The function of carnosic acid in lipopolysaccharides-induced hepatic and intestinal inflammation in poultry.

Inflammatory processes are often accompanied by oxidative stress and lipid peroxidation, which might lead to cellular and organ damage. Carnosic acid (CA), an active component found in rosemary, exhibits pharmacological properties including antioxidative, anti-inflammatory, and antiviral effects. The aim of this research was to investigate whether CA can mitigate lipopolysaccharide (LPS)-induced oxidative stress and inflammatory responses in poultry and to understand its underlying mechanisms. We administered CA to broiler chickens via oral gavage and treated them with LPS, followed by analysis of the effects of different dosages of CA on body weight, antioxidative capacity, and inflammatory factors. Carnosic acid had no significant impact on the body weight of broiler chickens. However, serum analysis indicated that the middle dose of CA effectively enhanced the antioxidative capacity and reduced levels of oxidative stress and inflammation-related factors. Moreover, in the liver, CA demonstrated the ability to regulate the expression of proteins such as heat shock protein 60 (HSP60), heat shock protein 70 (HSP70), and P38 mitogen-activated protein kinase (P38), suggesting its protective role against liver damage induced by LPS. In the intestinal tract of broiler chickens, CA regulated the expression and localization of proteins including HSP60, HSP70, NFE2 like bZIP transcription factor 2 (Nrf2), and P38, while also influencing the expression of inflammatory markers such as protein tyrosine phosphatase receptor type C (CD45), and connexin (Cx). These findings revealed the potential protective mechanisms of CA in alleviating oxidative stress and inflammatory damage induced by LPS in poultry. Carnosic acid notably enhanced the chickens' antioxidative capacity by modulating the expression of key proteins, thereby reducing oxidative stress and inflammatory response levels. This study provides a deeper comprehension of the protective mechanisms of CA and its potential impact on avian health.

Evaluation of sustainability of mycorrhizal industry development in Fujian Province-based on a combination of CRITIC empowerment method and cloud model.

The sustainable development of mycorrhizal industry is the key to solve the problem of "mycorrhizal forestry contradiction". As a major province of edible mushroom production and forestry resources in China, Fujian Province is also an important origin of mycorrhizal technology research and development, so it is more typical and practical to establish an index system to evaluate the sustainability of mycorrhizal industry development in Fujian Province. Through research interviews and data collection, a sustainable capacity evaluation system of mycorrhizal industry was established with 21 indicators in six dimensions: economic, ecological, social, cultural, political, and technological. A combination of CRITIC empowerment method and cloud model was used to evaluate the sustainability of mycorrhizal industry development in Fujian Province. The results show that although the economic sustainability of the mycorrhizal industry in Fujian Province is average, the overall development trend is good and there are not too many problems. The sustainability of ecological, social and technological levels all have large differences in the development of indicators and the overall development status is average, but overall, the ecological, social and technological levels show a steady forward development from 2017 to 2020. The cultural and political dimensions of sustainability not only have large differences in the development of indicators and an average overall development status, but also have a small development span from 2017 to 2020 and a slow overall development.

A study on the influencing factors and related paths of farmer's participation in food safety governance-based on DEMATEL-ISM-MICMAC model.

Farmers' participation in food safety governance is an important part of food safety social co-governance, and the accurate identification of its influencing factors and their related paths is of guiding significance to the scientific decision-making of food safety governance. The system of influencing factors of farmers' participation in food safety governance was constructed from four dimensions, and the influence network of each dimension was revealed by decision laboratory analysis (DEMATEL). The hierarchical structure and correlation path of influencing factors were determined by interpretive structural model (ISM), and the attributes of influencing factors were further classified by cross influence matrix multiplication (MICMAC). The results show that the influencing factors of farmers' participation in food safety governance can be divided into seven levels, among which the level of education and the status of village cadres are the fundamental characteristic factors. The degree of rural informatization, the intensity of government supervision, the promotion of village committees, the response of the government and the degree of disclosure of government information are the deep core factors, and risk cognition, political trust and family eating habits are special factors. Taking the importance and attribute status of farmers' participation in food safety governance into decision-making considerations is of great significance to improve the efficiency of food safety governance.

Evaluation of the etiology and risk factors for maternal sepsis: A single center study in Guangzhou, China.

