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1.
J Inflamm Res ; 14: 5687-5697, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754215

RESUMO

Purpose: The role of NLRP3 inflammasome in the progression of many diseases has been increasingly recognized. However, the function of this molecular assembly in the development and progression of B-cell non-Hodgkin's lymphoma remains unclear. Patients and Methods: In this study, we investigated the polymorphisms in the NLRP3 inflammasome associated genes in 281 patients with B-cell non-Hodgkin's lymphoma and 385 age- and gender-matched healthy controls. Results: We found that IL-18 (rs1946518) and NFκB-94 ins/del (rs28362491) contributed to susceptibility to B-cell non-Hodgkin's lymphoma. Specifically, the allele "G" in IL-18 (rs1946518) and allele "ins" in NFκB-94 ins/del (rs28362491) were significantly associated with the risk of disease. The AA genotype of CARD8 (rs2043211) and the higher level of serum lactate dehydrogenase (LDH) led to statistically poorer B-cell non-Hodgkin's lymphoma survival. Less frequent genotype TT of CARD8 (rs2043211) was observed in patients with higher LDH level, clinical stages III-IV of disease, and IPI 3-5, although the relationship did not reach statistical significance. However, IPI is an independent prognostic factor for B-cell non-Hodgkin's lymphoma. Conclusion: IL-18 (rs1946518) and NFκB-94 ins/del (rs28362491) gene polymorphisms appear to be the factors influencing the risk of B-cell non-Hodgkin's lymphoma. CARD8 (rs2043211) polymorphisms are important factors for the survival of patients with this disease.

2.
Dev Comp Immunol ; 128: 104321, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34798199

RESUMO

MDM2 (mouse double-minute) and p53 form a negative feedback loop and play a prominent role in preventing the induction of uncontrolled apoptosis. To better understand their potential roles in oyster Crassostrea hongkongensis, MDM2 and p53 homologs were first isolated and cloned in C. hongkongensis (named ChMDM2 and Chp53), and their mRNA expression patterns in tissues and developmental stages were analyzed. Multiple sequence alignment analysis and phylogenetic analysis of ChMDM2 and Chp53 displayed a high degree of homology and conservation. In addition, exposure to Vibrio coralliilyticus resulted in DNA damage and apoptosis in the hemocytes of C. hongkongensis, and found that the mRNA expression level of ChMDM2 was decreased, while the relative expression of Chp53 was significantly increased in the hemocytes and gills. Furthermore, fluorescence from ChMDM2-EGFP and Chp53-Red were found to be distributed in the nucleus of HEK293T cells. Besides, dual-luciferase reporter assays showed that ChMDM2 antagonized with Chp53 and participates in p53 signaling pathway. In addition, the interaction between ChMDM2 and Chp53 was confirmed strongly by Co-immunoprecipitation assays. Furthermore, the results of RNAi showed that ChMDM2 and Chp53 participated in apoptosis which induced infection of V. coralliilyticus. Taken together, our results characterized the features of ChMDM2 and Chp53, which played a critical role in apoptosis of C. hongkongensis.

3.
Bioengineered ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34839787

RESUMO

Sepsis-induced myocardial dysfunction (SIMD) is ubiquitous in septic shock patients and is associated with high morbidity and mortality rates. Heat shock protein 22 (Hsp22), which belongs to the small HSP family of proteins, is involved in several biological functions. However, the function of Hsp22 in lipopolysaccharide (LPS)-induced myocardial injury is not yet established. This study was aimed at investigating the underlying mechanistic aspects of Hsp22 in myocardial injury induced by LPS. In this study, following the random assignment of male C57BL/6 mice into control, LPS-treated, and LPS + Hsp22 treated groups, relevant echocardiograms and staining were performed to scrutinise the cardiac pathology. Plausible mechanisms were proposed based on the findings of the enzyme-linked immunosorbent assay and western blotting assay. A protective role of Hsp22 against LPS-induced myocardial injury emerged, as evidenced from decreased levels of creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and enhanced cardiac function. The post-LPS administration-caused spike in inflammatory cytokines (IL-1ß, IL-6, TNF-α and NLRP3) was attenuated by the Hsp22 pre-treatment. In addition, superoxide dismutase (SOD) activity and B-cell lymphoma-2 (Bcl2) levels were augmented by Hsp22 treatment resulting in lowering of LPS-induced oxidative stress and cardiomyocyte apoptosis. In summary, the suppression of LPS-induced myocardial injury by Hsp22 overexpression via targeting of inflammation, oxidative stress, and apoptosis in cardiomyocytes paves the way for this protein to be employed in the therapy of SIMD.

