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1.
Circ Res ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31910739

RESUMO

Rationale: Bone marrow kinase on the X chromosome (BMX) is highly expressed in the arterial endothelium from the embryonic stage to the adult stage in mice. It is also expressed in microvessels and the lymphatics in response to pathological stimuli. However, its role in endothelial permeability and sepsis remains unknown. Objective: We aimed to delineate the function of BMX in thrombin-mediated endothelial permeability and the vascular leakage that occurs with sepsis in cecal ligation and puncture (CLP) models.Methods and Results: The CLP model was applied to wild-type and BMX knockout mice to induce sepsis. Meanwhile, the electric cell-substrate impedance sensing assay was used to detect trans-endothelial electrical resistance in vitro and the modified Miles assay was used to evaluate vascular leakage in vivo. We showed that BMX loss caused lung injury and inflammation in early CLP-induced sepsis. Disruption of BMX increased thrombin-mediated permeability in mice and cultured endothelial cells (ECs) by 2-3-fold. The expression of BMX in macrophages, neutrophils, platelets and lung epithelial cells was undetectable compared with that in ECs, indicating that endothelium dysfunction, rather than leukocyte and platelet dysfunction, was involved in vascular permeability and sepsis. Mechanistically, biochemical and cellular analyses demonstrated that BMX specifically repressed thrombin-protease-activated receptor 1 (PAR1) signaling in ECs by directly phosphorylating PAR1 and promoting its internalization and deactivation. Importantly, pre-treatment with the selective PAR1 antagonist SCH79797 rescued BMX loss-mediated endothelial permeability and pulmonary leakage in early CLP-induced sepsis. Conclusions: Acting as a negative regulator of PAR1, BMX promotes PAR1 internalization and signal inactivation through PAR1 phosphorylation. Moreover, BMX-mediated PAR1 internalization attenuates endothelial permeability to protect vascular leakage during early sepsis.

2.
Dalton Trans ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31799571

RESUMO

Rechargeable lithium-ion batteries (LIBs) for potentially low-cost and high-energy-density storage have been intensively researched to meet ever-growing demands. Achieving higher storages and understanding the transporting and storing diffusion process of Li ions are still great challenges. Herein, a porous crystalline polyoxometalate-based metal-organic framework (POM@MOF), H2[CuII4(Htrz)5(H2O)2][MoVI4CuII4O26]0.5·3H2O, with defect sites as a LIB electrode material is reported. The Li-ion diffusion process in the material was investigated using ex situ X-ray photoelectron spectroscopy (XPS) and off-line powder X-ray diffraction (PXRD), indicating that O atoms of POM nano-clusters can be regarded as Li-ion acceptors (storage sites); meanwhile the defect sites (uncoordinated N atoms or -N-H groups) in the crystalline material also participate in the Li-ion storage. The reported porous crystalline POM@MOF material with defects delivers a remarkable Li-ion storage capacity of ca. 700 mA h g-1 in 200 cycles at a current density of 100 mA g-1.

3.
Artif Cells Nanomed Biotechnol ; 47(1): 4284-4292, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810385

RESUMO

LncRNA LINC01518 was previously reported to be upregulated in oesophageal squamous cell carcinoma (ESCC) tissues compared with normal tissues. However, there are no previous studies concerning the specific function and molecular mechanism of LINC01518 in ESCC. LINC01518 and miR-1-3p expression levels in ESCC cells were detected by qRT-PCR. Cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry analysis, respectively. The relationships between LINC01518, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) and miR-1-3p were explored by luciferase reporter assay. The alteration of the PIK3CA/protein kinase B (Akt) pathway was examined by Western blot. We found that LINC01518 expression was upregulated and miR-1-3p expression was downregulated in ESCC cells. LINC01518 knockdown inhibited cell proliferation and promoted apoptosis in ESCC cells. In addition, LINC01518 functioned as a competing endogenous RNA (ceRNA) for miR-1-3p in ESCC cells and miR-1-3p downregulation blocked the effects of LINC01518 knockdown on cell proliferation and apoptosis in ESCC cells. Moreover, PIK3CA was identified as a target of miR-1-3p and LINC01518 knockdown inhibited the PIK3CA/Akt pathway by upregulating miR-1-3p in ESCC cells. In conclusion, LINC01518 knockdown inhibited tumorigenicity in ESCC cells by suppression of PIK3CA/Akt pathway through upregulating miR-1-3p.