BACKGROUND: Maternal sepsis is a major cause of gestational morbidity and neonatal mortality worldwide and particularly in China. AIM: To evaluate the etiology of maternal sepsis and further identify its risk factors. METHODS: In this retrospective study, we evaluated 70698 obstetric patients who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 1, 2009 and June 30, 2018. Subjects were divided into sepsis group and non-sepsis group based on the incidence of sepsis. Data about medical history (surgical and obstetric history) and demographic information were collected. The Mann-Whitney U test was used to compare patient age, gestational age and duration of hospitalization between the two groups. Univariate and multivariate logistic regression models were used to analyze the etiology and the risk factors for maternal sepsis. Unadjusted and adjusted odds ratios (OR) are reported. RESULTS: A total of 561 of 70698 obstetric patients were diagnosed with infection; of the infected patients, 492 had non-sepsis associated infection (87.7%), while 69 had sepsis (12.3%). The morbidity rate of maternal sepsis was 9.76/10000; the fatality rate in the sepsis group was 11.6% (8/69). Emergency admission (OR = 2.183) or transfer (OR = 2.870), irregular prenatal care (OR = 2.953), labor induction (OR = 4.665), cervical cerclage (OR = 14.214), first trimester (OR = 6.806) and second trimester (OR = 2.09) were significant risk factors for maternal sepsis. CONCLUSION: Mode of admission, poor prenatal care, labor induction, cervical cerclage, first trimester and second trimester pregnancy were risk factors for maternal sepsis. Escherichia coli was the most common causative organism for maternal sepsis, and the uterus was the most common site of infection.

A Pyroptosis-Related Gene Signature for Predicting Survival in Glioblastoma.

BACKGROUND: In this study, a prognostic model based on pyroptosis-related genes was established to predict overall survival (OS) in patients with glioblastoma (GBM). METHODS: The gene expression data and clinical information of GBM patients were obtained from The Cancer Genome Atlas (TCGA), and bioinformatics analysis of differentially expressed genes was performed. LASSO Cox regression model was used to construct a three-pyroptosis-related gene signature, and validation was performed using an experimental cohort. RESULTS: A total of three pyroptosis-related genes (CASP4, CASP9, and NOD2) were used to construct a survival prognostic model, and experimental validation was performed using an experimental cohort. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curves (AUC) was 0.921, 0.840, and 0.905 at 1, 3, and 5 years, respectively. Functional analysis revealed that T-cell activation, regulation of T-cell activation, leukocyte cell-cell adhesion, and positive regulation of cell adhesion among other immune-related functions were enriched, and immune-related processes were different between the two risk groups. CONCLUSION: In this study, a novel prognostic model based on three pyroptosis-related genes is constructed and used to predict the prognosis of GBM patients. The model can accurately and conveniently predict the 1-, 3-, and 5-year OS of GBM patients.

Porf-2 Inhibits Tumor Cell Migration Through the MMP-2/9 Signaling Pathway in Neuroblastoma and Glioma.

Tumor migration and invasion are key pathological processes that contribute to cell metastasis as well as treatment failure in patients with malignant tumors. However, the mechanisms governing tumor cell migration remain poorly understood. By analyzing the tumor-related database and tumor cell lines, we found that preoptic regulatory factor-2 (Porf-2) is downexpressed in both neuroblastoma and glioma. Using in vitro assays, our data demonstrated that the expression of Porf-2 inhibits tumor cell migration both in neuroblastoma and glioma cell lines. Domain-mutated Porf-2 plasmids were then constructed, and it was found that the GAP domain, which plays a role in the inactivation of Rac1, is the functional domain for inhibiting tumor cell migration. Furthermore, by screening potential downstream effectors, we found that Porf-2 can reduce MMP-2 and MMP-9 expression. Overexpression of MMP-2 blocked the inhibitory effect of Porf-2 in tumor cell migration both in vitro and in vivo. Taken together, we show for the first time that Porf-2 is capable of suppressing tumor cell migration via its GAP domain and the downregulation of MMP-2/9, suggesting that targeting Porf-2 could be a promising therapeutic strategy for nervous system tumors.

Mycobacterium chubuense hand infection.

Mycobacterium chubuense is a scotochromogenic rapidly growing mycobacterium (RGM), a nontuberculous mycobacterium (NTM)that was first characterized in 1981. This case report describes a rare case of M. chubuense infection in the right hand of a 53-year-old man who lived in the coastal areas of Zhejiang province, China. To the best of our knowledge, this is only the second reported case of a M. chubuense infection worldwide, the first in a hand. Culture of lesion were positive for Mycobacterium chubuense, which was confirmed by PCR and sequencing. This case report complementsthe literature regarding M. chubuense infection.

