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1.
Br J Haematol ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31725190

RESUMO

We explored the prognostic factors for children with very high-risk (VHR) Philadelphia chromosome (Ph) negative B-cell acute lymphoblastic leukaemia (B-ALL) and compared the therapeutic effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo-HSCT) as post-remission treatment in these patients undergoing first complete remission (CR1). A total of 104 paediatric patients with VHR B-ALL in CR1 were retrospectively enrolled in this study, including 42 receiving unmanipulated haplo-HSCT (Group A) and 62 receiving ongoing chemotherapy (Group B). Estimated 3-year overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) at 36·2 months median follow-up were 69·5 ± 4·7%, 63·5 ± 4·8% and 32·4 ± 4·7%, respectively. Maintenance of persistent positive or conversion from negative to positive of measurable residual disease (MRD) and chemotherapy were independent risk factors associated with inferior long-term survival and higher CIR. OS, DFS, and CIR differed significantly between the groups in patients with persistent positive or negative-to-positive MRD. Haplo-HSCT may be an option for children with VHR Ph-negative B-ALL in CR1, especially for patients with persistent positive or negative-to-positive MRD, and could achieve better survival than intensive chemotherapy as post-remission treatment.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31678189

RESUMO

Transcription factor c-Jun is a member of AP-1 transcription complex that can be induced by various pathogens and plays a broad regulatory role in vertebrate immune response. In this study, the complete c-Jun cDNA of large yellow croaker Larimichthys crocea (Lcc-Jun) was cloned, whose open reading frame (ORF) is 984 bp long and encodes a protein of 327 amino acids (aa). The deduced Lcc-Jun protein contains three highly conserved domains, a transactivation domain (TAD, Met1-His118), a DNA binding domain (DBD, Lys218-Arg243), and a Leucine zipper domain (LZD, Leu271-Leu299), as found in other specie c-Jun. Lcc-Jun was constitutively expressed in all examined tissues, with the higher levels in blood, heart, and head kidney. Its transcripts were not only induced in spleen and head kidney by poly (I: C) or LPS, but also up-regulated in primary head kidney leukocytes (PKL), macrophages (PKM), and granulocytes (PKG), suggesting that Lcc-Jun may be involved in immune responses induced by poly (I: C), a viral mimic, and LPS, a Gram-negative bacterial component. Overexpression of Lcc-Jun in PKL increased the expression of cytokines and transcription factors involved in T helper 1 (Th1: TNF-α, IFN-γ, and T-bet) and Th2 (IL-4/13 A/B, IL-6, and GATA3) cell development and differentiation, suggesting that Lcc-Jun may play a role in regulation of Th1/Th2 cell response. These results therefore led us to suggest that the c-Jun-mediated signaling pathways may have an important immune-modulatory function in teleost fish.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31704470

RESUMO

Basiliximab has been used successfully as a second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in adult patients after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) but has not been studied separately in the pediatric setting. We retrospectively reviewed 100 pediatric patients after haplo-HSCT receiving basiliximab for grades II (57%), III (27%), and IV (16%) SR-aGVHD between January 2015 and December 2017. The median number of basiliximab doses was 4 (range, 2-9). The day 28 overall response rate (ORR) was 85%, with complete response (CR) in 74% of patients, partial response (PR) in 11% of patients, and no response in 15% of patients. The day 28 ORR was 94.6% in skin SR-aGVHD, 81.6% in gut SR-aGVHD, and 66.7% in liver SR-aGVHD. Infectious complications included bacterial infection (11%), presumed or documented fungal infections (7%), CMV viremia (53%), EBV viremia (11%), HHV-6 viremia (7%), and HSV viremia (1%). The 3-year overall survival (OS), disease-free survival (DFS), nonrelapse mortality (NRM), and relapse rates between responders and nonresponders were 81.3% vs. 46.7% (P<0.001), 79.0% vs. 46.7% (P=0.001), 6.1% vs. 33.3% (P<0.001), and 14.9% vs. 20.0% (P=0.46), respectively. We conclude that basiliximab is an effective second-line agent for pediatric patients with SR-aGVHD after haplo-HSCT, particularly for skin SR-aGVHD.

