In-situ-reduced synthesis of cyano group modified g-C3N4/CaCO3 composite with highly enhanced photocatalytic activity for nicotine elimination.

Graphite carbon nitride has many excellent properties as a two-dimensional semiconductor material so that it has a wide application prospect in the field of photocatalysis. However, the traditional problems such as high recombination rate of photogenerated carriers limit its application. In this work, we introduce nitrogen deficiency into g-C3N4 to solve this problem a simple and safe in-situ reduction method. g-C3N4/CaCO3 was obtained by a simple and safe one-step calcination method with industrial-grade micron particles CaCO3. Cyano group modification was in-situ reduced during the thermal polymerization process, which would change the internal electronic structure of g-C3N4. The successful combination of g-C3N4 and CaCO3 and the introduction of cyanide have been proved by Fourier transform infrared spectroscopy and X-ray photoelectron spectrometer. The formation of the cyano group, an electron-absorbing group, promotes the effective separation of photogenic electron hole pairs and inhibits the recombination of photogenic carriers. These advantages result in the generation of more •O2- and 1O2 in the catalytic system, which increases the photocatalytic efficiency of nicotine degradation by ten times. Furthermore, the degradation process of nicotine has been studied in this work to provide a basis for the degradation of nicotine organic pollutants in the air.

Mechanically stimulated osteocytes reduce the bone-metastatic potential of breast cancer cells in vitro by signaling through endothelial cells.

Bone metastases occur in 65% to 75% of patients with advanced breast cancer and significantly worsen their survival and quality of life. We previously showed that conditioned medium (CM) from osteocytes stimulated with oscillatory fluid flow, mimicking bone mechanical loading during routine physical activities, reduced the transendothelial migration of breast cancer cells. Endothelial cells are situated at an ideal location to mediate signals between osteocytes in the bone matrix and metastasizing cancer cells in the blood vessels. In this study, we investigated the specific effects of flow-stimulated osteocytes on the interaction between endothelial cells and breast cancer cells in vitro. We observed that CM from flow-stimulated osteocytes reduced endothelial permeability by 15% and breast cancer cell adhesion onto endothelial monolayers by 18%. The difference in adhesion was abolished with anti-intercellular adhesion molecule 1 (ICAM-1) neutralizing antibodies. Furthermore, CM from endothelial cells conditioned in CM from flow-stimulated osteocytes significantly altered the gene expression in bone-metastatic breast cancer cells, as shown by RNA sequencing. Specifically, breast cancer cell expression of matrix metallopeptidase 9 (MMP-9) was downregulated by 62%, and frizzled-4 (FZD4) by 61%, when the osteocytes were stimulated with flow. The invasion of these breast cancer cells across Matrigel was also reduced by 47%, and this difference was abolished by MMP-9 inhibitors. In conclusion, we demonstrated that flow-stimulated osteocytes downregulate the bone-metastatic potential of breast cancer cells by signaling through endothelial cells. This provides insights into the capability of bone mechanical regulation in preventing bone metastases; and may assist in prescribing exercise or bone-loading regimens to patients with breast cancers.

Zn(II)-curcumin solid dispersion impairs hepatocellular carcinoma growth and enhances chemotherapy by modulating gut microbiota-mediated zinc homeostasis.

Zinc(II) complexes of curcumin display moderate cytotoxicity towards cancer cells at low micromolar concentrations. However, the clinical use of zinc(II) complexes is hampered by hydrolytic insolubility and poor bioavailability and their anticancer mechanisms remain unclear. Here, we investigated the efficacy and mechanism of action of a polyvinylpyrrolidone (PVP-k30)-based solid dispersion of Zn(II)-curcumin (ZnCM-SD) against hepatocellular carcinoma (HCC) in vitro and in vivo. In vitro assays revealed ZnCM-SD not only reduced the viability of HepG2 cells and SK-HEP1 cells in a dose-dependent manner, but also potently and synergistically enhanced cell growth inhibition and cell death in response to doxorubicin by regulating cellular zinc homeostasis. ZnCM-SD was internalized into the cells via non-specific endocytosis and degraded to release curcumin and Zn2+ ions within cells. The anticancer effects also occur in vivo in animals following the oral administration of ZnCM-SD, without significantly affecting the weight of the animals. Interestingly, ZnCM-SD did not reduce tumor growth or affect zinc homeostasis in HepG2-bearing mice after gut microbiome depletion. Moreover, administration of ZnCM-SD alone or in combination with doxorubicin significantly attenuated gut dysbiosis and zinc dyshomeostasis in a rat HCC model. Notably, fecal microbiota transplantation revealed the ability of ZnCM-SD to regulate zinc homeostasis and act as a chemosensitizer for doxorubicin were dependent on the gut microbiota. The crucial role of the gut microbiota in the chemosensitizing ability of ZnCM-SD was confirmed by broad-spectrum antibiotic treatment. Collectively, ZnCM-SD could represent a simple, well-tolerated, safe, effective therapy and function as a novel chemosensitizing agent for cancer.