4.
Huan Jing Ke Xue ; 40(9): 4160-4168, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854881

RESUMO

Ca2+ is an important microbial growth factor that can affect the activity, flocculation, and sedimentation of activated sludge. In order to study the roles of Ca2+ in the activated sludge system, the activity changes of ammonium oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) were analyzed using the specific oxygen uptake rates (SOURAOB and SOURNOB). The changes in composition and structure of extracellular polymeric substances (EPS) were analyzed using Fourier transform infrared spectroscopy (FTIR) and three-dimensional excitation emission fluorescence spectroscopy (3D-EEM). The effects of Ca2+on the nitrification activity and microbial metabolites were investigated. The results showed that when the Ca2+concentration increased from 0.45 mmol·L-1 to 3 mmol·L-1, SOURAOB and SOURNOB increased from 6.3 mg·(g·h)-1 to 10.4 mg·(g·h)-1 and from 2.3 mg·(g·h)-1 to 3.7 mg·(g·h)-1, respectively. The EPS concentrations increased from 68 mg·g-1 to 93 mg·g-1, and the flocculation ability (FA) of the sludge was improved. When the Ca2+ concentration was higher than 3 mmol·L-1, SOURAOB and SOURNOBboth decreased. The FA was maintained at about 30%, and the particle size of the sludge continued to increase. Based on FTIR analysis, the main components of EPS were always amino, amide Ⅰ, and carboxyl with an increase in Ca2+ concentration. Based on EEM analysis, the composition of loosely-bound (LB)-EPS did not change, and humic acid substances appeared in the tightly-bound (TB)-EPS at low nitrification rates. Low concentrations of Ca2+ promoted nitrification activity and flocculation of the sludge. However, high concentrations of Ca2+ led to a decline in the sludge nitrification activity.

5.
Cell Mol Neurobiol ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31863221

RESUMO

Cerebral glycogen is principally localized in astrocytes rather than in neurons. Glycogen metabolism has been implicated in higher brain functions, including learning and memory, yet the distribution patterns of glycogen in different types of astrocytes have not been fully described. Here, we applied a method based on the incorporation of 2-NBDG, a D-glucose fluorescent derivative that can trace glycogen, to investigate glycogen's distribution in the brain. We identified two types of astrocytes, namely, 2-NBDGI (glycogen-deficient) and 2-NBDGII (glycogen-rich) cells. Whole-cell patch-clamp and fluorescence-activated cell sorting (FACS) were used to separate 2-NBDGII astrocytes from 2-NBDGI astrocytes. The expression levels of glycogen metabolic enzymes were analyzed in 2-NBDGI and 2-NBDGII astrocytes. We found unique glycogen metabolic patterns between 2-NBDGI and 2-NBDGII astrocytes. We also observed that 2-NBDGII astrocytes were mainly identified as fibrous astrocytes but not protoplasmic astrocytes. Our data reveal cell type-dependent glycogen distribution and metabolism patterns, suggesting diverse functions of these different astrocytes.

