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2.
Animals (Basel) ; 11(3)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799557

RESUMO

The aim of this experiment was to evaluate the effect of a phytogenic feed additive (PFA) on growth performance and nutrient digestibility of broilers fed corn and soybean meal-based diets containing two different levels of crude protein. A 2 × 2 completely randomized factorial arrangement (eight replicates/treatment, 30 birds/replicate) was conducted with a positive control (PC) and negative control (NC) containing crude protein at standard or reduced by 1.5% (equivalent to a reduction of 15 g/kg), respectively, and supplementation of PFA at 0 or 125 ppm of diet. There were no significant interactions found between PFA and CP levels in the current study. Main effect analysis showed that during 0-42 d of age NC diets decreased body weight gain (p < 0.05), but increased feed intake (p < 0.05) and feed conversion ratio (FCR, p < 0.01), whereas supplementation of PFA resulted in a lower FCR (p < 0.01). The ileal nutrient digestibility was reduced (p < 0.05) in the broilers fed a reduced protein diet at 21 d compared to the standard protein level group, but there were no effects for PFA levels. Similarly, supplementing PFAs showed no effects on digestive enzyme (Alkaline phosphatase, amylase, and lipase) activity in jejunal digesta and jejunal brush border enzyme (maltase, sucrase, and aminopeptidase) activity. Supplementation of PFA downregulated (p < 0.05) the mRNA expressions of cytochrome P450 1A and interleukin 6 in the ileum but had no effects on nutrient transporter genes in the jejunum. In conclusion, supplementation of PFA reduced broiler FCR during the whole grow-out period and positively regulated the immune responses in the ileum.

3.
J Diabetes Res ; 2021: 9526701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33490288

RESUMO

The induction of inflammation and cytokine storm was proposed to play a critical role in COVID-19. This study is aimed at investigating the relationship between glucose metabolism and the inflammatory state of inpatients with COVID-19. 71 inpatients with COVID-19 were classified into nondiabetes mellitus (NDM) group, impaired fasting glucose (IFG) group, and diabetes mellitus (DM) group. The average hospitalization days were significantly shorter in DM patients when compared with patients in the IFG group and NDM group. CD4+ T cell percentage was higher while CD8+ T cells percentage was lower in the DM group than those in the NDM group. The serum levels of IL-6, IL-2, IL-10, and INF-γ in the DM group were upregulated when compared with those in the NDM group. The serum levels of TNF-α, IL-4, IL-2, IL-10, and INF-γ were significantly higher in the DM group than those in the IFG group. A significant difference was observed in CD4+ T cell, CD4+/CD8+ ratio percentage, IL-6, and IL-10 between the NDM group and DM group with adjusted BMI. In conclusion, COVID-19 patients with elevated glucose levels have promoted cytokine profiles and immune response.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Diabetes Mellitus Tipo 2/imunologia , Mediadores da Inflamação/imunologia , /imunologia , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , /epidemiologia , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo
4.
Biomacromolecules ; 22(2): 800-810, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33320540

RESUMO

Dual-cross-linked network (DCN) hydrogels with multiresponsive and self-healing properties are attracting intensive interests due to their enhanced mechanical strength for a wide range of applications. Herein, we developed a DCN hydrogel that combines a dynamic imine and a benzoxaboronic ester with a neutral pKa value (∼7.2) as dual linkages and contains biocompatible zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) [poly(MPC)] as the backbone. Oscillatory rheology result indicated shear strengthening mechanical properties compared to the single-cross-linked network (SCN) hydrogels, which use either imine bond or benzoxaboronic ester as the linkage alone. Due to the coexistence of stimuli-responsive imine and benzoxaboronic ester, the DCN hydrogels show sensitive multiple responsiveness to pH, sugar, and hydrogen peroxide. The dynamic nature of the dual linkages endows the DCN hydrogels with excellent self-healing ability after fracture. More importantly, the excellent biocompatibility and performance in three-dimensional (3D) cell encapsulation were established by a cytotoxicity Live/Dead assay, indicating DCN hydrogel's great potential as a cell culture scaffold. The biocompatible poly(MPC)-based backbone and the rapid formation of the cross-linking network make the DCN hydrogels promising candidates for future biomedical applications.

