Drug-resistance reversal in colorectal cancer cells by destruction of flotillins, the key lipid rafts proteins.

Multi-drug resistance (MDR) of tumor cells attenuates the efficacy of anticancer drugs and has become the main reason for chemotherapy failure. It is indispensable to establish an effective way to reverse multi-drug resistance. Our previous work has shown that down-regulation of the ERK/MAPK signaling pathway activity can reverse the drug-resistance of resistant cells. Further-more, the effect of signal transduction is strongly associated with lipid rafts. The drug-resistance is reversed successfully after lipid rafts are destroyed by heptakis(2, 6-di-O-methyl)-ß-cyclodextrin (MßCD). However, the reversal of the drug-resistance is not associated with down-regulation of the expression of ERK1/2. Cell membrane permeability may increase when lipid rafts are destroyed by MßCD, causing the reversal of drug-resistance due to an increase in accumulation of the drugs in the cytoplasm. To minimize the influence of MßCD on the cell membrane structure, we selected flotillin, a marker protein of lipid rafts, as the target molecule, to further investigate the mechanism of changes in drug resistance after destruction of the lipid rafts. The effect of flotillin on the reversal of the drug resistance was examined using an RNA interference (RNAi) in a retrovirus system in human drug-resistant strains of colorectal cancer cell line HCT-15. The results demonstrate that flotillin-1 downregulation by RNAi (Flot1-RNAi) reduced the drug resistance, caused cell cycle arrest and decreased the expression of ERK1/2; however, apoptosis was not significantly affected. Knockdown of flotillin-2 by RNAi (Flot2-RNAi) had effects similar to those of Flot1-RNAi except that the effects on expression of ERK1/2 and apoptosis were different. Screening of multiple pathways indicated that the PI3K/Akt signaling pathway was closely related. This experiment demonstrates the association between PI3K and drug resistance through the activation of PI3K and suggests that PI3K may play a key role during the development of resistance in CRC. The results reveal that the levels of IRS-1 and PI3K proteins in the Flot1-RNAi and Flot2-RNAi groups were significantly down-regulated. Knockdown of flotillins by RNAi reduced the resistance of HCT-15/ADM cells; the results investigations of the Akt pathway indicate a decrease in resistance after lipid raft destruction. These data confirm that knockdown of flotillin reduces the resistance of HCT-15/ADM cells, and the mechanism may be relevant to the PI3K/Akt pathway. Additionally, flotillin may be used as a potential target for chemotherapy in the treatment of colorectal cancer.

Skeletal development of the chondrocranium in the tongue sole Cynoglossus semilaevis (Pleuronectiformes: Cynoglossidae).

This study provides a comprehensive description of chondrocranial development before, during and after larval metamorphosis in the tongue sole Cynoglossus semilaevis, a commercially valuable flatfish in China. Samples were collected at regular intervals ranging from 1 to 23 days post hatching (dph). Based on observations of cleared and double-stained specimens and images from sections stained with safranin O-fast green, major morphological events during early development were described. No cartilaginous structure was visible at hatching. From 2 dph onwards, cartilaginous structures such as the trabecular bar and some elements of the mandibular, hyoid and branchial arches appeared. At this time also, cartilaginous structures of the neurocranium started to form. Hypertrophic chondrocytes could be observed in many splanchnocranium elements at 5 dph. The start of ossification was indicated by alizarin red stain visible at 14 dph. At 17 dph, most of the cartilaginous skeleton was ossified. Soon after, the right eye started to migrate and pass through a slit beneath the dorsal-fin base and above the skull. Metamorphosis was complete at 20 dph, at which time the dorsal-fin base cartilage extended onto the anterior region of the head. Meanwhile, extremities of the hyoid and branchial arch elements remained cartilaginous. At 23 dph, endochondral ossification of the splanchnocranium was nearly complete. Unlike previous observations of other Pleuronectiformes, our study indicates that endochondral ossification of C. semilaevis skull cartilage occurs before metamorphosis.

[Fatty acid synthase interacts with signal transducer and activator of transcription 3 to promote migration and invasion in liver cancer cells].

Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant tumor worldwide. Metastasis is a marker of cancer deterioration in patients with liver cancer and a major cause of death. In order to develop effective therapeutic strategies, it is urgent to study the molecular basis of liver cancer metastasis. Methods: Immunohistochemistry was used to detect the expression of fatty acid synthase (FASN) in HCC. Wound healing and transwell cell invasion assays was used to confirm the role of FASN in liver cancer migration and invasion. Proteins that interacted with FASN were identified using iTRAQ (isobaric tag for relative and absolute quantification). Co-immunoprecipitation (Co-IP) and cellular immunofluorescence analysis were used to assess the interaction between FASN and signal transduction and transcription activator 3 (STAT3). The expression of STAT3, p-STAT3, matrix metalloproteinase (MMP)-2 and MMP-9 was detected after FASN knockdown using Western blot method. Statistical analysis was performed using the t-test. Results: Immunohistochemistry showed that the expression of FASN in HCC tissue was higher than that in adjacent tissues. iTRAQ, Co-IP and immunofluorescence analysis revealed that FASN interacted with STAT3. Western blot analysis showed that the expression of p-STAT3, MMP-2 and MMP-9 decreased after FASN knockdown. Conclusion: FASN may promote the metastasis of liver cancer by interacting with STAT3 and affecting the expression of MMP-2/MMP-9.

A novel synthetic route for high-index faceted iron oxide concave nanocubes with high T2 relaxivity for in vivo MRI applications.

Iron oxide nanoparticles (IONPs) with high-index facets have shown great potential as high performance T2 contrast agents for MRI. Previous synthetic approaches focused mainly on ion-directed or oxidative etching methods. Herein, we report a new synthetic route for preparing high-index faceted iron oxide concave nanocubes using a bulky coordinating solvent. Through the systematic replacement of a non-coordinating solvent, 1-octadecene, with trioctylamine, the solvent interaction with the nanoparticle surface is modified, thereby, promoting the growth evolution of the IONPs from spherical to concave cubic morphology. The presence of the bulky trioctylamine solvent results in particle size increase and the formation of nanoparticles with enhanced shape anisotropy. A well-defined concave nanocube structure was evident from the early stages of particle growth, further confirming the important role of bulky coordinating solvents in nanoparticle structural development. The unique concave nanocube morphology has a direct influence on the magnetic properties of the IONPs, ultimately leading to an ultra-high T2 relaxivity (862.2 mM-1 s-1), and a 2-fold enhancement in T2*-weighted in vivo MRI contrast compared to spherical IONP analogs.

Scutellaria barbata flavonoids alleviate memory deficits and neuronal injuries induced by composited Aß in rats.

BACKGROUND: The aim of the present study was to investigate the effects of Scutellaria barbata flavonoids (SBF) on memory impairment and neuronal injury induced by amyloid beta protein 25-35 in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-ß1 (RHTGF-ß1) (composited Aß) in rats. METHODS: The composited Aß-treated model of Alzheimer's disease (AD)-like memory impairment and neuronal injury was established in male rats by right intracerebroventricular injection of composited Aß, and the effects of SBF were assessed using this rat model. Spatial learning and memory of rats were assessed in the Morris water maze, and neuronal injury was assessed by light and electron microscopy with hematoxylin-eosin or uranyl acetate and lead nitrate-sodium citrate staining, respectively. RESULTS: In the Morris water maze, memory impairment was observed in 94.7% of the composited Aß-treated rats. The composited Aß-treated rats took longer than sham-operated rats to find the hidden platform during position navigation and reversal learning trials. They also spent less time swimming in the target quadrant in the probe trial. Optical and electron microscopic observations showed significant neuropathological changes including neuron loss or pyknosis in hippocampus, typical colliquative necrosis in cerebral cortex, mitochondrial swelling and cristae fragmentation and a large number of lipofuscin deposits in the cytoplasm. Treatment with SBF (35-140 mg/kg) reduced the memory impairment and neuronal injury induced by composited Aß. CONCLUSION: SBF-mediated improvement of composited Aß-induced memory impairment and neuronal injury in rats provides an appropriate rationale for evaluating SBF as a promising agent for treatment of AD.

Neutral alpha-1,4-glucosidase and fructose levels contribute to discriminating obstructive and nonobstructive azoospermia in Chinese men with azoospermia.