4.
Anal Bioanal Chem ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728594

RESUMO

Monitoring and imaging glutathione (GSH) in living systems is an essential tool to determine the key roles of GSH in biological pathways, but most fluorescent sensors can only be used in vitro because of their potential biotoxicity. Here, a peptide-based fluorescent sensor, FP, has been successfully designed and synthesized based on the biocompatibility of the peptide backbone and low toxicity. The design strategy of FP contains a specific spatial structure of the peptide sequence which selectively binds to Cu2+, triggering fluorescence quenching. Interestingly, the fluorescence of FP can be fully restored by GSH, due to the strong binding between Cu2+ and the GSH sulfhydryl groups. Finally, the sensor is highly sensitive and selective for imaging GSH both in vitro and in vivo with low toxicity. Thus, FP with its strong "on-off-on" fluorescence changes is a powerful way to image GSH both in cells and zebrafish larvae to study the GSH pathway.

5.
Mol Vis ; 25: 489-501, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588173

RESUMO

Purpose: Primary congenital glaucoma (PCG) is an autosomal recessive eye disorder, accounting for 0.01%-0.04% of blindness around the world. Unfortunately, the molecular characteristics concerning the pathogenic mechanisms of the disease remain poorly understood. Methods: Here, for the first time, we employed gas chromatography coupled to time-of-flight mass spectrometry (GC/TOF MS) to reveal comprehensively the metabolic characteristics of PCG. Results: First, 363 metabolites were detected in 50 aqueous humor (AH) samples from 30 patients with PCG, 10 patients with congenital cataracts (CCs), and 10 patients with aged-related cataracts (ARCs). Second, 290 metabolites in total were found in another 15 patients with PCG and 10 patients with primary open angle glaucoma (POAG). A further analysis suggested that patients with PCG had a significantly distinct metabolomics profile. Three amino acid-associated metabolites, including glycine, urea, and phenylalanine, were identified to be significantly different (p≤0.05) in relation to PCG. Meanwhile, three glaucoma-associated single nucleotide polymorphisms (SNPs), rs7114303, rs9364602, and rs2165241, were determined to be related to these three metabolites. The results here indicate that certain amino acid-associated metabolites and their metabolisms are key regulatory elements and metabolic pathways in the pathogenesis of PCG. Conclusions: Collectively, this work not only extended our understanding of the molecular characteristics of PCG, but also presented glycine as a potential biomarker for earlier diagnosis and may provide new therapeutic strategies for the disease.

6.
Sci Rep ; 9(1): 12778, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484978

RESUMO

The demand for alternatives to antibiotics to improve the growth performance of food animals is increasing. Defensins constitute the first line of defence against pathogens in the innate immune system of animals and humans. A transgenic Chlorella ellipsoidea strain producing mNP-1 (a mutated rabbit defensin NP-1) was previously obtained in our laboratory. In this study, a process for producing the transgenic strain on a large scale was developed, and the C. ellipsoidea strain producing mNP-1 was used as a feed additive to improve the health and growth performance of chickens. The volume of C. ellipsoidea producing mNP-1 can be scaled up to 10,000 L with approximately 100 g/L dry biomass, and the mNP-1 content of transgenic microalgal powder (TMP) was 90-105 mg/L. A TMP-to-regular feed ratio of 1‰, as the optimal effective dose, can promote the growth of broiler chickens by increasing weight by 9.27-12.95%. mNP-1 can improve duodenum morphology by promoting long and thin villi and affect the microbial community of the duodenum by increasing the diversity and abundance of beneficial microbes. These results suggested that transgenic Chlorella producing mNP-1 can be industrially produced and used as an effective feed additive and an alternative to antibiotics for improving the health and growth performance of broiler chickens or other types of food animals/poultry.

