Effects of polypropylene microplastics on carbon dioxide dynamics in intertidal mangrove sediments.

Microplastics (MPs) in soil can influence CO2 dynamics by altering organic carbon (OC) and microbial composition. Nevertheless, the fluctuation of CO2 response attributed to MPs in mangrove sediments is unclear. This study explores the impact of micro-sized polypropylene (mPP) particles on the carbon dynamics of intertidal mangrove sediments. In the high-tide level sediment, after 28 days, the cumulative CO2 levels for varying mPP dosages were as follows: 496.86 ± 2.07, 430.38 ± 3.84 and 447.09 ± 1.72 mg kg-1 for 0.1%, 1% and 10% (w/w) mPP, respectively. The CO2 emissions were found to be increased with a 0.1% (w/w) mPP level and decreased with 1% and 10% (w/w) mPP at high-tide level sediment, suggesting a tide level-specific dose dependence of the CO2 emission pattern in mangrove sediments. Overall, results indicated that the presence of mPP in mangrove sediments would potentially affect intertidal total CO2 storage under given experimental conditions.

Maternal immune activation alters fetal and neonatal microglia phenotype and disrupts neurogenesis in mice.

BACKGROUND: Activation of microglia, increase in cortical neuron density, and reduction in GABAergic interneurons are some of the key findings in postmortem autism spectrum disorders (ASD) subjects. The aim of this study was to investigate how maternal immune activation (MIA) programs microglial phenotypes and abnormal neurogenesis in offspring mice. METHODS: MIA was induced by injection of lipopolysaccharide (LPS, i.p.) to pregnant mice at embryonic (E) day 12.5. Microglial phenotypes and neurogenesis were investigated between E15.5 to postnatal (P) day 21 by immunohistochemistry, flow cytometry, and cytokine array. RESULTS: MIA led to a robust increase in fetal and neonatal microglia in neurogenic regions. Homeostatic E15.5 and P4 microglia are heterogeneous, consisting of M1 (CD86+/CD206-) and mixed M1/M2 (CD86+/CD206+)-like subpopulations. MIA significantly reduced M1 but increased mixed M1/M2 microglia, which was associated with upregulation of numerous cytokines with pleotropic property. MIA resulted in a robust increase in Ki67+/Nestin+ and Tbr2+ neural progenitor cells in the subventricular zone (SVZ) of newborn mice. At juvenile stage, a male-specific reduction of Parvalbumin+ but increase in Reelin+ interneurons in the medial prefrontal cortex was found in MIA offspring mice. CONCLUSIONS: MIA programs microglia towards a pleotropic phenotype that may drive excessive neurogenesis in ASD patients. IMPACT: Maternal immune activation (MIA) alters microglial phenotypes in the brain of fetal and neonatal mouse offspring. MIA leads to excessive proliferation and overproduction of neural progenitors in the subventricular zone (SVZ). MIA reduces parvalbumin+ while increases Reelin+ interneurons in the prefrontal cortex. Our study sheds light on neurobiological mechanisms of abnormal neurogenesis in certain neurodevelopmental disorders, such as autism spectrum disorder (ASD).

Investigating the effects and mechanisms of Erchen Decoction in the treatment of colorectal cancer by network pharmacology and experimental validation.

