Andrographolide ameliorates hepatic steatosis by suppressing FATP2-mediated fatty acid uptake in mice with nonalcoholic fatty liver disease.

Excessive intrahepatocellular lipid accumulation or steatosis is caused by abnormal lipid metabolism and a common character of nonalcoholic fatty liver disease (NAFLD), which may progress into cirrhosis and hepatocellular cancer. Andrographolide (Andro) is the primary active ingredient extracted from Andrographis paniculata, showing a protective role against dietary steatosis with the mechanism not fully understood. In this study, we showed that administration of Andro (50, 100, and 200 mg/kg/day for 8 weeks, respectively) attenuated obesity and metabolic syndrome in high-fat diet (HFD)-fed mice with improved glucose tolerance, insulin sensitivity, and reduced hyperinsulinemia, hyperglycemia, and hyperlipidemia. HFD-fed mice presented hepatic steatosis, which was significantly prevented by Andro. In vitro, Andro decreased the intracellular lipid droplets in oleic acid-treated LO2 cells. The selected RT-PCR array revealed a robust expression suppression of the fatty acid transport proteins (FATPs) by Andro treatment. Most importantly, we found that Andro consistently reduced the expression of FATP2 in both the oleic acid-treated LO2 cells and liver tissues of HFD-fed mice. Overexpression of FATP2 abolished the lipid-lowering effect of Andro in oleic acid-treated LO2 cells. Andro treatment also reduced the fatty acid uptake in oleic acid-treated LO2 cells, which was blunted by FATP2 overexpression. Collectively, our findings reveal a novel mechanism underlying the anti-steatosis effect of Andro by suppressing FATP2-mediated fatty acid uptake, suggesting the potential therapeutic application of Andro in the treatment of NAFLD.

Folic Acid-Targeted Etoposide Cubosomes for Theranostic Application of Cancer Cell Imaging and Therapy.

BACKGROUND The aim of this study was to develop a novel Poloxamer-based drug delivery system featuring a tumor-targeting folate moiety, which was expected to provide better targeting properties and therapeutic effects compared with the traditional cubosomes (Cubs). MATERIAL AND METHODS Both folate-modified Cubs containing etoposide (ETP-Cubs-FA) and normal cubic nanoparticles loaded with etoposide (ETP-Cubs) were prepared through the fragmentation of bulk gels under the homogenization condition of 1500 bar, and a mean particle size of around 180 nm was obtained with a narrow size distribution. The cubosomes were further characterized by differential scanning calorimetry (DSC) and Polarized light microscopy (PLM). The release of ETP in vitro from these nanoparticles was found to be 82.5% at 36 h, showing a sustained release property compared with the free drug administration. RESULTS Folate-modified cubosomes exhibited best anti-proliferative activity followed by normal cubosomes and the free drug. A further cell uptake study of Rhodamine B-loaded Cubs-FA (Rh-B-Cubs-FA) showed a marked increase of cellular accumulation compared with free Rh-B and Rh-B-loaded Cubs (Rh-B-Cubs). In vivo Rh-B-based tumor imaging demonstrated that Cubs-FA specifically targeted the tumor tissue. CONCLUSIONS The folate-modified cubosomes containing ETP may be a promising drug candidate for antitumor treatment.

iTRAQ-Based Quantitative Proteomic Analysis of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a common disease in the southern provinces of China with a poor prognosis. To better understand the pathogenesis of NPC and identify proteins involved in NPC carcinogenesis, we applied iTRAQ coupled with two-dimensional LC-MS/MS to compare the proteome profiles of NPC tissues and the adjacent non-tumor tissues. We identified 54 proteins with differential expression in NPC and the adjacent non-tumor tissues. The differentially expressed proteins were further determined by RT-PCR and Western blot analysis. In addition, the up-regulation of HSPB1, NPM1 and NCL were determined by immunohistochemistry using tissue microarray. Functionally, we found that siRNA mediated knockdown of NPM1 inhibited the migration and invasion of human NPC CNE1 cell line. In summary, this is the first study on proteome analysis of NPC tissues using an iTRAQ method, and we identified many new differentially expressed proteins which are potential targets for the diagnosis and therapy of NPC.

[Progress of mesoporous silica nanoparticles in targeting drug delivery system of antitumor drug].

