Camellia oil exhibits anti-fatigue property by modulating antioxidant capacity, muscle fiber, and gut microbial composition in mice.

Camellia seed oil (CO) has high nutritional value and multiple bioactivities. However, the specific anti-fatigue characteristics and the implied mechanism of CO have not yet been fully elucidated. Throughout this investigation, male C57BL/6J mice, aged 8 weeks, underwent exhaustive exercise with or without CO pretreatment (2, 4, and 6 mL/kg BW) for 28 days. CO could extend the rota-rod and running time, reduce blood urea nitrogen levels and serum lactic acid, and increase muscle and hepatic glycogen, adenosine triphosphate, and anti-oxidative indicators. Additionally, CO could upregulate the mRNA and Nrf2 protein expression levels, as well as enhance the levels of its downstream antioxidant enzymes and induce the myofiber-type transformation from fast to slow and attenuate the gut mechanical barrier. Moreover, CO could ameliorate gut dysbiosis by reducing Firmicutes to Bacteroidetes ratio at the phylum level, increasing the percentage of Alistipes, Alloprevotella, Lactobacillus, and Muribaculaceae, and decreasing the proportion of Dubosiella at the genus level. In addition, specific bacterial taxa, which were altered by CO, showed a significant correlation with partial fatigue-related parameters. These findings suggest that CO may alleviate fatigue by regulating antioxidant capacity, muscle fiber transformation, gut mechanical barrier, and gut microbial composition in mice. PRACTICAL APPLICATION: Our study revealed that camellia seed oil (CO) could ameliorate exercise-induced fatigue in mice by modulating antioxidant capacity, muscle fiber, and gut microbial composition in mice. Our results promote the application of CO as an anti-fatigue functional food that targets oxidative stress, myofiber-type transformation, and microbial community.

Structural Analysis and Novel Mechanism of Enteromorpha prolifera Sulfated Polysaccharide in Preventing Type 2 Diabetes Mellitus.

A water-soluble polysaccharide (EP) was purified from edible algae Enteromorpha prolifera. Gel permeation chromatography (GPC), ion chromatography (IC), and fourier transform infrared (FT-IR) were performed to characterize its structure. EP was defined as a low molecular weight (6625 Da) composed of rhamnose, glucose, glucuronic acid, xylose, galactose, arabinose, and mannose. Moreover, it was a sulfated polysaccharide with a degree of substitution (DS) of 1.48. Then, the high-fat diet/streptozotocin (HFD/STZ) induced diabetic mouse model was established to support evidence for a novel hypoglycemic mechanism. Results showed that blood glucose (47.32%), liver index (7.65%), epididymal fat index (16.86%), serum total cholesterol (26.78%) and triglyceride (37.61%) in the high-dose EP (HEP) group were significantly lower than those in the HFD group. Noticeably, the content of liver glycogen in the HEP group was significantly higher (62.62%) than that in the HFD group, indicating the promotion of glycogen synthesis. These beneficial effects were attributed to significantly increased protein kinase B (AKT) phosphorylation and its downstream signaling response. Further studies showed that diabetic mice exhibited excessive O-GlcNAcylation level and high expression of O-linked ß-D-N-acetylglucosamine transferase (OGT), which were decreased by 62.21 and 30.43% in the HEP group. This result suggested that EP had a similar effect to OGT inhibitors, which restored AKT phosphorylation and prevented pathoglycemia. This work reveals a novel hypoglycemic mechanism of EP, providing a theoretical basis for further studies on its pharmacological properties in improvement of T2DM.

Effects of exposure to the explosive and environmental pollutant 2,4,6-trinitrotoluene on ovarian follicle development in rats.

