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1.
J Hazard Mater ; 421: 126726, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34330079

RESUMO

Carbon-based catalysts with heteroatom doping and hollow structures are desired for advanced oxidation processes (AOPs). Herein, dual-shelled Co, N, and S codoped hollow carbon nanocages were developed by wrapping zeolitic imidazolate framework-67 (ZIF-67) with trithiocyanuric acid (TCA) and performing subsequent carbonization. The optimal composite catalyst (Co-NC-CoS) exhibited excellent catalytic performance toward different organic pollutants. Almost complete removal of 4-NP (60 mg/L-1) was achieved within 20 min by 10 mg of catalyst and 0.2 g/L-1 peroxymonosulfate (PMS). Moreover, the catalyst showed good stability and reusability. The effects of catalyst and PMS dose, pollutant concentration, pH and common anions were investigated, and reactive oxygen species (ROS) were studied by scavenger experiments and electron paramagnetic resonance (EPR) tests. The results show that multidoped atoms S, Co and N all contributed to the degradation system. Several lines of evidence suggested that S could change the catalytic process from Co3+/Co2+ to Co3+/Co2+/Co0 reduction due to its low redox potential. Degradation was achieved through both radical and nonradical pathways, where sulfate radicals (SO4·Ì¶), hydroxyl radicals (·OH) and singlet oxygen (1O2) were primary reactive species. Overall, this work may suggest that the novel multi heteroatom-doped catalysts with complex structures can be developed for environmental remediation.

2.
Infect Drug Resist ; 14: 4503-4510, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744441

RESUMO

Objective: The aim of this study was to use whole-genome sequencing to characterize Klebsiella pneumoniae SKp2F and Klebsiella variicola SKv2E, both carrying bla KPC, co-isolated from the same sputum specimen. Methods: Antimicrobial susceptibility testing was performed using microbroth dilution. Biofilm formation was determined by crystal violet staining and virulence was measured by a serum killing assay. Whole-genome sequencing of SKp2F and SKv2E was performed using an Illumina sequencer and the genetic characteristics were analyzed by computer. Results: SKp2F and SKv2E were sensitive only to tigecycline and polymyxin among the tested antibiotics. The biofilm-forming ability of SKv2E is stronger than that of SKp2F. The grades of serum resistance of SKp2F and SKv2E are 4 and 3. MLST analysis of the 6,115,610 bp and 5,403,687 bp of SKv2E and SKp2F showed associations with ST1615 and ST631, respectively. SKv2E carried 13 resistance genes (bla KPC-2, bla TEM-1A, bla LEN17, aadA16, arr-3, qnrB4, oqxA/B, dfrA27, sul1, tetD, fosA, qacEΔ1) and SKp2F carried 23 (bla KPC-2, bla CTX-M-3, bla TEM-1B, bla CTX-M-65, bla SHV-27, aac(6')-IIa, rmtB, arr-3, aph(3')-Ia, aadA16, qnrS1, aac(6')-Ib-cr, qnrB91, oqxA/B, mph(A), tet(A), fosA, dfrA27, and two copies of qacEΔ1-sul1). Most of them were carried by various mobile genetic elements, such as IncFIB(K)/IncFII(K)/IncFII(Yp), IncFII(K) plasmid, Tn6338, and In469. Both SKv2E and SKp2F carried a large number of virulence factors, including type 1 and 3 fimbriae, capsule, aerobactin (iutA), ent siderophore (entABCDEFS, fepABCDGfes), and salmochelin (iroE/iroEN). SKv2E also carried type IV pili (pilW), fimbrial adherence (steB, stfD), and capsule biosynthesis gene (glf). Conclusion: bla KPC-2-carrying K. variicola and K. pneumoniae, which carried multiple resistance genes, virulence factors, and highly similar mobile genetic elements, were identified from the same specimen, indicating that clinical samples may carry multiple bacteria. We should avoid misidentification, and bear in mind that resistance genes carrying mobile genetic elements can be transmitted or integrated between bacteria in the same host.