7.
BMJ Open ; 9(9): e028904, 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31501106

RESUMO

OBJECTIVES: Upper body fat has been associated with an unfavourable cardiometabolic risk. We aimed to investigate the associations between mid-upper arm circumference (MUAC), a novel indicator of upper body fat, and a wide spectrum of cardiometabolic risk profiles in Chinese population. DESIGN AND SETTING: Cross-sectional analyses were performed using data from a well-defined community in 2014, Shanghai, China. PARTICIPANTS: A total of 6287 Chinese adults (2310 men and 3977 women) aged 40 years or older. OUTCOME MEASURES: Multivariable logistic regression model was used to examine the associations of MUAC with cardiometabolic disorders including central obesity, diabetes, hypertension, hypertriglyceridaemia, low high-density lipoprotein (HDL) cholesterol and subclinical atherosclerosis. RESULTS: In the overall participants, after multivariable adjustment, each 1 SD (3.13 cm) increment in MUAC was positively associated with central obesity (OR 2.05; 95% CI 1.85 to 2.28), hypertension (OR 1.10; 95% CI 1.03 to 1.19) and low HDL cholesterol (OR 1.10; 95% CI 1.01 to 1.22). Multivariable-adjusted ORs for subclinical atherosclerosis were gradually increased across increasing quartiles of MUAC with the lowest quartile as reference (quartile 2: OR 1.31; 95% CI 1.09 to 1.58; quartile 3: OR 1.33; 95% CI 1.10 to 1.62; quartile 4: OR 1.45; 95% CI 1.16 to 1.80; p for trend=0.005). Similar but more prominent associations were observed among women than men. In addition, MUAC was significantly interacted with diabetes (p for interaction=0.04) and insulin resistance (p for interaction=0.01) on subclinical atherosclerosis. CONCLUSION: A greater MUAC was positively associated with higher risks of several cardiometabolic disorders and subclinical atherosclerosis in Chinese adults.

8.
J Hematol Oncol ; 12(1): 87, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477147

RESUMO

BACKGROUND: Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. METHODS: We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. RESULTS: Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0-1), or moderate graft mononuclear cell (MNC) counts (6-10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0-1). CONCLUSIONS: Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.

9.
Front Med ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31512033

RESUMO

Chronic graft-versus-host disease (cGVHD) is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia (n = 280). The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria. A total of 169 patients suffered from cGVHD. The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD (total, 66.0% vs. 53.7%, P = 0.031; moderate to severe, 42.4% vs. 30.1%, P = 0.036) than the patients who had 1 to 2 loci mismatched. The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD (49.2% vs. 32.9%, P = 0.024) compared with the patients who had other donors. The patients who had grades III to IV acute GVHD (aGVHD) had higher 8-year incidence of cGVHD (total, 88.0% vs. 50.4%, P < 0.001; moderate to severe, 68.0% vs. 27.0%, P < 0.001) compared with the patients without aGVHD. In multivariate analysis, grades III to IV aGVHD was the only independent risk factor for cGVHD. Thus, further interventions should be considered in patients with severe aGVHD to prevent cGVHD.

10.
Nat Commun ; 10(1): 4415, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562329

RESUMO

Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4+ T follicular helper (Tfh) cells are the main subset regulating autoreactive B cells. Here we report a CXCR5+PD1+ Tfh subset of CD8+ T cells whose development and function are negatively modulated by Stat5. These CD8+ Tfh cells regulate the germinal center B cell response and control autoantibody production, as deficiency of Stat5 in CD8 T cells leads to an increase of CD8+ Tfh cells, resulting in the breakdown of B cell tolerance and concomitant autoantibody production. CD8+ Tfh cells share similar gene signatures with CD4+ Tfh, and require CD40L/CD40 and TCR/MHCI interactions to deliver help to B cells. Our study thus highlights the diversity of follicular T cell subsets that contribute to the breakdown of B-cell tolerance.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31424628