Although 2,4,6-trinitrotoluene (TNT) is a dangerous carcinogen in environmental pollution, information on the reproductive effects of TNT explosive contamination is limited. To explore the possible ovarian effects, TNT explosive-exposed rat models were established, and Wistar female rats were exposed to low and high TNT (40 g and 80 g, air and internal) explosives. After a month of exposure, the estrous cycle, ovarian histopathology, and follicle counting were conducted. Serum hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-Müllerian hormone (AMH), progesterone, testosterone, and estradiol were detected, and the mRNA and protein expression of steroidogenic enzymes were measured. The results showed that the diestrus phase duration was significantly (P < 0.05) increased in the high TNT-exposed groups. In addition, the proportions of preantral follicles were significantly (P < 0.05) decreased in the high TNT-exposed groups, as well as the proportions of atretic follicles. The serum estradiol levels were significantly (P < 0.05) increased, and the follicle-stimulating hormone and luteinizing hormone levels were significantly (P < 0.05) decreased in the high TNT-exposed groups. The mRNA levels of steroidogenic acute regulatory protein (Star), cytochrome P450 cholesterol side chain cleavage (Cyp11a1, Cyp17a1 and Cyp19a1), hydroxysteroid dehydrogenase 3b (Hsd3b) and steroidogenic factor-1 (SF-1) were significantly (P < 0.05) increased in the TNT-exposed groups. The protein levels of Star, Cyp11a1 and Hsd3b were increased (P < 0.05) in the TNT-exposed groups. These results indicate that the exposure of rats to TNT explosive can subsequently affect ovarian follicle development, suggesting that the mechanism may involve disrupting steroidogenesis.

Efficacy of Laser in Hair Removal: A Network Meta-analysis.

BACKGROUND: Laser hair removal is an increasingly prevalent trend of cosmetic procedures. The purpose of this study was to assess the effectiveness of hair reduction among several types of laser interventions. METHODS: The selected studies searched in PubMed and EMBASE were assessed for quality of evidence, and extracted data on absolute hair count and hair reduction rate. Qualitative data were synthesized using standardized mean difference (SMD) in frequentist network meta-analysis because various measurement units were used among selected studies. Inconsistency and small study effects were examined by design-by-treatment interaction model and comparison-adjusted funnel plot. RESULTS: A total of 13 randomized controlled trials (RCTs) (n = 652) were contributed to network meta-analysis. Pooled results revealed that diode laser showed significantly lower absolute hair count within three-month (SMD = -13.21, 95% confidence interval [CI]: -22.25 to -4.17) and around six months follow-up (SMD = -11.01, 95% CI: -18.24 to -3.77) as compared with those in control group, but no significant difference among laser interventions. All side effects observed were transient without leaving any permanent scars. CONCLUSION: Eliminating unwanted hair with lasers or intense pulsed light is safe and effective; however, which type of intervention is more beneficial in the long-term process should be studied with a longer follow-up time.

Conjugated linoleic acid alleviates glycolipid metabolic disorders by modulating intestinal microbiota and short-chain fatty acids in obese rats.

Although conjugated linoleic acid (CLA) has been shown to have anti-obesity properties, the effect and mechanism of CLA in alleviating glycolipid metabolism disorders remains unclear. In this work, it was observed that rats fed a high-fat diet (HFD) had lower body weight and body fat levels after 9 weeks of low-dose and high-dose CLA interventions. The results of blood biochemical indices showed that CLA significantly reduced the levels of total cholesterol, triglycerides, fasting blood glucose and insulin. Additionally, high-dose CLA could restore the intestinal microbiota composition, including increasing the relative abundances of short-chain fatty acid (SCFA)-producing microbiota, such as Dubosiella, Faecalibaculum and Bifidobacterium; decreasing the relative abundances of Enterococcus and Ruminococcus_2; and increasing the content of SCFAs in feces and serum. Further analysis showed that high-dose CLA could increase the expression levels of Insr, Irs-2, Akt and Glut4 in the liver tissue of HFD-induced obese rats. Consistently, high dose of CLA could reversibly improve the downregulation of INSR, AKT, PI3K and GLUT4 protein expression caused by HFD and reverse the decline in AKT phosphorylation levels. Correlation clustering analysis with a heatmap showed that the changes in specific microbiota induced by high-dose CLA were correlated with changes in obesity-related indices and gene expression. The molecular docking analysis showed that the molecular docking of SCFAs with the IRS-2, AKT and GLUT4 proteins had high linking activity. The results supported that CLA can alleviate glycolipid metabolic imbalances associated with obesity by altering the intestinal microbiota to induce the production of SCFAs and thereby activate the INSR/IRS-2/AKT/GLUT4 pathway. This study supports CLA may be preferentially used by the intestinal microbiota of the host to promote its health.

Effects of ketogenic diet on cognitive functions of mice fed high-fat-high-cholesterol diet.