5.
Cancer Manag Res ; 12: 12021-12028, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262652

RESUMO

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease that has been spreading very fast worldwide. Up to now, there is scarce information regarding the clinical features and short-term outcomes of infected patients with cancer. Methods: We performed a retrospective study in Wuhan Union Hospital from Feb 14, 2020, to Mar 15, 2020, China. Data were retrieved including demographic and clinical features, laboratory findings, and outcome data. Patients were classified into the discharged group and undischarged group by the 4-week outcomes from admission. Difference analysis and correlation analysis were performed between the two groups. Results: A total of 37 patients were enrolled in the study, including 27 cancer survivors in routine follow-up. Breast cancer (18.9%) was the most frequent cancer type, and common symptoms included cough (54.1%), fever (48.6%), and fatigue (27%). Lymphocytopenia and hypoproteinemia were much frequent in patients who had received chemotherapy, radiotherapy, or surgery within the past month. However, the concentration of D-dimer (median: 3.75 vs 0.43, P =0.010) and fibrin degradation products (median: 23.60 vs 1.80, P =0.002) were evidently increased in this population compared with cancer survivors. At the end of follow-up, 83.8% of the enrolled patients were discharged. Among the discharged, women (48.6%) and cancer survivors (67.6%) showed better short-term outcomes. The elevated level of FDP was significantly higher in the undischarged group (median: 21.85 vs 2.00, P =0.049). The proportion of CD3-positive lymphocyte cells and CD4-positive lymphocytes was correlated with short-term outcomes. Conclusion: Peripheral lymphocyte subset (CD3-positive and CD4-positive) on admission as a novel biomarker had a potential association with early efficacy. Cancer survivors in routine follow-up would achieve better short-term outcomes. COVID-19 patients with cancer should gain more attention and close monitoring.

6.
BMC Complement Med Ther ; 20(1): 347, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203388

RESUMO

BACKGROUND: The aerial parts of Salvia miltiorrhiza, which was considered to be the waste part and discarded during the root harvest, is rich in protocatechuic aldehyde (PAI). This study investigated the health-promoting effects of extracts and PAI from the aerial parts of Salvia miltiorrhiza, including its anti-inflammatory effects and the underlying mechanisms of action in vitro and in vivo. METHOD: Purification of the sample paste of Salvia miltiorrhiza was accomplished using HPLC analysis. TheMTT (Methylthiazolyldiphenyl-tetrazolium bromide) assay was employed to determine the cell viability. The production of inflammatory factors was detected by ELISA assays. The histopathological analysis was used to analyse the lungs and livers of mice treated with PAI. Western blot was performed to reveal the mechanism of PAI in anti-inflammatory. RESULTS: The extracts and PAI from the aerial parts of Salvia miltiorrhiza inhibited TNF-α, IL-6 production and promoted the production of IL-10 in vivo in mice and in vitro in the macrophage cell line RAW264.7. NF-κB and MAPKs kinase phosphorylation were also suppressed by PAI in vivo and in vitro, indicating that PAI exhibited an anti-inflammatory effect. CONCLUSION: These findings suggest that the aerial parts of Salvia miltiorrhiza extract may serve as potential protective agents for inflammatory.

7.
Signal Transduct Target Ther ; 5(1): 248, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110061

RESUMO

Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow. The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression. Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs. Among these new drugs, we focussed on thioredoxin (Trx). Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways. The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses. In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF). Taken together, these findings suggest that Trx may be the ideal drug for treating COPD.