3.
Front Public Health ; 9: 763246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790646

RESUMO

Background: Leisure provides opportunities for urban and rural residents to relax, recover their vitality, and improve their personal growth, development, and well-being. However, the impact of the leisure participation process, types, obstacles, participation motivation, and satisfaction on health is not very clear, especially the impact of leisure behavior on health, and is worthy of in-depth discussion. Objective: The objective of this study was to explore the impact of social capital and leisure participation on the self-rated health of urban residents in China so as to provide an important reference for national health promotion activities. Methods: the questionnaire on the relationship between social capital, leisure behavior, and self-rated health was compiled by ourselves. The residents participating in leisure and fitness in 25 residential fitness centers in Chengdu were investigated in the morning and evening, and the obtained data were processed by exploratory and confirmatory factor analysis. Results: (1) Social capital had no direct influence on leisure hindrance; leisure motivation and leisure participation had no direct influence on self-rated health. (2) Leisure satisfaction has a direct positive impact on self-rated health, while leisure hindrance has a significant negative impact on self-rated health. (3) Social capital has a direct positive impact on leisure satisfaction, and social capital has a direct positive impact on self-rated health. Leisure satisfaction plays an intermediary role in the path of social capital affecting self-rated health, and the intermediary force exceeds the direct impact of social capital on self-rated health. Conclusion: The effect of leisure satisfaction on self-rated health is higher than that of social capital, and it plays an intermediary role in the impact path of social capital on self-rated health. Therefore, how to make urban community residents with different backgrounds obtain leisure satisfaction through leisure activities is an important topic of national health promotion.


Assuntos
Capital Social , China , Nível de Saúde , Humanos , Atividades de Lazer , População Urbana
4.
Mol Biol Rep ; 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837150

RESUMO

BACKGROUND: MicroRNA-1290 (miR-1290) has been reported to be involved in many diseases and play a key role during the development process. However, the role of miR-1290 in atherosclerosis (AS) is still unclear. METHODS AND RESULTS: The current study showed that the expressions of miR-1290 were high in serum of patients with hyperlipidemia. The functional role of miR-1290 were then investigated in human umbilical vein endothelial cells (HUVECs). Here, we found that miR-1290 expressions were notably enhanced in HUVECs mediated by IL-8. miR-1290 inhibitor repressed monocytic THP-1 cells adhesion to HUVECs by regulating ICAM-1 and VCAM-1, inhibited proliferation through regulating cyclinD1 and PCNA, and inhibited inflammatory response by regulating IL-1ß. Mechanistically, we verified that miR-1290 mimic was able to directly target the 3'-UTR of GSK-3ß mRNA using luciferase reporter assay. Knockdown of GSK-3ß (si-GSK-3ß) promoted HUVECs adhesion and the expression of IL-1ß, and partially restore the depression effect of miR-1290 inhibitor on HUVECs adhesion and inflammation. In contrast, si-GSK-3ß inhibited the proliferation of HUVECs and the expression of cyclinD1 and PCNA. CONCLUSIONS: In summary, our study revealed that miR-1290 promotes IL-8-mediated the adhesion of HUVECs by targeting GSK-3ß. However, GSK-3ß is not the target protein for miR-1290 to regulate the proliferation of HUVECs. Our findings may provide potential target in atherosclerosis treatment.

5.
Mol Cancer Res ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782371

RESUMO

The relationship between the checkpoint kinase Chk1 and the STAT3 pathway was examined in multiple myeloma (MM) cells. Gene expression profiling of U266 cells exposed to low (nM) Chk1 inhibitor (PF-477736) concentrations revealed STAT3 pathway-related gene down-regulation (e.g., BCL-XL, MCL-1, c-Myc), findings confirmed by RT-PCR. This was associated with marked inhibition of STAT3 Tyr705 (but not Ser727) phosphorylation, dimerization, nuclear localization, DNA binding, STAT3 promoter activity by ChIP assay, and down-regulation of STAT-3-dependent proteins. Similar findings were obtained in other MM cells and with alternative Chk1 inhibitors (e.g., prexasertib, CEP3891). While PF did not reduce GP130 expression or modify SOCS or PRL-3 phosphorylation, the phosphatase inhibitor pervanadate antagonized PF-mediated Tyr705 dephosphorylation. Significantly, PF attenuated Chk1-mediated STAT3 phosphorylation in in vitro assays. SPR analysis suggested Chk1/STAT3 interactions and PF reduced Chk1/STAT3 co-immunoprecipitation. Chk1 CRISPR knockout or shRNA knockdown cells also displayed STAT3 inactivation and STAT-3-dependent protein down-regulation. Constitutively active STAT3 diminished PF-mediated STAT3 inactivation and down-regulate STAT3-dependent proteins while significantly reducing PF-induced DNA damage (rH2A.X formation) and apoptosis. Exposure of cells with low basal phospho-STAT3 expression to IL-6 or human stromal cell conditioned medium activated STAT3, an event attenuated by Chk1 inhibitors. PF also inactivated STAT3 in primary human CD138+ MM cells and tumors extracted from an NSG MM xenograft model while inhibiting tumor growth. Implications: These findings identify a heretofore unrecognized link between the Chk1 and STAT3 pathways and suggest that Chk1 pathway inhibitors warrant attention as novel and potent candidate STAT3 antagonists in myeloma.

