Preparation, Characterization, and Anti-Lung Cancer Activity of Tetrandrine-Loaded Stealth Liposomes.

Background: Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, is a potential candidate for cancer chemotherapy. However, Tet has poor aqueous solubility and a short half-life, which limits its bioavailability and efficacy. Liposomes have been widely utilized to enhance the bioavailability and efficacy of drugs. Methods: In this study, Tet-loaded stealth liposomes (S-LPs@Tet) were prepared by ethanol injection method. Furthermore, physicochemical characterisation, biopharmaceutical behaviour, therapeutic efficacy, and biocompatibility of S-LPs@Tet were assessed. Results: The prepared S-LPs@Tet had an average particle size of 65.57 ± 1.60 nm, a surface charge of -0.61 ± 0.10 mV, and an encapsulation efficiency of 87.20% ± 1.30%. The S-LPs@Tet released Tet in a sustained manner, and the results demonstrated that the formulation remained stable for one month. More importantly, S-LPs significantly enhanced the inhibitory ability of Tet on the proliferation and migration of lung cancer cells, and enabled Tet to escape phagocytosis by immune cells. Furthermore, in vivo studies confirmed the potential for long-circulation and potent tumor-suppressive effects of S-LPs@Tet. Moreover, ex vivo and in vivo safety experiments demonstrated that the carrier material S-LPs exhibited superior biocompatibility. Conclusion: Our research suggested that S-LPs@Tet has potential applications in lung cancer treatment.

Discovery of potential quality markers of Fritillariae thunbergii bulbus in pneumonia by combining UPLC-QTOF-MS, network pharmacology, and molecular docking.

Fritillariae thunbergii bulbus (FTB) is a popular Chinese herbal medicine with various applications in respiratory diseases. The quality evaluation of FTB has been insufficient to date, as the active ingredients and mechanisms of action of FTB remain unclear. This study proposes a novel strategy for exploring the quality markers (Q-markers) of FTB based on UPLC-QTOF-MS analysis, network pharmacology, molecular docking, and molecular dynamics (MD) simulation. A total of 26 compounds in FTB were identified by UPLC-QTOF-MS. Ten of these compounds were screened as Q-markers based on network pharmacology for their anti-pneumonia effects, including imperialine, peimisine, peiminine, ebeiedinone, zhebeirine, puqiedine, 9-hydroxy-10,12-octadecadienoic acid, (9Z,12Z,15Z)-13-hydroxy-9,12,15-octadecatrienoic acid, 9,12,15-octadecatrienoic acid, and (2E,4Z,7Z,10Z,13Z,16Z,19Z)-2,4,7,10,13,16,19-docosaheptaenoic acid methyl ester (DAME). These Q-markers were predicted to act on multiple targets and pathways associated with pneumonia. Molecular docking results revealed that most of the Q-markers showed high affinity with at least one of the main targets of pneumonia, and the top ten complexes were confirmed with MD simulation. Network pharmacology indicated that FTB may act on the TNF signaling pathway, HIF-1 signaling pathway, JAK-STAT signaling pathway, etc. The results demonstrated that imperialine (P8), peimisine (P9), peiminine (P11), ebeiedine (P15), zhebeirine (P16), and puqiedine (P18) may be potential Q-markers of FTB, and AKT1, IL-6, VEGFA, TP53, EGFR, STAT3, PPARG, MMP9, and CASP3 may be promising therapeutic targets for pneumonia treatment that are worthy of further research.

Mechanism of Huo-Xue-Qu-Yu Formula in Treating Nonalcoholic Hepatic Steatosis by Regulating Lipid Metabolism and Oxidative Stress in Rats.

Huo-Xue-Qu-Yu formula (HXQYF) is a prescription consisting of Ginkgo biloba leaf and Paeonia lactiflora Pall. for treating hyperlipidemia and NAFLD in China. Here, we investigated the hepatic and renal function, oxidative stress and lipid metabolism, and potential mechanisms of HXQYF on nonalcoholic fatty liver disease (NAFLD) rat models. NAFLD rat models were induced with high-fat diet (HFD) and 10% fructose water for 18 weeks and orally administered with or without HXQYF simultaneously. The results showed that HXQYF (22.5, 45, 90 mg/kg) significantly improved blood lipid levels via reducing serum TC, TG, LDL-C, and APOB values and elevating HDL-C and APOA1 levels in NAFLD rats. The higher levels of ALT, AST, CR, and BUN in serum induced by HFD were reduced by HXQYF. HE staining showed that HXQYF (90 mg/kg) reduced the accumulation of fat droplets and alleviated inflammatory response in liver cells. Three doses of HXQYF exhibited notable antioxidant effects by elevating SOD, GSH, and CAT activities and decreasing MDA and OH-1 levels in the liver. Furthermore, abnormal lipid metabolism caused by HFD was alleviated by HXQYF, which was associated with the upregulation of PPAR-α, AdipoR2, and CPT1 mRNAs as well as the downregulation of CYP2E1 and SREBP-1c mRNAs in liver tissue. In conclusion, our work verified that HXQYF could reduce the degree of hepatic steatosis, suppress oxidative stress, and attenuate lipid metabolism, thus preventing NAFLD.

[Ethanol extraction technology of Epimedii Folium and protective effect of ethanol extract on chondrocyte].

