Paeonol Protects Memory after Ischemic Stroke via Inhibiting β-Secretase and Apoptosis

Poststroke dementia commonly occurs following stroke, with its pathogenesis related to β-amyloid production and apoptosis. The present study evaluate the effects of paeonol, one of the phenolic phytochemicals isolated from the Chinese herb Paeonia suffruticosa Andrews (MC), on protection from memory loss after ischemic stroke in the subacute stage. Rats were subjected to transient middle cerebral artery occlusion (tMCAo) with 10 min of ischemia. The data revealed that paeonol recovered the step-through latency in the retrieval test seven days after tMCAo, but did not improve the neurological deficit induced by tMCAo. Levels of Amyloid precursor protein (APP)- and beta-site APP cleaving enzyme (BACE; β-secretase)-immunoreactive cells, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells decreased in the paeonol-administered group. Western blotting revealed decreased levels of Bax protein in mitochondria and apoptosis-inducing factor (AIF) in cytosol following paeonol treatment. In conclusion, we speculate that paeonol protected memory after ischemic stroke via reducing APP, BACE, and apoptosis. Supression the level of Bax and blocking the release of AIF into cytosol might participate in the anti-apoptosis provided by paeonol

Neuroprotective Effect of Paeonol Mediates Anti-Inflammation via Suppressing Toll-Like Receptor 2 and Toll-Like Receptor 4 Signaling Pathways in Cerebral Ischemia-Reperfusion Injured Rats

Paeonol is a phenolic compound derived from Paeonia suffruticosa Andrews (MC) and P. lactiflora Pall (PL). Paeonol can reduce cerebral infarction volume and improve neurological deficits through antioxidative and anti-inflammatory effects. However, the anti-inflammatory pathway of paeonol remains unclear. This study investigated the relationship between anti-inflammatory responses of paeonol and signaling pathways of TLR2 and TLR4 in cerebral infarct. We established the cerebral ischemia-reperfusion model in Sprague Dawley rats by occluding right middle cerebral artery for 60 min, followed by reperfusion for 24 h. The neurological deficit score was examined, and the brains of the rats were removed for cerebral infarction volume and immunohistochemistry (IHC) analysis. The infarction volume and neurological deficits were lower in the paeonol group (pretreatment with paeonol; 20 mg/kg i.p.) than in the control group (without paeonol treatment). The IHC analysis revealed that the number of TLR2-, TLR4-, Iba1-, NF-κB- (P50-), and IL-1β-immunoreactive cells and TUNEL-positive cells was significantly lower in the paeonol group; however, the number of TNF-α-immunoreactive cells did not differ between the paeonol and control groups. The paeonol reveals some neuroprotective effects in the model of ischemia, which could be due to the reduction of many proinflammatory receptors/mediators, although the mechanisms are not clear

Knockdown of PsbO leads to induction of HydA and production of photobiological H2 in the green alga Chlorella sp. DT

Green algae are able to convert solar energy to H2 via the photosynthetic electron transport pathway under certain conditions. Algal hydrogenase (HydA, encoded by HYDA) is in charge of catalyzing the reaction: 2H+ + 2e− ↔ H2 but usually inhibited by O2, a byproduct of photosynthesis. The aim of this study was to knockdown PsbO (encoded by psbO), a subunit concerned with O2 evolution, so that it would lead to HydA induction. The alga, Chlorella sp. DT, was then transformed with short interference RNA antisense-psbO (siRNA-psbO) fragments. The algal mutants were selected by checking for the existence of siRNA-psbO fragments in their genomes and the low amount of PsbO proteins. The HYDA transcription and the HydA expression were observed in the PsbO-knockdown mutants. Under semi-aerobic condition, PsbO-knockdown mutants could photobiologically produce H2 which increased by as much as 10-fold in comparison to the wild type

Open lung biopsy in early-stage acute respiratory distress syndrome

INTRODUCTION: Acute respiratory distress syndrome (ARDS) has heterogeneous etiologies, rapid progressive change and a high mortality rate. To improve the outcome of ARDS, accurate diagnosis is essential to the application of effective early treatment. The present study investigated the clinical effects and safety of open lung biopsy (OLB) in patients with early-stage ARDS of suspected non-infectious origin. METHODS: We undertook a retrospective study of 41 patients with early-stage ARDS (defined as one week or less after intubation) who underwent OLB in two medical intensive care units of a tertiary care hospital from 1999 to 2005. Data analyzed included baseline characteristics, complication rate, pathological diagnoses, treatment alterations, and hospital survival. RESULTS: The age of patients was 55 ± 17 years (mean ± SD). The average ratio of arterial partial pressure of oxygen (PaO(2)) to fraction of inspired oxygen (FiO(2)) was 116 ± 43 mmHg (mean ± SD) at biopsy. Seventeen patients (41%) were immunocompromised. Postoperative complications occurred in 20% of patients (8/41). All biopsies provided a pathological diagnosis with a diagnostic yield of 100%. Specific pathological diagnoses were made for 44% of patients (18/41). Biopsy findings led to an alteration of treatment modality in 73% of patients (30/41). The treatment alteration rate was higher in patients with nonspecific diagnoses than in patients with specific diagnoses (p = 0.0024). Overall mortality was 50% (21/41) and was not influenced by age, gender, pre-OLB oxygenation, complication rate, pathological results, and alteration of treatment. There was no surgery-related mortality. The survival rate for immunocompromised patients was better than that for immunocompetent patients (71% versus 33%; p = 0.0187) in this study. CONCLUSION: Our retrospective study suggests that OLB was a useful and acceptably safe diagnostic procedure in some selected patients with early-stage ARDS

