Based on HPLC and HS-GC-IMS Techniques, the Changes in the Internal Chemical Components of Schisandra chinensis (Turcz.) Baill. Fruit at Different Harvesting Periods Were Analyzed.

Schisandra chinensis, as a traditional Chinese herbal medicine, has clear pharmacological effects such as treating asthma, protecting nerves and blood vessels, and having anti-inflammatory properties. Although the Schisandra chinensis fruit contain multiple active components, the lignans have been widely studied as the primary pharmacologically active compound. The volatile chemical components of Schisandra chinensis include a large amount of terpenes, which have been proven to have broad pharmacological activities. However, when to harvest to ensure the highest accumulation of pharmacologically active components in Schisandra chinensis fruits is a critical issue. The Schisandra chinensis fruit trees in the resource nursery were all planted in 2019 and began bearing fruit in 2021. Their nutritional status and tree vigor remain consistently good. The content of lignans and organic acids in the fruits of Schisandra chinensis over seven different harvest periods was tested, and the results of high-performance liquid chromatography (HPLC) indicated that the lignan content was higher, at 35 mg/g, in late July, and the organic acid content was higher, at 72.34 mg/g, in early September. If lignans and organic acids are to be selected as raw materials for pharmacological development, the harvest can be carried out at this stage. Using HS-GC-IMS technology, a total of 67 volatile flavor substances were detected, and the fingerprint of the volatile flavor substances in the different picking periods was established. It was shown by the results that the content of volatile flavor substances was the highest in early August, and 16 flavor substances were selected by odor activity value (OAV). The variable importance in projection (VIP) values of 16 substances were further screened, and terpinolene was identified as the key volatile flavor substance that caused the aroma characteristics of Schisandra chinensis fruit at different harvesting periods. If the aroma component content of Schisandra chinensis fruit is planned to be used as raw material for development and utilization, then early August, when the aroma component content is higher, should be chosen as the time for harvest. This study provides a theoretical basis for the suitable harvesting time of Schisandra chinensis for different uses, and promotes the high-quality development of the Schisandra chinensis industry.

Understanding and including 'pink-collar' workers in employment-based travel demand models.

The segmentation of commuters into either blue or white-collar workers remains is still common in urban transport models. Internationally, models have started to use more elaborate segmentations, more reflective of changes in labour markets, such as increased female participation. Finding appropriate labour market segmentations for commute trip modelling remains a challenge. This paper harnesses a data-driven approach using unsupervised clustering-applied to 2017-20 South East Queensland Travel Survey (SEQTS) data. Commuter types are grouped by occupational, industry, and socio-demographic variables (i.e., gender, age, household size, household vehicle ownership and worker skill score). The results show that at a large number of clusters (i.e., k = 8) a highly distinct set of commuter types can be observed. But model run times tend to require a much smaller number of market segments. When only three clusters are formed (k = 3) a market segmentation emerges with one female-dominated type ('pink collar'), one male-dominated type ('blue collar') and one with both genders almost equally involved ('white collar'). There are nuances as to which workers are included in each segment, and differences in travel behaviours across the three types. 'Pink collar' workers are mostly comprised of female clerical and administrative workers, community and personal service workers and sales workers. They have the shortest median commutes for both private motorised and active transport modes. The approach and methods should assist transport planners to derive more accurate and robust market segmentations for use in large urban transport models, and, better predict the value of alternative transport projects and policies for all types of commuters.

Flavor Quality Analysis of Ten Actinidia arguta Fruits Based on High-Performance Liquid Chromatography and Headspace Gas Chromatography-Ion Mobility Spectrometry.

Actinidia arguta is a fruit crop with high nutritional and economic value. However, its flavor quality depends on various factors, such as variety, environment, and post-harvest handling. We analyzed the composition of total soluble sugars, titratable acids, organic acids, and flavor substances in the fruits of ten A. arguta varieties. The total soluble sugar content ranged from 4.22 g/L to 12.99 g/L, the titratable acid content ranged from 52.55 g/L to 89.9 g/L, and the sugar-acid ratio ranged from 5.39 to 14.17 at the soft ripe stage. High-performance liquid chromatography (HPLC) showed that citric, quinic, and malic acids were the main organic acids in the A. arguta fruits. Headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) detected 81 volatile compounds in 10 A. arguta varieties, including 24 esters, 17 alcohols, 23 aldehydes, 7 ketones, 5 terpenes, 2 acids, 1 Pyrazine, 1 furan, and 1 benzene. Esters and aldehydes had the highest relative content of total volatile compounds. An orthogonal partial least squares discriminant analysis (OPLS-DA) based on the odor activity value (OAV) revealed that myrcene, benzaldehyde, methyl isobutyrate, α-phellandrene, 3-methyl butanal, valeraldehyde, ethyl butyrate, acetoin, (E)-2-octenal, hexyl propanoate, terpinolene, 1-penten-3-one, and methyl butyrate were the main contributors to the differences in the aroma profiles of the fruits of different A. arguta varieties. Ten A. arguta varieties have different flavors. This study can clarify the differences between varieties and provide a reference for the evaluation of A. arguta fruit flavor, variety improvement and new variety selection.