Detoxification and immunoprotection of Zn(II)-curcumin in juvenile Pacific white shrimp (Litopenaeus vannamei) feed with aflatoxin B1.

Aflatoxins, which was produced by Aspergillus flavus or Aspergillus parasiticus fungi during grain and feed processing or storage, could cause severe health problems and reduction of yield during shrimp cultures. To evaluate toxic effects of aflatoxin B1 (AFB1) in juvenile Pacific white shrimp (Litopenaeus vannamei) and potential protective effect of Zn(II)-curcumin (Zn-CM), four experimental diets (control, 500 µg/kg AFB1, 500 µg/kg AFB1+100 mg/kg Zn-CM, 500 µg/kg AFB1+200 mg/kg Zn-CM) were formulated in quadruplicate to feed the shrimp for 8 weeks. The results revealed that AFB1 could induce significant decrease in final body weight (FBW), weight gain (WG, %) and visible variations of the hepatopancreas structures in L.vannamei. Compared with AFB1 group, AFB1+100 mg/kg Zn-CM group significantly ameliorated the toxic effects of AFB1 on growth performance, while AFB1+100 mg/kg Zn-CM group had no effect on growth performance. Dietary AFB1+100 mg/kg Zn-CM enhanced phenoloxidase (PO) (P < 0.05) activity. Both dietary AFB1+100 mg/kg Zn-CM and AFB1+200 mg/kg Zn-CM reduced inducible nitric oxide synthase (iNOS) activity and glutathione (GSH) level, decreased the content of malondialdehyde (MDA) (P < 0.05) in hepatopancreas compared with AFB1 group. Transmission electron microscopy (TEM) analysis demonstrated that Zn-CM could relieve the microvilli transformation and mitochondria accumulation reduction caused by AFB1. Consequently, the results demonstrated that suitable Zn-CM could mitigate the AFB1-induced hepatotoxicity and immunotoxicity effects on L.vannamei.

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (P<0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P<0.01). qBase(+) was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P<0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation.

Zn(II)-curcumin prevents cadmium-aggravated diabetic nephropathy by regulating gut microbiota and zinc homeostasis.

Background: Diabetic nephropathy (DN) is known as the most common complication of diabetes, resulting from a complex inheritance-environment interaction without effective clinical treatments. Herein, we revealed the protective effects and mechanisms of Zn(II)-curcumin, a curcumin derivative, against streptozotocin-induced DN in rats in the presence or absence of cadmium exposure. Methods: The present study focused on investigating the therapy of Zn(II)-curcumin against cadmium-aggravated DN by regulating gut microbiota, metabolism, inflammation and zinc homeostasis based on pathological changes, TLR4/NF-κB signaling pathway, inductively coupled plasma-mass spectrometry (ICP-MS), 16S rRNA gene sequencing and gas chromatography-mass spectrometer (GC-MS). Results: We found Zn(II)-curcumin significantly mitigated the cadmium-aggravated phenotypes of diabetic nephropathy, as indicated by the remission of renal dysfunction, pathological changes, inflammation and zinc dyshomeostasis in streptozotocin-treated rats exposed to cadmium. Administration of Zn(II)-curcumin significantly alleviated the dysbiosis of gut microbiota and the changes of serum metabolite profiles in rats treated with streptozotocin in combination with cadmium. Notably, fecal microbial transplantation identified the ability of Zn(II)-curcumin to regulate renal function, inflammation and zinc homeostasis was partly dependent on the gut microbiota. Conclusion: These findings revealed that Zn(II)-curcumin alleviated cadmium-aggravated diabetic nephropathy by reshaping the gut microbiota and zinc homeostasis, which provided unique insights into the mechanisms of the treatment and prevention of diabetic nephropathy.