4.
PLoS One ; 16(10): e0253858, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618818

RESUMO

Research indicates that Staphylococcus aureus colonization in the elderly with predisposing risks is associated with subsequent infection. However, the molecular epidemiology and risk factors for S. aureus colonization among residents and staff in nursing homes (NHs) in China remain unclear. A multicenter study was conducted in three NHs in Shanghai between September 2019 and October 2019. We explored the prevalence, molecular epidemiology, and risk factors for S. aureus colonization. All S. aureus isolates were characterized based on antimicrobial resistance, virulence genes, multilocus sequence typing (MLST), staphylococcus protein A (spa) typing, and staphylococcal cassette chromosome mec (SCCmec) typing. NH records were examined for potential risk factors for S. aureus colonization. S. aureus and methicillin-resistant S. aureus (MRSA) isolates were detected in 109 (100 residents and 9 staff, 19.8%, 109/551) and 28 (24 residents and 4 staff, 5.1%, 28/551) subjects among 496 residents and 55 staff screened, respectively. Compared to methicillin-susceptible S. aureus isolates, all 30 MRSA isolates had higher resistance rates to most antibiotics except minocycline, rifampicin, linezolid, vancomycin, and teicoplanin. Sequence type (ST) 1 (21.3%) was the most common sequence type, and t127 (20.5%) was the most common spa type among 122 S. aureus isolates. SCCmec type I (70%) was the dominant clone among all MRSA isolates. CC1 (26/122, 21.3%) was the predominant complex clone (CC), followed by CC398 (25/122, 20.5%), CC5 (20/122, 16.4%) and CC188 (18/122, 14.8%). Female sex (OR, 1.70; 95% CI, 1.04-2.79; P = 0.036) and invasive devices (OR, 2.19; 95% CI, 1.26-3.81; P = 0.006) were independently associated with S. aureus colonization.


Assuntos
Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , China , Análise Fatorial , Feminino , Genótipo , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Epidemiologia Molecular/métodos , Tipagem de Sequências Multilocus , Casas de Saúde , Fatores de Risco , Infecções Estafilocócicas/tratamento farmacológico , Fatores de Virulência/genética
5.
Front Immunol ; 12: 746017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621277

RESUMO

Vibrio species are ubiquitously distributed in marine environments, with important implications for emerging infectious diseases. However, relatively little is known about defensive strategies deployed by hosts against Vibrio pathogens of distinct virulence traits. Being an ecologically relevant host, the oyster Crassostrea hongkongensis can serve as an excellent model for elucidating mechanisms underlying host-Vibrio interactions. We generated a Vibrio alginolyticus mutant strain (V. alginolyticus △ vscC ) with attenuated virulence by knocking out the vscC encoding gene, a core component of type III secretion system (T3SS), which led to starkly reduced apoptotic rates in hemocyte hosts compared to the V. alginolyticus WT control. In comparative proteomics, it was revealed that distinct immune responses arose upon encounter with V. alginolyticus strains of different virulence. Quite strikingly, the peroxisomal and apoptotic pathways are activated by V. alginolyticus WT infection, whereas phagocytosis and cell adhesion were enhanced in V. alginolyticus △ vscC infection. Results for functional studies further show that V. alginolyticus WT strain stimulated respiratory bursts to produce excess superoxide (O2•-) and hydrogen peroxide (H2O2) in oysters, which induced apoptosis regulated by p53 target protein (p53tp). Simultaneously, a drop in sGC content balanced off cGMP accumulation in hemocytes and repressed the occurrence of apoptosis to a certain extent during V. alginolyticus △ vscC infection. We have thus provided the first direct evidence for a mechanistic link between virulence of Vibrio spp. and its immunomodulation effects on apoptosis in the oyster. Collectively, we conclude that adaptive responses in host defenses are partially determined by pathogen virulence, in order to safeguard efficiency and timeliness in bacterial clearance.

