The Guizhi Gancao Decoction Attenuates Myocardial Ischemia-Reperfusion Injury by Suppressing Inflammation and Cardiomyocyte Apoptosis.

Guizhi Gancao Decoction (GGD) is a well-known traditional Chinese herbal medicine for the treatment of various cardiovascular diseases, such as myocardial ischemia-reperfusion (I/R) injury and arrhythmia. However, the mechanism by which GGD contributes to the amelioration of cardiac injury remains unclear. The aim of this study was to investigate the potential protective role of GGD against myocardial I/R injury and its possible mechanism. Consistent with the effect of the positive drug (Trimetazidine, TMZ), we subsequently validated that GGD could ameliorate myocardial I/R injury as evidenced by histopathological examination and triphenyltetrazolium chloride (TTC) staining. Moreover, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated that GGD suppressed myocardial apoptosis, which may be related to the upregulation of Bcl-2, PPARα, and PPARγ and downregulation of Bax, caspase-3, and caspase-9. Pretreatment with GGD attenuated the levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin- (IL-) 6, and IL-1ß in serum by inhibiting Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. These results indicated that GGD exhibits cardioprotective effects on myocardial I/R injury through inhibition of the TLR4/NF-κB signaling pathway, which led to reduced inflammatory response and the subsequent cardiomyocyte apoptosis.

Valsartan regulates TGF-ß/Smads and TGF-ß/p38 pathways through lncRNA CHRF to improve doxorubicin-induced heart failure.

This study investigated the interaction among valsartan (VAL), TGF-ß pathways, and long non-coding RNA (lncRNA) cardiac hypertrophy-related factor (CHRF) in doxorubicin (DOX)-induced heart failure (HF), and explored their roles in DOX-induced HF progression. HF mice models in vivo were constructed by DOX induction. The expression of CHRF and TGF-ß1 in hearts was detected, along with cardiac function, caspase-3 activity, and cell apoptosis. Primary myocardial cells were pretreated with VAL, followed by DOX induction in vitro for functional studies, including the detection of cell apoptosis with terminal deoxynucleotidyl transferase dUTP nick-end labeling and the expression of proteins associated with TGF-ß1 pathways. HF models were established in vivo and in vitro. Expression of CHRF and TGF-ß1 was up-regulated, and cell apoptosis and caspase-3 activity were increased in the hearts and cells of the HF models. VAL supplementation alleviated the cardiac dysfunction and injury in the HF process. Moreover, overexpressed CHRF up-regulated TGF-ß1, promoted myocardial cell apoptosis, and reversed VAL's cardiac protective effect, while interference of CHRF (si-CHRF) did the opposite. Down-regulation of CHRF reversed the increased expression of TGF-ß1 and the downstream proteins induced by pcDNA-TGF-ß1 in HL-1 cells, while overexpression of CHRF reversed the VAL's cardiac protective effect in vivo. In conclusion, VAL regulates TGF-ß pathways through lncRNA CHRF to improve DOX-induced HF.

Common variants of KCNJ10 are associated with susceptibility and anti-epileptic drug resistance in Chinese genetic generalized epilepsies.

To explore genetic mechanism of genetic generalized epilepsies (GGEs) is challenging because of their complex heritance pattern and genetic heterogeneity. KCNJ10 gene encodes Kir4.1 channels and plays a major role in modulating resting membrane potentials in excitable cells. It may cause GGEs if mutated. The purpose of this study was to investigate the possible association between KCNJ10 common variants and the susceptibility and drug resistance of GGEs in Chinese population. The allele-specific MALDI-TOF mass spectrometry method was used to assess 8 single nucleotide polymorphisms (SNPs) of KCNJ10 in 284 healthy controls and 483 Chinese GGEs patients including 279 anti-epileptic drug responsive patients and 204 drug resistant patients. We found the rs6690889 TC+TT genotypes were lower frequency in the GGEs group than that in the healthy controls (6.7% vs 9.5%, p = 0.01, OR = 0.50[0.29-0.86]). The frequency of rs1053074 G allele was lower in the childhood absence epilepsy (CAE) group than that in the healthy controls (28.4% vs 36.2%, p = 0.01, OR = 0.70[0.53-0.93]). The frequency of rs12729701 G allele and AG+GG genotypes was lower in the CAE group than that in the healthy controls (21.2% vs 28.4%, p = 0.01, OR = 0.74[0.59-0.94] and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72-0.96], respectively). The frequency of rs12402969 C allele and the CC+CT genotypes were higher in the GGEs drug responsive patients than that in the drug resistant patients (9.3% vs 5.6%, OR = 1.73[1.06-2.85], p = 0.026 and 36.3% vs 48.1%, p = 0.01, OR = 0.83[0.72-0.96], respectively). This study identifies potential SNPs of KCNJ10 gene that may contribute to seizure susceptibility and anti-epileptic drug resistance.

