Tryptanthrin derivative CY-1-4 nanoparticle induces ferroptosis in B16-F10 cells / 药学学报

CY-1-4 is a tryptanthrin derivative exhibiting antitumor activity. The solubility of CY-1-4 was poor and the corresponding mechanism needs further study. To solve this problem, we prepared nanoparticles encapsulated with CY-1-4 (CY-1-4 NPs) by nanoprecipitation method using poly(caprolactone) (PCL) and poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) as carriers to improve solubility. We then explored whether CY-1-4 NPs induced B16-F10 cytotoxicity via ferroptosis by determining the effect of CY-1-4 NPs on reactive oxygen (ROS) levels, repairing efficacy of lipid reactive oxygen inhibitor ferrostatin-1 and iron chelator deferoxamine (DFO), and potentiation of protoporphyrin (PPIX) induced B16-F10 cell death. The results showed that nanoparticlated strategy significantly improved solubility of CY-1-4. With the particle size about 116 nm, encapsulating efficacy was about 83% and the drug loading capacity was about 4.80%. Ferroptosis mechanistic studies indicated that CY-1-4 NPs could improve the ROS level in B16-F10 cells, whereas ferrostatin-1 and DFO could partly inhibited the cytotoxicity and PPIX could potentiated the cytotoxicity of CY-1-4 NPs in B16-F10 cells. These results showed that ferroptosis was one of the cell death mechanisms induced by tryptanthrin derivative CY-1-4 nanoparticle.

Clinical study of carotid endarterectomy and carotid artery stenting in treating carotid artery stenosis in the elderly / 中华老年医学杂志

Objective To investigate the clinical efficacy and safety of carotid endarterectomy (CEA)and carotid artery stenting(CAS)for the treatment of carotid artery stenosis in the elderly.Methods Clinical data of 116 elderly patients aged over 65 years with carotid artery stenosis were retrospectively analyzed.Of 116 patients,73 patients underwent CAS(the CAS group) and 32 received CEA(the CEA group).The success rate,30-day perioperative complications and follow-up results were compared between the two groups.Results There was no significant difference in the success rate (96.8％ vs.100.0％,P ＞ 0.05),30-day perioperative complications,such as bradycardia (6.25％ vs.4.5％,x2 =0.228,P=0.663),acute myocardial infarction(0.0 vs.1.4％,x2 =0.432,P=0.511),transient hypotension(6.3％ vs.8.1％,x2 =0.114,P =0.735),ischemic stroke(6.3％ vs.6.8％,x2 =0.009,P =0.923),and cerebral hyperperfusion syndrome (18.8 ％ vs.10.8％,x2 =0.009,P =0.923),between the CEA and CAS groups.The incidence of persistent hypotension was lower in the CEA group than in the CAS group(3.1％ vs.17.6％,x2 =4.398,P=0.036).No significant difference was found in carotid artery restenosis(moderate:6.3％ vs.8.1％,x2 =0.114,P =0.735;severe:3.1 ％ vs.2.7％,x2=0.014,P=0.905)and ipsilateral stroke(3.1％ vs.5.4％,x2 =0.279,P=0.598)between the CEA and CAS groups at one-year fellow-up.Conclusions Both CEA and CAS have good effieacies in treating carotid artery stenosis in the elderly,while the incidence of persistent hypotension is higher with CAS than with CEA.

Pathogenesis of diabetic cognitive dysfunction and intervention by traditional Chinese medicine / 中国药理学通报

Diabetic cognitive dysfunction (DCD) is a common chronic complication of diabetes mellitus with sophisticated path-ogenesis which has not yet been fully elucidated. In this review paper, the mechanisms of metabolic abnormalities, insulin re-sistance,endoplasmic reticulum stress,neuronal calcium dysho-meostasis, in ammation, blood brain barrier impairment, and mitochondrial injury associated with DCD are reviewed. In addi-tion,the prevention and treatment of DCD by traditional Chinese medicines (TCMs) and the effective compounds are comprehen-sively summarized, in order to provide an updated overview on the DCD pathogenesis,as well as the scientific evidence under-pinning the use of TCM interventions for the treatment and pre-vention of DCD.

