Phase Separation of Biomacromolecules and Its Important Role in Transcriptional Regulation / 生物化学与生物物理进展

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

The effect of catheter based renal synthetic denervation on renin-angiotensin-aldosterone system in patients with resistant hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>to explore the effect of catheter based renal synthetic denervation on renin-angiotensin-aldosterone system (RAAS) and blood pressure reduction in patients with resistant hypertension. and assess the validity and security of the treatment.</p><p><b>METHODS</b>Ten patients with resistant hypertension from June 2011 to December 2011 were retrospectively reviewed, and then all of 10 patients screened for eligibility were allocated to renal denervation. Primary endpoints were changes of office blood pressure at 1 week, 1, 3 and 6 months after procedure. We assessed the effectiveness of renal sympathetic denervation with heart rate (HR), renin activity (PRA), angiotensin II (AngII), aldosterone (Ald), and creatinine (Cr) before and 2 weeks after procedure.</p><p><b>RESULTS</b>Office blood pressure after catheter-based renal denervation decreased by 22.8/9.1 mm Hg (1 mm Hg = 0.133 kPa), 34.8/14.7 mm Hg, 42.6/20.7 mm Hg, 43.2/21.6 mm Hg, at 1 week, 1, 3 and 6 months, respectively (P < 0.001). Meanwhile, the level of PRA, AngII, Ald decreased by (1.11 ± 0.89) ng×ml(-1)×h(-1) (P = 0.003), (17.06 ± 13.82) ng/L (P = 0.004), (404.5 ± 285.8) ng/L (P = 0.002), respectively; and heart rate decreased by 5.1 bpm (P = 0.002). However, the Cr level and eGFR did not change significantly (P > 0.05).</p><p><b>CONCLUSION</b>Catheter-based renal sympathetic denervation can reduce the level of renin activity, angiotensin II and aldosterone, and causes substantial and sustained blood-pressure reduction.</p>

Efficacy of catheter-based renal denervation in mongrel neurogenic hypertensive dogs / 中华心血管病杂志

<p><b>OBJECTIVE</b>Hypertension is the most common risk factor for cardiovascular diseases and stroke. Renal sympathetic hyperactivity is associated with hypertension. The aim of this study was to explore the efficacy of renal denervation for hypertension.</p><p><b>METHODS</b>Eighteen mongrel neurogenic hypertensive dogs were divided into intervention [mean arterial pressure: (150.6 ± 18.8) mm Hg (1 mm Hg = 0.133 kPa) plus renal sympathetic denervation by percutaneous catheter-based radiofrequency, n = 10] and control [mean arterial pressure (147.4 ± 13.2) mm Hg, n = 8] group. Mean arterial pressure before and at 2, 4, 6 and 10 weeks after procedure was invasively measured. Renin activity (PRA), angiotensin II (AngII), aldosterone (Ald), and creatinine (Cr) were detected at 2, 6 and 10 weeks after procedure.</p><p><b>RESULTS</b>Mean arterial pressure remained unchanged in control group. In intervention group, mean arterial pressure (MAP) decreased to (130.4 ± 14.1) mm Hg, (136.2 ± 17.1) mm Hg, (128.7 ± 14.7) mm Hg and (126.1 ± 12.7) mm Hg respectively at 2, 4, 6, and 10 weeks after procedure. Meanwhile, the level of PRA, AngII, Ald significantly reduced post procedure compared with pre-procedural level (P < 0.05) and the Cr level remained unchanged post procedure (P > 0.05).</p><p><b>CONCLUSION</b>Sympathetic nervous system plays an important role in the progression of hypertension. Catheter-based renal denervation results in substantial and sustained blood-pressure reduction in this model.</p>

Surgical treatment of congenital heart diseases in pediatric patients with body weight less than 10 kg / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To report the experience of the surgical treatment of congenital heart diseases (CHD) in pediatric patients with body weight less than 10 kg.</p><p><b>METHODS</b>Between January 2000 and December 2007, 105 children with CHD, aged 2 months to 3 years and weighing between 3.5 to 10 kg, underwent surgical treatment. Of the 105 patients, 56 were concomitant with moderate to severe pulmonary hypertension or repeated pulmonary infections, and 35 with complex cardiac abnormalities. Operations were performed through median sternotomy with moderate hypothermic cardiopulmonary bypass in 88 cases, with normothermic extracorporeal circulation on beating heart in 14 cases, and with deep hypothermic circulatory arrest in 3 cases.</p><p><b>RESULTS</b>There were 5 early deaths (4.8%). During a follow-up of 2 month to 3 year, 97 survivors with corrective procedure had no late mortality or complications with NYHA class I of cardiac function, excepting 2 cases with little residual shunt. Three survivors with palliative procedure enjoyed higher quality of life.</p><p><b>CONCLUSIONS</b>The surgical treatment of CHD in pediatric patients with body weight less than 10 kg seems to be feasible and safe, with satisfactory early and long-term results.</p>