Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 370
Filtrar
1.
Anaesthesia ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31833064

RESUMO

It is unknown whether systolic blood pressure augmentation during endovascular thrombectomy improves clinical outcomes. This pilot randomised controlled trial aimed to assess the feasibility of differential systolic blood pressure targeting during endovascular thrombectomy procedures for anterior circulation ischaemic stroke. Fifty-one eligible patients fulfilling the national criteria for endovascular thrombectomy were randomly assigned to receive either standard or augmented systolic blood pressure management from the start of anaesthesia to recanalisation of the target vessel. Systolic blood pressure targets for the standard and augmented groups were 130-150 mmHg and 160-180 mmHg, respectively. The study achieved all feasibility targets, including a recruitment rate of 3.5 participants per week and median (IQR [range]) of mean systolic blood pressure separation between groups of 139 (135-143 [115-154]) vs. 167 (150-175 [113-188]) mmHg, p < 0.001. Data completeness was 99%. Independent functional recovery at 90 days (modified Rankin Scale 0, 1 or 2) was achieved in 30 (59%) patients, which is consistent with previously published data. There were no safety concerns with trial procedures. In conclusion, a large randomised controlled efficacy trial of standard vs. augmented systolic blood pressure management during endovascular thrombectomy is feasible.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31765604

RESUMO

RATIONALE: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown. OBJECTIVES: To evaluate the effect of oral treprostinil compared to placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy. METHODS: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for >30 days prior to randomization and had a 6-minute walk distance ≥150 m. The primary end point was the time to first adjudicated clinical worsening event: death, hospitalization due to worsening PAH, initiation of inhaled or parenteral prostacyclin therapy, disease progression, or unsatisfactory long-term clinical response. RESULTS: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio 0.74; 95% confidence interval [CI], 0.56 to 0.97; P=0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal-pro-brain natriuretic peptide, all favored oral treprostinil treatment at week 24 and beyond. A non-invasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from study weeks 12 through 60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting. CONCLUSIONS: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www.clinicaltrials.gov, ID NCT01560624.

3.
Zhonghua Nei Ke Za Zhi ; 58(10): 751-757, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31594173

RESUMO

Objective: To investigate the characteristics of body composition (BC) in gout patients and its clinical significance. Methods: Consecutive gout patients were recruited between August 2017 and December 2018. Demographic information, clinical characteristics and comorbidities were collected. BC was assessed by bioelectric impedance analysis including body fat percentage (BF%), trunk and limb BF%, appendicular skeletal muscle index. Overfat was defined by BF% ≥25% for male and ≥35% for female. The association between BC and serum uric acid (sUA) was evaluated by multiple linear regression. Results: A total of 362 gout patients were recruited with median age 38 (30, 52) years, 96.1% (348/362) were male. Mean sUA was (551±133) µmol/L. The mean BF% was (25.8±6.4)% with 53.6%(194/362) patients overfat. Male gout patients with overfat showed more affected joints [4(2, 6) vs. 2(2, 5)], higher sUA [(576±126)µmol/L vs. (523±134) µmol/L], higher prevalence of dyslipidemia [70.1%(131/187) vs. 54.0%(87/161)], metabolic syndrome [60.8%(118/187) vs. 28.0%(47/161)], fatty liver [58.2%(113/187) vs. 35.1%(59/161)] and hypertension [44.4%(83/187) vs. 25.5%(41/161)] than male patients with normal fat (all P<0.05). Their BF%, trunk BF% and limb BF% were positively correlated with the numbers of affected joints, sUA, metabolic syndrome, fatty liver, and hypertension, respectively (r=0.154-0.435, all P<0.05). Multivariable linear regression suggested that BF% (ß=4.29, P=0.020) and trunk BF% (ß=9.11, P=0.007), but not limb BF%, were positively correlated with sUA. Conclusion: Overfat is very common in gout patients. The proportion of trunk fat in male patients is positively correlated with sUA. When assessing obesity in gout patients clinically, body composition analysis should be performed simultaneously.


Assuntos
Composição Corporal/fisiologia , Gota/diagnóstico , Obesidade/epidemiologia , Ácido Úrico/sangue , Adulto , Dislipidemias/epidemiologia , Feminino , Gota/sangue , Gota/epidemiologia , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/sangue , Prevalência
5.
Artigo em Chinês | MEDLINE | ID: mdl-31315358