The effects of carotid artery stenting on ophthalmic artery blood flow in ischemic ophthalmopathy patients / 中华眼底病杂志

Objective To observe the effects of carotid artery stenting (CAS) on ophthalmic artery blood flow in patients with ischemic ophthalmopathy (IOP).Methods A prospective case-control study.Sixty IOP patients (60 eyes) who met inclusive criteria for CAS were enrolled in this study.There was 50％ stenosis of internal carotid artery on one side at least confirmed by color doppler flow imaging (CDFI).Among 60 eyes,there were 3 eyes with central retinal artery occlusion,15 eyes with retinal vein occlusion,37 eyes with ischemic optic neuropathy,5 eyes with ocular ischemia syndrome.The patients were randomly divided into CAS group (32 eyes of 32 patients) and medicine therapy group (28 eyes of 28 patients).The difference of age (t=1.804) and sex (x2=1.975) between two groups was not significant (P＞0.05).The examinations of fundus fluorescein angiography (FFA),CDFI and digital substraction angiography (DSA) were performed before,1 week and 6 months after treatment.The following parameters were recorded:arm-retinal circulation time (A-Rct),peak systolic velocity (PSV),end-diastolic velocity (EDV),and resistance index (RI) in the ophthalmic artery (OA) and central retinal artery (CRA),and the best corrected visual acuity (BCVA).Results There was no significant differences in A-Rct (t=1.354) and BCVA (t=0.376) between the two groups before treatment (P＞0.05).Also,there was no significant differences in PSV (t=-0.294,-2.446),EDV (t=0.141,-0.305),and RI (t=-0.222,-0.694) of OA and CRA between the two groups before treatment before treatment (P＞0.05).Compared with the medicine therapy group,the lower A-Rct was found in the CAS group at different time points after the treatment.The difference was significant on 1 week after treatment (t=-3.205,P＜0.05),but not on 6 months after treatment (t=1.345,P＞0.05).The BCVA of eyes in the two groups were increasing with the extending of time of therapy.Compared with the medicine therapy group,the better BCVA was found in the CAS group at different time points after the treatment (t=0.800,1.527;P＜0.05).Compared with the medicine therapy group,the higher PSV,EDV and lower RI of OA and CRA were found in the CAS group at different time points after the treatment.(P＜0.05).Conclusion Compared with conventional medicine therapy,CAS shows earlier effects in improving ocular hemodynamics for IOP patients with carotid artery stenosis,which benefits visual function improvement of the patients.

Protective effects and underlying mechanisms of Panax notoginseng saponins against SH-SY5Y cell apoptosis induced by 6-hydroxydopamine / 药学学报

The aim of this study is to investigate the protective effects of Panax notoginseng saponins (PNS) against 6-hydroxydopamine (6-OHDA)-induced apoptosis in SH-SY5Y cells and the possible underlying mechanisms. Cell viability was examined by MTT assay. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) were measured using the respective assay kits. Apoptosis was measured by TUNEL kit, JC-1 and ROS was measured by staining with fluorescent dyes. The activation of caspase-3 was measured with the caspase-3 assay kit. The expression of nuclear protein Nrf2 and HO-1 were determined by Western blot. PNS had significant protective effects against 6-OHDA-induced apoptosis in SH-SY5Y cells in a time- and dose-dependent manner. PNS could attenuate 6-OHDA-induced suppression of SOD, GAT, GSH-Px (PPP<0.01). Moreover, PNS pretreatment increased the expression of the nuclear Nrf2 and up-regulate HO-1. The protective effects of PNS could be inhibited by HO-1 inhibitor SnPP. In conclusion, PNS has significant protective effects against 6-OHDAinduced apoptosis in SH-SY5Y cells. The possible mechanisms of PNS are due to PNS-mediated activation of Nrf2, up-regulation of HO-1 and inhibition of oxidative stress.

Effects of Qizhi Jiangtang capsule on dermal ulcer in type 2 diabetic rats / 中国中药杂志

The effect of Qizhi Jiangtang vapsule (QJC) on degree of dermal ulcer cicatrization in 2 type diabetic rats was studied. Except the rats for blank group, other male Wistar rats were used to establish type 2 diabetic model by feeding with high sugar and high fat diet for four weeks and intraperitonally injecting with 30 mg•kg⁻¹ streptozotocin (STZ). After that, the rats were divided into balanced groups according to blood sugar, and received corresponding drugs for treatment for 8 weeks. At the end of week 8, 2 cm diameter circular incision was done on the back of rats. After that, the rats were administered continuously for10 days. Area of ulcer surface was detected every two days. After the last administration, wound granulation tissues were cut down to conduct pathological examination and detect the expression of VEGF, PI3K, p-ERK protein in wound tissues. The results showed that compared with the model group, after application of Qizhi Jiangtang capsule (2.24 g•kg⁻¹), the wound was significantly reduced on day 6 and day 10 of wound formation; inflammation reaction on ulcer surface was significantly reduce; Qizhi Jiangtang capsule can increase VEGF expression in the wound tissues of diabetic rats, and inhibit ERK phosphorylation. It can be concluded that Qizhi Jiangtang capsule can promote skin ulcer healing for diabetes rats, and its mechanism may be related to regulating the expression of VEGA and p-ERK proteins.

