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1.
Eur J Pain ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069125

RESUMO

BACKGROUND: An integrated score that globally assesses perioperative pain experience and rationally weights each component has not yet been developed. METHODS: A development dataset specific to adult Chinese patients undergoing orthopaedic surgery was obtained from PAIN OUT (1985 qualified patients of 2244). A more recent validation dataset obeying the same conditions was obtained from the Chinese Anaesthesia Shared-database Platform (1004 qualified patients of 1032). Outcomes were assessed using the International Pain Outcomes Questionnaire (IPO-Q), which comprises key patient-level outcomes of perioperative pain management, including pain experience and perceptions of care. Using principal component analysis and regression models, a composite score (CS) was inferred to integrate pain experience. The discrimination of the CS for dissatisfaction and desire for more pain treatment was compared with that of the worst pain score. RESULTS: A CS was developed from the 12 items of the IPO-Q regarding pain experience. The weight for calculating the CS was worst pain 11, least pain 17, time spent in severe pain 11, interference with activity in bed 9, interference with breathing deeply or coughing 10, interference with sleep 9, anxiety 12, helplessness 12, nausea 0, drowsiness 2, itch 5 and dizziness 2. In external validation, the CS indicated superior discrimination to the worst pain in predicting dissatisfaction (p < 0.001) and desire for more pain treatment (p < 0.001). CONCLUSIONS: This study introduced a methodology to integrate outcomes regarding perioperative pain experience into a CS, which was based on the weight of each item. SIGNIFICANCE: This novel methodology sheds additional light on the riveting issue of carefully integrating several measures into a composite endpoint, which may be useful for quality improvement purposes when addressing the impact of a change in clinical practice.

2.
Heart Lung ; 57: 54-58, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36057186

RESUMO

BACKGROUND: There is limited research on clinical indicators for clinicians to judge the hypercoagulability of COPD patients. OBJECTIVE: The aim in this study was to evaluate the level changes of fibrinogen (FIB), d-dimer (D-D), and mean platelet volume (MPV) in plasma during the stable phase of chronic obstructive pulmonary disease (COPD), as compared with acute exacerbation of COPD (AECOPD). METHODS: A total of 240 patients admitted with COPD in our hospital and 60 healthy people were enrolled in this prospective study using data from August 2016 to August 2017. Patients were allocated to AECOPD or stable COPD group. The levels of white blood cell (WBC) count, absolute neutrophil counts (NEU%), activated partial thromboplastin time (APTT), prothrombin time (PT), and hypoxia inducible factor-1(HIF-1) were detected. The MPV, D-D, and the FIB level were also determined and compared between groups. RESULTS: The WBC count, NEU%, FIB, and D-D were significantly higher in the AECOPD group than in the stable COPD group and the healthy group (P < 0.05), while the MPV, APTT and PT was significantly lower in the AECOPD group than in the stable COPD group and the healthy group (P < 0.05). Additionally, MPV was significantly negatively correlated with WBC count (r=-0.798) and NEU% (r=-0.749) in the AECOPD group (P < 0.05); and the percentage of forced expiratory volume in one second (FEV1) in the predicted value was significantly negatively correlated with D-D (r=-0.891) and FIB (r=-0.656) (P <0.05). CONCLUSION: We demonstrated that, for patients hospitalized for exacerbation of COPD, MPV may indeed be a valid indicator of inflammation and a marker of thrombosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36078364

