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1.
FASEB J ; 35(5): e21526, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33813773

RESUMO

Discovering safe and effective drugs that promote neuron regeneration is an essential strategy for the recovery of central nervous system injuries. In this study, we found that L-leucine, an essential amino acid obtained from both supplements and food sources, could dramatically boost axonal outgrowth and regeneration. First, the effects of L-leucine on neurons were evaluated by cell apoptosis, survival, and death assays, and the results showed no changes in these processes after treatment. By live cell imaging, L-leucine was found to remarkably increase axonal length and growth velocity after axotomy. We also verified that L-leucine enhanced p-mTOR/p-S6K activation in neurons by testing with an mTOR inhibitor, rapamycin. Thereafter, we investigated the effects of L-leucine on the spinal cord injury in vivo. A mouse model of spinal cord hemi-section was established, and L-leucine was administered by tail intravenous injection. Basso mouse scale values revealed that L-leucine could improve functional recovery after injury. It was also notable that L-leucine treatment promoted axon growth across chondroitin sulfate proteoglycan (CSPG) areas. Furthermore, we used CSPGs as inhibitory environmental cues and clarified that L-leucine significantly enhanced axonal outgrowth and regeneration by promoting p-mTOR and p-S6K activation. Therefore, our study is the first to report that L-leucine promotes axonal regeneration in vitro and in vivo and could be candidate drug for axonal re-growth and nervous functional recovery.

2.
Eur J Med Chem ; 218: 113398, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33823392

RESUMO

A series of novel benzothiazinone derivatives containing a N-(amino)piperazine moiety, based on the structure of WAP-1902 discovered in our lab, were designed and synthesized as new anti-TB agents. Many of the compounds exhibited excellent in vitro activity against both drug-sensitive MTB strain H37Rv and multidrug-resistant clinical isolates (MIC: < 0.016 µg/mL), and good safety index (CC50: >64 µg/mL). Especially compound 1o displayed low hERG cardiac toxicity and acceptable oral pharmacokinetic profiles, indicating its promising potential to be a lead compound for future antitubercular drug discovery.

3.
Medicine (Baltimore) ; 100(14): e25278, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832094

RESUMO

ABSTRACT: A kinase interacting protein 1 (AKIP1) is upregulated in cancer cells/tissues and associated with deteriorative tumor features, while it has not been investigated in tongue squamous cell carcinoma (TSCC). The goal of this study was to measure AKIP1 expression and analyze its correlation with clinical feature and prognosis in TSCC patients.We retrospectively reviewed 194 TSCC patients, whose formalin fixed paraffin-embedded (FFPE) tumor tissue specimens and paired adjacent tissue specimens were accessible for AKIP1 detection by immunohistochemistry (IHC). Whereas only 107 patients whose fresh-frozen tumor tissue and paired fresh-frozen adjacent tissue that were still available in storage were included for AKIP1 mRNA detection by real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR).AKIP1 expression (both the protein detected by IHC and mRNA detected by RT-qPCR) was higher in TSCC tissue than that in adjacent tissue. In addition, both tumor AKIP1 mRNA and protein expressions were correlated with advanced N stage and TNM stage, while they were not correlated with other clinical features in TSCC patients. As for survival, there was a correlation of AKIP1 mRNA with poor overall survival (OS), while the correlation of AKIP1 protein expression with OS was of limited statistical significance.There is an upregulation of AKIP1 in TSCC and it correlates with lymph node metastasis as well as unfavorable prognosis in TSCC patients.