Objective: Erchen Decoction (ECD), a well-known traditional Chinese medicine, exerts metabolism-regulatory, immunoregulation, and anti-tumor effects. However, the action and pharmacological mechanism of ECD remain largely unclear. In the present study, we explored the effects and mechanisms of ECD in the treatment of CRC using network pharmacology, molecular docking, and systematic experimental validation. Methods: The active components of ECD were obtained from the TCMSP database and the potential targets of them were annotated by the STRING database. The CRC-related targets were identified from different databases (OMIM, DisGeNet, GeneCards, and DrugBank). The interactive targets of ECD and CRC were screened and the protein-protein interaction (PPI) networks were constructed. Then, the hub interactive targets were calculated and visualized from the PPI network using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. In addition, the molecular docking was performed. Finally, systematic in vitro, in vivo and molecular biology experiments were performed to further explore the anti-tumor effects and underlying mechanisms of ECD in CRC. Results: A total of 116 active components and 246 targets of ECD were predicted based on the component-target network analysis. 2406 CRC-related targets were obtained from different databases and 140 intersective targets were identified between ECD and CRC. 12 hub molecules (STAT3, JUN, MAPK3, TP53, MAPK1, RELA, FOS, ESR1, IL6, MAPK14, MYC, and CDKN1A) were finally screened from PPI network. GO and KEGG pathway enrichment analyses demonstrated that the biological discrepancy was mainly focused on the tumorigenesis-, immune-, and mechanism-related pathways. Based on the experimental validation, ECD could suppress the proliferation of CRC cells by inhibiting cell cycle and promoting cell apoptosis. In addition, ECD could inhibit tumor growth in mice. Finally, the results of molecular biology experiments suggested ECD could regulate the transcriptional levels of several hub molecules during the development of CRC, including MAPKs, PPARs, TP53, and STATs. Conclusion: This study revealed the potential pharmacodynamic material basis and underlying molecular mechanisms of ECD in the treatment of CRC, providing a novel insight for us to find more effective anti-CRC drugs.

Single Shot Multibox Detector Automatic Polyp Detection Network Based on Gastrointestinal Endoscopic Images.

PURPOSE: In order to resolve the situation of high missed diagnosis rate and high misdiagnosis rate of the pathological analysis of the gastrointestinal endoscopic images by experts, we propose an automatic polyp detection algorithm based on Single Shot Multibox Detector (SSD). METHOD: In the paper, SSD is based on VGG-16, the fully connected layer is changed to a convolutional layer, and four convolutional layers with successively decreasing scales are added as a new network structure. In order to verify the practicability, it is not only compared with manual polyp detection but also with Mask R-CNN. RESULTS: Multiple experimental results show that the mean Average Precision (mAP) of the SSD network is 95.74%, which is 12.4% higher than the manual detection and 5.7% higher than the Mask R-CNN. When detecting a single frame of image, the detection speed of SSD is 8.41 times that of manual detection. CONCLUSION: Based on the traditional pattern recognition algorithm and the target detection algorithm using deep learning, we select a variety of algorithms to identify and classify polyps to achieve efficient detection results. Our research demonstrates that deep learning has a lot of room for development in the field of gastrointestinal image recognition.

Long non-coding RNA DPP10-AS1 exerts anti-tumor effects on colon cancer via the upregulation of ADCY1 by regulating microRNA-127-3p.

Herein we hypothesized that DPP10-AS1 could affect the development of colon cancer via the interaction with miR-127-3p and adenylate cyclase 1 (ADCY1). After sorting of CD133 positive cells, sphere formation, colony formation, proliferation, invasion, migration, and apoptosis were detected to explore the involvement of DPP10-AS1 and miR-127-3p in the colon cancer stem cell (CCSC) properties through gain- and loss-of function approaches. Furthermore, tumor xenograft in nude mice was conducted to investigate the effect of DPP10-AS1 and miR-127-3p on tumor growth in vivo. Poorly expressed DPP10-AS1 and ADCY1, while highly expressed miR-127-3p were found in CCSCs. Low expression of DPP10-AS1 was correlated with TNM stage, lymphatic node metastasis, and tumor differentiation. Upregulation of DPP10-AS1 increased ADCY1 protein expression, decreased the protein expression of CCSC-related factors, inhibited sphere formation, colony formation, proliferation, invasion and migration, and accelerated apoptosis of HT-29 and SW480 cells by suppressing the expression of miR-127-3p. Further, the above in vitro findings were also confirmed by in vivo assays. Taken together, this study demonstrates that DPP10-AS1 inhibits CCSC proliferation by regulating miR-127-3p and ADCY1, providing fresh insight into a promising novel treatment strategy for colon cancer.

Microfluidics for the rapid detection of Escherichia coli O157:H7 using antibody-coated microspheres.