6.
J Pharmacol Exp Ther ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882454

RESUMO

Unraveling the molecular mechanisms by which genetic variants of cytochrome P450 2A6 (CYP2A6) lead to different metabolic phenotypes remains a long-standing but important challenge. CYP2A6 is an enzyme involved in the metabolism of several clinical drugs as well as the metabolic activation of carcinogenic nitrosamines. Herein, CYP2A6 genotypes and phenotypes, as indicated by protein content (by LC-MS/MS) and metabolic activities (Vmax, CL), were determined for 90 human liver samples. We determined the median, range, and inter-individual and intra-individual variation of CYP2A6 content and activity at the microsomal, liver tissue, and whole liver level and predicted hepatic in vivo clearance by in vitro-in vivo extrapolation based on CYP2A6-mediated coumarin metabolism by each CYP2A6 genotype. These results reveal how different CYP2A6 genotypes yield different phenotypic traits in protein content and enzyme activity. For relative Vmax, CL and protein content, the intra-individual percentage coefficients of variation (ICVs) were 41.0% (18.8-125.1%), 28.5% (2.39-133.5%) and 27.8% (2.68-88.0%), respectively. The high ICVs implied large intra-individual variation at different levels, sometimes in a genotype-dependent manner. Inter-genotype analysis revealed that the CYP2A6*4 allele demonstrated the most obvious effect on phenotypic outcomes, both in protein content and in metabolic activity. Indeed, decreased CYP2A6 protein content with the CYP2A6*4 genotype might explain the decreased metabolic activity from the molecular to the organismal level. These findings may allow useful predictions for CYP2A6-mediated drug metabolism on an individual patient basis in accord with the goal of achieving personalized medicine. SIGNIFICANCE STATEMENT: We provide the median, range, and inter-individual and intra-individual variation in CYP2A6 content at the microsomal, liver tissue, and whole liver level by LC-MS/MS as well as activities at the protein, microsomal, liver tissue, and whole liver level both in vitro and at the organismal level based on CYP2A6-mediated coumarin metabolism with each CYP2A6 genotype, thereby allowing us to elucidate how different CYP2A6 genotypes yield differing phenotypic traits (protein content and enzyme activity), facilitating the development of personalized medicine.

7.
Nutrients ; 11(12)2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31847246

RESUMO

This study aimed to examine the effects of four weeks of a low-carbohydrate diet (LC) and incorporated exercise training on body composition and cardiometabolic health. Fifty-eight overweight/obese Chinese females (age: 21.2 ± 3.3 years, body mass index (BMI): 25.1 ± 2.8 kg/m2) were randomly assigned to the control group (CON, n = 15), the LC control group (LC-CON, n = 15), the LC and high-intensity interval training group (LC-HIIT, n = 15), or the LC and moderate-intensity continuous training group (LC-MICT, n = 13). Subjects consumed a four week LC, whereas LC-HIIT and LC-MICT received extra training 5 d/week (LC-HIIT: 10 × 6 s cycling interspersed with 9 s rest, MICT: 30 min continuous cycling at 50-60% VO2peak). After intervention, the three LC groups demonstrated significant reductions in body weight (-2.85 kg in LC-CON, -2.85 kg in LC-HIIT, -2.56 kg in LC-MICT, p < 0.001, η2 = 0.510), BMI (p < 0.001, η2 = 0.504) and waist-to-hip ratio (p < 0.001, η2 = 0.523). Groups with extra training (i.e., LC-HIIT and LC-MICT) improved VO2peak by 14.8 and 17.3%, respectively. However, fasting glucose and blood lipid levels remained unchanged in all groups. Short-term LC is a useful approach to improve body composition in overweight/obese Chinese females. Incorporated exercise training has no additional effects on weight loss, but has additional benefits on cardiorespiratory fitness, and HIIT is more time efficient than the traditional MICT (2.5 min vs. 30 min).

8.
Huan Jing Ke Xue ; 40(10): 4678-4684, 2019 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854838

RESUMO

A pot experiment was carried out to simulate soil contaminated by sulfamethoxazole at different concentrations. The community structure of soil microorganisms was investigated using Illumina high-throughput sequencing, and 64 subtypes of antibiotic resistance genes (ARGs) resistant to six classes of antibiotic were also analyzed by PCR and droplet digital PCR. The results showed that soil contamination with sulfamethoxazole had no significant effect on fungal diversity after 120 days (P>0.05) whereas bacterial diversity was significantly reduced (P<0.05). The microbial community structure of the contaminated soil changed significantly, with the dominant bacterial and fungal genera being significantly different from the control soil. Sulfamethoxazole contamination resulted in an increase in ARG diversity, and the abundance of the sulfonamide resistance gene sul1 increased significantly (P<0.05). However, the abundance of the sulfonamide resistance gene sul2, the quinolone resistance genes floR and cmlA1, and the tetracycline resistance genes tet(34), tetG2, tetG1,tetM, and tetA/P did not show significant changes in the contaminated soil (P>0.05).