8.
Toxins (Basel) ; 12(9)2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899719

RESUMO

Deoxynivalenol (DON) is a mycotoxin found in grains that poses a potential threat to human and animal health, and the gastrointestinal tract is the primary target organ. There are few studies focused on the toxicology of DON to rabbits, especially on the relation among DON, microbiota, and the gut-associated lymphoid tissue. A total of 30 weaned rabbits (35 d) were evenly divided into the control group and DON group (1.5 mg/kg bodyweight (BW)) based on their body weight. After a 24-day trial, the ultrastructures of the sacculus rotundus and vermiform appendix were observed using a scanning electron microscope and transmission electron microscopy. The morphology and microflora in the ileum, caecum, and colon were also examined. The results proved that the ultrastructure of the sacculus rotundus and vermiform appendix, as well as the integrity of the intestinal barrier (especially for the ileum), were impaired after DON was administrated to the rabbits. Compared to the control group, the relative abundance and diversity of the microflora decreased in all three intestinal segments in the DON group, particularly in the ileum and caecum. In conclusion, the toxic effect of DON on weaned rabbits may be performed by destroying the structure of the sacculus rotundus and vermiform appendix, as well as affecting the structure and diversity of the intestinal flora.

9.
Chem Commun (Camb) ; 56(83): 12542-12545, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-32940288

RESUMO

An RGD-peptide conjugated ruthenium(ii) complex has been developed, which functions as a two-photon absorption (TPA) photodynamic therapy (PDT) agent for ablating tumours by selectively targeting the mitochondria of integrin αvß3-rich tumour cells. This approach offers a new and effective design and application for tumour-targeting metallo-anticancer drugs via two-photon PDT.

10.
Front Immunol ; 11: 2160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983180

RESUMO

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide. Measuring the prevention and control of the disease has become a matter requiring urgent focus. Objective: Based on coronavirus disease 2019 (COVID-19) clinical data from Wuhan, we conducted an in-depth analysis to clarify some of the pathological mechanisms of the disease and identify simple measures to predict its severity early on. Methods: A total of 230 patients with non-mild COVID-19 were recruited, and information on their clinical characteristics, inflammatory cytokines, and T lymphocyte subsets was collected. Risk factors for severity were analyzed by binary logistic regression, and the associations of neutrophil-to-lymphocyte ratios (N/LRs) with illness severity, disease course, CT grading, inflammatory cytokines, and T lymphocyte subsets were evaluated. Results: Our results showed that the N/LRs were closely related to interleukin (IL)-6 and IL-10 (P < 0.001, P = 0.024) and to CD3+ and CD8+ T lymphocytes (P < 0.001, P = 0.046). In particular, the N/LRs were positively correlated with the severity and course of the disease (P = 0.021, P < 0.001). Compared to the values at the first test after admission, IL-6 and IL-10 were significantly decreased and increased, respectively, as of the last test before discharge (P = 0.006, P < 0.001). More importantly, through binary logistic regression, we found that male sex, underlying diseases (such as cardiovascular disease), pulse, and N/LRs were all closely related to the severity of the disease (P = 0.004, P = 0.012, P = 0.013, P = 0.028). Conclusions: As a quick and convenient marker of inflammation, N/LRs may predict the disease course and severity level of non-mild COVID-19; male sex, cardiovascular disease, and pulse are also risk factors for the severity of non-mild COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Índice de Gravidade de Doença , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Biomarcadores , Doenças Cardiovasculares , Infecções por Coronavirus/virologia , Feminino , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Pulso Arterial , Fatores de Risco , Fatores Sexuais
11.
ACS Nano ; 14(9): 12125-12132, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32808759

RESUMO

This article reports on a noninvasive approach in detecting and following-up individuals who are at-risk or have an existing COVID-19 infection, with a potential ability to serve as an epidemic control tool. The proposed method uses a developed breath device composed of a nanomaterial-based hybrid sensor array with multiplexed detection capabilities that can detect disease-specific biomarkers from exhaled breath, thus enabling rapid and accurate diagnosis. An exploratory clinical study with this approach was examined in Wuhan, China, during March 2020. The study cohort included 49 confirmed COVID-19 patients, 58 healthy controls, and 33 non-COVID lung infection controls. When applicable, positive COVID-19 patients were sampled twice: during the active disease and after recovery. Discriminant analysis of the obtained signals from the nanomaterial-based sensors achieved very good test discriminations between the different groups. The training and test set data exhibited respectively 94% and 76% accuracy in differentiating patients from controls as well as 90% and 95% accuracy in differentiating between patients with COVID-19 and patients with other lung infections. While further validation studies are needed, the results may serve as a base for technology that would lead to a reduction in the number of unneeded confirmatory tests and lower the burden on hospitals, while allowing individuals a screening solution that can be performed in PoC facilities. The proposed method can be considered as a platform that could be applied for any other disease infection with proper modifications to the artificial intelligence and would therefore be available to serve as a diagnostic tool in case of a new disease outbreak.