4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(3): 338-343, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33834977

RESUMO

OBJECTIVE: To explore a medical big data algorithm to screen the core indicators in clinical database that can be used to evaluate the prognosis of elderly patients with pneumonia. METHODS: Based on the clinical database of a Beijing Chaoyang Hospital Consortium Chaoyang Emergency Ward in Beijing Chaoyang Hospital, Capital Medical University, patients with pulmonary infection were selected through the big data retrieval technology. According to the prognosis at the time of discharge, they were divided into death group and survival group. The general data of patients were collected, including gender, age, blood gas and laboratory indices. A computer language called Python was used to make batch calculations of key indicators that affect mortality in elderly patients with pneumonia. Logistic regression analysis was used to analyze the relationship between laboratory indicators and patients' prognosis. Receiver operating characteristic curve (ROC curve) was drawn to analyze the predictive value of screening method for patients' prognosis. RESULTS: A total of 265 patients were included in the study, 64 died and 201 survived. The data of the first detection indexes of each patient after admission were collected, and 23 key indicators with significant differences were selected from 472 indicators: blood routine indicators (n = 7), blood gas indicators (n = 3), tumor markers indicators (n = 3), coagulation related indicators (n = 4), and nutrition and organ function indicators (n = 6). (1) The key indicators of blood gas in patients died of pneumonia: Cl- was 97-111 mmol/L in 51.6% (33 cases) of patients, lactic acid (Lac) was 0.5-2.5 mmol/L in 81.2% (52 cases) of patients, and H+ was 0-46 mmol/L in 87.5% (56 cases) of patients. (2) The key indicators of blood routine of patients died of pneumonia: hemoglobin count (Hb) of 46.9% (30 cases) patients was 80-109 g/L, the eosinophils proportions (EOS%) in 67.2% (43 cases) patients was 0.000-0.009, the lymphocytes proportions (LYM%) in 51.6% (33 cases) patients was 0.00-0.09, the red blood cell count (RBC) in 50.0% (32 cases) patients was (3.0-3.9)×1012/L, the white blood cell count (WBC) in 54.7% (35 cases) patients was (0.0-9.9)×109/L, and the red blood cell volume distribution width coefficientof variability (RDW-CV) in 48.4% (31 cases) patients was 10.0%-14.9%, serum C-reactive protein (CRP) was 0.0-49.9 mg/L in 48.4% (31 cases) patients. (3) The key indicators of tumor markers in patients died of pneumonia: 76.6% (49 cases) of patients had negative free prostate specific antigen/total prostate specific antigen (FPSA/TPSA, the ratio was 0), 92.2% (59 cases) had cytokeratin 19 fragment (CYFRA21-1) between 0.0-11.0 µg/L, and 75.0% (48 cases) had carbohydrate antigen 125 (CA125) between 0-104 kU/L. (4) The key coagulation indexes of patients died of pneumonia: 68.8% (44 cases) of patients had activated partial thromboplastin time (APTT) of 57-96 s, 73.4% (47 cases) of patients had D-dimer of 0-6 mg/L, 93.8% (60 cases) of patients had thrombin time (TT) of 14-22 s, and 89.1% (57 cases) of patients had adenosine diphosphate (ADP) inhibition rate of 0%-53%. (5) Nutrition and organ function key indicatorsin patients died of pneumonia: 92.2% (59 cases) of brain natriuretic peptide (BNP) in patients with 0, 46.9% (30 cases) of patients had prealbumin (PA) of 71-140 mg/L, 90.6% (58 cases) of the patients with uric acid (UA) for 21-41 µmol/L, 75.0% (48 cases) of the patients with albumin (Alb) to 10-20 g/L, 93.5% (60 cases) of patients had albumin/globulin ratio (A/G ratio) of 0-0.9, 84.4% (54 cases) of the patients with lactate dehydrogenase (LDH) from 0-6.68 µmol/L×s-1×L-1. (6) Logistic regression analysis and ROC curve analysis: Logistic regression analysis showed that PA and Lac were the prognostic factors. PA could reduce the risk of death by 0.9%, Lac could increase the risk of death by 69.4%; the area under ROC curve (AUC) between laboratory indicators and the prediction effect of death prediction model for patients' prognosis was 0.80, which showed that the classification effect was better, and this study model could better predict the prognosis of elderly patients with pneumonia. CONCLUSIONS: By using big data technology, 23 core indicators for evaluating the prognosis of elderly patients with pneumonia can be screened from the clinical database of emergency ward, which provides a new perspective and method for clinical evaluation of the prognosis of elderly patients with pneumonia.

