performed 30-69 times, with an average of 37.0 times. The hospital stay was 6-23 days, with an average of 10.3 days. All incisions healed by first intention. All patients were followed up 12-37 months, with an average of 18.3 months. X-ray film re-examination showed that all fractures healed, the healing time was 12-21 weeks, with an average of 14.3 weeks. After operation, 3 cases had shoulder stiffness and 1 case had fracture malunion. At last follow-up, the Neer score of shoulder joint function was 49-97, with an average of 83.1. Among them, 38 cases were excellent, 13 cases were good, 10 cases were fair, and 3 cases were poor. The excellent and good rate was 79.7%. The excellent and good rate of patients with two-part fractures was 82.1% (23/28), and the excellent and good rate of patients with three-part fractures was 77.8% (28/36). Conclusion: The "door-shaft method" not only reduces the difficulty of the Joystick technique in the reduction of proximal humerus fractures, but also provides auxiliary stability. It is used for limited open reduction and internal fixation with locking plate to treat the two- and three-part fractures of the proximal humerus, which can achieve good effectiveness.


Assuntos
Fraturas do Ombro , Ombro , Idoso , Placas Ósseas , Feminino , Fixação Interna de Fraturas , Humanos , Úmero , Masculino , Estudos Retrospectivos , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Resultado do Tratamento
11.
Microb Biotechnol ; 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34165875

RESUMO

Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes unsatisfactory. Antimicrobial photodynamic therapy (aPDT) is a non-invasive alternative suitable for the treatment of superficial fungal infections. This work investigated the photodynamic inactivation efficacy and effects of aloe-emodin (AE), a natural photosensitizer (PS) against T. rubrum microconidia in vitro, and evaluated the treatment effects of AE-mediated aPDT for T. rubrum-caused tinea corporis in vivo and tinea unguium ex vivo. The photodynamic antimicrobial efficacy of AE on T. rubrum microconidia was evaluated by MTT assay. The inhibition effect of AE-mediated aPDT on growth of T. rubrum was studied. Intracellular location of AE, damage induced by AE-mediated aPDT on cellular structure and surface of microconidia and generation of intracellular ROS were investigated by microscopy and flow cytometry. The therapeutic effects of AE-mediated aPDT against dermatophytosis were assessed in T. rubrum-caused tinea corporis guinea pig model and tinea unguium ex vivo model. AE-mediated aPDT effectively inactivated T. rubrum microconidia in a light energy dose-dependent manner and exhibited strong inhibitory effect on growth of T. rubrum. Microscope images indicated that AE is mainly targeted to the organelles and caused damage to the cytoplasm of microconidia after irradiation through generation of abundant intracellular ROS. AE-mediated aPDT demonstrated effective therapeutic effects for T. rubrum-caused tinea corporis on guinea pig model and tinea unguium in ex vivo model. The results obtained suggest that AE is a potential PS for the photodynamic treatment of dermatophytosis caused by T. rubrum, but its permeability in skin and nails needs to be improved.

13.
Front Chem ; 9: 675346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937209

RESUMO

Antioxidation is very important in medicine and food. The current evaluation technologies often have many shortcomings. In this work, an improved electrochemical sensing platform for the evaluation of antioxidant activity has been proposed. A hydrogel was prepared based on graphene oxide, zinc ions, and chitosan. Zinc ions play the role of crosslinking agents in hydrogels. The structure of chitosan can be destroyed by injecting hydrogen peroxide into the hydrogel, and the free zinc ions can diffuse to the surface of the electrode to participate in the electrochemical reaction. This electrochemical sensor can evaluate the antioxidant activity by comparing the current difference of zinc reduction before and after adding the antioxidant. With the help of graphene oxide, this hydrogel can greatly enhance the sensing effect. We conducted tests on 10 real samples. This proposed electrochemical platform has been successfully applied for evaluating the antioxidant activity of Scutellaria baicalensis, and the results were compared to those obtained from the 2,2-diphenyl-1-picrylhydrazyl-based traditional analysis technique.

14.
Photodiagnosis Photodyn Ther ; 34: 102311, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33930578

RESUMO

BACKGROUND AND AIM: Antimicrobial photodynamic therapy (aPDT) has shown great potential for treatment of superficial or localized multidrug-resistant (MDR) Acinetobacter baumannii infections. The purpose of this study was to investigate the cytotoxicity and in vivo safety of aloe-emodin (AE), and its photodynamic treatment efficacy against MDR A. baumannii infections. METHODS: The cytotoxicity (dark toxicity) and phototoxicity of AE to human immortalized keratinocytes and mice fibroblasts were detected by CCK-8 kit. Low and high doses of AE were intravenously injected into mice to evaluate the safety of AE in vivo. Bioluminescent MDR A. baumannii strain was employed to establish the infection model on BALB/c mice after skin scald, and infection status and therapeutic effect of AE-mediated aPDT were assessed by animal imaging system. The peripheral blood of mice was analyzed by flow cytometer. RESULTS: AE had low cytotoxicity to human immortalized keratinocytes and mice fibroblasts, and had certain phototoxicity to these cells under light irradiation. The in vivo experiments demonstrated that AE caused no obvious effects on the weight and pathological changes of mice. AE-mediated aPDT was effective in the treatment of MDR A. baumannii caused infections in mice after skin scald. CONCLUSIONS: AE has potential to be used in the photodynamic treatment of MDR A. baumannii caused superficial infections after scald.


