Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 762
Filtrar
1.
Nat Neurosci ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570863

RESUMO

It was recently reported that a magnetic actuator, Magneto, can control neuronal firings at magnetic strength as low as 50 mT (ref. 1), offering an exciting non-invasive approach to manipulating neuronal activity in a variety of research and clinical applications. We investigated whether Magneto can be used to manipulate electric properties of Purkinje cells in the cerebellum, which play critical roles in motor learning and emotional behaviors2. Surprisingly, we found that the application of a magnetic field did not change any electrical properties of Purkinje cells expressing Magneto, raising serious doubt about the previous claim that Magneto can readily be used as a magnetic actuator1.

2.
JMIR Mhealth Uhealth ; 7(9): e12606, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31573936

RESUMO

BACKGROUND: Physical inactivity is a risk factor for chronic noncommunicable diseases. Insufficient physical activity has become an important public health problem worldwide. As mobile apps have rapidly developed, physical activity apps have the potential to improve the level of physical activity among populations. OBJECTIVE: This study aimed to evaluate the effect of physical activity apps on levels of physical activity among college students. METHODS: A Web-based questionnaire was used to survey college students in Beijing from December 27, 2017, to January 5, 2018. According to a previous survey, 43% of college students using physical activity apps and 36% of those who never used such apps achieved the physical activity recommendations. In this study, the sample size was calculated to be 500. The questionnaire consisted of 5 parts: the use of physical activity apps, sports habits, social support, self-efficacy, and social demographic information. Structural equation modeling was used to test the relationships between the use of physical activity apps, self-efficacy, social support, and level of physical activity. RESULTS: Of the 1245 participants, 384 college students (30.8%) used physical activity apps (in the past month). Of these 384 students, 191 (49.7%) gained new friends via the app. College students who were using physical activity apps had a higher level of physical activity and higher scores for social support and self-efficacy (P<.001) than those who did not use such apps. The use of physical activity apps significantly affected the mediating effect of physical activity level through social support (beta=.126; P<.001) and self-efficacy (beta=.294; P<.001). Gender played an important role in app use, self-efficacy, and physical activity in the mediation model: male users spent more time on physical activity and had higher self-efficacy scores (P<.001). CONCLUSIONS: This study focused on college students in Beijing and found that the use of physical activity apps is associated with higher physical activity levels among these students. This effect is mainly through the mediation effect of social support and self-efficacy, rather than the direct effect of physical activity apps. The use of physical activity apps is associated with a higher social support level and higher self-efficacy score. Furthermore, a high social support level and high self-efficacy score are associated with higher physical activity levels.

3.
J Am Heart Assoc ; 8(19): e012495, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31566104

RESUMO

Background The pathophysiological process of calcific aortic valve disease (CAVD) is similar to that of atherosclerosis. Leptin accelerates the process of atherosclerosis. We sought to examine the relationship between leptin and CAVD. Methods and Results Serum leptin was measured in 397 consecutive patients undergoing standard transthoracic echocardiography and Doppler flow imaging. Multiple logistic regression analyses were used to assess the association between leptin and CAVD. Western blotting was performed to detect the expression of phosphorylated and total extracellular signal-regulated kinase. Serum leptin (median) was higher in 200 patients with CAVD than that in 197 non-CAVD controls (20.07 versus 9.03 ng/mL; P<0.01). Leptin correlated positively with age (r=0.37, P<0.01) and negatively with estimated glomerular filtration rate (r=-0.37, P<0.01). Multivariate analysis indicated that elevated leptin was an independent determinant for the presence of CAVD (P<0.01). Receiver-operating characteristic curve analysis of leptin to detect the presence of CAVD showed that the area under the curve was 0.74 (95% CI, 0.69-0.79; P<0.01). The diagnostic value of leptin for the detection of CAVD was higher among younger patients (aged ≤65 years) or those with at least mildly reduced renal function (estimated glomerular filtration rate ≤82.06 mL/min per 1.73 m2). The activation of extracellular signal-regulated kinase 1/2 was stronger in calcific aortic valves than in normal aortic valves. Conclusions Elevated leptin is associated with the presence of CAVD, especially among younger patients or those with renal dysfunction.