5.
Lancet ; 397(10279): 1075-1084, 2021 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743869

RESUMO

BACKGROUND: Wuhan was the epicentre of the COVID-19 outbreak in China. We aimed to determine the seroprevalence and kinetics of anti-SARS-CoV-2 antibodies at population level in Wuhan to inform the development of vaccination strategies. METHODS: In this longitudinal cross-sectional study, we used a multistage, population-stratified, cluster random sampling method to systematically select 100 communities from the 13 districts of Wuhan. Households were systematically selected from each community and all family members were invited to community health-care centres to participate. Eligible individuals were those who had lived in Wuhan for at least 14 days since Dec 1, 2019. All eligible participants who consented to participate completed a standardised electronic questionnaire of demographic and clinical questions and self-reported any symptoms associated with COVID-19 or previous diagnosis of COVID-19. A venous blood sample was taken for immunological testing on April 14-15, 2020. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. We did two successive follow-ups between June 11 and June 13, and between Oct 9 and Dec 5, 2020, at which blood samples were taken. FINDINGS: Of 4600 households randomly selected, 3599 families (78·2%) with 9702 individuals attended the baseline visit. 9542 individuals from 3556 families had sufficient samples for analyses. 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2, with a baseline adjusted seroprevalence of 6·92% (95% CI 6·41-7·43) in the population. 437 (82·1%) of 532 participants who were positive for pan-immunoglobulins were asymptomatic. 69 (13·0%) of 532 individuals were positive for IgM antibodies, 84 (15·8%) were positive for IgA antibodies, 532 (100%) were positive for IgG antibodies, and 212 (39·8%) were positive for neutralising antibodies at baseline. The proportion of individuals who were positive for pan-immunoglobulins who had neutralising antibodies in April remained stable for the two follow-up visits (162 [44·6%] of 363 in June, 2020, and 187 [41·2%] of 454 in October-December, 2020). On the basis of data from 335 individuals who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralising antibody levels did not significantly decrease over the study period (median 1/5·6 [IQR 1/2·0 to 1/14·0] at baseline vs 1/5·6 [1/4·0 to 1/11·2] at first follow-up [p=1·0] and 1/6·3 [1/2·0 to 1/12·6] at second follow-up [p=0·29]). However, neutralising antibody titres were lower in asymptomatic individuals than in confirmed cases and symptomatic individuals. Although titres of IgG decreased over time, the proportion of individuals who had IgG antibodies did not decrease substantially (from 30 [100%] of 30 at baseline to 26 [89·7%] of 29 at second follow-up among confirmed cases, 65 [100%] of 65 at baseline to 58 [92·1%] of 63 at second follow-up among symptomatic individuals, and 437 [100%] of 437 at baseline to 329 [90·9%] of 362 at second follow-up among asymptomatic individuals). INTERPRETATION: 6·92% of a cross-sectional sample of the population of Wuhan developed antibodies against SARS-CoV-2, with 39·8% of this population seroconverting to have neutralising antibodies. Our durability data on humoral responses indicate that mass vaccination is needed to effect herd protection to prevent the resurgence of the epidemic. FUNDING: Chinese Academy of Medical Sciences & Peking Union Medical College, National Natural Science Foundation, and Chinese Ministry of Science and Technology. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , /imunologia , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , /epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Imunidade Coletiva/imunologia , Imunidade Humoral , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Vacinação em Massa/organização & administração , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Adulto Jovem
6.
J Int Med Res ; 49(3): 300060521999558, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33752450

