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1.
Food Funct ; 10(11): 7081-7090, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670358

RESUMO

This study was conducted to investigate the effects of stocking density and dietary nicotinamide (NAM) and butyrate sodium (BA) supplementation on the growth performance, liver mitochondrial function and gut microbiota of broilers at high stocking density. A total of 342, 26-d-old Cobb500 broilers were divided into 5 groups with 6 replicates. Treatments were as follows: (a) Low stocking density (L, 9 birds per cage); (b) High stocking density (H, 12 birds per cage); (c) H + 50 ppm NAM; (d) H + 500 ppm BA; (e) H + 50 ppm NAM + 500 ppm BA (COMB). The results showed that high stocking density significantly reduced the feed intake and body weight gain of broilers, while COMB improved the growth performance at high stocking density. High stocking density significantly reduced the liver metallothionein content, liver mitochondrial membrane potential and the activities of Na+K+-ATPase and Ca2+Mg2+-ATPase. In contrast, the liver metallothionein contents in the NAM, BA and COMB fed group were higher than those in the H group. COMB increased the activity of ATPase as well, but it failed to enhance the mitochondrial membrane potential. Stocking density also affected gut microbiota of broilers. The high-density group increased the relative abundance of Blautia. Supplementation of BA and NAM increased the abundance of Lactobacillus and Bifidobacteria, respectively. In conclusion, a combination of NAM and BA can improve the performance, antioxidant capacity, mitochondrial function and intestinal microbiota of broilers at high stocking density.

2.
Zootaxa ; 4586(3): zootaxa.4586.3.10, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31716123

RESUMO

The Labomimus Sharp fauna in Taiwan is represented by a single species. In this paper, three new species are described and illustrated: L. dadongmontis sp. nov., L. dilaticeps sp. nov., and L. sugayai sp. nov. The key to species of the L. shibatai Sawada-group is updated to accommodate the two new species placed in this group.


Assuntos
Besouros , Distribuição Animal , Estruturas Animais , Animais , China , Taiwan
3.
Artigo em Inglês | MEDLINE | ID: mdl-31742891

RESUMO

It is widely accepted that hypertension constitutes a significant cardiovascular risk factor and that treating high blood pressure (BP) effectively reduces cardiovascular risk. An important issue in Asia is not just the high prevalence of hypertension, particularly in some countries, but also the low level of awareness and treatment rates in many regions. The 2017 update of the American College of Cardiology/American Heart Association hypertension guidelines raised the question about which BP threshold should be used to diagnose and treat hypertension. Although there is a theoretical rationale for a stricter BP criterion in Asia given the ethnic-specific features of hypertension in the region, the majority of countries in Asia have retained a diagnostic BP threshold of ≥140/90 mm Hg. Although lowering thresholds might make theoretical sense, this would increase the prevalence of hypertension and also markedly reduce BP control rates. In addition, there are currently no data from robust randomized clinical trials of the benefits of the lower targets in preventing cardiovascular disease and reducing cardiovascular risk, particularly in high-risk patients and especially for Asian populations. There is also no defined home BP treatment target level for an office BP treatment target of 130/80 mm Hg. However, in this regard, in the interim, lifestyle modifications, including reducing body weight and salt intake, should form an important part of hypertension management strategies in Asia, while studies on treating at lower BP threshold level in Asians and getting to lower BP targets will be helpful to inform and optimize the management of hypertension in the region.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31696632

