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1.
J Affect Disord ; 260: 334-341, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521871

RESUMO

BACKGROUND: To investigate mental and physical health comorbidity with chronic back or neck pain in the Chinese population, and assess the level of disability associated with chronic back or neck pain. METHODS: Data were derived from a large-scale and nationally representative community survey of adult respondents on mental health disorders in China (n = 28,140). Chronic back or neck pain, other chronic pain conditions and chronic physical conditions were assessed by self-report. Mental disorders were assessed by the Composite International Diagnostic Interview (CIDI). Role disability during the past 30 days was assessed with the World Health Organization Disability Assessment Schedule (WHO-DAS-II). RESULTS: The 12-month prevalence of chronic back or neck pain was 10.8%. Most of respondents with chronic back or neck pain (71.2%) reported at least one other comorbid condition, including other chronic pain conditions (53.4%), chronic physical conditions (37.9%), and mental disorders (23.9%). It was found by logistic regression that mood disorders (OR = 3.7, 95%CI:2.8-4.8) showed stronger association with chronic back or neck pain than anxiety disorders and substance disorders. Most common chronic pains and physical conditions were significantly associated with chronic back or neck pain. Chronic back or neck pain was associated with role disability after controlling for demographics and for comorbidities. Physical and mental comorbidities explained 0.7% of the association between chronic back or neck pain and role disability. CONCLUSIONS: Chronic back or neck pain and physical-mental comorbidity is very common in China and chronic back or neck pain may increase the likelihood of other physical and mental diseases. This presents a great challenge for both clinical treatment and public health education. We believe that further study needs to be conducted to improve the diagnostic and management skills for comorbidity conditions.

2.
Carbohydr Polym ; 228: 115385, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635747

RESUMO

A novel copper(II)-ß-cyclodextrin and CuO functionalized graphene oxide composite (CD-CuO/NH2-GO) was successfully synthesized by reacting mono-6-O-toluenesulfonyl-copper(II)-ß-cyclodextrin with amino and CuO functionalized graphene oxide. The characterization results showed that the CD-CuO/NH2-GO was well-characterized and has a BET surface area of 746.5 m2 g-1 and good thermal stability, and CD and CuO were uniformly dispersed. The unique structure of CD-CuO/NH2-GO is conducive to the synergistic effect of the different components, especially for the inclusion ability of CD. Benefiting from that, CD-CuO/NH2-GO could quickly and efficiently remove the thiophenic sulfides, which are difficult to be economically removed by hydrodesulfurization. The removal efficiency for the three sulfides was in the order of benzothiophene > dibenzothiophene > thiophene. The desulfurization process of benzothiophene has the fastest desulfurization rate (0.121 g mg-1 min-1) and maximum sulfur capacity (12.75 mg S g-1). The different molecular inclusion ability of CD for the thiophenic sulfides demonstrates the difference in the desulfurization of CD-CuO/NH2-GO. The work highlights the synthesis and the potential application in fuel desulfurization of supramolecular GO composite nanomaterials.

3.
Ther Drug Monit ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31688833

RESUMO

BACKGROUND: A liquid chromatography-mass spectrometry assay to determine plasma dabigatran concentrations has been available for routine clinical use at our tertiary institutions since 2017. The aim of the study was to describe (1) the use of the assay over time; (2) the indications for testing; and (3) subsequent dabigatran prescribing decisions. METHODS: Patients for whom dabigatran concentrations were measured were identified by using the laboratory database, and clinical data were extracted from the associated electronic health records. RESULTS: There were 233 samples in 24 months. The use of dabigatran increased over time, with a mean (95% CI) increase of +0.5 (0.3-0.7) samples per month. Dabigatran concentrations ranged from < 1 to 1060 µg/L. The main reasons for testing were uncertainty about impact on renal function and drug interactions (39%), to inform prescribing decisions after thromboembolic or bleeding events (21%), and for investigation following dose-adjustment (16%). Dabigatran dose was changed after 30% (68/233) of assay results. CONCLUSIONS: The clinical use of the dabigatran assay has increased, with almost one-third of results associated with a subsequent change in dabigatran prescribing.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31730927