RESUMO

Arsenic (As(III)), more toxic and with less affinity than arsenate (As(V)), is hard to remove from the aqueous phase due to the lack of efficient adsorbents. In this study, a core-shell structured MnO2@La(OH)3 nanocomposite was synthesized via a facile two-step precipitation method. Its removal performance and mechanisms for As(V) and As(III) were investigated through batch adsorption experiments and a series of analysis methods including the transformation kinetics of arsenic species in As(III) removal, FTIR, XRD and XPS. Solution pH could significantly influence the removal efficiencies of arsenic. The adsorption process of As(V) occurred rapidly in the first 5 h and then gradually decreased, whereas the As(III) removal rate was relatively slower. The maximum adsorption capacities of As(V) and As(III) were up to 138.9 and 139.9 mg/g at pH 4.0, respectively. For As(V) removal, the inner-sphere complexes of lanthanum arsenate were formed through the ligand exchange reactions and coprecipitation. The oxidation of As(III) to the less toxic As(V) by δ-MnO2 and subsequently the synergistic adsorption process by the lanthanum hydroxide on the MnO2@La(OH)3 nanocomposite to form lanthanum arsenate were the dominant mechanisms of As(III) removal. XPS analysis indicated that approximately 20.6% of Mn in the nanocomposite after As(III) removal were Mn(II). Furthermore, a small amount of Mn(II) and La(III) were released into solution during the process of As(III) removal. These results confirm its efficient performance in the arsenic-containing water treatment, such as As(III)-contaminated groundwater used for irrigation and As(V)-contaminated industrial wastewater.


Assuntos
Arsênio , Nanocompostos , Poluentes Químicos da Água , Purificação da Água , Adsorção , Arseniatos , Arsênio/análise , Concentração de Íons de Hidrogênio , Cinética , Lantânio , Compostos de Manganês/química , Óxidos/química , Poluentes Químicos da Água/análise , Purificação da Água/métodos
4.
Biomed Res Int ; 2022: 8717950, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060145

RESUMO

Introduction: The effect of sulodexide (SLX) on obstructive jaundice- (OJ-) induced acute lung injury (ALI) in rats was examined in this study. Methods: In this study, 48 rats were randomly assigned to one of six groups: sham, OJ, OJ+saline, OJ+SLX (0.5 mg/ml/d), OJ+SLX (1 mg/ml/d), and OJ+SLX (2 mg/ml/d). The pathological lung injury was assessed by histological analysis and lung injury grading. ELISA kits were used to evaluate the expression of IL-6, IL-1, TNF-α, and syndecan-1 (SDC-1) in bronchoalveolar lavage fluids (BALFs). Commercial assay kits were performed to evaluate malondialdehyde (MDA) production and catalase (CAT) activity in lung tissues. The apoptosis was assessed by TUNEL assay. The lung microvascular permeability was investigated using Evans blue leakage, lung wet/dry weight (W/D) ratio, and lung permeability index (LPI). SDC-1, claudin-5, ZO-1, and VE cadherin expression levels in lung tissues were measured using Western blot. Results: The OJ-induced ALI rats showed severe lung injury. The value of IL-6, IL-1ß, TNF-α, and SDC-1 in BALFs was remarkedly increased in the OJ group. MDA content, apoptotic area, apoptotic molecules, and SDC-1 level were all higher in the OJ group's lung tissues than in the sham group. CAT activity, Evans blue leakage, W/D ratio, LPI, and expression of claudin-5, ZO-1, and VE cadherin were all lower in the OJ group compared to the sham group. The degenerative alterations in lung tissue improved after 7 days of treatment with 2 mg/ml SLX. The BALFs had lower amounts of IL-6, IL-1, TNF-α, and SDC-1. The SLX therapy reduced MDA levels while restoring CAT activity. In lung tissues, SLX reduced apoptotic area and SDC-1 expression. SLX reduced lung microvascular permeability by raising the expression of Claudin-5, ZO-1, and VE-cadherin in lung tissue when compared to the OJ group. Conclusion: The results suggested that SLX attenuates OJ-induced ALI in rats by protecting the pulmonary microvascular endothelial barrier.


Assuntos
Lesão Pulmonar Aguda , Glicosaminoglicanos , Icterícia Obstrutiva , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Animais , Antioxidantes , Caderinas , Claudina-5 , Modelos Animais de Doenças , Azul Evans/efeitos adversos , Glicosaminoglicanos/farmacologia , Interleucina-6 , Icterícia Obstrutiva/complicações , Ratos , Fator de Necrose Tumoral alfa
5.
BMC Geriatr ; 22(1): 730, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064357

