Effects of hydroxysafflor yellow A on rats with collagen-induced arthritis.

Hydroxysafflor yellow A (HSYA) from safflower (Carthamus tinctorius L.) possesses several medicinal properties. However, it is unknown whether HSYA is effective in the treatment of rheumatoid arthritis (RA). Hence, we investigated the effects of HSYA on the inflammation and synovial damage in rats with collagen-induced arthritis (CIA) by subjecting them to treatment with different doses of HSYA. Our results revealed that HSYA could significantly reduce paw swelling, pathological manifestations, and serum cytokine levels in rats with CIA. The HSYA-treated groups showed increased antioxidant enzyme activity in the serum and decreased expression of inflammatory mediators in the synovial tissues. Furthermore, HSYA treatment inhibited extracellular signal-regulated kinase (ERK) signalling pathway activation. Notably, the highest dose of HSYA (20 mg/kg) exhibited the best effects against RA symptoms. Therefore, our findings suggest that HSYA alleviates the inflammatory response and synovial damage in rats with CIA by inhibiting the ERK signalling pathway.

The Effects of Lycium Barbarum Polysaccharide (LBP) in a Mouse Model of Cerulein-Induced Acute Pancreatitis.

BACKGROUND Acute pancreatitis is an inflammatory disease of the pancreas associated with high patient morbidity. Lycium barbarum polysaccharide (LBP), a traditional Chinese medicine with an active component extracted from the goji berry, has previously been reported to have anti-inflammatory effects. This study aimed to investigate the effects of LBP in a mouse model of cerulein-induced acute pancreatitis. MATERIAL AND METHODS Acute pancreatitis was induced by intraperitoneal injection of cerulein in C57BL/6 wild-type mice or nuclear factor erythroid-2-related factor 2 (NRF2) gene knockout mice. LBP or normal saline was administrated by gavage once daily for one week before the induction of acute pancreatitis. At 12 hours after the first intraperitoneal injection of cerulein, the mice were euthanized. Blood and pancreatic tissue were sampled for histology and for the measurement of pro-inflammatory cytokines, serum amylase, and lipase. RESULTS In the untreated mouse model of cerulein-induced acute pancreatitis, amylase and lipase levels were increased, and these levels were reduced by LBP treatment when compared with vehicle treatment. In the untreated mouse model, histology of the pancreas showed edema and inflammation, which were reduced in the LBP-treated mice. In the untreated mouse model, increased levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were found, which were reduced in the LBP-treated mice. NRF2 gene knockout mice with cerulein-induced acute pancreatitis showed reduced anti-inflammatory effects of LBP treatment. LBP increased the expression of NRF2 and heme oxygenase-1 (HO-1). CONCLUSIONS In a mouse model of cerulein-induced acute pancreatitis, LBP reduced inflammation by upregulating NRF2 and HO-1.

Pyridinium and indole orientation determines the mitochondrial uncoupling and anti-cancer efficiency of F16.

F16 is a mitochondria-targeted, broad-spectrum anticancer agent in the pre-clinic cancer therapy. Here we developed two fluorescent isomers of F16 (o-F16 and m-F16) with entirely different photophysical properties, uncoupling activity, and cytotoxicity by merely modifying the linking orientation of pyridinium and indole units. Individually, o-F16 acted as a strong uncoupler to reduce the mitochondrial respiration efficiency, while m-F16 could hardly uncouple the mitochondrial respiration due to its poor proton dissociation capability. Owing to their intrinsic fluorescence, o-F16 and m-F16 could specifically image mitochondria in the green and red channel, respectively. This work could provide useful information for the development of uncouplers and design of mitochondrial-targeted drugs.

[Effects of soil wetting pattern on the soil water-thermal environment and cotton root water consumption under mulched drip irrigation].

Abstract: To explore the effects of soil wetting pattern on soil water-thermal environment and water consumption of cotton root under mulched drip irrigation, a field experiment with three drip intensities (1.69, 3.46 and 6.33 L · h(-1)), was carried out in Shihezi, Xinjiang Autonomous Region. The soil matric potential, soil temperature, cotton root distribution and water consumption were measured during the growing period of cotton. The results showed that the main factor influencing the soil temperature of cotton under plastic mulch was sunlight. There was no significant difference in the soil temperature and root water uptake under different treatments. The distribution of soil matrix suction in cotton root zone under plastic mulch was more homogeneous under ' wide and shallow' soil wetting pattern (W633). Under the 'wide and shallow' soil wetting pattern, the average difference of cotton root water consumption between inner row and outer row was 0.67 mm · d(-1), which was favorable to the cotton growing trimly at both inner and outer rows; for the 'narrow and deep' soil wetting pattern (W169), the same index was 0.88 mm · d(-1), which was unfavorable to cotton growing uniformly at both inner and outer rows. So, we should select the broad-shallow type soil wetting pattern in the design of drip irrigation under mulch.

A novel bifunctional mitochondria-targeted anticancer agent with high selectivity for cancer cells.