Assuntos
Antibacterianos , Microbiota , Sulfametoxazol , Resistência Microbiana a Medicamentos , Genes Bacterianos , Solo
9.
EMBO Rep ; 20(12): e48375, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31668005

RESUMO

Outcomes for metastatic Ewing sarcoma and osteosarcoma are dismal and have not changed for decades. Oxidative stress attenuates melanoma metastasis, and melanoma cells must reduce oxidative stress to metastasize. We explored this in sarcomas by screening for oxidative stress sensitizers, which identified the class I HDAC inhibitor MS-275 as enhancing vulnerability to reactive oxygen species (ROS) in sarcoma cells. Mechanistically, MS-275 inhibits YB-1 deacetylation, decreasing its binding to 5'-UTRs of NFE2L2 encoding the antioxidant factor NRF2, thereby reducing NFE2L2 translation and synthesis of NRF2 to increase cellular ROS. By global acetylomics, MS-275 promotes rapid acetylation of the YB-1 RNA-binding protein at lysine-81, blocking binding and translational activation of NFE2L2, as well as known YB-1 mRNA targets, HIF1A, and the stress granule nucleator, G3BP1. MS-275 dramatically reduces sarcoma metastasis in vivo, but an MS-275-resistant YB-1K81-to-alanine mutant restores metastatic capacity and NRF2, HIF1α, and G3BP1 synthesis in MS-275-treated mice. These studies describe a novel function for MS-275 through enhanced YB-1 acetylation, thus inhibiting YB-1 translational control of key cytoprotective factors and its pro-metastatic activity.

10.
J Sci Med Sport ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31690491

RESUMO

OBJECTIVES: It is unclear whether exercise modality (moderate-intensity continuous [MCE]; high-intensity interval [HIE]) and menstrual cycle phase (follicular [FP]; luteal [LP]), individually or in combination, mediate the commonly observed exercise-induced elevation in cardiac troponin T (cTnT). This study examines cTnT responses to MCE and HIE during both the FP and LP. DESIGN: Randomised crossover study. METHODS: Seventeen healthy, eumenorrheic women completed four trials including MCE (60% VO2max steady-state cycling until 300kJ) and work-equivalent HIE (repeated 4-min cycling at 90% VO2max interspersed with 3-min rest) during both the FP and LP. The FP and LP were verified based on ovarian hormones. Serum cTnT was assessed using a high-sensitivity assay before, immediately after, and 1 (1HR), 3 (3HR) and 4 (4HR) hours after exercise. cTnT values were corrected for plasma volume changes. RESULTS: cTnT was significantly elevated (p<0.05) post-exercise in both MCE (at 3HR and 4HR) and HIE (at 1HR, 3HR and 4HR). No statistically significant difference (p>0.05) in peak post-exercise cTnT, which mostly occurred at 3HR, was seen among the four trials (median [range], ngl-1: 5.2 [1.7-18.1] after MCE during FP; 4.8 [1.7-24.9] after MCE during LP, 8.2 [3.9-24.8] after HIE during FP and 6.9 [1.7-23.1] after HIE during LP). CONCLUSIONS: A single 300kJ bout of both MCE or HIE resulted in a significant post-exercise increase in cTnT, with no differences in peak cTnT response between menstrual cycle phases or between exercise modes, but the cTnT elevation occurs slightly earlier after HIE.

11.
J Ginseng Res ; 43(4): 499-507, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31695559

RESUMO

Background: Ginsenoside Rb1 (Rb1), a dominant component from the extract of Panax ginseng root, exhibits neuroprotective functions in many neurological diseases. This study was intended to investigate whether Rb1 can attenuate cisplatin-induced memory impairments and explore the potential mechanisms. Methods: Cisplatin was injected intraperitoneally with a dose of 5 mg/kg/wk, and Rb1 was administered in drinking water at the dose of 2 mg/kg/d to rats for 5 consecutive wk. The novel objects recognition task and Morris water maze were used to detect the memory of rats. Nissl staining was used to examine the neuron numbers in the hippocampus. The activities of superoxide dismutase, glutathione peroxidase, cholineacetyltransferase, acetylcholinesterase, and the levels of malondialdehyde, reactive oxygen species, acetylcholine, tumor necrosis factor-α, interleukin-1ß, and interleukin-10 were measured by ELISA to assay the oxidative stress, cholinergic function, and neuroinflammation in the hippocampus. Results: Rb1 administration effectively ameliorates the memory impairments caused by cisplatin in both novel objects recognition task and Morris water maze task. Rb1 also attenuates the neuronal loss induced by cisplatin in the different regions (CA1, CA3, and dentate gyrus) of the hippocampus. Meanwhile, Rb1 is able to rescue the cholinergic neuron function, inhibit the oxidative stress and neuroinflammation in cisplatin-induced rat brain. Conclusion: Rb1 rescues the cisplatin-induced memory impairment via restoring the neuronal loss by reducing oxidative stress and neuroinflammation and recovering the cholinergic neuron functions.