6.
Front Oncol ; 11: 688615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631523

RESUMO

Objective: To investigate the impact of the human papillomavirus (HPV) status on head and neck squamous cell carcinoma (HNSCC) arising from different anatomic subsites. Methods: HNSCC patients with known HPV status from the Surveillance, Epidemiology, and End Results (SEER) database between 2010-2015 were included in our analysis. Patients were classified into three categories of HNSCC according to Site recode ICD-O-3/WHO 2008 and Primary Site-labeled, namely, oropharynx, hypopharynx, and nasopharynx. Logistic regression model was conducted to evaluate the relationship between patient characteristics and HPV status. Kaplan-Meier methods and COX regression analysis were used to analyze survival data. Results: A total of 9,943 HNSCC patients with known HPV status from the SEER database were enrolled, with 6,829 (68.7%) HPV-positive patients. HPV-positive and HPV-negative HNSCC were distinct and had different clinical and socioeconomic features (all P < 0.001). Primary sites, socioeconomical factors (age, sex, marital status, and race), and pathological features (TNM stage and grade) were closely related with HPV status (all P < 0.001). HPV-positive status was a favorable prognostic marker in HNSCC patients with cancers of the oropharynx and hypopharynx (all P < 0.001), but was not in nasopharyngeal carcinoma patients (P = 0.843). A total of 8,933 oropharyngeal carcinoma (OPC) and 558 hypopharyngeal carcinoma (HPC) patients were divided into the training and validation cohorts with a ratio of 1:1. Significant prognostic factors of the OS yielded by multivariate COX analysis in the training cohort were integrated to construct nomograms for OPC and HPC patients. The prognostic models showed a good discrimination with a C-index of 0.79 ± 0.007 and 0.73 ± 0.023 in OPC and HPC, respectively. Favorable calibration was reflected by the calibration curves. Additionally, corresponding risk classification systems for OPC and HPC patients based on the nomograms were built and could perfectly classify patients into low-risk, intermediated-risk, high-risk groups. OS in the three risk groups was accurately differentiated and showed a good discrimination. Conclusion: HPV positivity was associated with an improved survival in HNSCC patients with cancers of the oropharynx and hypopharynx. Nomograms and corresponding risk classification systems were constructed to assist clinicians in evaluating the survival of OPC and HPC patients.

7.
Cardiol Res Pract ; 2021: 3300884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691776

RESUMO

Objective: To assess the value of N-terminal probrain natriuretic peptide (NT-proBNP) in short-term and long-term follow-up after a modified Fontan procedure. Methods: We retrospectively enrolled children who had undergone a modified Fontan procedure in the Heart Center of Guangzhou Women and Children's Medical Center from January 2014 to September 2020 and collected data on NT-proBNP values before bidirectional Glenn procedure, before Fontan procedure, and on 1, 3, 7, 30, 90, and 180 days and 1, 2, 3, 4, 5, and 6 year after Fontan procedure. The relationship between changes in NT-proBNP levels and the outcomes in children was analyzed. Results: A total of 108 children (78 boys and 30 girls, mean age: 54.62 ± 29.38 weeks) were included in the analysis. According to one-way analysis of variance, the left ventricular type and biventricular type of single ventricle physiology showed shorter duration on cardiopulmonary bypass during the operation and lower levels of NT-proBNP after the operation than the right ventricular type and univentricular type physiology. Conclusion: NT-proBNP is a good indicator for mid and long-term follow-up after a modified Fontan procedure. The left ventricular type and biventricular type of single ventricle physiology show better mid and long-term benefits from the modified Fontan procedure than the right ventricular type and univentricular type physiology.

