Cerebral Arterial Stiffness as Measured Based on the Pulse Wave Velocity Is Associated With Intracranial Artery Calcification in Patients With Acute Stroke

Background@#and Purpose By measuring a newly defined parameter, the carotid–cerebral pulse wave velocity (ccPWV), this study aimed to determine the association of intracranial artery calcification (IAC) with arterial stiffness as reflected by the pulse wave velocity between the carotid and middle cerebral arteries using transcranial Doppler sonography in patients with acute stroke. @*Methods@#We recruited 146 patients with ischemic stroke from our stroke center. Computed tomography of the head was used to assess the presence and severity of IAC. Arterial stiffness was evaluated using ccPWV. Data are presented as quartiles of ccPWV. A multivariable logistic regression model was used to assess the independent relationship between ccPWV and IAC. @*Results@#The IAC prevalence increased with the ccPWV quartile, being 54%, 76%, 83%, and 89% for quartiles 1, 2, 3, and 4, respectively (p<0.001) as did IAC scores, with median [interquartile range] values of 0 [0–2], 3 [2–4], 4 [2–5], and 5 [4–6], respectively (p<0.001). After additionally adjusting for age and hypertension, a significant correlation was only found between quartiles 3 and 4 of ccPWV and IAC scores. The odds ratio (95% confidence interval) for the IAC scores was 1.78 (1.28–2.50) (p=0.001) in quartile 4 of ccPWV and 1.45 (1.07–1.95) (p=0.015) in quartile 3 compared with quartile 1. @*Conclusions@#We found that in patients with acute ischemic stroke, ccPWV was positively related to the degree of IAC. Future longitudinal cohort studies may help to identify the potential role of IAC in the progression of cerebral arterial stiffness.

Advances in cell nuclear mechanobiology and its regulation mechanisms / 生物医学工程学杂志

As an important intracellular genetic and regulatory center, the nucleus is not only a terminal effector of intracellular biochemical signals, but also has a significant impact on cell function and phenotype through direct or indirect regulation of nuclear mechanistic cues after the cell senses and responds to mechanical stimuli. The nucleus relies on chromatin-nuclear membrane-cytoskeleton infrastructure to couple signal transduction, and responds to these mechanical stimuli in the intracellular and extracellular physical microenvironments. Changes in the morphological structure of the nucleus are the most intuitive manifestation of this mechanical response cascades and are the basis for the direct response of the nucleus to mechanical stimuli. Based on such relationships of the nucleus with cell behavior and phenotype, abnormal nuclear morphological changes are widely used in clinical practice as disease diagnostic tools. This review article highlights the latest advances in how nuclear morphology responds and adapts to mechanical stimuli. Additionally, this article will shed light on the factors that mechanically regulate nuclear morphology as well as the tumor physio-pathological processes involved in nuclear morphology and the underlying mechanobiological mechanisms. It provides new insights into the mechanisms that nuclear mechanics regulates disease development and its use as a potential target for diagnosis and treatment.

External Counterpulsation Reduces Beat-to-Beat Blood Pressure Variability When Augmenting Blood Pressure and Cerebral Blood Flow in Ischemic Stroke

BACKGROUND AND PURPOSE: External counterpulsation (ECP) is a noninvasive method used to enhance cerebral perfusion by elevating the blood pressure in ischemic stroke. However, the response of the beat-to-beat blood pressure variability (BPV) in ischemic stroke patients during ECP remains unknown. METHODS: We enrolled recent ischemic stroke patients and healthy controls. Changes in the blood flow velocities in bilateral middle cerebral arteries and the continuous beat-to-beat blood pressure before, during, and after ECP were monitored. Power spectral analysis revealed that the BPV included oscillations at very low frequency (VLF; <0.04 Hz), low frequency (LF; 0.04-0.15 Hz), and high frequency (HF; 0.15-0.40 Hz), and the total power spectral density (TP; <0.40 Hz) and LF/HF ratio were calculated. RESULTS: We found that ECP significantly increased the systolic and diastolic blood pressures in both stroke patients and controls. ECP decreased markedly the systolic and diastolic BPVs at VLF and LF and the TP, and the diastolic BPV at HF when compared with baseline. The decreases in diastolic and systolic BPV reached 37.56% and 23.20%, respectively, at VLF, 21.15% and 12.19% at LF, 8.76% and 16.59% at HF, and 31.92% and 23.62% for the total TP in stroke patients, which did not differ from those in healthy controls. The change in flow velocity on the contralateral side was positively correlated with the total TP systolic BPV change induced by ECP (r=0.312, p=0.035). CONCLUSIONS: ECP reduces the beat-to-beat BPV when increasing the blood pressure and cerebral blood flow velocity in ischemic stroke patients. ECP might be able to improve the clinical outcome by decreasing the beat-to-beat BPV in stroke patients, and this should be explored further in future studies.