RESUMO

BACKGROUND: Postoperative delirium (POD) is a common complication among elderly patients after surgery. It is unclear whether the systemic immune-inflammation index (SII) can be a predictor of POD. We explored the prognostic value of the SII in predicting POD in elderly patients undergoing non-neurosurgery and non-cardiac surgery in a large retrospective cohort. METHODS: We enrolled elderly patients undergoing non-neurosurgery and non-cardiac surgery between January 2014 and August 2019. Univariate and multivariate logistic regression analyses were performed to explore the correlation between POD and the SII value as both a continuous and categorical variable. Then, propensity score matching (PSM) analysis was applied to eliminate the confounding effect of covariates and prove our results. Subgroup analyses were then performed to discover the association between the SII and POD in different subgroups. RESULTS: A total of 29,608 patients with a median age of 70 years (IQR: 67-74) were enrolled in the retrospective cohort. The cut-off value of the SII was 650, which was determined by the receiver operating characteristic (ROC) curve. The ORs of an SII value > 650 was 2.709 (95% CI:2.373-3.092, P < 0.001), 1.615 (95% CI:1.384-1.882, P < 0.001), 1.855 (95% CI:1.602-2.146, P < 0.001), and 1.302 (95% CI:1.106-1.531, P = 0.001) for prediction of POD in univariate model and three multivariate regression models. After PSM, the OR of an SII value > 650 was 1.301 (95% CI: 1.062-1.598, P = 0.011). The subgroup analysis indicated that the SII indicates a significantly increased risk of POD in patients with Hb < 130 g/L, 4*109/L < WBC ≤ 10*109/L, albumin < 39 g/L, or duration of MAP < 60 mmHg ≥ 5 min. The SII was found to be a useful prognostic predictor of POD for patients of different ages, sexes, and ASA classifications. CONCLUSIONS: The SII had a predictive value for POD in patients undergoing non-neurosurgery and non-cardiac surgery. As an index generated from routine blood tests, the SII has advantages regarding cost and time. After further validation, the SII may provide a new option for POD prediction.


Assuntos
Delírio , Idoso , Estudos de Coortes , Delírio/diagnóstico , Delírio/etiologia , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Prognóstico , Estudos Retrospectivos
6.
Nat Genet ; 54(8): 1167-1177, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35915169

RESUMO

To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.


Assuntos
Estudo de Associação Genômica Ampla , Neoplasias Pulmonares , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Proteínas de Ligação a RNA/genética
7.
Front Immunol ; 13: 885253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990617

RESUMO

Enterotoxigenic Escherichia coli (ETEC) infection induced post-weaning diarrhea is one of the leading causes of morbidity and mortality in newly weaned pigs and one of the significant drivers for antimicrobial use in swine production. ETEC attachment to the small intestine initiates ETEC colonization and infection. The secretion of enterotoxins further disrupts intestinal barrier function and induces intestinal inflammation in weaned pigs. ETEC infection can also aggravate the intestinal microbiota dysbiosis due to weaning stress and increase the susceptibility of weaned pigs to other enteric infectious diseases, which may result in diarrhea or sudden death. Therefore, the amount of antimicrobial drugs for medical treatment purposes in major food-producing animal species is still significant. The alternative practices that may help reduce the reliance on such antimicrobial drugs and address animal health requirements are needed. Nutritional intervention in order to enhance intestinal health and the overall performance of weaned pigs is one of the most powerful practices in the antibiotic-free production system. This review summarizes the utilization of several categories of feed additives or supplements, such as direct-fed microbials, prebiotics, phytochemicals, lysozyme, and micro minerals in newly weaned pigs. The current understanding of these candidates on intestinal health and disease resistance of pigs under ETEC infection are particularly discussed, which may inspire more research on the development of alternative practices to support food-producing animals.


Assuntos
Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Enteropatias , Doenças dos Suínos , Animais , Antibacterianos/farmacologia , Diarreia/veterinária , Resistência à Doença , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/veterinária , Enteropatias/veterinária , Suínos , Desmame
8.
Front Oncol ; 12: 845765, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936748