Assuntos
Testes Respiratórios/instrumentação , Infecções por Coronavirus/diagnóstico , Nanoestruturas , Pneumonia Viral/diagnóstico , Grupo com Ancestrais do Continente Asiático , Betacoronavirus , Biomarcadores/análise , Testes Respiratórios/métodos , China , Confiabilidade dos Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Sistema Respiratório , Sensibilidade e Especificidade
12.
Stroke Vasc Neurol ; 5(3): 242-249, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32641446

RESUMO

During the COVID-19 epidemic, the treatment of critically ill patients has been increasingly difficult and challenging. During the epidemic, some patients with neurological diseases also have COVID-19, which could be misdiagnosed and cause silent transmission and nosocomial infection. Such risk is high in a neurological intensive care unit (NCU). Therefore, prevention and control of epidemic in critically ill patients is of utmost importance. The principle of NCU care should include comprehensive screening and risk assessment, weighing risk against benefits and reducing the risk of COVID-19 transmission while treating patients as promptly as possible.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/prevenção & controle , Infecção Hospitalar/prevenção & controle , Controle de Infecções/normas , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Unidades de Terapia Intensiva/normas , Doenças do Sistema Nervoso/terapia , Neurologia/normas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Consenso , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Estado Terminal , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/transmissão , Infecção Hospitalar/virologia , Interações Hospedeiro-Patógeno , Humanos , Doenças do Sistema Nervoso/diagnóstico , Saúde do Trabalhador , Segurança do Paciente , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Medição de Risco , Fatores de Risco , Resultado do Tratamento
13.
Phytother Res ; 34(12): 3189-3199, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32648634

RESUMO

Vancomycin (VCM) is an effective chemotherapeutic agent commonly used against gram-positive microorganisms but has serious nephrotoxic side effects that limit its effectiveness. New therapeutics and strategies are urgently needed to combat VCM associated nephrotoxicity. In this study, we determined the protective effect of chlorogenic acid (CA) in a rat model of VCM-induced nephrotoxicity. VCM administration led to markedly elevated blood urea nitrogen and serum creatinine levels that could be prevented with CA co-administration. VCM-mediated oxidative stress was also significantly attenuated by CA as reflected by decreased malondialdehyde and nitric oxide in VCM-treated kidneys. CA administration also prevented the VCM-mediated decrease in the renal antioxidative enzyme activities of glutathione reductase, glutathione peroxidase, and catalase and led to increased levels of reduced glutathione that had been depleted by VCM. Moreover, CA administration clearly inhibited VCM-induced expression of nuclear factor-kappa B, inducible nitric oxide synthase and the downstream pro-inflammatory mediators tumor necrosis factor-α and interleukins 1ß and 6. Apoptotic markers were also markedly down-regulated with CA. Overall, CA treatment mitigated VCM-induced oxidative and nitrosative stresses and countered the apoptotic and inflammatory effects of VCM. Notably, CA did not affect the antibacterial activity of VCM in vitro.

14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(5): 554-558, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32576346