6.
Front Genet ; 12: 722601, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659345

RESUMO

Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer death worldwide. Hence, for a better understanding of tumor microenvironment and to seek for novel molecular targets for esophageal cancer, we performed related studies on two histopathological subtypes of esophageal cancer: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Bioinformatic analyses were conducted based on the RNA-seq, genomic mutation, and clinical data from TCGA and GEO cohorts. We clustered patients into high-immunity and low-immunity groups through the ssGSEA results. The ESTIMATE algorithm was used to evaluate the tumor microenvironment. Patients with high immunity in both ESCC and EAC had lower tumor purity and poor survival. Subsequently, CIBERSORT was performed to learn about the detailed difference of tumor-infiltrating lymphocytes (TILs) between high- and low-immunity patients. Specific increase of M2 macrophages and decrease of activated dendric cells can be observed in ESCC and EAC, respectively. The most enriched functions and pathways of high-immunity patients were immunoglobulin complex, MHC class II protein complex, and allograft rejection according to the GO terms and KEGG. Two prognostic immune-related multi-lncRNA risk models were constructed and validated by ROC curve and PCA in ESCC and EAC. High-risk patients in both subtypes had poor survival, advanced clinical characteristics, and higher drug susceptibility except cisplatin and sorafenib. In addition, the tumor mutation burden (TMB) was positively correlated with the risk level in the ESCC and EAC and showed distinct differences between the two subtypes. In summary, we comprehensively analyzed the tumor microenvironment for two subtypes of esophageal cancer, identified two multi-lncRNA signatures predictive for the prognosis, and explored the possibility of the signatures to forecast drug susceptibility as well as TMB for the first time. The findings may serve as a conceptual basis for innovative strategy of individualized immunotherapy for esophageal cancer.

7.
Nanomaterials (Basel) ; 11(10)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34685178

RESUMO

MXenes are a new class of two-dimensional (2D) materials with promising applications in many fields because of their layered structure and unique performance. In particular, the physical barrier properties of two-dimensional nanosheets make them suitable as barriers against hydrogen. Herein, MXene coatings were prepared on pipe steel by a simple spin-coating process with a colloidal suspension. The hydrogen resistance was evaluated by electrochemical hydrogen permeation tests and slow strain rate tests, and the corrosion resistance was assessed by potentiodynamic polarization. The results reveal that MXene coatings offer excellent hydrogen resistance and corrosion protection by forming a barrier against diffusion. Experimentally, the hydrogen permeability of the MXene coating is one third of the substrate, and the diffusion coefficient decreases as well. The mechanistic study indicates that the hydrogen resistance of the MXene coatings is affected by the number of spin-coated layers, while the concentration of the d-MXene colloidal suspension determines the thickness of a single coating. However, damage to the sample surface caused by the colloidal suspension that contains H+ and F- may limit the improvement of the hydrogen resistance. This paper reveals a new application of 2D MXene materials as a novel efficient barrier against hydrogen permeation and the subsequent alleviation of hydrogen embrittlement in the steel substrate.