RESUMO

Background: Growing evidence suggests that colorectal cancer (CRC) should be considered a heterogeneous disease. The right side (RCC) and left side (LCC) colorectal cancer have different clinical characteristics and immune landscapes. The aim of this study was to analyze differential expression and prognostic correlation of immune-related factors between RCC and LCC. Methods: The gene expression profile and clinical characteristics of CRC patients were retrieved from The Cancer Genome Atlas data portal (n=525). Using a deconvolution algorithm, immune cell infiltration in RCC and LCC based on the RNA-seq data was analyzed. Differentially expressed genes (DEGs) were obtained by performing differential gene expression analysis. Immune-related DEGs were derived by the intersection with immune-related factors downloaded from the IMMPORT database. To further validate the findings, we applied immunohistochemical (IHC) staining of a CRC tissue microarray (TMA). The distribution of immune cells in RCC and LCC and changes in the expression of immune molecules on their membranes were verified. The expression levels of circulating cytokines were measured by flow cytometry to detect the cytokines secreted by immune cells in RCC and LCC. Furthermore, to reveal the prognostic value of differential immune factors on RCC and LCC patients, survival analysis based on mRNA levels using TCGA cohort and survival analysis using protein levels was performed using our CRC patients. Results: The infiltration of immune cells differed between RCC and LCC, the infiltration degree of macrophages M0 was significantly higher in LCC, while the infiltration degree of differentiated macrophages M1 and M2, CD4+ T and CD8+ T cells was significantly higher in RCC. The expression of related molecules by immune cells also differed between RCC and LCC. The expression of 7 genes in RCC was higher than that in LCC, which were CCR5, CD209, CD8A, HCK, HLA-DPB1, HLA-DQA1, HLA-DRA, respectively. Meanwhile, the expression of 2 genes in LCC was higher than in RCC, which were IL-34 and PROCR. Patients with RCC having high expression of HLA-DQA1 mRNA or proteins had better survival and LCC patients with high expression of IL 34 mRNA or protein had better survival. Conclusions: In this study, we comprehensively compared differences in immune cells and regulating factors between left and right colorectal cancer. Different expression patterns and their effects on survival were identified. The analysis of immune-related factors may provide a theoretical basis for precise immunotherapy of RCC and LCC.

9.
J Neuroinflammation ; 19(1): 176, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799259

RESUMO

BACKGROUND: Metabolic dysregulation and disruption of immune homeostasis have been widely associated with perioperative complications including perioperative ischemic stroke. Although immunometabolite S-2-hydroxyglutarate (S-2HG) is an emerging regulator of immune cells and thus triggers the immune response, it is unclear whether and how S-2HG elicits perioperative ischemic brain injury and exacerbates post-stroke cognitive dysfunction. METHODS: Perioperative ischemic stroke was induced by transient middle cerebral artery occlusion for 60 min in C57BL/6 mice 1 day after ileocecal resection. CD8+ T lymphocyte activation and invasion of the cerebrovascular compartment were measured using flow cytometry. Untargeted metabolomic profiling was performed to detect metabolic changes in sorted CD8+ T lymphocytes after ischemia. CD8+ T lymphocytes were transfected with lentivirus ex vivo to mobilize cell proliferation and differentiation before being transferred into recombination activating gene 1 (Rag1-/-) stroke mice. RESULTS: The perioperative stroke mice exhibit more severe cerebral ischemic injury and neurological dysfunction than the stroke-only mice. CD8+ T lymphocyte invasion of brain parenchyma and neurotoxicity augment cerebral ischemic injury in the perioperative stroke mice. CD8+ T lymphocyte depletion reverses exacerbated immune-mediated cerebral ischemic brain injury in perioperative stroke mice. Perioperative ischemic stroke triggers aberrant metabolic alterations in peripheral CD8+ T cells, in which S-2HG is more abundant. S-2HG alters CD8+ T lymphocyte proliferation and differentiation ex vivo and modulates the immune-mediated ischemic brain injury and post-stroke cognitive dysfunction by enhancing CD8+ T lymphocyte-mediated neurotoxicity. CONCLUSION: Our study establishes that S-2HG signaling-mediated activation and neurotoxicity of CD8+ T lymphocytes might exacerbate perioperative ischemic brain injury and may represent a promising immunotherapy target in perioperative ischemic stroke.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , Disfunção Cognitiva , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Encéfalo/metabolismo , Lesões Encefálicas/metabolismo , Isquemia Encefálica/metabolismo , Linfócitos T CD8-Positivos , Disfunção Cognitiva/metabolismo , Glutaratos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/metabolismo , Camundongos , Camundongos Endogâmicos C57BL
10.
J Mol Biol ; 434(19): 167756, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35870648