RESUMO

Objective: To explore the role of autophagy in PM2.5-induced inflammation in human nasal epithelial cells and related mechanism. Methods: Human nasal epithelial cells were exposed to different concentration of PM2.5 for different times, and the expression levels of microtubule-associated protein-1 light chain-3 Ⅱ (LC3 Ⅱ) and Beclin1 proteins were measured by Western blot. The typical autophagosome and autolysosome were observed by using transmission electron microscopy (TEM). To observe autophagic flux, mRFP-GFP-LC3 plasmid was transfected to nasal epithelial cells and the punctate staining of mRFP-GFP-LC3 were determined by confocal laser scanning microscope. The expression of inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell culture supernatant were assessed by enzyme-linked immunosorbent assay (ELISA). To assess the role of autophagy in PM2.5-mediated inflammation, autophagy related gene Atg5 and Beclin-1 were silenced by siRNA knockdown, and inflammatory cytokines were analyzed.GraphPad Prism 6.0 was used for statistical analysis. Results: PM2.5 exposure increased the expression of LC3 Ⅱ and Beclin-1 proteins in a dose- (in PM2.5 group with concentration of 0, 15, 30, 60, 120 µg/ml, the expression of LC3 Ⅱ was 0.021±0.001(x±s), 0.037±0.002, 0.058±0.005, 0.075±0.006, 0.085±0.004, respectively, F=126.8, P<0.05; the expression of Beclin-1 was 0.002±0.000, 0.003±0.000, 0.005±0.000, 0.007±0.001, 0.008±0.001, respectively, F=137.3, P<0.05) and time-dependent manner (in PM2.5 group with exposure time of 0, 3, 6, 12, 24 h, the expression of LC3Ⅱ was 0.160±0.007, 0.222±0.003, 0.251±0.015, 0.483±0.029, 0.585±0.035, respectively, F=215.3, P<0.05; the expression of Beclin-1 was 0.059±0.002, 0.080±0.002, 0.087±0.002, 0.183±0.007, 0.228±0.005, respectively, F=137.3, P<0.05) in human nasal epithelial cells. TEM analysis showed typical autophagosome and autolysosome in cells after PM2.5 exposure for 24 h. PM2.5 significantly increased the number of yellow and red dots representing autophagosomes and autolysosomes respectively, indicating autophagic flux was elevated. Moreover, PM2.5 enhanced the secretion of inflammatory cytokines such as IL-6 and TNF-α, which was dramatically prevented by Atg5-siRNA and Beclin-1-siRNA. Conclusion: Autophagy plays an important role in PM2.5-caused inflammation response in nasal epithelial cells, which can induce release of inflammatory factors such as IL-6 and TNF-α and advance the inflammatory reaction.


Assuntos
Autofagia/imunologia , Células Epiteliais/imunologia , Inflamação/imunologia , Mucosa Nasal/imunologia , Material Particulado/imunologia , Proteína Beclina-1/biossíntese , Humanos , Interleucina-6/biossíntese , Proteínas Associadas aos Microtúbulos/biossíntese , Material Particulado/efeitos adversos , Fator de Necrose Tumoral alfa/biossíntese
6.
Pulm Circ ; 9(3): 2045894019856471, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215336

RESUMO

Treprostinil, a prostacyclin analogue, is approved for the treatment of pulmonary arterial hypertension (PAH) in adults. Transition from parenteral to oral treprostinil has been successfully accomplished in adults with PAH but not in children. In this multicenter study, pediatric patients treated with parenteral (Cohort 1) or inhaled (Cohort 2) treprostinil were transitioned to oral treprostinil. Prostacyclin-naïve individuals on background oral PAH therapy received oral treprostinil as add-on therapy (Cohort 3). Successful transition was oral treprostinil dose maintenance through week 24. Patients were monitored for adverse events (AEs), 6-min walk distance (6MWD), PAH symptoms, World Health Organization (WHO) Functional Class (FC), cardiac magnetic resonance imaging (cMRI), cardiopulmonary exercise testing (CPET), and quality of life through 24 weeks. A total of 32 patients were enrolled in the study; 23 (72%) were girls (mean age = 12.2 years). All patients were on background oral PAH therapy. Overall, patients (96.9%) maintained transition to oral treprostinil; one patient (Cohort 1) transitioned to oral treprostinil, then back to parenteral after experiencing syncope and WHO FC change from II to III. Cohorts 1, 2, and 3 received a final mean oral treprostinil dose of 5.6, 3.3, and 4.5 mg t.i.d., respectively. All cohorts had variable changes in 6MWD, cMRI, and CPET. Overall, 12 serious AEs were reported. All patients had drug-related AEs including headache (81%), diarrhea (69%), nausea (66%), vomiting (66%), and flushing (56%). Pediatric patients maintained transition to oral treprostinil with preservation of exercise capacity and WHO FC. Prostanoid-related AEs were most common and similar to those reported in adults.