RESUMO

With the development of aquaculture industry, high-carbohydrate diet is used to stimulate protein-sparing effect and reduce feed cost. However, fish utilize carbohydrates poorly in general, and instead, high level of carbohydrates in the diet influence the growth condition of fish. How to alleviate the side effects of high carbohydrate diet on fish health has attracted more and more attentions. In the present study, Nile tilapia (Oreochromis niloticus) were fed with 25% and 45% of carbohydrate diet for eight weeks. Higher body weight but lower resistance to pathogen was found in 45% carbohydrate diet group. Higher expression level of inflammation cytokines, increased expression of total NF-κB protein and phosphorylated NF-κB protein (p-NF-κB) were detected in higher carbohydrate group. Concentration of short-chain fatty acids (SCFAs) was measured and the results indicated that high-carbohydrate diet decreased acetate content in the intestine. In order to detect the relationship between the decreased concentration of acetate and lower resistance to pathogen in high-carbohydrate group, 45% of carbohydrate diets (HC) supplemented with different concentrations of sodium acetate (HC + LA, 100 mmol/L; HC + MA, 200 mmol/L; HC + HA, 400 mmol/L) were used to raise Nile Tilapia for eight weeks. The results indicated that addition of 200 mmol/L sodium acetate (HC + MA) reduced the mortality when fish were challenged with Aeromonas hydrophila. Furthermore, we also found that addition of 200 mmol/L sodium acetate mainly inhibited p38 mitogen-activated protein kinase (p38MAPK) and NF-κB phosphorylation to decrease the expression level of inflammation cytokines (IL-8, IL-12, TNF-α and IL-1ß) in the intestine. The present study indicated that certain concentration of sodium acetate could alleviate high-carbohydrate induced intestinal inflammation mainly by suppressing MAPK activation and NF-κB phosphorylation.

5.
EBioMedicine ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31707150

RESUMO

BACKGROUND: Recurrent implantation failure (RIF) remains a critical and challenging problem in assisted reproductive technology mainly due to impaired decidualization. The endocytic and transcytotic activity in the endometrium are crucial for decidualization. The most representative endocytic gene is the C-terminal Eps15 homology domain-containing 1 (EHD1), but whether EHD1-mediated endocytic function is responsible for embryo implantation during decidualization remains unclear. METHODS: A transcriptomic analysis was performed to evaluate the differentially expressed genes between the fertile control and RIF group. The expression and location of EHD1 in endometrial tissues were further examined by IHC, qRT-PCR and Western blotting. The transduction of an EHD1 recombinant adenovirus into human endometrial stromal cells was performed to investigate relevant decidualization marker genes. Additionally, a microarray analysis following the adenovirus-mediated overexpression of EHD1 was conducted to identify EHD1-related changes in HESCs, and the potential molecular mechanisms were further confirmed through immunofluorescence and coimmunoprecipitation analyses. FINDINGS: An RNA-seq analysis demonstrated that EHD1 expression was significantly higher in the mid-secretory endometrium of the RIF group than in that of the fertile control group. The analysis of the menstrual cycle showed that expression of EHD1 increased in the mid-proliferative phase and showed a gradual decrease in the mid-secretory and decidual phases. Furthermore, EHD1 overexpression impaired decidualization by suppressing the expression of prolactin and insulin-like growth factor binding protein-1 and the formation of the cytoskeleton. The mechanistic analysis revealed the EHD1 regulated LRP5/6 protein function through the endocytic pathway, and subsequently suppressed the Wnt4/ß-catenin pathway during decidualization. In addition, a Wnt4 agonist improved an impaired decidualization process. INTERPRETATION: Regulation of the EHD1-Wnt4 pathway might serve as a promising therapeutic strategy for improving endometrial receptivity in RIF women.

