508 research outputs found
Ligustrazine Inhibits the Migration and Invasion of Renal Cell Carcinoma
Ligustrazine is a Chinese herb (Chuanxiong) approved for use as a medical drug in China. Recent evidence suggests that ligustrazine has promising antitumor properties. Our preliminary results showed that ligustrazine could inhibit the growth of human renal cell carcinoma (RCC) cell lines. However, the complicated molecular mechanism has not been fully revealed. Therefore, the purpose of this study to investigate the mechanism of ligustrazine resistance in human RCC cells. Cell proliferation, migration, invasion, and colony-formation ability of RCC cells A498 were detected by MTT assay, clonal formation rates, and transwell chamber assay in vitro. The expression of epithelialâmesenchymal transition (EMT)ârelated proteins were analyzed using western blot test. The effect of ligustrazine on the growth of A498 cells in nude mice was investigated in vivo. Our results showed that ligustrazine could significantly inhibit the proliferation, migration, and invasion of A498 both in vivo and vitro. Western blot analysis showed that the expressions of EMT-related, N-cadherin, snail, and slug proteins were significantly decreased in A498 in the ligustrazine treatment group. This study indicated that ligustrazine could significantly inhibit the malignant biological behaviors of RCC cell lines, possibly by inhibiting the EMT process
Inhibition of Drug Resistance of Staphylococcus aureus by Efflux Pump Inhibitor and Autolysis Inducer to Strengthen the Antibacterial Activity of β-lactam Drugs
Spatial-temporal analysis of malaria and the effect of environmental factors on its incidence in Yongcheng, China, 2006â2010
BACKGROUND: In 2003, Plasmodium vivax malaria has re-emerged in central eastern China including Yongcheng prefecture, Henan Province, where no case has been reported for eleven years. Our goals were to detect the space-time distribution pattern of malaria and to determine significant environmental variables contributing to malaria incidence in Yongcheng from 2006 to 2010, thus providing scientific basis for further optimizing current malaria surveillance and control programs. METHODS: This study examined the spatial and temporal heterogeneities in the risk of malaria and the influencing factors on malaria incidence using geographical information system (GIS) and time series analysis. Univariate analysis was conducted to estimate the crude correlations between malaria incidence and environmental variables, such as mosquito abundance and climatic factors. Multivariate analysis was implemented to construct predictive models to explore the principal environmental determinants on malaria epidemic using a Generalized Estimating Equation (GEE) approach. RESULTS: Annual malaria incidence at town-level decreased from the north to south, and monthly incidence at prefecture-level demonstrated a strong seasonal pattern with a peak from July to November. Yearly malaria incidence had a visual spatial association with yearly average temperature. Moreover, the best-fit temporal model (model 2) (QICâ=â16.934, P<0.001, R(2)â=â0.818) indicated that significant factors contributing to malaria incidence were maximum temperature at one month lag, average humidity at one month lag, and malaria incidence of the previous month. CONCLUSIONS: Findings supported the effects of environment factors on malaria incidence and indicated that malaria control targets should vary with intensity of malaria incidence, with more public resource allocated to control the source of infections instead of large scale An. sinensis control when malaria incidence was at a low level, which would benefit for optimizing the malaria surveillance project in China and some other countries with unstable or low malaria transmission
Trimodal Therapy: A Tumor Vascularâ Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia (Adv. Sci. 8/2018)
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145503/1/advs201870048.pd
A Tumor Vascularâ Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia
Vascularâ targeted photodynamic therapy (VTP) is a recently approved strategy for treating solid tumors. However, the exacerbated hypoxic stress makes tumor eradication challenging with such a single modality approach. Here, a new graphene oxide (GO)â based nanosystem for rationally designed, interlocking trimodal cancer therapy that enables VTP using photosensitizer verteporfin (VP) (1) with codelivery of banoxantrone dihydrochloride (AQ4N) (2), a hypoxiaâ activated prodrug (HAP), and HIFâ 1ĂÂą siRNA (siHIFâ 1ĂÂą) (3) is reported. The VTPâ induced aggravated hypoxia is highly favorable for AQ4N activation into AQ4 (a topoisomerase II inhibitor) for chemotherapy. However, the hypoxiaâ induced HIFâ 1ĂÂą acts as a â hidden brake,â through downregulating CYP450 (the dominant HAPâ activating reductases), to substantially hinder AQ4N activation. siHIFâ 