99Tcm-HL91乏氧显像评价小鼠移植瘤放疗疗效

目的为^99Tc^m-4，9-二氮-3，3，10，10-四甲基十二烷-2，11-二酮肟（HL91）乏氧显像评价肿瘤放疗疗效提供依据。方法15只H22肝癌细胞小鼠移植瘤模型分成3组，每组各5只。A组不进行放疗；B组单次放疗25Gy后即刻进行^99Tc^m-HL91显像；C组单次放疗25Gy48h后进行^99Tc^m-HL91显像，计算B、C组放疗前后同一感兴趣区（ROI）内肿瘤组织与正常脑组织放射性计数比值（T／N）；测定A、B、C组凋亡细胞、G1期和S期细胞比例及观察肿瘤组织放疗前后病理变化。结果（1）B组放疗后T／N值较放疗前显著增高（P〈0．05）；C组放疗后T／N值较放疗前显著降低（P〈0．05）。（2）A、B、C组凋亡细胞之间比例差异具有统计学意义（P〈0．05，A〈B〈C）。（3）C组S期细胞所占比例明显低于A、B组，G1期细胞比例明显高于A、B组（P〈0．05）；C组肿瘤组织光学显微镜下可见凋亡细胞和大量细胞碎片。结论^99Tc^m-HL91显像是一种有价值的评价放疗疗效的手段。     

绿茶素(TP-91)抗肿瘤作用的实验研究

 目的：研究绿茶素对肿瘤的预防和辅助治疗作用。方法：采用我院从湖北绿茶提取的绿茶素(TP91)进行了多项指标综合观察的抗肿瘤实验。瘤株为小鼠S180，Hela细胞和EAC。结果：(1)TP91具明显抗癌作用，对S180的抑瘤率达43.6%，体外试验对Hela细胞和EAC细胞均有抑制作用，药物作用2小时后癌细胞死亡率分别为93%和45%；(2)给药后血液高凝状态缓解、CAMP升高、SOD活性增强，外周血T淋巴细胞百分率上升、以及肿瘤间质肥大细胞数增多；(3)检出TP91含有硒、锗等20种元素。结论：提示绿茶素(TP91)在肿瘤一级预防和辅助治疗中具有良好发展前景。     

Integrative studies to design and validate wearable footwear among neuropathic patients

Uncontrolled high blood sugar levels leads to diabetic neuropathy, which is usually develops slowly. Damaged nerves stop sending messages or may send message slowly at the wrong times. The propsed model is an insole for individuals with peripheral neuropathy conditions, where the peak plantar pressure value is measured at specified locations of the foot by means of a pressure sensor, which can be accessed via a mobile applications; Simultaneously, a stimulation is given at acupressure points of the foot to relieve pain at definite intervals of time, based on the signals from the controller. A controller is being used to perform these operations which will be transmitted to the mobile application via Bluetooth terminal.     

Solution structure of the regulatory domain of human cardiac troponin C in complex with the switch region of cardiac troponin I and W7: The basis of W7 as an inhibitor of cardiac muscle contraction

The solution structure of Ca²⁺-bound regulatory domain of cardiac troponin C (cNTnC) in complex with the switch region of troponin I (cTnI_147-163) and the calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfinamide (W7), has been determined by NMR spectroscopy. The structure reveals that the W7 naphthalene ring interacts with the terminal methyl groups of M47, M60, and M81 as well as aliphatic and aromatic side chains of several other residues in the hydrophobic pocket of cNTnC. The H3 ring proton of W7 also contacts the methyl groups of I148 and M153 of cTnI_147-163. The N-(6-aminohexyl) tail interacts primarily with the methyl groups of V64 and M81, which are located on the C- and D-helices of cNTnC. Compared to the structure of the cNTnC•Ca²⁺•W7 complex (Hoffman, R. M. B. and Sykes, B. D. (2009) Biochemistry 48, 5541-5552), the tail of W7 reorients slightly toward the surface of cNTnC while the ring remains in the hydrophobic pocket. The positively charged -NH₃⁺ group from the tail of W7 repels the positively charged R147 of cTnI_147-163. As a result, the N-terminus of the peptide moves away from cNTnC and the helical content of cTnI_147-163 is diminished, when compared to the structure of cNTnC•Ca²⁺•cTnI_147-163 (Li, M. X., Spyracopoulos, L., and Sykes B. D. (1999) Biochemistry 38, 8289-8298). Thus the ternary structure cNTnC•Ca²⁺•W7•cTnI_147-163 reported in this study offers an explanation for the ∼ 13-fold affinity reduction of cTnI_147-163 for cNTnC•Ca²⁺ in the presence of W7 and provides a structural basis for the inhibitory effect of W7 in cardiac muscle contraction. This generates molecular insight into structural features that are useful for the design of cTnC-specific Ca²⁺-desensitizing drugs.     