9.
J Aging Health ; : 8982643211045546, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517775

RESUMO

Background: Medication-related problems in older Blacks with diabetes mellitus (DM) are not well established. Objectives: To describe the frequency of medication-related problems in older Blacks with DM presenting to the emergency department (ED). Methods: The study was a cross-sectional analysis of baseline data from a randomized controlled trial evaluating Blacks aged ≥60 years of age presenting to the ED. Polypharmacy, potentially inappropriate medication (PIM) use, and anticholinergic score were evaluated. Results: Of 168 patients (median age = 68, range 60-92), most (n = 164, 98%) were taking ≥5 medications, and 67 (39.9%) were taking a PIM. A majority (n = 124, 74%) were taking a medication with an anticholinergic score ≥1. Number of medications was correlated with number of PIMs (r = .22, p = .004) and anticholinergic score (r = .50, p < .001). Conclusion: Polypharmacy and PIM use was common in older Blacks with DM.

11.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 293-296, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374243

RESUMO

Objective: To investigate the effects of glutamine on exercise-induced fatigue, skeletal muscle oxidation and liver cell apoptosis in rats. Methods: Twenty SPF grade SD rats aged at 8 week and weight from 180 to 220 g, were divided into control group and glutamine-treated group after one week of feeding, 10 rats in each group. The rats in the glutamine group were treated with glutamine at the dose of 1.0 g/(kg·d)by intragastric administration, and the rats in control group were administrated with equal volume of normal saline. After 7 days, the exhaustion test was conducted, the content of glutathione (GSH) was detected by high-performance liquid chromatography. Superoxide dismutase (SOD), malondialdehyde (MDA), lactic acid (2-hydroxypropanoic acid (LD) were detected by enzyme-linked immunosorbent assay, and the creatine kinase(CK) was detected by electroluminescence. Activities of CK, Lactate dehydrogenase (LDH), and expression levels of Bcl-2 and Bax mRNA were detected by fluorescence quantitative RT-PCR. Results: The duration of exhaustion in the glutamine group was greater than that in the control group (P<0.05). The serum glutathione level in the glutamine group was lower than that in the control group (P<0.05). After exhaustion, the levels of GSH, SOD and MDA in serum and skeletal muscle of the glutamine group were higher than those of the control group significantly differences (P< 0.05). The serum Bax mRNA level in the glutamine group was lower than that in the control group significantly (P<0.05). The serum bcl-2 mRNA level in the glutamine group was higher than that in the control group significantly (P<0.05). Conclusion: Glutamine can effectively alleviate exercise-induced fatigue in rats, reduce the oxidation degree of skeletal muscle, and decrease the apoptosis rate of liver cells.


Assuntos
Apoptose , Glutamina , Animais , Fadiga , Fígado , Malondialdeído , Músculo Esquelético , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase
12.
Angew Chem Int Ed Engl ; 60(44): 23771-23776, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34405502

RESUMO

Thermally activated delayed fluorescence (TADF) materials with through-space charge transfers (CT) have attracted particularly interest recently. However, the slow reverse intersystem crossing (RISC) and radiative decay always limit their electroluminescence performances. Herein, TADF molecules with ortho-linked multiple donors-acceptor (ortho-Dn -A) motif are developed to create near-degenerate excited states for the reinforcement of spin-orbit coupling. The incorporation of both through-bond and through-space CT enlarges oscillator strength. The optimal ortho-D3 -A compound exhibits a photoluminescence quantum yield of ca. 100 %, a high RISC rate of 2.57×106  s-1 and a high radiative decay rate of 1.00×107  s-1 simultaneously. With this compound as the sensitizer, a TADF-sensitized-fluorescent organic light-emitting diode shows a maximum external quantum efficiency of 31.6 % with an ultrapure green Commission Internationale de L'Eclairage y coordinate value of 0.69.