7.
Zhonghua Xue Ye Xue Za Zhi ; 40(5): 417-421, 2019 May 14.
Artigo em Chinês | MEDLINE | ID: mdl-31207708

RESUMO

Objective: To monitor the WT1 mRNA level and its dynamic changes in patients with myelodysplastic syndromes (MDS) after hypomethylating agents (HMA) , as well as to assess the significance of WT1 mRNA levels and its dynamic changes in evaluating the efficacy of HMA and distinguishing the disease status of heterogeneous patients with stable disease (SD) . Methods: Bone marrow or peripheral blood samples of 56 patients with MDS who underwent hypomethylating agents (≥4 cycles) from November 2009 to March 2018 were tested by real-time quantitative polymerase chain reaction (PCR) to detect the expression of WT1 mRNA, and to observe the correlation between the dynamic changes of WT1 mRNA expression and clinical efficacy and prognosis of patients. Results: WT1 mRNA expression levels of MDS patients decreased significantly after 3 cycles of hypomethylating agent treatment. Besides, the WT1 mRNA expression levels of patients increased significantly after diseases progression. According to the dynamic changes of WT1 mRNA expression levels during SD, 45 cases could be further divided into increased group and non-increased group. In those SD patients with increased WT1 mRNA expression level, the ratio of suffering disease progression or transformation to AML was 95.65% (22/23) , whereas the ratio turned to be 9.09% (2/22) for the non-increased group (χ(2)=33.852, P<0.001) . Compared with those SD patients reporting no increase in WT1 mRNA expression level, the overall survival[17 (95%CI 11-23) months vs not reached, P<0.001] and progression-free survival [13 (95%CI 8-18) months vs not reached, P<0.001] of those SD patients reporting increase in WT1 mRNA expression level were significantly shorter. Conclusion: WT1 mRNA expression level is a useful indicator to assess the efficacy of hypomethylating agents in MDS patients. Especially in patients with SD, detection of the changes in WT1 mRNA expression level is able to predict disease progression and help to make clinical decision.


Assuntos
Síndromes Mielodisplásicas , Proteínas WT1/genética , Medula Óssea , Humanos , Síndromes Mielodisplásicas/genética , Prognóstico , RNA Mensageiro
8.
BMC Plant Biol ; 19(1): 172, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039740

RESUMO

BACKGROUND: Angiosperm sex chromosomes, where present, are generally recently evolved. The key step in initiating the development of sex chromosomes from autosomes is the establishment of a sex-determining locus within a region of non-recombination. To better understand early sex chromosome evolution, it is important to determine the process by which recombination is suppressed around the sex determining genes. We have used the dioecious angiosperm kiwifruit Actinidia chinensis var. chinensis, which has an active-Y sex chromosome system, to study recombination rates around the sex locus, to better understand key events in the development of sex chromosomes. RESULTS: We have confirmed the sex-determining region (SDR) in A. chinensis var. chinensis, using a combination of high density genetic mapping and fluorescent in situ hybridisation (FISH) of Bacterial Artificial Chromosomes (BACs) linked to the sex markers onto pachytene chromosomes. The SDR is a subtelomeric non-recombining region adjacent to the nucleolar organiser region (NOR). A region of restricted recombination of around 6 Mbp in size in both male and female maps spans the SDR and covers around a third of chromosome 25. CONCLUSIONS: As recombination is suppressed over a similar region between X chromosomes and between and X and Y chromosomes, we propose that recombination is suppressed in this region because of the proximity of the NOR and the centromere, with both the NOR and centromere suppressing recombination, and this predates suppressed recombination due to differences between X and Y chromosomes. Such regions of suppressed recombination in the genome provide an opportunity for the evolution of sex chromosomes, if a sex-determining locus develops there or translocates into this region.


Assuntos
Actinidia/genética , Cromossomos de Plantas , Recombinação Genética , Cromossomos Sexuais , Actinidia/citologia , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos , Variação Genética , Hibridização in Situ Fluorescente , Repetições de Microssatélites
9.
Artigo em Chinês | MEDLINE | ID: mdl-31137096