RESUMO

Histone chaperones, which constitute an interaction and functional network involved in all aspects of histone metabolism, have to date been identified only in eukaryotes. The Epstein-Barr virus tegument protein BKRF4 is a histone-binding protein that engages histones H2A-H2B and H3-H4, and cellular chromatin, inhibiting the host DNA damage response. Here, we identified BKRF4 as a bona fide viral histone chaperone whose histone-binding domain (HBD) forms a co-chaperone complex with the human histone chaperone ASF1 in vitro. We determined the crystal structures of the quaternary complex of the BKRF4 HBD with human H3-H4 dimer and the histone chaperone ASF1b and the ternary complex of the BKRF4 HBD with human H2A-H2B dimer. Through structural and biochemical studies, we elucidated the molecular basis for H3-H4 and H2A-H2B recognition by BKRF4. We also revealed two conserved motifs, D/EL and DEF/Y/W, within the BKRF4 HBD, which may represent common motifs through which histone chaperones target H3-H4 and H2A-H2B, respectively. In conclusion, our results identify BKRF4 as a histone chaperone encoded by the Epstein-Barr virus, representing a typical histone chaperone found in a non-eukaryote. We envision that more histone chaperones await identification and characterization in DNA viruses and even archaea.


Assuntos
Infecções por Vírus Epstein-Barr , Chaperonas de Histonas , Proteínas de Ciclo Celular/metabolismo , Cromatina , Herpesvirus Humano 4/genética , Chaperonas de Histonas/metabolismo , Histonas/metabolismo , Humanos , Ligação Proteica , Proteínas Virais/metabolismo
11.
Contrast Media Mol Imaging ; 2022: 9627663, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795881

RESUMO

Objective: To explore the effect of 3D Slicer preoperative planning and intraoperative guidance with mobile phone virtual reality (VR) technology on brain glioma surgery. Methods: By means of retrospective study, the data of 77 brain glioma patients treated in the neurosurgery departments at The Second Affiliated Hospital of Wannan Medical College and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2015 to January 2022 were analyzed, and the patients were divided into the experimental group (EG, n = 38) and the control group (CG, n = 39) according to the surgical modalities. Before surgery, all patients received positron emission tomography-computed tomography (PET/CT) scanning and magnetic resonance imaging (MRI) examination. For patients in EG, the DICOM format images acquired from PET-CT and MRI examinations were imported with the 3D Slicer software for 3D visual fusion reconstruction, acquiring VR images, and developing detailed preoperative planning. Then, the reconstructed images were imported into the Sina software on a mobile phone, and the surgery was performed with the assistance of VR technology; for patients in CG, traditional 2D images were used for tumor contour drawing by the subjective visual method, and the craniotomy was performed under a traditional microscope. Patients' surgery indicators and Karnofsky Performance Scale (KPS) scores were compared between the two groups. Results: The number of cases with total resection, rate of total resection, hospital stay after surgery, and surgery time were significantly better in EG than in CG (P < 0.05); after treatment, the KPS score was significantly higher in EG than in CG (75.66 ± 4.01 vs 65.36 ± 5.23, P < 0.001). Conclusion: Combining 3D Slicer preoperative planning with intraoperative mobile phone VR technology can promote the accuracy of brain glioma surgery, which is conducive to effectively removing tumors while protecting patients' neural function.


Assuntos
Telefone Celular , Glioma , Realidade Virtual , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , China , Glioma/diagnóstico por imagem , Glioma/cirurgia , Humanos , Imageamento Tridimensional/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Tecnologia
12.
Food Res Int ; 158: 111553, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35840246