6.
PLoS Med ; 16(11): e1002975, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31743352

RESUMO

BACKGROUND: The Sustainable Development Goals (SDGs), adopted by all United Nations (UN) member states in 2015, established a set of bold and ambitious health-related targets to achieve by 2030. Understanding China's progress toward these targets is critical to improving population health for its 1.4 billion people. METHODS AND FINDINGS: We used estimates from the Global Burden of Disease (GBD) Study 2016, national surveys and surveillance data from China, and qualitative data. Twenty-eight of the 37 indicators included in the GBD Study 2016 were analyzed. We developed an attainment index of health-related SDGs, a scale of 0-100 based on the values of indicators. The projection model is adjusted based on the one developed by the GBD Study 2016 SDG collaborators. We found that China has achieved several health-related SDG targets, including decreasing neonatal and under-5 mortality rates and the maternal mortality ratios and reducing wasting and stunting for children. However, China may only achieve 12 out of the 28 health-related SDG targets by 2030. The number of target indicators achieved varies among provinces and municipalities. In 2016, among the seven measured health domains, China performed best in child nutrition and maternal and child health and reproductive health, with the attainment index scores of 93.0 and 91.8, respectively, followed by noncommunicable diseases (NCDs) (69.4), road injuries (63.6), infectious diseases (63.0), environmental health (62.9), and universal health coverage (UHC) (54.4). There are daunting challenges to achieve the targets for child overweight, infectious diseases, NCD risk factors, and environmental exposure factors. China will also have a formidable challenge in achieving UHC, particularly in ensuring access to essential healthcare for all and providing adequate financial protection. The attainment index of child nutrition is projected to drop to 80.5 by 2025 because of worsening child overweight. The index of NCD risk factors is projected to drop to 38.8 by 2025. Regional disparities are substantial, with eastern provinces generally performing better than central and western provinces. Sex disparities are clear, with men at higher risk of excess mortality than women. The primary limitations of this study are the limited data availability and quality for several indicators and the adoption of "business-as-usual" projection methods. CONCLUSION: The study found that China has made good progress in improving population health, but challenges lie ahead. China has substantially improved the health of children and women and will continue to make good progress, although geographic disparities remain a great challenge. Meanwhile, China faced challenges in NCDs, mental health, and some infectious diseases. Poor control of health risk factors and worsening environmental threats have posed difficulties in further health improvement. Meanwhile, an inefficient health system is a barrier to tackling these challenges among such a rapidly aging population. The eastern provinces are predicted to perform better than the central and western provinces, and women are predicted to be more likely than men to achieve these targets by 2030. In order to make good progress, China must take a series of concerted actions, including more investments in public goods and services for health and redressing the intracountry inequities.

7.
BMC Complement Altern Med ; 19(1): 309, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718632

RESUMO

BACKGROUND: Sheng Mai San (SMS) has been proven to exhibit cardio-protective effects. This study aimed to explore the molecular mechanisms of SMS on hyperglycaemia (HG)-induced apoptosis in H9C2 cells. METHODS: HG-induced H9C2 cells were established as the experimental model, and then treated with SMS at 25, 50, and 100 µg/mL. H9C2 cell viability and apoptosis were quantified using MTT and Annexin V-FITC assays, respectively. Furthermore, Bcl-2/Bax signalling pathway protein expression and Fas and FasL gene expression levels were quantified using western blotting and RT-PCR, respectively. RESULTS: SMS treatments at 25, 50, 100 µg/mL significantly improved H9C2 cell viability and inhibited H9C2 cell apoptosis (p < 0.05). Compared to the HG group, SMS treatment at 25, 50, and 100 µg/mL significantly downregulated p53 and Bax expression and upregulated Bcl-2 expression (p < 0.05). Moreover, SMS treatment at 100 µg/mL significantly downregulated Fas and FasL expression level (p < 0.05) when compared to the HG group. CONCLUSION: SMS protects H9C2 cells from HG-induced apoptosis probably by downregulating p53 expression and upregulating the Bcl-2/Bax ratio. It may also be associated with the inhibition of the Fas/FasL signalling pathway.

8.
Parkinsonism Relat Disord ; 69: 125-133, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31751864

RESUMO

BACKGROUND: Mutations in the SPAST gene are the most frequent cause of hereditary spastic paraplegia (HSP). We aim to extend the mutation spectrum of spastic paraplegia 4 (SPG4) and carried out experiment in vitro to explore the influence of the SPAST gene mutation on the function of corresponding protein. METHODS: Whole-exome sequencing (WES) combined with multiplex ligation-dependent probe amplification (MLPA) were performed in a cohort of 150 patients clinically diagnosed with HSP. We focus on screening for mutations in SPAST gene and carrying out functional experiments to assess the effects of the novel variants. RESULTS: A total of 34 different mutations in the SPAST gene were identified, of which 10 were novel, including 1 missense (c.1479T > A), 1 nonsense (c.766G > T), 3 splicing (c.1413 + 1_1413+4delGTAA, c.1729-1G > A and c.1536+2T > G) and 5 frameshift mutations (c.1094delC, c.885dupA, c.517_518delAG, c.280delG and c.908dupC). For 7 novel non-splicing mutations, functional study showed that accumulated M1 spastin colcocalized with microtubules which was different from a uniformly diffused M87 spastin. While an impairment in severing activity was observed in both mutant M1 and mutant M87, except for c.280delG. All 3 novel splicing variants w ere predicted to affect splicing by using bioinformatic programs. However, only c.1536+2T > G had no influence on splice site in vitro, which conflicts with the in-silico analysis. CONCLUSION: We genetically diagnosed 40 SPG4 patients. All the novel non-splicing mutations except for c.280delG were certified to exert an effect on the microtubule-severing and all the novel splicing mutations other than c.1536+2T > G would cause abnormal splicing of the spastin.