RESUMO

Objective: To investigate the effect of PM2.5 exposure on nasal inflammatory cytokines and nasal mucosal pathology in a rat model of allergic rhinitis (AR). Methods: Twenty-four healthy female SD rats were randomly divided into 3 groups by random number table method, with 8 rats in each group: normal control group (NC group), ovalbumin (OVA) induced AR model (AR group), and AR model group inhaled to PM2.5 at 200 µg/m(3), 3 h/d, for 30 d (ARE group). Nasal symptoms including sneezing, nasal rubs and nasal secretion were recorded. Levels of OVA specific IgE in serum, interleukin 6 (IL-6) and tumor necrosis factor-ɑ (TNF-ɑ) in nasal irrigating solution were measured by enzyme-linked immunosorbent assay (ELISA). The histopathological changes of nasal mucosa were observed by HE staining. SPSS 17.0 software was used to analyze the data. Results: The number of sneezing, nasal rubs and the amount of nasal secretion in the ARE group were significantly higher than that in the AR group and the NC group (number of sneezing (15.38±1.68) times/15 min vs (11.63±1.13) times/15 min vs (1.75±0.71) times/15 min, number of nasal rubs (27.75±2.12) times/15 min vs (21.25±2.96) times/15 min vs (5.25±1.04) times/15 min, amount of nasal secretion (18.90±2.07) mg vs (13.83±1.81) mg vs (3.78±0.41) mg, F values was 236.089, 224.139, 183.971, respectively, all P<0.001). Statistically significant differences in OVA specific IgE, IL-6 and TNF-ɑ levels were observed in ARE group exceeded AR group and NC group (OVA specific IgE (25.42±2.51) ng/ml vs (18.07±1.07) ng/ml vs (1.47±0.26) ng/ml, IL-6 (123.30±18.86) pg/ml vs (63.49±11.29) pg/ml vs (16.87±3.29) pg/ml, TNF-ɑ (162.50±38.15) pg/ml vs (72.96±11.28) pg/ml vs (27.52±4.15) pg/ml, F values was 481.604, 138.277, 63.938, respectively, all P<0.001). HE staining showed that the nasal epithelial cells of NC group were intact and neatly arranged. Nasal mucosa epithelial cells were arranged in disorder in AR group, with tissue structure swelling. Partial shedding of nasal epithelial cells, mucosal basement membrane thickening, submucosal tissue interstitial edema, vasodilation and gland hyperplasia were found in ARE group. Conclusion: An increase inflammatory factors level such as IL-6 and TNF-ɑ aggravates pathological damage of nasal mucosa in a rat model of AR by exposure to PM2.5.


Assuntos
Eosinófilos , Mucosa Nasal , Rinite Alérgica , Animais , Modelos Animais de Doenças , Feminino , Mucosa Nasal/imunologia , Ovalbumina , Material Particulado , Ratos , Ratos Sprague-Dawley , Rinite Alérgica/imunologia
10.
Zhonghua Yi Xue Za Zhi ; 99(7): 505-509, 2019 Feb 19.
Artigo em Chinês | MEDLINE | ID: mdl-30786347

RESUMO

Objective: To explore the effect of cathepsin (Cat) S in primary biliary cholangitis (PBC). Methods: The serum of PBC patients and Hepatitis B virus (HBV) patients were collected in Peking Union Medical College Hospital from August 2016 to July 2017 and the liver tissue of PBC were collected from March 2010 to July 2013. Indirect enzyme-linked immunosorbent assay (ELISA) was used to detect the serum concentrations of total-and pro-Cat S respectively in 24 PBC patients, 24 Hepatitis B patients and 24 healthy controls. The relation between the serum levels of Cat S and cholestasis biochemical indexes and the serum levels of immunoglobulin (Ig) M, G were analyzed. Immunofluorescence analysis of liver tissue was performed to detect macrophage infiltration and Cat S expression. The data was analyzed by student's t-test, spearman correlation analysis, and receiver operating characteristic (ROC) curve was used to obtain an optimal cutoff value. Results: The serum levels of total-Cat S, pro-Cat S and active-Cat S in PBC group were significantly higher than those in healthy controls and HBV controls (P<0.05). There was a correlation between serum total-Cat S and ALP and GGT in patients with PBC (P<0.05). There was a moderate correlation between pro-Cat S and ALP and GGT (P<0.05) and total Cat S was associated with IgG (P<0.05). The area under ROC curve (AUC) of total-Cat S, pro-Cat S and active-Cat S was 0.85(P<0.01), 0.65(P<0.05) and 0.77(P<0.01), respectively. The optimal cut-off value was 11.30、7.81 and 5.93 pg/L, respectively, with the sensitivity of 0.81, 0.53 and 0.53 and specificity of 0.82, 0.81 and 0.96. Liver tissue immunofluorescence revealed macrophage infiltration in the liver of PBC patients. The average percentage of macrophages and Cat S co-expressed cells in mononuclear cells was 23.77%. Conclusion: The expression of Cat S in serum of patients with PBC is significantly higher than that of healthy controls and HBV patients, and is related to IgG and serum ALP, r-GT levels. Liver tissue macrophages were co-expressed with Cat S. Cat S may participate in the process of antigen presentation in the pathogenesis of PBC.


Assuntos
Colangite , Cirrose Hepática Biliar , Catepsinas , Humanos
11.
Clin Exp Dermatol ; 44(4): e110-e117, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30734345