A strategy for detecting absorbed bioactive compounds for quality control in the water extract of rhubarb by ultra performance liquid chromatography with photodiode array detector.

OBJECTIVE: To detect absorbed bioactive compounds of the water extract whose pharmacodynamic effect was craniocerebral protection for quality control assessment. METHODS: Anthraquinones in water extract of rhubarb (WER), in cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI) and in ipsilateral cortex of TBI rats following oral WER were respectively explored by ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method developed in the present study. The effects of anthraquinones absorbed into injured cortex on superoxidase dismutase (SOD) activity in TBI rats were detected. The antioxidative anthraquinones absorbed into target organ were evaluated for quality control of WER. RESULTS: Anthraquinones in WER were aloe-emodin, rhein, emodin, chrysophanol, and physcion. Only the last anthraquinone was found in CSF and in ipsilateral cortex under this chromatographic condition. Physcion increased SOD activity in TBI rats significantly. CONCLUSIONS: Physcion was the main active compound of rhubarb against craniocerebral injury via antioxidant pathway. According to our strategy, the exploration of physcion suggested the possibility of a novel quality control of WER in treating TBI injury.

Dan-Shen-Yin protects the heart against inflammation and oxidative stress induced by acute ischemic myocardial injury in rats.

Dan-Shen-Yin (DSY) is a well-known traditional Chinese formula which is widely used in clinical practice for the treatment of coronary heart disease (CHD) and has produced a favorable effect in China. The present study was designed to examine whether or not acute oral DSY can protect the heart against myocardial infarction in acute myocardial ischemic rats. If so, we would then investigate the anti-inflammatory and anti-oxidant mechanisms involved. The left anterior descending coronary artery was occluded to induce myocardial ischemia in the hearts of Sprague-Dawley rats. At the end of the 3-h ischemic period (or 24 h for infarction size), we measured the myocardial infarction size, inflammatory factors and the activities of anti-oxidative enzymes. DSY reduced the infarction size and the serum levels of C-reactive protein, interleukin-6, tumour necrosis factor-α and malondialdehyde and increased the activities of superoxide dismutase and the serum levels of glutathione. The results show that DSY exerts significant cardioprotective effects against acute ischemic myocardial injury in rats, possibly through its anti-inflammatory and anti-oxidant properties, and may thus be used as a potential therapeutic reagent for the treatment of CHD.

Prognostic significance of urine neutrophil gelatinase-associated lipocalin in patients with septic acute kidney injury.

Acute kidney injury (AKI) is a common clinical problem which occurs in critically ill patients. Sepsis is now recognized as the most important contributing factor to AKI in this population. In clinical practice, certain studies have explored the urine neutrophil gelatinase-associated lipocalin (uNGAL) and the urine kidney injury molecule-1 (uKIM-1) as diagnostic and prognostic indices of AKI. Yet, it remains unclear whether uNGAL and uKIM-1 are associated with measures of disease severity and with adverse clinical outcomes in patients with established septic AKI of mixed cause and severity. Ninety-two septic patients with AKI were enrolled in a pilot study to test whether uKIM and uNGAL levels predict 180-day mortality. We initially performed univariate Cox proportional hazards analyses incorporating multiple demographic, clinical and laboratory variables. As a result, the APACHE II score (p= 0.014) and uNGAL (p= 0.015) were identified as independent predictors of 180-day mortality. On the other hand, there was no statistical difference in event-free survival between patients with and without higher serum creatinine, creatinine clearance and uKIM-1 (data not shown). In conclusion, uNGAL may be a promising predictor for septic patients with AKI, resulting in a clear increase in 180-day mortality. Further clinical evaluation of uNGAL is underway.