RESUMO

OBJECTIVE: To summarize the clinical and pathological features of patients with cardiac lymphoma. METHODS: The general conditions, clinical features, pathological types, and prognostic indices of 37 patients with cardiac lymphoma treated in our hospital were analyzed. RESULTS: Among the 37 patients, only one had primary cardiac lymphoma, and the other 36 patients had secondary cardiac lymphoma. The cardiac manifestations were mainly chest tightness, shortness of breath, increased heart rates, and electrocardiographic abnormality caused by pericardial effusion, but myocardial enzyme levels were normal in all patients. Only three patients displayed solid heart-occupying manifestations. These lesions were mainly located in the right atrium, and the masses were all larger than 5 cm. The pathological type was diffuse large B cell lymphoma that did not arise from the germinal center in all three patients. CONCLUSIONS: Cardiac lymphoma was mostly secondary, and pericardial effusion was the primary objective sign. Moreover, cardiac lymphoma was characterized by a high international prognostic index, late stage, and high rates of T and NK cell lymphoma. Most cases were accompanied by serous cavity effusion, extranodal involvement of important organs, elevated lactate dehydrogenase levels, hypoalbuminemia, and normal myocardial enzyme levels.

7.
Plant Dis ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33787309

RESUMO

Powdery mildew of wheat, caused by Blumeria graminis f. sp. tritici (Bgt), is a destructive disease of wheat. Cultivation of resistant varieties is the most cost-effective disease management strategy. Previous studies reported that chromosome 3Sl#2 present in Chinese Spring (CS)-Aegilops longissima 3Sl#2(3B) disomic substitution line TA3575 conferred resistance to powdery mildew. In this study, we further located the powdery mildew resistance gene(s) to the short arm of chromosome 3Sl#2 (3Sl#2S) by evaluating for Bgt-resistance of newly developed CS-Ae. longissima 3Sl#2 translocation lines. Meanwhile, TA7545, a previously designated CS-Ae. longissima 3Sl#3 disomic addition line, was re-identified as an isochromosome 3Sl#3S addition line and evaluated to confer resistance to powdery mildew, thus locating the resistance gene(s) to the short arm of chromosome 3Sl#3 (3Sl#3S). Based on transcriptome sequences of TA3575, ten novel chromosome 3SlS-specific markers were developed, of which, five could be used to distinguish between 3Sl#2S and 3Sl#3S derived from Ae. longissima accessions TL20 and TA1910 (TAM4), and the remaining five could identify both 3Sl#2S and 3Sl#3S. Besides, CL897, one of five markers specific to both 3Sl#2S and 3Sl#3S, could be used to detect Pm13 located at chromosome 3Sl#1S from Ae. longissima accession TL01 in diverse wheat genetic backgrounds. The powdery mildew resistance genes on chromosomes 3Sl#2S and 3Sl#3S, the CS-Ae. longissima 3Sl#2 translocation lines, and the 3SlS-specific markers developed in this study will provide new germplasm resources for powdery mildew resistance breeding and facilitate the transfer of Bgt-resistance genes into common wheat.

8.
Mol Cell Biochem ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33770315

RESUMO

Angiogenesis is critical to establishing a successful pregnancy. The chemokine (C-X-C motif) ligand 1 (CXCL1) is a small cytokine belonging to the CXC chemokine family that is an important chemokine involved in the processes of angiogenesis and arteriogenesis; however, little is known about its role in decidual angiogenesis. Effects of CXCL1 on cell proliferation and migration (propidium iodide staining and wound healing assays) of HUVEC cells were determined. The angiogenesis roles of CXCL1 in HUVEC-HTR8/SVneo co-culture system were detected by the tube formation assay. Signal transduction pathways in HUVEC cells in response to CXCL1 were determined by in-cell western analyses. In vivo, mice were injected with (1) PBS (Group A) or (2) CXCL1-neutralizing antibody (Group B) or (3) CXCL1-neutralizing antibody plus recombinant VEGF-A protein (Group C) from E1 to E5 and sacrificed at E6.5 of pregnancy. The decidual angiogenesis in mice was examined by immunohistochemistry of cluster designation 34 (CD34), and the expression levels of vascular endothelial growth factor-A (VEGF-A) in the decidual cells and vascular endothelial growth factor receptor 2 (VEGFR2) in decidual vascular endothelial cells were also tested. Exogenous recombinant human CXCL1 supported endothelial cell proliferation and migration, and this effect was blocked by CXCL1-neutralizing antibody or CXCR2 inhibitor SB265610. The tube formation of HUVEC-HTR8/SVneo co-culture system was significantly stimulated by CXCL1, but this effect was markedly abrogated once they were pretreated with CXCL1-neutralizing antibody or CXCR2 inhibitor SB265610. In addition, the level of vascular endothelial growth factor A (VEGF-A) expression in HUVEC cells was increased by CXCL1, and this level was suppressed by CXCL1-neutralizing antibody or CXCR2 inhibitor SB265610. In vivo, compared with Group A (n = 3), decidual angiogenesis was significantly reduced in Group B by CD34 immunostaining. But compared with Group B, decidual angiogenesis was significantly increased in Group C. In addition, the expression of VEGF-A and VEGFR2 was significantly increased after neutralizing of CXCL1 in Group B. In conclusions, CXCL1 may play essential roles in decidual angiogenesis during the first trimester, and this function may be mediated in part via altering VEGF-A expression.