4.
Acta Haematol ; : 1-10, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597158

RESUMO

BACKGROUND: The aim of this study was to detect the expression of long noncoding RNA small nucleolar RNA host gene 18 (SNHG18) andsemaphorin 5A (SEMA5A) genes in multiple myeloma (MM) patients and to explore the correlation of the expression of these genes with the clinical characteristics and prognosis of MM patients. METHODS: Forty-seven newly diagnosed MM, 18 complete remission MM, 13 refractory/relapse MM, and 22 iron deficiency anemia (serving as control) samples were extracted at the Department of Hematology, Second Affiliated Hospital of Xian Jiaotong University between January 2015 and December 2016. The clinical features of the MM patients are summarized. Real-time quantitative PCR was performed to analyze the relative expression levels of the SNHG18 and SEMA5Agenes. The clinical characteristics and overall survival (OS) of the MM patients were statistically analyzed while measuring different levels of SNHG18 and SEMA5Agene expression. At the same time, the correlation between the expression of SNHG18 and SEMA5A was also analyzed. RESULTS: The analysis confirmed that SNHG18 and its possible target gene SEMA5A were both highly expressed in newly diagnosed MM patients. After analyzing the clinical significance of SNHG18 and SEMA5A in MM patients, we found that the expression of SNHG18 and SEMA5A was related to the Durie-Salmon (DS), International Staging System (ISS), and Revised International Staging System (R-ISS) classification systems, and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART; p < 0.05). Moreover, we observed a significant difference in OS between the SNHG18/SEMA5A high expression group and the low expression group. We found a positive correlation between SNHG18 and SEMA5A expression (r = 0.709, p < 0.01). Surprisingly, the expected median OS times of both the SNHG18 and SEMA5Ahigh expression groups were significantly decreased, which was in contrast to those of both the SNHG18 and SEMA5Alow expression groups and the single-gene high expression group (p < 0.05). CONCLUSION: High expression of both SNHG18 and SEMA5A is associated with poor prognosis in patients with MM.

5.
Clin Genet ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31571197

RESUMO

Multiple morphological abnormalities of the sperm flagella (MMAF) is a rare autosomal recessive inherited disorder associated with male infertility. To date, 14 genetic causative genes have been identified in MMAF, which can only explain the genetic causes of ~60% of MMAF cases. Here, we report a man with primary infertility, who had a typical MMAF phenotype. Whole-exome sequencing (WES) was performed on the patient and a homozygous mutation (c. 2675 G>A [p. Trp892*]) was identified in cilia and flagella-associated protein 65 (CFAP65) gene, which is primarily expressed in the testis. Another loss-of-function mutation of CFAP65 has been detected in a MMAF patient, and the orthologue of CFAP65 also plays a vital role in sperm motility in chickens. Our experimental observations on human subjects suggested that CFAP65 is involved in sperm flagellum structure and assembly and that loss-of-function mutations could lead to male infertility in humans by causing the MMAF phenotype.

6.
Life Sci ; 235: 116835, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31493480

RESUMO

Sleep is crucial to improve athlete performance and their circadian rhythm, but sleep patterns may be disturbed because athletes participate in several competitions. In addition, intensive training programs can cause muscle pain and psychological stress in athletes, resulting in a lack of sleep. Sleep also plays a critical role in the recovery of muscle injury induced by exercise. The current study evaluated the effect of sleep deprivation on the recovery of muscle injury induced by high-intensity exercise in a mouse model. In this study, 28 mice were randomly assigned to four groups (N = 7): control (Control), exercise (EX), sleep deprivation (SD), and sleep deprivation with exercise (EX+SD). The mice from the EX and EX+SD groups were subjected to high-intensity swimming. The results showed that 72-h sleep deprivation increased food intake and reduced body weight. However, the manipulation of 8-week exercise and/or 72-h sleep deprivation did not have any effect in the elevated plus maze task and tail suspension test. Interestingly, the EX+SD group exhibited improved memory performance in the Morris water maze and impaired motor activity in the open field test. According to the TNF-α level and aspartate aminotransferase (AST), and creatine phosphokinase (CK) activities, only the EX+SD group exhibited muscle impairment. Overall, high-intensity exercise may cause muscle injury, and adequate sleep can recover muscle damage. However, sleep deprivation reduces protein synthesis, which decreases the ability to restore muscle damage and aggravates the harmful effect of high-intensity exercise.