9.
J Immunol ; 203(10): 2614-2620, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31578271

RESUMO

Mucosal-associated invariant T (MAIT) cells play a key role in local and systemic immune responses. Studies suggest that type 2 diabetes (T2D) is associated with alterations in the human MAIT cell response. However, the mechanisms that regulate the survival and homeostasis of human MAIT cells are poorly defined. In this study, we demonstrate that the costimulatory TNF superfamily receptor OX40 was highly expressed in MAIT cells of patients with T2D. Compared with OX40-negative MAIT cells, OX40-positive MAIT cells showed a high activation and a memory phenotype. Surprisingly, OX40 expression was negatively correlated with the frequency of MAIT cells in the peripheral blood of T2D patients. Increased cleaved caspase-3 levels were observed in OX40+-expressing MAIT cells in T2D patients. In vitro, activated OX40 signaling by recombinant OX40L protein promoted caspase-3 activation and apoptosis of MAIT cells. Inhibition of caspase-3 restored apoptosis of MAIT cells induced by OX40 signaling. These results identify OX40 as an amplifier of activation-induced cell death of human blood MAIT cells and shed new light on the regulation of MAIT cells in the phase of immune responses in T2D.

10.
Diabetes ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31658956

RESUMO

It is estimated that ∼1% of European-ancestry patients clinically diagnosed with type 1 diabetes (T1D) actually have monogenic forms of the disease. Because of the much lower incidence of true T1D in East Asians, we hypothesised that the percentage would be much higher.To test this, we sequenced the exome of 82 Chinese Han patients clinically diagnosed as T1D but negative for three autoantibodies. Analysis focused on established or proposed mongenic diabetes genes.We found credible mutations in 18 of the 82 autoantibody-negative patients (19.5%). All mutations had consensus pathogenicity support by five algorithms. As in Europeans, the most common gene was HNF1A (MODY3), in 6/18 cases. Surprisingly, almost as frequent were diallelic mutations in WFS1, known to cause Wolfram syndrome but also described in non-syndromic cases. Fasting C-peptide varied widely and was not predictive.Given the 27.4% autoantibody negativity in Chinese and 22% mutation rate, we estimate that around 6% of Chinese with a clinical T1D diagnosis have monogenic diabetes.Our findings support universal sequencing of autoantibody-negative cases as standard of care in East Asian patients with a clinical T1D diagnosis. Non-syndromic diabetes with WSF1 mutations is not rare in Chinese. Its response to alternative treatments should be investigated.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1374-1379, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607286

RESUMO

OBJECTIVE: To investigate the influence of oridonin on the killing activity of NK-92 MI cells targeting THP1 and the related mechanism. METHODS: The killing activity of NK-92 MI to THP1 before and after oridonin treatment was detected by LDH release assay; the expression of natural killer cell ligands activating receptor D (NKG2D, including MICA, MICB, ULBP1, ULBP2 and ULBP3) was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot respectively; the expression of cytokine TNF-α, TNF-ß and IFN-γ in the co-culture supernatant of NK-92 MI cells and THP1 cells were measured by ELISA. RESULTS: The killing efficiency after oridonin treatment at different effector-target ratio (1:1, 5:1, 10:1) was all significantly up-regulated in comparison with that before oridonin treatment (P<0.05). QRT-PCR and Western blot showed that the expressions of mRNA and protein levels of MICB, ULBP1, ULBP2 increased to varying degree (P<0.05), but the expression levels of MICA and ULBP3 were not statistically significant between experimental group and control group (P>0.05). ELISA results indicated that IFN-γ and TNF-ß release were significantly increased after oridonin treatment (P<0.05), however, the TNF-α release was not statistically different in comparison with control group (P>0.05). CONCLUSION: Oridonin can significantly improve killing efficiency of NK-92 MI on THP1, that might be related with up-regulation of MICB, ULBP1 and ULBP2 expression and promotion of IFN-γ and TNF-ß release.