Currently, chemotherapy is one of the main therapy for cancer. But the traditional antitumor drugs are systemic distribution in vivo, they are difficult to achieve an effective drug concentration in the tumor tissue and don't have the ability to distinguish normal cells and tumor cells by themselves, that cause systemic toxicity easily and can not meet the clinical needs. With the research on mesoporous silica nanoparticles (MSNs) deepening, more and more attention in the drug delivery system have been payed to in recent years, because of its unique physicochemical structure characteristics, it has the effect on specific targets, directly inhibits the tumor cell growth, reduces the side effects to normal cells, tissues and organs and can be long-term medication, etc. It is expected to be excellent carriers of antitumor drugs. MSNs application in the field of cancer treatment has now become a hot research field of medicine. In this paper, the latest research about MSNs in antitumor drugs targeting delivery system from 2008 to 2015 is summarized, including the application of MSNs separately in antitumor drug targeting, passive targeting, active targeting, physical or chemical conditions response targeting and other compound targeting drug delivery system. We expect it to provide a reference to the toxicity reducing and efficacy enhancing and further development of chemical medicine, natural medicine and monomeric compound of chinese herbal medicine.

Prophylactic lamivudine to improve the outcome of HBsAg-positive lymphoma patients during chemotherapy: a systematic review and meta-analysis.

Hepatitis B viral (HBV) reactivation in lymphoma patients undergoing chemotherapy is associated with significant morbidity and mortality. Increasingly, lamivudine is being used to prevent hepatitis B reactivation. To assess the effects of prophylactic lamivudine on reactivation and mortality following chemotherapy in lymphoma patients who are hepatitis B surface antigen (HBsAg)-positive, we searched Medline/PubMed, Ovid MEDLINE, EMBASE, Web of Knowledge and the Cochrane Library for studies through November 2013. Statistical analysis was performed using REVMAN. Fourteen studies consisting of 636 patients were included in the analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis due to HBV reactivation in patients with lamivudine prophylaxis was significantly lower than those with no prophylaxis. Risk ratios [RRs] were 0.25 (95% confidence intervals [CI] 0.13-0.51; P=0.0001), 0.40 (95% CI 0.26-0.63; P<0.0001), and 0.21 (95% CI 0.09-0.51; P=0.0005) respectively. In addition, patients given prophylactic lamivudine had significant reductions in overall mortality and mortality attributable to HBV reactivation compared with control group. Risk ratios [RRs] were 0.45 (95% CI 0.29-0.70; P=0.0004) and 0.41 (95% CI 0.20-0.84; P=0.01) respectively. Chemotherapy disruption was not significantly different between the two groups. Risk ratios [RRs] were 0.34 (95% CI 0.09-1.26; P=0.11). Prophylactic therapy with lamivudine for HBsAg-positive lymphoma patients who are undergoing chemotherapy may reduce the risk for HBV reactivation, hepatitis due to HBV reactivation, overall mortality and mortality attributable to HBV reactivation. Additionally, patients with preventive lamivudine had a trend towards the decreased incidence of chemotherapy disruption.

[Effects of Ca2+ on photosynthetic parameters of Pinellia ternata and accumulations of active components in heat stress].

OBJECTIVE: To study the effect of exogenous Ca2+ on photosynthetic parameters of Pinellia ternate and accumulations of active components under high temperature stress. METHOD: The pigment contents of P. ternata leaves, photosynthesis parameters and chlorophyll fluorescence parameters of P. ternata leaves, the contents of guanosine, adenosine and polysaccharide in P. ternata tubers were measured based on different concentrations of exogenous Ca2+ in heat stress when the plant height of P. ternata was around 10 cm. RESULT: The contents of total chlorophyll and ratio of chlorophyll a/b were relatively higher by spaying Ca2+. Compared with the control, spaying 6 mmol x L(-1) Ca2+ significantly enhanced the net photosynthetic rate (Pn), transpiration (Tr) and stomatal limitation (L8), but reduced intercellular CO2 concentration (C) in P. ternata leaves. With the increase of Ca2+ concentration, maximal PS II efficiency (Fv/Fm), actual photosynthetic efficiency (Yield) and photochemical quenching coefficient (qP) initially increased and then decreased, however, minimal fluorescence (Fo) and non-photochemical quenching coefficient (NPQ) went down first and then went up. The contents of guanosine and polysaccharide and dry weight of P. ternata tubers showed a tendency of increase after decrease, and the content of adenosine increased with the increase of Ca2+ concentration. The content of guanosine and polysaccharide in P. ternata tubers and its dry weight reached maximum when spaying 6 mmol x L(-1) Ca2+. CONCLUSION: With the treatment of calcium ion, the inhibition of photosynthesis and the damage of PS II system were relieved in heat stress, which increased the production of P. ternata tubers.

Cytosolic CD38 protein forms intact disulfides and is active in elevating intracellular cyclic ADP-ribose.

