This study is to investigate the effects of paeoniflorin on cerebral blood flow and the balance of PGI2/TXA2 of rats with focal cerebral ischemia-reperfusion injury. A total of 72 SD rats (3) were randomly divided into 6 groups: sham operation group, cerebral ischemia-reperfusion model group (I/R gourp), low (10 mg.kg-1), middle (20 mg.kg-1) and high (40 mg.kg-1) doses of paeoniflorin groups and nimrnodipine group. Focal cerebral ischemia in rats was made by inserting a monofilament suture into internal carotid artery for 90 min and then reperfused for 24 h. The effects of paeoniflorin on neurological deficit scores and the infarction volume of brain were detected. Relative regional cerebral blood flow (rCBF) was continuously monitored over ischemic hemispheres by laser-Doppler flowmetry (LDF). The expression of COX-2 in hippocampal CAl region was estimated by immunohistochemistry and the contents of prostacyclin I2 (PGI2), thromboxane A2 (TXA2), and ratio of PGIJ2/TXA2 in serum were measured by ELISA kits. Paeoniflorin significantly ameliorated neurological scores, reduced the infarction volume, and increased regional cerebral blood flow relative to the I/R group. In addition, paeoniflorin could inhibit COX-2 expression and the release of TXA2 and prevent the downregulation of PGI2 induced by I/R injury. The neuroprotective effects of paeoniflorin against focal cerebral ischemia-reperfusion rats might be attributed to improve the supply of injured hemisphere blood flow and adjust the balance between PGI2/TXA2.
6-Ketoprostaglandin F1 alpha ; blood ; Animals ; Brain ; blood supply ; CA1 Region, Hippocampal ; metabolism ; Cyclooxygenase 2 ; metabolism ; Glucosides ; isolation & purification ; pharmacology ; Infarction, Middle Cerebral Artery ; blood ; metabolism ; pathology ; physiopathology ; Male ; Monoterpenes ; isolation & purification ; pharmacology ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Paeonia ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Regional Blood Flow ; drug effects ; Reperfusion Injury ; metabolism ; physiopathology ; Thromboxane B2 ; blood

Aim To study whether there was arterial heterogeneity and association with L-type calcium channel (LCC) in different parts of arteries in re-sponse to certain vasoconstrictor. Methods The aor-ta, renal arteries and coronary arteries were dissected from rats. Arterial ring contractions induced by pheny-lephrine (Phe), 5-hydroxyl tryptamine (5-HT) or U46619 in concentration-dependent manner were meas-ured using the Multi Myograph system and the response to nifedipne was observed. Results (1) Phe had no obvious effect on the tension of coronary artery,but in-duced concentration-dependent vasoconstriction in aor-ta and renal artery,and pEC50of aorta was significantly higher than that of renal artery (P<0.05). The inhi-bition rate of nifedipine on the aortic contractile re-sponses was significantly higher than that of renal arter-y (P<0.05). (2) The contraction induced by 5-HT on aorta was not obvious, but was significant on renal artery and coronary artery. The inhibitory rate of nife-dipine on coronary artery vasoconstriction was signifi-cantly higher than that of renal artery (P <0.05). (3) U46619 could induce aorta,renal artery and coro-nary artery concentration- dependent contraction, but the Emaxof them were both higher than that of renal ar-tery (P<0.05). And the pEC50of aorta was the lar-gest (P<0.05). Nifedipine significantly inhibited the contraction of aorta, renal artery and coronary artery induced by U46619 with the greatest inhibitory rate on the coronary artery vasoconstriction and minimal inhibi-tion on aortic vasoconstriction. Conclusions The re-sponse to certain vasoconstrictor is different among aor-ta, renal artery and coronary artery in rats, and the contraction mediated by L-type calcium channel is also different.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

Exosome is a specific subset of vesicles from intracellular origin vesicles containing varies of microRNAs, mRNAs, proteins and lipids. It has been demonstrated that contents of exosomes could be altered due to different physiological and pathological stress, which could be used as clinical biomarker to reveal the disease state. In addition, according to previous studies, exosomes could exert protective roles for cardiovascular diseases such as atherosclerosis, myocardial infarction and ischemia/reperfusion injury, etc. The aim of this review is to summarize current research progress on exosomes, related implications in diagnosis and treatment of cardiovascular diseases and corresponding mechanisms.

