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1.
Mol Biol Rep ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792826

RESUMO

Epithelial-mesenchymal transition (EMT), transforming growth factor ß(TGF-ß) and reactive oxygen species(ROS) plays a central role in cancer metastasis. Moreover, nicotinamide adenine dinucleotide phosphate 4(NOX4) is one of the main sources of ROS in lung cancer cells suggesting that NOX4 is associated with tumor cell migration. NF-κB(Nuclear factor-Kappa-B) is known to regulate ROS-mediated EMT process by activating Snail transcription factor in A549 cells. The purpose of this study was to explore the relationship between NF-κB and NOX4 in ROS production during TGF-ß induced EMT process. Several fractions have been pooled to evaluates the EMT process on lung cancer cells through real-time PCR, Western Blot and flow cytometry with DCFH-DA probe etc. Cells proliferation and migration activities were monitored by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and wound healing assay respectively. The result showed that TGF-ß induction decreased the expression of E-cadherin, increased the Vimentin and the EMT transcription factor Snail in A549 cells. DPI (Diphenyleneiodonium chloride, an inhibitor of NOX4) inhibited the NOX4 expression and reduced ROS production induced by TGF-ß, but didn't affect the activation of NF-κB induced by TGF-ß (P > 0.05). BAY11-7082 (an inhibitor of NF-κB) inhibited the NF-κB (p65) expression and prevented the increase of NOX4 expression and ROS production induced by TGF-ß (P < 0.001), which has also verified reduced TGF-ß induced cell migration by inhibiting the EMT process, and also reduced cell proliferation of A549 cells (P < 0.001). The current research confirmed the TGF-ß mediated EMT process via NF-κB/NOX4/ROS signaling pathway, NF-κB and NOX4 are likely to be the potential therapeutic targets for lung cancer metastasis.

2.
BMC Musculoskelet Disord ; 22(1): 328, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33810786

RESUMO

BACKGROUND: Limited studies were available to investigate the prevalence of deep vein thrombosis (DVT) on admission in elderly patients with intertrochanteric fractures. The aim of present study was to evaluate risk factors and the prevalence of pre-admission DVT in elderly patients with intertrochanteric fractures. METHODS: This retrospective study included 788 elderly patients with intertrochanteric fracture who were eligible for this study from January 1, 2010, to December 31, 2019. Color doppler ultrasonography was performed for DVT detection at admission. All patients' clinical data were collected. Univariate analysis and stepwise backward multivariate logistic regression were used to identify the risk factors contributing to the occurrence of DVT. RESULTS: The overall prevalence of pre-admission DVT in patients with intertrochanteric fractures was 20.81% (164 of 788 patients). The mean time from injury to admission was 2.1 days in the total population, 2.96 and 1.87 days in patients with and without DVT. Univariate analysis showed that significantly elevated risk of DVT were found in patients with longer time from injury to admission, high energy injury, lower Hb value, higher BMI, diabetes, chronic obstructive pulmonary disease (COPD), atrial fibrillation, dementia, varicose veins, higher age-adjusted CCI, higher ASA class and A3 type intertrochanteric fractures (P < 0.05). The adjusted multivariate logistic regression analysis demonstrated that longer time from injury to admission, high energy trauma, COPD, lower Hb, diabetes and A3 type intertrochanteric fractures were independent risk factors of pre-admission DVT. CONCLUSIONS: A high prevalence of pre-admission DVT was found in elderly Chinese patients with intertrochanteric fractures. Therefore, surgeons should be aware of the high prevalence of DVT for elderly patients with intertrochanteric fractures in order to prevent intraoperative and postoperative PE and other lethal complications.