8.
IEEE Trans Cybern ; PP2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665755

RESUMO

This article considers the problem of fixed-time prescribed event-triggered adaptive asymptotic tracking control for nonlinear pure-feedback systems with uncertain disturbances. The fuzzy-logic system (FLS) is introduced to deal with the unknown nonlinear functions in the system. By constructing a new type of Lyapunov function, the restrictive requirement that the upper bounds of the partial derivative of the unknown system functions need to be known is relaxed during the controller design process. At the same time, by developing a novel fixed-time performance function (FPF), the fixed-time prescribed performance (FPP) can be achieved, that is, the tracking error can converge to the neighborhood of the origin in a fixed time and finally converges to zero asymptotically. In addition, the event-triggered strategy is developed to reduce the waste of communication resources. The proposed control law can ensure that all the signals of the system are bounded. Meanwhile, the Zeno behavior can be effectively avoided. Finally, an example is provided to prove the effectiveness of the proposed scheme.

9.
Ann Clin Microbiol Antimicrob ; 20(1): 63, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488786

RESUMO

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae has become a public health concern. This study aimed to compare the clinical outcomes of patients with nonurinary source bacteraemia caused by ESBL-producing Escherichia coli (E. coli) or Klebsiella pneumoniae (ESBL-producing EK) receiving ß-lactam/ß-lactamase inhibitor combinations (BLICs) versus carbapenem treatment and assess the risk factors of mortality with these two drugs. METHODS: We conducted a retrospective single-centre study of adult hospitalised patients with ESBL-producing EK bloodstream infection (BSI) from nonurinary source at our centre over a 4-year period. One hundred and eighty patients who received BLICs or carbapenems were included in the analysis. The outcome variables were 14-day treatment failure and 30-day mortality. For more reliable results, propensity score analysis was performed to compare the efficacy of the two drugs and analyse their risk factors for 30-day mortality. RESULTS: Out of 180 patients, 114 received BLICs, and 66 received carbapenem therapy. Compared to carbapenem-treated patients, those treated with BLICs were older and had higher age-adjusted Charlson comorbidity index, but they had shorter stay in the hospital. Additionally, their Pitt bacteraemia score, SOFA score, rate of leukaemia, and immune compromise were lower. After propensity score matching (PSM), the baseline characteristics of patients in the two treatment groups were balanced. BLICs were associated with a higher 14-day treatment failure rate (20.6%, 13/63) than carbapenems (16.3%, 7/43), although the difference was not significant in either univariate analysis (P = 0.429) or multivariate analysis (P = 0.122). And the 30-day mortality rate in BTG (11.1%, 7/63) and CTG (11.6%, 5/43) did not significantly differ (univariate analysis, P = 0.926; multivariate analysis, P = 0.420). In the multivariate analysis, after PSM, leukaemia was the only independent predictor of mortality in both BTG and CTG. CONCLUSIONS: Our study showed that BLICs had higher 14-day treatment failure rate compared with carbapenems, although there were no statistically significant differences because of the small number of patients, therefore, further evaluation of the efficacy of BLICs is needed.

10.
Front Endocrinol (Lausanne) ; 12: 701116, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512547

RESUMO

Purpose: This study aimed to investigate the value of diffusion tensor imaging to assess renal injury in a rat model of preclinical diabetic nephropathy. Methods: Twenty-eight male Sprague Dawley rats were divided into two groups: the normal control (NC) group of 10 rats and the diabetic nephropathy (DN) group of 18 rats. Eight weeks after diabetes induction by streptozotocin, 3.0-T magnetic resonance (MR) imaging (b = 0 and 600 s/mm2, 15 diffusion directions) using a 32-channel knee coil was performed. After MR imaging, we measured serum creatinine, and collected double kidney tissues for pathology. The apparent diffusion coefficients(ADC) and fractional anisotropy(FA) values of the renal cortex and medulla were calculated for all kidneys. Physiological parameters, laboratory parameters, and imaging results were compared between the two groups. Results: All DN group animals developed hyperglycemia, polyuria, and emaciation. Serum creatinine was not significantly different between the groups (P > 0.05). Urinary albumin at 2, 4, and 8 weeks was higher in the DN group than in the NC group but <20 µg/min (P < 0.05). Pathologically, renal damage in the DN rats was observed. The ADC value was significantly increased in DN animals in the cortex (1.75×10-3mm2/s),medulla(1.53×10-3mm2/s)compared with NC group(cortex, 1.52×10-3mm2/s; medulla,1.35×10-3mm2/s). The FA value was significantly reduced in DN animals in the cortex (0.21),medulla(0.25)compared with NC group(cortex,0.26;medulla,0.3). Conclusions: Increased apparent diffusion coefficients and decreased fractional anisotropy values on diffusion tensor imaging were associated with preclinical DN. Diffusion tensor imaging may be useful in early, non-invasive, quantitative detection, and therapy monitoring of DN.