Sphingosine Promotes Fiber Early Elongation in Upland Cotton.

Sphingolipids play an important role in cotton fiber development, but the regulatory mechanism is largely unclear. We found that serine palmitoyltransferase (SPT) enzyme inhibitors, myriocin and sphingosine (dihydrosphingosine (DHS) and phytosphingosine (PHS)), affected early fiber elongation in cotton, and we performed a sphingolipidomic and transcriptomic analysis of control and PHS-treated fibers. Myriocin inhibited fiber elongation, while DHS and PHS promoted it in a dose-effect manner. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we found that contents of 22 sphingolipids in the PHS-treated fibers for 10 days were changed, of which the contents of 4 sphingolipids increased and 18 sphingolipids decreased. The transcriptome analysis identified 432 differentially expressed genes (238 up-regulated and 194 down-regulated) in the PHS-treated fibers. Among them, the phenylpropanoid biosynthesis pathway is the most significant enrichment. The expression levels of transcription factors such as MYB, ERF, LBD, and bHLH in the fibers also changed, and most of MYB and ERF were up-regulated. Auxin-related genes IAA, GH3 and BIG GRAIN 1 were up-regulated, while ABPs were down-regulated, and the contents of 3 auxin metabolites were decreased. Our results provide important sphingolipid metabolites and regulatory pathways that influence fiber elongation.

[Pharmacological researches of curcumin solid dispersions in treatment of cancer].

OBJECTIVE: To investigate the anticancer effect of curcumin Solid Dispersions (SDs). METHODS: Curcumin SDs were prepared by patent technology. The anticancer effect of curcumin SDs were investigated by vivo and vitro tests of SCG-7901, BEL-7402, S-180 and Ehrlich ascites tumor models. RESULTS: The results showed that Curcumin SDs had markedly anticancer effect and could improve the anticancer effect of cisplatin. CONCLUSION: Curcumin SDs could be developed into one kind of adjuvant drug for anticancer, as it has markedly anticancer effect, and could improve the anticancer effects of cisplatin.

Reduction of breast cancer extravasation via vibration activated osteocyte regulation.

Physical exercise benefits breast cancer patients by reducing cancer progression and promoting bone health. However, intense exercise is physically challenging for bedridden, disabled, or aged patients. As an exercise surrogate, low-magnitude (<1 g) high-frequency (>30 Hz) (LMHF) vibration has gained growing interest in recent years, but its effects on bone metastasis remain unknown. We used a microfluidic co-culture platform that mimics bone-cancer environments to study the impact of vibration on breast cancer extravasation. LMHF vibration activated osteocytes, the primary mechanosensing cells in bones, which reduced cancer extravasation by 43%. We further studied the vibration mechanism by demonstrating the important role of the Piezo1 ion channel in osteocyte mechanotransduction. Chemical activation of Piezo1 enhanced osteocyte inhibition of cancer extravasation under vibration at the early time point. These data indicated that LMHF vibration could inhibit cancer extravasation, suggesting that vibration may suppress bone metastasis in breast cancer patients.

Magnetic Measurement and Stimulation of Cellular and Intracellular Structures.