13.
Exp Cell Res ; 406(1): 112761, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34339675

RESUMO

Stresses, such as neurohumoral activation, induced pathological cardiac hypertrophy is the main risk factor for heart failure. The ubiquitin-proteasome system (UPS) plays a key role in maintaining protein homeostasis and cardiac function. However, research on the role and mechanism of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is limited. Here, we observe that the deubiquitinating enzyme ubiquitin-specific protease 12(USP12) is upregulated in Ang II-induced hypertrophic hearts and primary neonatal rat cardiomyocytes (NRCMs). Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy, while overexpression of USP12 have the opposite effect. USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo. Moreover, we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3, a methyltransferase which catalyze N6-methyladenosine (m6A) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy. Upregulation of METTL3 reverse the reduction of myocardial hypertrophy induced by USP12 silencing in NRCMs. In contrast, knockdown of METTL3 attenuate the aggravation of myocardial hypertrophy in USP12-overexpressing NRCMs. Furthermore, we discover that USP12 promote the expression of METTL3 via upregulating p300. Mechanistically, USP12 binds and stabilizes p300, thereby activating the transcription of its downstream gene METTL3. Finally, our data show that USP12 is partially dependent on the stabilization of p300 to activate METTL3 expression and promote myocardial hypertrophy. Taken together, our results demonstrate that USP12 acts as a pro-hypertrophic deubiquitinating enzyme via enhancing p300/METTL3 axis, indicating that targeting USP12 could be a potential treatment strategy for pathological cardiac hypertrophy.


Assuntos
Cardiomegalia/genética , Proteína p300 Associada a E1A/genética , Metiltransferases/genética , Miócitos Cardíacos/metabolismo , Ubiquitina Tiolesterase/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Angiotensina II/administração & dosagem , Animais , Animais Recém-Nascidos , Cardiomegalia/induzido quimicamente , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Proteína p300 Associada a E1A/metabolismo , Regulação da Expressão Gênica , Masculino , Metiltransferases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos Cardíacos/citologia , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação
14.
Ying Yong Sheng Tai Xue Bao ; 32(7): 2545-2554, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34313073

RESUMO

The middle and upper reaches of Ganjiang River is an important functional area for soil and water conservation in the southeastern hills of China. It is important to analyze the land use change and their driving forces at different spatial and temporal scales to maintain and optimize the local ecological functions. We analyzed the land use structure and land use dynamics in the middle and upper reaches of Ganjiang River from 1980-2018 based on 1 km spatial resolution land use data, and analyzed the spatial heterogeneity and driving factors of land use change using principal component analysis (PCA), ordinary least squares (OLS) and geographically weighted regression (GWR). From 1980-2018, the main land use types in the study area were forests (proportion 69.4%-71%) and cultivated land (proportion 20.8%-20.9%). Land use dynamic degree of build-up land and unused land were larger, and the comprehensive land use dynamic degree gradually increased, especially in 2010-2018. The GWR model had a better fitting effect on the analysis of land use change drivers, which was better in 98.6% of the area. Among the influencing factors of the spatial heterogeneity of land use change in the study area, the natural environment factors were the most obvious, with a restrictive role. The socio-economic factors were the secondary in importance, with a promoting role. The comprehensive influence of natural and social factors were weak and complex.


Assuntos
Florestas , Rios , China , Conservação dos Recursos Naturais , Solo , Regressão Espacial
15.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34208945

RESUMO

Intense pulsed electric fields (PEF) are a novel modality for the efficient and targeted ablation of tumors by electroporation. The major adverse side effects of PEF therapies are strong involuntary muscle contractions and pain. Nanosecond-range PEF (nsPEF) are less efficient at neurostimulation and can be employed to minimize such side effects. We quantified the impact of the electrode configuration, PEF strength (up to 20 kV/cm), repetition rate (up to 3 MHz), bi- and triphasic pulse shapes, and pulse duration (down to 10 ns) on eliciting compound action potentials (CAPs) in nerve fibers. The excitation thresholds for single unipolar but not bipolar stimuli followed the classic strength-duration dependence. The addition of the opposite polarity phase for nsPEF increased the excitation threshold, with symmetrical bipolar nsPEF being the least efficient. Stimulation by nsPEF bursts decreased the excitation threshold as a power function above a critical duty cycle of 0.1%. The threshold reduction was much weaker for symmetrical bipolar nsPEF. Supramaximal stimulation by high-rate nsPEF bursts elicited only a single CAP as long as the burst duration did not exceed the nerve refractory period. Such brief bursts of bipolar nsPEF could be the best choice to minimize neuromuscular stimulation in ablation therapies.