RESUMO

Ambulatory blood pressure monitoring (ABPM) can measure 24-hour blood pressure (BP), including nocturnal BP and diurnal variations. This feature of ABPM could be of value in Asian populations for preventing cardiovascular events. However, no study has yet investigated regarding the use of ABPM in actual clinical settings in Asian countries/regions. In this study, 11 experts from 11 countries/regions were asked to answer questionnaires regarding the use of ABPM. We found that its use was very limited in primary care settings and almost exclusively available in referral settings. The indications of ABPM in actual clinical settings were largely similar to those of home BP monitoring (HBPM), that is, diagnosis of white-coat or masked hypertension and more accurate BP measurement for borderline clinic BP. Other interesting indications, such as nighttime BP patterns, including non-dipper BP, morning BP surge, and BP variability, were hardly adopted in daily clinical practice. The use of ABPM as treatment guidance for detecting treated but uncontrolled hypertension in the Asian countries/regions didn't seem to be common. The barrier to the use of ABPM was primarily its availability; in referral centers, patient reluctance owing to discomfort or sleep disturbance was the most frequent barrier. ABPM use was significantly more economical when it was reimbursed by public insurance. To facilitate ABPM use, more simplified indications and protocols to minimize discomfort should be sought. For the time being, HBPM could be a reasonable alternative.

5.
Environ Pollut ; : 113641, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31767230

RESUMO

Cadmium, Cu, Pb and Zn concentrations and distribution in soil, wheat, and the potential for human heavy metal accumulation near a Pb smelting affected area were investigated. Farm land soil, wheat grain and scalp hair samples were collected from three villages (named QD, GF and BS) with increasing distance from a large Pb smelter in China. Soil Cd and Pb concentrations exceeded national standards 46-100% of the time, depending on location. Soil and wheat grain Cd, Cu, Pb and Zn concentrations increased as distance to the smelter decreased. Similarly, greater Cd, Cu and Pb concentrations were present in human scalp hair for those residents living closest to the smelter. Decreasing trends existed for hair-to-wheat grain ratios for Cd and Pb as distance to the smelter increased. Results suggest that as distance to the smelter decreases, human heavy metal absorption via the consumption of metal-contaminated food products (e.g., wheat) increases.

6.
Gastroenterology ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711924

RESUMO

BACKGROUND & AIMS: Pancreatic tumors undergo rapid growth and progression, become resistant to chemotherapy, and recur after surgery. We studied the functions of the solute carrier family 39 member 4 (SLC39A4, also called ZIP4), which regulates concentrations of intracellular zinc and is increased in pancreatic cancer cells, in cell lines and mice. METHODS: We obtained 93 pancreatic cancer specimens (tumor and adjacent non-tumor tissues) from patients who underwent surgery and gemcitabine chemotherapy and analyzed them by immunohistochemistry. ZIP4 and/or ITGA3 or ITGB1 were overexpressed or knocked down with small hairpin RNAs in AsPC-1 and MIA PaCa-2 pancreatic cancer cells lines, and in pancreatic cells from KPC and KPC-ZEB1 knockout mice, and pancreatic spheroids were established; cells and spheroids were analyzed by immunoblots, reverse transcription PCR, and liquid chromatography tandem mass spectrometry. We studied transcriptional regulation of ZEB1, ITGA3, ITGB1, JNK, and ENT1 by ZIP4 using chromatin precipitation and luciferase reporter assays. Nude mice were given injections of genetically manipulated AsPC-1 and MIA PaCa-2 cells and growth of xenograft tumors and metastases was measured. RESULTS: In pancreatic cancer specimens from patients, increased levels of ZIP4 associated with shorter survival times. MIA PaCa-2 cells that overexpressed ZIP4 had increased resistance to gemcitabine, 5-FU, and cisplatin, whereas AsPC-1 cells with ZIP4 knockdown had increased sensitivity to these drugs. In mice, xenograft tumors grown from AsPC-1 cells with ZIP4 knockdown were smaller and more sensitive to gemcitabine. ZIP4 overexpression significantly reduced accumulation of gemcitabine in pancreatic cancer cells, increased growth of xenograft tumors in mice, and increased expression of the integrin subunits ITGA3 and ITGB1; expression of ITGA3 and ITGB1 was reduced in cells with ZIP4 knockdown. Pancreatic cancer cells with ITGA3 or ITGB1 knockdown had reduced proliferation and formed smaller tumors in mice, despite overexpression of ZIP4; spheroids established from these cells had increased sensitivity to gemcitabine. We found ZIP4 to activate STAT3 to induce expression of ZEB1, which induced expression of ITGA3 and ITGB1 in KPC cells. Increased ITGA3 and ITGB1 expression and subsequent integrin α3ß1 signaling, via JNK, inhibited expression of the gemcitabine transporter ENT1, which reduced gemcitabine uptake by pancreatic cancer cells. ZEB1-knockdown cells had increased sensitivity to gemcitabine. CONCLUSIONS: In studies of pancreatic cancer cell lines and mice, we found that ZIP4 increases expression of the transcription factor ZEB1, which activates expression of ITGA3 and ITGB1. The subsequent increase in integrin α3ß1 signaling, via JNK, inhibits expression of the gemcitabine transporter ENT1, so that cells take up smaller amounts of the drug. Activation of this pathway might help mediate resistance of pancreatic tumors to chemotherapeutic agents.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31773883