11.
Biomedicines ; 9(9)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34572430

RESUMO

Up to now, the chemotherapy approaches for glioblastoma were limited. 1-[2-Thiazolylazo]-2-naphthol (named as NSC139021) was shown to significantly inhibit the proliferation of prostate cancer cells by targeting the atypical protein kinase RIOK2. It is documented that RIOK2 overexpressed in glioblastoma. However, whether NSC139021 can inhibit the growth of glioblastoma cells and be a potential drug for glioblastoma treatment need to be clarified. In this study, we investigated the effects of NSC139021 on human U118MG, LN-18, and mouse GL261 glioblastoma cells and the mouse models of glioblastoma. We verified that NSC139021 effectively inhibited glioblastoma cells proliferation, but it is independent of RIOK2. Our data showed that NSC139021 induced cell cycle arrest at G0/G1 phase via the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway in G1/S checkpoint regulation. In addition, NSC139021 also increased the apoptosis of glioblastoma cells by activating the p53 signaling pathway and increasing the levels of Bax and cleaved caspase 3. Furthermore, intraperitoneal administration of 150 mg/kg NSC139021 significantly suppressed the growth of human and mouse glioblastoma in vivo. Our study suggests that NSC139021 may be a potential chemotherapy drug for the treatment of glioblastoma by targeting the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway.

12.
PLoS One ; 16(9): e0257294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34516579

RESUMO

RATIONALE AND OBJECTIVES: This study aimed to compare the volume computed tomography dose index (CTDIvol), dose length product (DLP), and size-specific dose estimate (SSDE), with the China and updated 2017 American College of Radiology (ACR) diagnostic reference levels (DRLs) in chest CT examinations of adults based on the water-equivalent diameter (Dw). MATERIALS AND METHODS: All chest CT examinations conducted without contrast administration from January 2020 to July 2020 were retrospectively included in this study. The Dw and SSDE of all examinations were calculated automatically by "teamplay". The CTDIvol and DLP were displayed on the DICOM-structured dose report in the console based on a 32cm phantom.The differences in patient CTDIvol, DLP, and SSDE values between groups were examined by the one-way ANOVA. The differences in patient CTDIvol, DLP, and SSDE values between the updated 2017 ACR and the China DRLs were examined with one sample t-tests. RESULTS: In total 14666 chest examinations were conducted in our study. Patients were divided into four groups based on Dw:270 (1.84%) in 15-20 cm group, 10287 (70.14%) in the 21-25 cm group, 4097 (27.94%) in the 26-30 cm group, and 12 (0.08%) patients had sizes larger than 30 cm. CTDIvol, DLP, and SSDE increased as a function of Dw (p<0.05). CTDIvol was smaller than SSDE among groups (p<0.05). The mean CTDIvol and DLP values were lower than the 25th, 50th, and 75th percentile of the China DRLs (p <0.05). The CTDIvol, DLP, and SSDE were lower than the 50th and 75th percentiles of the updated 2017 ACR DRLs (p <0.05) among groups. CONCLUSIONS: SSDE takes into account the influence of the scanning parameters, patient size, and X-ray attenuation on the radiation dose, which can give a more realistic estimate of radiation exposure dose for patients undergoing CT examinations. Establishing hospital's own DRL according to CTDIvol and SSDE is very important even though the radiation dose is lower than the national DRLs.


Assuntos
Tomografia Computadorizada por Raios X/métodos , Adulto , China , Níveis de Referência de Diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Valores de Referência , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/normas
13.
Int J Med Sci ; 18(14): 3090-3096, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34400879

RESUMO

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and agonistic antibodies against TRAIL death receptors (DR) can induce apoptosis preferentially in tumor cells while causing virtually no damage to normal cells. However, their therapeutic potential is limited by occurring resistance in tumor cells, including non-small cell lung cancer (NSCLC). Thus, elucidation of the molecular targets and signaling pathways responsible for TRAIL resistance is imperative for devising effective therapeutic strategies for TRAIL resistant cancers. In the present study, we demonstrated that inhibition of Bromodomain-containing protein 4 (BRD4) or genetic knock-down of BRD4, an epigenetic reader and master transcription coactivator, can sensitize lung cancer cells to TRAIL. This sensitization is in a caspase-dependent manner. Inhibition of BRD4 by small molecule inhibitor (+)-JQ-1 and genetic knock-down of BRD4 can both recruit the FADD and activate caspases. The sensitization did not regulate the death receptors DR4 and DR5. Moreover, BRD4 inhibition can block TRAIL-induced IKK activation by suppressing the transcriptional activity of NF-κB. These findings indicate that targeting combination therapy with TRAIL and BRD4 inhibitors can be a promising strategy to overcome TRAIL resistance in NSCLC.