Mitochondria have recently emerged as novel targets for cancer therapy due to its important roles in fundamental cellular function. Discovery of new chemotherapeutic agents that allow for simultaneous treatment and visualization of cancer is urgent. Herein, we demonstrate a novel bifunctional mitochondria-targeted anticancer agent (FPB), exhibiting both imaging capability and anticancer activity. It can selectively accumulate in mitochondria and induce cell apoptosis. Notably, it results in much higher toxicity toward cancer cells owing to much higher uptake by cancer cells. These features make it highly attractive in cancer imaging and treatment.

[Real-time irrigation forecast of cotton mulched with plastic film under drip irrigation based on meteorological date].

It is important to improve the real-time irrigation forecasting precision by predicting real-time water consumption of cotton mulched with plastic film under drip irrigation based on meteorological data and cotton growth status. The model parameters for calculating ET0 based on Hargreaves formula were determined using historical meteorological data from 1953 to 2008 in Shihezi reclamation area. According to the field experimental data of growing season in 2009-2010, the model of computing crop coefficient Kc was established based on accumulated temperature. On the basis of crop water requirement (ET0) and Kc, a real-time irrigation forecast model was finally constructed, and it was verified by the field experimental data in 2011. The results showed that the forecast model had high forecasting precision, and the average absolute values of relative error between the predicted value and measured value were about 3.7%, 2.4% and 1.6% during seedling, squaring and blossom-boll forming stages, respectively. The forecast model could be used to modify the predicted values in time according to the real-time meteorological data and to guide the water management in local film-mulched cotton field under drip irrigation.

Toxicity of CdTe QDs with different sizes targeted to HSA investigated by two electrochemical methods.

QDs have large scale application in many important areas with potential of unintentional exposure to the environment or organism during processing of a nanotechnology containing product's life cycle. In this paper, two classical electrochemical methods, cyclic voltammetry and electrochemical impedance spectroscopy were applied to investigate the influence of particle sizes of CdTe QDs on their toxicity targeted to human serum albumin (HSA) under simulative physiological conditions. The results show that the toxicity of yellow emitting QDs (YQDs) on HSA is slightly stronger than that of the green-emitting (GQDs) and red-emitting QDs (RQDs). We also compared these two classical electrochemical methods with the traditional fluorescence spectroscopy through the above results. The electrochemical methods may be more accurate and comprehensive to investigate the toxicity of QDs at the biomacromolecular level under certain conditions, though fluorescence spectroscopy is simpler and more sensitive.

Adhesion of quantum dots-induced membrane damage of Escherichia coli.

The toxicity of CdTe QDs modified with three different ligands, namely mercaptopropionic acid (MPA), N-acetyl-L-cysteine (NAC), and glutathione (GSH), were investigated via microcalorimetric, spectroscopic, and microscopic methods. The three ligand-modified QDs have nearly identical hydrodynamic size. The results of the calorimetric experiments and optical density measurements indicate that the QDs inhibited the growth of Gram-negative Escherichia coli. The toxicity order of the three QDs is MPA-CdTe QDs>GSH-CdTe QDs>NAC-CdTe QDs. The inhibitory effects of the QDs, cadmium chloride (CdCl(2)), MPA, and the CdCl(2) and MPA mixture on E. coli growth indicate that the toxicity mechanism of QDs may be related to their bacterial adhesion. When dispersed in the cell suspensions, QDs tend to have their high surface energy reduced through adsorption to the bacterial surface, as confirmed by transmission electron microscopy and inductively coupled plasma atomic emission spectroscopy results. Furthermore, the effect of QDs on the membrane fluidity and permeability was investigated. GSH-CdTe QDs have a greater effect on the membrane function of E. coli than those of MPA-CdTe and NAC-CdTe QDs. This result may be attributed to the stronger lipophilicity of GSH compared with those of MPA and NAC.

Synthesis of F16 conjugated with 5-fluorouracil and biophysical investigation of its interaction with bovine serum albumin by a spectroscopic and molecular modeling approach.

5-Fluorouracil (5-FU) has been widely used as a chemotherapy agent in the treatment of many types of solid tumors. Investigation of its antimetabolites led to the development of an entire class of fluorinated pyrimidines. However, the toxicity profile associated with 5-FU is significant and includes diarrhea, mucositis, hand-foot syndrome and myelosuppression. In aiming at reducing of the side effects of 5-FU, we have designed and synthesized delocalized lipophilic cations (DLCs) as a vehicle for the delivery of 5-FU. DLCs accumulate selectively in the mitochondria of cancer cells because of the high mitochondrial transmembrane potential (ΔΨm). Many DLCs exhibited anti-cancer efficacy and were explored as potential anti-cancer drugs based on their selective accumulation in the mitochondria of cancer cells. F16, the DLC we used as a vehicle, is a small molecule that selectively inhibits tumor cell growth and dissipates mitochondrial membrane potential. The binding of the conjugate F16-5-FU to bovine serum albumin (BSA) was investigated using spectroscopic and molecular modeling approaches. Fluorescence quenching constants were determined using the Stern-Volmer equation to provide a measure of the binding affinity between F16-5-FU and BSA. The activation energy of the interaction between F16-5-FU and BSA was calculated and the unusually high value was discussed in terms of the special structural block indicated by the molecular modeling approach. Molecular modeling showed that F16-5-FU binds to human serum albumin in site II, which is consistent with the results of site-competitive replacement experiments. It is suggested that hydrophobic and polar forces played important roles in the binding reaction, in accordance with the results of thermodynamic experiments.