RESUMO

The Hypertension Cardiovascular Outcome Prevention and Evidence in Asia (HOPE Asia) Network was set up to improve the management of hypertension in Asia with the ultimate goal of achieving "zero" cardiovascular events. Asia is a diverse continent, and the prevalence of hypertension has increased over the last 30 years. There are a number of Asia-specific features of hypertension and hypertension-related cardiovascular complications, which means that a region-specific approach is needed. White-coat hypertension will become more of an issue over time as Asian populations age, and masked hypertension is more prevalent in Asian than in Western countries. Identifying and treating masked hypertension is important to reduce cardiovascular risk. Abnormal patterns of blood pressure (BP) variability common in Asia include exaggerated early morning BP surge and nocturnal hypertension. These are also important cardiovascular risk factors that need to be managed. Home blood pressure monitoring (HBPM) is an important tool for detecting white-coat and masked hypertension, and monitoring BP variability, and practices in Asia are variable. Use of HBPM is important given the Asia-specific features of hypertension, and strategies are needed to improve and standardize HBPM usage. Development of HBPM devices capable of measuring nocturnal BP along with other information and communication technology-based strategies are key developments in the widespread implementation of anticipation medicine strategies to detect and prevent cardiovascular events in patients with hypertension. Region-wide differences in hypertension prevalence, control, and management practices in Asia highlight the importance of information sharing to facilitate best practices.

8.
Med Sci Sports Exerc ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31764468

RESUMO

INTRODUCTION: There is a paucity of information on the clustering of cardiometabolic risk factors in young adults and how this clustering may vary based on whether or not they perform sufficient levels of physical activity. METHODS: We analyzed baseline data from 346 young adults (23.3±4.4 y) participating in the Healthy Body Healthy U (HBHU) clinical trial from 2015-2018. Cardiometabolic risk factors were measured according to standard procedures and moderate-to-vigorous intensity physical activity (MVPA) was determined by accelerometry. A cardiometabolic clustering score (CCS; ranging from 0 to 5) was created from five biomarkers according to whether or not a standard clinical risk cut point was exceeded (0=no; 1=yes): abdominal circumference [>102 cm (men) or >88 cm (women)]; HbA1c (≥ 5.7%); HDL-C [<40 mg/dL (men) or <50 mg/dL (women)]; SBP (≥ 130 mmHg); and DBP (≥85 mmHg). Cardiometabolic dysregulation (CD) was defined as a CCS > 3. Multiple logistic regression determined the independent association between level of MVPA and CD, while adjusting for sex, race/ethnicity, sedentary time, and smoking. RESULTS: The prevalence of CD was 18% (22% in men; 17% in women). We observed a non-linear graded association between MPA and CD. Participants performing 150-300 min/week of MVPA significantly lowered their odds of CD by 66% (OR=0.34; 95% CI=0.16, 0.75), while those exceeding 300 min/week lowered their odds by 61% (OR=0.39; 95% CI: 0.18, 0.86), compared with those performing <150 min/week, independent of obesity and the other covariables.Recommended levels of moderate-intensity physical activity is significantly associated with a lower odds of CD and thus may prevent or diminish the need for expensive pharmaceutical treatment over the remainder of the lifespan.