RESUMO

BACKGROUND: This study aimed to determine the impact of the pre- and post-minimal residual disease (MRD) status as well as the peri-transplant MRD kinetics on clinical outcomes in pediatric ALL patients who received haploidentical allografts. METHODS: A retrospective study (n = 166) was performed. MRD was determined using multiparameter flow cytometry. RESULTS: Pediatric ALL patients with pre-MRDneg had a lower cumulative incidences of relapse (CIR) compared to those with pre-MRDpos (19.7% vs. 41.2%, P = 0.009). Compared to post-MRDneg group, patients with post-MRDpos experienced higher CIR (81.0% vs. 15.9%, P < 0.001), inferior LFS (14.3% vs. 66.9%, P < 0.001) and OS (19.1% vs. 66.9%, P < 0.001). In regard to peri-MRD kinetics, compared with the MRD-decreasing group and MRDneg/MRDneg group, MRD-increasing group had higher CIR, lower probabilities of LFS and OS (P < 0.001). Compared to pre-MRDneg/post-MRDneg group, a higher CIR was found in the pre-MRDpos/post-MRDpos group (66.7% vs. 12.5%, P < 0.001), pre-MRDpos/post-MRDneg group (32.0% vs. 12.5%, P = 0.016), and pre-MRDneg/post-MRDpos group (91.7% vs. 12.5%, P < 0.001). A lower incidence of LFS and OS were found in pre-MRDpos/post-MRDpos group and pre-MRDneg/post-MRDpos group than in pre-MRDneg/post-MRDneg group (P < 0.05). Multivariate analyses confirmed the association of pre-MRD status, post-MRD status, and peri-MRD kinetics with outcomes (P < 0.05). CONCLUSIONS: The results indicate that, in the pediatric ALL subgroup, not only pre-MRD status or post-MRD status but also peri-SCT MRD dynamics, were associated with an increased CIR after haploidentical allografts. Patients are put into different risk group based on MRD kinetics versus single time MRD status. © 2019 International Clinical Cytometry Society.

12.
Oxid Med Cell Longev ; 2019: 8407206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379990

RESUMO

Purpose: Oxidative stress induced by reduced blood circulation is a critical pathological damage to retinal ganglion cells (RGCs) in glaucoma. We previously showed that green tea extract (GTE) and its catechin constituents alleviate sodium iodate-induced retinal degeneration in rats. Here, we investigated the therapeutic effect of GTE on ischemia-induced RGC degeneration in rats. Methods: RGC degeneration was induced by ischemic reperfusion in adult Fischer F344 rats. Green tea extract (Theaphenon E) was intragastrically administered 4 times within 48 hours after ischemia. RGC survival, pupillary light reflex, expressions of cell apoptosis, oxidative stress, and inflammation-related proteins were studied. Results: Ischemic reperfusion significantly induced apoptotic RGCs, RGC loss, and larger constricted pupil area compared to the untreated normal rats. Expressions of activated caspase-3 and caspase-8, Sod2, and inflammation-related proteins as well as p38 phosphorylation were significantly upregulated in the ischemia-injured rats. Compared to the saline-fed ischemic rats, significantly higher number of surviving RGCs, less apoptotic RGCs, and smaller constricted pupil area were observed in the GTE-fed ischemic rats. GTE also reduced the increased protein expressions caused by ischemic injury but enhanced the Jak phosphorylation in the retina. Notably, green tea extract did not affect the survival of RGCs in the uninjured normal rats. Conclusions: In summary, GTE offers neuroprotection to RGCs under ischemic challenge, suggesting a potential therapeutic strategy for glaucoma and optic neuropathies.

13.
Atherosclerosis ; 289: 8-13, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31437611

RESUMO

BACKGROUND AND AIMS: Epidemiological evidence on the association between elevated lipoprotein (a) (Lp (a)) with risk of stroke remains inconsistent. We aimed to investigate the association between serum Lp (a) level and the risk of stroke among middle-aged and elderly Chinese. METHODS: A community-based prospective cohort study of 8500 participants aged 40 years or older was conducted in Jiading district, Shanghai, China, in 2010. The incident strokes were documented at follow-up visit during 2014-2015. RESULTS: During a mean follow-up of 5.1 years, 444 incident cases of stroke occurred. The incidences of stroke were 4.44%, 5.14% and 6.14% from the lowest to the highest serum Lp (a) tertile, respectively. A significant association between serum Lp (a) tertile and the risk of incident stroke was observed (p for trend<0.05). Compared with individuals in the lowest tertile of serum Lp (a), the multivariable adjusted hazards ratio (HR) and 95% confidence interval (CI) for incident stroke in Lp (a) tertile 3 were 1.34 (1.06-1.70). CONCLUSIONS: Serum Lp (a) concentration was associated with increased risk of incident stroke in Chinese adults.