Spectroscopic studies on the interactions between CdTe quantum dots coated with different ligands and human serum albumin.

This paper investigates the interactions between human serum albumin (HSA) and CdTe quantum dots (QDs) with nearly identical hydrodynamic size, but capped with four different ligands (MPA, NAC, and GSH are negatively charged; CA is positively charged) under physiological conditions. The investigation was carried out using fluorescence spectroscopy, circular dichroism (CD) spectra, UV-vis spectroscopy, and dynamic light scattering (DLS). The results of fluorescence quenching and UV-vis absorption spectra experiments indicated the formation of the complex of HSA and negatively charged QDs (MPA-CdTe, NAC-CdTe, and GSH-CdTe), which was also reconfirmed by the increasing of the hydrodynamic radius of QDs. The K(a) values of the three negatively charged QDs are of the same order of magnitude, indicating that the interactions are related to the nanoparticle itself rather than the ligands. ΔH<0 and ΔS>0 implied that the electrostatic interactions play predominant roles in the adsorption process. Furthermore, it was also proven that QDs can induce the conformational changes of HSA from the CD spectra and the three-dimensional fluorescence spectra of HSA. However, our results demonstrate that the interaction mechanism between the positively charged QDs (CA-CdTe) and HSA is significantly different from negatively charged QDs. For CA-CdTe QDs, both the static and dynamic quenching occur within the investigated range of concentrations. According to the DLS results, some large-size agglomeration also emerged.

Synthesis of three novel anionic gemini surfactants and comparative studies of their assemble behavior in the presence of bovine serum albumin.

Three novel anionic sulfonate gemini surfactants, sodium 4,4'-(10,19-dioxo-9,11,18,20-tetraazaoctacosane-9,20-diyl) dibenzenesulfonate (Surfactant I), sodium 4,4'-(12,21-dioxo-11,13,20,22-tetraazadotriacontane-11,22-diyl) dibenzenesulfonate (Surfactant II), and sodium 4,4'-(14,23-dioxo-13,15,22,24-tetraazahezatriacontane-13,24-diyl) dibenzenesulfonate (Surfactant III), with different lengths of hydrophobic tail have been synthesized, and their assembly behavior in the presence of bovine serum albumin (BSA) has been studied using spectral methods and molecular modeling methods at physiological pH and 298 K. Critical micelle concentrations (CMCs) of the three surfactants have been determined by surface tension measurements. Despite the obvious decrease of CMC with the increase of tail length, fluorescence spectra have shown much closer CAC in the presence of BSA. Surfactant II shows the highest CAC of 3.19 × 10(-5) mol L(-1) compared with the other two. The polarity of the microenvironment in BSA-surfactant systems has been investigated using pyrene as the probe. In addition, far-UV CD spectra studied the change of the secondary structure content of BSA caused by the three surfactants. The features of the assembly behavior were discussed by three concentration regions. Surfactant II could unfold the protein much more efficiently than the other two surfactants at low concentration, but at high concentration, the change of the secondary structure and the formation of hydrophobic microenvironment show a direct relationship to the length of the hydrophobic tail with the increase of the surfactant concentration.

Spectroscopic, structural and thermodynamic properties of chlorpyrifos bound to serum albumin: A comparative study between BSA and HSA.

Chlorpyrifos (CPF) is a widely used organophosphate insecticide which could bind with human serum albumin (HSA) and bovine serum albumin (BSA). The binding behavior was studied employing fluorescence, three-dimensional fluorescence, Circular dichroism (CD) spectroscopy, UV-vis absorption spectroscopy, electrochemistry and molecular modeling methods. The fluorescence spectra revealed that CPF causes the quenching of the fluorescence emission of serum albumin. Stern-Volmer plots were made and quenching constants were thus obtained. The results suggested the formation of the complexes of CPF with serum albumins, which were in good agreement with the results from electrochemical experiments. Association constants at 25°C were 3.039 × 10(5) mol L(-1) for HSA, and 0.3307 × 10(5) mol L(-1) for BSA, which could affect the distribution, metabolism, and excretion of pesticide. The alterations of protein secondary structure in the presence of CPF were confirmed by the evidences from UV and CD spectra. Site competitive experiments also suggested that the primary binding site for CPF on serum albumin is close to tryptophan residues 214 of HSA and 212 of BSA, which was further confirmed by molecular modeling.

A novel pH-sensitive (±)-α-tocopherol-5-fluorouracil adduct with antioxidant and anticancer properties.

A novel pH-sensitive (±)-α-tocopherol-5-fluorouracil (VE-5-FU) adduct with antioxidant and anticancer properties for antioxidant-based cancer chemoprevention was synthesized and utilized for selective drug release in the stomach.