Characterization of Key Compounds of Organic Acids and Aroma Volatiles in Fruits of Different Actinidia argute Resources Based on High-Performance Liquid Chromatography (HPLC) and Headspace Gas Chromatography-Ion Mobility Spectrometry (HS-GC-IMS).

Actinidia arguta, known for its distinctive flavor and high nutritional value, has seen an increase in cultivation and variety identification. However, the characterization of its volatile aroma compounds remains limited. This study aimed to understand the flavor quality and key volatile aroma compounds of different A. arguta fruits. We examined 35 A. arguta resource fruits for soluble sugars, titratable acids, and sugar-acid ratios. Their organic acids and volatile aroma compounds were analyzed using high-performance liquid chromatography (HPLC) and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS). The study found that among the 35 samples tested, S12 had a higher sugar-acid ratio due to its higher sugar content despite having a high titratable acid content, making its fruit flavor superior to other sources. The A. arguta resource fruits can be classified into two types: those dominated by citric acid and those dominated by quinic acid. The analysis identified a total of 76 volatile aroma substances in 35 A. arguta resource fruits. These included 18 esters, 14 alcohols, 16 ketones, 12 aldehydes, seven terpenes, three pyrazines, two furans, two acids, and two other compounds. Aldehydes had the highest relative content of total volatile compounds. Using the orthogonal partial least squares discriminant method (OPLS-DA) analysis, with the 76 volatile aroma substances as dependent variables and different soft date kiwifruit resources as independent variables, 33 volatile aroma substances with variable importance in projection (VIP) greater than 1 were identified as the main aroma substances of A. arguta resource fruits. The volatile aroma compounds with VIP values greater than 1 were analyzed for odor activity value (OAV). The OAV values of isoamyl acetate, 3-methyl-1-butanol, 1-hexanol, and butanal were significantly higher than those of the other compounds. This suggests that these four volatile compounds contribute more to the overall aroma of A. arguta. This study is significant for understanding the differences between the fruit aromas of different A. arguta resources and for scientifically recognizing the characteristic compounds of the fruit aromas of different A. arguta resources.

Analysis of Volatile Components in Dried Fruits and Branch Exudates of Schisandra chinensis with Different Fruit Colors Using GC-IMS Technology.

To investigate the volatile components of Schisandra chinensis (Turcz.) Bail (commonly known as northern Schisandra) of different colors and to explore their similarities and differences, to identify the main flavor substances in the volatile components of the branch exudates of northern schisandra, and finally to establish a fingerprint map of the volatile components of the dried fruits and branch exudates of northern Schisandra of different colors, we used GC-IMS technology to analyze the volatile components of the dried fruits and branch exudates of three different colors of northern Schisandra and established a fingerprint spectra. The results showed that a total of 60 different volatile chemical components were identified in the branch exudates and dried fruits of Schisandra. The components of germplasm resources with different fruit colors were significantly different. The ion mobility spectrum and OPLS-DA results showed that white and yellow fruits were more similar compared to red fruits. The volatile components in dried fruits were significantly higher than those in branch exudates. After VIP (variable importance in projection) screening, 41 key volatile substances in dried fruits and 30 key volatile substances in branch exudates were obtained. After screening by odor activity value (OAV), there were 24 volatile components greater than 1 in both dried fruits and branch exudates. The most important contributing volatile substance was 3-methyl-butanal, and the most important contributing volatile substance in white fruit was (E)-2-hexenal.

Comprehensive Evaluation of Ten Actinidia arguta Wines Based on Color, Organic Acids, Volatile Compounds, and Quantitative Descriptive Analysis.