Assuntos
Eletroporação/instrumentação , Fibras Nervosas/fisiologia , Potenciais de Ação , Animais , Anuros , Técnicas Eletroquímicas , Eletrodos
16.
Cancer Cell Int ; 21(1): 343, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217264

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), derived from renal tubular epithelial cells, is the most common malignant tumor of the kidney. The study of key genes related to the pathogenesis of ccRCC has become important for gene target therapy. METHODS: Bioinformatics analysis of The Cancer Genome Atlas (TCGA), the NCBI Gene Expression Omnibus (GEO) database, USUC Xena database, cBioPortal for Cancer Genomics, and MethSurv were performed to examine the aberrant genetic pattern and prognostic significance of leucine-rich repeat kinase 2 (LRRK2) expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression. The regulation of ccRCC tumor cell lines proliferation by LRRK2 was examined by CCK8 assay. RESULTS: Bioinformatics analysis showed that LRRK2 expression was up-regulated and largely correlated with DNA methylation in ccRCC. The up-regulation of LRRK2 was confirmed in ccRCC tissue immunohistochemically and by protein analysis. The level of expression was related to gender, pathological grade, stage, and metastatic status of ccRCC patients. Meanwhile, Kaplan-Meier analysis showed that high expression of LRRK2 correlates to a better prognosis; knockdown of LRRK2 expression attenuated the proliferation ability of ccRCC tumor cell lines; protein-protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR. CONCLUSION: We found that LRRK2 may play an important role in the tumorigenesis and progression of ccRCC. Our findings provided a potential predictor and therapeutic target in ccRCC.

17.
Bioelectrochemistry ; 141: 107876, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34171507

RESUMO

Stimulation and electroporation by nanosecond electric pulses (nsEP) are distinguished by a phenomenon of bipolar cancellation, which stands for a reduced efficiency of bipolar pulses compared to unipolar ones. When two pairs of stimulating electrodes are arrayed in a quadrupole, bipolar cancellation inhibits nsEP effects near the electrodes, where the electric field is the strongest. Two properly shaped and synchronized bipolar nsEP overlay into a unipolar pulse towards the center of the electrode array, thus canceling the bipolar cancellation (a "CANCAN effect"). High efficiency of the re-created unipolar nsEP outweighs the weakening of the electric field with distance and focuses nsEP effects to the center. In monolayers of CHO, BPAE, and HEK cells, CANCAN effect achieved by the interference of two bipolar nsEP enhanced electroporation up to tenfold, with a peak at the quadrupole center. Introducing a time interval between bipolar nsEP prevented the formation of a unipolar pulse and eliminated the CANCAN effect. Strong electroporation by CANCAN stimuli killed cells over the entire area encompassed by the electrodes, whereas the time-separated pulses caused ablation only in the strongest electric field near the electrodes. The CANCAN approach is promising for uniform tumor ablation and stimulation targeting away from electrodes.