Effects of Qizhi Jiangtang capsule on protein expressions of InsR, PI3K, GLUT2 and p-JNK in hepatic tissues of rats with type 2 diabetes / 中国中药杂志

To observe the hypoglycemic effect of Qizhi Jiangtang capsule in rats with type 2 diabetes, and investigate the preliminary mechanism of its hypoglycemic effect, type 2 diabetes rat models were established by high glucose and high fat combined with small dose of streptozotocin (STZ). After continuous administration for 6 weeks, blood glucose, and glycosylated serum protein (GSP) levels were detected in all of the animals; immunohistochemistry assay was used to detect the number of islet β cells; Western blot assay was used to detect the protein expression levels of insulin receptor (InsR), phosphoinositide-3 kinases (PI3K), glucose transporter-2 (GLUT2) and phosphorylated Jun N-terminal kinases (p-JNK)in hepatic tissues. The results showed that Qizhi Jiangtang capsule could reduce the blood sugar and GSP levels in serum in animals with type 2 diabetes mellitus, increase the level of insulin in serum and number of islet β cells, increase the protein expression levels of InsR, PI3K and GLUT2, and reduce the level of p-JNK protein expression. In conclusion, Qizhi Jiangtang capsule has relatively stable hypoglycemic effect, and the mechanism may be associated with increasing the number of islet β cells and level of insulin in serum, up-regulating the protein expression levels of InsR, PI3K and GLUT2, down-regulating the level of p-JNK protein expression in hepatic tissues, and reducing the level of insulin in hepatic tissues.

Cognitive function of male recruits exposed to 3 700 maltitude for different periods: A comparison between 3 months and 15 months / 第二军医大学学报

Objective To compare the cognitive function changes of newly-recruited male soldiers after exposure to 3 700 m altitude for 3 months and 15 months. Methods Using "pretest-posttest design", we selected 22 newly-recruited male soldiers in this experiment, and 8 cognitive function variables, namely, the reaction and motion time, speed-perception, time-perception, depth-perception, operating-dexterity, memory span, short-term memory and attention span were analyzed by paired comparison for 3 months and 15 months. Results Compared with soldiers exposed for 3 months, those exposed for 15 months had significantly increased reaction time (P<0.05), significantly decreased operating-dexterity performance (P<0.05), and significantly improved memory (P<0.05). The depth-perception was more liable to have the "see close" phenomenon. Conclusion Compared to those exposed to high altitude environment for 3 months, newly-recruited male soldiers exposed for 15 months have a more apparent damage to the reaction time, depth-perception, operating-dexterity and attention.

Inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma: in vitro and in vivo studies

OBJECTIVE@#To investigate the inhibitory effect of humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on growth of human hepatocellular carcinoma both in vitro and in vivo, which may be a potential agents with sensitivity and targeting ability for human hepatocellular cancer.@*METHODS@#Humanized anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate was previously constructed using ribosome display technology and antibody conjugate technology. In this combined in vitro and in vivo study, the inhibitory effects of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles conjugate on tumor growth, invasion, and metastasis was observed with human liver carcinoma cell line Bel7402 and normal cell L02 by MTT assay, Tanswell assay, Hochest33258 staining, and DNA ladder analysis. The anticancer activity and distribution of anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles was then verified in a mouse model of Bel7402 xenografts.@*RESULTS@#Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly inhibited the proliferation of Bel7402 in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay while had almost no effects on L02 cells. And the apoptosis inducing effects were proved by Hochest33258 staining and DNA ladder analysis. Transwell assay found that the drug also inhibited the metastasis ability of tumor cells. Furthermore, anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles significantly delayed the growth of Bel7402 xenografts after administration (92.9%), followed by As2O3-stealth nanoparticles, anti-VEGFR-2 ScFv, and As2O3 (61.4%, 58.8%, 20.5%, P<0.05). The concentration of As2O3 in anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles group was more selectively.@*CONCLUSIONS@#Anti-VEGFR-2 ScFv-As2O3-stealth nanoparticles is a potent and selective anti-hepatocellular carcinoma agent which could inhibit the growth of liver cancer as a targeting agent both in vitro and in vivo and also significantly inhibit angiogenesis.