8.
Oncol Rep ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31524278

RESUMO

Colorectal cancer (CRC), a commonly occurring malignant tumor in the gastrointestinal tract, is the third leading cause of cancer­related deaths worldwide. FK506­binding proteins (FKBPs) comprise an immunophilin family that are involved in the carcinogenesis, progression and chemoresistance of cancers, including CRC. FKBP3 (also known as FKBP25) is a nuclear protein that is a member of the FKBP family and is correlated with the activity of histone deacetylase 2 (HDAC2). However, the role of FKBP3 and HDAC2 in oxaliplatin resistance in CRC and the potential molecular mechanisms are still poorly understood. In the present study, the expression of FKBP3, HDAC2 and related­genes was detected by real­time PCR and western blot analysis. Furthermore, cell apoptosis was detected by flow cytometry (FCM). We found high expression of FKBP3 and HDAC2 in CRC tissues. In vitro, primary CRC cells with high expression of FKBP3 and HDAC2 were insensitive to oxaliplatin. Downregulation of FKBP3 significantly increased the sensitivity of primary CRC cells to oxaliplatin, reduced expression of HDAC2, permeability glycoprotein (P­gp) and phosphorylated AKT (p­AKT), and increased expression of phosphatase and tensin homolog (PTEN) and cleaved caspase­3. Accordingly, upregulation of FKBP3 had the opposite effect. Furthermore, downregulation of HDAC2 significantly counteracted FKBP3­induced oxaliplatin resistance in CRC cells. Our data revealed that oxaliplatin resistance in CRC cells is positively associated with FKBP3 and HDAC2 expression, and FKBP3 downregulation could attenuate oxaliplatin resistance in CRC cells by reducing HDAC2 expression and possibly through regulation of the PTEN/AKT pathway.

9.
Zhongguo Zhen Jiu ; 39(9): 953-6, 2019 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-31544383

RESUMO

OBJECTIVE: To compare the clinical effect of the herbal cake-separated moxibustion with new-type moxibustion device combined with bladder function exercise and simple bladder function exercise on improving urinary retention after spinal cord injury. METHODS: Sixty-eight patients were randomly divided into a control group and an observation group, 34 cases in each group. The bladder function exercise was given in the control group. On the basis of the treatment in the control group, herbal cake-separated moxibustion with new-type moxibustion decice was applied at Shenque (CV 8), Guanyuan (CV 4), Qihai (CV 6), Zhongji (CV 3) for 30 min, once a day in the observation group. The two groups were treated for 4 weeks as a course, 2 courses of treatment were needed. Bladder maximum volume, bladder residual urine volume and urinary tract infection before and after treatment were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: The total effective rate in the observation group was 88.2% (30/34), which was better than 64.7% (22/34) in the control group (P<0.05). The increase of bladder maximum volume and decrease of bladder residual urine volume in the observation group were significantly better than those in the control group (P<0.01). At the 4th, 6th and 8th weeks for treatment, the improvement of urinary tract infection in the observation group was better than that in the control group (P<0.05). CONCLUSION: At the same time of bladder function training, herbal cake-separated moxibustion with new-type moxibustion device could improve urinary retention after spinal cord injury.