9.
J Cell Mol Med ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729180

RESUMO

Generating universal human umbilical mesenchymal stem cells (UMSCs) without immune rejection is desirable for clinical application. Here we developed an innovative strategy using CRISPR/Cas9 to generate B2M- UMSCs in which human leucocyte antigen (HLA) light chain ß2-microglobulin (B2M) was deleted. The therapeutic potential of B2M- UMSCs was examined in a mouse ischaemic hindlimb model. We show that B2M- UMSCs facilitated perfusion recovery and enhanced running capability, without inducing immune rejection. The beneficial effect was mediated by exosomes. Mechanistically, microRNA (miR) sequencing identified miR-24 as a major component of the exosomes originating from B2M- UMSCs. We identified Bim as a potential target of miR-24 through bioinformatics analysis, which was further confirmed by loss-of-function and gain-of-function approaches. Taken together, our data revealed that knockout of B2M is a convenient and efficient strategy to prevent UMSCs-induced immune rejection, and it provides a universal clinical-scale cell source for tissue repair and regeneration without the need for HLA matching in the future.

10.
Int J Biol Macromol ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31743716

RESUMO

The sericin protein from silk-processing waste added to the normal diet at 0.8% (g%) level was administered orally to type 2 diabetic (T2D) mice to investigate its hypoglycaemic effects and mechanism. The oral protein is in the form of silk sericin hydrolysate, obtained from a boiling treatment of 0.025% calcium hydroxide solution. The protein significantly decreased fasting blood glucose, fasting plasma insulin, and glycosylated serum protein levels; improved oral glucose tolerance and insulin tolerance, and enhanced antioxidative activities. The protein could ameliorate the pathological damage in pancreatic ß-cells and the liver tissue. It enhanced the expression of key proteins and enzymes, including insulin receptor, insulin receptor substrate, PI3K, phosphorylated-AKT, hepatic kinase, GLUT4, glycogen synthase, GSK3ß, GLK, PFK1, PKM2, and AMPKα, which are related to insulin metabolism and glycolysis. The protein also reduced the expression of G6Pase, PCK, and ACC, which are related to gluconeogenesis and lipid metabolism in the liver, and decreased the expression of TNF-α, IL-6, P65, and IKKß related to inflammation. In general, sericin could maintain normal glucose levels and regulate insulin secretion, insulin and lipid metabolism, and inhibition of inflammation. Therefore, sericin protein could be developed into a novel functional health food with significantly hypoglycaemic effect.

11.
J Hazard Mater ; : 121471, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31677914

RESUMO

In this work, porous SiO2 coated AlxFeyZr1-x-yO2 solid superacid nanoparticles with negative charge (CS-SAFZr) were synthesized via hydrolysis, sulfation and sulfonation, and characterized by SEM, TEM, XRD, BET and so on. The results show that the size of CS-SAFZr nanoparticles prepared under the optimum preparation conditions is around 80 nm, thickness of the porous SiO2 shell is about 20 nm, Hammett acidity is -16.197 and ion exchange capacity (IEC) is 0.98 mmol·g-1. Correspondingly, ferrum (Fe) and aluminum (Al) elements are successfully doped into the ZrO2 lattice and the doped nanoparticles present a specific surface area of 396.2 m2 g-1 with abundant hydroxyl and sulfonic acid groups on the surface. To investigate the properties of the nanoparticles as the filler, polyvinylidene fluoride (PVDF) was used as a candidate to prepare CS-SAFZr/PVDF ultrafiltration (UF) composite membranes and the performance were characterized via cleaning and desalinating seawater. Results indicate that the CS-SAFZr nanoparticles strengthen their compatibility with the membrane via hydrogen bonds and improve performances of PVDF membrane. The suspended solid and conductivity decline ratio of permeate seawater was 1.8 mg L-1 and 13.20% respectively, indicating that CS-SAFZr/PVDF membrane performs seawater cleaning and partial desalination. Therefore, CS-SAFZr nanoparticles can be a promising candidate to modify PVDF membrane for cleaning and desalinating seawater.