3.
Orthop Surg ; 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33818010

RESUMO

OBJECTIVE: To investigate the risk factors for, and outcomes of, preoperative asymptomatic pulmonary embolism (PE) in patients ≥60 years old following delayed operation for hip fracture. METHODS: From March 2017 to December 2018, 90 patients aged ≥60 years with hip fracture who suffered a delay in surgery were recruited to this prospective study following admission to our hospital. Computed tomography pulmonary angiography (CTPA) was used to detect preoperative asymptomatic PE and calculated its incidence. Time from injury to admission, baseline characteristics, medical comorbidities, and blood biomarker levels were evaluated as potential risk factors. Logistic regression analysis was used to identify risk factors. Mortality and major bleeding events were recorded and compared between individuals with PE and without. Data were analyzed by t-test, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis. RESULTS: The incidence of preoperative asymptomatic PE was 18.9% (17/90 patients). In the univariate analysis, the risk factors for preoperative asymptomatic PE were male sex, hypertension, cerebrovascular accident, smoking, plasma D-dimer level, potassium level, urea level, creatinine level, and cysteine level. Multivariate logistic regression analysis showed that the risk of preoperative asymptomatic PE was higher in patients with hypertension (odds ratio [OR] = 10.048; 95% confidence interval [CI], 1.118-90.333), cerebrovascular accident (OR = 20.135; 95% CI, 1.875-216.164), smoking (OR = 48.741; 95% CI, 4.155-571.788), high plasma D-dimer levels (OR = 1.200; 95% CI, 1.062-157.300), and high plasma potassium levels (OR = 12.928; 95% CI, 1.062-157.300). All patients were followed up for 21.0 months (range, 2 to 36 months). Mortality within the first year postoperatively was higher in patients with PE (29.41% vs 9.59%, P = 0.046). CONCLUSIONS: In view of the high incidence of preoperative asymptomatic PE and the inferior prognosis in individuals with PE, routine CTPA examination for preoperative asymptomatic PE could be useful for patients aged ≥60 years with hip fracture for whom surgery is delayed.

4.
Clin Spine Surg ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33769977

RESUMO

STUDY DESIGN: A retrospective single-center study. OBJECTIVE: We aimed to compare the clinical outcomes of cervical spine fracture accompanied with ankylosing spondylitis (ASCSF) treated by single posterior approach (PA) and combined anterior-posterior approach (CA) for patients who were followed up for >1 year. SUMMARY OF BACKGROUND DATA: For ASCSF patients, surgical treatment has been widely accepted as a recommendable therapeutic option. But the optimal surgical approach is still under controversy, and few studies have focused on the comparison between PA and CA. MATERIALS AND METHODS: From February 2007 to March 2019, 53 patients were enrolled and divided into the PA group (34 cases) and CA group (19 cases). Their general characteristics and clinical materials were recorded. From the aspects of reduction distance, bone fusion, neurological functional restoration, and postoperative complications, patients' surgical outcomes were evaluated qualitatively and quantitatively. RESULTS: The reduction degree of dislocation (mean PA=2.05 mm, mean CA=2.36 mm, P=0.94) was close between the 2 groups. Besides, with a similar follow-up period (P=0.10), the rate of bone fusion (both 100%) and neurological functional restoration (PA=31.03%, CA=35.29%, P=0.77) were also without significant difference. The occurrence rate of postoperative complications tended to be higher in the CA group (31.58% vs. 23.53%) but with no significant difference (P=0.52). Nevertheless, the surgical duration time (mean=209.15 min) and blood loss (average=388.91 mL) of PA group were significantly less than CA group (mean duration time=285.34 min, mean blood loss=579.27 mL) (P<0.01). CONCLUSIONS: Compared with to the CA approach and with the equally significant outcome, surgery by single PA was feasible and should be positively recommended for ASCSF patients, especially for those accompanying with a severe chin-on-chest deformity or poor physical conditions which restrain patients from tolerating a long surgery or major surgical trauma.

5.
J Mater Chem B ; 9(11): 2594-2612, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33666632

RESUMO

Bone infection is a devastating disease characterized by recurrence, drug-resistance, and high morbidity, that has prompted clinicians and scientists to develop novel approaches to combat it. Currently, although numerous biomaterials that possess excellent biocompatibility, biodegradability, porosity, and mechanical strength have been developed, their lack of effective antibacterial ability substantially limits bone-defect treatment efficacy. There is, accordingly, a pressing need to design antibacterial biomaterials for effective bone-infection prevention and treatment. This review focuses on antibacterial biomaterials and strategies; it presents recently reported biomaterials, including antibacterial implants, antibacterial scaffolds, antibacterial hydrogels, and antibacterial bone cement types, and aims to provide an overview of these antibacterial materials for application in biomedicine. The antibacterial mechanisms of these materials are discussed as well.