10.
Shanghai Kou Qiang Yi Xue ; 28(3): 259-263, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31489412

RESUMO

PURPOSE: This study was aimed to figure out the way that cyclic-stretch influenced the apoptosis of myoblasts and evaluate the importance of PERK and its possible mechanism involved. METHODS: L6 rat myoblasts were cultured in vitro and mechanical stimulation model was constructed successfully. The myoblasts were imposed tension for 0, 2, 6, 12 and 24 hours respectively by multi-channel cell stress loading system. The force value was 15% cell deformation and the frequency was 10 cycles/min. Each cycle was consisted of stretch for 3 seconds and relaxation for 3 seconds, and the group without tension was used as the control group. The apoptotic myoblasts were dyed by DAPI and observed through fluorescence microscopy to detect the apoptosis rate; the mRNA levels of PERK and CHOP in different groups were detected by real-time PCR and protein levels of PERK and p-PERK in different groups were detected by Western blot. PERK inhibitor was used to clear the role of PERK in apoptosis induced by cyclic-stretch and clarify the relationship between the endoplasmic reticulum stress and apoptosis induced by cyclic-stretch. SPSS 17.0 software package was used to analyze the data statistically. RESULTS: DAPI nuclear stain showed that cyclical tensile stress can induce apoptosis in vitro cultured myoblast. Apoptosis rate showed a trend of rising gradually over time, peaked at 24 h. After dealt with the inhibitor of PERK, the apoptosis rate of the 24 h group under the cyclic stretch showed no difference compared with the control. The results of real- time PCR showed that the mRNA of CHOP was increased with the extension loading time, while the mRNA of PERK showed no difference compared with the control. Western blot results showed that the protein level of p-PERK was increased with the extension of loading time, while the expression of PERK showed no difference compared with the control group. When PERK inhibitor added, the mRNA level of CHOP along with the protein expression level of p-PERK showed no significant difference compared to the control. CONCLUSIONS: PERK signaling pathway is involved in the apoptosis of myoblasts induced by cyclic stretch, and the possible mechanism may be closely related to the phosphorylation of PERK.

11.
J Med Genet ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501240

RESUMO

BACKGROUND: Male infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre flagella resulting in severely decreased motility. Previous studies reported several MMAF-associated genes accounting for approximately half of MMAF cases. METHODS AND RESULT: We conducted genetic analysis using whole-exome sequencing in 88 Han Chinese MMAF probands. CFAP65 homozygous mutations were identified in four unrelated consanguineous families, and CFAP65 compound heterozygous mutations were found in two unrelated cases with MMAF. All these CFAP65 mutations were null, including four frameshift mutations (c.1775delC [p.Pro592Leufs*8], c.3072_3079dup [p.Arg1027Profs*41], c.1946delC [p.Pro649Argfs*5] and c.1580delT [p.Leu527Argfs*31]) and three stop-gain mutations (c.4855C>T [p.Arg1619*], c.5270T>A [p.Leu1757*] and c.5341G>T [p.Glu1781*]). Additionally, two homozygous CFAP65 variants likely affecting splicing were identified in two MMAF-affected men of Tunisian and Iranian ancestries, respectively. These biallelic variants of CFAP65 were verified by Sanger sequencing and were absent or very rare in large data sets aggregating sequence information from various human populations. CFAP65, encoding the cilia and flagella associated protein 65, is highly and preferentially expressed in the testis. Here we also generated a frameshift mutation in mouse orthologue Cfap65 using CRISPR-Cas9 technology. Remarkably, the phenotypes of Cfap65-mutated male mice were consistent with human MMAF. CONCLUSIONS: Our experimental observations performed on both human subjects and on Cfap65-mutated mice demonstrate that the presence of biallelic mutations in CFAP65 causes the MMAF phenotype and impairs sperm motility.