9.
Inorg Chem ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33761745

RESUMO

A facile spray pyrolysis method is introduced to construct the hollow CeO2-Al2O3 spheres with atomically dispersed Fe. Only nitrates and ethanol were involved during the one-step preparation process using the ultrasound spray pyrolysis approach. Detailed explorations demonstrated that differences in the pyrolysis temperature of the precursors and heat transfer are crucial to the formation of the hollow nanostructure. In addition, iron species were in situ atomically dispersed on the as-formed CeO2-Al2O3 hollow spheres via this strategy, which demonstrated promising potential in transferring syn-gas to valuable gasoline products.

10.
Adv Mater ; : e2100098, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33733490

RESUMO

As a typical inflammatory disease with chronic pain syndromes, rheumatoid arthritis (RA) generally requires long-term treatment with frequent injection administration at 1-2 times per day, because common medications such as interleukin1 receptor antagonist (IL1ra) have poor bioavailability and very limited half-life residence. Here a novel strategy to fabricate nanotherapeutic formulations employing genetically engineered IL1ra protein complexes, yielding ultralong-lasting bioefficacy is developed rationally. Using rat models, it is shown that these nanotherapeutics significantly improved drug regimen to a single subcutaneous administration in a 14-day therapy, suggesting their extraordinary bioavailability and ultralong-acting pharmacokinetics. Specifically, the half-life and bioavailability of the nanoformulations are boosted to the level of 30 h and by 7 times, respectively, significantly greater than other systems. This new strategy thus holds great promise to potently improve patient compliance in RA therapy, and it can be adapted for other therapies that suffer similar drawbacks.

11.
Neural Plast ; 2021: 8812362, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708250

RESUMO

Shi-Zhen-An-Shen decoction (SZASD), a Chinese herbal medicine that is a liquor extracted from plants by boiling, has been reported to be effective in treating schizophrenia. However, the mechanism is unclear. Abnormal demyelination has been implicated in schizophrenia. The aim of this study was to investigate the effect of SZASD on myelin in demyelinated mice exhibiting schizophrenia-like behaviors. Sixty male C57BL/6 mice were randomly divided into six groups (n = 10 per group): (1) control group, (2) cuprizone (CPZ, a copper chelator that induced demyelination, 0.2% w/w)+saline, (3) CPZ+low-dose SZASD (8.65 g·kg-1·d-1), (4) CPZ+medium-dose SZASD (17.29 g·kg-1·d-1), (5) CPZ+high-dose SZASD (25.94 g·kg-1·d-1), and (6) CPZ+quetiapine (QTP, an atypical antipsychotic that served as a positive treatment control, 10 mg·kg-1·d-1). Mice in groups 2-6 were treated with CPZ added to rodent chow for six weeks to induce demyelination. During the last two weeks, these mice were given an oral gavage of sterile saline, SZASD, or quetiapine. Behavioral tests and brain analyses were conducted after the last treatment. The brain expression of myelin basic protein (MBP) and neuregulin-1 (NRG-1) was assessed using immunohistochemistry and Western blots. CPZ induced significant schizophrenia-like behaviors in the mice, including reduced nest-building activity and sensory gating deficits. Hyperlocomotor activity was accompanied by significant reductions in MBP expression in the corpus callosum, hippocampus, and cerebral cortex. However, both QTP and SZASD significantly reversed the schizophrenia-like behaviors and demyelination in CPZ-fed mice. The QTP and medium-dose SZASD resulted in better therapeutic effects compared to the low and high SZASD doses. Reduced NRG-1 expression was observed in CPZ-fed mice compared with controls, but neither QTP nor SZASD showed significant influence on NRG-1 expression in the hippocampus. Together, SZASD showed a therapeutic effect on demyelinated mice, and the improvement of demyelination might not be through the NRG-1 pathway.