6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(3): 255-259, 2021 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-33751536

RESUMO

OBJECTIVE: To report on the clinical features and result of genetic testing for a child featuring immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. METHODS: Clinical records, genetic testing, laboratory investigation and treatment of the child were summarized in addition with a comprehensive review of the literature. RESULTS: The 3-year-old boy was administered due to intractable diarrhea, recurrent infections, liver dysfunction and failure to thrive, though no diabetes or skin disorder was observed. Laboratory testing showed elevated liver enzymes and total IgE, decreased albumin and electrolyte imbalance. Gastrointestinal endoscopy revealed erosion and granules in the duodenum, and edema in the terminal ileum and colon. Biopsies showed villous atrophy in the duodenum and terminal ileum. Genetic testing revealed that the patient has carried a missense c.1087A>G (p.I363V) variant in the exon 10 of the FOXP3 gene. He was treated with enteral and parenteral nutrition, anti infection and Sirolimus, and was waiting for hemopoietic stem cell transplantation. CONCLUSION: Although IPEX syndrome usually occur during infancy, it should not be ruled out solely based on the age, and its presentation can be variable. For male children with refractory diarrhea, autoimmune disorder and growth retardation, the diagnosis should be suspected and confirmed by genetic testing.


Assuntos
Diabetes Mellitus Tipo 1/congênito , Diarreia , Doenças Genéticas Ligadas ao Cromossomo X , Doenças do Sistema Imunitário/congênito , Poliendocrinopatias Autoimunes , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diarreia/genética , Fatores de Transcrição Forkhead/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Testes Genéticos , Humanos , Doenças do Sistema Imunitário/genética , Masculino , Mutação , Poliendocrinopatias Autoimunes/genética
7.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 39(1): 58-63, 2021 Feb 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33723938

RESUMO

OBJECTIVES: This study aimed to investigate the association between periodontal indexes and biomarkers in gingival crevicular fluid (GCF) and preterm birth (PTB) in pregnancy, as well as to assess the clinical value of these indexes as predictors of PTB. METHODS: A nested case-control study was conducted. A total of 300 systematically healthy pregnant women were selected within 36 weeks of gestation and grouped according to the enrolled weeks. Periodontal indexes, including probing depth (PD), bleeding index (BI), gingival index (GI), and five biomarkers in GCF, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were measured at the enrolled date. The detailed birth outcome was recorded. RESULTS: Only women at 24-28 weeks of gestation per PTB case (four full-term births) were selected as controls subjects, PTB displayed significantly greater GI, BI, and 8-OHdG (P<0.05). Logistic regression analysis revealed that BI and 8-OHdG were the dependent risk factors of PTB (OR=5.90, P=0.034; OR=1.18, P=0.045, respectively). The areas under the receiver operating characteristic curve (ROC) of BI and 8-OHdG were 0.80 and 0.69, and that of the combined detection was 0.82, which was larger than the individual detection, although the differences were not significant (P>0.05). CONCLUSIONS: Increased BI and 8-OHdG at 24-28 weeks of gestation are risk factors for PTB. Their combined detection may have some value in the prediction of PTB, but further studies with a larger sample size are needed to explore it and thus provide experiment evidence for establishing an early warning system for PTB in pregnant women with periodontal disease.


Assuntos
Líquido do Sulco Gengival , Nascimento Prematuro , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Índice Periodontal , Gravidez
8.
J Orthop Surg Res ; 16(1): 196, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731160

RESUMO

BACKGROUND: The best treatment for acute Achilles tendon ruptures remains controversial. No cohort studies have compared different immobilisation durations after open surgery. This retrospective cohort study aimed to determine the optimal duration of immobilisation after this surgery. METHODS: A total of 266 patients with acute Achilles tendon rupture were divided into 4 groups (A, B, C, and D) according to immobilisation duration of 0, 2, 4, and 6 weeks, respectively. All patients underwent the same suture technique with a similar rehabilitation protocol and were examined clinically at 2, 4, 6, 8, 10, 12, 14, 16, 24, and 48 weeks, with a final follow-up at a mean of 22.3 months postoperatively. The primary outcome was the time of return to light sports activity (LSA). Secondary outcomes included range of motion (ROM) and single-legged heel rise height (SHRH). Data on operation time, complications, visual analogue pain scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, and Achilles tendon Total Rupture score (ATRS) were also collected. Demographic baseline data were analysed using one-way analysis of variance; outcome parameters were analysed using Kruskal-Wallis H test, and complications were analysed using Fisher's exact test. Statistical significance was considered at P ≤ 0.05. RESULTS: VAS scores decreased significantly, reaching 0 in all groups after 12 weeks. The AOFAS and ATRS scores were significantly different between the groups from weeks 2 to 12 (P<0.001) and weeks 2 to 16 (P<0.001), respectively. All the mean scores showed better results in group B than in the other groups. In terms of recovery time of ROM, SHRH, and LSA, groups A and B were significantly faster than groups C and D (P<0.001). There were 13 (13/266, 4.9%) complications: 5 superficial infections, 3 deep venous thrombosis, and 5 trauma-related re-ruptures. On the last follow-up, all complications had recovered. There were no significant differences in complications between the groups. CONCLUSIONS: Immobilisation for 2 weeks after this open surgery is the best choice for early rehabilitation and weight-bearing while minimising pain and other complications.

