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Crocetin is a natural carotenoid compound isolated from Gardenia jasminoids Ellis. Our previous study shows that crocetin inhibits angiotensin II (Ang II)-induced vascular smooth muscle cells (VSMCs) proliferation. To further explore the mechanism by which crocetin inhibits VSMCs proliferation, in the present study we examined the effect of crocetin on cell cycle progression and cell cycle regulatory proteins. Flow cytometry analysis showed that Ang II elicited significant increase in the percentage of VSMCs in the S phase, with a concomitant decline in the percentage of VSMCs in the G0/G1 phase. However, on pretreatment of VSMCs with crocetin, the percentage of VSMCs in the S phase decreased, while that in the G0/G1 phase increased significantly. In addition, Ang II-induced increase of cell proliferation index was also decreased by crocetin. Western blotting analysis indicated that crocetin markedly inhibited the protein expression of cyclin D1 but not cyclin E. Crocetin also increased the level of cyclin-dependent kinase inhibitor (CDKI) p27kip1 but not CDKI p21waf1/cip1. In conclusion, our present results suggest that the inhibition of cell cycle G1/S transition in VSMCs by crocetin can be attributed, at least in part, to its suppression of cyclin D1 and elevation of CDKI p27kip1. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study aims to investigate the protective role of crocetin, a natural antioxidant, against cytotoxicity produced by exposure to norepinephrine (NE) in primary cultured rat cardiac myocytes. Reactive oxygen species (ROS) and Ca2+ in cells were evaluated by fluorescence microplate reader using 6-carboxy-2',7'-dichlorofluorescein and fluoro-3-acetoxymethyl ester, respectively. Lipid peroxidation was quantified using thiobarbituric acid-reactive substances. The activities of superoxide dismutase (SOD) and contents of glutathione (GSH) were detected by xanthine/xanthime oxidase-mediated ferricytochrome c reduction assay, and recycling effection of glutathione disulfide with GSH reductase and NADPH, respectively. The apoptotic cells were assayed by fluorescein diacetate (FDA)-ethidium bromide (EB) two-staining method. Intracellular accumulation of ROS, Ca2+, and products of lipid peroxidation resulting from NE were significantly reduced by crocetin. Preincubation of primary cultured rat cardiac myocytes with crocetin remarkably prevented the decrease in SOD activity and quantities of GSH induced by NE. The percentage of NE-induced apoptosis in the cells was decreased by FDA-EB two-staining assay after pretreated with crocetin. The results showed that crocetin may ameliorate NE-induced injury in cardiac myocytes by enhanced SOD activity and increased quantities of GSH, decreased lipid peroxidation and Ca2+ in cells, and apoptosis death ratio that may represent the cellular mechanisms for its cardioprotective role. [ABSTRACT FROM AUTHOR]

Abstract: Crocetin, a carotenoid compound, was isolated from Gardenia jasminoids Ellis. Our recent study shows that crocetin inhibits angiotensin II-induced extracellular signal-regulated kinases 1/2 (ERK1/2) activation and subsequent proliferation in vascular smooth muscle cells (VSMCs). To further explore the mechanism involved, in the present study, we investigated the effect of Ca2+ in the activation of ERK1/2 and whether Ca2+ is involved in the suppression by crocetin of angiotensin II-induced ERK1/2 activation. Our findings showed that crocetin pretreatment partially attenuated both the intracellular Ca2+ mobilization and the extracellular Ca2+ influx induced by angiotensin II. Moreover, angiotensin II-induced ERK1/2 activation was completely abolished by acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N ′,N′-tetraacetic acid (BAPTA-AM), an intracellular Ca2+ chelator, and partially inhibited by EGTA, an extracellular Ca2+ chelator, or verapamil, an L-type Ca2+ channel blocker. These findings suggest that Ca2+ may play an important role in angiotensin II-induced ERK1/2 activation in VSMCs, and Ca2+-dependent pathway may be involved in the inhibitory effect by crocetin of angiotensin II-induced ERK1/2 activation. [Copyright &y& Elsevier]