From single-pole magnetic tweezers to robotic magnetic-field generation systems, the development of magnetic micromanipulation systems, using electromagnets or permanent magnets, has enabled a multitude of applications for cellular and intracellular measurement and stimulation. Controlled by different configurations of magnetic-field generation systems, magnetic particles have been actuated by an external magnetic field to exert forces/torques and perform mechanical measurements on the cell membrane, cytoplasm, cytoskeleton, nucleus, intracellular motors, etc. The particles have also been controlled to generate aggregations to trigger cell signaling pathways and produce heat to cause cancer cell apoptosis for hyperthermia treatment. Magnetic micromanipulation has become an important tool in the repertoire of toolsets for cell measurement and stimulation and will continue to be used widely for further explorations of cellular/intracellular structures and their functions. Existing review papers in the literature focus on fabrication and position control of magnetic particles/structures (often termed micronanorobots) and the synthesis and functionalization of magnetic particles. Differently, this paper reviews the principles and systems of magnetic micromanipulation specifically for cellular and intracellular measurement and stimulation. Discoveries enabled by magnetic measurement and stimulation of cellular and intracellular structures are also summarized. This paper ends with discussions on future opportunities and challenges of magnetic micromanipulation in the exploration of cellular biophysics, mechanotransduction, and disease therapeutics.

[Pharmacological researches of curcumin solid dispersions on experimental gastric ulcer].

OBJECTIVE: To research the pharmacological action of curcumin solid dispersions (SDs, curcumin and polyvinylpyrrolidone (PVP) k30 in the ratio of 1:8) was investigated on experimental gastric ulcer in rats and mice. METHOD: Animals were randomly divided into several experimental groups. Each group consisted of 10 animals. The control group received PVP vehicle (720 mg x kg(-1), po) throughout the course of the experiments. The treatment groups received different doses of curcumin SDs (equivalent to curcumin 10, 30 and 90 mg x kg(-1), po), and ranitidine (27 mg x kg(-1), po) was used as the positive control. In acetic acid-induced gastric ulcers model, serum NO, plasma ET and gastric ulcer indexes of rats were measured after oral administration for 14 d. In rat ulcer model induced by pylorus-ligature, gastric volume pepsin and gastric ulcer indexes of rats were measured after oral administration for 3 d and pylorus-ligature inducement for 16 h. Gastric ulcer indexes of mice were measurement after oral administration for 3 d and subcutaneous injection reserpine 10 mg x kg(-1). RESULT: The results showed that curcumin SDs (equivalent to curcumin 30, and 90 mg x kg(-1), po) could reduce the ulcer indexes 4.59 +/- 0.96 and 3.33 +/- 0.93 (P < 0.01), and increase serum NO level (29.75 +/- 5.90) mmol x L(-1) (P < 0.05) and (39.63 +/- 12.73) mmol x L(-1) (P < 0.01), compared to gastric index 5.87 +/- 0.48 and NO level (23.63 +/- 5.73) mmol x L(-1) in control group. Compared to plasma ET (163.65 +/- 63.84) ng x L(-1) in control group, curcumin SDs (equivalent to 90 mg x kg(-1), po) could decrease plasma ET level (104.22 +/- 63.84) ng x L(-1) (P < 0.05). Compared to gastric ulcer indexes 4.25 +/- 0.71 of control group in rat pylorus-ligature model, curcumin SDs (equivalent to curcumin 90 mg x kg(-1)) could reduce gastric ulcer to 2.38 +/- 0.74 (P < 0.01). Compared to gastric volume (14.61 +/- 1.80) mL, acidity of gastric juice (87.70 +/- 9.84) mmol x L(-1), and the activity of pepsin (408.63 +/- 41.75) U x mL(-1), curcumin SDs (equivalent to curcumin 30, 90 mg x kg(-1)) could reduce gastric volume to (12.68 +/- 1.46) mL (P < 0.05) and (9.99 +/- 0.79) mL (P < 0.01), reduce acidity of gastric juice to (77.62 +/- 8.34) mmol x L(-1) (P < 0.05) and (65.77 +/- 8.19) mmol x L(-1) (P < 0.01), inhibit the activity of pepsin to (358.13 +/- 37.44) U x mL(-1) (P < 0.05) and (292.13 +/- 41.93) U x mL(-1) (P < 0.01). In reserpine-induce gastric ulcer model, curcumin SDs (equivalent to curcumin 30, 90 mg x kg(-1)) could reduce gastric ulcer indexes to 3.88 +/- 0.40 and 3.03 +/- 0.64 (P < 0.01), compared to that of control group 5.13 +/- 0.59. CONCLUSION: Several animal gastric ulcer models prove that curcumin SDs has anti-gastric ulcer effects by inhibiting gastric acid secretion, reducing gastric juice acidity, inhibiting the activity of pepsin and promoting healing of ulcer. These findings show a potential application of curcumin SDs as an anti-ulcerogenic drug.