12.
Microb Biotechnol ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739583

RESUMO

Pseudomonas putida KT2440 is becoming a new robust metabolic chassis for biotechnological applications, due to its metabolic versatility, low nutritional requirements and biosafety status. We have previously engineered P. putida KT2440 to be an efficient propionate producer from L-threonine, although the internal enzymes converting propionyl-CoA to propionate are not clear. In this study, we thoroughly investigated 13 genes annotated as potential thioesterases in the KT2440 mutant. One thioesterase encoded by locus tag PP_4975 was verified to be the major contributor to propionate production in vivo. Deletion of PP_4975 significantly decreased propionate production, whereas the performance was fully restored by gene complement. Compared with thioesterase HiYciA from Haemophilus influenza, thioesterase PP_4975 showed a faster substrate conversion rate in vitro. Thus, this study expands our knowledge on acyl-CoA thioesterases in P. putida KT2440 and may also reveal a new target for further engineering the strain to improve propionate production performance.

13.
Scand J Gastroenterol ; : 1-4, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33715585

RESUMO

Gastroesophageal variceal bleeding is a severe complication of cirrhotic portal hypertension. Endoscopic treatment is recommended as the first-line therapy for gastroesophageal variceal bleeding, and its therapeutic effect is closely related to the visualization of endoscopy. We reported 2 cases of gastric variceal bleeding in which clear endoscopic visualization was obtained with two simple approaches assisted by suction tube and stone retrieval basket, respectively. Endoscopic treatments were successfully conducted after the removal of giant blood clots. Serious complications were not found.

14.
Angiology ; : 33197211000492, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33719591

RESUMO

Strong inflammatory indicators such as C-reactive protein (CRP), high-sensitivity CRP (hsCRP), and hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT), and red blood cell distribution width (RDW), may be related with contrast-induced nephropathy (CIN). Our meta-analysis aimed at exploring the relationship between these indicators and CIN incidence among patients undergoing coronary intervention. Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and Science Direct from their inception to June 3, 2020. Meta-analysis was performed on pooled eligible studies. Finally, 26 studies involving 29 454 patients were included. Pooled analysis revealed that patients with higher CRP (odds ratio [OR] = 1.06, 95% CI: 1.01-1.12, P = .02), hsCRP (OR = 1.03, 95% CI: 1.01-1.06, P = .004), NLR (OR = 1.11, 95% CI: 1.01-1.20, P = .02), RDW (OR = 1.35, 95% CI: 1.19-1.53, P < .001), and lower HCT (OR = 0.94, 95% CI: 0.92-0.97, P = .003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR = 1.12, 95% CI: 0.99-1.26, P = .07). Pre-angiography CRP/hsCRP and some hematological indices are associated with CIN.