RESUMO

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is a chronic pruritic skin disorder. The genetic basis of familial (f)PLCA involves mutations in the oncostatin M receptor (OSMR) and interleukin-31 receptor A (IL31RA) genes, but the disease pathophysiology is not fully understood. AIM: To investigate the OSMR mutation spectrum in patients with sporadic (s)PLCA/fPLCA, lichen/macular PLCA in mainland China. METHODS: This study was carried out on 64 patients with sPLCA, along with 36 with fPLCA and 10 unaffected individuals collected from 23 unrelated Chinese families. Genomic DNA was extracted from peripheral blood samples. Mutation screening of 17 OSMR exons was performed by Sanger sequencing. RESULTS: PLCA lesions are typically localized to the shins, forearm and back. Sequence analysis of OSMR exons demonstrated that the OSMR missense mutation rate in patients with fPLCA (63.89%) was significantly higher than that in patients with sPLCA (34.38%). The male/female ratio of patients carrying a homozygous OSMR mutation (0.29) was significantly lower than that of patients carrying a heterozygous OSMR mutation (1.08; P < 0.05) and of patients with wildtype OSMR (1.75; P < 0.01). Age of onset of PLCA with OSMR homozygous mutation (median age 20 years) was earlier than that of PLCA with OSMR heterozygous mutation (median age 32 years; P < 0.01) or PLCA with wildtype genotype (median age 32 years; P < 0.01). CONCLUSION: The present data indicate OSMR mutations as not only the main cause of fPLCA, but also the potential source of the pathogenesis of sPLCA, although the exact molecular mechanism remains unknown.


Assuntos
Amiloidose Familiar/genética , Grupo com Ancestrais do Continente Asiático/genética , Dermatopatias Genéticas/genética , Adolescente , Adulto , Idoso , Amiloidose Familiar/patologia , Criança , China , Éxons , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Mutação de Sentido Incorreto , Subunidade beta de Receptor de Oncostatina M , Linhagem , Receptores de Interleucina , Análise de Sequência de DNA/métodos , Dermatopatias Genéticas/patologia , Adulto Jovem
12.
Animal ; 13(9): 1826-1833, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30789107

RESUMO

Alanyl-glutamine (Ala-Gln), a highly soluble and stable glutamine dipeptide, is known to improve gut integrity and function. The aim of this study was to evaluate whether dietary Ala-Gln supplementation could improve growth performance, intestinal development and digestive-absorption function in weaned piglets. A total of 100 purebred Yorkshire piglets weaned at 21 days of age were assigned randomly to four dietary treatment groups and fed a basal diet (control group) or a basal diet containing 0.15%, 0.30% and 0.45% Ala-Gln, respectively. Compared with the control group, piglets fed the Ala-Gln diets had higher average daily gain and lower feed : gain and diarrhea rate (P < 0.05). Moreover, dietary Ala-Gln supplementation increased villous height and villous height : crypt depth ratio in duodenum and jejunum (P < 0.05), as well as the activities of maltase and lysozyme in jejunum mucosa (P < 0.05). In addition, a decrease in serum diamine oxidase activity and crypt depth in duodenum and jejunum was observed in piglets fed the Ala-Gln diets (P < 0.05). Serum cytosolic phospholipase A2 (cPLA2) concentration and gene expression of cPLA2, Na+-dependent glucose transporter 1, glucose transporter 2 and peptide transporter 1 in jejunum were increased by feeding Ala-Gln diets relative to control diet (P < 0.05). These results indicated that feeding Ala-Gln diet has beneficial effects on the growth performance of weaned piglets, which associated with maintaining intestinal morphology and digestive-absorption function.


Assuntos
Suplementos Nutricionais , Dipeptídeos/farmacologia , Suínos/crescimento & desenvolvimento , Animais , Dieta/veterinária , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/anatomia & histologia , Intestinos/efeitos dos fármacos , Masculino , Suínos/anatomia & histologia , Suínos/metabolismo , Desmame
13.
Zhonghua Shao Shang Za Zhi ; 35(1): 40-47, 2019 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-30678400