Crocin, the digentiobiosyl ester of crocetin, was investigated for its cytoprotective effect on hydrogen peroxide-induced injury in bovine aortic endothelial cells (BAECs). The morphology of BAECs was observed by inverted phase contrast and electron microscopy. The MTT assay was used to measure cell viability. Cell apoptosis was evaluated by DNA argarose gel electrophoresis. The cells treated with H 2 O 2 (200 μM) showed apoptotic changes as revealed by cell shrinkage, condensation of nuclei, membrane blebbing and formation of apoptotic body. A concentration-dependent inhibition of cell injury was seen in cultures treated with crocin at dosages ranging from 1 to 10 μM. Furthermore, in the H 2 O 2 -treated group, agarose gel electrophoresis displayed a “DNA ladder”. Whereas in the 10 μM crocin-pretreated group, cells remained intact and no “DNA ladder” was observed in agarose gel electrophoresis. Only very little DNA debris appeared on DNA-fragmentation analysis in the 1 μM crocin-pretreated group. Our data demonstrated that crocin has preventive effects on the cell apoptosis induced by H 2 O 2 , which may contribute to its utilisation for cardiovascular diseases (e.g., atherosclerosis and hypertension). [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is an exceptionally deadly disease, whereas effective therapeutic drugs for CRC have declined over the past few decades. Natural products have become a reliable source of anticancer drugs. Previously we isolated an alkaloid named (-)- N -hydroxyapiosporamide (NHAP), which exerts potent antitumor effects, but its effect and mechanism in CRC remain unclear. This study aimed to reveal the antitumor target of NHAP and identify NHAP as a promising lead compound for CRC. Various biochemical methods and animal models were used to investigate the antitumor effect and molecular mechanism for NHAP. These results showed that NHAP exhibited potent cytotoxicity, induced both apoptosis and autophagic cell death of CRC cells, and inhibited the NF-κB signaling pathway by blocking the interaction of the TAK1-TRAF6 complex. NHAP also markedly inhibited CRC tumor growth in vivo without obvious toxicities and possessed good pharmacokinetic characteristics. These findings identify, for the first time, that NHAP is an NF-κB inhibitor with potent antitumor activity in vitro and in vivo . This study clarifies the antitumor target of NHAP against CRC, which will contribute to the future development of NHAP as a novel therapeutic lead compound for CRC.

Spine is one of the most important organs in the human body. One of the most commonly used method for the treatment of spinal diseases is the internal fixation and accurate placement of pedicle screw, which is a key factor of spinal surgery. However, due to the large differences as to the appearance of pedicles, it is hard to place the pedicle screw precisely, which will cause complication. Therefore, to find a new real-time intra-operative monitoring method with navigation is the direction of clinical application research. In this paper, a new method was firstly proposed. This method combined computer tomography (CT) values and near-infrared spectroscopy (NIRs) measurement data to guide the PS placement, and the relationship between NIRs parameters and CT values along the PS trajectory in vertebrae was investigated. First, we took pig vertebrae as samples and different puncture paths were planned. Second, a near-infrared monitoring device was utilized in experiments of fresh pig vertebrae to acquire the best NIRs monitoring pattern factors. Finally, the correlation function between NIRs data and CT values pattern factors was obtained. The results showed that CT values have a linear relationship with NIRs monitoring pattern factors, which provide references for real-time monitoring method in pedicle screw fixation surgery. This model can be applied in monitoring the pedicle screw implantation and alarming. The proposed method will be potential in improving the accuracy of PS placement and reduce the risk caused by the misplacement of pedicle screw.

Crocetin, a naturally occurring carotenoid, possesses antioxidant and antiatherosclerotic properties, of which the underlying mechanism remains unclear. In the present study, we examined the effects of crocetin (0.1, 1, 10 μmol·L(-1)) on angiotensin II (Ang II, 0.1 μmol·L(-1)) induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and monocyte-endothelial cell adhesion. The effects of crocetin on the activation of nuclear factor kappa B (NF-κB) and intracellular reactive oxygen species (ROS) were also observed. The results demonstrated that crocetin notably suppressed Ang II induced NF-κB activation (P<0.01) and VCAM-1 expression (P<0.05, P<0.01) in HUVECs, accompanied by a markedly reduced monocyte-endothelial cell adhesion (P<0.05, P<0.01). In addition, preincubation with crocetin resulted in a significant enhancement of cellular antioxidant capacity (P<0.05, P<0.01), while Ang II induced intracellular ROS decreased markedly (P<0.05, P<0.01). These results indicated that crocetin was capable of suppressing Ang II induced VCAM-1 expression and monocyte-endothelial cell adhesion by suppression of NF-κB activation, which might be derived from the enhancement of antioxidant capacity and subsequent reduction of intracellular ROS.