15.
Int J Mol Sci ; 22(4)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672337

RESUMO

Runt-related transcription factor-3 (Runx3) is a tumor suppressor, and its contribution to melanoma progression remains unclear. We previously demonstrated that Runx3 re-expression in B16-F10 melanoma cells changed their shape and attenuated their migration. In this study, we found that Runx3 re-expression in B16-F10 cells also suppressed their pulmonary metastasis. We performed microarray analysis and uncovered an altered transcriptional profile underlying the cell shape change and the suppression of migration and metastasis. This altered transcriptional profile was rich in Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) annotations relevant to adhesion and the actin cytoskeleton and included differentially expressed genes for some major extracellular matrix (ECM) proteins as well as genes that were inversely associated with the increase in the metastatic potential of B16-F10 cells compared to B16-F0 melanoma cells. Further, we found that this altered transcriptional profile could have prognostic value, as evidenced by myelin and lymphocyte protein (MAL) and vilin-like (VILL). Finally, Mal gene expression was correlated with metastatic potential among the cells and was targeted by histone deacetylase (HDAC) inhibitors in B16-F10 cells, and the knockdown of Mal gene expression in B16-F0 cells changed their shape and enhanced the migratory and invasive traits of their metastasis. Our study suggests that self-entrapping of metastatic Runx3-negative melanoma cells via adhesion and the actin cytoskeleton could be a powerful therapeutic strategy.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33683097

RESUMO

An optical organic vapor sensor array based on colorimetric or fluorescence changes quantified by spectroscopy provides an efficient method for realizing rapid identification and detection of organic vapor, but improving the sensitivity of the optical organic vapor sensor is challenging. Here, AIE/polymer (AIE, ggregation-induced emission) composites into microwires arrays are fabricated as organic vapor sensors with specific recognition and high sensitivity for different vapors using the capillary-bridge-mediated assembly method. Such organic vapor sensor successfully detects organic vapor relying on a swelling-induced fluorescence change of the AIE/polymer composites, combating the unique property of AIE molecules and vapor absorption-induced polymer swelling. A series of AIE/polymer composites into microwires arrays with four different groups on the AIE molecule and four different side chains on the polymer is fabricated to detect four different organic vapors. The mechanism for improved sensitivity of the AIE/polymer composites microwires arrays sensors is the same because of the similar polarity between the group of AIE molecules and the vapor molecules. Molecular design of the side chains of the polymer and the groups of AIE molecules based on the polarity of the targeted vapor molecule can enhance the sensitivity of the sensors to the subparts per million level.

17.
J Neuroinflammation ; 18(1): 65, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33673857

RESUMO

BACKGROUND: As a classic innate immunity pathway, Toll-like receptor 4 (TLR4) signaling has been intensively investigated for its function of pathogen recognition. The receptor is located not only on immune cells but also on sensory neurons and spinal glia. Recent studies revealed the involvement of neuronal TLR4 in different types of pain. However, the specific role of TLR4 signaling in the pain symptom of endometriosis (EM) remains obscure. METHODS: The rat endometriosis model was established by transplanting uterine horn tissue into gastrocnemius. Western blotting and/or immunofluorescent staining were applied to detect high mobility group box 1 (HMGB1), TLR4, myeloid differentiation factor-88 adaptor protein (MyD88), and nuclear factor kappa-B-p65 (NF-κB-p65) expression, as well as the activation of astrocyte and microglia. The antagonist of TLR4 (LPS-RS-Ultra, LRU) and MyD88 homodimerization inhibitory peptide (MIP) were intrathecally administrated to assess the behavioral effects of blocking TLR4 signaling on endometriosis-related pain. RESULTS: Mechanical hyperalgesia was observed at the graft site, while HMGB1 was upregulated in the implanted uterine tissue, dorsal root ganglion (DRG), and spinal dorsal horn (SDH). Compared with sham group, upregulated TLR4, MyD88, and phosphorylated NF-κB-p65 were detected in the DRG and SDH in EM rats. The activation of astrocytes and microglia in the SDH was also confirmed in EM rats. Intrathecal application of LRU and MIP alleviated mechanical pain on the graft site of EM rats, with decreased phosphorylation of NF-κB-p65 in the DRG and reduced activation of glia in the SDH. CONCLUSIONS: HMGB1-TLR4-MyD88 signaling pathway in the DRG and SDH may involve in endometriosis-related hyperpathia. Blockade of TLR4 and MyD88 might serve as a potential treatment for pain in endometriosis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33647184