Actinidia arguta wine is a low-alcoholic beverage brewed from A. arguta with a unique flavor and sweet taste. In this study, the basic physicochemical indicators, color, organic acid, and volatile aroma components of wines made from the A. arguta varieties 'Kuilv', 'Fenglv', 'Jialv', 'Wanlv', 'Xinlv', 'Pinglv', 'Lvbao', 'Cuiyu', 'Tianxinbao', and 'Longcheng No.2' were determined, and a sensory evaluation was performed. The findings show that 'Tianxinbao' produced the driest extract (49.59 g/L), 'Kuilv' produced the most Vitamin C (913.46 mg/L) and total phenols (816.10 mg/L), 'Jialv' produced the most total flavonoids (477.12 mg/L), and 'Cuiyu' produced the most tannins (4.63 g/L). We analyzed the color of the A. arguta wines based on CIEL*a*b* parameters and found that the 'Kuilv' and 'Longcheng No.2' wines had the largest L* value (31.65), the 'Pinglv' wines had the greatest a* value (2.88), and the 'Kuilv' wines had the largest b* value (5.08) and C*ab value (5.66) of the ten samples. A total of eight organic acids were tested in ten samples via high-performance liquid chromatography (HPLC), and we found that there were marked differences in the organic acid contents in different samples (p < 0.05). The main organic acids were citric acid, quinic acid, and malic acid. The aroma description of a wine is one of the keys to its quality. A total of 51 volatile compounds were identified and characterized in ten samples with headspace gas chromatography-ion mobility spectrometry, including 24 esters, 12 alcohols, 9 aldehydes, 3 aldehydes, 2 terpenes, and 1 acid, with the highest total volatile compound content in 'Fenglv'. There were no significant differences in the types of volatile compounds, but there were significant differences in the contents (p < 0.05). An orthogonal partial least squares discriminant analysis (OPLS-DA) based on the odor activity value (OAV) showed that ethyl butanoate, ethyl pentanoate, ethyl crotonate, ethyl isobutyrate, butyl butanoate, 2-methylbutanal, ethyl isovalerate, and ethyl hexanoate were the main odorant markers responsible for flavor differences between all the A. arguta wines. Sensory evaluation is the most subjective and effective way for consumers to judge A. arguta wine quality. A quantitative descriptive analysis (QDA) of the aroma profiles of ten grapes revealed that the 'fruity' and 'floral' descriptors are the main and most essential parts of the overall flavor of A. arguta wines. 'Tianxinbao' had the highest total aroma score. The flavor and quality of A. arguta wines greatly depend on the type and quality of the A. arguta raw material. Therefore, high-quality raw materials can improve the quality of A. arguta wines. The results of the study provide a theoretical basis for improving the quality of A. arguta wines and demonstrate the application prospects of HS-GC-IMS in detecting A. arguta wine flavors.

Effects of physical exercise on blood pressure during pregnancy.

OBJECTIVE: Effect of physical exercise on pregnant women currently has become a hot topic in prenatal health care. In this study, A meta-analysis was conducted on account of Randomized Controlled Trial (RCT). It focused on evaluating the effect of physical exercise intervention on blood pressure so that could provide certain evidence for health care during pregnancy. METHODS: Results of relevant studies were retrieved from PubMed, Embase, Web of Science and the Cochrane Library, and all of these included studies were evaluated according to the Cochrane collaboration's tool for assessing the risk of bias. Stata 15.1 was used for meta-analysis, and mean difference (MD) was used as statistic for pooled analysis. The effect values were combined by conventional meta-analysis and Bayesian meta-analysis respectively, and the consistency of pooled results was considered as well. RESULTS: A total of 18 RCT studies were included in the quantitative analysis. The conventional meta-analysis showed differences in blood pressure between intervention group and control group (P < 0.05). Systolic and diastolic blood pressures of intervention group were 3.19 mmHg (95% CI: -5.13, -1.25) and 2.14 mmHg (95% CI: -4.26, -0.03) lower than that of control group, respectively. Bayesian meta-analysis showed that both systolic and diastolic pressure among intervention group decreased by 3.34 mmHg (95% CrI: -5.15, -1.56) and 2.14 mmHg (95% CrI: -3.79, - 0.50), respectively. Subgroup analysis supported that as long as healthy pregnant women participated in exercises, their blood pressure could be slightly regulated, while hypertension susceptible pregnant women significantly lowered blood pressure. CONCLUSION: Exercise intervention during pregnancy is beneficial to lower or normalize blood pressure, and this research provides clues for follow-up studies.