RESUMO

To investigate the effects of adipose-derived mesenchymal stem cells (AMSCs) from type 2 diabetes mellitus patients on wound healing of pressure ulcers in mice. Methods: (1) In September 2016, the subcutaneous adipose tissue of a 60-year-old woman with type 2 diabetes mellitus was harvested, and then AMSCs were extracted by collagenase digestion and cultured. The third passage of cells were used for subsequent experiments. The morphology of cells was observed, and their osteogenic, chondrogenic, and adipogenic differentiation abilities were identified. The expressions of cell surface markers CD90, CD105, CD73, and CD34 were detected by flow cytometer (n=3). (2) Sixteen female C57BL/6 wild-type mice aged 6-8 weeks were selected, and one pressure ulcer wound was created on each side of the spine of each mouse by pressing the skin with two magnets. The two wounds of each mouse were paired and divided into diabetic AMSCs group and negative control group, injected with 100 µL phosphate buffer solution (PBS) containing green fluorescent protein-labeled AMSCs (1×10(6) cells) and 100 µL PBS, respectively. The wound healing status of the two groups within post injection day (PID) 21 was observed, and their wound healing rates on PID 5, 13, and 17 were calculated. Three mice were sacrificed on PID 11 and 21, respectively, and tissue of three wounds was harvested from each group. The skin structure was observed by hematoxylin-eosin staining, the collagen deposition was evaluated by Masson staining, and the positive expression of CD31, i. e., the number of new blood vessels was counted by immunohistochemistry. Wound tissue samples of two groups prepared on PID 21 as above-mentioned were harvested, and the positive cell rate of S100, representing the regeneration of Schwann cells, was detected by immunohistochemistry. Wound tissue samples of diabetic AMSCs group prepared on PID 11 as above-mentioned were harvested, and the colonization of AMSCs was observed by fluorescence tracer method. Data were processed with paired t test and Bonferroni correction. Results: (1) The third passage of cells isolated and cultured from the subcutaneous adipose tissue of a type 2 diabetes mellitus patient grew adherently to the wall in a long spindle and vortex-like manner. After induction, the cells showed osteogenic, chondrogenic, and lipogenic differentiation abilities. The positive expression rates of CD90, CD105, and CD73 on the cell surface were higher than 90.00%, and the expression rate of CD34 was 0.46%. The cells were identified as AMSCs. (2) The mice wounds of diabetic AMSCs group healed quickly, and all the wounds healed completely on PID 17, while the mice wounds in negative control group were not completely closed at this time, and there was still scab on the surface. On PID 5, 13, and 17, the healing rates of mice wounds of diabetic AMSCs group were (35.6±6.5)%, (87.1±2.5)%, and 100.0%, respectively, significantly higher than (19.8±7.2)%, (66.2±5.2)%, and (86.9±5.3)% of negative control group (t=6.49, 14.31, 9.73, P<0.05). Compared with that of negative control group, the inflammatory cell infiltration was reduced in mice wounds tissue of diabetic AMSCs group on PID 11, and thicker epidermis and dermis as well as regenerated skin appendages were observed on PID 21. On PID 11 and 21, the collagen percentages of mice wounds tissue in diabetic AMSCs group was (48.3±1.3)% and (54.1±1.7)%, respectively, significantly higher than (41.4±1.7)% and (50.3±1.2)% of negative control group (t=6.98, 3.99, P<0.01). On PID 11 and 21, the numbers of new blood vessels in mice wounds tissue of diabetic AMSCs group were 17.2±1.3 and 18.0±2.1, respectively, significantly more than 8.0±1.4 and 14.0±1.5 of negative control group (t=10.69, 3.38, P<0.01). On PID 21, the S100 positive cell percentage in mice wounds tissue of diabetic AMSCs group was (1.76±0.12)%, significantly higher than (0.55±0.03)% of negative control group (t=21.68, P<0.001). On PID 11, the colonization of AMSCs in mice wounds tissue of diabetic AMSCs group was observed. Conclusions: Transplantation of AMSCs from type 2 diabetic mellitus patients can accelerate wound healing of pressure ulcers in mice by promoting angiogenesis, collagen deposition, and Schwann cell regeneration.


Assuntos
Células-Tronco Mesenquimais , Lesão por Pressão/terapia , Cicatrização , Animais , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL
14.
J Natl Med Assoc ; 111(2): 122-133, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30100090

RESUMO

INTRODUCTION: Black individuals continue to be underrepresented in clinical trials despite efforts by the National Institutes of Health and the Federal Drug Administration to increase their enrollment. Health care providers play a critical role in the recruitment of patients into clinical trials, as they have established relationships and are uniquely positioned to make referrals for participation. While prior initiatives have focused on training black physicians to conduct clinical research, we sought to determine the potential of utilizing a professional organization as a resource to identify established investigators to champion recruitment of underrepresented racial and ethnic populations. The Association of Black Cardiologists (ABC) is a non-profit organization with a mission to eliminate racial and ethnic disparities in cardiovascular disease and may provide a conduit for recruiting investigators. The purpose of this study was to examine the feasibility of using the ABC membership to identify investigators with an established track record in clinical trials. METHODS/RESULTS: Utilizing a roster of ABC members, we searched Scopus to quantify ABC member publications from 1999 to 2015 and identify members who have been active in clinical trials. Within the membership of 2037 individuals, we identified 794 with peer-reviewed publications, and 109 who co-authored manuscripts involving randomized clinical trials. The manuscripts largely focused on hypertension and heart failure, conditions that have a disproportionately greater affect on black individuals. CONCLUSION: Members of the ABC have varied amounts of research productivity. We identified a group of experienced investigators to engage in efforts aimed at recruiting/enrolling underrepresented racial and ethnic populations in clinical trials of cardiovascular disease.


