The overall decline in MWSS observed with age may be due to a decrease in flow. However, the marked drop in MWSS between the 48-57 and 58-67 age groups corresponded with an increase in diameter and systolic blood pressure rather than a significant drop in flow.

Since human coronavirus (HCoVs) was first described in the 1960s, seven strains of respiratory human coronaviruses have emerged and caused human infections. After the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), a pneumonia outbreak of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) has represented a pandemic threat to global public health in the 21st century. Without effectively prophylactic and therapeutic strategies including vaccines and antiviral drugs, these three coronaviruses have caused severe respiratory syndrome and high case-fatality rates around the world. In this review, we detail the emergence event, origin and reservoirs of all HCoVs, compare the differences with regard to structure and receptor usage, and summarize therapeutic strategies for COVID-19 that cause severe pneumonia and global pandemic.

Extracellular matrix (ECM) stiffness has profound effects on the regulation of cell functions. DNA methylation is an important epigenetic modification governing gene expression. However, the effects of ECM stiffness on DNA methylation remain elusive. Here, it is reported that DNA methylation is sensitive to ECM stiffness, with a global hypermethylation under stiff ECM condition in mouse embryonic stem cells (mESCs) and embryonic fibroblasts compared with soft ECM. Stiff ECM enhances DNA methylation of both promoters and gene bodies, especially the 5’ promoter regions of pluripotent genes. The enhanced DNA methylation is functionally required for the loss of pluripotent gene expression in mESCs grown on stiff ECM. Further experiments reveal that the nuclear transport of DNA methyltransferase 3‐like (DNMT3L) is promoted by stiff ECM in a protein kinase C α (PKCα)‐dependent manner and DNMT3L can be binding to Nanog promoter regions during cell–ECM interactions. These findings unveil DNA methylation as a novel target for the mechanical sensing mechanism of ECM stiffness, which provides a conserved mechanism for gene expression regulation during cell–ECM interactions.

Background: In China, the combination of herb Salvia miltiorrhiza Bge. (Danshen) and Carthamus tinctorius L. (Honghua) is an effective treatment for stroke. A previous study showed that the combination of four herbal components: danshensu (DSS), hydroxysafflor yellow A (HSYA), salvianolic acid A (SAA), and salvianolic acid B (SAB) was effective for treatment of cerebral ischemia-reperfusion (I/R) injury in rats. However, the pharmacokinetic characteristics of this formula require further investigation. The present study investigated the pharmacokinetic differences between each component of in two formulas in cerebral I/R injury rats. The influencing factors may affect the compatibility of components were analyzed.Methods: Focal cerebral I/R was induced by middle cerebral artery occlusion (MCAO). Rats that underwent MCAO were randomly divided into two groups and administered treatments through the tail vein. Blood samples were collected at predetermined time points following administration. The concentrations of DSS, HSYA, SAB, and SAA in rat plasma were determined using HPLC-DAD, and the main pharmacokinetic parameters were calculated. Pharmacokinetic parameters were calculated using DAS 3.2.6 software and SPSS 23.0 statistical analysis software.Results: Our results showed that DSS, HSYA, SAB, and SAA in MCAO model rats had statistically significant differences in two formulas. For DSS and SAA, pharmacokinetic parameters with statistically significant differences including AUC (0−t) , AUMC (0−t) , MRT (0−t) , VRT (0−t) , t 1/2z , V z , CL z , and C max (P < 0.01). For HSYA, significant differences in the parameters including AUC (0−t) , AUMC (0−t) , MRT (0−t) , VRT (0−t) (P < 0.01), CL z and C max (P < 0.05). Conclusion:The difference in pharmacokinetic parameters in response to each component may have been due to differences in the dosages of the components (HSYA, SAA, SAB) and the compatibility of components. Meanwhile, there were many Frontiers in Pharmacology | www.frontiersin.org January 2020 | Volume 10 | Article 1598 1

Guhong injection (GHI) is a drug for ischemic stroke created by combining safflower, a traditional Chinese medicine, and aceglutamide, a Western medicine. In this study, we investigated the curative effect of GHI on cerebral ischemia–reperfusion (I/R) injury via the PKC/HIF-1α pathway in rats. Adult male Sprague Dawley rats were randomly divided into seven groups: sham-operated, middle cerebral artery occlusion (MCAO), GHI, nimodipine injection (NMDP), MCAO + LY317615 (PKC inhibitor), GHI + LY317615, and NMDP + LY317615. After establishing an MCAO rat model, we performed neurological deficit testing, 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay, Western blotting, and q-PCR to detect the brain damage in rats. Compared with the MCAO group, the GHI and GHI + LY317615 group showed neurological damage amelioration as well as decreases in serum hypoxia-inducible factor-1α (HIF-1α), protein kinase C (PKC), and erythropoietin levels; brain HIF-1α and inducible nitric oxide synthase protein expression; and brain HIF-1α and NOX-4 mRNA expression. These effects were similar to those in the positive control groups NMDP and NMDP + LY317615. Thus, our results confirmed GHI can ameliorate cerebral I/R injury in MCAO rats possibly via the PKC/HIF-1α pathway.