Salt Restriction and Angiotensin-Converting Enzyme Inhibitor Improve the Responsiveness of the Small Artery in Salt-Sensitive Hypertension.

For salt-sensitive hypertension (SSH), salt restriction and angiotensin-converting enzyme (ACE) inhibitors are essential treatments, but their effect on the function of resistance arteries is unclear. Here, we present an intravital study to detect the effect of salt restriction and ACE inhibitors on the function of the mesenteric small artery (MSA) in SSH. Dahl salt-sensitive rats were randomized into the following groups: ACE inhibitor gavage, salt restriction, ACE inhibitor combined with salt restriction, and high-salt diet. After a 12-week intervention, the mesenteric vessels maintained their perfusion in vivo, and the changes in the diameter and blood perfusion of the MSAs to norepinephrine (NE) and acetylcholine (ACh) were detected. Switching from a high-salt diet to a low-salt diet (i.e., salt restriction) attenuated the vasoconstriction of the MSAs to NE and promoted the vasodilatation to ACh, while ACE inhibitor improved the vasodilatation more obviously. Pathologically, changes in local ACE, AT1R, and eNOS expression were involved in these processes induced by a high-salt diet. Our study suggests that salt restriction and ACE inhibitor treatment improve high salt intake-induced MSA dysfunction in SSH, and salt restriction is a feasible and effective treatment. Our findings may provide a scientific basis for the treatment of hypertension.

Unveiling the Time Course Mechanism of Bone Fracture Healing by Transcriptional Profiles.

BACKGROUND: Bone fracture healing is a time-consuming and high-priority orthopedic problem worldwide. OBJECTIVE: Discovering the potential mechanism of bone healing at a time course and transcriptional level may better help manage bone fracture. METHODS: In this study, we analyze a time-course bone fracture healing transcriptional dataset in a rat model (GSE592, GSE594, and GSE1371) of Gene Expression Omnibus (GEO). RNA was obtained from female Sprague-Dawley rats with a femoral fracture at the initial time (day 3) as well as early (week 1), middle (week 2), and late (week 4) time periods, with nonfracture rats used as control. Gene Ontology (GO) functional analysis and pathway examinations were performed for further measurements of GSEA and hub genes. RESULTS: Results indicated that the four stages of bone fracture healing at the initial, early, middle, and late time periods represent the phases of hematoma formation, callus formation, callus molding, and mature lamellar bone formation, respectively. Extracellular organization was positively employed throughout the four stages. At the hematoma formation phase, the muscle contraction process was downregulated. Antibacterial peptide pathway was downregulated at all phases. The upregulation of Fn1 (initial, early, middle, and late time periods), Col3a1 (initial, early, and middle time periods), Col11a1 (initial and early time periods), Mmp9 (middle and late time periods), Mmp13 (early, middle, and late time periods) and the downregulation of RatNP-3b (initial, early, middle, and late time periods) were possible symbols for bone fracture healing and may be used as therapeutic targets. CONCLUSION: These findings suggest some new potential pathways and genes in the process of bone fracture healing and further provide insights that can be used in targeted molecular therapy for bone fracture healing.

Identification of the genetic central dogma in osteogenic differentiation of MSCs by osteoinductive medium from transcriptional data sets.

Background: The genetic central dogma (GCD) has been demonstrated its essential function in many biological processes and diseases. However, its roles in the process of osteogenic differentiation of mesenchymal stem cells (MSCs) remain unclear. Methods: In this project, we analyzed an online database of osteogenic differentiation of MSCs after 14 days and 28 days by osteoinductive medium (GSE83770). The differentially expressed genes were screened by GEO2R, with further conducting of KEGG pathways using DAVID. In addition, protein-protein interactions of the enriched pathways were performed using STRING with marked hub genes measured by the CytoHubba. Hub genes were verified by quantitative reverse-transcription polymerase chain reaction. Results: Results showed that six pathways related to GCD, including DNA replication, Aminoacyl-tRNA biosynthesis, Mismatch repair, Ribosome, Spliceosome, and RNA degradation pathways enriched in the early stage (14 days vs. undifferentiated MSCs) of osteogenesis. The Lysosome pathway was highly enriched in the late stage (28 vs. 14 days) of osteogenesis, and Ribosome pathway plays a key role throughout the entire process (28 days vs. undifferentiated MSCs) of osteogenesis. Conclusion: Both DNA replication and protein translation were functionally worked in the early stage of osteogenesis, whereas the Lysosome pathway was the only GCD-related one in the late stage of osteogenesis. The GCD-related Ribosome pathway occupied the entire process of osteogenesis.