Pachymic acid ameliorates bleomycin-induced pulmonary fibrosis through inhibiting endoplasmic reticulum stress in rats.

The effect of pachymic acid (PA) on pulmonary fibrosis in rats was expected to be investigated in this study. Firstly, bleomycin (BLM) was used to establish pulmonary fibrosis rat model, then PA (10, 20, or 40 mg/kg) was intragastrically administered to the rats for 14 days. Subsequently, a variety of tests was performed to observe changes in sample tissues after different treatments. Briefly, the degree of pulmonary edema in rats was assessed through dry/wet weight ratio. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were used to observe the pathological injury and fibrosis of lung tissue. Biochemical kits were applied to measure the levels of hydroxyproline (Hyp), transforming growth factor beta-1 (TGFß-1), malondialdehyde (MDA), reactive oxygen species (ROS), and adenosine triphosphate (ATP) and the activities of superoxide dismutase (SOD) and catalase (CAT) in rat lung tissues of each group. The mitochondrial DNA (mtDNA) copy number in rat lung tissue was tested using qRT-PCR. Additionally, the western blot was employed to detect the expression levels of pulmonary fibrosis-related proteins and endoplasmic reticulum (ER) stress-related proteins in each group of rat lung tissue. By virtue of experimental verification above, PA was discovered to alleviate BLM-induced pulmonary edema, pulmonary fibrosis and histopathological damage. On the one hand, PA treatment decreased Hyp and TGF-ß1 levels and down-regulated pulmonary fibrosis-related protein expression [collagen I, α-smooth muscle actin (α-SMA), and fibronectin] in the lung tissue of BLM rats. On the other hand, it significantly increased the levels of SOD, CAT and ATP while decreased the activities of MDA and ROS in BLM rat lung tissues. In addition, the expression levels of ER stress-related proteins [glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), Caspase 9, and activating transcription factor 4 (ATF4)] were significantly down-regulated in the lung tissue of BLM rats after PA treatment. Collectively, PA may ameliorate BLM-induced pulmonary fibrosis and histopathological damage in rats through inhibiting ER stress and improving mitochondrial function.

Platelet-rich Plasma Improves Radiotherapy-induced Emotional Disorder and Cognitive Dysfunction, Neuroinflammation in Aged Rats by Inhibiting the Activation of NLRP3 Inflammasomes.

Although radiotherapy (RT) is the preferred treatment for elderly patients with brain tumors, certain negative effects can't be ignored. Fortunately, platelet-rich plasma (PRP) presents with a promising potential for the treatment of neurological diseases. Therefore, this study aimed to explore the effect of PRP on neuroinflammation, emotional disorder and cognitive dysfunction induced by RT in aged rats. Firstly, whole brain RT (WBRT) model was established by whole brain irradiation with 10 Gy of 6-MeV electron beam in rats. Next, twenty 20-month-old female SD rats were divided into four groups (sham group, PRP group, WBRT group, and WBRT + PRP group) according different treatments. After that, the cognitive dysfunction and depression-like behavior of rats were examined by novel object recognition test (NORT), Morris water maze test (MWM), open field test (OFT) and elevated plus maze test (EPM). Besides, immunohistochemistry was used to detect the expression of microglial marker protein Iba-1 in rat hippocampus; enzyme linked immunosorbent assay (ELISA) to examine the levels of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (IL-1ß), IL-18, and monocyte chemoattractant protein 1 (MCP-1) in rat hippocampus; real-time quantitative reverse transcription PCR (qRT-PCR) and western blot to measure the levels of neurotrophic factors brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B receptor (TrkB), and nerve growth factor (NGF) in rat hippocampus; and western blot also to observe the protein expression levels of NOD-like receptor protein 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC), and IL-1ß in rat hippocampus. After experiments, some results obtained were shown as follows. PRP could significantly improve learning and memory ability and depression-like behavior, increase the level of neurotrophic factors, inhibit the activation of microglia and decrease the level of pro-inflammatory factors in WBRT rats. In addition, PRP significantly inhibited the activation of NLRP3 inflammasomes. To sum up, PRP can ameliorate neuroinflammation, emotional disorder and cognitive dysfunction induced by RT in aged rats, and the mechanism may be related to its inhibitory effect on NLRP3 inflammasome activation.

Intracoronary arterial retrograde thrombolysis with percutaneous coronary intervention: a novel use of thrombolytic to treat acute ST-segment elevation myocardial infarction.

BACKGROUND: Clearance of coronary arterial thrombosis is necessary in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing urgent percutaneous coronary intervention (PCI). There is currently no highly-recommended method of thrombus removal during interventional procedures. We describe a new method for opening culprit vessels to treat STEMI: intracoronary arterial retrograde thrombolysis (ICART) with PCI. METHODS & RESULTS: Eight patients underwent ICART. The guidewire was advanced to the distal coronary artery through the occlusion lesion. Then, we inserted a microcatheter into the distal end of the occluded coronary artery over the guidewire. Urokinase (5-10 wu) mixed with contrast agents was slowly injected into the occluded section of the coronary artery through the microcatheter. The intracoronary thrombus gradually dissolved in 3-17 min, and the effect of thrombolysis was visible in real time. Stents were then implanted according to the characteristics of the recanalized culprit lesion to achieve full revascularization. One patient experienced premature ventricular contraction during vascular revascularization, and no malignant arrhythmias were seen in any patient. No reflow or slow flow was not observed post PCI. Thrombolysis in myocardial infarction flow grade and myocardial blush grade post-primary PCI was 3 in all eight patients. No patients experienced bleeding or stroke. CONCLUSIONS: ICART was accurate and effective for treating intracoronary thrombi in patients with STEMI in this preliminary study. ICART was an effective, feasible, and simple approach to the management of STEMI, and no intraprocedural complications occurred in any of the patients. ICART may be a breakthrough in the treatment of acute STEMI.

Development and validation of clinical risk score to predict the cardiac rupture in patients with STEMI.

BACKGROUND: Cardiac rupture (CR) is a fatal complication of ST-elevation myocardial infarction (STEMI) with poor prognosis. The aim of this study was to develop and validate practical risk score to predict the CR after STEMI. METHODS: A total of 11,234 STEMI patients from 7 centers in China were enrolled in our study, we firstly developed a simplified fast-track CR risk model from 7455 STEMI patients, and then prospectively validated the CR risk model using receiver-operating characteristic (ROC) curves by the other 3779 consecutive STEMI patients. This trial is registered with ClinicalTrials.gov, number NCT02484326. RESULTS: The incidence of CR was 2.12% (238/11,234), and the thirty-day mortality in CR patients was 86%. We developed a risk model which had 7 independent baseline clinical predictors (female sex, advanced age, anterior myocardial infarction, delayed admission, heart rate, elevated white blood cell count and anemia). The CR risk score system differentiated STEMI patients with incidence of CR ranging from 0.2% to 13%. The risk score system demonstrated good predictive value with area under the ROC of 0.78 (95% CI 0.73-0.84) in validation cohort. Primary percutaneous coronary intervention decreased the incidence of CR in high risk group (3.9% vs. 6.2%, p<0.05) and very high risk group (8.0% vs. 15.2%, p<0.05). CONCLUSIONS: A simple risk score system based on 7 baseline clinical variables could identify patients with high risk of CR, for whom appropriate treatment strategies can be implemented.