14.
Sci China Life Sci ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31432375

RESUMO

This study evaluated the influence of the degree of donor bone marrow (BM) hyperplasia on patient clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twelve patients received allo-HSCT from hypoplastic BM donors between January 2010 and December 2017. Forty-eight patients whose donors demonstrated BM hyperplasia were selected using a propensity score matching method (1:4). Primary graft failure including poor graft function and graft rejection did not occur in two groups. In BM hypoplasia and hyperplasia groups, the cumulative incidence (CI) of neutrophil engraftment at day 28 (91.7% vs. 93.8%, P=0.75), platelet engraftment at day 150 (83.3% vs. 93.8%, P=0.48), the median time to myeloid engraftment (14 days vs. 14 days, P=0.85) and platelet engraftment (14 days vs. 14 days, P=0.85) were comparable. The 3-year progression-free survival, overall survival, CI of non-relapse mortality and relapse were 67.8% vs. 71.7% (P=0.98), 69.8% vs. 77.8% (P=0.69), 18.5% vs. 13.6% (P=0.66), and 10.2% vs. 10.4% (P=0.82), respectively. In multivariate analysis, donor BM hypoplasia did not affect patient clinical outcomes after allo-HSCT. If patients have no other suitable donor, a donor with BM hypoplasia can be used for patients receiving allo-HSCT if the donor Complete Blood Count and other examinations are normal.

15.
JAMA Cardiol ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365039

RESUMO

Importance: Whether optimal cardiovascular health metrics may counteract the risk of cardiovascular events among patients with prediabetes or diabetes is unclear. Objective: To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with subsequent development of cardiovascular disease (CVD) among participants with prediabetes or diabetes as compared with participants with normal glucose regulation. Design, Setting, and Participants: The China Cardiometabolic Disease and Cancer Cohort Study was a nationwide, population-based, prospective cohort study of 20 communities from various geographic regions in China. The study included 111 765 participants who were free from CVD or cancer at baseline. Data were analyzed between 2011 and 2016. Exposures: Prediabetes and diabetes were defined according to the American Diabetes Association 2010 criteria. Seven ICVHMs were adapted from the American Heart Association recommendations. Main Outcomes and Measures: The composite of incident fatal or nonfatal CVD, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure. Results: Of the 111 765 participants, 24 881 (22.3%) had normal glucose regulation, 61 024 (54.6%) had prediabetes, and 25 860 (23.1%) had diabetes. Mean (SD) age ranged from 52.9 (8.6) years to 59.4 (8.7) years. Compared with participants with normal glucose regulation, among participants with prediabetes, the multivariable-adjusted hazard ratio for CVD was 1.34 (95% CI, 1.16-1.55) for participants who had 1 ICVHM or less and 0.57 (95% CI, 0.43-0.75) for participants who had at least 5 ICVHMs; among participants with diabetes, the hazard ratios for CVD were 2.05 (95% CI, 1.76-2.38) and 0.80 (95% CI, 0.56-1.15) for participants who had 1 ICVHM or less and at least 5 ICVHMs, respectively. Such pattern of association between ICVHM and CVD was more prominent for participants younger than 55 years (prediabetes and at least 5 ICVHMs: hazard ratio [HR], 0.32; 95% CI, 0.16-0.63; 1 ICVHM or less: HR, 1.58, 95% CI, 1.13-2.21; diabetes and at least 5 ICVHMs: HR, 0.99; 95% CI, 0.44-2.26; 1 ICVHM or less: HR, 2.46; 95% CI, 1.71-3.54; compared with normal glucose regulation) than for participants 65 years or older (prediabetes and at least 5 ICVHMs: HR, 0.80; 95% CI, 0.50-1.26; 1 ICVHM or less: HR, 1.01; 95% CI, 0.79-1.31; diabetes and at least 5 ICVHMs: HR, 0.79; 95% CI, 0.46-1.35; 1 ICVHM or less: HR, 1.73; 95% CI, 1.36-2.22, compared with normal glucose regulation; P values for interaction ≤.02). Additionally, the hazard ratio for CVD per additional ICVHM was 0.82 (95% CI, 0.79-0.86) among participants with prediabetes and was 0.85 (95% CI, 0.80-0.89) among participants with diabetes. Conclusions and Relevance: Participants with prediabetes or diabetes who had 5 or more ICVHMs exhibited lower or no significant excess CVD risks compared with the participants with normal glucose regulation.