1ĂÂą is rationally adopted to suppress the HIFâ 1ĂÂą expression upon hypoxia and further enhance AQ4N activation. This trimodal nanosystem significantly delays the growth of PCâ 3 tumors in vivo compared to the control nanoparticles carrying VP, AQ4N, or siHIFâ 1ĂÂą alone or their pairwise combinations. This multimodal nanoparticle design presents, the first example exploiting VTP to actively induce hypoxia for enhanced HAP activation. It is also revealed that HAP activation is still insufficient under hypoxia due to the hidden downregulation of the HAPâ activating reductases (CYP450), and this can be well overcome by GO nanoparticleâ mediated siHIFâ 1ĂÂą intervention.Vascularâ targeted photodynamic therapy (VTP) is integrated with hypoxiaâ activated prodrug (AQ4N) and HIFâ 1ĂÂą siRNA (siHIFâ 1ĂÂą) for interlocking trimodal therapy. The VTPâ induced aggravated hypoxia is exploited for efficient AQ4N activation for chemotherapy. HIFâ 1ĂÂą induced by hypoxia acts as a â hidden brake,â through downregulating CYP450 reductases, to hinder AQ4N activation. siHIFâ 1ĂÂą is rationally adopted to suppress HIFâ 1ĂÂą expression upon VTP to enhance AQ4N activation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145505/1/advs661-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145505/2/advs661.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145505/3/advs661_am.pd
Isolation, Purification, Identification and Hypolipidemic Activity of Lipase Inhibitory Peptide from Chlorella pyrenoidosa
In this study, pancrelipase inhibitory peptides (PES) from an enzymatic protein hydrolysate of Chlorella pyrenoidosa were isolated and purified by ultrafiltration and Sephadex gel chromatography. The in vivo hypolipidemic activity of PES was evaluated by fat deposition and the levels of triglyceride (TG) and total cholesterol (TC) in Caenorhabditis elegans fed a high sugar diet. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the peptide sequence of PES, and molecular docking was used to select potential pancreatic lipase inhibitory peptides, and the pancreatic lipase inhibitory activity of the synthesized peptides was verified. The results showed that PES had good hypolipidemic activity at a concentration of 1 mg/mL; it inhibited lipid deposition by 22.5%, and reduced the levels of TG and TC by 27.4% and 29.4%, respectively. In total, 999 peptides were identified, and four potential lipase inhibitory peptides were obtained. Among them, FLGPF had the best inhibitory effect on pancreatic lipase, with an inhibition rate of 50.12% at 8 mg/mL. The inhibition was reversible and non-competitive, with an inhibition constant of 5.23 mg/mL. Molecular docking showed that FLGPF could better bind to human pancreatic triacylglycerol lipase (PTL) via Ď-hydrogen, Ď-cation and hydrogen bond interactions. This study can provide a theoretical reference for the development and utilization of C. pyrenoidosa protein-derived hypolipidemic peptide
Sensitivity enhancement of a Cu (II) metal organic framework-acetylene black-based electrochemical sensor for ultrasensitive detection of imatinib in clinical samples
Imatinib (IMB), an anticancer drug, is extensively used for chemotherapy to improve the quality of life of cancer patients. The aim of therapeutic drug monitoring (TDM) is to guide and evaluate the medicinal therapy, and then optimize the clinical effect of individual dosing regimens. In this work, a highly sensitive and selective electrochemical sensor based on glassy carbon electrode (GCE) modified with acetylene black (AB) and a Cu (II) metal organic framework (CuMOF) was developed to measure the concentration of IMB. CuMOF with preferable adsorbability and AB with excellent electrical conductivity functioned cooperatively to enhance the analytical determination of IMB. The modified electrodes were characterized using X-rays diffraction (XRD), X-ray photoelectron spectroscopy (XPS), fourier transform infrared (FT-IR), ultraviolet and visible spectrophotometry (UV-vis), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), energy dispersive Xâray spectroscopy (EDS), brunauerâemmettâteller (BET) and barrettâjoynerâhalenda (BJH) techniques. Analytical parameters such as the ratio of CuMOF to AB, dropping volumes, pH, scanning rate and accumulation time were investigated through cyclic voltammetry (CV). Under optimal conditions, the sensor exhibited an excellent electrocatalytic response for IMB detection, and two linear detection ranges were obatined of 2.5Â nM-1.0Â ÎźM and 1.0â6.0Â ÎźM with a detection limit (DL) of 1.7Â nM (S/N = 3). Finally, the good electroanalytical ability of CuMOF-AB/GCE sensor facilitated the successful determination of IMB in human serum samples. Due to its acceptable selectivity, repeatability and long-term stability, this sensor shows promising application prospects in the detection of IMB in clinical samples
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