13.
Front Cell Neurosci ; 13: 447, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749684

RESUMO

Social deficiency is one of the core syndromes of autism spectrum disorders (ASD), for which the underlying developmental mechanism still remains elusive. Anterior cingulate cortex (ACC) plays a key role in integrating social information and regulating social behavior. Recent studies have indicated that synaptic dysfunction in ACC is essential for ASD social defects. In the present study, we investigated the development of synapses and the roles of glycogen synthase kinase 3ß (GSK-3ß), which mediates multiple synaptic signaling pathways in ACC by using Shank3b -/- mice (a widely used ASD mouse model). Our data revealed that Shank3b mutation abolished the social induced c-Fos expression in ACC. From 4 weeks post-birth, neurons in Shank3b -/- ACC exhibited an obvious decrease in spine density and stubby spines. The length and thickness of post-synaptic density (PSD), the expression of vesicular glutamate transporter 2 (vGlut2) and glutamate receptor 2 (GluR2), and the frequency of miniature excitatory post-synaptic currents (mEPSCs) were significantly reduced in Shank3b -/-ACC. Interestingly, the levels of phosphorylated GSK-3ß (Ser9), which inhibits the activity of GSK-3ß, decreased along the same time course as the levels of GluR2 increased in ACC during development. Shank3b mutation leads to a dramatic increase of pGSK-3ß (Ser9), and decrease of pPSD95 (a substrate of GSK-3ß) and GluR2. Local delivery of AAV expressing constitutively active GSK-3ß restored the expression of GluR2, increased the spine density and the number of mature spines. More importantly, active GSK-3ß significantly promoted the social activity of Shank3b -/- mice. These data, in together, indicate that decrease of GSK-3ß activity in ACC may contribute to the synaptic and social defects of Shank3b -/- mice. Enhancing GSK-3ß activity may be utilized to treat ASD in the future.

14.
J Mol Cell Cardiol ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31751569

RESUMO

OBJECTIVE: Sick sinus syndrome (SSS) is associated with loss of HCN4 (hyperpolarization-activated cyclic nucleotide-gated potassium channel 4) function in the cardiac conduction system. The underlying mechanism for SSS remains elusive. This study is to investigate how mitochondrial oxidative stress induces HCN4 downregulation associated with in sick sinus syndrome. METHODS AND RESULTS: Trx2lox/lox mice were crossed with α-myosin heavy chain (α-Mhc)-Cre and Hcn4-CreERT2 deleter mice to generate Trx2 deletion mice in the whole heart (Trx2cKO) and in the conduction system (Trx2ccsKO), respectively. Echocardiography was applied to measure hemodynamics and heart rhythm. Histological analyses, gene profiling and chromatin immunoprecipitation were performed to define the mechanism by which thioredoxin-2 (Trx2) regulates HCN4 expression and cardiac function. Trx2cKO mice displayed dilated cardiomyopathy, low heart rate, and atrial ventricular block (AVB) phenotypes. Immunofluorescence revealed that HCN4 expression was specifically reduced within the sinoatrial node in Trx2cKO mice. Interestingly, Trx2ccsKO mice displayed low heart rate and AVB without dilated cardiomyopathy. Both mRNA and protein levels of HCN4 were reduced in the sinoatrial node, suggesting transcriptional HCN4 regulation upon Trx2 deletion. ChIP indicated that the binding of MEF2 to the HCN4 enhancer was not altered by Trx2 deletion; however, histone 3 acetylation at the MEF2 binding site was decreased, and expression of histone deacetylase 4 (HDAC4) was elevated following Trx2 deletion. Moreover, HDAC4 binding to the HCN4 enhancer was mediated by MEF2. Mitochondrial ROS were increased by Trx2 deletion and importantly, mitochondria-specific ROS scavenger MitoTEMPO suppressed HDAC4 elevation, HCN4 reduction, and sinus bradycardia in Trx2ccsKO mice. CONCLUSION: In the conduction system, Trx2 is critical for maintaining HCN4-mediated normal heart rate. Loss of Trx2 reduces HCN4 expression via a mitochondrial ROS-HDAC4-MEF2C pathway and subsequently induces sick sinus syndrome in mice.

16.
Materials (Basel) ; 12(23)2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766516

RESUMO

To date it has not been possible to produce metallic glass strips with a thickness larger than 150 m via single-roller melt spinning technique, and it remains challenging to produce thick metallic glass strips. In this work, a multiple twin-roller casting technique is proposed for producing thick metallic glass and metallic glass composite strips. A triple twin-roller casting device, as a specific case of the multiple twin-roller, was designed and manufactured. The triple twin-roller device possesses a high cooling rate and involves a long contact time between the melt and the strip, which makes it an efficient technique for producing metallic glass strips that avoids crystallization, although the solidification temperature ranges of metallic glasses are as wide as several hundred Kelvins. The two prepared metallic glass (MG) strips are in a fully amorphous state, and the MG strip shows excellent capacity of stored elastic energy under 3-point bending. Furthermore, the Ti-based metallic glass composite strip produced via the triple twin-roller casting exhibits a novel microstructure with much finer and more homogenously orientated -Ti crystals, as compared with the microstructure of metallic glass composites produced by the common copper mold casting technique.

17.
Basic Res Cardiol ; 114(6): 43, 2019 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587086

RESUMO

Impairment of cardiac lymphatic vessels leads to cardiac lymphedema. Recent studies have suggested that stimulation of lymphangiogenesis may reduce cardiac lymphedema. However, effects of lymphatic endothelial progenitor cells (LEPCs) on cardiac lymphangiogenesis are poorly understood. Therefore, this study investigated effectiveness of LEPC transplantation and VEGF-C release with self-assembling peptide (SAP) on cardiac lymphangiogenesis after myocardial infarction (MI). CD34+VEGFR-3+ EPCs isolated from rat bone marrow differentiated into lymphatic endothelial cells after VEGF-C induction. VEGF-C also stimulated the cells to incorporate into the lymphatic capillary-like structures. The functionalized SAP could adhere with the cells and released VEGF-C sustainedly. In the condition of hypoxia and serum deprivation or abdominal pouch assay, the SAP hydrogel protected the cells from apoptosis and necrosis. At 4 weeks after intramyocardial transplantation of the cells and VEGF-C loaded with SAP hydrogel in rat MI models, cardiac lymphangiogenesis was increased, cardiac edema and reverse remodeling were reduced, and cardiac function was improved significantly. Delivery with SAP hydrogel favored survival of the engrafted cells. VEGF-C released from the hydrogel promoted differentiation and incorporation of the cells as well as growth of pre-existed lymphatic vessels. Cardiac lymphangiogenesis was beneficial for elimination of the inflammatory cells in the infarcted myocardium. Moreover, angiogenesis and myocardial regeneration were enhanced after reduction of lymphedema. These results demonstrate that the combined delivery of LEPCs and VEGF-C with the functionalized SAP promotes cardiac lymphangiogenesis and repair of the infarcted myocardium effectively. This study represents a novel therapy for relieving myocardial edema in cardiovascular diseases.

18.
Exp Ther Med ; 18(5): 3375-3382, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31602211

RESUMO

Botulinum toxin A (BTX-A) is a promising therapeutic modality against trigeminal neuralgia (TN) with certain controversies pertaining to its application. To provide further information on factors influencing the treatment outcomes of BTX-A, a retrospective study with 152 patients with TN treated with BTX-A was performed. The starting time and duration of the therapeutic effect, as well as side effects, of BTX-A in the treatment of TN were analyzed by sex, age, course of disease, number of branches and injected dose. A total of 136 patients exhibited symptom improvement within 2 weeks following BTX-A treatment as evaluated using a visual analog scale (VAS). The effect of BTX-A was sustained throughout the initial 6 months of the follow-up and was demonstrated to persist for as long as 28 months. Female sex, short disease course and high injection dose (>70 units) were associated with lower long-term VAS scores. Patients receiving short-term medium-(50-70 units) or high-dose injections were more likely to be completely cured. Patients with a median disease course (1-10 years) or multiple branches were more likely to exhibit facial asymmetry. Based on the stratified analysis, female patients with a median disease course (1-10 years) exhibited a higher incidence of side effects and male patients achieved better treatment outcomes with high BTX-A doses. BTX-A effectively alleviated patients with TN in both short or long term, although the treatment efficacy may depend on patient characteristics.

19.
MBio ; 10(5)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615964

RESUMO

ADP ribosylation factor (Arf) small GTPase family members are involved in vesicle trafficking and organelle maintenance in organisms ranging from Saccharomyces cerevisiae to humans. A previous study identified Magnaporthe oryzae Arf6 (MoArf6) as one of the Arf proteins that regulates growth and conidiation in the rice blast fungus M. oryzae, but the remaining family proteins remain unknown. Here, we identified six additional Arf proteins, including MoArf1, MoArl1, MoArl3, MoArl8, MoCin4, and MoSar1, as well as their sole adaptor protein, MoGga1, and determined their shared and specific functions. We showed that the majority of these proteins exhibit positive regulatory functions, most notably, in growth. Importantly, MoArl1, MoCin4, and MoGga1 are involved in pathogenicity through the regulation of host penetration and invasive hyphal growth. MoArl1 and MoCin4 also regulate normal vesicle trafficking, and MoCin4 further controls the formation of the biotrophic interfacial complex (BIC). Moreover, we showed that Golgi-cytoplasm cycling of MoArl1 is required for its function. Finally, we demonstrated that interactions between MoArf1 and MoArl1 with MoGga1 are important for Golgi localization and pathogenicity. Collectively, our findings revealed the shared and specific functions of Arf family members in M. oryzae and shed light on how these proteins function through conserved mechanisms to govern growth, transport, and virulence of the blast fungus.IMPORTANCE Magnaporthe oryzae is the causal agent of rice blast, representing the most devastating diseases of rice worldwide, which results in losses of amounts of rice that could feed more than 60 million people each year. Arf (ADP ribosylation factor) small GTPase family proteins are involved in vesicle trafficking and organelle maintenance in eukaryotic cells. To investigate the function of Arf family proteins in M. oryzae, we systematically characterized all seven Arf proteins and found that they have shared and specific functions in governing the growth, development, and pathogenicity of the blast fungus. We have also identified the pathogenicity-related protein MoGga1 as the common adaptor of MoArf1 and MoArl1. Our findings are important because they provide the first comprehensive characterization of the Arf GTPase family proteins and their adaptor protein MoGga1 functioning in a plant-pathogenic fungus, which could help to reveal new fungicide targets to control this devastating disease.

20.
J Coll Physicians Surg Pak ; 29(10): 932-936, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564264

RESUMO

OBJECTIVE: To evaluate the efficiency and safety of the transabdominal preperitoneal (TAPP) technique with or without preserved uterine round ligament for the repair of femoral hernias (FHs), on the female patients treated at a single centre. STUDY DESIGN: Comparative-descriptive study. PLACE AND DURATION OF STUDY: Department of General Surgery Center, Linyi People's Hospital, Shandong University, from January 2010 to December 2016. METHODOLOGY: A total of 62 patients were randomly divided into traditional TAPP (T-TAPP) group and modified TAPP (M-TAPP) group, and all the procedures had been successfully completed. The operative time, recurrences and complications were investigated and compared. RESULTS: Twenty-six patients were randomised into T-TAPP group and 36 patients were randomised into M-TAPP group. There was no obvious difference in terms of age and body mass index between the two groups. The follow-up period was 24 to 90 months. Uterine prolapse occurred in five patients in T-TAPP group, but none in the M-TAPP group. There was significant difference between the two groups (p<0.05). There was also no significant difference in terms of postoperative infection or recurrence of hernia between the two groups nor was there any significant difference between the two groups in development of seroma, post-procedure pain and foreign body sensation during the long-term follow-up. CONCLUSION: The modified TAPP is a safe technique with a very low rate of recurrence and a low incidence of chronic pain, which retained the function of the uterine round ligament. It is an ideal method for the treatment of femoral hernia in female.

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