Fourier transform infrared spectroscopy (FTIRS) and microimaging technique have been integrated together to evolve into Fourier transform infrared spectroscopic imaging (FTIRI) system. This system can provide not only the morphological information of the sample by visible image and FTIR image, but also the abundant information on the spectral, component and structure of specimen by FTIRS, especially of the heterogeneous solid mixture. The richer and more visualized information obtained by FTIRI greatly raised the research efficiency and usability of the spectral technique in biomedicine, pharmacology, forensic medicine, material science and chemistry, etc. The present paper depicts FTIRI development process, system structure, imaging principle and mode selection; and then introduces that FTIRI opened a new area of investigation for biomedicine, namely, research on bone disease by FTIRI. Then the paper illustrates the related research findings and progress in FTIRI use for osteopetrosis, osteogenesis imperfecta, osteoporosis and osteomalacia, as well as a couple of limitations. The prospective study for FTIRI in biomedical research field is also addressed.

Objective: To access the effect of wireless biofeedback therapy on bruxism., Methods: Ten voluntary bruxers (seven female and three male, mean age 26.1 years) were invited to participate in this clinical research. An electric resistance strain gauge was embedded in the position of canine of a maxillary splint for monitoring the abnormal clenching or grinding movement of teeth during sleep. The relevant details of bruxism events, including value of relative force, occurring time and duration were recorded and analyzed by the receiver device and monitoring program respectively. Meanwhile, for the purpose of nerve system and muscle relaxation, a watch-style device around the patient's wrist will vibrate to alert the patient of teeth grinding or clenching if the value of biting force and duration exceed the threshold. Total average episodes of bruxism and duration was observed during eight hours sleep, and was analyzed with one-way analysis of variance in SPSS 19.0 by the end of 6th week and three months following biofeedback therapy., Results: The average episodes of bruxism has declined dramatically from (9.8 ± 2.2) times to (3.0 ± 1.2) times during one night (P < 0.05), and the average duration of bruxism events was reduced from (20.7 ± 12.2) s to (10.0 ± 3.4) s (P < 0.05) after six weeks biofeedback therapy. By the end of three months, the average episodes declined to (2.9 ± 1.2) times (P < 0.05), and the average duration decline to (9.2 ± 2.9) s (P < 0.05) with contrast to preliminary night., Conclusions: The pressure-based wireless biofeedback device is able to monitoring clenching and grinding of bruxism. The results suggest that biofeedback therapy may be an effective, novel and convenient measure for treatment of bruxism according to several months therapy.

Functionality near infrared spectroscopy (fNIRs) technology was utilized in the present paper to explore functional properties of brain tissue of rat model of Parkinson's disease(PD). Imaging data of rat model were detected by small animal MRI and CT; and characteristic parameters of striatum of rat brain were detected by fNIRs system. Experimental results show that, between PD and normal rat, there is no obvious change in morphological structure, but significant differences existed in reduced scattering coefficient (mu's) and cerebral blood volume (CBV) of rat striatum; there exists correlation between parameters (mu's, CB3V) obtained by fNIRs and parameters (cerebral blood flow (CBF), CBV) obtained by CT perfusion (CTP). These results indicate that fNIRs can be used as important reference for PD research.

Near infrared spectroscopy (NIRs) technology was utilized for assessing effects in treating traumatic brain edema (TBE). Firstly, models for rats with traumatic brain edema were copied according to Feeney's apparatus. Then rats were given mannitol with different dosages (large and little) according to their groups. Simultaneously rat's brain tissues were monitored in vivo and real-time by NIRs mini-invasive detector developed by the authors' laboratory. And the water content of the brain tissues was measured by the wet and dry weight method at 1, 6, 24, 72 and 120 h after the injury and the treatment. Then, effects in treating TBE with different dosages were assessed by analyzing reduced scattering coefficient (micro'(s)) data measured by NIRs and brain water content (BWC) before and after injecting dehydration. Finally, the authors found that reduced scattering coefficient (micro'(s)) of rat's local cortex is a good indicator of assessing effects of treatment of TBE and that may be a preferable approach to assessing effects in vivo and real-time in treatment of brain injury.