9.
Neurochem Res ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675461

RESUMO

A growing number of studies have shown that air fine particulate matter (PM2.5) pollution is closely associated with neuroinflammation in humans. Militarine, a glucosyloxybenzyl 2-isobutylmalate compound isolated from Bletilla striata, has been found to exert significant neuroprotective effects. However, the anti-inflammatory, antioxidant and antiapoptotic effects of militarine on PM2.5-stimulated BV-2 microglial cells have not been reported. This study aimed to investigate the protective effects of militarine against PM2.5-induced cytotoxicity and its mechanism in BV-2 microglial cells. Our results revealed that pretreatment with 0.31-1.25 µg/mL militarine reversed the morphological changes caused by PM2.5 and decreased proinflammatory cytokine generation and gene expression in PM2.5-treated BV-2 cells. In particular, tumor necrosis factor-α and interleukin-6 expression was inhibited in a dose-dependent manner. Notably, militarine markedly inhibited the upregulation of Toll-like receptor 4, Toll-like receptor 2, and cyclo-oxygenase-2 expression at both the mRNA and protein levels and reduced NF-κB pathway-associated protein expression. Immunofluorescence analysis showed that militarine suppressed NF-κB activity through inhibiting p65 nuclear translocation. Our data suggested that militarine alleviated neuroinflammation in BV-2 microglial cells, possibly by inhibiting the expression of neuroinflammatory cytokines through the TLR/NF-κB signaling pathway. Additionally, militarine significantly reduced PM2.5-mediated reactive oxygen species (ROS) generation and cell apoptosis and restored the mitochondrial membrane potential (MMP; ΔΨm). Collectively, these findings demonstrate that militarine played a protective role against PM2.5-induced damage in BV-2 cells by exerting anti-inflammatory, antioxidant, and antiapoptotic effects.

10.
Echocardiography ; 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33715241

RESUMO

The COVID-19 pandemic has presented countless new challenges for healthcare providers including the challenge of differentiating COVID-19 infection from other diseases. COVID-19 infection and acute endocarditis may present similarly, both with shortness of breath and vital sign abnormalities, yet they require very different treatments. Here, we present two cases in which life-threatening acute endocarditis was initially misdiagnosed as COVID-19 infection during the height of the pandemic in New York City. The first was a case of Klebsiella pneumoniae mitral valve endocarditis leading to papillary muscle rupture and severe mitral regurgitation, and the second a case of Streptococcus mitis aortic valve endocarditis with heart failure due to severe aortic regurgitation. These cases highlight the importance of careful clinical reasoning and demonstrate how cognitive errors may impact clinical reasoning. They also underscore the limitations of real-time reverse transcription-polymerase chain reaction (RT-PCR) for SARS-CoV-2 testing and illustrate the ways in which difficulty interpreting results may also influence clinical reasoning. Accurate diagnosis of acute endocarditis is critical given that surgical intervention can be lifesaving in unstable patients.

11.
Chaos ; 31(2): 023115, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33653076

RESUMO

To precisely analyze the fractal nature of a short-term time series under the multiscale framework, this study introduces multiscale adaptive multifractal analysis (MAMFA) combining the adaptive fractal analysis method with the multiscale multifractal analysis (MMA). MAMFA and MMA are both applied to the two kinds of simulation sequences, and the results show that the MAMFA method achieves better performances than MMA. MAMFA is also applied to the Chinese and American stock indexes and the R-R interval of heart rate data. It is found that the multifractal characteristics of stock sequences are related to the selection of the scale range s. There is a big difference in the Hurst surface's shape of Chinese and American stock indexes and Chinese stock indexes have more obvious multifractal characteristics. For the R-R interval sequence, we find that the subjects with abnormal heart rate have significant shape changes in three areas of Hurst surface compared with healthy subjects, thereby patients can be effectively distinguished from healthy subjects.