RESUMO

Listeria monocytogenes is a significant foodborne health hazard in many products and may survive and grow when making fermented meat sausages. The objective of this study was to investigate the competition between lactic acid bacteria (LAB) and L. monocytogenes during simultaneous fermentation and drying (SFD) of meat sausages. Sausages made from irradiated ground beef (90% lean), salt, sugar, and sodium nitrite were inoculated with a 4-stain cocktail of LAB (2 Lactobacillus plantarum and 2 Lb. brevis strains) and a 5-strain cocktail of L. monocytogenes, individually or in combination, and incubated (30 °C, relative humidity 76%) for 5 days to undergo SFD. The changes in the populations of LAB and L. monocytogenes were monitored to determine the growth kinetics and examine the competitive growth between the two. L. monocytogenes grew in the sausage samples unhindered without LAB but was suppressed by LAB during SFD. The interaction between LAB and L. monocytogenes could be described by a modified Lotka-Volterra equation. The decreases of pH and aw in sausages could be related to the SFD time using segmented linear models. The competition model could accurately predict the growth of LAB and L. monocytogenes during SFD and may be used to improve the safety of semi-dry and dry fermented meat sausages.


Assuntos
Lactobacillales , Listeria monocytogenes , Animais , Bovinos , Fermentação , Microbiologia de Alimentos , Carne
13.
Front Oncol ; 12: 849024, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837113

RESUMO

Objective: Methylation of the promoters of SHOX2 and RASSF1A are potentially informative biomarkers for the diagnosis of early lung adenocarcinoma (LUAD). Abnormal methylation of SHOX2 and RASSF1A promoters may promote the occurrence and facilitate the progression of LUAD. Materials and Methods: We selected 54 patients with early LUAD and 31 patients with benign lung nodules as a NJDT cohort and evaluated their DNA methylation and mRNA sequencing levels. The DNA methylation sequencing, mRNA sequencing, and clinical data for patients with LUAD were obtained from The Cancer Genome Atlas, and served as a TCGA cohort. We evaluated the diagnostic potential of a SHOX2 and RASSF1A combined promoter methylation assay for detection of early LUAD in the NJDT cohort. Then we explored the promoter methylation levels of SHOX2 and RASSF1A and their gene expression between normal and tumor samples at different stages in both cohorts. Pathways enriched between tumor and normal samples of methylation-positive patients in the NJDT cohort were analyzed. Results: In the NJDT cohort, the sensitivity of the combined promoter methylation assay on tumor samples was 74.07%, the sensitivity on paired tumor and paracancerous samples was 77.78%, and the specificities in both contexts were 100%. The combined promoter methylation-positive patients had clinicopathologic features including older age, larger tumors, deeper invasion, and higher Ki-67 expression. In both cohorts, SHOX2 expression increased and RASSF1A expression decreased in tumor samples. The promoter methylation level of SHOX2 and RASSF1A was significantly higher in tumor samples at stage I-II than that in normal samples. The promoter methylation levels of these two genes were both negative associated with their expression in early tumor samples. In the NJDT cohort, methylation-positive patients of both individual SHOX2 and RASSF1A assays exhibited upregulation of folate acid metabolism and nucleotide metabolism in tumor samples. The SHOX2 methylation-positive and RASSF1A methylation-positive patients showed the downregulation of pathways related to cell proliferation and apoptosis and pathways involved in DNA repair, cell growth and cell adhesion, respectively. Conclusion: The combined promoter methylation assay for SHOX2 and RASSF1A can be used for screening and diagnosis of early LUAD, with good sensitivity and specificity. The promoter methylation levels of SHOX2 and RASSF1A were associated with their abnormal mRNA expression, and affected DNA instability, cell proliferation, apoptosis and tumor microenvironment in patients with LUAD.

14.
Pharmaceutics ; 14(7)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35890264

RESUMO

Combinations of two different therapeutic modalities of VEGF inhibitors against angiogenesis can cooperatively impede breast cancer tumor growth and enhance therapeutic efficacy. Itraconazole (ITZ) is a conventional antifungal drug with high safety; however, it has been repurposed to be a multi target anti-angiogenesis agent for cancer therapy in recent years. In the present study, composite nanoparticles co-loaded with ITZ and VEGF siRNA were prepared in order to investigate their anti-angiogenesis efficacy and synergistic anticancer effect against breast cancer. The nanoparticles had a suitable particle size (117.9 ± 10.3 nm) and weak positive surface charge (6.69 ± 2.46 mV), as well as good stability and drug release profile in vitro. Moreover, the nanoparticles successfully escaped from endosomes and realized cell apoptosis and cell proliferation inhibition in vitro. In vitro and in vivo experiments showed that the nanoparticles could induce the silencing of VEGF-related expressions as well as anti-angiogenesis efficacy, and the co-loaded ITZ-VEGF siRNA NPs could inhibit tumor growth effectively with low toxicity and side effects. Taken together, the as-prepared delivery vehicles are a simple and safe nano-platform that improves the antitumor efficacy of VEGF siRNA and ITZ, which allows the repositioning of the generic drug ITZ as a great candidate for antitumor therapy.