12.
J Clin Hypertens (Greenwich) ; 21(11): 1654-1663, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31603618

RESUMO

A subgroup analysis of the nationwide, cross-sectional 3B STUDY was performed to understand the current blood pressure (BP) control status and treatment patterns in Chinese diabetes patients as well as to identify factors associated with BP control. The demographic data, anthropometric parameters, and laboratory results were collected from 24 512 type 2 diabetes patients. The BP goal was a systolic BP <130 mm Hg and a diastolic BP <80 mm Hg regardless of a history of hypertension or current antihypertensive treatment. The overall prevalence of hypertension was 59.9% with geographical differences. Among the diabetes patients with hypertension, 76.9% received antihypertensive medicines. Calcium channel blockers (39.3%), angiotensin II receptor antagonists (26.6%), and then ß-blockers (14.0%) or angiotensin-converting enzyme inhibitors (13.6%) were frequently used for BP control. Only 17.5% (n = 2658) of diabetes patients with hypertension reached the recommended target BP. Body mass index <24 kg/m2 , urban resident, frequent physical activity, good adherence to medication, comorbidity with cardiovascular disease, achieving glycemic goal (HbA1c <7.0%), achieving lipid goal (low-density lipoprotein cholesterol <2.59 mmol/L) were independent factors that predicted achievement of target BP goal. On the contrary, comorbidity with chronic kidney disease predicted failure to achieve target BP goal. Patients who were treated in a cardiology department or lived in the North were more likely to achieve BP goals. A considerable proportion of diabetic patients failed to achieve guideline-recommended BP targets. More aggressive efforts should be made to overcome the diverse barriers and facilitate the optimization of diabetes management.

13.
Bone Joint J ; 101-B(10): 1209-1217, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564156

RESUMO

AIMS: There is an increasing demand for hip arthroplasty in China. We aimed to describe trends in in-hospital mortality after this procedure in China and to examine the potential risk factors. PATIENTS AND METHODS: We included 210 450 patients undergoing primary hip arthroplasty registered in the Hospital Quality Monitoring System in China between 2013 and 2016. In-hospital mortality after hip arthroplasty and its relation to potential risk factors were assessed using multivariable Poisson regression. RESULTS: During the study period, 626 inpatient deaths occurred within 30 days after hip arthroplasty. Mortality decreased from 2.9% in 2013 to 2.6% in 2016 (p for trend = 0.02). Compared with their counterparts, old age, male sex, and divorced or widowed patients had a higher rate of mortality (all p < 0.05). Risk ratio (RR) for mortality after arthroplasty for fracture was two-fold higher (RR 2.0, 95% confidence interval (CI) 1.5 to 2.6) than that for chronic disease. RRs for mortality were 3.3 (95% CI 2.7 to 3.9) and 8.2 (95% CI 6.5 to 10.4) for patients with Charlson Comorbidity Index (CCI) of 1 to 2 and CCI ≥ 3, respectively, compared with patients with CCI of 0. The rate of mortality varied according to geographical region, the lowest being in the East region (1.8%), followed by Beijing (2.1%), the North (2.9%), South-West (3.6%), South-Central (3.8%), North-East (4.1%), and North-West (5.2%) regions. CONCLUSION: While in-hospital mortality after hip arthroplasty in China appears low and declined during the study period, discrepancies in mortality after this procedure exist according to sociodemographic factors. Healthcare resources should be allocated more to underdeveloped regions to further reduce mortality. Cite this article: Bone Joint J 2019;101-B:1209-1217.