16.
BMC Ophthalmol ; 19(1): 170, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382918

RESUMO

BACKGROUND: To assess bioactive transforming growth factor-ß2 (TGFß2) and secreted frizzled-related protein-1 (SFRP1) levels in aqueous humor (AH) of different types of glaucoma. METHODS: AH samples were obtained immediately before ophthalmic surgery with a 27-gauge needle attached to a microsyringe from 126 eyes (105 patients) divided into five groups: cataract (control), primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), primary angle-closure suspects (PACS), and acute angle-closure glaucoma (AACG). Bioactive TGFß2 and SFRP1 levels were assayed by ELISA. RESULTS: The concentration of TGFß2 in AH of POAG patients, but not CACG, PACS, or AACG patients, was significantly higher than control eyes. However, within the AACG group, although the TGFß2 levels in AH did not differ significantly from the control level when all AACG patients were grouped together, there were differences when the AACG patients were divided into high and normal intraocular pressure (IOP); TGFß2 of AACG patients with high IOP (> 21 mmHg) was significantly higher than those with normal IOP. AH levels of SFRP1 were not significantly different among the groups. However, a statistical significant, negative correlation between SFRP1 and IOP existed in the POAG group. POAG patients with high IOP had lower levels of SFRP1 than those with normal IOP. In contrast, a significant, positive correlation between SFRP1 level and IOP was detected in the AACG group. AACG patients with high IOP had a higher level of SFRP1 than those with normal IOP. Concentrations of TGFß2 and SFRP1 did not correlate significantly with each other, or with age. CONCLUSIONS: These results indicate that AH levels of TGFß2 and SFRP1 showed different profiles in different types of glaucomas.


Assuntos
Humor Aquoso/metabolismo , Glaucoma de Ângulo Fechado/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Pressão Intraocular/fisiologia , Proteínas/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Idoso , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Glaucoma de Ângulo Fechado/fisiopatologia , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade
17.
Orphanet J Rare Dis ; 14(1): 190, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391115

RESUMO

BACKGROUND: Wolfram Syndrome (WFS) is a rare autosomal recessive neurodegenerative disease which has a wide spectrum of manifestations including diabetes insipidus, diabetes mellitus, optic atrophy and deafness. WFS1 and CISD2 are two main causing genes of WFS. The aim of this study was to illustrate the ophthalmologic manifestations and determine the genotype of Chinese WFS patients. RESULTS: Completed ophthalmic examinations and family investigations were performed on 4 clinically diagnosed WFS patients from 4 unrelated families. Genetic testing was done by the next generation sequencing of candidate genes. One patient carried a homozygous mutation (c.272_273del) in CISD2, two patients carried compound heterozygous mutations (c.1618 T > G + c.2020G > A and c.1048 T > A + c.2020G > A) in WFS1, and one patient carried a heterozygous mutation (c.937C > T) in WFS1. Three of them were novel mutations. CONCLUSIONS: Our study indicated WFS in Chinese is a neurodegenerative disease with both wide spectrum of clinical features and genetic heterogeneity. We found three novel mutations in WFS patients, and to our best knowledge, this is the first report of Chinese WFS patient with mutation in CISD2.