Energy Expenditure Estimation of Tabata by Combining Acceleration and Heart Rate.

Tabata training plays an important role in health promotion. Effective monitoring of exercise energy expenditure is an important basis for exercisers to adjust their physical activities to achieve exercise goals. The input of acceleration combined with heart rate data and the application of machine learning algorithm are expected to improve the accuracy of EE prediction. This study is based on acceleration and heart rate to build linear regression and back propagate neural network prediction model of Tabata energy expenditure, and compare the accuracy of the two models. Participants (n = 45; Mean age: 21.04 ± 2.39 years) were randomly assigned to the modeling and validation data set in a 3:1 ratio. Each participant simultaneously wore four accelerometers (dominant hand, non-dominant hand, right hip, right ankle), a heart rate band and a metabolic measurement system to complete Tabata exercise test. After obtaining the test data, the correlation of the variables is calculated and passed to linear regression and back propagate neural network algorithms to predict energy expenditure during exercise and interval period. The validation group was entered into the model to obtain the predicted value and the prediction effect was tested. Bland-Alterman test showed two models fell within the consistency interval. The mean absolute percentage error of back propagate neural network was 12.6%, and linear regression was 14.7%. Using both acceleration and heart rate for estimation of Tabata energy expenditure is effective, and the prediction effect of back propagate neural network algorithm is better than linear regression, which is more suitable for Tabata energy expenditure monitoring.

Niemann-Pick Disease Type C: Induced Pluripotent Stem Cell-Derived Neuronal Cells for Modeling Neural Disease and Evaluating Drug Efficacy.

Niemann-Pick disease type C (NPC) is a rare neurodegenerative disorder caused by recessive mutations in the NPC1 or NPC2 gene that result in lysosomal accumulation of unesterified cholesterol in patient cells. Patient fibroblasts have been used for evaluation of compound efficacy, although neuronal degeneration is the hallmark of NPC disease. Here, we report the application of human NPC1 neural stem cells as a cell-based disease model to evaluate nine compounds that have been reported to be efficacious in the NPC1 fibroblasts and mouse models. These cells are differentiated from NPC1 induced pluripotent stem cells and exhibit a phenotype of lysosomal cholesterol accumulation. Treatment of these cells with hydroxypropyl-ß-cyclodextrin, methyl-ß-cyclodextrin, and δ-tocopherol significantly ameliorated the lysosomal cholesterol accumulation. Combined treatment with cyclodextrin and δ-tocopherol shows an additive or synergistic effect that otherwise requires 10-fold higher concentration of cyclodextrin alone. In addition, we found that hydroxypropyl-ß-cyclodextrin is much more potent and efficacious in the NPC1 neural stem cells compared to the NPC1 fibroblasts. Miglustat, suberoylanilide hydroxamic acid, curcumin, lovastatin, pravastatin, and rapamycin did not, however, have significant effects in these cells. The results demonstrate that patient-derived NPC1 neural stem cells can be used as a model system for evaluation of drug efficacy and study of disease pathogenesis.

Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.

Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

Osteopontin is a mediator of the lateral migration of neuroblasts from the subventricular zone after focal cerebral ischemia.

We and others have shown that focal cerebral ischemia induces lateral migration of neuroblasts from the ipsilateral subventricular zone (SVZ) to the ischemic striatum. The signaling pathways underlying this phenomenon are not fully understood. The present study examined the role of osteopontin (OPN) in post-ischemic lateral migration of neuroblasts. Focal ischemia was induced by transient middle cerebral artery occlusion in adult spontaneous hypertensive rats. The expression of OPN in the ischemic brain was evaluated by immunohistochemistry, which showed that an up-regulation of OPN expression in the ipsilateral striatum at day 3, 7, 14 and 1 month of reperfusion with a peak at day 7. Double staining showed co-localization of OPN with ED1(+) macrophages/microglia in the ischemic regions. Inhibition of OPN activity by infusing a neutralizing antibody against OPN into the ischemic striatum significantly decreased the area covered with doublecortin(+) neuroblasts in the ipsilateral striatum. In vitro, OPN treatment did not affect the proliferation of neural progenitors, but induced an increased trans-well and radial migration of neural progenitors. The cultured neural progenitors expressed the OPN receptors CD44 and integrin beta(1). Blockade of the CD44 receptor had no effects on OPN mediated trans-well and radial migration of neural progenitors. However, blockade of integrin beta(1) receptor abolished the migration of neural progenitors in the absence or the presence of OPN. These results suggest that up-regulated expression of OPN produced by macrophages/microglia in the ischemic brain is an attractant and inducer for the lateral migration of neuroblasts from the SVZ to the injured region.