18.
J Pathol Clin Res ; 7(5): 507-516, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34062050

RESUMO

Carcinoma arising from a mucinous cystic neoplasm (MCN) of the pancreas is termed MCN with associated invasive carcinoma (MCN-AIC) in the fifth WHO classification of digestive tumors (2019). The prognosis of this malignancy varies depending on the relationship of the invasive carcinoma to the cyst capsule, but limited data are available. This study identified 165 surgically resected MCNs including 15 MCN-AICs from a single center between 2008 and 2018 and analyzed their clinicopathologic features. The results confirmed that non-invasive MCNs were completely cured by surgery. All MCN-AICs showing an encapsulated invasion pattern (defined as invasive carcinoma limited to the ovarian-type stroma, cystic septa, and capsule) had an excellent prognosis with a 5-year survival rate of 100%, even when the size of the invasive component was up to stage T2. By contrast, MCN-AICs with extracapsular involvement had unfavorable clinical outcomes. Our study demonstrates that the pattern of invasion of MCN-AIC can predict patient prognosis. Pathologic stage T1 and T2 encapsulated MCN-AICs may be completely cured with surgical resection alone or when combined with postoperative chemotherapy.

19.
Bioengineered ; 12(1): 2810-2819, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34180358

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs. However, the underlying etiology and mechanisms remain unclear. This study was performed to identify potential therapeutic targets for SLE using bioinformatics methods. First, 584 differentially expressed genes were identified based on the GSE61635 dataset. Tissue-specific analyses, enrichment analyses, and Protein-Protein interaction network were successively conducted. Furthermore, ELISA was performed to confirm the expression levels of key genes in the control and SLE blood samples. The findings revealed that tissue-specific expression of markers of the hematological system (25.5%, 28/110) varied significantly. CCL2, MMP9, and RSAD2 expression was markedly increased in the SLE samples compared with controls. In conclusion, the identified key genes (CCL2, MMP9, and RSAD2) may act as possible therapeutic targets for the treatment of SLE.

20.
Parasit Vectors ; 14(1): 309, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099029

RESUMO

BACKGROUND: Haemaphysalis longicornis is an obligate hematophagous ectoparasite that transmits a variety of pathogens causing life-threatening diseases in humans and animals. Paramyosin (Pmy) is not only an invertebrate-specific myofibrillar protein but also an important immunomodulatory protein. Therefore, it is one of the ideal candidate antigens for vaccines. METHODS: We conducted two vaccine trials to evaluate the protective efficacy of Pmy recombinant protein (rPmy) and peptide vaccine (KLH-LEE). Each rabbit was immunized with three doses of rPmy or KLH-LEE adjuvanted with Freund's complete/incomplete at 500 µg/dose at 2-week intervals before challenge with 40 female H. longicornis/rabbit. PBS plus adjuvant, Trx or KLH was used as control group. The antibodies of rabbits were detected by ELISA. Then, female ticks were fed on the rabbits until detachment. RESULTS: ELISA results showed that both vaccines induced rabbits to produce antibodies. Compared with the Trx group, the engorgement weight, oviposition and hatchability of the rPmy group decreased by 8.87%, 26.83% and 38.86%, respectively. On the other hand, engorgement weight, oviposition and hatchability of female ticks in the KLH-LEE group correspondingly resulted in 27.03%, 53.15% and 38.40% reduction compared with that of the KLH group. Considering the cumulative effect of vaccination on the evaluated parameters, results showed 60.37% efficacy of the rPmy vaccine formulation and 70.86% efficacy in the KLH-LEE group. CONCLUSIONS: Pmy and particularly epitope LEE have potential for further development of an effective candidate vaccine to protect the host against tick infection. GRAPHIC ABSTARCT.


Assuntos
Proteínas de Artrópodes/administração & dosagem , Ixodidae/imunologia , Coelhos/imunologia , Infestações por Carrapato/veterinária , Tropomiosina/administração & dosagem , Vacinas/administração & dosagem , Animais , Anticorpos/sangue , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Imunização , Ixodidae/genética , Coelhos/sangue , Coelhos/parasitologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Infestações por Carrapato/sangue , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controle , Tropomiosina/genética , Tropomiosina/imunologia , Vacinas/genética , Vacinas/imunologia , Vacinas de Subunidades/administração & dosagem , Vacinas de Subunidades/genética , Vacinas de Subunidades/imunologia
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