Nowadays, whether neutral alpha-1,4-glucosidase (NAG) and fructose levels are contributed to discriminating obstructive and nonobstructive azoospermia in Chinese azoospermic patients remains unclear. In this study, we retrospectively analysed the levels of NAG and fructose in 229 patients with obstructive azoospermia and 415 patients with nonobstructive azoospermia from three different medical central. Results indicated that NAG and fructose levels in patients with nonobstructive azoospermia were significantly higher compared with those with obstructive azoospermia (P < 0.05). According to the reference value of NAG and fructose defined by the World Health Organization (WHO, 2010), decreased level of NAG was observed in 77.3% of patients with obstructive azoospermia, which was significantly higher than those with nonobstructive azoospermia (55.2%, P < 0.0001). Low level of fructose was observed in 48.0% of patients with obstructive azoospermia, which is also obviously higher than those with nonobstructive azoospermia (31.8%, P < 0.0001). Moreover, the decrease of both NAG and fructose was only recorded in 3.7% of patients with SCO syndrome, 5.0% of patients with severe hypospermatogenesis and 18.2% of patients with maturation arrest. Therefore, our results indicated that NAG and fructose levels are contributed to discriminating obstructive and nonobstructive azoospermia in Chinese patients based on the histological types of testes.

Cavity modes with optical orbital angular momentum in a metamaterial ring based on transformation optics.

In this work, we theoretically study the cavity modes with transverse orbital angular momentum in metamaterial ring based on transformation optics. The metamaterial ring is designed to transform the straight trajectory of light into the circulating one by enlarging the azimuthal angle, effectively presenting the modes with transverse orbital angular momentum. The simulation results confirm the theoretical predictions, which state that the transverse orbital angular momentum of the mode not only depends on the frequency of the incident light, but also depends on the transformation scale of the azimuthal angle. Because energy dissipation inevitably reduces the field amplitude of the modes, the confined electromagnetic energy and the quality factor of the modes inside the ring are also studied in order to evaluate the stability of those cavity modes. The results show that the metamaterial ring can effectively confine light with a high quality factor and maintain steady modes with the orbital angular momentum, even if the dimension of the ring is much smaller than the wavelength of the incident light. This technique for exploiting the modes with optical transverse orbital angular momentum may provides a unique platform for applications related to micromanipulation.

Iron Oxide and Titanium Dioxide Nanoparticle Effects on Plant Performance and Root Associated Microbes.

In this study, we investigated the effect of positively and negatively charged Fe3O4 and TiO2 nanoparticles (NPs) on the growth of soybean plants (Glycine max.) and their root associated soil microbes. Soybean plants were grown in a greenhouse for six weeks after application of different amounts of NPs, and plant growth and nutrient content were examined. Roots were analyzed for colonization by arbuscular mycorrhizal (AM) fungi and nodule-forming nitrogen fixing bacteria using DNA-based techniques. We found that plant growth was significantly lower with the application of TiO2 as compared to Fe3O4 NPs. The leaf carbon was also marginally significant lower in plants treated with TiO2 NPs; however, leaf phosphorus was reduced in plants treated with Fe3O4. We found no effects of NP type, concentration, or charge on the community structure of either rhizobia or AM fungi colonizing plant roots. However, the charge of the Fe3O4 NPs affected both colonization of the root system by rhizobia as well as leaf phosphorus content. Our results indicate that the type of NP can affect plant growth and nutrient content in an agriculturally important crop species, and that the charge of these particles influences the colonization of the root system by nitrogen-fixing bacteria.

Equol promotes rat osteoblast proliferation and differentiation through activating estrogen receptor.

Phytoestrogens have been suggested as alternative treatment for postmenopausal osteoporosis. Equol, a metabolite of daidzein, has been shown to inhibit bone loss in ovariectomized mice and rats. However, whether or not equol influences the formation of bone has not yet been investigated. Therefore, we investigated the effect of equol on the proliferation and differentiation of rat primary osteoblasts and explored the involved mechanisms. Different equol concentrations significantly promoted the proliferation of osteoblasts after 48- and 72-h incubations. The alkaline phosphatase (ALP) activity also increased significantly in all of the equol and 17ß-estradiol (E2) groups, except for the lowest (0.01 µM) equol group. Equol also significantly elevated the osteocalcin levels. The effects of equol on osteoblast proliferation, ALP activity, and osteocalcin levels were blocked by the estrogen receptor (ER) antagonist ICI182780. After a 24-h incubation, the expression of protein kinase C alpha (PKCα) in osteoblasts was significantly increased by equol. In conclusion, our study demonstrated that equol could promote the proliferation and differentiation of rat osteoblasts through activating the ER-PKCα-related signaling pathway, suggesting that equol could promote bone formation. These results suggest that equol could be a potential alternative agent for the management of postmenopausal osteoporosis.