Galectin-3 mediates post-ischemic tissue remodeling.

Galectin-3 (Gal-3) is a member of a class of carbohydrate-binding proteins and plays a role in a number of cellular functions such as cell proliferation, angiogenesis and differentiation. We observed an up-regulated expression of Gal-3 in the ischemic brain following transient middle cerebral artery occlusion in rats. Compared to the brain of sham-operated rats, the expression of Gal-3 was increased in the ischemic striatum at day 1 of reperfusion. The number of Gal-3+ cells in the ischemic brain was further increased at day 2 and day 3, and peaked at day 7 of reperfusion. The up-regulated expression of Gal-3 persisted from day 14 to 2 months after reperfusion. Double staining showed co-localization of Gal-3 with OX-42+ cells, glial fibrillary acidic protein (GFAP)+ and ED1+ cells, suggesting that activated microglia/infiltrating macrophages and activated astrocytes are the primary source of Gal-3 in the ischemic brain. In the in vitro setting, Gal-3 treatment dose-dependently stimulated the proliferation of endothelial cells and neural progenitors. Blockade of Gal-3 activity by infusing a neutralizing antibody against Gal-3 into the ischemic striatum decreased ischemia-induced angiogenesis and the proliferation of neural progenitors. These results suggest that Gal-3 expressed by activated microglia/infiltrating macrophages and astrocytes in the ischemic brain may play a role in post-ischemic tissue remodeling by enhancing angiogenesis and neurogenesis.

Persistent migration of neuroblasts from the subventricular zone to the injured striatum mediated by osteopontin following intracerebral hemorrhage.

We investigated intracerebral hemorrhage (ICH)-induced lateral migration of neuroblasts and the mechanism underlying this migration. ICH model was induced by collagenase injection into the striatum of adult wild-type and osteopontin (OPN) knockout mice. In the wild-type mice, the lateral migration of neuroblasts from the ipsilateral subventricular zone (SVZ) towards the hematoma started at day 3 and continued up to day 28 after ICH. In addition to migrating towards the hematoma, neuroblasts also migrated to the area of ipsilateral striatum remote to the hematoma. The migrating neuroblasts were closely associated with activated astrocytes and blood vessels in the injured striatum. Following ICH, the expression of OPN was up-regulated in the ipsilateral striatum from day 1 to day 28. In vitro, OPN treatment did not affect the proliferation of neural progenitors, but enhanced the trans-well and radial migration of neural progenitors. In vivo, OPN deficiency did not affect the proliferation of neural progenitors in the SVZ. However, following ICH a significant decrease in lateral neuroblast migration was observed in the OPN knockout mice compared with the wild-type mice. These results suggest that increased OPN expression in the injured striatum plays a significant role in the lateral migration of neuroblasts following ICH.

Neuroprotective effects of mesenchymal stem cells derived from human embryonic stem cells in transient focal cerebral ischemia in rats.

Embryonic mesenchymal stem cells (eMSCs) were first derived from human embryonic stem cells (hESCs) overexpressing green fluorescence protein (GFP). They expressed CD29, CD44, CD73, CD105, CD166 and nestin, but not CD34, CD45, CD106 SSEA-4 or Oct3/4. Twenty million eMSCs in 1 mL of phosphate-buffered saline (PBS) were injected into the femoral veins of spontaneously hypertensive rats after transient middle cerebral artery occlusion. The migration and differentiation of the eMSCs in the ischemic brain were analyzed. The results revealed that eMSCs migrated to the infarction region and differentiated into neurons, which were positive for beta-tubulin III, microtubule-associated protein 2 (MAP2), HuC, neurofilament and human nuclear antibody, and to vascular endothelial cells, which were positive for von Willebrand factor (vWF). The transplanted cells survived in the infarction region for at least 4 weeks. Adhesive removal function significantly improved in the first week after cell transplantation, and rotarod motor function significantly improved starting from the second week. The infarction volume in the eMSC group was significantly smaller than that in the PBS control group at 4 weeks after infusion. The results of this study show that when administered intravenously, eMSCs differentiated into neuronal and endothelial cells, reduced the infarction volume, and improved behavioral functional outcome significantly in transient focal cerebral ischemia.