Assuntos
Acinetobacter baumannii , Aloe , Anti-Infecciosos , Emodina , Fotoquimioterapia , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana Múltipla , Emodina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
15.
Nuklearmedizin ; 60(4): 283-288, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33836553

RESUMO

OBJECTIVE: The intracranial brachytherapy has been applied for decades, however, no results with long-term follow-up have been reported. This study investigated the long-term efficiency of intra-tumoral injection of 131I-chTNT in patients with deep-seated glioma. METHOD: Thirty-five patients undergoing 131I-chTNT brachytherapy between December 2004 and May 2009 were enrolled. 131I-chTNT was injected at a dose of 1.5 mCi/cm3 at an interval of 1 month for consecutive 3 times. Serial ECT scan and MRI were performed during follow-up. Progression-free survival (PFS) and overall survival (OS) were analyzed. Adverse reactions were graded with WHO Toxicity Grading Scale for determining the severity of adverse events. RESULTS: ECT scan showed that enhanced accumulation of radioactive agents in the tumor lasted for more than 30 days. Three months after final injection, tumor complete remission (CR) was observed in 4 patients (11.4 %), partial remission (PR) in 11 cases (31.4 %), stable disease (SD) in 10 cases (28.6 %) and progressive disease (PD) in 10 cases (28.6 %). At 6-month, CR, PR, SD and PD were 2, 6, 12 and 15 respectively. After 10 years of follow-up, median progression-free survival (PFS) and overall survival (OS) were 5.4 and 11.4 months. One-year survival was 45.7 %, two and five-year survival was 8.6 %, ten-year survival was 5.7 %. Multivariate analysis showed that pathological grade and tumor diameter were independent prognostic factors for PFS and OS. Grade I-II adverse events occurred after drug injection, including nausea, fever, headache, hairloss and fatigue. CONCLUSION: 131I-chTNT intracranial brachytherapy is efficient and safe for patients with deep-seated glioma. It is a reliable option for inoperable glioma patients.


Assuntos
Braquiterapia , Glioma , Seguimentos , Glioma/diagnóstico por imagem , Glioma/radioterapia , Humanos , Radioisótopos do Iodo/uso terapêutico
16.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(2): 228-230, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33825388

RESUMO

This study established a rapid ECG screening system through the application of wearable ECG equipment. The closed-loop and self-service process of ECG inspection, data collection, transmission and printing have been realized. The new rapid ECG screening system docking with HIS system in the hospital, forming a new intelligent mode of rapid ECG screening. This paper introduces the design of the intelligent mode of ECG rapid screening from the aspects of hardware, software, wearable ECG examination equipment, and briefly describes its implementation path and technical scheme. With the rapid ECG screening system, human power can be saved, the timeliness of ECG examination can be enhanced. The level of ECG diagnosis in the basic units can be improved through building a multiple medical centers which is rely on the cloud platform.


Assuntos
Eletrocardiografia , Dispositivos Eletrônicos Vestíveis , Desenho de Equipamento , Humanos , Pesquisa , Software
17.
Front Cell Neurosci ; 15: 632354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889074