12.
Sensors (Basel) ; 21(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668928

RESUMO

Small satellite synthetic aperture radar (SAR) has become a new development direction of spaceborne SAR due to its advantages of flexible launch, short development cycle, and low cost. However, there are fewer researches on distributed small satellite multiple input multiple output (MIMO) SAR. This paper proposes an ultra-high resolution imaging method for the distributed small satellite spotlight MIMO-SAR, which applies the sub-aperture division technique and the sub-aperture image coherent fusion algorithm to MIMO-SAR. After deblurring the sub-aperture signal, the large bandwidth signal is obtained by using an improved time domain bandwidth synthesis (TBS) method, and then the ultra-high resolution image is obtained by using a sub-aperture image coherent fusion algorithm. Simulation results validate the feasibility and effectiveness of the proposed approach.

13.
Schizophr Res ; 231: 67-69, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33770628

RESUMO

OBJECTIVE: To explore pharmacogenetic relationships of NRG1 genotypes with neurocognitive performance and clinical symptoms after 12 week treatment of risperidone in Chinese Han first-episode schizophrenia. METHODS: A cohort of 221 patients with schizophrenia were recruited for this research. Finally 177 untreated first-episode patients were clinically evaluated with the Positive and Negative Syndrome Scale (PANSS), Raven's Standard Progressive Matrices (RSPM), Digit Vigilance Test (DVT), Digit Span (DS), underwent genotyping for five polymorphisms of NRG1, and completed a 12-week prospective study of risperidone monotherapy. RESULTS: 1. After risperidone treatment of 12 weeks, the total scores, positive score, negative score and general score of PANSS decreased significantly; the scores of RSPM, DVT and DS increased significantly. 2. No significant association with PANSS scores at baseline or change in scores after 12 weeks'treatment was found with any of the five SNPs. There was also neither significant association of DVT, DS or RSPM at baseline with any of the five SNPs. 3. After risperidone treatment of 12 weeks, rs3924999 and rs35753505 showed significant association with change in DVT and in RSPM in which there were significant differences among different genotype groups. CONCLUSION: This study suggested pharmacogenetic relationships between NRG1 variants and changes in cognition response with exposure to 12 weeks of treatment with risperidone. Two variants, rs3924999 and rs35753505, in the NRG1 gene were associated with the changes in attention and reasoning ability after risperidone treatment of 12 weeks.

14.
J Affect Disord ; 286: 33-39, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33676261

RESUMO

BACKGROUND: We conducted a survey to investigate the prevalence and factors associated with anxiety and depressive symptoms among patients hospitalized with hematological malignancies after chimeric antigen receptor T-cell (CAR-T) therapy. METHODS: In total, 130 eligible patients completed the Self-Rating Anxiety Scale and Self-Rating Depression Scale at week 4 after CAR-T cell infusion. We collected sociodemographic information during the same period. We studied factors associated with anxiety and depressive symptoms using logistic regression analysis. RESULTS: The prevalence of anxiety and depressive symptoms at week 4 after infusion were 13.8% and 40.0%, respectively. A cutoff value of 50 or above indicates significantly anxiety and depressive symptoms. Binary logistic regression analysis showed that high school education and above (OR = 0.22, 95% CI = 0.06-0.78) and middle age (OR = 0.16, 95% CI = 0.03-0.90) were associated with lower risk of anxiety symptoms, and increased odds of depressive symptoms was associated with old age (OR = 11.39, 95% CI = 2.50-51.88), non-manual occupations before illness (OR = 3.72, 95% CI = 1.20-11.58), and higher healthcare expenditure (OR = 3.93, 95% CI = 1.50-10.33), while lower risk of depressive symptoms was associated with rural household location (OR = 0.25, 95% CI = 0.08-0.76) and being cared for by spouse (OR = 0.12, 95% CI = 0.02-0.63). CONCLUSIONS: Patients receiving CAR-T therapy with lower education background, old ages, urban household location, or who used to work as non-manual workers require more attention and psychological care. Support from a spouse and medical expense deductions from the government may help patients develop positive attitudes.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33598875