CD38 catalyzes the synthesis of cyclic ADP-ribose (cADPR), a Ca(2+) messenger responsible for regulating a wide range of physiological functions. It is generally regarded as an ectoenzyme, but its intracellular localization has also been well documented. It is not known if internal CD38 is enzymatically active and contributes to the Ca(2+) signaling function. In this study, we engineered a novel soluble form of CD38 that can be efficiently expressed in the cytosol and use cytosolic NAD as a substrate to produce cADPR intracellularly. The activity of the engineered CD38 could be decreased by mutating the catalytic residue Glu-226 and increased by the double mutation E146A/T221F, which increased its cADPR synthesis activity by >11-fold. Remarkably, the engineered CD38 exhibited the ability to form the critical disulfide linkages required for its enzymatic activity. This was verified by using a monoclonal antibody generated against a critical disulfide, Cys-254-Cys-275. The specificity of the antibody was established by x-ray crystallography and site-directed mutagenesis. The engineered CD38 is thus a novel example challenging the general belief that cytosolic proteins do not possess disulfides. As a further refinement of this approach, the engineered CD38 was placed under the control of tetracycline using an autoregulated construct. This study has set the stage for in vivo manipulation of cADPR metabolism.

[Correlation between pressure and volume parameters of septic shock patients with cardiac depression].

OBJECTIVE: To investigate the characteristics and influence of cardiac depression on patients with septic shock. METHODS: Seventy seven septic shock patients treated from January 2005 to June 2009 were retrospectively studied, they were divided into two groups based on cardiac index (CI) after early resuscitation, high CI group: CI >/= 3 L/(min.m(2)), low CI group: CI < 3 L/(min.m(2)). Rate of goal achievement, prognosis and whether the global end diastolic volume index (GEDI) increases with central venous pressure (CVP) growth of the two groups were compared. RESULTS: There were 38 patients in the low CI group, and 39 patients in the high CI group. Compared with patients in the high CI group, patients in the low CI group had older age and higher APACHE II score (P < 0.05). Compared with patients in the high CI group, patients in the low CI group had higher mortality rate and lower rate of goal achievement (P < 0.05). In low CI group, 16 patients' GEDI didn't increase with CVP growth, and in high CI group only 6 patients' GEDI didn't increase with CVP growth (P < 0.05); In low CI group, patients whose GEDI didn't increase with CVP growth had higher arterial lactate, lower ScvO(2), lower rate of goal achievement and worse prognosis than patients whose GEDI increased with CVP growth(P < 0.05). CONCLUSIONS: For septic shock patients, correlation between CVP and GEDI can reflect cardiac function. Especially for patients with low CI, GEDI doesn't increase with CVP growth is a signal of cardiac depression and can be an early indicator of worse prognosis. Older septic shock patients and those with higher APACHE II score tend to have the complication of cardiac depression.

[Effects of soy isoflavone on levels of low-grade inflammatory peptides in rats with insulin resistance].

OBJECTIVE: To explore the effects of soy isoflavone (SIF) on low-grade inflammation in rats with high-fat diet-induced insulin resistance (IR) and explore the mechanisms of SIF in improving insulin sensitivity. METHODS: The rats with high-fat diet-induced IR were randomly divided into one model control group and 3 SIF groups gavaged with SIF water solutions at the doses of 50, 150, and 450 mg/kg, respectively. One month after the treatment, fasting blood glucose (FBG), fasting insulin (FINS), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP), resistin and adiponectin in the serum were detected by enzymatic method, radioimmunoassay, or enzyme-linked immunosorbent assay. RESULTS: In the 150 and 450 mg/kg SIF groups, fasting body-weights, visceral adipose tissue deposition, FINS, resistin, TNF-alpha in serum, and IR index were lowered in comparison with the model control group, and in 450 mg/kg SIF group, serum IL-6 level was obviously lowered, and adiponectin increased. No differences were found in serum C-reactive protein levels between the 3 SIF groups. CONCLUSION: Soy isoflavone may ameliorate insulin sensitivity by decreasing visceral adipose deposition and adjusting low-grade inflammatory molecules derived from white adipose tissue.

[Effects of soy isoflavone on gene expression of resistin in insulin-resistance rats].