14.
Blood Adv ; 5(19): 3776-3788, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34464977

RESUMO

Interactions between the inhibitor of apoptosis protein antagonist LCL161 and the histone deacetylase inhibitor panobinostat (LBH589) were examined in human multiple myeloma (MM) cells. LCL161 and panobinostat interacted synergistically to induce apoptosis in diverse MM cell lines, including those resistant to bortezomib (PS-R). Similar interactions were observed with other histone deacetylase inhibitors (MS-275) or inhibitors of apoptosis protein antagonists (birinapant). These events were associated with downregulation of the noncanonical (but not the canonical) NF-κB pathway and activation of the extrinsic, caspase-8-related apoptotic cascade. Coexposure of MM cells to LCL161/LBH589 induced TRAF3 upregulation and led to TRAF2 and NIK downregulation, diminished expression of BCL-XL, and induction of γH2A.X. Ectopic expression of TRAF2, NIK, or BCL-XL, or short hairpin RNA TRAF3 knock-down, significantly reduced LCL161/LBH589 lethality, as did ectopic expression of dominant-negative FADD. Stromal/microenvironmental factors failed to diminish LCL161/LBH589-induced cell death. The LCL161/LBH589 regimen significantly increased cell killing in primary CD138+ cells (N = 31) and was particularly effective in diminishing the primitive progenitor cell-enriched CD138-/19+/20+/27+ population (N = 23) but was nontoxic to normal CD34+ cells. Finally, combined LCL161/LBH589 treatment significantly increased survival compared with single-agent treatment in an immunocompetent 5TGM1 murine MM model. Together, these findings argue that LCL161 interacts synergistically with LBH589 in MM cells through a process involving inactivation of the noncanonical NF-κB pathway and activation of the extrinsic apoptotic pathway, upregulation of TRAF3, and downregulation of TRAF2/BCL-XL. Notably, this regimen overcomes various forms of resistance, is active against primary MM cells, and displays significant in vivo activity. This strategy warrants further consideration in MM.


Assuntos
Inibidores de Histona Desacetilases , Mieloma Múltiplo , Animais , Caspase 8/genética , Linhagem Celular Tumoral , Inibidores de Histona Desacetilases/farmacologia , Humanos , Camundongos , Mieloma Múltiplo/tratamento farmacológico , NF-kappa B
15.
Cell Mol Neurobiol ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196879

RESUMO

The only food and drug administration (FDA)-approved drug currently available for the treatment of acute ischemic stroke is tissue plasminogen activator (tPA), yet the therapeutic benefits of this drug are partially outweighed by the increased risk of hemorrhagic transformation (HT). Analysis of the NIH trial has shown that cigarette smoking protected tPA-treated patients from HT; however, the underlying mechanism is not clear. Nicotinic acetylcholine receptors (nAChR) has shown anti-inflammatory effect and modulation nAChR could be a strategy to reduce ischemia/reperfusion-induced blood-brain barrier (BBB) damage. Since melatonin could regulate the expression of α7nAchR and melatonin's neuroprotective effect against ischemic injury is mediated via α7nAChR modulation, here, we aim to test the hypothesis that melatonin reduces ischemia and reperfusion (I/R)-induced BBB damage through modulation of α7nACh receptor (α7nAChR). Mice were subjected to 1.5 h ischemia and 24 h reperfusion and at the onset of reperfusion, mice received intraperitoneal administration (i.p.) of either drug or saline. Mice were randomly assigned into five groups: Saline; α7nAChR agonist PNU282987; Melatonin; Melatonin+Methyllycaconitine (MLA, α7nAChR antagonist), and MLA group. BBB permeability was assessed by detecting the extravasation of Evan's blue and IgG. Our results showed that I/R significantly increased BBB permeability accompanied by occludin degradation, microglia activation, and high mobility group box 1 (HMGB1) release from the neuron. In addition, I/R significantly induced neuronal loss accompanied by the decrease of CREB-regulated transcriptional coactivator 1 (CRTC1) and p-CREB expression. Melatonin treatment significantly inhibited the above changes through modulating α7nAChR. Taken together, these results demonstrate that melatonin provides a protective effect on ischemia/reperfusion-induced BBB damage, at least in part, depending on the modulation of α7nAChR.