12.
Transl Stroke Res ; 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31494833

RESUMO

The aim of this study was to assess the association between admission to stroke centers for acute ischemic stroke and complications and mortality during hospitalization in a Chinese population by means of an observational study using data from the China Stroke Center Data-Sharing Platform. We compared in-hospital complications and mortality for patients admitted with acute ischemic stroke (N = 13,236) between November 1, 2018 and December 31, 2018 at stroke center (SH) and non-stroke center (CH) hospitals using distance to hospitals as an instrumental variable to adjust for potential prehospital selection bias. The results showed that complication rates during hospitalization among ischemic stroke patients who received thrombolytic therapy (n = 11,203) were lower in the SH group than in the CH group: 11.1% vs 15.7% (absolute difference, - 5.11% [95% CI, - 6.05 to - 3.99%], odds ratio [OR] 0.85 [95% CI, 0.74 to 0.92]). The incidence of intracranial hemorrhage was reduced from 4.2 to 3.2%: SH group vs CH group, 3.2% vs 4.2% (absolute difference, - 1.24% [95% CI, - 1.65 to - 0.82%], OR 0.83 [95% CI, 0.69 to 0.0.98]). Furthermore, the total mortality rate in the SH group was also lower than in the CH group: SH group vs CH group, 2.2% vs 3.0% (absolute difference, - 0.92% [95% CI, - 1.48 to - 0.53%], OR 0.85 [95% CI, 0.73 to 0.96]). The data showed that admission to SH hospitals was associated with a lower risk of treatment complications and death for patients with an acute ischemic stroke receiving thrombolytic therapy.

13.
J Vis Exp ; (150)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31498306

RESUMO

Aberrant changes in endothelial phenotype and morphology are considered to be initial events in the pathogenesis of atherosclerosis. Direct observation of the intact endothelium will provide valuable information for understanding the cellular and molecular events in the dysfunctional endothelial cells. Here, we describe a modified en face immunofluorescence staining technique which enables scientists to obtain clear images of the intact endothelial surface and analyze the molecule expression patterns in situ. The method is simple and reliable for observing the entire endothelial monolayer at different sites of the aorta. This technique may be a promising tool for understanding the pathophysiology of atherosclerosis, especially at an early stage.

14.
J Surg Res ; 245: 1-12, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394402

RESUMO

BACKGROUND: The process of aortic injury, repair, and remodeling during aortic aneurysm and dissection is poorly understood. We examined the activation of bone marrow (BM)-derived and resident aortic cells in response to aortic injury in a mouse model of sporadic aortic aneurysm and dissection. MATERIALS AND METHODS: Wild-type C57BL/6 mice were transplanted with green fluorescent protein (GFP)+ BM cells. For 4 wk, these mice were either unchallenged with chow diet and saline infusion or challenged with high-fat diet and angiotensin II infusion. We then examined the aortic recruitment of GFP+ BM-derived cells, growth factor production, and the differentiation potential of GFP+ BM-derived and GFP- resident aortic cells. RESULTS: Aortic challenge induced recruitment of GFP+ BM cells and activation of GFP- resident aortic cells, both of which produced growth factors. Although BM cells and resident aortic cells equally contributed to the fibroblast populations, we did not detect the differentiation of BM cells into smooth muscle cells. Interestingly, aortic macrophages were both of BM-derived (45%) and of non-BM-derived (55%) origin. We also observed a significant increase in stem cell antigen-1 (Sca-1)+ stem/progenitor cells and neural/glial antigen 2 (NG2+) cells in the aortic wall of challenged mice. Although some of the Sca-1+ cells and NG2+ cells were BM derived, most of these cells were resident aortic cells. Sca-1+ cells produced growth factors and differentiated into fibroblasts and NG2+ cells. CONCLUSIONS: BM-derived and resident aortic cells are activated in response to aortic injury and contribute to aortic inflammation, repair, and remodeling by producing growth factors and differentiating into fibroblasts and inflammatory cells.