RESUMO

Complex coacervation enables important wet adhesion processes in natural and artificial systems. However, existed synthetic coacervate adhesives show limited wet adhesion properties, non-thermoresponsiveness, and inferior biodegradability, greatly hampering their translations. Herein, by harnessing supramolecular assembly and rational protein design, we present a temperature-sensitive wet bioadhesive fabricated through recombinant protein and surfactant. Mechanical performance of the bioglue system is actively tunable with thermal triggers. In cold condition, adhesion strength of the bioadhesive was only ~50 kPa. By increasing temperature, the strength presented up to 600 kPa, which is remarkably stronger than other biological counterparts. This is probably due to the thermally triggered phase transition of the engineered protein and the formation of coacervate, thus leading to the enhanced wet adhesion bonding. This strategy holds great promise for the fabrication of smart biomaterials such as new generation of thermo-responsive patches for healthcare applications.

19.
Front Cell Infect Microbiol ; 11: 631960, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718281

RESUMO

Enterocytozoon hepatopenaei (EHP) infection has become a significant threat in shrimp farming industry in recent years, causing major economic losses in Asian countries. As there are a lack of effective therapeutics, prevention of the infection with rapid and reliable pathogen detection methods is fundamental. Molecular detection methods based on polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) have been developed, but improvements on detection speed and convenience are still in demand. The isothermal recombinase polymerase amplification (RPA) assay derived from the recombination-dependent DNA replication (RDR) mechanism of bacteriophage T4 is promising, but the previously developed RPA assay for EHP detection read the signal by gel electrophoresis, which restricted this application to laboratory conditions and hampered the sensitivity. The present study combined fluorescence analysis with the RPA system and developed a real-time RPA assay for the detection of EHP. The detection procedure was completed in 3-7 min at 39°C and showed good specificity. The sensitivity of 13 gene copies per reaction was comparable to the current PCR- and LAMP-based methods, and was much improved than the RPA assay analyzed by gel electrophoresis. For real clinical samples, detection results of the real-time RPA assay were 100% consistent with the industrial standard nested PCR assay. Because of the rapid detection speed and the simple procedure, the real-time RPA assay developed in this study can be easily assembled as an efficient and reliable on-site detection tool to help control EHP infection in shrimp farms.

20.
Biomed Chromatogr ; : e5108, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33650162

RESUMO

A rapid ultra-fast liquid chromatography tandem mass spectrometry method was developed and validated to determine ginsenosides Rk1 and Rg5, a pair of isomers, in rat plasma, which was successfully applied to their pharmacokinetic studies. Two ginsenosides were given to male Sprague-Dawley rats via intragastrical and intravenous routes, respectively, and the impact of double bond position on the pharmacokinetic features of the two ginsenosides was elucidated in rats. Ginsenoside Rg3 was used as internal standard and ethyl acetate was applied to extract analytes and internal standard. Chromatographic separation was carried out on a reverse-phase UPLC HSS T3 column (100 × 2.1 mm, 1.8 µm). The flow rate was set to 0.4 ml/min. The fragmentation transition was m/z 765.4 → m/z 101.1 for two ginsenosides. The mobile phases were composed of 0.1% formic acid aqueous solution and acetonitrile. The linear range was 2-1,000 ng/ml for the two ginsenosides. Intra- and inter-day precisions were <11.67%, and accuracy fluctuated from -7.44 to 6.78%. The extraction recovery, matrix effect and stability were within acceptable levels. After treatment with ginsenosides Rk1 and Rg5, some differences were found in their pharmacokinetic profiles in rats. The maximum plasma drug concentration and the area under the plasma drug concentration-time curve of ginsenoside Rg5 were about 5 times bigger than those of ginsenoside Rk1 after oral administration, and 3 times higher after intravenous administration. The oral bioavailabilities of ginsenosides Rk1 and Rg5 were 0.67 and 0.97%, respectively. The results indicated that ∆20(22) -ginsenosides showed better pharmacokinetic features than ∆20(21) -ginsenosides with the same glycosylation.

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