16.
IEEE Trans Image Process ; 30: 6609-6622, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34270426

RESUMO

Colorization in monochrome-color camera systems aims to colorize the gray image IG from the monochrome camera using the color image RC from the color camera as reference. Since monochrome cameras have better imaging quality than color cameras, the colorization can help obtain higher quality color images. Related learning based methods usually simulate the monochrome-color camera systems to generate the synthesized data for training, due to the lack of ground-truth color information of the gray image in the real data. However, the methods that are trained relying on the synthesized data may get poor results when colorizing real data, because the synthesized data may deviate from the real data. We present a self-supervised CNN model, named Cycle CNN, which can directly use the real data from monochrome-color camera systems for training. In detail, we use the Weighted Average Colorization (WAC) network to do the colorization twice. First, we colorize IG using RC as reference to obtain the first-time colorization result IC . Second, we colorize the de-colored map of RC , i.e. RG , using the concatenated image of IG and Cb/Cr channels of the first-time colorization result IC , i.e. ICCb and ICCr , as reference to obtain the second-time colorization result RC ' . In this way, for the second-time colorization result RC ' , we use the Cb and Cr channels of the original color map RC as ground-truth and introduce the cycle consistency loss to push RC 'Cb/Cr ≈ RCCb/Cr . Also, for the Y channel of the first-time colorization result ICY , we propose the Global Curve Adjustment (GCA) network and the structure similarity loss to encourage the structure similarity between ICY and IG . In addition, we introduce a spatial smoothness loss within the WAC network to encourage spatial smoothness of the colorization result. Combining all these losses, we could train the Cycle CNN using the real data in the absence of the ground-truth color information of IG . Experimental results show that we can outperform related methods largely for colorizing real data.

17.
Sci Rep ; 11(1): 12283, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112869

RESUMO

Radiotherapy-related caries is a complication of radiotherapy for nasopharyngeal carcinoma; however, factors influencing the occurrence, accurate prediction of onset, and protective factors of radiotherapy-related caries remain unclear. This study analyzed risk factors, disease predictors, and protective factors for radiotherapy-related caries in nasopharyngeal carcinoma. This prospective study included 138 nasopharyngeal carcinoma patients receiving radical radiotherapy at our hospital during June 2012-December 2016 and were followed up for dental caries. Patients' clinical data on radiotherapy were collected, dynamic monitoring was performed to assess changes in oral pH values, and a questionnaire survey was administered to collect patients' lifestyle habits. Time-dependent cox regression trees, event-free Kaplan-Meier curve, Mann-Whitely U test were used to analysis the results. The median follow-up time was 30 (12-60) months. Radiotherapy-related caries occurred in 28 cases (20.3%). Univariate analyses showed that radiotherapy-related caries was associated with patient's age, oral saliva pH value, green tea consumption, and radiation dose to sublingual glands, but not with the radiation dose to the parotid and submandibular glands. Multivariate analysis showed that oral saliva pH value [hazard ratio (HR) = 0.390, 95% confidence interval = 0.204-0.746] was an independent prognostic factor for radiotherapy-related caries. Patients with oral saliva pH values ≤ 5.3 in the 9th month after radiotherapy represented a significantly higher risks for radiotherapy-related caries (p < 0.001). Green tea consumption was associated with the occurrence of radiotherapy-related caries, and oral saliva pH values could predict the occurrence of radiotherapy-related caries. Limiting radiation doses to sublingual glands can reduce the occurrence of radiotherapy-related caries.


Assuntos
Suscetibilidade à Cárie Dentária , Cárie Dentária/etiologia , Concentração de Íons de Hidrogênio , Carcinoma Nasofaríngeo/complicações , Radioterapia/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/radioterapia , Modelos de Riscos Proporcionais , Radioterapia/métodos , Medição de Risco , Fatores de Risco , Fatores de Tempo
18.
J Glob Antimicrob Resist ; 26: 148-153, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34118479