15.
Patient Educ Couns ; 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31447198

RESUMO

OBJECTIVE: To determine whether the joint use of the transtheoretical model and latent profile analysis could help us better understand the shared characteristics of patients with diabetes and explore the association of patients' latent classes and glucose control. METHODS: Five hundred twenty-three (523) patients with diabetes were included in the study. The questionnaire evaluated patients' stages of change for medication-taking, diet control, exercise, and glucose-monitoring. Latent profile analysis was performed based on the four indicators. RESULTS: Patients were classified into four latent groups and defined as follows: good medication-taking/good lifestyle (GM/GL, 41.7%), poor medication-taking/poor lifestyle (PM/PL, 27.7%), good medication-taking/poor lifestyle (GM/PL, 21.6%), and poor medication-taking/good lifestyle (PM/GL, 9.0%). Patients in the PM/PL group were generally younger and better educated while those in the GM/GL group exhibited the opposite pattern. Compared with patients in the PM/PL group, those in the PM/GL and GM/GL groups had significantly lower HbA1c values (PM/GL: standardized ß = -0.694, P =  0.007; GM/GL: standardized ß = -0.499, P =  0.003). CONCLUSION: With the help of the transtheoretical model and latent profile analysis, future study could cluster homogeneous patients before the initiation of intervention and provide tailored instructions to different types of patients accordingly. PRACTICE IMPLICATIONS: A combination of the transtheoretical model and latent profile analysis could shed some light into future diabetic interventions.

16.
Theranostics ; 9(16): 4678-4687, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367249

RESUMO

Rationale: PD1/PD-L1 immune checkpoint inhibitors have shown promising results for several malignancies. However, PD1/PD-L1 signaling and its therapeutic significance remains largely unknown in intrahepatic cholangiocarcinoma (ICC) cases with complex etiology. Methods: We investigated the expression and clinical significance of CD3 and PD1/PD-L1 in 320 ICC patients with different risk factors. In addition, we retrospectively analyzed 7 advanced ICC patients who were treated with PD1 inhibitor. Results: The cohort comprised 233 patients with HBV infection, 18 patients with hepatolithiasis, and 76 patients with undetermined risk factors. PD-L1 was mainly expressed in tumor cells, while CD3 and PD1 were expressed in infiltrating lymphocytes of tumor tissues. PD1/PD-L1 signals were activated in tumor tissues, and expression was positively correlated with HBV infection and lymph node invasion. More PD1+ T cells and higher PD-L1 expression were observed in tumor tissues of ICC patients with HBV infection compared to patients with hepatolithiasis or undetermined risk factors. More PD1+ T cells and/or high PD-L1 expression negatively impacted the prognosis of patients with HBV infection but not those with hepatolithiasis. Multivariate analysis showed PD1/PD-L1 expression was an independent indicator of ICC patient prognosis. Advanced ICC patients with HBV infection and less PD1+ T cells tended to have good response to anti-PD1 therapy. Conclusion: Hyperactivated PD1/PD-L1 signals in tumor tissues are a negative prognostic marker for ICCs after resection. HBV infection- and hepatolithiasis-related ICCs have distinct PD1/PD-L1 profiles. Further, PD1+ T cells could be used as a biomarker to predict prognosis and assay the efficiency of anti-PD1 immunotherapy in ICC patients with HBV infection.

17.
J Coll Physicians Surg Pak ; 29(9): 900-901, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31455493

RESUMO

The aim of this study was to compare the levels of erythropoietin (Epo), semaphorins 3A (Sema 3A) and pigment epithelium derived factors (PEDF) in serum and aqueous humor of those with neovascular glaucoma (NVG) and patients with cataract. It was an experimental study carried out from January 2016 to September 2018. Seventy-three NVG patients were selected as NVG group, and 73 cataract patients were selected as cataract group. The levels of Epo and sema 3A in serum and aqueous humor in NVG group were higher than those in cataract group (both p <0.001), and the level of PEDF in serum and aqueous humor in NVG group were lower than those in cataract group (p <0.001). Compared with cataract patients, NVG patients had higher levels of Epo and sema 3A in serum and aqueous humor and lower levels of PEDF.