AIM:To investigate the changes of cardiac structure and function in rats with type 2 diabetic melli-tus(T2DM),and to explore the mechanisms underlying diabetic cardiomyopathy.METHODS:The cardiac structure and function were measured by echocardiography in Zucker diabetic fatty(ZDF)rats and their control Zucker lean(ZL)rats. The size of the cardiomyocytes was determined by wheat germ agglutinin staining.The protein expression of atrial natriuretic peptide(ANP),β-myosin heavy chain(β-MHC), receptor for advanced glycation end products(RAGE), L-type cal-cium channel α1C subunit(CaV1.2)and Orai1 was assessed by Western blot.RESULTS:Compared with the ZL control rats,the thickness of left ventricular wall,ejection fraction(EF),fractional shortening(FS)and the sizes of cardiomyo-cytes were significantly increased,and diastolic function was decreased in the ZDF rats(P<0.05).The protein expression of β-MHC, ANP, RAGE and Orai1 was increased, while the expression of Ca V1.2 was decreased in ZDF rats(P <0.05).CONCLUSION:T2DM rats show the prominent features including cardiomyocyte hypertrophy,ventricular hyper-trophy and compensatory enhancement of cardiac function, and the Ca2+handling and increase in RAGE expression may play important roles in the processes.

BACKGROUND: Endotoxin tolerance (ET) is a protective phenomenon in which pre-treatment with a tolerance dose of lipopolysaccharide (LPS) leads to dramatically elevated survival. Accumulating evidence has shown that peripheral T cells contribute to the induction of ET. However, what happens to T cell development in the thymus under ET conditions remains unclear. The purpose of this study was to analyze the alterations in thymocyte populations (double-positive [DP] and single-positive [SP] cells) under ET conditions. METHODS: Mice were intraperitoneally injected with LPS at a concentration of 5 mg/kg to establish an LPS tolerance model and were divided into two groups: a group examined 72 h after LPS injection (72-h group) and a group examined 8 days after LPS injection (8-day group). Injection of phosphate-buffered saline was used as a control (control group). Changes in thymus weight, cell counts, and morphology were detected in the three groups. Moreover, surface molecules such as CD4, CD8, CD44, CD69, and CD62L were analyzed using flow cytometry. Furthermore, proliferation, apoptosis, cytokine production, and extracellular signal-regulated kinase (ERK) pathway signaling were analyzed in thymocyte populations. The polymorphism and length of the T-cell receptor (TCR) β chain complementarity-determining region 3 (CDR3) were analyzed using capillary electrophoresis DNA laser scanning analysis (ABI 3730). RESULTS: Thymus weight and cell counts were decreased in the early stage but recovered by the late stage in a murine model of LPS-induced ET. Moreover, the proportions of DP cells (control: 72.130 ± 4.074, 72-h: 10.600 ± 3.517, 8-day: 84.770 ± 2.228), CD4+ SP cells (control: 15.770 ± 4.419, 72-h: 44.670 ± 3.089, 8-day: 6.367 ± 0.513), and CD8+ SP cells (control: 7.000 ± 1.916, 72-h: 34.030 ± 3.850, 8-day: 5.133 ± 0.647) were obviously different at different stages of ET. The polymorphism and length of TCR β chain CDR3 also changed obviously, indicating the occurrence of TCR rearrangement and thymocyte diversification. Further analysis showed that the expression of surface molecules, including CD44, CD69, and CD62L, on thymocyte populations (DP and SP cells) were changed to different degrees. Finally, the proliferation, apoptosis, cytokine production, and ERK pathway signaling of thymocyte populations were changed significantly. CONCLUSION These data reveal that alterations in thymocyte populations might contribute to the establishment of ET.
Animals ; CD4-Positive T-Lymphocytes ; Cell Differentiation ; Endotoxins/toxicity* ; Flow Cytometry ; Mice ; Signal Transduction ; Thymocytes ; Thymus Gland

Aim To observe the effects of sacubitril/valsartan (Sac/Val, LCZ696) on atrial remodeling and atrial fibrillation (AF) susceptibility in spontaneously hypertensive rats (SHR). Methods Twenty-four 7-week-old male SHR were randomly divided into SHR group, SHR + Val group (30 mg · kg

Aim To explore type 1 diabetes mice and the advance glycation end products (AGE) involved in electrical remodeling of atrial myocytes. Methods The diabetic mouse model was induced by intraperitoneal injection of STZ; action potential duration, and the current density of I

Aim To investigate the role of Ca

Aim To observe whether the mechanosensitive ion channel Piezo1 was involved in the senescence of atrial fibroblasts by activating β-catenin based on our previous study which found marked increase of Piezo1 mRNA in senescent atrial fibroblasts. Methods Primary mouse atrial fibroblasts (MAFs) were isolated from male C57BL/6 mice (3-4 weeks) by enzyme digestion, and tert-butyl hydroperoxide (TBHP) was used to induce the senescence of cells. The ratio of senescent cells was detected by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein levels of Piezo1, β-catenin/p-β-catenin, senescence-associated proteins p53 and p21 in the cells treated with TBHP (100 μmol · L