Comparative analysis between breast conventional mammography and amplificatory mammography with partial compression in 65 cases of breast cancer / 中国基层医药

Objective To discuss the correlationship between the diagnosis of surgical pathology and the signs of malignancy which is both displayed by breast conventional mammography and amplificatory mammography with partial compression.Methods 65 cases with breast cancer were examined by both breast conventional mammography and amplificatory mammography with partial compression.The results of the two methods were analyzed.Results In all 65 cases of breast cancer,the comparison between breast conventional mammography and amplificatory mammography with partial compression could provide 16/60 cases in the X-ray signs of malignancy,which were in accordance with pathological examination results,19/41cases in the occurrence of calcification,13/37 cases in ductal calcification,0/4 cases in mixed type calcification,18/46 and 14/59 cases in the occurrence of lobulation and spicule signs.Conclusion Amplificatory mammography with partial compression can provide better insight in breast cancer than conventional mammography,especially in the region of dense shadow,small calcification and dense breast lesions,amplificatory mammography with partial compression can provide higher accuracy in diagnosis,especially for early breast cancer.

Protect effects and the underlying mechanisms of myricitrin against vascular endothelial cells apoptosis induced by oxidative stress / 药学学报

This study is to report the study of protective effects of myricitrin against oxidative stress-induced apoptosis of vascular endothelial cells and the investigation of the possible mechanisms of action of myricitrin. The model of H2O2-induced apoptosis of vascular endothelial cells was used to determine the protective effects of myricitrin. The levels of LDH, MDA and the activities of SOD, NO were measured using the respective kits. The H2O2-induced apoptosis of vascular endothelial cells was detected using MTT reduction, TUNEL assay, JC-1 and ROS staining. The activation of Caspase-3 was also measured by fluorometry. The expression of apoptosis-related proteins was determined with Western blotting assay. Myricitrin had significant protective effects against H2O2-induced apoptosis of vascular endothelial cells in a time- and dose-dependent manner. The results show that myricitrin could attenuate H2O2-induced decrease in the activities of SOD (P < 0.01). Myricitrin could decrease the levels of LDH, MDA and increase cell viability and the mitochondrial membrane potential (P < 0.01). Myricitrin had protective effects in a dose-dependent manner between 32 micromol x L(-1) to 64 micromol x L(-1). Myricitrin pretreatment could attenuate H2O2-induced increase of p-ERK. Moreover, myricitrin pretreatment could up-regulate the expression of the anti-apoptotic protein Bcl-2, down-regulate the expression of the pro-apoptotic protein Bax, and decrease the expression of Caspase-3, 9. In conclusion, myricitrin had significant protective effects against H2O2-induced apoptosis of vascular endothelial cells. Myricitrin can enhance the activities of anti-oxidative enzymes and decrease the production of free radicals. The possible mechanisms of action of myricitrin are due to myricitrin-mediated inhibition of phosphorylation of the apoptosis signaling pathways-related kinase ERK, up-regulation of the expression of the anti-apoptotic protein, and down-regulation of the expression of the pro-apoptotic protein.

Differential effect of simulated microgravity on myogenic tone of middle cerebral and mesenteric small arteries in rats / 生理学报

The aim of the present study was to investigate the effect of a short-term (3-day) simulated microgravity with and without daily dorsoventral gravitation (-G(x)) for 1 h on myogenic tone and vasoconstrictor responsiveness of the middle cerebral artery and mesenteric third-order small artery in rats. The tail-suspension (SUS) model was used to simulate cardiovascular deconditioning due to microgravity. Daily restoring to normal standing (STD) posture for 1 h was adopted to provide -G(x) as the countermeasure. Segments of middle cerebral artery and mesenteric third-order small artery were isolated and cannulated. Vascular diameters in response to increased intraluminal pressure (from 20 mmHg to 120 mmHg, by 20 mmHg steps) of isolated arteries under no-flow conditions were recorded by a Pressure Myograph System in both physiologic salt solution (PSS) (active diameter, Da) and calcium-free PSS (passive diameter, Dp). The myogenic tone was calculated by (Dp-Da)/Dpx100%. Vasoconstrictor responsiveness of the isolated middle cerebral artery to serotonin and that of small mesenteric artery to phenylephrine were assessed in the PSS under an intraluminal pressure of 40 mmHg. The results showed that SUS induced an enhancement of the myogenic tone and vasoconstrictor responsiveness in the isolated middle cerebral artery but a depression of those in the small mesenteric artery. Daily STD for 1 h prevented the depression of myogenic tone and vasoconstrictor responsiveness in the small mesenteric artery, but did not prevent the functional enhancement in the middle cerebral artery. These data suggest that a short-term simulated microgravity may result in different alterations in the function of the cerebral artery and the resistance vessel in the hind-body. Moreover, only the decrease of function in these resistance vessels, not in the cerebral arteries, can be prevented by such a countermeasure of daily STD for 1 h.