Zn(ii)-Curcumin supplementation alleviates gut dysbiosis and zinc dyshomeostasis during doxorubicin-induced cardiotoxicity in rats.

Doxorubicin is a powerful anticancer agent used to treat a variety of human neoplasms. However, the clinical use of doxorubicin is hampered by cardiotoxicity and effective cardioprotective adjuvants do not exist. Dietary zinc, an essential nutrient, is required to maintain steady-state tissue zinc levels and intestinal homeostasis and may yield therapeutic benefits in diseases associated with zinc dysregulation or gut dysbiosis. Here, we investigated the effects of dietary Zn(ii)-curcumin (ZnCM) solid dispersions on gut dysbiosis and zinc dyshomeostasis during doxorubicin-induced cardiotoxicity in rats. Rats were injected with multiple low doses of doxorubicin and orally administered ZnCM daily over four weeks. Daily administration of ZnCM not only alleviated Dox-induced gut dysbiosis-as indicated by the increased Firmicutes-to-Bacteroidetes ratio and the maintenance of the relative abundances of major beneficial bacteria including Clostridium_XIVa, Clostridium_IV, Roseburia, Butyricicoccus and Akkermansia-but also maintained intestinal barrier integrity and decreased the lipopolysaccharide (LPS) contents of feces and plasma. ZnCM also significantly attenuated doxorubicin-induced zinc dyshomeostasis, which was mirrored by preservation of zinc levels and expression of zinc-related transporters. Furthermore, ZnCM significantly improved heart function and reduced cardiomyocyte apoptosis and myocardial injury in doxorubicin-treated rats. Notably, the regulation of zinc homeostasis and cardioprotective and microbiota-modulating effects of ZnCM were transmissible through horizontal feces transfer from ZnCM-treated rats to normal rats. Thus, ZnCM supplementation has potential as an effective therapeutic strategy to alleviate gut dysbiosis and zinc dyshomeostasis during doxorubicin-induced cardiotoxicity.

Microfluidic platform for studying osteocyte mechanoregulation of breast cancer bone metastasis.

Bone metastasis is a common, yet serious, complication of breast cancer. Breast cancer cells that extravasate from blood vessels to the bone devastate bone quality by interacting with bone cells and disrupting the bone remodeling balance. Although exercise is often suggested as a cancer intervention strategy and mechanical loading during exercise is known to regulate bone remodeling, its role in preventing bone metastasis remains unknown. We developed a novel in vitro microfluidic tissue model to investigate the role of osteocytes in the mechanical regulation of breast cancer bone metastasis. Metastatic MDA-MB-231 breast cancer cells were cultured inside a 3D microfluidic lumen lined with human umbilical vein endothelial cells (HUVECs), which is adjacent to a channel seeded with osteocyte-like MLO-Y4 cells. Physiologically relevant oscillatory fluid flow (OFF) (1 Pa, 1 Hz) was applied to mechanically stimulate the osteocytes. Hydrogel-filled side channels in-between the two channels allowed real-time, bi-directional cellular signaling and cancer cell extravasation over 3 days. The applied OFF was capable of inducing intracellular calcium responses in osteocytes (82.3% cells responding with a 3.71 fold increase average magnitude). Both extravasation distance and percentage of extravasated side-channels were significantly reduced with mechanically stimulated osteocytes (32.4% and 53.5% of control, respectively) compared to static osteocytes (102.1% and 107.3% of control, respectively). This is the first microfluidic device that has successfully integrated stimulatory bone fluid flow, and demonstrated that mechanically stimulated osteocytes reduced breast cancer extravasation. Future work with this platform will determine the specific mechanisms involved in osteocyte mechanoregulation of breast cancer bone metastasis, as well as other types of cancer metastasis and diseases.

[Studies on solubility enhancement of curcumin by Polyvinylpyrrolidione K30].