Assuntos
Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/mortalidade , Causas de Morte , Mortalidade Hospitalar/tendências , Sistema de Registros , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/métodos , China , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Distribuição de Poisson , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Falha de Prótese , Estudos Retrospectivos , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
14.
EMBO Mol Med ; 11(11): e10515, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31609088

RESUMO

TGFß is important during pancreatic ductal adenocarcinoma (PDA) progression. Canonical TGFß signaling suppresses epithelial pancreatic cancer cell proliferation; as a result, inhibiting TGFß has not been successful in PDA. In contrast, we demonstrate that inhibition of stromal TGFßR2 reduces IL-6 production from cancer-associated fibroblasts, resulting in a reduction of STAT3 activation in tumor cells and reversion of the immunosuppressive landscape. Up to 7% of human PDA have tumor cell-specific deficiency in canonical TGFß signaling via loss of TGFßR2. We demonstrate that in PDA that harbors epithelial loss of TGFßR2, inhibition of TGFß signaling is selective for stromal cells and results in a therapeutic benefit. Our study highlights the potential benefit of TGFß blockade in PDA and the importance of stratifying PDA patients who might benefit from such therapy.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31622005

RESUMO

Increasing life expectancy in the population means that the prevalence of hypertension in China will increase over the coming decades. Although awareness and control rates have improved, the absolute rates remain unacceptably low. Cardiovascular disease (CVD) is the biggest killer in China, and sharp increases in the prevalence of CVD risk factors associated with rapid lifestyle changes will contribute to ongoing morbidity and mortality. This highlights the importance of effectively diagnosing and managing hypertension, where home blood pressure monitoring (HBPM) has an important role. Use of HBPM in China is increasing, particularly now that Asia-specific guidance is available, and this out-of-office BP monitoring tool will become increasingly important over time. To implement these recommendations and guidelines, a Web-based and WeChat-linked nationwide BP measurement system is being established in China. Local guidelines state that both HBPM and ambulatory blood pressure monitoring should be implemented where available. In China, hypertension is managed most often using calcium channel blockers, followed by angiotensin receptor blockers or angiotensin-converting enzyme inhibitors. Key barriers to hypertension control in China are low awareness and control rates.

16.
BMC Cancer ; 19(1): 881, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488082

RESUMO

BACKGROUND: Gene expression profiling of rare cancers has proven challenging due to limited access to patient materials and requirement of intact, non-degraded RNA for next-generation sequencing. We customized a gene expression panel compatible with degraded RNA from formalin-fixed, paraffin-embedded (FFPE) patient cancer samples and investigated its utility in pathway activity profiling in patients with metaplastic breast cancer (MpBC). METHODS: Activity of various biological pathways was profiled in samples from nineteen patients with MpBC and 8 patients with invasive ductal carcinoma with triple negative breast cancer (TNBC) phenotype using a custom gene expression-based assay of 345 genes. RESULTS: MpBC samples of mesenchymal (chondroid and/or osteoid) histology demonstrated increased SNAI1 and BCL2L11 pathway activity compared to samples with non-mesenchymal histology. Additionally, late cornified envelope and keratinization genes were downregulated in MpBC compared to TNBC, and epithelial-to-mesenchymal transition (EMT) and collagen genes were upregulated in MpBC. Patients with high activity of an invasiveness gene expression signature, as well as high expression of the mesenchymal marker and extracellular matrix glycoprotein gene SPARC, experienced worse outcomes than those with low invasiveness activity and low SPARC expression. CONCLUSIONS: This study demonstrates the utility of gene expression profiling of metaplastic breast cancer FFPE samples with a custom counts-based assay. Gene expression patterns identified by this assay suggest that, although often histologically triple negative, patients with MpBC have distinct pathway activation compared to patients with invasive ductal TNBC. Incorporation of targeted therapies may lead to improved outcome for MpBC patients, especially in those patients expressing increased activity of invasiveness pathways.

17.
Protein Sci ; 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31495993

RESUMO

Chromosome region maintenance 1 (CRM1) exports nuclear export signal (NES) containing cargos from nucleus to cytoplasm and plays critical roles in cancer and viral infections. Biochemical and biophysical studies on this protein were often obstructed by its low purification yield and stability. With the help of PROSS server and NES protection strategy, we successfully designed three small fragments of CRM1, each made of four HEAT repeats and capable of binding to NESs in the absence of RanGTP. One of the fragments, C7, showed dramatically improved purification yield, thermostability, mechanostability, and resistance to protease digestion. We showed by isothermal titration that the protein kinase inhibitor NES binds to C7 at 1.18 µM affinity. Direct binding to C7 by several reported CRM1 inhibitors derived from plants were verified using pull-down assays. These fragments might be useful for the development of CRM1 inhibitors towards treatment of related diseases. The strategy applied here might help to tackle similar problems encountered in different fields.