The risk of false inclusion of a relative in parentage testing – an in silico population study

Aim To investigate the potential of false inclusion of a close genetic relative in paternity testing by using computer generated families. Methods 10 000 computer-simulated families over three generations were generated based on genotypes using 15 short tandem repeat loci. These data were used in assessing the probability of inclusion or exclusion of paternity when the father is actually a sibling, grandparent, uncle, half sibling, cousin, or a random male. Further, we considered a duo case where the mother’s DNA type was not available and a trio case including the mother’s profile. Results The data showed that the duo scenario had the highest and lowest false inclusion rates when considering a sibling (19.03 ± 0.77%) and a cousin (0.51 ± 0.14%) as the father, respectively; and the rate when considering a random male was much lower (0.04 ± 0.04%). The situation altered slightly with a trio case where the highest rate (0.56 ± 0.15%) occurred when a paternal uncle was considered as the father, and the lowest rate (0.03 ± 0.03%) occurred when a cousin was considered as the father. We also report on the distribution of the numbers for non-conformity (non-matching loci) where the father is a close genetic relative. Conclusions The results highlight the risk of false inclusion in parentage testing. These data provide a valuable reference when incorporating either a mutation in the father’s DNA type or if a close relative is included as being the father; particularly when there are varying numbers of non-matching loci

A novel strategy for sibship determination in trio sibling model

Aim To use a virtually simulated population, generated from published allele frequencies based on 15 short tandem repeats (STR), to evaluate the efficacy of trio sibship testing and sibling assignment for forensic purposes. Methods Virtual populations were generated using 15 STR loci to create a large number of related and unrelated genotypes (10 000 trio combinations). Using these virtual populations, the probability of related and unrelated profiles can be compared to determine the chance of inclusions of being siblings if they are true siblings and the chance of inclusion if they are unrelated. Two specific relationships were tested – two reference siblings were compared to a third true sibling (3S trio, sibling trio) and two reference siblings were compared to an unrelated individual (2S1U trio, non-sibling trio). Results When the likelihood ratio was greater than 1, 99.87% of siblings in the 3S trio population were considered as siblings (sensitivity); 99.88% of non-siblings in the 2S1U trio population were considered as non-siblings (specificity); 99.9% of both populations were identified correctly as siblings and non-siblings; and the accuracy of the test was 99.88%. Conclusions The high sensitivity and specificity figures when using two known siblings compared to a putative sibling are significantly greater than when using only one known relative. The data also support the use of increasing number of loci allowing for greater confidence in genetic identification. The system established in this study could be used as the model for evaluating and simulating the cases with multiple relatives

A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer

Crosstalk between the androgen receptor (AR) and other signaling pathways in prostate cancer (PCa) severely affects the therapeutic outcome of hormonal therapy. Although anti-androgen therapy prolongs overall survival in PCa patients, resistance rapidly develops and is often associated with increased AR expression and upregulation of the HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually fails due to the reciprocal feedback loop. Previously, we reported that wedelolactone, apigenin, and luteolin are the active compounds in Wedelia chinensis herbal extract, and act synergistically to inhibit the AR activity in PCa. Here, we further demonstrated that an herbal extract of W. chinensis (WCE) effectively disrupted the AR, HER2/3, and AKT signaling networks and therefore enhanced the therapeutic efficacy of androgen ablation in PCa. Furthermore, WCE remained effective in suppressing AR and HER2/3 signaling in an in vivo adapted castration-resistant PCa (CRPC) LNCaP cell model that was insensitive to androgen withdrawal and second-line antiandrogen, enzalutamide. This study provides preclinical evidence that the use of a defined, single plant-derived extract can augment the therapeutic efficacy of castration with significantly prolonged progression-free survival. These data also establish a solid basis for using WCE as a candidate agent in clinical studies

The risk of false inclusion of a relative in parentage testing - an in silico population study FORENSIC SCIENCE

Aim To investigate the potential of false inclusion of a close genetic relative in paternity testing by using computer generated families. Methods 10 000 computer-simulated families over three generations were generated based on genotypes using 15 short tandem repeat loci. These data were used in assessing the probability of inclusion or exclusion of paternity when the father is actually a sibling, grandparent, uncle, half sibling, cousin, or a random male. Further, we considered a duo case where the mother's DNA type was not available and a trio case including the mother's profile. Results The data showed that the duo scenario had the highest and lowest false inclusion rates when considering a sibling (19.03 ± 0.77%) and a cousin (0.51 ± 0.14%) as the father, respectively; and the rate when considering a random male was much lower (0.04 ± 0.04%). The situation altered slightly with a trio case where the highest rate (0.56 ± 0.15%) occurred when a paternal uncle was considered as the father, and the lowest rate (0.03 ± 0.03%) occurred when a cousin was considered as the father. We also report on the distribution of the numbers for non-conformity (non-matching loci) where the father is a close genetic relative. Conclusions The results highlight the risk of false inclusion in parentage testing. These data provide a valuable reference when incorporating either a mutation in the father's DNA type or if a close relative is included as being the father; particularly when there are varying numbers of non-matching loci