Multimode Computed-Tomography-Guided Thrombolysis under a Prolonged Time Window in Acute Ischemic Stroke Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is an independent risk factor for intracranial hemorrhage in patients receiving recombinant-tissue-type plasminogen activator (rt-PA) thrombolytic therapy. Research showed that patients with acute ischemic stroke (AIS) could benefit from multimode computed-tomography- (CT-) guided intravenous thrombolysis over 4.5 hours. The medical data of patients with AIS in our center were retrospectively reviewed, and the data of the multimode CT-guided thrombolytic therapy or nonthrombolytic therapy within different time windows (3-9 hours) were evaluated. 134 AIS cases were selected successfully and divided into three groups: patients with AF treated by rt-PA (AF rt-PA), patients with AF not treated by rt-PA (AF non-rt-PA), and patients without AF treated by rt-PA (non-AF rt-PA). After correcting for the baseline NIH Stroke Scale (NIHSS), sex, age, and hypertension data, the comparison results showed that the NIHSS improved significantly at hospital discharge for rt-PA-treated patients (n = 47) compared to non-rt-PA-treated patients with AIS (n = 31) with AF (P = 0.0156). The NIHSS evaluation at 90 days of follow-up also improved in rt-PA-treated patients (P = 0.0157). The NIHSS at hospital discharge was higher in AF rt-PA-treated patients compared to non-AF rt-PA-treated patients (P = 0.0167) after correction; the difference was not statistically significant at 90 days of follow-up (P = 0.091). Our research showed that the neural function improved after 3-9 hours of thrombolytic therapy with rt-PA in patients with AIS and AF. If there is no thrombolytic taboo, the patients could benefit from the thrombolytic therapy, although the onset time window has been extended to 9 hours.

A method of ultrasound diagnosis for unilateral peripheral entrapment neuropathy based on multilevel side-to-side image contrast.

Individual variations have been reported in the existing methods for examining peripheral entrapment neuropathy, by which limited sites can be examined. In this study, the patients with unilateral carpal tunnel syndrome (CTS), cubital tunnel syndrome (CuTS) and radial nerve compression (RNC) were selected as research subjects and an ultrasound technique was proposed based on multilevel side-to-side image contrast for the diagnosis of unilateral peripheral entrapment neuropathy. According to the statistical analysis of 62 patients with CTS, CuTS or RNC, the diagnostic thresholds of the cross-sectional area swelling ratio (CSASR) for diagnosis of CTS, CuTS or RNC were 1.22, 1.51 and 1.50, respectively. The surgical therapeutic thresholds of CSASR for the treatment of CTS, CuTS and RNC were 1.48, 1.67 and 3.04, respectively. When the maximal CSASR of the diseased nerve was greater than or equal to the diagnostic threshold, the nerve compression could be diagnosed. If it was less than the diagnostic threshold, nerve compression was excluded. Conservative treatment was indicated when the maximal CSASR of the diseased nerve was less than the therapeutic threshold. When the maximal CSASR was greater than or equal to the therapeutic threshold, surgical treatment was indicated, and the nerve release procedure was selected. The novel multilevel side-to-side image contrast ultrasound technique proposed in this study can substantially reduce the impact of individual variation and explore the full course of the diseased nerve. It is a novel approach for diagnosis, treatment selection, and determination of treatment sites of unilateral peripheral entrapment neuropathy.

DAX1 promotes cervical cancer cell growth and tumorigenicity through activation of Wnt/ß-catenin pathway via GSK3ß.

DAX1 is well known for its fundamental role in several types of cancer, while its biological role in cervical cancer remains largely unexplored. The expression of DAX1 in cervical carcinoma tissue was examined using immunohistochemistry and western blot. The effects of DAX1 silencing on the cell growth, tumor formation, and CSC (cancer stem cell) characteristics were also investigated. DAX1 expressed a gradual increase from normal cervix to high-grade squamous intraepithelial lesions, and consequently to cervical cancer. Silence of DAX1 significantly inhibited the cell growth, tumorigenicity, and tumorsphere formation. Furthermore, the TOP/FOP-Flash reporter assay revealed that Wnt/ß-catenin pathway was significantly inactivated in DAX1-silenced cervical cancer cells with the downregulation of Wnt/ß-catenin targeting genes, including cyclinD1 and c-myc. Moreover, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assay confirmed that DAX1 transcriptionally repressed glycogen synthase kinase 3ß (GSK3ß), an inhibitor of the Wnt/ß-catenin pathway, by physically interacting with -666~-444 motif on the GSK3ß promoter. Additionally, the blockage of GSK3ß by CHIR-99021 resulted in a significant increase of CSC characteristics induced by the silence of DAX1. Our data demonstrated that DAX1 is overexpressed in cervical cancer, and that it promotes cell growth and tumorigenicity through activating Wnt/ß-catenin pathway mediated by GSK3ß.