Long-term dietary intake of elevated levels of refined sugars, fats and cholesterols is among the factors causing cognitive impairment. Ketone bodies can be used as an alternative energy source when glucose is not available. The study investigated the effects of a ketogenic diet (medium chain triglyceride, MCT) on cognitive performance after a long-term consumption of a high-fat-high-cholesterol diet using a mice model. Seventy eight-week-old male C57BL/6 mice were fed an HFHC diet for 16 weeks to establish a model of an HFHC dietary pattern, before receiving intervention diets containing MCT diet or with Metformin for another 8 weeks in the second part of the experiment. Spatial learning, memory performance, and cortical and hippocampal protein expression levels were assessed. After consuming the HFHC diet for 16 weeks and subsequently receiving the MCT diet for 8 weeks, results showed that the mice fed a MCT diet had significantly better spatial learning and memory performance, lower expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), glial fibrillary acidic protein (GFAP), amyloid protein precursor (APP) and phosphate tau, and higher expression of brain-derived neurotrophic factor (BDNF) than the mice fed the HFHC diet. Long-term consumption of an HFHC diet caused a decline in cognitive functions and increased the risk factors for neurodegeneration, such as BBB permeability, neuropathy and inflammation. An MCT diet can be considered as an option for slowing down the early stage of neurodegeneration in mice.

Sulfated Polysaccharides from Enteromorpha prolifera Attenuate Lipid Metabolism Disorders in Mice with Obesity Induced by a High-Fat Diet via a Pathway Dependent on AMP-Activated Protein Kinase.

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.

Sulfated Polysaccharides from Enteromorpha prolifera Attenuate Lipid Metabolism Disorders in Mice with Obesity Induced by a High-Fat Diet via a Pathway Dependent on AMP-Activated Protein Kinase.

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.

Electromagnetic navigation bronchoscopic localization versus percutaneous CT-guided localization for thoracoscopic resection of small pulmonary nodules.

BACKGROUND: Identification of small pulmonary nodules is challenging in a limited intrathoracic field during minimally invasive video-assisted thoracoscopic surgery (VATS), and preoperative localization is required. Various techniques have been reported with some failure and complications. Here, we compare the feasibility and safety between electromagnetic navigation bronchoscopic marking and computed tomography (CT)-guided percutaneous marking using indocyanine green (ICG) and iopamidol. METHODS: A total of 47 patients with small-sized pulmonary nodules, scheduled to undergo video-assisted thoracoscopic limited resection, were enrolled in this study. A mixture of diluted ICG and iopamidol was injected into the lung parenchyma as a marker, using CT-guided percutaneous or electromagnetic navigation bronchoscopic injection techniques and the results were examined and compared. RESULTS: A total of 35 and 12 patients underwent preoperative marking by percutaneous injection and electromagnetic navigation bronchoscopic injection, respectively, in which a marker was detected in 33/35 (94.3%) and 12/12 (100%) patients. No combination of these procedures was performed in any patient. All markers were successfully detected in three patients who underwent injection marking at two different lesion sites. Pneumothorax occurred in five patients (14%) in the percutaneous marking group, which was relieved in all patients without the necessity for chest tube drainage. No other complication was observed in this study. CONCLUSIONS: Electromagnetic navigation bronchoscopic injection techniques using indocyanine green fluorescence plus iopamidol are safe and effective, and comparable with CT-guided localization. Furthermore, a bronchoscopic approach enables marking of multiple lesion areas without increasing patient risk, especially for puncture-related pneumothorax. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Either computed tomography (CT)-guided percutaneous or electromagnetic navigation bronchoscopic injection techniques can be used for preoperative marking of pulmonary nodules with indocyanine green (ICG) fluorescence. WHAT THIS STUDY ADDS: Indocyanine green (ICG) is a safe and easily detectable fluorescent marker for video-assisted thoracoscopic surgery (VATS). A bronchoscopic injection approach enables marking of multiple lesion areas without increasing the risk of pneumothorax.

Purification and characterization of the major protein isolated from Semen Armeniacae Amarum and the properties of its thermally induced nanoparticles.

From the aqueous extract of Semen Armeniacae Amarum, a major protein isolate was purified and characterized as a novel member of the 11S globulin family, which is composed of three polypeptides linked by disulfide bond. Furthermore, the feasibility of using the isolated protein for fabricating nanocarriers was investigated. The results indicate that thermal treatment of the globulin induced the rearrangement of the disulfide bond to form homodimers of acid polypeptides during the formation of nanoparticles. The harvested nanoparticles produced by heat-induced assembly are spherical in shape, with an average size of 92 nm and exhibited low cytotoxicity to L-02 and MDCK cell lines. These nanoparticles are capable to encapsulate paclitaxel, estimated the maximum encapsulation efficiency of paclitaxel loaded to the nanoparticles was 92.6% and the maximum release of paclitaxel was 57.4%. This research suggests that the screening of traditional herbal extracts could provide a novel source of protein nanocarriers.

Technology-embedded health education on nutrition for middle-aged and older adults living in the community.

Mobile technology provides young adults important support for self-directed learning, but whether there is related support for older adults is not clear. This study aims to determine whether 1) nutrition education combined with mobile technology-supported teaching improves knowledge of and self-efficacy for a healthy diet; 2) if adults who reported reviewing the electronic course material or searching health information online, showed significantly greater progress in knowledge of and self-efficacy for a healthy diet than did those who did not adopt the electronic support. A total of 35 middle-aged and older adults were recruited from the community. Enrollees who were unable to read, who participated in the course fewer than five times, who did not take the post-test, or who did not return complete questionnaires at the pre-test were excluded. Overall, 21 participants were finally analyzed, and 14 participated in the qualitative investigation. The study interventions included three traditional nutrition lectures and three touch-screen tablet computer lessons to access the Internet and nutrition applications. Structured and semi-structured questionnaires were used to collect both quantitative and qualitative data and record participants' Internet use conditions at home. Participants' nutrition knowledge significantly improved (meanpost-pre = 1.19, p = 0.001) and their self-efficacy about a healthy diet showed marginal improvement (meanpost-pre = 0.22, p = 0.07). Nutrition knowledge was positively correlated with their intensity of surfing the Internet (r = 0.46, p < 0.05), or reviewing the electronic course material (r = 0.48, p < 0.05) but not correlated with reviewing paper course material (r = 0.19, p = 0.09). Qualitative results showed that participants reported feeling freshness, joyfulness, and great achievement because of the combined course material. Technology-supported learning combined with traditional health education might provide great opportunities for positive behavioral change, even in older adults without any previous Internet experience.

The safety and risk factors of revision adenoidectomy in children and adolescents: A nationwide retrospective population-based cohort study.

OBJECTIVE: To investigate the safety of adenoidectomy and risk factors of re-adenoidectomy, and intend to provide evidence-based information to clinicians for further consideration. METHODS AND MATERIALS: This study was based on data obtained from Taiwan's National Health Insurance Research Database from the period 2002-2011. We utilized that data from the hospitalization group and collected information regarding those individuals who accepted adenoidectomy with or without tonsillectomy and post-adenoidectomy bleeding. Thereafter, we performed univariate and multi-variate analysis to explore the possible risk factors of re-adenoidectomy. RESULTS: A total of 5435 individuals who accepted a first adenoidectomy with or without tonsillectomy were collected. After further tracing treatment of these individuals, 107 (1.97%) accepted the revision adenoidectomy until 2011. Post-op bleeding was approximately 0.28%. The revision rate associated with patient age showed the following: 0-4 years (0.61%), 4-12 years (2.06%) and 12-18 years (2.56%). The revision rate associated with surgeon age showed: 28-41 years (1.42%), 41-50 years (2.96%), 50-65 years (2.74%); the surgeons' surgery volume showed low (4.34%), medium (0.71%), and higher (1.02%). There are 4 diseases (otitis media with effusion, sinusitis, chronic pharyngitis, and sleep disorder) that showed a significant relationship with the revision rate when subject to univariate and multivariate analysis. The revision rate incorporating hospital locations, volumes and levels revealed no significant difference with each other. CONCLUSIONS: Adenoidectomy is a generally safe surgical procedure, with low complication and low revision rate. Our study indicated that the revision rate of adenoidectomy might be lower when performed by young visiting staff with medium to higher surgical volume in the medium to higher volume hospital. If patients had diseases such as otitis media with effusion, sinusitis, chronic pharyngitis, and sleep disorder, they would be subject to higher rate of re-adenoidectomy. Surgeons should be aware and sufficiently explain this information to the parents before surgery.

Boiling-induced nanoparticles and their constitutive proteins from Isatis indigotica Fort. root decoction: Purification and identification.

Colloidal particles are essential components of sun-dried Isatis indigotica Fort. roots (Ban-Lan-Gen in Chinese, BLG) decoction. Nanoparticles (NPs) were isolated from BLG decoction with size exclusion chromatography and characterized. Their average diameter is ∼120 nm, reversibly responding to pH and temperature changes. They promoted the growth of normal cells but suppressed that of cancerogenic cells and macrophages. Two constitutive glycated proteins were identified from the NPs, namely BLGP1 and BLGP2. Their N-terminal amino acid sequences were V-X-R-E-V-V-K-D-I and V-V-R-E-V-V-K-D-I-A-G-A-V-Q-T-N-E-Q-Y. Their full-length cDNA sequences were cloned to obtain the highly homological amino acid sequences of non-glycated proteins, whose theoretical molecular weights are 21831.64 Da and 21841.67 Da. Using pepsin hydrolysis and mass spectrometry, four possible glycation adducts were identified in BLGP1, whereas one in BLGP2. To conclude, bioactive nanoparticles isolated from the herbal decoction are intelligent nanoassemblies composed of a new boiling-stable protein. Glycation plays a critical role in heat-induced formation of these nanoassemblies. The novel, intelligent, safe and stable nano-carriers for drug delivery may be developed using BLG NPs as prototype.

Identification of Up- and Down-Regulated Proteins in Pemetrexed-Resistant Human Lung Adenocarcinoma: Flavin Reductase and Calreticulin Play Key Roles in the Development of Pemetrexed-Associated Resistance.

Drug resistance is one of the major causes of cancer chemotherapy failure. In the current study, we used a pair of lung adenocarcinoma cell lines, A549 and the pemetrexed-resistant A549/PEM cells, as a model to monitor resistance-dependent cellular responses and identify potential therapeutic targets. By means of 2D differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), we investigated the global protein expression alterations induced by pemetrexed treatment and resistance. The proteomic result revealed that pemetrexed exposure obviously altered the expression of 81 proteins in the A549 cells, whereas no significant response was observed in the similarly treated A549/PEM cells, hence implying an association between these proteins and the drug-specific response. Moreover, 72 proteins including flavin reductase and calreticulin demonstrated differential expression between the A549 and A549/PEM cells, indicating baseline resistance. Additional tests employed siRNA silencing, protein overexpression, cell viability analysis, and analysis of apoptosis to examine and confirm the potency of flavin reductase and calreticulin proteins in the development of pemetrexed resistance. In summary, by using a proteomic approach, we identified numerous proteins, including flavin reductase and calreticulin, involved in pemetrexed drug resistance-developing mechanisms. Our results provide useful diagnostic markers and therapeutic candidates for pemetrexed-resistant lung cancer treatment.

Mitochondrial proteomics with siRNA knockdown to reveal ACAT1 and MDH2 in the development of doxorubicin-resistant uterine cancer.

Mitochondria are key organelles in mammary cells in responsible for a number of cellular functions including cell survival and energy metabolism. Moreover, mitochondria are one of the major targets under doxorubicin treatment. In this study, low-abundant mitochondrial proteins were enriched for proteomic analysis with the state-of-the-art two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assistant laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy to compare and identify the mitochondrial protein profiling changes in response to the development of doxorubicin resistance in human uterine cancer cells. The mitochondrial proteomic results demonstrate more than fifteen hundred protein features were resolved from the equal amount pooled of three purified mitochondrial proteins and 101 differentially expressed spots were identified. In which, 39 out of these 101 identified proteins belong to mitochondrial proteins. Mitochondrial proteins such as acetyl-CoA acetyltransferase (ACAT1) and malate dehydrogenase (MDH2) have not been reported with the roles on the formation of doxorubicin resistance in our knowledge. Further studies have used RNA interference and cell viability analysis to evidence the essential roles of ACAT1 and MDH2 on their potency in the formation of doxorubicin resistance through increased cell viability and decreased cell apoptosis during doxorubicin treatment. To sum up, our current mitochondrial proteomic approaches allowed us to identify numerous proteins, including ACAT1 and MDH2, involved in various drug-resistance-forming mechanisms. Our results provide potential diagnostic markers and therapeutic candidates for the treatment of doxorubicin-resistant uterine cancer.

Preparation and in vitro characterization of pluronic-attached polyamidoamine dendrimers for drug delivery.

CONTEXT: Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as drug carriers. And little study about whether pluronic-attached PAMAM dendrimers could be potential drug delivery systems has been carried on. OBJECTIVE: Pluronic F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers. METHODS: Two conjugation ratios of PF127-attached PAMAM dendrimers were synthesized. (1)H nuclear magnetic resonance ((1)H-NMR), Fourier transform infrared spectrum (FTIR), element analysis and ninhydrin assay were used to characterize the conjugates. Size, zeta potential and critical micelle concentrations (CMC) were also detected. And DOX was incorporated into the hydrophobic interior of the conjugates. Studies on their drug loading and drug release were carried on. Furthermore, hemolysis and cytotoxicity assay were used to evaluate the toxicity of the conjugates. RESULTS AND DISCUSSION: PF127 was successfully conjugated to the fifth generation PAMAM dendrimer at two molar ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The conjugates showed an increased size and a reduced zeta potential. And higher CMC values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer, PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of 57% conjugation ratio. And the maximum is ∼12.87 DOX molecules per conjugate molecule. Moreover, the complexes showed a sustained release behavior compared to pure DOX. CONCLUSION: Findings from the in vitro study show that the PF127-attached PAMAM dendrimers may be potential carriers for drug delivery.

Identification of up- and down-regulated proteins in doxorubicin-resistant uterine cancer cells: reticulocalbin-1 plays a key role in the development of doxorubicin-associated resistance.

Drug resistance is a frequent cause of failure in cancer chemotherapy treatments. In this study, a pair of uterine sarcoma cancer lines, MES-SA, and doxorubicin-resistant partners, MES-SA/DxR-2µM cells and MES-SA/DxR-8µM cells, as a model system to investigate resistance-dependent proteome alterations and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to perform this research and the results revealed that doxorubicin-resistance altered the expression of 208 proteins in which 129 identified proteins showed dose-dependent manners in response to the levels of resistance. Further studies have used RNA interference, H2A.X phosphorylation assay, cell viability analysis, and analysis of apoptosis against reticulocalbin-1 (RCN1) proteins, to prove its potency on the formation of doxorubicin resistance as well as the attenuation of doxorubicin-associated DNA double strand breakage. To sum up, our results provide useful diagnostic markers and therapeutic candidates such as RCN1 for the treatment of doxorubicin-resistant uterine cancer.

Proteomic analysis of rhein-induced cyt: ER stress mediates cell death in breast cancer cells.

Rhein is a natural product purified from herbal plants such as Rheum palmatum, which has been shown to have anti-angiogenesis and anti-tumor metastasis properties. However, the biological effects of rhein on the behavior of breast cancers are not completely elucidated. To evaluate whether rhein might be useful in the treatment of breast cancer and its cytotoxic mechanism, we analyzed the impact of rhein treatment on differential protein expression as well as redox regulation in a non-invasive breast cancer cell line, MCF-7, and an invasive breast cancer cell line, MDA-MB-231, using lysine- and cysteine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF mass spectrometry. This proteomic study revealed that 73 proteins were significantly changed in protein expression; while 9 proteins were significantly altered in thiol reactivity in both MCF-7 and MDA-MB-231 cells. The results also demonstrated that rhein-induced cytotoxicity in breast cancer cells mostly involves dysregulation of cytoskeleton regulation, protein folding, the glycolysis pathway and transcription control. A further study also indicated that rhein promotes misfolding of cellular proteins as well as unbalancing of the cellular redox status leading to ER-stress. Our work shows that the current proteomic strategy offers a high-through-put platform to study the molecular mechanisms of rhein-induced cytotoxicity in breast cancer cells. The identified differentially expressed proteins might be further evaluated as potential targets in breast cancer therapy.

An application of virtual microscopy in the teaching of an oral and maxillofacial pathology laboratory course.

OBJECTIVE: The aim of this study is to share the experience of establishing a virtual microscope and telepathology system for the oral and maxillofacial pathology laboratory course in a dental school. STUDY DESIGN: A dot-slide system has been used to generate digitized microscopic slides, which are placed on an image server that is available online. RESULTS: Using software that is available as a free download (OlyVIA), students are able to select a teaching slide record, view at magnifications comparable with those of a conventional microscope, and navigate to any area on the matching virtual slide image that is stored on the image server database. Before class, the students can review the findings of the virtual teaching slides at any time or any place via broadband internet by using the instructions available on DVD. During class, students report and discuss the histological findings of the virtual teaching slides with tutors who evaluate, test, and make constructive comments on the presentations in a Web-based computer classroom. After class, students can revise the histological findings of the microscopic virtual slides available on the server. CONCLUSIONS: Virtual microscopy has many advantages over real microscopy in oral and maxillofacial pathology education. Furthermore, telepathology could also be applied in other pathological services, such as intraoperative frozen sections, routine surgical pathology, and subspecialty consultation.