This study developed a novel method for the rapid detection of Escherichia coli (E. coli) O157:H7 on a microfluidic platform. First, the concentration of bacteria in a sample was determined with the adenosine triphosphate (ATP) method. Then, the specific detection of E. coli was achieved in a microfluidic chip by the immune-microsphere technique. The influences of the culture time, flow rate and capture time on the detection of the target bacteria were investigated systematically. Generally, with increasing capture time, more bacteria could be captured by the microspheres, which had a positive effect on bacterial detection. Furthermore, the sensitivity and specificity of the method were also tested. The results showed that this method could specifically detect E. coli with a sensitivity as high as 49.1 cfu/µL; the consumption of bacteria was 1 µL, and the reagent was at the microliter level. The testing time can be controlled within one and a half hours, and the cost of testing was approximately RMB 10. The method described in this article is simple and accurate and has great application value in bacterial detection for medical diagnostics.

Enhanced oral bioavailability and bioefficacy of phloretin using mixed polymeric modified self-nanoemulsions.

Phloretin (Ph) is a natural active ingredient with wide biological properties. However, its poor water-solubility and low oral bioavailability limit the application significantly in functional food and drug. This study was to explore the mixed polymer Pluronic® F127 and P123 modified the different triglycerides (LCT, MCT, SCT) in self-nanoemulsions (SNEs) for enhancing the oral bioavailability and bioefficacy of Ph. The SNEs were characterized in terms of physical property study, lipolysis study, pharmacokinetic study, and anti-inflammatory effect. The water-solubility of LCT-Ph-SNE increased 3000-fold compared with Ph solution. Pharmacokinetic study of SNEs and other carriers (HP-ß-CD, PVP) results indicated that LCT-Ph-SNE was 7.9-fold more bioavailable compared with unformulated Ph. The anti-inflammatory activity of LCT-Ph-SNE in vivo represented a 6.8-fold enhancement compared with unformulated Ph. This novel SNE formulation may also be used for other poorly soluble ingredients with high loading capacity, which made a significant impact on functional food and drug.

C-H Functionalization via Remote Hydride Elimination: Palladium Catalyzed Dehydrogenation of ortho-Acyl Phenols to Flavonoids.

Although deprotonation of electron-poor C-H bonds to carbon anions with bases has long been known and widely used in organic synthesis, the hydride elimination from electron-rich C-H bonds to carbon cations or partial carbocations for the introduction of nucleophiles is a comparatively less explored area. Here we report that the carbonyl ß-C(sp3)-H bond hydrogens of ortho-acyl phenols could be substituted by intramolecular phenolic hydroxyls to form O-heterocycles, followed by dehydrogenation of the O-heterocycle into flavonoids. The cascade reaction is catalyzed by Pd/C without added oxidants and sacrificing hydrogen acceptors.

Evaluation of Clinical Nursing Information System in Taiwan Regional Hospital.

The purpose of this study was to evaluate the Clinical Nursing Information System (CNIS) in Taiwan regional hospital. In 2016, a total of 333 nurses responded to the Technology Acceptance Model-based questionnaire after 15 months of CNIS implementation. The results showed positive acceptance toward CNI, especially among those nurses who were younger, those who worked as administrative managers or in non-critical care units, and had advanced computer skills.

Erythropoietin Ameliorates Neonatal Hypoxia-Ischemia-Induced Neurobehavioral Deficits, Neuroinflammation, and Hippocampal Injury in the Juvenile Rat.

The hematopoietic growth factor erythropoietin (EPO) has been shown to be neuroprotective against hypoxia-ischemia (HI) in Postnatal Day 7 (P7)-P10 or adult animal models. The current study was aimed to determine whether EPO also provides long-lasting neuroprotection against HI in P5 rats, which is relevant to immature human infants. Sprague-Dawley rats at P5 were subjected to right common carotid artery ligation followed by an exposure to 6% oxygen with balanced nitrogen for 1.5 h. Human recombinant EPO (rEPO, at a dose of 5 units/g) was administered intraperitoneally one hour before or immediately after insult, followed by additional injections at 24 and 48 h post-insult. The control rats were injected with normal saline following HI. Neurobehavioral tests were performed on P8 and P20, and brain injury was examined on P21. HI insult significantly impaired neurobehavioral performance including sensorimotor, locomotor activity and cognitive ability on the P8 and P20 rats. HI insult also resulted in brain inflammation (as indicated by microglia activation) and neuronal death (as indicated by Jade B positive staining) in the white matter, striatum, cortex, and hippocampal areas of the P21 rat. Both pre- and post-treatment with rEPO significantly improved neurobehavioral performance and protected against the HI-induced neuronal death, microglia activation (OX42+) as well as loss of mature oligodendrocytes (APC-CC1+) and hippocampal neurons (Nissl+). The long-lasting protective effects of rEPO in the neonatal rat HI model suggest that to exert neurotrophic activity in the brain might be an effective approach for therapeutic treatment of neonatal brain injury induced by hypoxia-ischemia.