[Effect of serum restriction on insulin like growth factor-1 expressions and invasiveness in human trophoblast HTR-8/SVneo cells in vitro].

OBJECTIVE: To explore the effect of serum restriction on the invasiveness and expressions of insulin-like growth factor-1 (IGF-1) and matrix metalloproteinase-2 (MMP-2) in human trophoblast HTR-8/SVneo cells in vitro. METHODS: HTR-8/SVneo cells were cultured in the presence of 1%, 5%, or 10% fetal bovine serum (FBS) for 48 h. Fluorescence quantitative PCR and immunofluorescence staining were employed to examine the changes in IGF-1 and MMP-2 expressions at both the mRNA and protein levels in HTR-8/SVneo cells; MTT assay and Transwell invasion assay were used to assess the changes of the cell proliferation and the cell invasion ability, respectively. MMP-2 expression, cell proliferation and invasiveness were also assessed in the cells treated with recombinant human IGF-1. RESULTS: HTR-8/SVneo cells exhibited significantly lowered cell proliferation in cultures containing low concentrations of FBS (P<0.05). The expressions of IGF-1 and MMP-2 at both mRNA and protein levels were significantly down-regulated and the invasiveness was significantly lowered in cells cultured in the medium containing 1% FBS as compared with those of cells cultured in the presence of 5% and 10% FBS (P<0.05). Treatment of the cells with recombinant human IGF-1 significantly up-regulated MMP-2 expression (P<0.05) and increased the cell invasiveness (P<0.05). CONCLUSIONS: FBS restriction down-regulates IGF-1 expression in human trophoblast HTR-8/SVneo cells and suppress the cell invasiveness possibly by suppressing MMP-2 expression. Treatment with recombinant human IGF-1 can up-regulate MMP-2 expression and promote the invasiveness of HTR-8/SVneo cells.

Transcriptome profiling of the subventricular zone and dentate gyrus in an animal model of Parkinson's disease.

Adult neurogenesis in the subventricular zone (SVZ), as well as in the subgranular zone contributes to brain maintenance and regeneration. In the adult brain, dopamine (DA) can regulate the endogenous neural stem cells within these two regions, while a DA deficit may affect neurogenesis. Notably, the factors that regulate in vivo neurogenesis in these subregions have not yet been fully characterized, particularly following DA depletion. In thi study, we performed RNA sequencing to investigate transcriptomic changes in the SVZ and dentate gyrus (DG) of mice in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This analysis identified differentially expressed genes which were involved in the regulation of transcription, immune response, extracellular region, cell junction and myelination. These genes partially displayed different temporal profiles of expression, some of which may participate in the metabolic switch related to neurogenesis. Additionally, the mitogen­activated protein kinase (MAPK) signaling pathway was shown to be been positively regulated in the SVZ, while it was negatively affected in the DG following MPTP administration. Overall, our findings indicate that exposure to MPTP may exert different effects on transcriptome profiling between the SVZ and DG.

[Clinical efficacy and safety of controlled-release dinoprostone insert: a multicenter retrospective study].

OBJECTIVE: To analyze the effectiveness and safety of controlled-release dinoprostone insert for term labor induction in the Pearl River Delta of Guangdong province. METHODS: Twenty hospitals using controlled-release dinoprostone insert for term labor induction in the Pearl River Delta of Guangdong province were stratified into provincial hospitals and municipal hospitals, and three hospitals of each level were selected as research units. According to the inclusion and exclusion criteria, 1390 pregnant women receiving term labor induction using controlled-release dinoprostone insert were retrospectively analyzed to evaluate the the effectiveness and safety with another 957 pregnant women with induced abortion using oxytocin as the control group. RESULTS: Compared with the control group, the controlled-release dinoprostone insert group showed a significantly longer length of the latent phase of labor (4.06∓2.65 vs 3.20∓2.08 h, P=0.003, 95%CI [0.182, 0.920]) and shorter lengths of the active phase (1.73∓1.32 vs 2.22∓1.75 h, P=0.000, 95%CI [-0.795, -0.363]) and the second stage of labor (0.49∓0.37 vs 0.54∓0.43 h, P=0.003, 95%CI [-0.137, -0.028]). No significant differences were found in the length of the first stage of labor, the vaginal delivery rate, adverse reactions, or fetal outcomes between the two groups. CONCLUSION: Controlled-release dinoprostone insert is effective and safe for labor induction at term.