Assuntos
Diterpenos de Caurano/farmacologia , Linhagem Celular Tumoral , Proteínas Ligadas por GPI , Antígenos de Histocompatibilidade Classe I , Humanos
12.
Obes Surg ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605365

RESUMO

BACKGROUND: Duodenal-jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction. Increasing evidence has demonstrated that brain insulin signaling plays an important role in the pathophysiology of type 2 diabetes. This study explores whether the antidiabetic effect of DJB is involved in brain insulin signaling activation and brain glucose utilization. METHODS: A diabetic rat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabetic rats. 18F-FDG PET scanning was used to detect glucose uptake in different organs, particularly in the brain. The levels of glucose transporters, glucose utilization-related proteins (HK1 and PFK2), insulin, and insulin signaling pathway-related proteins (InsR, IRS1/2, PI3K, and p-Akt) in the brain tissues were evaluated and analyzed. RESULTS: The results showed that DJB significantly improved basal glycemic parameters and reversed the decreasing glucose uptake in the brains of type 2 diabetic rats. DJB significantly increased not only the expression levels of brain insulin, IRS1/2, PI3K, and p-Akt but also the levels of the glucose utilization enzymes HK1 and PFK2 in the brain. CONCLUSION: These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.

13.
Mol Genet Genomic Med ; : e988, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566922

RESUMO

BACKGROUND: Pathogenic variants of ANKRD11 have been reported to cause KBG syndrome characterized by short stature, characteristic facial appearance, intellectual disability, macrodontia, and skeletal anomalies. However, the direct clinical relevance of ANKRD11 mutation with short stature is yet unknown. METHODS: Here, we report a Chinese boy with idiopathic short stature (ISS) based on clinical and genetic characteristics. Comprehensive medical evaluations were performed including metabolic studies, endocrine function tests, bone X-rays, and echocardiography. Whole-exome and Sanger sequencing was used to detect and confirm genetic mutations associated with short stature in this patient, respectively. The pathogenicity of the variant was further predicted by several in silico prediction tools and repositories of sequence variation. Twenty-four months follow-up was performed to observe the growth rate of the patient treated with recombinant human growth hormone (GH). RESULTS: One heterozygous point mutation (c.2579C>T) was confirmed in the ANKRD11 gene of the patient and inherited from his mother. This mutation site was located within the highly conservative region of ANKRD11 protein and predicted to be possibly damaging in several in silico prediction programs and repositories of sequence variation. Additionally, patient underwent GH replacement therapy for 24 months exhibited good response to the treatment. CONCLUSION: A heterozygous point mutation of AKNRD11 gene was identified in a Chinese patient with short stature phenotype. The patient was treated effectively with GH supplementation.

14.
Nanoscale ; 11(43): 20667-20675, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31642452

RESUMO

Retinal ischemia-reperfusion (I/R) injuries are involved in the universal pathological processes of many ophthalmic diseases, including glaucoma, diabetic retinopathy, and retinal arterial occlusion. The reason is that the ischemia-reperfusion injury is accompanied by the abnormal accumulation of reactive oxygen species (ROS), which can cause damage to retinal ganglion cells (RGCs), promote their apoptosis, and finally lead to the irreversible loss of the visual field. RGCs are specialized projection neurons that are situated in the inner retinal surface of the eye, and they transmit visual images into certain areas of the brain in the form of action potentials. Therefore, any damage that affects the viability of RGCs can cause visual field defects or even irreversible vision loss. There is no effective drug treatment in clinical practice for the loss of the visual field that is caused by the oxidation and apoptosis of RGCs. Hence, finding a drug with neuroprotective and antioxidant functions is urgently needed. As a new type of nanomaterial, tetrahedral framework nucleic acids (tFNAs) exhibit outstanding biocompatibility and have been shown in our previous studies to participate in the positive regulation of cell behavior. In this experiment, we first established a cellular model of oxidative stress in RGCs with tert-butyl peroxide (TBHP). Then, we primarily explored the antioxidant and neuroprotective effects of tFNAs after TBHP-induced oxidative stress and the main mechanisms by which the tFNAs function. Our research showed that tFNAs could reduce the production of reactive oxygen species (ROS) in cells and protect the cells from oxidative stress by regulating intracellular oxidation-related enzymes. In addition, tFNAs could simultaneously improve oxidative stress-induced apoptosis significantly via affecting the expression of apoptosis-related proteins. Finally, we confirmed by western blotting that the mechanism by which tFNAs prevent damage caused by oxidative stress involves activating the Akt/Nrf2 pathway. Our findings provide new ideas for the prevention and treatment of a series of diseases that are caused by oxidative stress to RGCs.