Neonatal systemic exposure to lipopolysaccharide enhances susceptibility of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life.

Brain inflammation via intracerebral injection with lipopolysaccharide (LPS) in early life has been shown to increase risks for the development of neurodegenerative disorders in adult rats. To determine if neonatal systemic LPS exposure has the same effects on enhancement of adult dopaminergic neuron susceptibility to rotenone neurotoxicity as centrally injected LPS does, LPS (2 µg/g body weight) was administered intraperitoneally into postnatal day 5 (P5) rats and when grown to P70, rats were challenged with rotenone, a commonly used pesticide, through subcutaneous minipump infusion at a dose of 1.25 mg/kg/day for 14 days. Systemically administered LPS can penetrate into the neonatal rat brain and cause acute and chronic brain inflammation, as evidenced by persistent increases in IL-1ß levels, cyclooxygenase-2 expression and microglial activation in the substantia nigra (SN) of P70 rats. Neonatal LPS exposure resulted in suppression of tyrosine hydroxylase (TH) expression, but not actual death of dopaminergic neurons in the SN, as indicated by the reduced number of TH+ cells and unchanged total number of neurons (NeuN+) in the SN. Neonatal LPS exposure also caused motor function deficits, which were spontaneously recoverable by P70. A small dose of rotenone at P70 induced loss of dopaminergic neurons, as indicated by reduced numbers of both TH+ and NeuN+ cells in the SN, and Parkinson's disease (PD)-like motor impairment in P98 rats that had experienced neonatal LPS exposure, but not in those without the LPS exposure. These results indicate that although neonatal systemic LPS exposure may not necessarily lead to death of dopaminergic neurons in the SN, such an exposure could cause persistent functional alterations in the dopaminergic system and indirectly predispose the nigrostriatal system in the adult brain to be damaged by environmental toxins at an ordinarily nontoxic or subtoxic dose and develop PD-like pathological features and motor dysfunction.

Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons.

Although the central nervous system melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepR(flox/flox)/POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose use and oxygen consumption, and reduce appetite. LepR(flox/flox)/POMC-Cre, wild-type, LepR(flox/flox), and POMC-Cre mice were instrumented for MAP and heart rate measurement by telemetry and venous catheters for infusions. LepR(flox/flox)/POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared with wild-type, LepR(flox/flox), and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepR(flox/flox)/POMC-Cre mice had normal MAP and heart rate compared with LepR(flox/flox) but lower MAP and heart rate compared with wild-type mice. After a 5-day control period, leptin was infused (2 µg/kg per minute, IV) for 7 days. In control mice, leptin increased MAP by ≈5 mm Hg despite decreasing food intake by ≈35%. In contrast, leptin infusion in LepR(flox/flox)/POMC-Cre mice reduced MAP by ≈3 mm Hg and food intake by ≈28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepR(flox/flox)/POMC-Cre mice. Leptin increased oxygen consumption in LepR(flox/flox)/POMC-Cre and wild-type mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain other than POMC neurons appear to play a key role in mediating the chronic effects of leptin on appetite and oxygen consumption.

Whole body hypothermia broadens the therapeutic window of intranasally administered IGF-1 in a neonatal rat model of cerebral hypoxia-ischemia.

To investigate whether whole body hypothermia after neonatal cerebral hypoxia-ischemia (HI) could broaden the therapeutic window of intranasal treatment of IGF-1 (iN-IGF-1), postnatal day 7 rat pups were subjected to right common carotid artery ligation, followed by 8% oxygen inhalation for 2h. After HI, one group of pups were returned to their dams and kept at room temperature (24.5±0.2°C). A second group of pups were subjected to whole body hypothermia in a cool environment (21.5±0.3°C) for 2 or 4h before being returned to their dams. Two doses of 50 µg recombinant human IGF-1 were administered intranasally at a 1h interval starting at 0, 2 or 4h after hypothermia. Hypothermia decreased the rectal temperature of pups by 4.5°C as compared to those kept at room temperature. While hypothermia or iN-IGF-1 administered 2h after HI alone did not provide neuroprotection, the combined treatment of hypothermia with iN-IGF-1 significantly protected the neonatal rat brain from HI injury. Hypothermia treatment extended the therapeutic window of IGF-1 to 6h after HI. The extended IGF-1 therapeutic window by hypothermia was associated with decreases in infiltration of polymorphonuclear leukocytes and activation of microglia/macrophages and with attenuation of NF-κB activation in the ipsilateral hemisphere following HI.

A psychometric evaluation of the Taiwan version of the Individual Workload Perception Scale.

AIM: The aim was to evaluate the psychometric properties of the Taiwan version of the Revised Individual Workload Perception Scale on staff nurses in southern Taiwan. BACKGROUND: Most psychometric measures of the nursing work environment were developed in North America and reflect nursing practice in Western health care environments. As these instruments are used most often in translation, it is important to inquire whether they appropriately capture the characteristics of nursing work in environments outside of the original contexts. DESIGN: A descriptive, cross-sectional study was conducted between 1 June-30 September 2009, with a convenience sample of 344 nurses providing direct patient care at a regional teaching hospital in southern Taiwan. The Taiwan version of the Revised Individual Workload Perception Scale was created by translating the original English language Individual Workload Perception Scale-Revised, which is used to measure the staff nurses' perceptions of their work environment. The Taiwan version of the Revised Individual Workload Perception Scale is a 24-item five-point Likert scale measuring manager support, peer support, unit support, workload and intent to stay. Content validity, construct validity and reliability of the Taiwan version of the Revised Individual Workload Perception Scale were evaluated. RESULTS: The content validity index of the Taiwan version of the Revised Individual Workload Perception Scale was 0.93. Cronbach's alpha for the total Taiwan version of the Revised Individual Workload Perception Scale was 0.88, with a range of 0.61-0.85 for the subscales. Factorial validity was supported using a five-factor model solution that accounted for 55.47% of the total variance for nursing work environment. Manager support had the highest explained variance (28.38%). CONCLUSIONS: Acceptable reliability and content validity were found; the Taiwan version of the Revised Individual Workload Perception Scale is recommended for measuring nurses' perceptions of their work environment. RELEVANCE TO CLINICAL PRACTICE: Psychometric properties of a scale such as the Individual Workload Perception Scale translate cross-culturally, with minor adjustments. The Taiwan version of the Revised Individual Workload Perception Scale can be used to provide data and analyses in comparisons with nursing work environment features internationally.

[A pilot study on the perspectives of hemodialysis room nurses on promoting advance directives].

BACKGROUND: Previous studies have shown that patients with end-stage renal disease experience a lower than optimal quality of dying and achieve a lower rate of advance directives (ADs) completion. Patients are frequently unaware of their option to withdraw from dialysis and also believe their physicians would oppose such a decision. Where there are inherent difficulties for medical staff in discussing end-of-life (EOL) issues with patients, patients on dialysis often develop a trusting, almost familial relationship with their nurses, who play a vital role in assisting patient and family to make EOL care decisions. PURPOSE: The purpose of this study was to explore the perspectives on advance directive discussion strategies of nurses working in hemodialysis rooms. METHODS: This was a descriptive-correlational research study that targeted 55 nurses working in a hemodialysis room at a regional hospital in southern Taiwan. Structured questionnaires were developed for this study that collected basic demographic information and assessed participant perspectives on discussing ADs. Data were analysed using descriptive statistics and deductive statistics, including independent t test, one-way ANOVA and Pearson correlation. RESULTS: Over 80% participants agreed that discussing ADs with patients could accurately identify patient preferences, improve EOL quality, and decrease family conflicts. However, 78.2% expressed that they did not have sufficient training to talk with patients about death and dying. Also, two-thirds (65.5%) worried about upsetting their patients, as they perceived their professional role as sustaining life (rather than helping prepare for death). Significant differences in discussing ADs with patients were found in respect to age and personal experience as well as with regard to whether the participant had discussed EOL care decisions with others. CONCLUSION: Discussing ADs with patients may improve EOL quality. Lack of training and negative perspectives represent major barriers. Therefore, teaching nurses how to engage in EOL care dialogue with patients and paying attention to patient EOL needs represent crucial tasks ahead.

[Exploring factors affecting meaning of life perceptions among ESRD elders].

BACKGROUND: The number of patient with end stage renal disease (ESRD) has been growing in Taiwan. Nearly 50% of ESRD sufferers are 65 years of age or older. The disease as well as issues related to patient physiology, psychology, and spiritual well-being are worth taking seriously. While research into this topic area has been conducted, most studies addressed issues in the physiological and psychological dimensions. Studies addressing the domain of spiritual well-being remain inadequate. The purpose of this study was to explore factors affecting meaning of life perceptions in ESRD elders. METHODS: Using a descriptive-correlation research approach, we employed purposive sampling to collect data from 80 ESRD elders currently under the care of a hemodialysis center in southern Taiwan. Research instruments used included a demographic questionnaire and Meaning in Life Scale. Data were analysed using SPSS 12.0 software. RESULTS: Findings showed that ESRD elders had relatively low meaning in life scores compared to the overall ESRD population in Taiwan. Influencing factors included education level, socio-economic status, and level of participation in leisure activities. CONCLUSION: Study findings may provide health professionals a better understanding of meaning of life perceptions amongst elders with ESRD, and, as a result, help them target better spiritual care and supportive interventions.

Intranasal administration of IGF-1 attenuates hypoxic-ischemic brain injury in neonatal rats.

To determine whether intranasal administration (iN) of recombinant human insulin-like growth factor-1 (rhIGF-1) provides neuroprotection to the neonatal rat brain following cerebral hypoxia-ischemia (HI), two doses of rhIGF-1 (50 microg at a 1 h interval) were infused into the right naris of postnatal day 7 (P7) rat pups with or without a prior HI insult (right common carotid artery ligation, followed by an exposure to 8% oxygen for 2 h). Our result showed that rhIGF-1 administered via iN was successfully delivered into the brain 30 min after the second dose. In the following studies rhIGF-1 was administered to P7 rat pups at 0, 1 or 2 h after HI at the dose described above. Pups in the control group received cerebral HI and vehicle treatment. Pups that underwent sham operation and vehicle treatment served as the sham group. Brain pathological changes were evaluated 2 and 15 days after HI. Our results showed that rhIGF-1 treatment up to 1 h after cerebral HI effectively reduced brain injury as compared to that in the vehicle-treated rats. Moreover, rhIGF-1 treatment improved neurobehavioral performance (tested on P5-P21) in juvenile rats subjected to HI. Our results further showed that rhIGF-1 inhibited apoptotic cell death, possibly through activating the Akt signal transduction pathway. rhIGF-1 enhanced proliferation of neuronal and oligodendroglial progenitors after cerebral HI as well. These data suggest that iN administration of IGF-1 has the potential to be used for clinical treatment.

Improvement of full-thickness skin graft survival by application of vascular endothelial growth factor in rats.

The effect of vascular endothelial growth factor (VEGF) on skin graft survival was studied in rats. Models of skin grafting on muscle and periosteum were designed. For the study of skin grafting on muscle model, 32 rats were divided into 4 groups. VEGF was administrated systemically after skin graft placement intrafascially injected into the recipient bed at the time of graft placement and topically applied to the recipient bed at the time of graft placement. Control groups consisted of grafts placed on sites without systemic or local VEGF treatment. With the study of skin grafting on periosteum, 40 rats were divided into 4 groups. VEGF was systemically, intraperiosteally, and topically applied to the recipient bed. The control animals received no treatment. On the fifth postoperative day, the survival area of each skin graft was measured and the graft was harvested for histology with CD31 immunohistochemical staining. The results showed that in skin grafting on muscle model, the mean viable percentage of the skin graft was 66.1% +/- 10.2% in the group receiving systemic application of VEGF and 56.1% +/- 9.8% in the group receiving VEGF intrafascia injection. The survival percentages were significantly higher than those found in the control group (22.5% +/- 7.7%) and the group with VEGF topical application (30.8% +/- 4.1%). In skin grafting on periosteum, the group receiving VEGF intraperiosteum injection reached a survival percentage of 50.5% +/- 4.3%, significantly higher than the groups with VEGF systemic application (28.7 +/- 5.5%), VEGF topical application (32.5% +/- 4.8%), and the control (25.8% +/- 6.0%). Histology showed that sections taken from grafts with VEGF intrafascia and intraperiosteum treatment revealed angiogenesis. The data demonstrated that administration of VEGF into the either muscular or periosteal recipient beds for skin grafting can improve the skin graft survival.

Neuroprotection of alpha-phenyl-n-tert-butyl-nitrone on the neonatal white matter is associated with anti-inflammation.

Our previous study has demonstrated that alpha-phenyl-tert-butyl-nitrone (PBN) provided neuroprotection to the neonatal white matter following cerebral hypoxia-ischemia (HI). Free radical scavenging was involved in the neuroprotection of PBN. To investigate if other mechanisms contribute to the neuroprotection of PBN, postnatal day 4 SD rats were subjected to bilateral common carotid artery ligation, followed by 8% oxygen exposure for 20min. A single dose of PBN (100mg/kg, i.p.) was given prior to the hypoxic exposure. Expression of inflammatory cytokines: interleukin-1beta (IL-1beta), inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) was determined by RT-PCR, ELISA and immunohistochemistry. Activation of transcriptional factor nuclear factor-kappa B (NF-kappaB) was measured by ELISA. PBN significantly inhibited HI-induced up-regulation of IL-1beta, TNF-alpha and iNOS mRNA expression at 4h following HI. PBN treatment also reduced the brain concentration of IL-1beta significantly and decreased the number of IL-1beta- or iNOS-expressing cells in the white matter area at 12h following HI. Moreover, PBN suppressed the HI-induced NF-kappaB activation at 1h after HI. The overall results indicate that besides free radical scavenging, anti-inflammation might partly contribute to the neuroprotection afforded by PBN on neonatal white matter following cerebral HI.

Minocycline attenuates hypoxia-ischemia-induced neurological dysfunction and brain injury in the juvenile rat.

To investigate whether minocycline provides long-lasting protection against neonatal hypoxia-ischemia-induced brain injury and neurobehavioral deficits, minocycline was administered intraperitoneally in postnatal day 4 Sprague-Dawley rats subjected to bilateral carotid artery occlusion followed by exposure to hypoxia (8% oxygen for 15 min). Brain injury and myelination were examined on postnatal day 21 (P21) and tests for neurobehavioral toxicity were performed from P3 to P21. Hypoxic-ischemic insults resulted in severe white matter injury, enlarged ventricles, deficits in the hippocampus, reduction in numbers of mature oligodendrocytes and tyrosine hydroxylase-positive neurons, damage to axons and dendrites, and impaired myelination, as indicated by the decrease in myelin basic protein immunostaining in the P21 rat brain. Hypoxic-ischemic insult also significantly affected physical development (body weight gain and eye opening) and neurobehavioral performance, including sensorimotor and locomotor function, anxiety and cognitive ability in the P21 rat. Treatments with minocycline significantly attenuated the hypoxia-ischemia-induced brain injury and improved neurobehavioral performance. The protection of minocycline was associated with its ability to reduce microglial activation. The present results show that minocycline has long-lasting protective effects in the neonatal rat brain in terms of both hypoxia-ischemia-induced brain injury and the associated neurological dysfunction.