Intraparenchymal endodermal cyst with spontaneous intracystic hemorrhage in the temporal lobe of an adult.

BACKGROUND: Endodermal cysts (EC) are rare but well-known congenial lesions of the central nervous system mainly located in the spinal subdural space. Intracranial ECs are rare and commonly encountered in the posterior cranial fossa as extra-axial lesions; an intraparenchymal location is exceedingly rare. A complete removal is the best surgical strategy and any residue can cause recurrence. It is necessary to exclude EC in patients with intracranial cystic lesions. We present a case of intraparenchymal EC with spontaneous intracystic hemorrhage in the temporal lobe of an adult. METHODS: A 43-year-old man presented with headache and memory deterioration. Brain computed tomography and magnetic resonance imaging showed a slightly enhanced temporal lobe cystic lesion, which was homogenously hyperintense on T1-and T2-weighted images. There was a suspicion of brain abscess at admission. The lesion was totally removed with a left subtemporal craniotomy. Histological examination revealed an EC with intracystic hemorrhage. RESULTS: The preoperative symptoms were relieved after surgery and 3-month follow-up magnetic resonance imaging found no cystic signs. CONCLUSION: This case suggests that EC should be considered in the differential diagnosis of intracranial cystic lesions and a complete removal is the best strategy of choice.

[Effect of implantation of cardiosphere-derived cells combined with rat heart tissue-derived extracellular matrix on acute myocardial infarction in rats].

OBJECTIVE: To investigate whether heart tissue-derived extracellular matrix (ECM) promotes the differentiation of cardiosphere-derived cells (CDCs) implanted in rat infracted myocardium to improve the cardiac structure and function. METHODS: Rat CDCs were cultured by cardiac explant methods, and ECM was prepared by decelluariztion method. In a Wistar rat model of acute myocardial infarction established by ligating the left anterior descending branch, IMDM solution, ECM suspension, 106 CDCs in IMDM solution, or 106 CDCs in ECM suspension were injected into the infracted rat myocardium (6 rats in each group). The cardiac function of the rats was evaluated by cardiac ultrasonography, and the percentage of positive heart fibrosis area after infarction was determined with Masson staining. The differentiation of implanted CDCs in the infarcted myocardium was detected using immunofluorescence assay for the markers of cardiac muscle cells (α-SA), vascular endothelial cells (vWF) and smooth muscle cells (α-SMA). RESULTS: Three weeks after acute myocardial infarction, the rats with injection of CDCs in ECM showed the highest left ventricular ejection fraction (LVEF) and percentage of fraction shortening with the lowest percentage of positive heart fibrosis area; implantation of CDCs with ECM resulted in significantly higher rates of CDC differentiation into cardiac muscle cells, vascular endothelial cells and smooth muscle cell (P<0.05). CONCLUSION: Heart-tissue derived ECM significantly promotes the differentiation of CDCs implanted in the infracted myocardium into cardiac muscle cells, vascular endothelial cells and smooth muscle cells to improve the cardiac structure and cardiac functions in rats.

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

bFGF binding cardiac extracellular matrix promotes the repair potential of bone marrow mesenchymal stem cells in a rabbit model for acute myocardial infarction.

To assess the effect of basic fibroblast growth factor-binding extracellular matrix (bFGF-ECM) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation on acute myocardial infarction (AMI) and explore the underlying mechenisms. Rabbit hearts were processed by decellularization with sodium dodecyl sulfate (SDS) perfusion, heparin immobilization, bFGF-binding and homogenization, for preparation of bFGF-binding cardiac ECM suspension (bFGF-ECM). Thereafter, the characteristics of bFGF release were analyzed in vitro. Following ligation of the mid-third of the left anterior descending artery, the rabbits were divided into a control group (no treatment), BMSCs group (BMSCs transplantation), bFGF-ECM group (bFGF-ECM implantation), and BMSCs + bFGF-ECM group (BMSCs and bFGF-ECM implantation). Apoptosis and differentiation of implanted BMSCs, and the left ventricular (LV) remodeling and function were assessed. The ex vivo proliferation, apoptosis, migration and differentiation of BMSCs were determined after exposure to bFGF and/or ECM. The ECM could sustainably release bFGF. 24 h and 6 weeks after the operation, improved viability and differentiation of the implanted BMSCs, as well as inhibited dilatation and preserved function of the left ventricle (LV), were significant in the BMSCs + bFGF-ECM group compared with other groups (P < 0.05), although BMSCs and ECM-bFGF groups also showed better results than control group (P < 0.05). Additionally, ECM and bFGF showed a synergistic effect on BMSCs proliferation, viability, migration and differentiation. The combination of bFGF-binding ECM and BMSCs implantation may promote myocardial regeneration and LV function, and become a new strategy for the treatment of AMI.

Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.

HGF and IGF-1 promote protective effects of allogeneic BMSC transplantation in rabbit model of acute myocardial infarction.

OBJECTIVES: To explore effects of hepatocyte growth factor (HGF) combined with insulin-like growth factor 1 (IGF-1) on transplanted bone marrow mesenchymal stem cells (BMSCs), for treatment of acute myocardial ischaemia. MATERIALS AND METHODS: After ligation of the left anterior descending artery, rabbits were divided into a Control group, a Factors group (HGF+IGF-1), a BMSC group and a Factors+BMSCs group. Allogenous BMSCs (1 × 10(7)) and/or control-released microspheres of 2 µg HGF+2 µg IGF-1 were intramyocardially injected into infarcted regions. Apoptosis and differentiation of implanted BMSCs, histological and morphological results, and cardiac remodelling and function were evaluated at different time points. In vitro, BMSCs were exposed to HGF, IGF-1 and both (50 ng/ml) and subsequently proliferation, migration, myocardial differentiation and apoptosis induced by hypoxia, were analysed. RESULTS: Four weeks post-operatively, the above indices were significantly improved in Factors+BMSCs group compared to the others (P < 0.01), although Factors and BMSCs group also showed better results than Control group (P < 0.05). In vitro, HGF promoted BMSC migration and differentiation into cardiomyocytes, but inhibited proliferation (P < 0.05), while IGF-1 increased proliferation and migration, and inhibited apoptosis induced by hypoxia (P < 0.05), but did not induce myocardial differentiation. Combination of HGF and IGF-1 significantly promoted BMSCs capacity for migration, differentiation and lack of apoptosis (P < 0.05). CONCLUSIONS: Combination of HGF and IGF-1 activated BMSCs complementarily, and controlled release of the two factors promoted protective potential of transplanted BMSCs to repair infarcted myocardium. This suggests a new strategy for cell therapies to overcome acute ischemic myocardial injury.

Delayed enrichment for c-kit and inducing cardiac differentiation attenuated protective effects of BMSCs' transplantation in pig model of acute myocardial ischemia.

OBJECTIVE: To investigate the effects of immature cardiomyocytes differentiated from c-kit(+) bone marrow mesenchymal stem cells (BMSCs) against acute myocardial infarction (AMI). METHODS: Miniswine passage 8 BMSCs were enriched for c-kit and induced by 5 µM 5-azacytidine (AZA) for 14 days, and a second enrichment for the dihydropyridine receptor subunit α2δ1 was performed (enriched BMSCs). Thereafter, enriched BMSCs were analyzed by determining cardiac differentiation, secretion function, and the effects of these secreted factors on cardiac stem cells (CSCs). Miniswine with AMI were divided into control, primary BMSCs' (PB), and enriched BMSCs' (EB) groups. Autologous BMSCs were intramyocardially injected into the ischemic regions in PB and EB groups. The following indices were evaluated at different time points, including paracrine of implanted BMSCs, histological and morphological analysis, myocardial perfusion, and cardiac function. RESULTS: As shown by in vitro study, enrichment + AZA significantly promoted BMSCs to express cardiac-specific markers and format action potential, but down-regulated the expression of VEGF and bFGF, consequently attenuated BMSCs-inducing CSCs proliferation, migration, and differentiation. The in vivo experiments revealed similar results like the in vitro 6 weeks postoperatively. And in EB group, there were decreased angiogenesis and myocardial perfusion, attenuated resident CSCs-mediated myocardial regeneration, and consequently impaired cardiac function compared with PB group. CONCLUSIONS: This pretreatment promoted BMSCs to differentiate into myocardiocytes both in vitro and in vivo, but impaired their paracrine function and effects on resident CSCs, suggesting that inducing cardiac differentiation alone may not improve protective effects of BMSCs transplantation on AMI.