RESUMO

Background: Ischemic stroke is the main cause of disability worldwide, leading to a serious socioeconomic burden. Ferroptosis is a non-apoptotic form of programmed cell death and is related to various diseases. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is considered a target of ferroptosis, but its specific role in ischemic stroke remains unclear. In this study, we investigate whether the inhibition of ACSL4 promotes the recovery of neurological function in a way that prevents ferroptosis. Methods: A transient cerebral ischemia model was established for mice by middle cerebral artery occlusion (MCAO); glutathione peroxidase 4 (GPx4), ACSL4 and cyclooxygenase 2 (COX2) were detected by Western blot, and changes to mitochondria were observed by a transmission electron microscope. A kit was used to determine iron levels and lipid peroxide indicators, such as glutathione peroxidase (GPx), reduced glutathione (GSH), total glutathione/oxidized glutathione (GSH/GSSG), lipid peroxidation, reactive oxygen species, superoxide and malonaldehyde. Following MCAO, a ferroptosis inhibitor, liproxstatin-1, was administered intranasally immediately at a concentration of 10 mg/kg. Rosiglitazone was used to inhibit ACSL4 and was administered intravenously 1 h before MCAO at a concentration of 0.4 mg/kg. Brain injury was determined by neurological deficit scores, neuroscore (28-point), corner test and gait analyses, at 24 and 72 h after stroke. Brain infarct volume was determined by 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining at 72 h after stroke. Results: After MCAO, GPx4 protein expression decreased, ACSL4 and COX2 protein expression increased, GPx activity decreased and iron accumulation. Transmission electron microscopy confirmed that the outer mitochondrial membrane of neurons had ruptured and mitochondrial cristae had decreased or disappeared. Liproxstatin-1 could significantly attenuate the decrease of GPx4 and the increase of COX2 after MCAO, dramatically reducing iron accumulation and decreasing GPx activity, accompanied by a marked reduction in changes in lipid peroxidation indicators. The use of rosiglitazone to inhibit ACSL4 could significantly improve neurological function and reduce the brain infarct volume at 72 h after stroke. Importantly, inhibiting ACSL4 could significantly attenuate the decline of GPx4 after MCAO and markedly attenuate iron accumulation and a decrease in GPx activity. Additionally, changes in lipid peroxidation indicators were also significantly inhibited. Conclusion: This study indicates that inhibiting ACSL4 can promote the recovery of neurological function after stroke by suppression of ferroptosis.

19.
Stereotact Funct Neurosurg ; 99(3): 181-186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33756470

RESUMO

OBJECTIVE: The aim of this study was to evaluate the efficacy of Gamma Knife radiosurgery (GKRS) as a salvage therapy for high-grade glioma in our center. METHODS: A total of 167 patients with malignant glioma were treated with GKRS in our Gamma Knife Center between January 2013 and December 2017; 140 patients (85 males and 55 females) were followed up and enrolled in our study. A single lesion was found in 110 cases, and multiple lesions were found in 30 cases; 108 cases received a single therapy, and in 32 cases, at least 2 GKRSs were performed. The median tumor volume was 13.5 cm3. The mean radiation dosage was 14.35 Gy (range, 6-18 Gy). MRI was performed regularly. The RANO criteria and Cox analysis were used to evaluate the therapeutic efficiency. RESULTS: Follow-up MRI showed the local control rate was 61.4% at 3 months after GKRS, 25.0% at 6 months, and 7.1% at 12 months. The mean and median progression-free survival (PFS) periods were 8.6 (95% CI, 6.3-11.0) and 4 (95% CI, 3.5-4.5) (range, 1-60) months, respectively. The overall survival (OS) after GKRS was 3-62 months, with a mean of 16.7 (95% CI, 14.6-18.9) months, and the median survival was 13 (95% CI, 12.1-13.9) months. The 1-, 2-, and 5-year survival rates were 51.4, 10.0, and 2.9%, respectively. No severe complications occurred. Cox regression showed that glioma pathology was closely related to prognosis (p < 0.05). The Karnofsky Performance Score had little influence on PFS (p > 0.05) but influenced OS significantly (p < 0.05). CONCLUSION: GKRS can be used to effectively treat malignant brain glioma and can therefore be used as an alternative treatment option.


Assuntos
Neoplasias Encefálicas , Glioma , Radiocirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Feminino , Glioma/diagnóstico por imagem , Glioma/radioterapia , Glioma/cirurgia , Humanos , Masculino , Intervalo Livre de Progressão , Terapia de Salvação
20.
Thorac Cancer ; 12(9): 1373-1381, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760397

RESUMO

BACKGROUND: This multicentre, open-label study evaluated the efficacy and safety of antiprogrammed death ligand 1 antibody SHR-1316 plus liposomal irinotecan and 5-fluorouracil as the first-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: Eligible patients received SHR-1316 (10 mg/kg), liposomal irinotecan (60 mg/m2 for the first cycle, 80 mg/m2 thereafter), and 5-fluorouracil (2400 mg/m2 ) every 14 days until disease progression, intolerable toxicity or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: We enrolled 23 patients between 11 March 2019 and 31 May 2019. The median follow-up duration was 15.2 months (95% CI 14.2-16.2). The median PFS was 8.5 months (95% CI 1.2-15.8), and ORR and DCR were 52.2% (95% CI 30.1-74.3) and 73.9% (95% CI 54.5-93.3), respectively. The median OS was 11.6 months (95% CI 6.7-16.6). The most common treatment-related grade 3-4 adverse events (AEs) were neutropenia (17.4%), nausea (13.0%), and anorexia (13.0%). Treatment-related serious AEs occurred in two patients. No treatment-related deaths occurred. CONCLUSIONS: SHR-1316 plus liposomal irinotecan and 5-fluorouracil has a promising efficacy and manageable safety profile, and could be a new first-line treatment approach for patients with unresectable locally advanced or distant metastatic ESCC.

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