18.
J Diabetes ; 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31290214

RESUMO

BACKGROUND: Unhealthy diet is one of the important risk factors of diabetes, which is one of the major public health problems in China. The Internet tools provide large-scale passively collected data that show people's dietary preferences and their relationship with diabetes risk. METHODS: 212 341 708 individuals' dietary preference labels were created based on Internet data from online search and shopping software. Metabolic data obtained from the 2010 China Noncommunicable Disease Surveillance, which had 98 658 participants, was used to estimate the relation between dietary preferences geographical distribution and diabetes risk. RESULTS: Chinese dietary preferences had different geographical distribution, which is related to the local climate and consumption level. Fried food preference proportion distribution was significantly positively correlated with diabetes prevalence, hypertension prevalence and body mass index (BMI). Similarly, grilled food preference proportion distribution had significantly positive correlation with the prevalence of diabetes and hypertension. In contrast, spicy food preference proportion distribution was negatively correlated with diabetes prevalence. Sweet food preference proportion distribution was positively related to diabetes prevalence. Using dietary preferences data to predict regional prevalence of diabetes, hypertension and BMI, the average values of error (95% CI) between the three paired predicted and observed values were 9.8% (6.9%-12.7%), 7.5% (5.0%-10.0%) and 1.6% (1.2%-2.0%), respectively. CONCLUSIONS: Fried food, grilled food, and sweet food preferences were positively related to diabetes risk whereas spicy food preference was negatively correlated with diabetes risk. Dietary preferences based on passively collected Internet data could be used to predict regional prevalence of diabetes, hypertension, and BMI and showed good value for public health monitoring.

19.
Cancer Discov ; 9(10): 1452-1467, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31285298

RESUMO

Altered expression of XPO1, the main nuclear export receptor in eukaryotic cells, has been observed in cancer, and XPO1 has been a focus of anticancer drug development. However, mechanistic evidence for cancer-specific alterations in XPO1 function is lacking. Here, genomic analysis of 42,793 cancers identified recurrent and previously unrecognized mutational hotspots in XPO1. XPO1 mutations exhibited striking lineage specificity, with enrichment in a variety of B-cell malignancies, and introduction of single amino acid substitutions in XPO1 initiated clonal, B-cell malignancy in vivo. Proteomic characterization identified that mutant XPO1 altered the nucleocytoplasmic distribution of hundreds of proteins in a sequence-specific manner that promoted oncogenesis. XPO1 mutations preferentially sensitized cells to inhibitors of nuclear export, providing a biomarker of response to this family of drugs. These data reveal a new class of oncogenic alteration based on change-of-function mutations in nuclear export signal recognition and identify therapeutic targets based on altered nucleocytoplasmic trafficking. SIGNIFICANCE: Here, we identify that heterozygous mutations in the main nuclear exporter in eukaryotic cells, XPO1, are positively selected in cancer and promote the initiation of clonal B-cell malignancies. XPO1 mutations alter nuclear export signal recognition in a sequence-specific manner and sensitize cells to compounds in clinical development inhibiting XPO1 function.This article is highlighted in the In This Issue feature, p. 1325.

20.
J Cell Physiol ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332789

RESUMO

Transforming growth factor ß (TGF-ß) is part of the transforming growth factor ß superfamily which is involved in many physiological processes and closely related to the carcinogenesis. Here, we discuss the TGF-ß structure, function, and its canonical Smads signaling pathway. Importantly, TGF-ß has been proved that it plays both tumor suppressor as well as an activator role in tumor progression. In an early stage, TGF-ß inhibits cell proliferation and is involved in cell apoptosis. In an advanced tumor, TGF-ß signaling pathway induces tumor invasion and metastasis through promoting angiogenesis, epithelial-mesenchymal transition, and immune escape. Furthermore, we are centered on updated research results into the inhibitors as drugs which have been studied in preclinical or clinical trials in tumor carcinogenesis to prevent the TGF-ß synthesis and block its signaling pathways such as antibodies, antisense molecules, and small-molecule tyrosine kinase inhibitors. Thus, it is highlighting the crucial role of TGF-ß in tumor therapy and may provide opportunities for the new antitumor strategies in patients with cancer.

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