RESUMO

Heat shock protein 70 (HSP70) is a key member of the HSP family that contributes to a pre-cancerous environment; however, its role in lung cancer remains poorly understood. The present study used geranylgeranylacetone (GGA) to induce HSP70 expression, and transforming growth factor-ß (TGF-ß) was used to construct an epithelial-mesenchymal transition (EMT) model by stimulating A549 cells in vitro. Western Blot was performed to detect protein levels of NADPH oxidase 4 (NOX4) and the EMT-associated proteins E-cadherin and vimentin both before and after HSP70 expression. Cell morphological changes were observed, and the effect of HSP70 on cell migration ability was detected via the wound healing. The results demonstrated that GGA at 50 and 200 µmol/L could significantly induce HSP70 expression in A549 cells (P < 0.05). Furthermore, HSP70 induced by 200 µmol/L GGA significantly inhibited the changes of E-cadherin, vimentin, and cell morphology induced by TGF-ß (P < 0.05), while HSP70 induced by 50 µmol/L GGA did not. The results of the wound healing assay indicated that 200 µmol/L GGA significantly inhibited A549 cell migration induced by TGF-ß. Taken together, the results of the present study demonstrated that overexpression of HSP70 inhibited the TGF-ß induced EMT process and changed the cell morphology and migratory ability induced by TGF-ß in A549 cells.

16.
PLoS Pathog ; 17(2): e1009317, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33600488

RESUMO

The transmembrane protein 33 (TMEM33) was originally identified as an endoplasmic reticulum (ER) protein that influences the tubular structure of the ER and modulates intracellular calcium homeostasis. However, the role of TMEM33 in antiviral immunity in vertebrates has not been elucidated. In this article, we demonstrate that zebrafish TMEM33 is a negative regulator of virus-triggered interferon (IFN) induction via two mechanisms: mitochondrial antiviral signaling protein (MAVS) ubiquitination and a decrease in the kinase activity of TANK binding kinase 1 (TBK1). Upon stimulation with viral components, tmem33 was remarkably upregulated in the zebrafish liver cell line. The IFNφ1 promoter (IFNφ1pro) activity and mRNA level induced by retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) were significantly inhibited by TMEM33. Knockdown of TMEM33 increased host ifn transcription. Subsequently, we found that TMEM33 was colocalized in the ER and interacted with the RLR cascades, whereas MAVS was degraded by TMEM33 during the K48-linked ubiquitination. On the other hand, TMEM33 reduced the phosphorylation of mediator of IFN regulatory factor 3 (IRF3) activation (MITA)/IRF3 by acting as a decoy substrate of TBK1, which was also phosphorylated. A functional domain assay revealed that the N-terminal transmembrane domain 1 (TM1) and TM2 regions of TMEM33 were necessary for IFN suppression. Finally, TMEM33 significantly attenuated the host cellular antiviral capacity by blocking the IFN response. Taken together, our findings provide insight into the different mechanisms employed by TMEM33 in cellular IFN-mediated antiviral process.

17.
BMC Surg ; 21(1): 96, 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33612111

RESUMO

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) with multiple pathological types is extremely rare in the clinic, but the recurrence rate and mortality these patients are high. At present, there is no standard treatment for such cases. CASE PRESENTATION: We reported a case of ureteral urothelial carcinoma with squamous cell carcinoma and sarcomatoid carcinoma differentiation and rapid ileal metastasis and reviewed the literature related to different pathological types of upper urinary tract tumours to explore the diagnosis, treatment and prognosis characteristics of the disease, enhance our understanding of its clinical manifestations and history of evolution and provide guidance for avoiding missed diagnosis and misdiagnosis. CONCLUSION: There is no standard treatment for urinary malignant tumours with multiple pathological types; radical surgery is considered a suitable choice. Chemotherapy, targeted drug therapy and immunotherapy may be beneficial to the survival of patients. In short, these patients have a high risk of recurrence and metastasis and a poor prognosis.