An In Vitro Study of the Structure-Activity Relationships of Sulfated Polysaccharide from Brown Algae to its Antioxidant Effect

Abstract

In this paper, the structure-activity relationships of chemically modified uronic acid polymer fragments from brown algae with regard to their antioxidant effects on H₂O₂-damaged lymphocyte were studied. The results indicated that the most potent antioxidant activity was obtained from the sulfated polysaccharide with ratio of mannuronate blocks (M-blocks) to guluronate blocks (G-blocks) of 3 to 1 and carboxyl residue unesterified. The sulfated G-blocks with esterified carboxyl residue also prevented lymphocyte from injury. However, the sulfated G-blocks bearing unesterified carboxyl residue hardly exerted antioxidant activity. These findings suggested that both M-blocks and esterified carboxyl residue were determinant structures in preventing lymphocyte from being oxidized by H₂O₂, indicating that the existence of M-blocks was more important in scavenging free radicals.     

Angelica sinensis polysaccharides inhibit endothelial progenitor cell senescence through the reduction of oxidative stress and activation of the Akt/hTERT pathway

Abstract

Context: Angelica sinensis (Oliv.) Diels (Apiaceae) polysaccharides (ASP) may play a key role in anti-ischemic activity. However, the anti-atherosclerotic activity and mechanism are unknown.

Objective: This study investigated the protective effects of ASP against ox-LDL-induced senescence of EPCs and explored its underlying molecular mechanisms.

Materials and methods: Mononuclear cells were isolated from bone marrow (BM) of SD rats and differentiated to EPCs. EPCs were exposed to oxidized low-density lipoprotein (ox-LDL, 10?µg/mL, 24?h) and incubated with or without high-dose (100?µg/mL, 48?h) or low-dose (20?µg/mL, 48?h) ASP. Another group of EPCs was pre-treated with Wortmannin (100?nM, 45?min), a PI3K/Akt inhibitor. EPC senescence, telomerase activity, and superoxide anion levels were assessed using SA-β-galactosidase staining, telomerase PCR-ELISA analysis, and DHE staining, respectively. The expression of related proteins, including Akt, p-Akt, hTERT, p-hTERT, and gp91phox, were detected using western blot.

Results: EPCs (47.3%) were SA-β-gal positive after treatment by ox-LDL, additionally, ox-LDL significantly increased superoxide anion levels (375% versus 100%), and inhibited telomerase activity (42% versus 100%). However, the pro-senescent effect of ox-LDL was attenuated about three-fold (16.7%), superoxide anion levels were decreased more than two-fold (148%), and telomerase activity was recovered partly (88% versus 42%) in the EPCs when treated with ASP (100?µg/mL). The immunoblotting confirmed that ASP attenuated inhibition of phosphorylation of Akt and hTERT induced by ox-LDL and down-regulated increased the expression of gp91-phox. Moreover, some effects of ASP were partially abrogated in the presence of Wortmannin.

Discussion: Ox-LDL induced senescence of EPCs via inhibition of telomerase activity, which was influenced by oxidative stress and the Akt/hTERT pathway. The inhibition of EPC senescence by ASP could be important for potential therapeutics.

Conclusion: Treatment of EPCs with ASP remarkably attenuates the harmful effects of ox-LDL via augmentation of Akt/hTERT phosphorylation and inhibition of oxidative stress.     

脑梗死患者的99mTc-HL91 SPECT乏氧显像

目的^99m Tc-HL91 SPECT检测不同亚型脑梗死患者的乏氧组织，探讨乏氧组织能否代表缺血半暗带。方法：对57例发病14d内的脑梗死患者和9例无脑病的对照者行辨^99m Tc-HL91 SPECT脑乏氧显像，显示乏氧组织。其中5例患者同时进行^99m Tc-HL91 SPECT脑血流灌注显像，1例患者行”F-FDG葡萄糖代谢显像。结果：对照组乏氧显像全部为阴性，30例脑梗死患者呈阳性，均为完全或部分前循环梗死，乏氧组织位于梗死灶外周。10例复查乏氧显像的患者乏氧组织均缩小或消失，其中1例乏氧组织持续存在至发病后第44天。脑血流显像提示，梗死侧大脑半球血流下降，其中2例乏氧显像呈阳性。葡萄糖显像提示，患者在发病后17d时梗死灶仍存在葡萄糖代谢，乏氧显像仍呈阳性。结论：一部分完全或部分前循环梗死患者存在乏氧组织，该组织代表可逆性损伤组织，可持续存在至亚急性期和慢性期。