15.
Diabetes Obes Metab ; 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31608548

RESUMO

AIM: To examine the relationship between baseline fasting C-peptide (FCP) and outcomes in insulin-naïve people with type 2 diabetes initiating basal insulin glargine 100 U/mL (Gla-100). MATERIALS AND METHODS: Post hoc pooled analysis of nine randomized, treat-to-target trials in patients with type 2 diabetes inadequately controlled on oral antihyperglycaemic drugs initiating once-daily Gla-100. Participants (n = 2165) were stratified at baseline according to FCP (≤0.40, >0.40-1.20, >1.20-2.00, >2.00 nmol/L). Glycaemic control, body weight, insulin dose and hypoglycaemia were determined at 24 weeks. RESULTS: At baseline low FCP levels were associated with longer known diabetes duration, lower body mass index and higher fasting plasma glucose (FPG). Following Gla-100 introduction, the mean HbA1c reduction at week 24 was similar in all four FCP groups, albeit fewer people in the lowest FCP group achieved HbA1c <7.0% versus FCP groups >0.40 nmol/L. By contrast, FPG reduction and proportion reaching FPG ≤5.6 mmol/L were greatest in the lowest FCP group, diminishing at higher FCP levels. Gla-100 dose at week 24 was lowest in the ≤0.40 nmol/L FCP group and highest in the >1.20 nmol/L FCP group. Incidence and event rate of overall, nocturnal and severe hypoglycaemia were higher at week 24 in groups with lower FCP levels. In multivariable regression analysis baseline FCP, concomitant sulphonylurea use and endpoint HbA1c were strong predictors of hypoglycaemia. CONCLUSIONS: FCP levels identified patients with type 2 diabetes experiencing different responses to basal insulin Gla-100. A low FCP identifies a markedly insulin-deficient, insulin-sensitive subgroup/phenotype with an enhanced risk of hypoglycaemia, which requires a low initial basal insulin dose, cautious titration and earlier addition of prandial glucose-lowering therapy.

16.
Cell Death Dis ; 10(11): 819, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659158

RESUMO

miR-18a has been reported to be upregulated in nasopharyngeal carcinoma (NPC) tissues by microarray assays. However, the roles and the underlying mechanisms of miR-18a in NPC remain poorly understood. Here we demonstrated by real-time RT-PCR that miR-18a expression is upregulated in NPC tissues, and positively correlated with tumor size and TNM stage. Moreover, miR-18a expression could be upregulated by NF-κB activation or Epstein-Barr virus encoded latent membrane protein 1 expression. The ectopic expression of miR-18a promoted NPC cell proliferation, migration and invasion, while the repression of miR-18a had opposite effects. Candidate genes under regulation by miR-18a were screened out through a whole-genome microarray assay, further identified by a reporter assay and verified in clinical samples. SMG1, a member of the phosphoinositide 3-kinase-related kinases family and an mTOR antagonist, was identified as functional target of miR-18a. Our results confirmed that miR-18a exerts its oncogenic role through suppression of SMG1 and activation of mTOR pathway in NPC cells. Importantly, in vivo xenograft tumor growth in nude mice was effectively inhibited by intratumor injection of miR-18a antagomir. Our data support an oncogenic role of miR-18a through a novel miR-18a/SMG1/mTOR axis and suggest that the antitumor effects of antagomir-18a may make it suitable for NPC therapy.