RESUMO

OBJECTIVE: To investigate the clinical significance of neutrophil-to-lymphocyte ratio (NLR) in classification of patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective analysis was performed on 72 patients with COVID-19 admitted to the critical ward of Cancer Center of Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan from February to March in 2020. The patients were divided into two groups: moderate type (non-severe group) and severe/critical type (severe group). The results of white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), interleukin-6 (IL-6) and D-dimer were collected at the 2nd day after admission from the two groups, and the NLR was calculated. The diagnostic value of WBC, NEU, LYM, IL-6, D-dimer and NLR on COVID-19 classification was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: A total of 72 COVID-19 patients were enrolled, among whom 52 were moderate, 17 were severe, and 3 were critical. The most common clinical manifestations of patients were fever (70.8%), cough (36.1%), chest tightness and breathlessness (37.5%), diarrhea (15.3%), fatigue (15.3%), vomiting and nausea (11.1%), occasionally accompanied by acute dyspnea (2.8%), and only one patient had no clinical symptom (1.4%). The levels of WBC, NEU, IL-6, D-dimer and NLR in the severe group were significantly higher than those in the non-severe group [WBC (×109/L): 7.81±3.65 vs. 5.34±1.69, NEU (×109/L): 5.83±3.13 vs. 3.24±1.53, IL-6 (ng/L): 133.63 (71.09, 249.61) vs. 28.05 (6.41, 101.24), D-dimer (mg/L): 0.86 (0.31, 2.56) vs. 0.33 (0.20, 0.71), NLR: 6.14±4.75 vs. 2.66±1.93, all P < 0.05], and the level of LYM was significantly lower than that in the non-severe group (×109/L: 1.09±0.56 vs. 1.49±0.74, P < 0.05). The results of ROC curve analysis showed that the areas under ROC curve (AUC) of WBC, NEU, LYM, IL-6, D-dimer and NLR for COVID-19 classification were 0.790 [95% confidence interval (95%CI) was 0.684-0.897), 0.869 (95%CI was 0.789-0.949), 0.719 (95%CI was 0.592-0.847), 0.790 (95%CI was 0.682-0.898), 0.676 (95%CI was 0.526-0.827), and 0.888 (95%CI was 0.814-0.963) respectively. The AUC of NLR was the highest, which was of high diagnostic value; when the optimum cut-off value of NLR was 3.00, the sensitivity was 100%, and the specificity was 73.1%. CONCLUSIONS: NLR can be used as a biomarker to predict classification of COVID-19 patients independently, which can provide a theoretical basis for the classification management of COVID-19 patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Neutrófilos , Pandemias , Pneumonia Viral , Humanos , Linfócitos , Prognóstico , Curva ROC , Estudos Retrospectivos
15.
Animals (Basel) ; 10(6)2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32503244

RESUMO

The objective of this study was to evaluate the effect of low-protein diets with amino acid supplementation on growth performance, carcass yield, meat quality and nitrogen excretion of broilers raised under hot climate conditions during the finisher period. In trial 1, broilers from 28 to 49 days of age were fed 18% crude protein (CP) as a positive control or 15% CP supplemented with (1) DL-methionine (Met) + L-lysine (Lys), (2) Met + Lys + L-Arginine (Arg), or (3) Met + Lys + L-Valine (Val). In trial 2, broilers from 30 to 45 days of age, were fed an 18% CP diet as a positive control or 15% CP supplemented with Met, Lys, Arg, Val, L-Isoleucine (Ile) or combination with glycine (Gly) and/or urea as nitrogen sources: (1) Met + Lys, (2) Met + Lys + Arg, (3) Met + Lys + Val, (4) Met + Lys + Ile, (5) Met + Lys + Arg +Val + Ile + Gly, and (6) Met+ Lys + Arg + Val + Ile + Gly + urea. Protein use was improved by feeding low-protein amino acid-supplemented diets as compared to the high-protein diet. Feeding 15% crude protein diet supplemented with only methionine and lysine had no negative effects on carcass yield, CP, total lipids and moisture% of breast meat while decreasing nitrogen excretion by 21%.

16.
Br J Cancer ; 123(2): 226-239, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32390005

RESUMO

BACKGROUND: Human urothelial carcinoma (UC) has a high tendency to recur and progress to life-threatening advanced diseases. Advanced therapeutic regimens are needed to control UC development and recurrence. METHODS: We pursued in vitro and in vivo studies to understand the ability of a triple combination of gemcitabine, romidepsin, and cisplatin (Gem+Rom+Cis) to modulate signalling pathways, cell death, drug resistance, and tumour development. RESULTS: Our studies verified the ability of Gem+Rom+Cis to synergistically induce apoptotic cell death and reduce drug resistance in various UC cells. The ERK pathway and reactive oxygen species (ROS) played essential roles in mediating Gem+Rom+Cis-induced caspase activation, DNA oxidation and damage, glutathione reduction, and unfolded protein response. Gem+Rom+Cis preferentially induced death and reduced drug resistance in oncogenic H-Ras-expressing UC vs. counterpart cells that was associated with transcriptomic profiles related to ROS, cell death, and drug resistance. Our studies also verified the efficacy and safety of the Gem plus Rom+Cis regimen in controlling UC cell-derived xenograft tumour development and resistance. CONCLUSIONS: More than 80% of UCs are associated with aberrant Ras-ERK pathway. Thus the compensatory combination of Rom with Gem and Cis should be seriously considered as an advanced regimen for treating advanced UCs, especially Ras-ERK-activated UCs.