RESUMO

OBJECTIVES: We aimed to determine the clinical impact of inappropriate empirical antibiotic treatment (IEAT) compared with appropriate empirical antibiotic treatment (AEAT) in hospitalised patients with urinary tract infections (UTIs) caused by Escherichia coli (E. coli). METHODS: This retrospective cohort study included adult patients with a primary diagnosis of UTI who were treated with empirical antibiotics at a tertiary hospital in southern China over a 2-year period. Clinical data of patients who received IEAT were compared with those of patients receiving AEAT. We used multivariable logistic regression to identify the predictors for receiving IEAT and the risk factors affecting clinical outcomes. RESULTS: A total of 213 patients were enrolled (median age, 61 years), of whom 103 (48.4%) received IEAT. IEAT was associated with empirical use of fluoroquinolones, male sex and age-adjusted Charlson comorbidity index (aCCI) score >6. Hospital length of stay (LOS) was longer for patients who received IEAT than for those who received AEAT (13.6 ± 8.6 days vs. 10.8 ± 7.9 days; P = 0.008). IEAT was an independent risk factor for longer LOS along with aCCI score ≥2, lung disease and cardiac disease. CONCLUSION: Empirical use of fluoroquinolones for UTIs should be avoided, especially in male patients with aCCI score >6. Improved empirical antimicrobial therapy may have a beneficial impact in reducing bacterial resistance and healthcare costs by decreasing the LOS. Therefore, interventions to promote in-depth antibiotic stewardship programmes in China are needed.


Assuntos
Gestão de Antimicrobianos , Infecções Urinárias , Adulto , Antibacterianos/uso terapêutico , Escherichia coli , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Urinárias/tratamento farmacológico
19.
Hortic Res ; 8(1): 103, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33931625

RESUMO

Botrytis cinerea is a major grapevine (Vitis spp.) pathogen, but some genotypes differ in their degree of resistance. For example, the Vitis vinifera cultivar Red Globe (RG) is highly susceptible, but V. amurensis Rupr Shuangyou (SY) is highly resistant. Here, we used RNA sequencing analysis to characterize the transcriptome responses of these two genotypes to B. cinerea inoculation at an early infection stage. Approximately a quarter of the genes in RG presented significant changes in transcript levels during infection, the number of which was greater than that in the SY leaves. The genes differentially expressed between infected leaves of SY and RG included those associated with cell surface structure, oxidation, cell death and C/N metabolism. We found evidence that an imbalance in the levels of reactive oxygen species (ROS) and redox homeostasis probably contributed to the susceptibility of RG to B. cinerea. SY leaves had strong antioxidant capacities and improved ROS homeostasis following infection. Regulatory network prediction suggested that WRKY and MYB transcription factors are associated with the abscisic acid pathway. Weighted gene correlation network analysis highlighted preinfection features of SY that might contribute to its increased resistance. Moreover, overexpression of VaWRKY10 in Arabidopsis thaliana and V. vinifera Thompson Seedless enhanced resistance to B. cinerea. Collectively, our study provides a high-resolution view of the transcriptional changes of grapevine in response to B. cinerea infection and novel insights into the underlying resistance mechanisms.

20.
Int J Food Sci Nutr ; : 1-11, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34000955

RESUMO

Evidence that common beverage consumption is associated with oral ecosystem. However, little is known about the effect of sugar-sweetened beverages (SSBs) on composition and functional potential of childhood oral microbiota. We aim to examine associations between SSBs consumption with oral microbiota diversity and function among school-aged children. Oral microbiota in buccal swab samples was collected from 180 children (11.3 ± 0.6 years) from an ongoing child growth and development cohort established in 2016, using 16S rDNA gene sequencing. Higher SSBs consumption (≥1 serving/day) was associated with lower oral microbiota richness and diversity. Children with higher SSBs consumption showed decreased abundance of genus Fusobacterium, Lachnoanaerobaculum, Soonwooa, Tannerella and Moraxella (p < 0.05). However, more SSBs intake selectively increases the dominance of aciduric bacteria (Neisseria and Streptococcus), which can lead to dental caries and other oral problems. Furthermore, PICRUSt analysis illustrated that oral microbiota was more conducive to the pathway activated of protein export (p = 0.020), D-glutamine and D-glutamate metabolism (p = 0.013), and pantothenate and CoA biosynthesis (p = 0.004), indicating vigorous microbial metabolism in oral bacterial community in higher SSBs intake groups. Overall, our finding suggests that higher SSBs consumption may disturb oral microecology and reduce diversity of microbiota during childhood, stimulating an increase in cariogenic genera, which contributes to increased susceptibility of SSBs-related oral diseases.

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