Molecular docking of anthocyanins constituents and HER-2 kinase domain / 生物工程学报

Anthocyanins are a ubiquitous group of water-soluble plant pigments of the flavonoid family, with anticancer property through HER-2 signaling pathway. Nowadays, molecular docking plays an important role in exposing the active sites and obtaining the bioactive conformation involving protein-ligand interactions. According to the crystal structure of HER-2 kinase domain and 12 main antitumor compounds of anthocyanins as well as ATP, a molecular docking study was performed by MVD program. All 12 compounds could bind to the same cavity of HER-2 kinase domain by high affinity (MolDock Score < -105 kJ/mol for anthocyanidins, < -130 kJ/mol for anthocyanidins-glc), where hydrophobic force and hydrogen bond played key roles. Additionally, this cavity overlapped with ATP binding (MolDock Score = -161 kJ/mol) domain; the binding of anthocyanins presumably interfered the H bond formation between ATP and HER-2. These results indicate that anthocyanins may competitively bind to ATP binding site in HER-2 kinase domain by suppressing HER-2 activation and downstream signaling cascade. This may provide useful theoretical instruction for the molecular mechanism of HER-2 kinase activity inhibition by anthocyanins in cancer prevention and treatment.

Theanine affects sedative effect of pentobarbital sodium in ICR mice / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effects of theanine on sedative effects induced by pentobarbital sodium.</p><p><b>METHOD</b>The locomotor activities of ICR mice induced by theanine (0.25, 0.5, 1.0, 2.0, 4.0 g x kg(-1)), pentobarbital sodium (5, 10 mg x kg(-1)) or the combination of both were determined with video-tracking system, and a novel index: Peripheral active time Peripheral time (PATP) was established. Hypnosis effect of combination of both was tested with right-reflex disappearance.</p><p><b>RESULT</b>Compared with normal saline (74.52 +/- 20.4)%, theanine alone decreased this PATP in dose-dependent manner from (62.03 +/- 21.11)%, (56.44 +/- 21.69)%, (31.13 +/- 17.2)%, (25.06 +/- 10.03)% to (17.21 +/- 7.43)% (P>0.05, P<0.05, P<0.01, P<0.01 and P<0.01, respectively). Compared with pentobarbital sodium (5 mg x kg(-1)), between 0.25 g x kg(-1) and 1.0 g x kg(-1) theanine combined with that decreased peripheral PATP from (28.30 +/- 17.57)%, (30.64 +/- 17.21)% to (24.28 +/- 9.59)% (all P<0.01), and increased by 2.0 g x kg(-1) reversely (61.95 +/- 19.39)%. Compared with normal saline, pentobarbital sodium (10 mg x kg(-1)) and the combination with theanine decreased significantly PATP (all P<0.01). Compared with pentobarbital sodium (10 mg x kg(-1)), 0.25 g x kg(-1) theanine combined with that increased PATP [(25.37 +/- 13.68)% vs (10.08 +/- 7.98)%, P<0.01)] and 0.5 g x kg(-1), 1.0 g x kg(-1) theanine could depresse that increase [(14.56 +/-10.10)%, (8.24 +/- 4.08)% vs (10.08 +/- 7.98)%]. Total distance and peripheral active time showed the same or similar tendency in theanine alone or combination with pentobarbital sodium . Theanine enchanced hypnosis effect of pentobarbital sodium in dose-dependent manner.</p><p><b>CONCLUSION</b>Theanine can affect the sedative effect of low dose pentobarbital sodium in bidirectional action style but not change the hypnosis effect.</p>