18.
Int J Mol Sci ; 20(16)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31408937

RESUMO

Wilms tumor 1 (WT1) oncoprotein is an intracellular oncogenic transcription factor which is barely expressed in normal adult tissues but over expressed in a variety of leukemias and solid cancers. WT1-derived HLA-A*02:01 T cell epitope, RMFPNAPYL (RMF), is a validated target for T cell-based immunotherapy. We generated two T cell receptor mimic antibody-drug conjugates (TCRm-ADCs), ESK-MMAE, and Q2L-MMAE, against WT1 RMF/HLA-A*02:01 complex with distinct affinities, which mediate specific antitumor activity. Although ESK-MMAE showed higher tumor growth inhibition ratio in vivo, the efficacy of them was not so promising, which might be due to low expression of peptide/HLA targets. Therefore, we explored a bispecific TCRm-ADC that exerted more potent tumor cytotoxicity compared with TCRm-ADCs. Hence, our findings validate the feasibility of the presenting intracellular peptides as the targets of ADCs, which broadens the antigen selection range of antibody-based drugs and provides new strategies for precision medicine in tumor therapy.

19.
Cardiovasc Diabetol ; 18(1): 100, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391045

RESUMO

BACKGROUND: Adverse cardiac remodeling after ST-segment elevation myocardial infarction (STEMI) is a major cause for poor cardiovascular outcomes such as heart failure. The predisposing factors and underlying mechanisms remain not fully understood. This study investigates the association of insulin resistance and dysglycemia with left ventricular (LV) remodeling after STEMI in non-diabetic patients. METHODS: A total of 485 non-diabetic subjects with STEMI who underwent primary percutaneous coronary intervention were consecutively enrolled and followed up for 12 months. Relation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and glucose levels to changes in echocardiography parameters was studied. RESULTS: Left ventricular dilation was detected in 49.1% of subjects at 12-month follow-up after STEMI, and was more severe in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and high HOMA-IR levels. HOMA-IR remained correlated to changes in LV dimensions after adjusting for confounding risk factors. Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI. A significant interaction term was present between HOMA-IR and IGT in the model (P = 0.001). CONCLUSIONS: Our study reveals that insulin resistance and dysglycemia are prevalent in non-diabetic patients with STEMI and are predictors of the post-infarction LV dilation. Trial registration Trials number, NCT02089360; registered on March 17, 2014.

20.
Int. braz. j. urol ; 45(4): 790-797, July-Aug. 2019. tab
Artigo em Inglês | LILACS-Express | ID: biblio-1019876

RESUMO

ABSTRACT Objective The purpose of this study was to determine whether the presence of obesity was related with symptoms of nocturnal enuresis (NE) and the efficacy of behavioral intervention in the treatment of NE. Materials and Method The patients diagnosed with primary monosymptomatic nocturnal enuresis (PMNE) were studied retrospectively. NE severity was classified as mild, moderate, and severe according to the frequency of enuresis. The children were divided into three groups, namely normal weight (5th-84th percentile), overweight (85th-94th percentile), and obesity (≥95th percentile), according to their Body Mass Index (BMI) percentage. The relationship between obesity level and enuresis severity was analyzed. After three months of behavioral therapy, the efficacy of treatment among normal, overweight, and obese groups were evaluated. Moreover, the predictive risk factors for treatment failure were investigated. Results The rates of severe enuresis in patients with normal weight, overweight, and obesity were 63.9%, 77.5%, and 78.6%, respectively. Obese children depicted higher odds of having severe enuresis compared with normal-weight children (OR: 1.571; 95% confidence interval [CI]: 1.196-2.065; P=0.001). The odds of presenting with severe enuresis were 1.99 times higher in children who are obese or overweight compared to children with normal weight (OR: 1.994; 95% CI: 1.349-2.946; P=0.001). The complete response of the normal group was higher than those of the overweight and obese groups (26.8% vs. 14.0%, P=0.010; 26.8% vs. 0.0%, P=0.000). Overweight children showed higher complete response than obese ones (14.0% vs. 0.0%, P=0.009). Logistic regression analysis revealed that obesity level and enuresis frequency were significantly related to the treatment failure of behavioral intervention. Conclusions Obesity is associated with severe enuresis and low efficacy of behavioral therapy in children with nocturnal enuresis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA