Search

The extracellular matrix (ECM) is a highly dynamic and complex network structure, which exists in almost all tissues and is the microenvironment that cells rely on for survival. ECM interacts with cells to regulate diverse functions, including differentiation, proliferation, and migration. Neutrophils are the most abundant immune cells in circulation and play key roles in orchestrating a complex series of events during inflammation. Neutrophils can also mediate ECM remodeling by providing specific matrix-remodeling enzymes (such as neutrophil elastase and metalloproteinases), generating neutrophil extracellular traps, and releasing exosomes. In turn, ECM can remodel the inflammatory microenvironment by regulating the function of neutrophils, which drives disease progression. Both the presence of ECM and the interplay between neutrophils and their extracellular matrices are considered an important and outstanding mechanistic aspect of inflammation. In this review, the importance of ECM will be considered, together with the discussion of recent advances in understanding the underlying mechanisms of the intricate interplay between ECM and neutrophils. A better comprehension of immune cell-matrix reciprocal dependence has exciting implications for the development of new therapeutic options for neutrophil-associated infectious and inflammatory diseases.

To evaluate the relationship between retinal nerve fiber layer (RNFL) thickness and other related parameters measured by spectral-domain optical coherence tomography and the refractive error of eyes.A total of 5394 subjects were enrolled in this population-based cohort study, who were divided into three groups by refractive state after they underwent a standardized ophthalmic examination: emmetropia (the absolute value should range from 0 to 0.5 D), low-moderate myopia (the absolute value of myopic error should range from 0.5 to 6 D), and high myopia (the absolute value of myopic error should be over than 6 D). R 3.6.1 software was adopted for statistical analysis.Two thousand five hundred fifty-two subjects (4548 eyes) were collected in this study, with an average age of 53.14 ± 10.64 years. There were significant differences among groups in average central corneal curvature, spherical equivalent, and axial length (P 0.001). The measurements of average retinal nerve fiber layer (RNFL) were 113.95 ± 10.62 μm, 112.97 ± 11.59 μm, and 101.88 ± 15.67 μm, respectively, in the emmetropia, low-moderate, and high myopia groups (P 0.001). Meanwhile, there was a decreasing trend of cup area, cup volume, disc area, and rim area in the high myopia group compared with the emmetropia group (P 0.001).The measurements of RNFL thickness vary greatly with refractive error, and this study indicated that it is of great significance for the accurate diagnosis of glaucoma to establish an individualized RNFL thickness database.

Although coal has made a huge contribution to the development of the economy and socie-ty and its economic benefits have often attracted much attention, little research has focused on the ecosystem services of coalfields. Based on remote sensing data, meteorological data, and soil data in Shanxi coalfields during 1986, 2000, and 2015, we estimated soil conservation and water yield using the InVEST model, assessed the net primary productivity of vegetation using the CASA mo-del, and estimated sand fixation using the RWEQ model. Further, we simulated the spatial patterns of ecosystem services (ESs) using the k-means cluster analysis method and analyzed the influence factors of ESs using the Geodetector model in Shanxi coalfield areas. The results showed that soil conservation service, water yield service, and sand fixation service increased continuously. The high-value area of soil conservation service was mainly concentrated in the north of Hedong coalfield and the northeast of Qinshui coalfield, while the low-value area was distributed in the southwestern edge of Datong coalfield. The high-value area of water yield service was mainly concentrated in the northeast of Qinshui coalfield, while the low-value area was distributed in the northeast of Qinshui coalfield, Xishan coalfield and northwestern Qinshui coalfield. The high-value area for vegetation production service was mainly concentrated in the southeast of Qinshui coalfield, while the low-value area was distributed in Datong coalfield, Ningwu coalfield, Xishan coalfield, and northern Hedong coalfield. The distribution of low- and high-value areas of sand fixation service was unfixed. Ecosystem service bundles could be divided into four categories. The first category belonged to soil conservation service bundle, mainly distributed in the northern Ningwu coalfield, the northern Hedong coalfield, and the northern Qinshui coalfield. The second was water yield service bundle, mainly distributed in Huoxi coalfield and southern Qinshui coalfield. The third category belonged to vegetation production service bundle, mainly distributed in parts of Qinshui coalfield. The fourth category belonged to sand fixation service bundle, mainly distributed in the southern part of Hedong coalfield and Qinshui coalfield. Soil conservation service was greatly affected by temperature, digital elevation model (DEM), and industrial output value, with q values of 0.5, 0.3, and 0.2, respectively. Water yield service was greatly affected by precipitation, temperature, and DEM, with q values of 0.8, 0.3, and 0.2, respectively. The industrial output value, precipitation, and temperature q values of vegetation production service were 0.7, 0.6, and 0.2, respectively. The main influen-cing factors of sand fixation service were precipitation, temperature, and DEM, while the q values were 0.7, 0.3, and 0.3, respectively. The spatial distribution of coalfields ESs and the relationship between multiple ESs were closely related to natural and human factors. Therefore, maintaining the coordination relationship between natural-human factors and ecological services would be helpful to the management of the land reclamation, ecological reconstruction, and the sustainable development of coalfields ecosystem.煤炭对人类经济社会的发展贡献巨大,其经济效益备受关注,然而煤田为人类提供的生态系统服务却往往易被忽视。本研究基于山西煤田1986、2000、2015年遥感数据、气象数据、土壤数据等,采用InVEST模型估算土壤保持量和产水量,CASA模型估算植被净初级生产力,RWEQ模型估算防风固沙,采用k-均值聚类分析和地理探测器模型模拟山西煤田生态系统服务的空间格局及影响机制。结果表明: 1986—2015年,研究区土壤保持服务、产水服务、植被生产服务和防风固沙服务呈持续增长态势。土壤保持服务高值区主要集中在河东煤田北部和沁水煤田东北部,低值区分布在大同煤田西南部边缘;产水服务高值区主要集中在沁水煤田东北部,低值区分布在西山煤田和沁水煤田西北部;植被生产服务高值区主要集中在沁水煤田东南部,低值区分布在大同煤田、宁武煤田、西山煤田和河东煤田北部;防风固沙服务低值区和高值区在研究区中的位置不固定。生态系统服务簇可分为4类,第一类属于土壤保持服务簇,主要分布在宁武煤田北部、河东煤田北部和沁水煤田北部;第二类属于产水服务簇,主要分布在霍西煤田和沁水煤田南部等地区;第三类属于植被生产服务簇,主要分布在沁水煤田局部;第四类属于防风固沙服务簇,主要分布在河东煤田南部和沁水煤田局部。土壤保持服务受气温、数字高程模型(DEM)、工业产值影响较大,q值分别为0.5、0.3、0.2;产水服务受降水、气温、DEM影响较大,q值分别为0.8、0.3、0.2;植被生产服务的工业产值、降水、气温q值分别为0.7、0.6、0.2;防风固沙服务的主要影响因素有降水、气温和DEM,q值分别为0.7、0.3、0.3。煤田生态系统服务的空间分布及多种生态系统服务之间的关系与自然和人为因素紧密相关,因此,保持自然和人为因子与生态服务之间良好的协调关系,有助于为煤田生态系统可持续发展、土地复垦与生态重建及管理政策的制定提供科学依据。.

The study aimed to evaluate dynamic changes in the liver microenvironment at 3 weeks, 3 months, and 6 months following donation after cardiac death liver transplantation (DCDLT) using multiparametric MRI, and further explore the correlation between the hepatic microenvironment and liver function after DCDLT.Twenty-seven patients after DCDLT (the LT group) at times of 3 weeks (LT-3W), 3 months (LT-3M), and 6 months (LT-6M) and 20 normal volunteers (the N group) underwent intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and blood oxygen level-dependent (BOLD) MR scanning. One-way repeated-measures ANOVA was used to compare MR parameters and liver volume (LV)/estimated standard liver volume (ESLV) at three follow-up times in the LT group. An independent sample t-test was used to compare MR parameters and LV/ESLV between each time of the LT group and the N group. Pearson and Spearman correlation analyses were employed to assess the correlation between MR parameters and liver blood indicators, LV/ESLV after DCDLT.After DCDLT, true diffusion coefficient (Dslow), pseudo diffusion coefficient (Dfast), perfusion fraction (PF), and apparent diffusion coefficient (ADC) values were increased, and fractional anisotropy (FA) and R2* values were decreased. Dfast values in the LT-3M and LT-6M were significantly higher than in the LT-3W. Compared to the LT-3W, PF and ADC values were significantly increased and R2* values were significantly decreased in the LT-6M (all P 0.05). All MR parameters in the LT-3W were significantly different from the N group, and Dfast and ADC values in the LT-6M remained significantly higher than in the N group (all P 0.05). In the LT group, Dslow, Dfast, PF, and ADC values were correlated with liver blood indicators and LV/ESLV (|r| = 0.364-0.561, all P 0.05).After DCDLT, the hepatic microenvironment showed an improving trend, which was correlated to the liver function. Except for the microcirculatory perfusion, the hepatic microenvironment was close to normality at six months.

Background: Abnormally activated mechanistic target of rapamycin (mTOR) pathway has been reported in several model animals with inherited metabolic myopathies (IMMs). However, the profiles of mTOR pathway in skeletal muscles from patients are still unknown. This study aimed to analyze the activity of mTOR pathway in IMMs muscles. Methods: We collected muscle samples from 25 patients with mitochondrial myopathy (MM), lipid storage disease (LSD) or Pompe disease (PD). To evaluate the activity of mTOR pathway in muscle specimens, phosphorylation of S6 ribosomal protein (p-S6) and p70S6 kinase (p-p70S6K) were analyzed by Western blotting and immunohistochemistry. Results: Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls (NC) (NC vs. LSD, U= 2.000, P= 0.024; NC vs. MM: U= 6.000, P= 0.043). Likewise, p-S6/S6 was also upregulated in muscles from all three subgroups of IMMs (NC vs. LSD, U= 0.000, P= 0.006; NC vs. PD, U= 0.000, P= 0.006; NC vs. MM, U= 1.000, P = 0.007). Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect. In MM muscles, most p-S6 positive fibers showed cytochrome C oxidase (COX) deficiency (U= 5.000, P= 0.001). In LSD and PD muscles, p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets (U= 0.000, P = 0.002) or basophilic materials (U= 0.000, P= 0.002). Conclusion: The mTOR pathway might be activated in myofibers with various metabolic defects, which might provide evidence for mTOR inhibition therapy in human IMMs. Key words: mTOR pathway; Mitochondrial myopathy; Lipid storage disease; Pompe disease

Background: Embryonic stem cells (ES) have a great potential for cell-based therapies in a regenerative medicine. However, the ethical and safety issues limit its clinical application. ES-derived extracellular vesicles (ES-EVs) have been reported suppress cellular senescence. Mesenchymal stem cells (MSCs) are widely used for clinical cell therapy. In this study, we investigated the beneficial effects of ES-EVs on aging MSCs to further enhancing their therapeutic effects. Methods: In vitro, we explored the rejuvenating effects of ES-EVs on senescent MSCs by senescence-associated β-gal (SA-β-gal) staining, immunostaining, and DNA damage foci analysis. The therapeutic effect of senescent MSC pre-treated with ES-EVs was also evaluated by using mouse cutaneous wound model. Results: We found that ES-EVs significantly rejuvenated the senescent MSCs in vitro and improve the therapeutic effects of MSCs in a mouse cutaneous wound model. In addition, we also identified that the IGF1/PI3K/AKT pathway mediated the antisenescence effects of ES-EVs on MSCs. Conclusions: Our results suggested that ES cells derived-extracellular vesicles possess the antisenescence properties, which significantly rejuvenate the senescent MSCs and enhance the therapeutic effects of MSCs. This strategy might emerge as a novel therapeutic strategy for MSCs clinical application.

In order to achieve safe and high-efficient photodynamic therapy (PDT), it was a powerful strategy of constructing O

Multifunctional nanoprobes with tumor microenvironment response are playing important roles in highly efficient theranostics of cancers. Herein, a kind of theranostic nanoprobe was synthesized by coating manganese dioxide (MnO2) on the surface of black commercial P25 titanium dioxide (b-P25). The resultant nanoprobe (b-P25@MnO2) possessed glutathione (GSH)-responsive magnetic resonance (MR) imaging and enhanced photothermal therapy (PTT). In tumor microenvironments, the excessive GSH was consumed by reacting with MnO2 to generate Mn2+ for GSH-responsive MR imaging, in which the longitudinal relaxation rate of b-P25@MnO2 was up to 30.44 mM-1 s-1, showing excellent cellular and intratumoral MR imaging. Moreover, the prepared b-P25@MnO2 exhibited stable and strong photothermal conversion capability with a high photothermal conversion efficiency of 30.67%, by which the 4T1 tumors disappeared completely, indicating safe and highly efficient PTT performance. The current work developed GSH-responsive b-P25@MnO2 nanoprobes, demonstrated for MR imaging and enhanced PTT in cancers.

To determine the impact of visual impairment (VI) on health-related quality of life (HRQoL) and to compare the health burden of VI in different areas in mainland China.A cohort of 6830 people from rural villages and a cohort of 3251 people from an urban city were included to receive comprehensive ophthalmologic examinations and complete the European Quality of Life-5 Dimensions 3 Levels (EQ-5D-3L) questionnaire. For urban and rural populations, a unified VI grouping standard was adopted: the eyes were classified into normal group, mild-moderate group, and severe group according to WHO standards, and then divided into 6 groups considering both eyes. We estimated the effects of VI on the EQ-5D index score using linear regression models and the association between VI and self-reported EQ-5D health problems using logistic regression models. Associations were assessed by the Spearman correlation coefficient.The prevalence of VI and the index scores of EQ-5D-3L for each subgroup of VI were higher for the rural cohort. In these two cohorts, the severity of VI in rural population (Spearman r = 0.205; p 0.0001) and urban population (Spearman r = 0.164; p 0.0001) is correlated with the EQ-5D index score. In the rural cohort, the difference in index scores with bilateral severe VI compared to those without VI, after adjusting for covariates, was - 0.053 for the rural cohort and - 0.084 for the urban cohort, respectively. In the rural cohort, the odds ratio for bilateral severe VI was 4.39 for mobility, 6.33 for self-care, and 5.88 for usual activities. The incidence of anxiety or depression and pain or discomfort in the urban cohort was greater; the OR for bilateral severe VI in the urban cohort was 4.75.VI has a negative impact on HRQoL in the rural and urban areas of China, especially in urban population. It is also more likely to cause anxiety or depression among the urban cohort, which deserves special attention.

Objectives To assess whether radiomics signature can identify aggressive behavior and predict recurrence of hepatocellular carcinoma (HCC) after liver transplantation. Methods Our study consisted of a training dataset (n = 93) and a validation dataset (40) with clinically confirmed HCC after liver transplantation from October 2011 to December 2016. Radiomics features were extracted by delineating regions-of-interest (ROIs) around the lesion in four phases of CT images. A radiomics signature was generated using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The association between radiomics signature and recurrence-free survival (RFS) was assessed. Preoperative clinical characteristics potentially associated with RFS were evaluated to develop a clinical model. A combined model incorporating clinical risk factors and radiomics signature was built. Results The stable radiomics features associated with the recurrence of HCC were simply found in arterial phase and portal phase. The prediction model based on the radiomics features extracted from the arterial phase showed better prediction performance than the portal vein phase or the fusion signature combining both of arterial and portal vein phase. A radiomics nomogram based on combined model consisting of the radiomics signature and clinical risk factors showed good predictive performance for RFS with a C-index of 0.785 (95% confidence interval [CI]: 0.674-0.895) in the training dataset and 0.789 (95% CI: 0.620-0.957) in the validation dataset. The calibration curves showed agreement in both training (p = 0.121) and validation cohorts (p = 0.164). Conclusions Radiomics signature extracted from CT images may be a potential imaging biomarker for liver cancer invasion and enable accurate prediction of HCC recurrence after liver transplantation.

Chemotherapy is one of the main strategies for cancer treatment, but its effective application is seriously limited by the development of drug resistance. In this study, we designed micellar vectors for doxorubicin based on amphiphilic copolymers sequentially linking β-cyclodextrin (β-CD), polylacticacid (PLA) or polycaprolactone (PCL) block, and polyethylene glycol (PEG) block to overcome drug resistance in human acute myeloid leukemia cells (HL60/ADR) overexpressing multidrug resistance protein 1 (MRP1). The significant enhancement in cytotoxicity and inhibited HL60/ADR tumor growth in mouse was achieved. More importantly, several analyses were performed to understand the interactions between various polymers and MRP1 at the cellular level. The results showed that the polymers did not show remarkable correlation of MRP1 gene and protein expression, but could decrease intracellular ATP, mitochondrial membrane potential and glutathione levels, which was greatly dependent on the molecular structure of polymers. In conclusion, these novel micelles can be considered as a kind of promising drug delivery system for tumor therapy to reverse drug resistance related to MRP1 overexpression.

Evolution and popularity are two keys of the Barabasi-Albert model, which generates a power law distribution of network degrees. Evolving network generation models are important as they offer an explanation of both how and why complex networks (and scale-free networks, in particular) are ubiquitous. We adopt the evolution principle and then propose a very simple and intuitive new model for network growth, which naturally evolves modular networks with multiple communities. The number and size of the communities evolve over time and are primarily subjected to a single free parameter. Surprisingly, under some circumstances, our framework can construct a tree-like network with clear community structures-branches and leaves of a tree. Results also show that new communities will absorb a link resource to weaken the degree growth of hub nodes. Our models have a common explanation for the community of regular and tree-like networks and also breaks the tyranny of the early adopter; unlike the standard popularity principle, newer nodes and communities will come to dominance over time. Importantly, our model can fit well with the construction of the SARS-Cov-2 haplotype evolutionary network.

To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P

Aptamers are single-stranded RNA or DNA ligands that can specifically bind to various molecular targets with high affinity. Owing to this unique character, they have become increasingly attractive in the field of drug delivery. In this study, we developed a multifunctional composite micelle (CM) with surface modification of aptamer AS1411 (Ap) for targeted delivery of doxorubicin (DOX) to human breast tumors. This binary mixed system consisting of AS1411 modified Pluronic F127 and beta-cyclodextrin-linked poly(ethylene glycol)-b-polylactide could enhance DOX-loading capacity and increase micelle stability. Cellular uptake of CM-Ap was found to be higher than that of untargeted CM due to the nucleolin-mediated endocytosis effect. In vivo study in MCF-7 tumor-bearing mice demonstrated that the AS1411-functionalized composite micelles showed prolonged circulation time in blood, enhanced accumulation in tumor, improved antitumor activity, and decreased cardiotoxicity. In conclusion, aptamer-conjugated multifunctional composite micelles could be a potential delivery vehicle for cancer therapy.

Given the American Psychological Association’s strong recommendation to always report effect sizes in research, scholars have a responsibility to provide complete information regarding their findings. The purposes of this study were to (a) determine the frequencies with which different effect sizes were reported in published, peer-reviewed articles in health education, promotion, and behavior journals and (b) discuss implications for reporting effect size in social science research. Across a 4-year time period (2010-2013), 1,950 peer-reviewed published articles were examined from the following six health education and behavior journals: American Journal of Health Behavior, American Journal of Health Promotion, Health Education & Behavior, Health Education Research, Journal of American College Health, and Journal of School Health. Quantitative features from eligible manuscripts were documented using Qualtrics online survey software. Of the 1,245 articles in the final sample that reported quantitative data analyses, approximately 47.9% ( n = 597) of the articles reported an effect size. While 16 unique types of effect size were reported across all included journals, many of the effect sizes were reported with little frequency across most journals. Overall, odds ratio/adjusted odds ratio ( n = 340, 50.1%), Pearson r/ r2 ( n = 162, 23.8%), and eta squared/partial eta squared ( n = 46, 7.2%) accounted for the most frequently used effect size. Quality research practice requires both testing statistical significance and reporting effect size. However, our study shows that a substantial portion of published literature in health education and behavior lacks consistent reporting of effect size.

OBJECTIVE To evaluate the spontaneous brain activity alterations in liver transplantation (LT) recipients using resting-state functional MRI. MATERIALS AND METHODS Twenty cirrhotic patients as transplant candidates and 25 healthy controls (HCs) were included in this study. All patients repeated the MRI study one month after LT. Amplitude of low-frequency fluctuation (ALFF) values were compared between cirrhotic patients (both pre- and post-LT) and HCs as well as between the pre- and post-LT groups. The relationship between ALFF changes and venous blood ammonia levels and neuropsychological tests were investigated using Pearson's correlation analysis. RESULTS In the cirrhotic patients, decreased ALFF in the vision-related regions (left lingual gyrus and calcarine), sensorimotor-related regions (left postcentral gyrus and middle cingulate cortex), and the default-mode network (bilateral precuneus and left inferior parietal lobule) were restored, and the increased ALFF in the temporal and frontal lobe improved in the early period after LT. The ALFF decreases persisted in the right supplementary motor area, inferior parietal lobule, and calcarine. The ALFF changes in the right precuneus were negatively correlated with changes in number connection test-A scores (r = 0.507, p < 0.05). CONCLUSION LT improved spontaneous brain activity and the results for associated cognition tests. However, decreased ALFF in some areas persisted, and new-onset abnormal ALFF were possible, indicating that complete cognitive function recovery may need more time.

Granulomatous prostatitis is an unusual form of prostatitis, and xanthogranulomatous prostatitis (XGP) is an even rarer granulomatous inflammation. Very few XGP cases have been reported in the literature. The reports concerning MRI features of XGP are even less. The present two cases of XGP in our report have different appearances from previous reports and are accompanied by abscess. We also exhibit the magnetic resonance spectroscopy and dynamic contrast-enhanced MRI characteristics, which have never been reported.

Objective To explore the efficiency, cost, and time for examination of one-stop-shop gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in preoperative evaluation for parent donors by comparing with multidetector computer tomography combined with conventional MR cholangiopancreatography (MDCT-MRCP). Materials and methods Forty parent donors were evaluated with MDCT-MRCP, and the other 40 sex-, age-, and weight-matched donors with Gd-EOB-DTPA-enhanced MRI. Anatomical variations and graft volume determined by pre- and intra-operative findings, costs and time for imaging were recorded. Image quality was ranked on a 4-point scale and compared between both groups. Results Gd-EOB-DTPA-enhanced MRI provided better image quality than MDCT-MRCP for the depiction of portal veins and bile ducts by both reviewers (p < 0.05), hepatic veins by one reviewer (p < 0.05), rather hepatic arteries by both reviewers (p < 0.01). Sixty-nine living donors proceeded to liver donation with all anatomical findings accurately confirmed by intra-operative findings. The “in-room” time of Gd-EOB-DTPA-enhanced MRI was 12 min longer than MDCT-MRCP. Gd-EOB-DTPA-enhanced MRI was cheaper than MDCT-MRCP (US$519.72 vs. US$631.85). Conclusion One-stop-shop Gd-EOB-DTPA-enhanced MRI has similar diagnostic accuracy as MDCT-MRCP and can provide additional benefit in terms of costs and convenience in preoperative evaluation for parent donors.

Introduction Testicular torsion is a urological emergency and infertility is a common complication due to ischemic injury. Surgical reduction and orchiopexy is indicated, but to date there is no effective method for restoration of spermatogenesis. The effects of mesenchymal stem cells (MSCs) on acute tissue injury have been demonstrated, and the abilities of paracrine support, differentiation and immune-modulation may benefit to testicular torsion-induced infertility. We investigate the therapeutic efficacy and the mechanisms of MSCs in testicular torsion-induced germ cell injury when injected locally. Methods Six to eight-week-old Sprague–Dawley rats received surgical 720 degree torsion for 3 hours, followed by detorsion on the left testis. 20 μl of phosphate-buffered saline (PBS) without or with 3 x 104 MSCs from human orbital fat tissues (OFSCs) were given for 10 rats, respectively, via local injection into the left testis 30 minutes before detorsion. 20 μl of PBS injection for 6 rats with surgical exposure without torsion served as sham control. Histopathology with Johnsen’s score analysis, Western blot analysis for superoxide dismutase 2, Bax, Caspase-3, human insulin growth factor-1 and human stem cell factor, malondialdehyde (MDA) assay in testis and plasma, hormones level including testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by ELISA Kits, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and fluorescence staining for P450, Sox-9 and VASA were performed. Results Animals were sacrificed and bilateral orchiectomy was performed 7 days after torsion-detorsion. Local injections of OFSCs prevented torsion-induced infertility judging from Johnsen's score. TUNEL assay and Western blot analysis on caspase 3 and Bax demonstrated that OFSCs prevented ischemic/reperfusion induced intrinsic apoptosis. MDA assay revealed that OFSCs significantly reduced the oxidative stress in the damaged testicular tissues. After the OFSC injection, serum testosterone secretion was increased, while the elevation of FSH triggered by testicular injury was balanced. OFSCs also produced stem cell factor in the damaged testis. Immunofluorescence staining revealed that most transplanted cells surrounded the Leydig cells. Some of transplanted cells differentiated into p450 expressing cells within 7 days. Conclusions Local injection of allogenic MSCs before surgical detorsion is a simple, clinical friendly procedure to rescue torsion-induced infertility.

Lung fibrosis is a poor prognostic factor for pulmonary adenocarcinoma, and the effect of a rigid microenvironment on cancer behavior is unclear. We cultured A549 cells on matrices of 0.2, 2, and 25 kPa to mimic the rigidities of normal lung parenchyma, progressive fibrotic change, and lung fibrosis, respectively. Lung tissue from patients with pulmonary adenocarcinoma was used to confirm the in vitro findings. Increased matrix rigidity promoted cell proliferation and upregulated the epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-Met), and Snail expression in A549 cells. A549 cells became more resistant to the EGFR inhibitor (Erlotinib) and c-Met inhibitor (PHA-665752) when matrix rigidity increased; however, a high concentration of PHA-665752 reversed the rigidity-induced morphological pleomorphism. In human lung tissue, expression of type I collagen was more consistent with clinical fibrosis than the expression of alpha-smooth muscle antibody was. c-Met- and Snail-expressing tumor cells, rather than EGFR-experssing cells, were localized with lung parenchyma rich in type I collagen. Our findings suggest that c-Met causes the rigidity-induced biophysical reaction in pulmonary adenocarcinoma. Treatment targeting both EGFR and c-Met should be considered for patients with lung fibrosis and who are abundant type I collagen expression in the tumor mass.

Background MicroRNA-21 (miR-21) is highly expressed in the plasma of colorectal cancer (CRC) patients. Thus, miR-21 may be a useful novel diagnostic biomarker for CRC. This meta-analysis aims to verify the diagnostic value of circulating miR-21 in CRC patients. Methods A literature search was conducted for publications that evaluated the diagnostic value of miR-21 for CRC. The quality of each study was scored with the Quality Assessment of Diagnostic Accuracy Studies. The bivariate meta-analysis model was employed to summarize the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Receiver operating characteristic curves were used to check the overall test performance. Results Five publications with six studies involving 579 patients and 266 controls were included in this meta-analysis. The pooled sensitivity was 77.4% [95% confidence interval (CI): 67.2%-85.1%], specificity was 84.6% (95% CI: 79.7%-88.5%), PLR was 5.02 (95% CI: 3.73-6.75), NLR was 0.27 (95% CI: 0.18-0.40), and DOR was 18.77 (95% CI: 10.41-33.83). The area under the summary ROC curve was 0.86. In addition, the results became prominent in the CRC group when a study that explored the advanced adenoma was excluded. Conclusion Circulating miR-21 may be a suitable diagnostic biomarker for CRC with moderate sensitivity and specificity. Further studies should evaluate the diagnostic value of miR-21 for CRC in the future.

CONTEXT:\ud Portulacerebroside A (PCA) is a novel cerebroside compound isolated from Portulaca oleracea L. (Portulacaceae), an edible and medicinal plant distributed in the temperate and tropical zones worldwide.\ud OBJECTIVE:\ud This study investigates the effects of PCA in human liver cancer HCCLM3 cells on metastasis and invasion.\ud MATERIALS AND METHODS:\ud After the cells were treated with PCA (2.5, 5, and 10 μg/ml) for 6, 12, 24, or 48 h, adhesion, transwell invasion, and scratch tests were conducted and cell functions were evaluated. Western blot and FQ-RT-PCR assays explored the mechanism of PCA-inhibited invasion and metastasis in the cells.\ud RESULTS:\ud The adhesion rate of the cells was suppressed at 0.5 h (79.4 ± 1.0, 68.7 ± 1.3, and 58.1 ± 1.3%, versus 100 ± 1.5% in the control), 1 h (78.2 ± 1.2, 70.9 ± 1.6, and 55.4 ± 1.9%, versus 100 ± 1.2% in the control), and 1.5 h (71.6 ± 1.1, 62.3 ± 0.9, and 50.4 ± 0.9%, versus 100 ± 1.1% in the control). The 24 h invasion ability was decreased (356.6 ± 11.2, 204.0 ± 17.6, and 113.0 ± 9.5%, versus 443.6 ± 15.4% in the control). The migration capability was also restrained by PCA for 24 h (324.8 ± 25.4, 250.4 ± 21.0, and 126.3 ± 10.1, versus 381.6 ± 30.6 in the control) and 48 h (470.3 ± 34.3, 404.0 ± 19.7, and 201.0 ± 15.4, versus 752.0 ± 63.6 in the control). There was an increase in the mRNA and protein expression levels of TIMP-2 and nm23-H1, inhibition in the mRNA expression of MTA1, MMP-2, and MMP-9, and suppression in the protein expression of MTA1, RhoA, Rac1/Cdc42, MMP-2, but not RhoC and MMP-9.\ud CONCLUSION:\ud PCA suppresses the invasion and metastasis of HCCLM3 cells possibly by modulation of the mRNA and protein expression of related parameters. This is the first study to reveal a new potential therapeutic application of PCA in antimetastatic therapy for liver cancer.

Mental retardation (MR) is one of the most frequent handicaps among children. Fetal iodine deficiency disorder (FIDD) is the commonest cause of preventable MR. However, not everyone in the iodine-deficient areas is affected and familial aggregation is common. This suggests that genetic factors may play an important role. Thyroid hormone (TH) plays an important role in fetal and early postnatal brain development. The thyroid-stimulating hormone (TSH, or thyrotropin) receptor (TSHR) is located on the surface of thyroid cells and binds TSH. It results in the production of thyroid hormones via the activation of adenylate cyclase and phospatidylinositol-dependent signaling pathways. Some researchers formulated the hypothesis that TSH receptor expression in the brain may be involved in local thyroid homeostasis through TSH stimulating the DIO2 activity. In the previous study, we have proposed that DIO2 may protect against FIDD in the iodine-deficient areas of China. The TSHR gene, which located on chromosome 14q31 is a potential candidate gene for susceptibility to FIDD. To investigate the potential genetic contribution of TSHR gene, we performed a case-control association study in Chinese Han population from the Qin-Ba mountain regions using four common SNPs in the gene (rs2284716, rs917986, rs2075173 and rs2075179). Pairwise linkage disequilibrium (LD) analysis showed that LD was observed between rs2284716 and rs917986 and between rs2075173 and rs2075179. Single-locus analysis found that all four SNPs in TSHR gene showed no association after correction for multiple testing. Haplotype analysis showed no significant differences in frequency for three sets of haplotypes based on the pariwise LD results. In conclusion, our association results suggest that TSHR gene is not a susceptibility gene for FIDD in the iodine-deficient areas of China.

Mesenchymal stromal cells (MSCs) have great potential to maintain glucose homeostasis and metabolic balance. Here, we demonstrate that in mice continuously fed with high-fat diet (HFD) that developed non–insulin-dependent diabetes, two episodes of systemic MSC transplantations effectively improve glucose tolerance and blood glucose homeostasis and reduce body weight through targeting pancreas and insulin-sensitive tissues and organs via site-specific mechanisms. MSCs support pancreatic islet growth by direct differentiation into insulin-producing cells and by mitigating the cytotoxicity of interleukin 1 (IL-1) and tumor necrosis factor-α (TNF-α) in the pancreas. Localization of MSCs in the liver and skeletal muscles in diabetic animals is also enhanced and therefore improves glucose tolerance, although long-term engraftment is not observed. MSCs prevent HFD-induced fatty liver development and restore glycogen storage in hepatocytes. Increased expression of IL-1 receptor antagonist and Glut4 in skeletal muscles after MSC transplantation results in better blood glucose homeostasis. Intriguingly, systemic MSC transplantation does not alter adipocyte number, but it decreases HFD-induced cell infiltration in adipose tissues and reduces serum levels of adipokines, including leptin and TNF-α. Taken together, systemic MSC transplantation ameliorates HFD-induced obesity and restores metabolic balance through multisystemic regulations that are niche dependent. Such findings have supported systemic transplantation of MSCs to correct metabolic imbalance.

Camptothecin (CPT) belongs to a group of monoterpenoidindole alkaloids (TIAs) and its derivatives such as irinothecan and topothecan have been widely used worldwide for the treatment of cancer, giving rise to rapidly increasing market demands. Genes from Catharanthus roseus encoding strictosidine synthase (STR) and geraniol 10-hydroxylase (G10H), were separately and simultaneously introduced into Ophiorrhiza pumila hairy roots. Overexpression of individual G10H (G lines) significantly improved CPT production with respect to non-transgenic hairy root cultures (NC line) and single STR overexpressing lines (S lines), indicating that G10H plays a more important role in stimulating CPT accumulation than STR in O. pumila. Furthermore, co-overexpression of G10H and STR genes (SG Lines) caused a 56% increase on the yields of CPT compared to NC line and single gene transgenic lines, showed that simultaneous introduction of G10H and STR can produce a synergistic effect on CPT biosynthesis in O. pumila. The MTT assay results indicated that CPT extracted from different lines showed similar anti-tumor activity, suggesting that transgenic O. pumila hairy root lines could be an alternative approach to obtain CPT. To our knowledge, this is the first report on the enhancement of CPT production in O. pumila employing a metabolic engineering strategy.

To observe the influence of music-electroacupuncture (EA) and pulse EA on locomotor activity and hippocampal neuron numbers and excitatory amino acid transporters (EAATs) mRNA expression in depression rats, so as to explore their mechanisms underlying improvement of depression in acupuncture clinic.Sixty SD rats were randomly divided into blank control, depression model, medication, pulse EA and music-EA groups, with 12 rats in each group. Depression model was established by using chronic unpredictable mild stress protocols combined with solitary feeding. Rats of the medication group were treated by oral administration of fluoxetine (a standard antidepressant, 2 mg/kg). EA was applied to "Baihui" (GV 20) and "Yintang" (EX-HN 3) for 20 min, once a day for 21 days. The animals' ethological changes were detected by using field tests for recording the number of crossing squares and the number of rearing. The number of hippocampal neurons were calculated under microscope after Nissl's staining of the hippocampal tissue section. Hippocampal EAAT 1 and EAAT 2 mRNA expression levels were assayed by fluorescent quantitative real-time POR.In comparison with the blank control group, the numbers of crossing and rearing movements, as well as the expression levels of hippocampal EAAT 1 and EAAT 2 mRNA were significantly lower in the model group (P0.01), while compared with the model group, the numbers of both crossing and rearing movements of the medication, pulse EA and music-EA groups were obviously increased (P0.01). Correspondingly, the expression levels of hippocampal EAAT 1 and EAAT 2 mRNA were considerably upregulated in the pulse EA and music-EA groups in comparison with the model group (P0.01). No significant differences were found among the medication, pulse EA and music-EA groups (P0.05). Results of Nissl's staining displayed that in the model group, the hippocampal neurons were loose in arrangement and some of them were absent, but in the medication, pulse EA and music-EA groups, the neurons were clear in shape and lined in order.Both pulse EA and music-EA can effectively improve the locomotor activity and hippocampal neuronal structure in depression rats which may be closely associated with their effects in upregulating hippocampal EAAT 1 and EAAT 2 mRNA expression.

The aim of this study was to determine the effectiveness of oral administration of lemon/orange juice in improving the visualization of pancreatic ducts on MRCP.MRCP images were generated before and at every 15 min for 90 min after oral administration of lemon/orange juice in a dose of 2 ml/kg in 20 volunteers and 26 patients. The pre- and post-administration images were compared and analyzed qualitatively and quantitatively.In 20 volunteers and 26 patients, the visualization at pancreatic duct of head, body, tail, accessory pancreatic duct, and branch duct was improved after juice administration. The diameter of pancreatic ducts was augmented, and the differences in the mean values before and after oral juice were highly significant at both sites in volunteers and patients (P0.01). In 20 volunteers and 26 patients, after juice administration, the best visualization of the pancreatic duct was achieved at (58.98 +/- 14.96) min and (59.41 +/- 13.79) min, respectively, and the overlap imaging of oral juice was especially observed at (42.86 +/- 10.92) min and (41.63 +/- 9.32) min, respectively.Orally lemon/orange juice is an effective method to improve MRCP imaging of pancreatic ducts. The lemon/orange juice should be administered at 60 min prior to MRCP.

Antizyme is a small protein induced by elevated intracellular polyamines. Antizyme binds specifically to ornithine decarboxylase (ODC) , targeting ODC for ubiquitin-independent degradation by the 26S protosome, which consequently reduces polyamine synthesis. Polyamine transport may also be regulated by antizyme, through which the cellular polyamine levels are maintained. In recent years, more and more studies focus on antizyme with the development of biotechnique. In this article, advancements in the antizyme family, synthesis, function and intracellular location are reviewed.

Objective To describe the multiparametric magnetic resonance imaging (MRI) appearance of prostate tuberculosis. Materials and methods Six patients with prostate tuberculosis were analyzed retrospectively. The mean age of the patients was 60.5 years (range, 48-67 years). The mean prostate specific antigen concentration was 6.62 ng/mL (range, 0.54-14.57 ng/mL). All patients underwent a multiparametric MRI examination. Results The histopathological results were obtained from biopsies in four men and from transurethral resection of the prostate in two men after the MRI examination. Nodular (33%, 2/6 patients) and diffuse lesions (67%, 4/6 patients) were seen on MRI. The nodular lesions were featured by extremely low signal intensity (similar to that of muscle) on T2-weighted imaging (T2WI). The T2WI signal intensity of the diffuse lesions was low but higher than that of muscle, which showed high signal intensity on diffusion weighted imaging and low signal intensity on an apparent diffusion coefficient map. MR spectroscopic imaging of this type showed a normal-like spectrum. Abscesses were found in one patient with the nodular type and in one with the diffuse type. Conclusion The appearance of prostate tuberculosis on MRI can be separated into multiple nodular and diffuse types. Multiparametric MRI may offer useful information for diagnosing prostate tuberculosis.

To investigate the role of serum-and-glucocorticoid-inducible-kinase-1 (SGK1) in colitis and its potential pathological mechanisms.SGK1 expression in mucosal biopsies from patients with active Crohn's disease (CD) and normal controls was detected by immunohistochemistry. We established an acute colitis model in mice induced by 2,4,6-trinitrobenzene sulfonicacid, and demonstrated the presence of colitis using the disease activity index, the histologic activity index and hematoxylin and eosin staining. The cellular events and potential mechanisms were implemented with small interference RNA and an inhibitor of signaling molecule (i.e., U0126) in intestinal epithelial cells (IECs). The interaction between SGK1 and the signaling molecule was assessed by co-immunoprecipitation.SGK1 expression was significantly increased in the inflamed epithelia of patients with active CD and TNBS-induced colitis model (0.58 ± 0.055 vs 0.85 ± 0.06, P0.01). At the cellular level, silencing of SGK1 by small interference RNA (siSGK1) significantly inhibited the phosphorylation of mitogen-activated protein kinase kinase 1 (MEK1) and the downstream molecule extracellular signal regulated protein kinase (ERK) 1/2, which induced the upregulation of p53 and Bcl-2-associated X protein, mediating the subsequent cellular apoptosis and proliferation in IECs. Cells treated with MEK1 inhibitor (i.e., U0126) before siSGK1 transfection showed a reversal of the siSGK1-induced cellular apoptosis.Our data suggested that SGK1 may protect IECs in colitis from tumor necrosis factor-α-induced apoptosis partly by triggering MEK/ERK activation.