Quantification of mRNA expression for angiotensinogen in rat arterial tissues by real-time PCR / 中国应用生理学杂志

<p><b>AIM</b>To develop a real-time PCR method for quantifying low abundance mRNA expression in rat arterial tissues and examine differential changes of angiotensinogen (AGT) gene expression in basilar and femoral arterial tissues after 8 weeks simulated weightlessness.</p><p><b>METHODS</b>After 8-wk of simulation, basilar and femoral arteries were harvested from both simulated weightless (SUS) and control (CON) rats. Then total RNA was extracted and reverse transcribed. The real-time PCR using TaqMan-MGB probe was performed to quantify AGT mRNA expression. The amplification efficiency (E) of PCR was calculated from the slope of standard curve. The threshold cycle (Ct) was detected by changes in fluorescence during a real-time PCR. Finally, the relative expression ratio of the target gene (AGT) to the reference gene (GAPDH) was calculated using E and Ct according to the mathematical model derived from the equation calculating the starting fluorescence (Ro).</p><p><b>RESULTS</b>After a 8-weeks simulated weightlessness, the AGT mRNA expression increased by 240 percent in basilar arterial, and decreased by 66 percent in femoral arterial tissues.</p><p><b>CONCLUSION</b>The specificity, sensitivity, precision, reproducibility, and simplicity of real-time PCR method using TaqMan-MGB probe make it particularly suitable for quantification of low abundance mRNA in arterial tissue from rats.</p>

CT and MRI Findings of the Spongiform Myelinopathy in Poisoning by Heroin / 实用放射学杂志

Objective To study CT and MRI findings of the spongiform myelinopathy in poisoning by heroin.Methods CT and MRI findings in 6 patients with spongiform myelinopathy in poisoning by heroin were retrospectively analyzed with review of literature.Results The lesions were located in white matter,they were multiform and symmetrically distributed.On plain CT scans,the lesions were low density.On MRI,the lesions were low signal on T1WI and high signal on T2WI.The border of lesions was clear or not and no enhancement appeared.MRI is precedent of CT in the diagnosis of this disease,totally 55 focal lesions in the brain ,4 in midbrain and 8 in cerebellum were displayed by MRI.Conclusion CT and MRI findings of the spongiform myelinopathy in poisoning by heroin are more characteristic,according to the drug taking history and central nervous system symptom of patients,differentiating this disease from the other demyelinating disease is not difficult.

The Experimental Research of Primary Technique Parameter in Fluid Attenuated Inversion Recovery / 实用放射学杂志

Objective To study the correlation between the main parameters and the effect of repression in MR fluid attenuated inversion recovery(FLAIR).Methods 0.5 unit was used in this experiment.The protein aqua of different material appearance and concentration was prepared.FLAIR was performed using the tube imitative experimented method and with different paramters.The best scan parameters were selected by comparison each other and their relativity was analysed.Results The best technical parameters:TR=4000~5000 ms,TE=90~100 ms,TI=1800~2000 ms.Conclusion TI is the key parameter in determining the repression effect,TR and TE only determine the scans time and layer number.FLAIR's repress result is stable,and it can estimate the protein content in the protein aqua.

Advances on Polyketide Biosynthesise by Microorganism and the Diversity of Polyketide Synthases / 微生物学通报

Polyketides are very large group of natural products with functional and structural diversity.Most of them are produced by microor- ganism and have medicinal activities,including antibiotic,anticancer,antifungal and antiparasitic properties.The researchs in this area have progressed greatly.More and more polyketides are discovered,on the other hand the mechanisms of biosynthesis of those various polyketides are researched more deeply and clearly.The article reviewed the progress of the research in the diversity of polyketide synthases and the mechanisms of polyketide biosynthesise.