Reliability, validity, usefulness, and sensitivity of a submaximal test of performing burpees in 3 minutes, in assessing and detecting changes in aerobic fitness of athletes during future prolonged self-isolation in a confined environment.

BACKGROUND: During a prolonged quarantine, there is a need to monitor aerobic fitness levels of trained individuals who are isolated with a simple fitness test that can be performed in confined space of their own homes. This study examined the reliability, validity, usefulness and sensitivity of a novel 3-min submaximal heart rate burpees test (or SubHR3-MBT) to assess and monitor changes in aerobic fitness, of trained athletes. In the SubHR3-MBT, male and female athletes performed 48 and 39 burpees respectively, within 3 min by following a constant beeping pace. The performance criterion of the SubHR3-MBT is the highest heart rate attained (or exercise HRpeak) at the end of 3-min (wherein a lower exercise HRpeak indicates a higher level of aerobic fitness). METHODS: A total of 40 male and female national athletes from various sports volunteered for the study. RESULTS: For reliability (Part 1), the SubHR3-MBT showed good relative and excellent reliability, with intraclass correlation coefficient 0.90 and coefficient of variation 2.6%, respectively. For validity (Part II), there was significant negative correlation between relative exercise HRpeak with respiratory gas-measured VO2max (r=-0.51, large; P<0.001). The test's technical error of measurement of 2.3 is slightly greater than its smallest worthwhile change of 1.5. For sensitivity (Part III), the athletes were tested twice for their SubHR3-MBT and VO2max, once at baseline and another at a followed-up test after >10 weeks. There was a significant correlation between the % change in relative exercise HRpeak with the % change in VO2max (r=-0.66, large; P<0.001). CONCLUSIONS: The SubHR3-MBT is a reliable, valid, marginally useful test and may be able to track changes in aerobic fitness in trained athletes with moderate levels of sensitivity, in case of future isolation due to pandemic occurrence.

Expanded morphological description of the recently described Lycodon zayuensis (Serpentes: Colubridae).

Lycodon is a species-rich genus that currently contains 72 named species. Lycodon zayuensis Jiang, Wang, Jin & Che, 2020, was described from Lower Chayu Town, Chayu County, Tibet, China, based on a single female holotype. During our recent field work, three additional specimens, including two females and one male, were collected and identified as L. zayuensis based on morphological comparison and the cytochrome b mitochondrial gene (1049 bp). Here, we provide an expanded description of this recently described species based on all known specimens.

A new species of bush frog (Anura, Rhacophoridae, Raorchestes) from southern Xizang, China.

Based on molecular evidence and morphological data, we describe a new species Raorchestes yadongensis sp. nov. from Yadong County, Xizang Autonomous Region, China. The new species can be distinguished based on a combination of the following characters: (1) small body size, SVL 17.8-24.1 mm in adult males; (2) head wider than long; (3) eye diameter about three times as much as tympanum diameter; (4) tympanum distinct; (5) fingers with rudimentary webbing and narrow lateral dermal fringes; relative finger lengths I < II < IV < III; number of subarticular tubercles in fingers 1, 1, 2, 1; (6) toes with rudimentary webbing and narrow lateral dermal fringes; relative toe lengths I < II < III < V < IV; number of subarticular tubercles in toes 1, 1, 2, 3, 2; inner metatarsal tubercle distinct, outer metatarsal tubercle absent; (7) tips of fingers and toes present discs, and discs pale brown or yellow in life; (8) tibiotarsal articulation reaching the tip of snout when adpressed; (9) milky nuptial pad present on the dorsal surface of first finger; (10) dorsal surface light brown with white warts, ventral surface with irregular white patches. The new species is currently known in Yadong County, Xizang, China, but may also occur in neighboring Bhutan and India. A key to Chinese species of the genus Raorchestes is also provided.

Self-management of depression among Chinese community individuals: A cross-sectional study using the transtheoretical model.

PURPOSE: To investigate the self-management of depression among members of a Chinese community. DESIGN AND METHODS: A cross-sectional survey was conducted in Wuhan. The Depression Prevention and Management Survey was used to identify 429 participants' stage of change, perceived benefits, process of change and self-efficacy, based on the transtheoretical model perspective. FINDINGS: A majority of participants (69.0%) were at the inactive stage of depression self-management. The mean score of the process of change was 87.62 (SD = 24.83). ANOVA analysis showed gender, education, and family function were significant influencing factors in the process of change. PRACTICE IMPLICATIONS: Mental health nurses need to target their approach to the level of the individual based on the transtheoretical model to assist them to enhance their awareness and motivation. More consideration should be given to gender, education, and family function in the context of depression self-management.

High field (9.4 Tesla) magnetic resonance imaging of cortical grey matter lesions in multiple sclerosis.

Multiple sclerosis is an inflammatory, degenerative disease of the central nervous system. The most obvious pathological change in multiple sclerosis is multifocal demyelination of the white matter, but grey matter demyelination may be of equal or even greater importance for its clinical manifestations. In order to assess the pathogenetic role of lesions in the grey and white matter, and to explore the association between demyelinated and non-lesional brain tissue, tools are needed to depict each of these tissue components accurately in vivo. Due to its sensitivity in detecting white matter lesions, T(2)-weighted magnetic resonance imaging at 1.5 T is important in the diagnosis of multiple sclerosis. However, magnetic resonance imaging at 1.5 T largely fails to detect grey matter lesions. In this study, we used T(2)-weighted magnetic resonance imaging at 9.4 T to detect grey matter lesions in fixed post-mortem multiple sclerosis motor cortex. Furthermore, we produced T(1), T(2) and magnetization transfer ratio maps, and correlated these indices with quantitative histology [neuronal density, intensity of immunostaining for myelin basic protein (reflecting myelin content) and phosphorylated neurofilament (reflecting axonal area)] using t-tests and multivariate regression. In 21 tissue samples, 28 cortical grey matter lesions were visible on both T(2)-weighted magnetic resonance imaging and sections immunostained for myelin basic protein, 15/28 being mixed white and grey matter and 11/28 subpial cortical grey matter lesions; 2/28 cortical grey matter lesions involved all layers of the cortex. Compared with non-lesional cortex, cortical grey matter lesions showed reduction of neuronal density (98/mm(2), SD = 34/mm(2;) versus 129/mm(2), SD = 44; P < 0.01), phosphorylated neurofilament (1/transmittance = 1.16; SD = 0.09 versus 1.24; SD = 0.1; P < 0.01) and magnetization transfer ratio (31.1 pu; SD = 11.9 versus 37.5 pu; SD = 8.7; P = 0.01), and an increase of T(2) (25.9; SD = 5 versus 22.6 ms; SD = 4.7; P < 0.01). Associations were detected between phosphorylated neurofilament and myelin basic protein (r = 0.58, P < 0.01), myelin basic protein and T(2) (r = -0.59, P < 0.01), and neuronal density and T(1) (r = -0.57, P < 0.01). All indices correlated with duration of tissue fixation, however, including the latter in the analysis did not fundamentally affect the associations described. Our data show that T(2)-weighted magnetic resonance imaging at 9.4 T enables detection of cortical grey matter lesion in post-mortem multiple sclerosis brain. The quantitative associations suggest that in cortical grey matter T(1) may be a predictor of neuronal density, and T(2) of myelin content (and-secondarily-axons). Successful translation of these results into in vivo studies using high field magnetic resonance imaging (e.g. 3 T and 7 T) will improve the assessment of cortical pathology and thereby have an impact on the diagnosis and natural history studies of patients with multiple sclerosis, as well as clinical trial designs for putative treatments to prevent cortical demyelination and neuronal loss.

Global computer-assisted appraisal of osteoporosis risk in Asian women: an innovative study.

AIMS AND OBJECTIVE: To develop a computer-assisted appraisal system of osteoporosis that can predict osteoporosis health risk in community-dwelling women and to use it in an empirical analysis of the risk in Asian women. BACKGROUND: As the literature indicates, health risk assessment tools are generally applied in clinical practice for patient diagnosis. However, few studies have explored how to assist community-dwelling women to understand the risk of osteoporosis without invasive data. DESIGN: A longitudinal, evidence-based study. METHOD: The first stage of this study is to establish a system that combines expertise in nursing, medicine and information technology. This part includes information from random samples (n = 700), including data on bone mineral density, osteoporosis risk factors, knowledge, beliefs and behaviour, which are used as the health risk appraisal system database. The second stage is to apply an empirical study. The relative risks of osteoporosis of the participants (n = 300) were determined with the system. The participants that were classified as at-risk were randomly grouped into experimental and control groups. Each group was treated using different nursing intervention methods. RESULTS: The sensitivity and specificity of the analytical tools was 75%. In empirical study, analysis results indicate that the prevalence of osteoporosis was 14.0%. Data indicate that strategic application of multiple nursing interventions can promote osteoporosis prevention knowledge in high-risk women and enhance the effectiveness of preventive action. CONCLUSIONS: The system can also provide people in remote areas or with insufficient medical resources a simple and effective means of managing health risk and implement the idea of self-evaluation and self-caring among community-dwelling women at home to achieve the final goal of early detection and early treatment of osteoporosis. RELEVANCE TO CLINICAL PRACTICE: This study developed a useful approach for providing Asia women with a reliable, valid, convenient and economical self-health management model. Health care professionals can explore the use of advanced information systems and nursing interventions to increase the effectiveness of osteoporosis prevention programmes for women.

Efficacy of controlling night-time noise and activities to improve patients' sleep quality in a surgical intensive care unit.

AIM: The aim of the study was to test the efficacy of sleep care guidelines for controlling night-time noise and improving sleep quality of patients in a surgical intensive care unit. BACKGROUND: Poor sleep quality places critically ill patients at greater risk for infection, complications and mortality. Environmental stimuli such as noises, continuous lighting and frequent care-related activities in an intensive care unit interfere with patients' sleep. DESIGN: The study used a quasi-experimental design. METHOD: Sixty surgical patients were recruited from an intensive care unit in Taiwan during December 2007-May 2008. The control group received the usual care, and the experimental group was cared for by nurses who followed the sleep care guidelines for noise and light reduction. Data were collected on noise level and sleep quality using the Sleep in the Intensive Care Unit Questionnaire, the Richards Campbell Sleep Questionnaire and a decibel meter. RESULTS: The results showed that both the peak sound level (χ(2) = 50.1, p < 0.001) and average noise level (χ(2) = 46.5, p < 0.001) were reduced significantly, after implementing the guidelines. The perceived noise (t = -2.07, p = 0.046) and sleep interruptions from care-related activities (t = 5.282, p < 0.001) and noises (t = 4.361, p < 0.001) were all significantly lower in the experimental group than in the control group. The experimental group also reported better sleep quality (t = -2.28, p = 0.027) and sleep efficiency (t = -2.03, p = 0.047) than did the control group. CONCLUSIONS: These results support the efficacy of the guidelines for controlling night-time noise and care activities to improve patients' sleep quality. RELEVANCE TO CLINICAL PRACTICE: Nurses should try to reduce external environmental stimuli and maintain an almost undisturbed period between midnight and 5:00 a.m. to enhance patients' sleep in a surgical intensive care unit.

A simple, economical, and effective portable paediatric mock circulatory system.

Ventricular assist devices (VADs) and total artificial hearts have been in development for the last 50 years. Since their inception, simulators of the circulation with different degrees of complexity have been produced to test these devices in vitro. Currently, a new path has been taken with the extensive efforts to develop paediatric VADs, which require totally different design constraints. This paper presents the manufacturing details of an economical simulator of the systemic paediatric circulation. This simulator allows the insertion of a paediatric VAD, includes a pumping ventricle, and is adjustable within the paediatric range. Rather than focusing on complexity and physiological simulation, this simulator is designed to be simple and practical for rapid device testing. The simulator was instrumented with medical sensors and data were acquired under different conditions with and without the new PediaFlowTM paediatric VAD. The VAD was run at different impeller speeds while simulator settings such as vascular resistance and stroke volume were varied. The hydraulic performance of the VAD under pulsatile conditions could be characterized and the magnetic suspension could be tested via manipulations such as cannula clamping. This compact mock loop has proven to be valuable throughout the PediaFlow development process and has the advantage that it is uncomplicated and can be manufactured cheaply. It can be produced by several research groups and the results of different VADs can then be compared easily.

Propofol alleviates intestinal ischemia/reperfusion injury in rats through p38 MAPK/NF-κB signaling pathway.

OBJECTIVE: The aim of this study was to investigate the influences of propofol on intestinal ischemia/reperfusion (I/R) injury in rats through the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. MATERIALS AND METHODS: The models of intestinal I/R injury were first successfully established. All rats were randomly divided into 4 groups, namely, S group, I/R group, P group and P + S group. Pathological-morphological changes, injury score and wet-to-dry weight ratio of intestinal tissues as well as oxidative stress indexes in each group of rats were detected. Enzyme-linked immunosorbent assay (ELISA) was applied to measure the levels of inflammatory factors such as creatine kinase-MB (CK-MB), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in each group of rats. Furthermore, Western blotting (WB) assay was applied to determine the protein expression levels of p38 MAPK and NF-κB in different groups. RESULTS: Intestinal tissue injury was the severest in I/R group, with the infiltration of massive inflammatory cells and oozing of blood (Figure 1A, I/R). Compared with those in I/R group, the infiltration of inflammatory cells and damage to intestinal villi were notably relieved in P group and P + S group, revealing that the intestinal mucosal injury was remarkably repaired in P group and P + S group (Figure 1A, P). Moreover, the intestinal tissue injury score was evidently higher in I/R group, P group and P + S group than that in S group (p<0.05). However, it was markedly lower in P group and P + S group than that in I/R group (p<0.05). I/R group, P group and P + S group exhibited significantly increased wet-to-dry weight ratio of intestinal tissues in comparison with S group (p<0.05). However, P group and P + S group exhibited distinctly lower wet-to-dry weight ratio of intestinal tissues than I/R group (p<0.05). The content of malondialdehyde (MDA) was reduced prominently, while that of superoxide dismutase (SOD) was elevated significantly in P group and P + S group in contrast with those in I/R group (p<0.05). On the contrary, P + S group displayed remarkably lower MDA content and higher SOD content than P group (p<0.05). The levels of CK-MB, TNF-α and IL-6 in the blood rose markedly in I/R group compared with those in S group (p<0.05). However, they declined evidently in P group and P + S group in contrast with those in I/R group (p<0.05). Besides, the protein expression level of phosphorylated p38 MAPK was significantly higher in I/R group, P group and P + S group than that in S group (p<0.05). However, no significant difference was observed in the protein expression of total p38 MAPK among the four groups (p>0.05). However, the protein expression level of phosphorylated p38 MAPK was distinctly down-regulated in P group and P + S group in comparison with that in I/R group (p<0.05). Finally, I/R group, P group and P + S group had a prominently higher protein expression level of NF-κB than S group (p<0.05). However, P group and P + S group exerted a significantly lower protein expression level of NF-κB than I/R group (p<0.05). CONCLUSIONS: Propofol decreases the release of inflammatory factors and alleviates intestinal edema by inhibiting the p38 MAPK/NF-κB signaling pathway, thereby mitigating and treating the intestinal I/R injury in rats.

Sevoflurane ameliorates adriamycin-induced myocardial injury in rats through the PI3K/Akt/GSK-3ß pathway.

OBJECTIVE: The aim of this study was to explore the effects of sevoflurane (SEV) pretreatment on Adriamycin (ADR)-induced myocardial injury through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathway. MATERIALS AND METHODS: A total of 24 rats weighing 200-250 g were divided into four groups, including: control group (C group), ADR injection group (ADR group), SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group). H9c2 cells were cultured in vitro and were divided into control group (C group), ADR treatment group (ADR group), and SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group) as well. Next, the content of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the serum was detected via Enzyme-Linked Immunosorbent Assay (ELISA). Hematoxylin-eosin (HE) staining assay was performed to determine the severity of myocardial injury. Meanwhile, the apoptosis rate of cells was detected through terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Additionally, Western blotting (WB) was employed to measure the protein expression levels of phosphorylated (p)-GSK-3ß, p-PI3K, Akt and p-Akt. RESULTS: Compared with C group, ADR significantly increased the content of AST, LDH and CK in the serum (p<0.01), reduced protein expression levels of p-GSK-3ß, p-PI3K and p-Akt (p<0.01), increased apoptosis rate (p<0.01), and induced myocardial injury. SEV pretreatment significantly alleviated the effect of ADR, manifested as significantly lowered content of AST, LDH and CK in the serum (p<0.01), distinctly elevated protein expression levels of p-GSK-3ß, p-PI3K and p-Akt (p<0.01), notably reduced apoptosis rate (p<0.01), and relieved myocardial injury. LY294002 remarkably inhibited the protective effect of SEV against myocardial injury (p<0.01) CONCLUSIONS: SEV is able to prominently ameliorate ADR-induced myocardial injury by regulating the phosphorylation level of the PI3K/Akt/GSK-3ß signaling pathway.