Assuntos
Carcinoma de Células Escamosas , Carcinoma de Células de Transição , Neoplasias Ureterais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/terapia , Diferenciação Celular , Humanos , Neoplasias Ureterais/patologia , Neoplasias Ureterais/terapia
18.
J Struct Biol ; 213(2): 107710, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33610655

RESUMO

KW-2478 is a promising anti-cancer lead compound targeting to the molecular chaperone heat shock protein 90 N (Hsp90N). Absence of complex crystal structure of Hsp90N-KW-2478, however, hampered further structure optimization of KW-2478 and understanding on the molecular interaction mechanism. Herein, a high-resolution complex crystal structure of Hsp90N-KW-2478 was determined by X-ray diffraction (XRD, resolution limit: 1.59 Å; PDB ID: 6LT8) and their molecular interaction was analyzed in detail, which suggested that KW-2478 perfectly bound in the N-terminal ATP-binding pocket of Hsp90 to disable its molecular chaperone function, therefore suppressed or killed cancer cells. The results from thermal shift assay (TSA, ΔTm, 18.82 ± 0.51 °C) and isothermal titration calorimetry (ITC, Kd, 7.30 ± 2.20 nM) suggested that there is an intense binding force and favorable thermodynamic changes during the process of KW-2478 binding with Hsp90N. Additionally, KW-2478 exhibited favorable anti-NSCLC activity in vitro, as it inhibited cell proliferation (IC50, 8.16 µM for A549; 14.29 µM for H1975) and migration, induced cell cycle arrest and promoted apoptosis. Thirty-six novel KW-2478 derivatives were designed, based on the complex crystal structure and molecular interaction analysis of Hsp90N-KW-2478 complex. Among them, twenty-two derivatives exhibited increased binding force with Hsp90N evaluated by molecular docking assay. The results would provide new guidance for anti-NSCLC new drug development based on the lead compound KW-2478.

19.
Food Chem ; 348: 129097, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-33515941

RESUMO

The aim of this study was to isolate and identify antibacterial peptides (ABPs) produced by lactic acid bacteria (LAB) in Chinese pickles. The cell-free supernatant collected from the culture of LAB with antibacterial activity against Staphylococcus aureus was used to purify ABPs. A total of 14 strains of LAB were found to have antibacterial activity. Among them, Lactobacillus fermentum (L. fermentum) SHY10 exhibited the most effective antibacterial activity. The antibacterial activity of cell-free supernatant reached the highest level after 20 h of L. fermentum SHY10 culture. Three novel ABPs were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In particular, the NQGPLGNAHR peptide showed antibacterial activity with an IC50 value of 0.957 mg/mL. In addition, molecular docking analysis revealed that this peptide interacted with DNA gyrase and dihydrofolate reductase by salt bridge formation, hydrogen bond interactions, and metal contact.


Assuntos
Antibacterianos/análise , Antibacterianos/isolamento & purificação , Lactobacillus fermentum/metabolismo , Peptídeos/análise , Peptídeos/isolamento & purificação , Antibacterianos/biossíntese , Alimentos e Bebidas Fermentados/microbiologia , Peptídeos/metabolismo
20.
Biomed Res Int ; 2021: 6905985, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506032

RESUMO

Background: The majority of lung cancers are adenocarcinomas, with the proportion being 40%. The patients are mostly diagnosed in the middle and late stages with metastasis and easy recurrence, which poses great challenge to the treatment and prognosis. Platinum-based chemotherapy is a primary treatment for adenocarcinoma, which frequently causes drug resistance. As a result, it is important to uncover the mechanisms of the chemoresponse of adenocarcinoma to platinum-based chemotherapy. Methods: The genes from the dataset GSE7880 were gathered into gene modules with the assistance of weighted gene coexpression network analysis (WGCNA), the gene trait significance absolute value (|GS|), and gene module memberships (MM). The genes from hub gene modules were calculated with a protein-protein interaction (PPI) network analysis in order to obtain a screening map of hub genes. The hub genes with both a high |GS| and MM and a high degree were selected. Furthermore, genes in the hub gene modules also went through a Gene Ontology (GO) functional enrichment analysis. Results: 11 hub genes in four hub gene modules (LY86, ACTR2, CDK2, CKAP4, KPNB1, RBBP4, SMAD4, MYL6, RPS27, TSPAN2, and VAMP2) were chosen as the significant hub genes. Through the GO function enrichment analysis, it was indicated that four modules were abundant in immune system functions (floralwhite), amino acid biosynthetic process (lightpink4), cell chemotaxis (navajowhite2), and targeting protein (paleturquoise). Four hub genes with the highest |GS| were verified by prognostic analysis.

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