17.
Angew Chem Int Ed Engl ; 59(37): 15987-15991, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32473088

RESUMO

Compared to 2PE (two-photon excitation) microscopy, 3PE microscopy has superior spatial resolution, deeper tissue penetration, and less defocused interference. The design of suitable agents with a large Stokes shift, good three-photon absorption (3PA), subcellular targeting, and fluorescence lifetime imaging (FLIM) properties, is challenging. Now, two IrIII complexes (3PAIr1 and 3PAIr2) were developed as efficient three-photon phosphorescence (3PP) agents. Calculations reveal that the introduction of a new group to the molecular scaffold confers a quadruple promotion in three-photon transition probability. Confocal and lifetime imaging of mitochondria using IrIII complexes as 3PP agents is shown. The complexes exhibit low working concentration (50 nm), fast uptake (5 min), and low threshold for three-photon excitation power (0.5 mW at 980 nm). The impressive tissue penetration depth (ca. 450 µm) allowed the 3D imaging and reconstruction of brain vasculature from a living specimen.

18.
Front Med (Lausanne) ; 7: 89, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32318576

RESUMO

This study aimed to determine the impact of HLA-B27 on clinical phenotype and renal function during follow-up periods in patients with ankylosing spondylitis (AS) and secondary IgA nephropathy (IgAN). This single-center retrospective study included 71 AS patients with secondary IgAN. Renal function decline was defined as a mean eGFR decline of more than 5 mL/min/1.73 m2 per year or progression into the dialysis stage. The association between HLA-B27 status and renal function decline was evaluated by univariable and multivariable Cox regression analyses. The results showed that seven (9.85%) of the 71 included patients were HLA-B27-negative. The median follow-up period was 4.0 years. HLA-B27-negative patients showed higher levels of uric acid (UA) than those who were HLA-B27-positive. Pathologically, a higher percentage of globally sclerotic glomeruli was observed in HLA-B27-negative patients. Survival analysis indicated that HLA-B27 negativity was associated with a significantly higher probability of renal function decline than HLA-B27 positivity. This significant association was also found in subgroup analyses of patients with either substantial proteinuria (more than 1.0 g per day) or interstitial fibrosis and tubular atrophy. Multivariable analysis showed that HLA-27 negativity was independently associated with renal function decline (HR 6.58; 95% CI 1.65 to 26.21; p = 0.008). In conclusion, HLA-B27 negativity is associated not only with a higher level of UA and a higher percentage of globally sclerotic glomeruli in AS patients with secondary IgAN but with renal function decline during follow-up periods.

19.
J Med Virol ; 92(10): 2004-2010, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32330303

RESUMO

Coronavirus disease (COVID-19), caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly developed into a pandemic since it was first reported in December 2019. Nucleic acid testing is the standard method for the diagnosis of viral infections. However, this method reportedly has a low positivity rate. To increase the sensitivity of COVID-19 diagnoses, we developed an IgM-IgG combined assay and tested it in patients with suspected SARS-CoV-2 infection. In total, 56 patients were enrolled in this study and SARS-CoV-2 was detected by using both IgM-IgG antibody and nucleic acid tests. Clinical and laboratory data were collected and analyzed. Our findings suggest that patients who develop severe illness might experience longer virus exposure times and develop a more severe inflammatory response. The IgM-IgG test is an accurate and sensitive diagnostic method. A combination of nucleic acid and IgM-IgG testing is a more sensitive and accurate approach for diagnosis and early treatment of COVID-19.

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