Assuntos
Afro-Americanos , Bibliometria , Pesquisa Biomédica/organização & administração , Cardiologia , Ensaios Clínicos como Assunto/organização & administração , Sociedades Médicas , Autoria , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Encaminhamento e Consulta
15.
Benef Microbes ; 10(7): 729-739, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31965842

RESUMO

Formula-fed infants are more susceptible to infectious diseases because they lack the maternal immune factors transferred from breast milk, while their own immune system is still immature. As timely probiotic administration was suggested to promote immune system development in formula-fed infants, this study aimed at assessing the safety and the effects of a probiotic supplement (Bifidobacterium infantis R0033, Bifidobacterium bifidum R0071, and Lactobacillus helveticus R0052) on mucosal immune competence and digestive function in formula-fed infants. Healthy infants (3.5-6 months old) were randomised to receive either probiotic- (n=66) or placebo-supplemented (n=66) formula once a day for four weeks. In the probiotics group, faecal secretory immunoglobulin A (SIgA) levels remained similar between visit 2 (baseline; V2) and visit 3 (end-of-treatment; V3), but decreased in the placebo group. Changes in SIgA levels following treatment (log10ΔV3-V2 [95%CI]) between the probiotic and placebo groups were statistically significant (23 ng/dl [-57;102] and -137 ng/dl [-212;-62], respectively (P=0.0044; ANCOVA)). While log10ΔV3-V2 [95%CI] for salivary SIgA levels increased in both groups, this trend was more pronounced in the probiotics than in the placebo group with an increase of 123 ng/dl [9;236] and 37 ng/dL [-72;147], respectively (P=0.2829; ANCOVA). The weekly average number of stools/day was significantly higher in the probiotics group compared to placebo during the last week of treatment for the per protocol population. There was no difference in microbiota composition or anthropometric parameters between groups. No serious adverse event was reported, and all adverse events were mild and unrelated to the product or study. Our results show that formula-fed infants receiving probiotics maintained higher faecal SIgA levels at the end of the four-week treatment period, suggesting a positive effect of probiotics on SIgA production. This study demonstrates the safety of this probiotic formulation in infants. Formula-fed infants may benefit from probiotics supplementation to sustain the development of mucosal immunity.

16.
Eur Rev Med Pharmacol Sci ; 22(23): 8063-8075, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30556841

RESUMO

OBJECTIVE: To investigate the role of NLRP12 in regulating Pseudomonas aeruginosa (P. aeruginosa) keratitis. MATERIALS AND METHODS: Real-Time-PCR and Western blot were performed to measure the NLRP12 level in corneas and bone marrow-derived macrophages (BMDMs) of C57BL/6 (B6) mice. B6 mice received a subconjunctival injection of lentivirus expressing active NLRP12 (NLRP12-lentivirus) or Ctl-lentivirus (as control), followed by infection of P. aeruginosa. The clinical score, slit lamp and bacterial plate count of mice were evaluated. In addition, myeloperoxidase (MPO) was detected to assess the infiltration of polymorphonuclear neutrophil (PMN). Cytokine levels were measured by Real Time-PCR and ELISA. Meanwhile, the bacterial burden was also evaluated. The activation of NF-κB signaling was determined by pIκBα/IκBα levels based on Western blot and NF-κB-dependent Luciferase activity on the basis of Luciferase assays using 293T cells. RESULTS: NLRP12 mRNA and protein levels were decreased in B6 corneas and BMDMs after P. aeruginosa infection. The over-expression of NLRP12 in B6 corneas significantly ameliorated the severity of corneal disease, bacterial burden, PMN infiltration and pro-inflammatory cytokine expression. In vitro analysis demonstrated that the up-regulation of NLRP12 suppressed pro-inflammatory cytokine production and enhanced bacterial clearance in RAW264.7 cells. The protein levels of pIκBα and IκBα were significantly decreased after NLRP12-lentivirus treatment compared with that of Ctl-lentivirus. NF-κB-dependent Luciferase activity was potently inhibited by NLRP12 infected with P. aeruginosa or cotransfected with the downstream signaling molecules including IKKα and IKKß in 293T cells. CONCLUSIONS: NLRP12 decreases the severity of P. aeruginosa keratitis, reduces corneal inflammation and bacterial burden through the down-regulation of the NF-κB signaling pathway.


Assuntos
Córnea/metabolismo , Infecções Oculares Bacterianas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ceratite/metabolismo , NF-kappa B/metabolismo , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/patogenicidade , Animais , Carga Bacteriana , Córnea/microbiologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Infecções Oculares Bacterianas/genética , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/prevenção & controle , Feminino , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Ceratite/genética , Ceratite/microbiologia , Ceratite/prevenção & controle , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Viabilidade Microbiana , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Neutrófilos/microbiologia , Infecções por Pseudomonas/genética , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/prevenção & controle , Células RAW 264.7 , Transdução de Sinais
17.
Artigo em Chinês | MEDLINE | ID: mdl-30400686