OBJECTIVE: To assess the effects of soy isoflavone (SIF) on improving insulin reistance (IR) status in IR rats induced by high-fat and high-sugar diet and explore the possible mechanisms. METHODS: IR rats were randomly divided into four groups according to their insulin resistance indices (IRI). The rats in one model control group and three SIF groups were fed via gavage with water solutions containing SIF at doses of 0 mg/ kg x bw, 50 mg/kg x bw, 150 mg/kg x bw, and 450 mg/kg x bw, respectively. After one month, fasting glucose, fasting insulin, resistin in serum, and resistin mRNA in adipocyte around kidney were detected by enzymologic method, radioimmunoassay, enzyme linked immunosorbent assay, and real time RT-PCR, respectively. RESULTS: Comparison between the model control group and the other groups revealed that serum resistin and resistin mRNA expression levels were lower in the 450 mg/kg x bw group, that insulin and IRI levels were lower in the 150 mg/ kg x bw group and 450 mg/kg x bw group, and that no differences in plasma glucose levels existed among the 4 groups. A positive correlation between IRI and serum resistin level (r = 0.355, P < 0.05) was observed. CONCLUSION: These results suggest that soy isoflavone may down-regulate resistin mRNA expression, decrease serum resistin level and enhance insulin sensitivity.

[Effects of soy isoflavone on low-grade inflammation in obese rats].

OBJECTIVE: To explore the effects of soy isoflavone (SIF) on low-grade inflammation in obese rats induced by high-fat diet, and to elucidate mechanisms of SIF in improving insulin sensitivity. METHODS: Obese rats were randomly divided into 4 groups: One model control group and 3 SIF groups that were given water solutions with SIF at 0 mg/(kg x d), 50 mg/(kg x d), 150 mg/(kg x d), and 450 mg/(kg x d), respectively. After one month, fasting glucose, fasting insulin, interleukin-6, tumor necrosis factor-alpha, C-reactive protein, resistin, and adiponectin in serum were detected by enzymic method, radioimmunoassay, and enzyme linked immunosorbent assay, respectively. RESULTS: In the 150 mg/(kg x d) group and 450 mg/(kg x d) group, fasting body-weights, viscera fatty deposition, and contents of insulin, interleukin-6, and tumor necrosis factor-alpha in serum were significantly lower; serum adiponectin levels were significantly higher; and serum resistin levels were significantly lower in the 450 mg/(kg d) group than those of the model control group. There was no difference in serum C-reactive protein levels among the 3 SIF groups. CONCLUSION: Soy isoflavone may improve the insulin sensitivity by decreasing viscera fatty deposition and adjusting low-grade inflammatory molecules derived from white adipose tissues.

[Effects and mechanism of ShenQi compound recipe on inflammation maker in GK rats].

OBJECTIVE: To explore the effects and mechanism of ShenQi Compound Recipe on inflammation maker of type 2 diabetes mellitus in GK rats. METHODS: Rats were ranodmly divided into Model group, Ramipril group (positive control, 1 mg/kg x d), SQCR low dosage (0.72 g/kg x d), SQCR high dosage group (2.88 g/kg x d) and Wistar control group. Each group was administrated correspondent substance respectively for 32 days. Determined C-reactive protein (CRP) by ELISA and tumour necrosis factor (TNF)-alpha by radioimmunassay. The mRNA expression of nuclear factor (NF)-kappaB p65 in aorta was determined by real time RT-PCR, and activation of it using immunohistochemistry staining. RESULTS: Concentrations of CRP and TNF-alpha in serum and the expression of mRNA and activation of NF-kappaB were all decreased in SQCR low and high dosage groups compared with model group (P < 0.05 or P < 0.01). CONCLUSION: These results suggest that SQCR can decrease the level of inflammation maker in serum, which may be resulted from reducing the mRNA expression and activation of NF-kappaB.

Synthesis and characterization of binuclear molybdenum-polycarboxylate complexes with sulfur bridges.

A group of four binuclear sulfur-bridged molybdenum-polycarboxylato complexes with homocitrate, citrate, cysteine, ethylenediaminetetraacetate ligands, respectively, have been synthesized and characterized. These complexes were prepared in order to study the interaction of Mo and homocitrate in the FeMo-co of nitrogenases. In the structures of K4(NH4)2[Mo2O2S2(C6H4O7)2].10H2O (2), (NH4)2[Mo2O2S2(C3H5SNO2)2].5H2O (3) and (NH4)2[Mo2O2S2(C10H12N2O8)].3.5H2O (4), molybdenum (V) atom adopts a distorted octahedral arrangement through a terminal oxygen atom, two bridging sulfur atoms and three atoms from the ligand (hydroxyl, alpha-, beta-carboxylates, sulfide or amine). The coordination mode of homocitrate ligand in K5(NH4)[Mo2O2S2(C7H5O7)2].3H2O.CH3OH (1) has been proposed in a tridentate fashion via its hydroxyl and a pair of carboxylate groups (alpha-, beta-carboxylates). The electrochemical properties of these complexes have been discussed.