18.
Biomed Pharmacother ; 118: 109379, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545278

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is one of the major complications of diabetes. Sericin and flavonoids are two bioactive substances which have been demonstrated to have some therapeutical effect on diabetic nephropathy. The aim of this paper is to investigate the effect of ethanolic extract (EE) rich in quercetin and kaempferol and their glucosides from the green cocoon of silkworm Bombyx mori on DN in type 2 diabetic (T2D) mice induced by high-fat and streptozotocin (STZ). METHODS: Ethanolic extract from the green cocoon shell of silkworm Bombyx mori was used as material. Diabetic mice were orally treated with three doses (150, 250 and 350 mg/kg) of the extract for 7 weeks, then the levels of oxidases and related inflammatory factors were measured in kidneys. RESULTS: Compared with the negative control, EE administration resulted in an evident reduction in blood glucose levels and an improvement of the body weight in diabetic mice. Oral EE could inhibit the expressions of renal tumour necrosis factor TNF-α, monocyte chemoattractant protein-1 (MCP-1), fibronectin (FN) and P38 mitogen-activated protein kinase (p38 MAPK) in T2D mice. Moreover, the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) were significantly elevated in T2D mice treated with EE. CONCLUSIONS: The activities of anti-fibrosis and anti-inflammation contributed to the renal protective effects by reducing oxidative stress, which might be mediated by the inhibition of the TNF-α-p38 MAP kinase signalling pathway. It is suggested that the ethanolic extract from silkworm green cocoon might be potential as an herbal medicine for DN.

19.
Mol Med Rep ; 20(4): 3802-3810, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485625

RESUMO

Glial cell line­derived neurotrophic factor (GDNF) is critical for the proliferation of spermatogonial stem cells (SSCs), but the underlying mechanisms remain poorly understood. In this study, an unbiased metabolomic analysis was performed to examine the metabolic modifications in SSCs following GDNF deprivation, and 11 metabolites were observed to decrease while three increased. Of the 11 decreased metabolites identified, glycylglycine was observed to significantly rescue the proliferation of the impaired SSCs, while no such effect was observed by adding sorbitol. However, the expression of self­renewal genes, including B­cell CLL/lymphoma 6 member B, ETS variant 5, GDNF family receptor α1 and early growth response protein 4 remained unaltered following glycylglycine treatment. This finding suggests that although glycylglycine serves an important role in the proliferation of SSCs, it is not required for the self­renewal of SSCs.

20.
J Clin Hypertens (Greenwich) ; 21(9): 1250-1283, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31532913

RESUMO

Hypertension is an important public health issue because of its association with a number of significant diseases and adverse outcomes. However, there are important ethnic differences in the pathogenesis and cardio-/cerebrovascular consequences of hypertension. Given the large populations and rapidly aging demographic in Asian regions, optimal strategies to diagnose and manage hypertension are of high importance. Ambulatory blood pressure monitoring (ABPM) is an important out-of-office blood pressure (BP) measurement tool that should play a central role in hypertension detection and management. The use of ABPM is particularly important in Asia due to the specific features of hypertension in Asian patients, including a high prevalence of masked hypertension, disrupted BP variability with marked morning BP surge, and nocturnal hypertension. This HOPE Asia Network document summarizes region-specific literature on the relationship between ABPM parameters and cardiovascular risk and target organ damage, providing a rationale for consensus-based recommendations on the use of ABPM in Asia. The aim of these recommendations is to guide and improve clinical practice to facilitate optimal BP monitoring with the goal of optimizing patient management and expediting the efficient allocation of treatment and health care resources. This should contribute to the HOPE Asia Network mission of improving the management of hypertension and organ protection toward achieving "zero" cardiovascular events in Asia.

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