RESUMO

Objective:The aim of this study is to the roles of nasal lavage fluid levels of MUC5AC, goblet cell hyperplasia and ultrastructure of nasal mucosa following ambient PM2.5 exposure in a rat model of allergic rhinitis(AR).Method:Female Sprague-Dawley rats were assigned randomly into 3 groups: a negative control group(NC group),an ovalbumin(OVA)-induced AR model group(AR group), and AR model group(ARE group) inhaled to PM2.5 at 200 µg/m³, 3 h/d, for 30 days. Nasal symptoms, levels of MUC5AC in nasal lavage fluid(NLF), were measured in each individual rat.Goblet cell hyperplasia were examined histologically with PAS-stained. Nasal mucosa tissue ultrastructure were observed by scanning electron microscope.Result:PM2.5 significantly increased the number of sneezes, nasal rubs and the amount of nasal secretion in rats with AR.Statistically significant differences in MUC5AC levels and goblet cell hyperplasia were observed between the AR model exposure to PM2.5 and the AR model group.The nasal mucosa of AR model exposure to PM2.5 was disordered,lodged,assembled and twisted.Conclusion:Our data indicate that an increase MUC5AC level in NLF and the development of nasal goblet cell hyperplasia may provide some clues for determining the pathogenic mechanisms of AR by exposure to PM2.5.

18.
Zhonghua Shao Shang Za Zhi ; 34(9): 653-656, 2018 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-30293371

RESUMO

Adipose-derived stem cells (ADSCs) are adult mesenchymal stem cells in adipose tissue with self-renewal and multi-directional differentiation potential. The application of ADSCs in the treatment of wounds has achieved good results. Because of its extensive sources, high content in vivo, low immunogenicity, slight injury to body when obtained, the clinical application prospect of ADSCs is promising. The reasons why diabetic wound is difficult to heal may be closely related to the increase of advanced glycation end products, long-term chronic inflammatory response, and peripheral neurologic dysfunction. The abnormal internal environment of diabetic patients can affect the biological function of ADSCs, which further affects wound healing. This article reviews the general feature, differentiation, proliferation, migration, secretion, and pro-angiogenic function of diabetic ADSCs.


Assuntos
Tecido Adiposo/citologia , Diabetes Mellitus/patologia , Diabetes Mellitus/terapia , Produtos Finais de Glicação Avançada , Células-Tronco/citologia , Cicatrização/fisiologia , Adipócitos , Animais , Produtos Biológicos , Diferenciação Celular , Humanos , Células-Tronco Mesenquimais
19.
Osteoarthritis Cartilage ; 26(12): 1733-1743, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30201491

RESUMO

OBJECTIVE: We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM). DESIGN: Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1ß induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1ß mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery. CONCLUSIONS: R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.


Assuntos
Artrite Experimental/prevenção & controle , Cartilagem Articular/metabolismo , Oligopeptídeos/uso terapêutico , Osteoartrite/prevenção & controle , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Avaliação Pré-Clínica de Medicamentos/métodos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/patologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Oligopeptídeos/farmacologia , Osteoartrite/metabolismo , Osteoartrite/patologia , Proteoglicanas/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Técnicas de Cultura de Tecidos
20.
Zhonghua Jie He He Hu Xi Za Zhi ; 41(8): 632-637, 2018 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-30138974

RESUMO

Objective: To analyze the relationship between TNF-α and pulmonary vascular remodeling in order to explore the pathogenesis of CTEPH. Methods: Autologous blood clots were repeatedly injected into the left jugular vein of rats to establish the CTEPH model. Then mean pulmonary artery pressure (mPAP), histopathology, the plasma level of TNF-α, and the expressions of mRNA and protein of TNF-α in pulmonary artery were measured. Results: In the experiment group, the mPAP and vessel wall area/total area (WA/TA) ratio gradually increased as emblism extended, and increased significantly compared with the sham operation group. The plasma TNF-α concentration in the experimental group increased significantly (P<0.05). The TNF-α proteins expressed in pulmonary artery in the 1-week, 2-week, and 4-week subgroups of experimental group increased significantly compared with the sham operation group (1.62±0.08 vs 0.85±0.12, P<0.05; 1.85±0.08 vs 0.89±0.13, P<0.05; 1.37±0.12 vs 0.91±0.15, P<0.05, respectively). Immunohistochemical results showed that TNF-α expression was higher in pulmonary artery endothelial cells of the experimental group compared with the sham operation group. The expression of pulmonary artery TNF-α protein was positively related with mPAP (r=0.605, P<0.01), and with WA/TA (r=0.629, P<0.01). The expression of serum TNF-α was positively related with that of pulmonary artery TNF-α protein (r=0.721, P<0.01). Conclusion: A rat model of CTEPH can be established by repeatedly introducing autologous blood clots into the pulmonary artery with injecting TXA. Thrombosis induced higher expression of TNF-α in pulmonary arterial endothelial cells, and released into the blood. TNF-α may play an important role in the development of CTEPH, especially by contributing to vascular remodeling and PH.


Assuntos
Hipertensão Pulmonar , Animais , Doença Crônica , Artéria Pulmonar , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Tromboembolia , Fator de Necrose Tumoral alfa , Remodelação Vascular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA