Delphinidin prevents hypoxia-induced mouse embryonic stem cell apoptosis through reduction of intracellular reactive oxygen species-mediated activation of JNK and NF-κB, and Akt inhibition

Delphinidin, gallic acid, betulinic acid, and ursolic acid, which are bio-active ingredients in a variety of fruits, vegetables, and herbs, have potent antioxidant activity and various biological activities. However, it is not clear whether these bio-active ingredients can significantly contribute to the protection of embryonic stem (ES) cells from hypoxia-induced apoptosis. In the present study, hypoxia-induced ES cells apoptosis with time, which were abrogated by pretreatment with all ingredients. Hypoxia-induced ROS generation was blocked by pretreatment with all ingredients in a dose-dependent manner, with the maximum ROS scavenging effect observed for delphinidin. Hypoxia increased phosphorylation of JNK and NF-κB were blocked by pretreatment of delphinidin as well as NAC. Hypoxia decreased phosphorylation of Akt^thr308 and ^ser473; these decreases were reversed by pretreatment with delphinidin or NAC. However, Akt inhibition did not affect NF-κB phosphorylation. Delphinidin attenuated the hypoxia-induced increase in Bax, cleaved caspase-9, cleaved caspase-3, and decrease in Bcl-2, which were diminished by pretreatment of Akt inhibitor. Hypoxia induced Bax translocation from the cytosol to mitochondria. Furthermore, hypoxia induced mitochondria membrane potential loss and cytochrome c release in cytosol, which were blocked by delphinidin pretreatment. Hypoxia induced cleavage of procaspase-9 and procaspase-3 which were blocked by delphinidin or SP600125, but Akt inhibitor abolished the protection effect of delphinidin. Moreover, inhibition of JNK and NF-κB abolished hypoxia-induced ES cell apoptosis and inhibition of Akt attenuated delphinidin-induced blockage of apoptosis. The results indicate that delphinidin can prevent hypoxia-induced apoptosis of ES cells through the inhibition of JNK and NF-κB phosphorylation, and restoration of Akt phosphorylation.     

Proteomic analysis of kidneys from selenoprotein M transgenic rats in response to increased bioability of selenium

Background

To characterize changes in global protein expression in kidneys of transgenic rats overexpressing human selenoprotein M (SelM) in response to increased bioabivility of selenium (Sel), total proteins extracted from kidneys of 10-week-old CMV/hSelM Tg and wild-type rats were separated by 2-dimensional gel electrophoresis and measured for changes in expression.

Results

Ten and three proteins showing high antioxidant enzymatic activity were up- and down-regulated, respectively, in SelM-overexpressing CMV/hSelM Tg rats compared to controls based on an arbitrary 2-fold difference. Up-regulated proteins included LAP3, BAIAP2L1, CRP2, CD73 antigen, PDGF D, KIAA143 homolog, PRPPS-AP2, ZFP313, HSP-60, and N-WASP, whereas down-regulated proteins included ALKDH3, rMCP-3, and STC-1. After Sel treatment, five of the up-regulated proteins were significantly increased in expression in wild-type rats, whereas there were no changes in CMV/hSelM Tg rats. Only two of the down-regulated proteins showed reduced expression in wild-type and Tg rats after Sel treatment.

Conclusions

These results show the primary novel biological evidences that new functional protein groups and individual proteins in kidneys of Tg rats relate to Sel biology including the response to Sel treatment and SelM expression.     

Prognostic Value of Cancer Stem Cell Marker Aldehyde Dehydrogenase in Ovarian Cancer: A Meta-Analysis

Objective

Aldehyde dehydrogenase (ALDH) has recently been reported as a marker of cancer stem-like cells in ovarian cancer. However, the prognostic role of ALDH in ovarian cancer still remains controversial. In this study, we aimed to evaluate the association between the expression of ALDH and the outcome of ovarian cancer patients by performing a meta-analysis.

Methods

We systematically searched for studies investigating the relationships between ALDH expression and outcome of ovarian cancer patients. Only articles in which ALDH expression was detected by immunohistochemical staining were included. A meta-analysis was performed to generate combined hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and disease-free survival (DFS).

Results

A total of 1,258 patients from 7 studies (6 articles) were included in the analysis. Our results showed that high ALDH expression in patients with ovarian cancer was associated with poor prognosis in terms of Os (HR, 1.25; 95% CI, 1.07-1.47; P = 0.005) and DFS (HR, 1.58; 95% CI, 1.00-2.49; P = 0.052), though the difference for DFS was not statistically significant. In addition, there was no evidence of publication bias as suggested by Begg’s and Egger’s tests (Begg’s test, P = 0.707; Egger’s test, P = 0.355).

Conclusion

The present meta-analysis indicated that elevated ALDH expression was associated with poor prognosis in patients with ovarian cancer.     

A Functional Variant rs1820453 in YAP1 and Breast Cancer Risk in Chinese Population

Background

To investigate the association between rs1820453 which located in the promoter region of yes-associated protein 1 (YAP1) gene and breast cancer (BC) risk.

Method and Findings

We conducted a hospital-based case-control study including a total of 480 BC cases and 545 cancer-free controls in Chinese population. Then the expression quantitative trait locus (e-QTL) analysis was performed to explore the possible function of rs1820453 to the YAP1 gene expression. The association between rs1820453 and BC risk was significantly identified with the odds ratio (OR) was 1.27 (95 % confidence interval (CI) =1.03-1.57) under allelic model when adjusted by age and menopausal status. In addition, the correlation analysis of rs1820453 and YAP1 expression level found that this variant was significantly associated with the gene expression in Chinese population. When compared with level of mRNA expression of the AA genotype (6.011±0.046), the mRNA expression level in CC genotype (5.903±0.026) was statistically lower (P=0.024).

Conclusion

The results from this study suggested that rs1820453 A>C change may affect the gene expression and contribute to the risk of developing BC in Chinese population though larger sample-size studies along with functional experiments were anticipated to warrant the results.     

Diabetic Patients Could Do As Well as Non-Diabetic Patients without Inflammation on Peritoneal Dialysis

Background

Diabetic patients on peritoneal dialysis (PD) have lower survival and are more likely complicated with inflammation than their non-diabetic counterparts. Here, we explored the interaction effects between diabetes and inflammation on the survival of PD patients.

Methods

Overall, 2,264 incident patients were enrolled from a retrospective cohort study in China. Patients were grouped according to the baseline levels of high-sensitive C-reactive protein (hsCRP, ≤3 mg/L or >3 mg/L) or serum albumin (SA, ≥38 g/L or <38 g/L). Then, several multivariable adjusted stratified Cox regression models were constructed for these groups to explore the predicted role of diabetes on all-cause or cardiovascular death under inflammatory or non-inflammatory conditions.

Results

Diabetics on PD were more likely to have inflammation than non-diabetics on PD, and they presented with elevated hsCRP (52.7% vs. 47.3%, P = 0.03) or decreased SA (77.9% vs. 62.7%, P < 0.001) levels. After stratification by size of center and controlling for confounding factors, diabetes was found to predict all-cause death in patients with hsCRP >3 mg/L or SA <38 g/L but not in patients with hsCRP ≤3 mg/L or SA ≥38 g/L. Similarly, the presence of diabetes was an indication of cardiovascular death in patients with hsCRP >3 mg/L or SA <38 g/L. However, if further adjusted by baseline cardiovascular disease, the predicted role of diabetes on death related to cardiovascular disease in patients with SA <38 g/L disappeared.

Conclusion

Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis. Active strategies should be implemented to improve inflammation status in diabetic patients on PD.     

Functional Recovery of Denervated Skeletal Muscle with Sensory or Mixed Nerve Protection: A Pilot Study

Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection) or sural nerve (sensory protection). The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve.     

抗肿瘤多肽研究进展

近些年,具有抗肿瘤生物活性的人工合成多肽受到广泛的关注.尽管受技术条件的制约,目前多数抗肿瘤肽类药物的半衰期较短,但抗肿瘤肽类药物具有其独特的优势:它们分子量小、抗肿瘤特异性高、免疫原性低,并且易于合成和改造.目前,多种抗肿瘤肽及其衍生物已上市或进入临床研究,以肽为基础的治疗不仅高效低毒,还可以增加肿瘤对其他治疗方法的敏感度,对于肿瘤的临床治疗将具有重要价值.综述了诱发肿瘤坏死活性肽、细胞凋亡肽及功能阻断肽等几种新型天然抗肿瘤活性肽诱发肿瘤死亡的作用,并归纳其应用前景.     

Chemical Composition and Antimicrobial Activity of the Essential Oil from the Edible Aromatic Plant Aristolochia delavayi

The essential oil obtained by hydrodistillation from the aerial parts of Aristolochia delavayi Franch. (Aristolochiaceae), a unique edible aromatic plant consumed by the Nakhi (Naxi) people in Yunnan, China, was investigated using GC/MS analysis. In total, 95 components, representing more than 95% of the oil composition, were identified, and the main constituents found were (E)‐dec‐2‐enal (52.0%), (E)‐dodec‐2‐enal (6.8%), dodecanal (3.35%), heptanal (2.88%), and decanal (2.63%). The essential oil showed strong inhibitory activity (96% reduction) of the production of bacterial volatile sulfide compounds (VSC) by Klebsiella pneumoniae, an effect that was comparable with that of the reference compound citral (91% reduction). Moreover, the antimicrobial activity of the essential oil and the isolated major compound against eight bacterial and six fungal strains were evaluated. The essential oil showed significant antibacterial activity against Providencia stuartii and Escherichia coli, with minimal inhibitory concentrations (MIC) ranging from 3.9 to 62.5 μg/ml. The oil also showed strong inhibitory activity against the fungal strains Trichophyton ajelloi, Trichophyton terrestre, Candida glabrata, Candida guilliermondii, and Cryptococcus neoformans, with MIC values ranging from 3.9 to 31.25 μg/ml, while (E)‐dec‐2‐enal presented a lower antifungal activity than the essential oil.