Impaired neurogenesis in adult type-2 diabetic rats.

Type-2 diabetes is an adult onset condition that affects millions of people worldwide. The ensuing hyperglycemia renders multiple organs to various complications and increases the risk of learning and memory impairment. The Goto-Kakizaki (GK) rat developed from normoglycemic Wistar-Kyoto (WKY) rat is a model for type-2 diabetes, with insulin resistance developing around 12 weeks of age. We presently analyzed the neural progenitor proliferation and survival of the newly generated cells in the dentate gyrus (DG) and the subventricular zone (SVZ) of 6 and 18 week-old GK and WKY rats. At 6 weeks of age, both GK and WKY cohorts showed similar blood glucose levels (112+/-14 mg/dL) and similar rates of neural progenitor proliferation. At 18 weeks of age, the GK rats showed significantly increased blood glucose levels (by 92+/-12%; p<0.05) and higher number of proliferating neural progenitor cells compared to WKY rats (by 183+/-16% in SVZ and by 36+/-5% in DG; p<0.05 in both cases). In both the neurogenic areas, 52+/-9% of the newly formed cells survived to 3 weeks in the 18 weeks old WKY rats, but in the GK rats only 16+/-7% of the new cells survived to 3 weeks. When cultured from the DG of the 18 week old rats in the presence of FGF2 and IGF1, the GK cohort yielded significantly lower number of neurospheres than the WKY cohort (by 69+/-7%; p<0.05). These results indicate that hyperglycemic environment induces proliferation of adult neural progenitors, but detrimental to their survival. Impaired neurogenesis might be a promoter of the decreased brain function in type-2 diabetes.

Substance P is a promoter of adult neural progenitor cell proliferation under normal and ischemic conditions.

OBJECT: Neurogenesis continues throughout the life of mammals in the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus (DG) of the hippocampus. The authors tested the potential of the neuropeptide substance P (SP) acting via the neurokinin-1 receptor (NK1R) in promoting the proliferation of adult rat neural progenitor cells (NPCs). METHODS: Focal ischemia was induced in spontaneously hypertensive rats by transient middle cerebral artery occlusion. Substance P and the NK1R antagonist L-703,606 were infused into the lateral ventricles of rats by using Alzet osmotic minipumps. Progenitor cell proliferation was evaluated with immunostaining for bromodeoxyuridine (BrdU) and immature neural marker doublecortin (DCX). Neurospheres were cultured from the SVZ of adult rats. RESULTS: Under in vitro conditions, SP (0.01-10 micromol/L) increased the proliferation of cultured NPCs, with a peak increase of 52 +/- 7% at 0.1 micromol/L. Substance P (0.1 micromol/L) continuously increased NPC proliferation from 6 hours to 5 days, which was prevented by L-703,606 (by 69-98%). The cultured NPCs expressed both SP and NK1R proteins, indicating that these effects are receptor specific. Continuous infusion of SP (1 micromol/L) into the lateral ventricles for 5 days significantly increased the number of proliferating NPCs (cells positive for both BrdU and DCX) in both the SVZ (by 173 +/- 24%, p < 0.05) and DG (by 82 +/- 12%, p < 0.05) in adult rats; however, infusion of L-703,606 (10 micromol/L) significantly prevented the postischemic induction of NPC proliferation in both the SVZ (by 84 +/- 6%, p < 0.05) and DG (by 63 +/- 7%, p < 0.05). CONCLUSIONS: Data in these studies indicated that SP plays a role in normal and ischemia-induced neurogenesis in the adult brain and thus could help central nervous system plasticity following injury.

Repairing brain after stroke: a review on post-ischemic neurogenesis.

Stroke is devastating as currently no therapies are available that can prevent stroke-induced neurological dysfunction in humans. With the recent observations that acute insults to adult brain stimulate new neuronal formation in various species of animals, optimism is building for a possible regeneration of stroke-damaged brain. This article reviewed the advances in the understanding of the molecular mechanisms of the various steps of neurogenesis with an emphasis on the endogenous mediators and exogenous promoters of neural progenitor proliferation, migration and survival in the post-ischemic adult brain.

Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration after focal cerebral ischemia.

Transient focal ischemia is known to induce proliferation of neural progenitors in adult rodent brain. We presently report that doublecortin positive neuroblasts formed in the subventricular zone (SVZ) and the posterior peri-ventricle region migrate towards the cortical and striatal penumbra after transient middle cerebral artery occlusion (MCAO) in adult rodents. Cultured neural progenitor cells grafted into the non-infarcted area of the ipsilateral cortex migrated preferentially towards the infarct. As chemokines are known to induce cell migration, we investigated if monocyte chemoattractant protein-1 (MCP-1) has a role in post-ischemic neuroblast migration. Transient MCAO induced an increased expression of MCP-1 mRNA in the ipsilateral cortex and striatum. Immunostaining showed that the expression of MCP-1 was localized in the activated microglia and astrocytes present in the ischemic areas between days 1 and 3 of reperfusion. Furthermore, infusion of MCP-1 into the normal striatum induced neuroblast migration to the infusion site. The migrating neuroblasts expressed the MCP-1 receptor CCR2. In knockout mice that lacked either MCP-1 or its receptor CCR2, there was a significant decrease in the number of migrating neuroblasts from the ipsilateral SVZ to the ischemic striatum. These results show that MCP-1 is one of the factors that attract the migration of newly formed neuroblasts from neurogenic regions to the damaged regions of brain after focal ischemia.

Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation.

The adult mammalian brain contains resident neural progenitors in the subgranular zone of the dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricles. The proliferation of neural progenitors increases after focal cerebral ischemia in both of these regions, but the mechanisms that promote ischemia-induced neural progenitor proliferation are not yet understood. We hypothesize that diffusible factors from the ischemic area play a role in this process as the DG is remote from the area of infarction. In this study, we observed that the peak of neural progenitor proliferation in the ipsilateral DG was between day 2 and day 4 of reperfusion after transient middle cerebral artery occlusion in adult spontaneously hypertensive rats. GeneChip and real-time PCR analysis showed a three- to 102-fold increase in the expression of 15 diffusible, mitogenic factors in the ischemic cortex at 3 days of reperfusion. Of these, insulin-like growth factor-1 (IGF-1) showed increased protein expression in the activated astrocytes in the ischemic penumbra. In addition, the progenitors in both the SVZ and DG showed IGF-1 receptor expression. Inhibiting IGF-1 activity by introcerebroventricular infusion of IGF-1 antibody significantly prevented the ischemia-induced neural progenitor proliferation. These results indicate that IGF-1 formed in the ischemic penumbra might be one of the diffusible factors that mediate post-ischemic neural progenitor proliferation.

[Anatomy study of superior and inferior gluteal artery perforator flap].

OBJECTIVE: To find anatomic basis for clinically modifying technique of harvesting superior and inferior gluteal artery perforator flap, in order to avoid muscle lossing in conventional superior and inferior myocutaneous flaps, keep the advantage such as large rich supplied volume soft tissue. METHODS: 5 cases 10 sides adult cadaver were used to study the numbers, position, Course of superior and inferior gluteal artery perforators. The position of perforators was located by ultrasound Doppler in 6 cases and 12 sides in patient's superior and inferior gluteal area. RESULTS: Superior and inferior gluteal artery originated from internal iliac artery. Several main perforators of large caliber were found in the paraischia and central portions of the gluteal muscle, its number was 10 - 15. The length of the vessels varies from 3 to 8 cm and their diameter from 1 - 1.5 mm. These significant perforators pass through the muscle itself and the fascial portion of the muscle to the overlying skin on the gluteal region. The dorsal branches of nervorum lumbalium perforate the deep fascia just above the iliac crest, lateral to the posterior superior iliac spine. If a nerve branch with a substantial diameter crosses the incision line, the nerve can be harvested within the flap. This nerve can be anastomosed to the anterior ramus of the lateral branch of the 4th intercostals nerve. In adult female, 3 - 5 perforators were located by ultrasound Doppler. They distributed in the triangle area among posterior superior iliac crest, the great trochanter and the coccyx. CONCLUSIONS: The area and diameter of perforators of superior gluteal artery were relatively confirmed. It's possible to harvest the perforator flap without any muscle. It has the advantage of conventional myocutaneous flap with out of its disadvantages. It's easy to detect those perforator by ultrasound Doppler clinically. The nerve can be harvested and anastomosed simultaneously. Because the inferior gluteal area is a weight loading area, we suggested to use superior gluteal artery perforator flap. This flap can be transferred pedicled to treat sacral pressure sores or to be transferred freely for the breast reconstruction.