OBJECTIVE: To study solubility enhancement of curcumin by Polyvinylpyrrolidione K30 (PVP K30). METHODS: Solid dispersion systems (SDS) of curcumin in PVP K30 were prepared at various weight ratios by co-evaporation of curcumin and PVP K30 ethanol solution. The differential scanning calorimetry (DSC) and powder X-ray diffractometer method were used to describe the status of curcumin in carriers, the UV spectrometry method for determination of curcumin in mediums was established. RESULTS: The curcumin SDS was successfully prepared, the UV spectrometry method was accurate and reliable, and no interference occurred from carrier. The solubility rate in vitro of curcumin was significantly raised. Compared to curcumin, the solubility of curcumin in SDS increased at least 880 folds. CONCLUSION: PVP K30 improves the solubility of curcumin well.

Microfluidics approach to investigate the role of dynamic similitude in osteocyte mechanobiology.

Fluid flow is an important regulator of cell function and metabolism in many tissues. Fluid shear stresses have been used to level the mechanical stimuli applied in vitro with what occurs in vivo. However, these experiments often lack dynamic similarity, which is necessary to ensure the validity of the model. For interstitial fluid flow, the major requirement for dynamic similarity is the Reynolds number (Re), the ratio of inertial to viscous forces, is the same between the system and model. To study the necessity of dynamic similarity for cell mechanotransduction studies, we investigated the response of osteocyte-like MLO-Y4 cells to different Re flows at the same level of fluid shear stress. Osteocytes were chosen for this study as flows applied in vitro and in vivo have Re that are orders of magnitude different. We hypothesize that osteocytes' response to fluid flow is Re dependent. We observed that cells exposed to lower and higher Re flows developed rounded and triangular morphologies, respectively. Lower Re flows also reduced apoptosis rates compared to higher Re flows. Furthermore, MLO-Y4 cells exposed to higher Re flows had stronger calcium responses compared to lower Re flows. However, by also controlling for flow rate, the lower Re flows induced a stronger calcium response; while degradation of components of the osteocyte glycocalyx reversed this effect. This work suggests that osteocytes are highly sensitive to differences in Re, independent of just shear stresses, supporting the need for improved in vitro flow platforms that better recapitulate the physiological environment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:663-671, 2018.

Determination of a new active steroid by high performance liquid chromatography with laser-induced fluorescence detection following the pre-column derivatization.

A sensitive analytical method for the determination of a new active steroid, butane acid-(5-androsten-17-one-3beta-ol)-diester (A1998), was developed by high performance liquid chromatography with laser-induced fluorescence detection following the pre-column derivatization with dansylhydrazine. The calibration curve for A1998 derivatization was found linear in the dynamic range from 0.025 to 5.0 microg/ml, with the precision less than 6% (CV) and the mean extraction efficiency greater than 92%. In 200 microl of plasma samples the limit of quantitation was as low as 0.025 microg/ml with a signal-to-noise ratio of 10. This assaying was further applied to the determination of the pharmacokinetic parameters of A1998 in rats with an intravenous injection of A1998. Values for clearance for elimination, volume of distribution at steady state and terminal half life in the above case were determined as 50.3+/-1.1 ml/min kg, 1329.0+/-111.0 ml/kg and 44.0+/-2.7 min, respectively.

[Effects of alligator Zhikegao on relieving cough dispelling phlegm and anti-inflammation].

OBJECTIVE: To research the effects of Alligator Zhikegao on relieving cough, dispelling phlegm and anti-inflammation. METHOD: The coughing tests in mice, the phenol red secreting tests in mice, ear edema tests in mice,and paw edema tests and subcutaneous cotton ball granuloma in rats were adopted for observing the related pharmacological effects of Alligator Zhikegao. RESULT: Alligator Zhikegao could obviously prolong the latent period and decrease the times of mouse coughing, and remarkably inhibit the mouse ear edema (P < 0.001), the rat paw edema and the hyperplasia of subcutaneous cotton ball granuloma in rats. Alligator Zhikegao 11.70 g x kg(-1) could significant improve the carbonic clearances of macrophages (P <0.05) and the hemolysin level in serum (P <0.01). CONCLUSION: Alligator Zhikegao has significant effects on relieving cough, dispelling phlegm, anti-inflammation and immunological regulation.

MicroRNA-378 enhances inhibitory effect of curcumin on glioblastoma.