15.
Front Cell Infect Microbiol ; 12: 922146, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811679

RESUMO

Background: Malaria is a global public health problem. China has had no case of indigenous malaria since 2016. However, imported cases of malaria remain an issue among travelers, overseas workers, and foreign traders. Although these cases are always asymptomatic, if they donate blood, there is a great risk of transfusion transmitted-malaria (TTM). Therefore, blood banks need a rapid screening tool to detect Plasmodium species. Methods: We designed an assay using recombinase-aided amplification (RAA) and a lateral-flow dipstick (LFD) (RAA-LFD) to detect the 18S ribosomal RNA gene of Plasmodium species. Sensitivity was evaluated using a recombinant plasmid and Plasmodium genomic DNA. Specificity was evaluated using DNA extracted from the blood of patients with malaria or other infectious parasites. For clinical assessment, blood samples from patients with malaria and blood donors were evaluated. Results: The RAA-LFD assay was performed in an incubator block at 37°C for 15 min, and the amplicons were visible to the naked eye on the flow dipsticks within 3 min. The sensitivity was 1 copy/µL of recombinant plasmid. For genomic DNA from whole blood of malaria patients infected with P. falciparum, P. vivax, P. ovale, and P. malariae, the sensitivity was 0.1 pg/µL, 10 pg/µL, 10-100 pg/µL, and 100pg/µL, respectively. The sensitivity of this assay was 100pg/µL. No cross-reaction with other transfusion-transmissible parasites was detected. Conclusions: The results demonstrated that this RAA-LFD assay was suitable for reliable field detection of Plasmodium species in low-resource settings with limited laboratory capabilities.


Assuntos
Malária Falciparum , Malária Vivax , Malária , Plasmodium , Humanos , Malária/diagnóstico , Malária/parasitologia , Malária Falciparum/parasitologia , Técnicas de Amplificação de Ácido Nucleico/métodos , Plasmodium/genética , Recombinases , Sensibilidade e Especificidade
16.
J Nanobiotechnology ; 20(1): 281, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705976

RESUMO

BACKGROUND: Oral chemotherapy is preferred for patients with cancer owing to its multiple advantages, including convenience, better patient compliance, and improved safety. Nevertheless, various physical barriers exist in this route that hamper the development of oral chemotherapeutic formulations, including destruction of drugs in the gastrointestinal tract (GIT), low permeability in enterocytes, and short residence time in the intestine. To overcome these limitations, it is necessary to design an efficient oral drug delivery system with high efficacy and improved safety. RESULTS: Herein, we designed novel glycocholic acid (GCA)-functionalized double layer nanoparticles (GCA-NPs), which can act via an endogenous pathway and in a temporally controlled manner in the intestine, to enhance the oral bioavailability of hydrophobic chemotherapeutic drugs such as paclitaxel (PTX). GCA-NPs were composed of quercetin (Qu)-modified liposomes (QL) coated with GCA-chitosan oligosaccharide conjugate (GCOS). The GCA-NPs thus prepared showed prolonged intestinal retention time and good GIT stability due to the presence of chitosan oligosaccharide (COS) and enhanced active transportation via intestinal apical sodium-dependent bile acid transporter (ASBT) due to the presence of GCA. GCA-NPs also efficiently inhibited intestinal P-gp induced by Qu. PTX-loaded GCA-NPs (PTX@GCA-NPs) had a particle size of 84 nm and an entrapment efficiency of 98% with good stability. As a result, the oral bioavailability of PTX was increased 19-fold compared to that of oral Taxol® at the same dose. Oral PTX@GCA-NPs displayed superior antitumor efficacy and better safety than Taxol® when administered intravenously. CONCLUSIONS: Our novel drug delivery system showed remarkable efficacy in overcoming multiple limitations and is a promising carrier for oral delivery of multiple drugs, which addresses several challenges in oral delivery in the clinical context.