17.
Blood Adv ; 3(19): 2836-2844, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31582392

RESUMO

In the absence of prospective studies that examine the effect of conditioning regimen intensity after T-cell-replete haploidentical transplant for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS), a retrospective cohort analysis was performed. Of the 1325 eligible patients (AML, n = 818; ALL, n = 286; and MDS, n = 221), 526 patients received a myeloablative regimen and 799 received a reduced-intensity regimen. Graft-versus-host disease prophylaxis was uniform with posttransplant cyclophosphamide, a calcineurin inhibitor, and mycophenolate mofetil. The primary end point was disease-free survival. Cox regression models were built to study the effect of conditioning regimen intensity on transplant outcomes. For patients aged 18 to 54 years, disease-free survival was lower (hazard ratio [HR], 1.34; 42% vs 51%; P = .007) and relapse was higher (HR, 1.51; 44% vs 33%; P = .001) with a reduced-intensity regimen compared with a myeloablative regimen. Nonrelapse mortality did not differ according to regimen intensity. For patients aged 55 to 70 years, disease-free survival (HR, 0.97; 37% vs 43%; P = .83) and relapse (HR, 1.32; 42% vs 31%; P = .11) did not differ according to regimen intensity. Nonrelapse mortality was lower with reduced-intensity regimens (HR, 0.64; 20% vs 31%; P = .02). Myeloablative regimens are preferred for AML, ALL, and MDS; reduced-intensity regimens should be reserved for those unable to tolerate myeloablation.

18.
Sci Rep ; 9(1): 14838, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619699

RESUMO

Late embryogenesis abundant (LEA) proteins belong to a large family that exists widely in plants and is mainly involved in desiccation processes during plant development or in the response to abiotic stresses. Here, we reported on an atypical LEA gene (IpLEA) related to salt tolerance from Ipomoea pes-caprae L. (Convolvulaceae). Sequence analysis revealed that IpLEA belongs to the LEA_2 (PF03168) group. IpLEA was shown to have a cytoplasmic localization pattern. Quantitative reverse transcription PCR analysis showed that IpLEA was widely expressed in different organs of the I. pes-caprae plants, and the expression levels increased following salt, osmotic, oxidative, freezing, and abscisic acid treatments. Analysis of the 1,495 bp promoter of IpLEA identified distinct cis-acting regulatory elements involved in abiotic stress. Induction of IpLEA improved Escherichia coli growth performance compared with the control under abiotic stresses. To further assess the function of IpLEA in plants, transgenic Arabidopsis plants overexpressing IpLEA were generated. The IpLEA-overexpressing Arabidopsis seedlings and adult plants showed higher tolerance to salt and drought stress than the wild-type. The transgenic plants also showed higher oxidative stress tolerance than the wild-type Arabidopsis. Furthermore, the expression patterns of a series of stress-responsive genes were affected. The results indicate that IpLEA is involved in the plant response to salt and drought, probably by mediating water homeostasis or by acting as a reactive oxygen species scavenger, thereby influencing physiological processes under various abiotic stresses in microorganisms and plants.

20.
Syst Biol Reprod Med ; : 1-9, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574241

RESUMO

HOXA10 is an important regulator of embryo adhesion. Reduced expression may contribute to embryo implantation failure. The expression of Nur77 and HOXA10 has been shown to be reduced in the endometrium of patients with recurrent implantation failure. In this study, we found that Nur77 was directly bound to the HOXA10 promoter and promoted HOXA10 protein expression in a dose-dependent manner in Ishikawa cells. Furthermore, the promoting effect of Nur77 on embryo adhesion was significantly blocked when endogenous HOXA10 expression was knocked down in Ishikawa cells. Moreover, the Nur77 agonist 6-MP was also confirmed to promote embryo adhesion. This study is the first to show that Nur77 promotes embryo adhesion by transcriptionally regulating HOXA10 expression. Nur77 and 6-MP may provide a basis to develop a new treatment for patients who suffer from embryo adhesion dysfunction. Abbreviations: HB-EGF: heparin-binding epidermal growth factor-like growth factor; HOXA10: homeobox A10; NGFI-B: nerve growth factor-induced gene B; RIF: recurrent implantation failure; RPL: recurrent pregnancy loss; 6-MP: 6-mercaptopurine; IGFBP-1: insulin-like growth factor binding protein-1; LIF: leukemia inhibitory factor; IL-1ß: Interleukin - 1ß; CRISPR/Cas9: Clustered Regularly Interspaced Short Palindromic Repeats; AF-1: activation function-1 domain; HIF-1α: hypoxia-inducible factor 1α; CREB: cAMP response element binding.

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