Uniform design-comprehensive scoring method was used to investigate the effects of ethanol dosage, ethanol concentration and extraction time, based on the evaluation index from transfer rates of epimedin A, epimedin B, epimedin C, icariin and baohuoside Ⅰ, which are the main active components in Epimedii Folium. Furthermore, the optimum conditions for the ethanol extraction process were determined by multiple linear stepwise regression and empirical test. Then, the ethanol extract of Epimedii Folium prepared according to the optimized technological conditions was used to intervene the injury model of chondrocyte induced by interleukin-1 beta(IL-1ß). Annexin V-FITC/PI staining flow cytometry was used to detect the apoptotic rate of chondrocyte and analyze the effect of ethanol extract of Epimedii Folium on chondrocyte injury model. The optimum conditions of ethanol extraction were as follows. Crude powder of Epimedii Folium was added with 18 times of 70% ethanol solution, and extracted for twice in the refluxing process, for 60 minutes each time. Under the conditions, the extraction rates of the above five active components were 94.21%, 94.76%, 93.85%, 96.17% and 96.85%, respectively. The optimized ethanol extraction process of Epimedii Folium was reasonable, feasible and reproducible. This ethanol extract could significantly reduce the early apoptotic rate, late apoptotic and necrotic rate, total apoptotic rate(P<0.05 or P<0.01) of chondrocyte injury model induced by IL-1ß, suggesting that the ethanol extract of Epimedii Folium can inhibit the apoptosis of chondrocytes induced by IL-1ß to a certain extent, which lays a foundation for further study on its prevention and treatment of osteoarthritis.

[Study on compatibility extraction technology of Rhei Radix et Rhizoma, Scutellariae Radix and Phellodendri Chinensis Cortex].

OBJECTIVE: To determine the optimum compatibility extraction technology of Rhei Radix et Rhizoma, Scutellariae Radix and Phellodendri Chinensis Cortex. METHOD: The drugs were combined respectively firstly, then use HPLC to determinate extraction rates of evaluating indicators including emodin, chrysophano, baicalin and berberine hydrochloride. Orthogonal experiment was used to detect the effect on concentration and volume of ethanol, times of extraction. RESULT: The extraction rates of evaluating indicators were relatively high in combined extraction of Rhei Radix et Rhizoma with Scutellariae Radix and single extraction of Phellodendri Chinensis Cortex. The optimized combined extraction were 12 times more than the volume of 60% ethanol solution, by boiling for 3 times, each for 1.0 hour, and that of single extraction were 10 times more than the volume of 60% ethanol solution, by boiling for 3 times, each for 1.0 hour. CONCLUSION: The optimized compatibility extraction technology is reasonable, stable and practical.

[Low-dose CT perfusion imaging based on pre-scan regulation and on reconstruction with sparsity constraints].

The long-period CT perfusion imaging leads to an excess amount of radiation dose to the patient. However, the radiation dose could be significantly reduced if a previous normal-dose image is acquired before a set of low-dose scans of perfusion, and a filtering processing is performed on the differences between the current low-dose images and the previous normal-dose image, then the results are added to the previous image. But the selection of plenty of parameters makes the algorithm complicated. This paper proposes an innovative approach performed in sinogram domain instead of in image domain. First a normal-dose image and a set of low-dose projection data are acquired before the perfusion. Second the perfusion information is commendably reconstructed with sparsity constraints of the differences between current low-dose perfusion sinograms and previous low-dose sinogram. Finally, the reconstructed perfusion information is added to the previous normal-dose image. The proposed method was validated by simulated experiments with a set of brain CT perfusion images, which showed that the new method provided more accurate perfusion information; the time-attenuation curve was more close to that for normal-dose scan and the mean transit time more repeatable.

[A new algorithm for affine motion compensation in PROPELLER MRI based on image domain].

Affine motion is common during PROPELLER magnetic resonance imaging (MRI) in abdomen or other soft tissues. The current algorithm, up till now, for affine motion compensation is based on frequency domain, which compensates the motion in k space and then reconstruct the final image based on gridding method. But aliasing and some tiny artifacts may exist. This paper proposed a new algorithm for affine motion compensation based on image domain. Firstly, exact affine motion information was obtained through the image registration, secondly k space coordinate was corrected for compensating the k space strips sampling density, then the images obtained from inverse FFT was compensated using motion information, finally the final results were composited after rotation. The experimental results showed that the proposed method could more effectively suppress the motion artifacts compared to the current algorithm.

Improving the maternal mortality ratio in Zhejiang Province, China, 1988-2008.

OBJECTIVE: maternal mortality remains a major public health problem in many countries. The aim of this paper is to describe the progress made in maternal health care in Zhejiang Province, China over 20 years in reducing the maternal mortality ratio (MMR). SETTING: Zhejiang Province is located on the mid-east coast of China, approximately 180km south of Shanghai, and has a population of 49 million. Almost all mothers give birth in hospitals or maternal and infant health institutes. METHOD: the annual maternal death audit reports from 1988 to 2008 were analysed. These reports were prepared annually by the Zhejiang Prenatal Health Committee after auditing each individual case. MEASUREMENTS AND FINDINGS: China has made considerable progress in reducing the MMR. Zhejiang has one of fastest developing economies in China, and since the 86 economic reforms of 1978, health care has improved rapidly and the MMR has declined. During the 1988-2008 period, 2258 maternal deaths were reported from 8,880,457 live births. During these two decades, the MMR decreased dramatically from 48.50 in 1988 to 6.57 per 100,000 in 2008. The MMR in migrant women dropped from 66.87 in 2003 to 21.67 per 100,000 in 2008. The rate of decline was more rapid in rural areas than in the city. There has been a decline in the proportion of deaths with direct obstetric causes and a corresponding increase in the proportion of indirect causes. The proportion of deaths classified as preventable has declined in the past two decades. Social factors are important in maternal safety, and on average 26.8% of maternal deaths were influenced by these factors. CONCLUSION: as the economy was developing, maternal safety was made a priority health issue by the Government and health workers. The provincial MMR has dropped rapidly and is now similar to the rates in developed countries and lower than that in the USA. However, more work is still needed to ensure that all mothers, including migrant workers, continue to have these low rates.