Assuntos
Quitosana , Nanopartículas , Administração Oral , Biomimética , Quitosana/química , Portadores de Fármacos/química , Humanos , Íleo , Nanopartículas/química , Oligossacarídeos , Paclitaxel , Quercetina
19.
Eur J Pharm Sci ; 175: 106231, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35671901

RESUMO

The synergistic therapy of malignant tumors with chemotherapy and photothermal therapy has attracted extensive researcher attention. With the further development of photosensitizers, photosensitizer delivery and stability are the urgent problem to be solved at present. In this study, the biodegradable hybrid micelles (HMs) nano system for co-delivery paclitaxel (PTX) and IR825, investigating the photosensitizer stability in the drug delivery system and therapeutic effectiveness in vitro or in vivo. The hybrid micelle (PTX/IR825-TAT HMs) was self-assembled through hydrophobic interactions between polyethyleneimine-polycaprolactone (PEI-PCL) and TAT peptide modifided-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol)5000 (TAT-PEG-DSPE). The results indicated that TAT HMs could successfully encapsulate IR825 PTX (PTX/IR825-TAT HMs). More importantly, IR825 encapsulated in hybrid micelles improved physiological stability, thermostability and photostability. In addition, the PTX released rapidly from PTX/IR825-TAT HMs in acidic and laser irradiation environments. In vitro cell analysis demonstrated that PTX/IR825-TAT HMs exhibited effective internalization of breast cancer cells. At the same time, PTX/IR825-TAT HMs with laser irradiation synergistically induced cancer cell apoptosis and death. indicating chemo-photothermal therapy synergistic therapeutic effect. In vivo antitumor studies showed that PTX/IR825-TAT HMs precisely reached the tumor tissue and convert light energy into heat energy under laser irradiation, PTX/IR825-TAT HMs had excellent synergistic antitumor efficiency compared to single chemotherapy and photothermal therapy.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Camundongos , Camundongos Endogâmicos BALB C , Micelas , Nanopartículas/química , Neoplasias/tratamento farmacológico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico
20.
Front Endocrinol (Lausanne) ; 13: 841256, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721703

RESUMO

Background: Although a variety of data showing that diabetes mellitus (DM) (Type 1 or Type 2) is associated with postoperative complication, there is still a lack of detailed studies that go through the specific diabetic subgroups. The goal of this meta-analysis is to assess the relationship between DM and various complications after non-cardiac surgery. Methods: We searched articles published in three mainstream electronic databases (PubMed, EMBASE, Web of science) before November, 2020. A random effects model was conducted since heterogeneity always exist when comparing results between different types of surgery. Results: This paper included 125 studies with a total sample size of 3,208,776 participants. DM was a risk factor for any postoperative complication (Odds ratio (OR)=1.653 [1.487, 1.839]). The risk of insulin-dependent DM (OR=1.895 [1.331, 2.698]) was higher than that of non-insulin-dependent DM (OR=1.554 [1.061, 2.277]) for any postoperative complication. DM had a higher risk of infections (OR=1.537 [1.322, 1.787]), wound healing disorders (OR=2.010 [1.326, 3.046]), hematoma (OR=1.369 [1.120, 1.673]), renal insufficiency (OR=1.987 [1.311, 3.013]), myocardial infarction (OR=1.372 [0.574, 3.278]). Meanwhile, DM was a risk factor for postoperative reoperation (OR=1.568 [1.124, 2.188]), readmission (OR=1.404 [1.274, 1.548]) and death (OR=1.606 [1.178, 2.191]). Conclusions: DM is a risk factor for any postoperative complications, hospitalization and death after non-cardiac surgery. These findings underscore the importance of preoperative risk factor assessment of DM for the safe outcome of surgical patients.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/cirurgia , Diabetes Mellitus Tipo 2/complicações , Humanos , Razão de Chances , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco
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