Glioblastoma multiforme is the most aggressive and common primary brain tumor, and is virtually incurable due to its therapeutic resistance to radiation and chemotherapy. Curcumin is a well-known phytochemical exhibiting antitumor activity on many human cancers including glioblastoma multiforme. Given the unique miRNA expression profiles in cancer cells compared to non-cancerous cells, we investigated whether these miRNA could be used to cancer therapy. In this report we show that miR-378, a glioblastoma multiforme down regulated miRNA, may enhance the inhibitory effect of curcumin on this cancer growth. Our results indicated that the inhibitory effect of curcumin was enhanced in miR-378-expressing stable U87 cells in vitro and in vivo, compared to control cells. MiR-378 was found to target p-p38 expression, underlying the observed phenotypic changes. Thus, we concluded that miR-378 enhances the response of glioblastoma multiforme to curcumin treatment, by targeting p38.

Taurine zinc solid dispersions enhance bile-incubated L02 cell viability and improve liver function by inhibiting ERK2 and JNK phosphorylation during cholestasis.

Dietary intakes of taurine and zinc are associated with decreased risk of liver disease. In this study, solid dispersions (SDs) of a taurine zinc complex on hepatic injury were examined in vitro using the immortalized human hepatocyte cell line L02 and in a rat model of bile duct ligation. Sham-operated and bile duct ligated Sprague-Dawley rats were treated with the vehicle alone or taurine zinc (40, 80, 160mg/kg) for 17days. Bile duct ligation significantly increased blood lipid levels, and promoted hepatocyte apoptosis, inflammation and compensatory biliary proliferation. In vitro, incubation with bile significantly reduced L02 cell viability; this effect was significantly attenuated by pretreatment with SP600125 (a JNK inhibitor) and enhanced when co-incubated with taurine zinc SDs. In vivo, administration of taurine zinc SDs decreased serum alanine aminotransferase and aspartate aminotransferase activities in a dose-dependent manner and attenuated the increases in serum total bilirubin, total cholesterol and low density lipoprotein cholesterol levels after bile duct ligation. Additionally, taurine zinc SDs downregulated the expression of interleukin-1ß and inhibited the phosphorylation of Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase2 (ERK2) in the liver after bile duct ligation. Moreover, taurine zinc SDs had more potent blood lipid regulatory and anti-apoptotic effects than the physical mixture of taurine and zinc acetate. Therefore, we speculate that taurine zinc SDs protect liver function at least in part via a mechanism linked to reduce phosphorylation of JNK and ERK2, which suppresses inflammation, apoptosis and cholangiocyte proliferation during cholestasis.

Protective effects of 5,4'-dihydroxy-3',5'-dimethoxy-7-O-beta-D -glucopyranosyloxy-flavone on experimental hepatic injury.

AIM: To investigate the pharmacological effects of rice flavone (5,4'-dihydroxy-3',5'-dimethoxy-7-O-beta-D-glucopyranosyloxy-flavone, RF) separated from panicle-differentiating to flowing rice on rat experimental hepatic injury. METHODS: Models of rat acute hepatic injury induced by carbon tetrachloride (CCl(4)) administration, rat hepatic fibrosis induced by thioacetamide, injury of primary cultured rat hepatocytes induced by CCl(4), respectively, were established. After treated with RF, content of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and albumin (Alb), hyaluronic acid (HA), the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and hydroxyproline (Hyp) were measured and liver tissue was observed pathologically by hematoxylin-eosin (HE) staining. Effects of RF on pathological changes, function index, enzyme of scavenging free radicals and blood rheology were evaluated. RESULTS: In model of rat acute hepatic injury induced by CCl(4), RF can significantly decrease the contents of serum ALT, AST, increase the content of Alb, improve the dropsy and fat denaturalization of hepatocytes. In model of rat hepatic fibrosis induced by thioacetamide, RF can inhibit the increase of HA, Hyp and whole blood viscosity, and improve the activities of GSH-Px and SOD, and inauricular microcirculation. CONCLUSION: RF has apparent protective effects on hepatic injury by increasing activity of GSH-Px and SOD, scavenging free radicals produced by CCl(4), reducing blood viscosity, and improving microcirculation and blood supply.