Lycium barbarum polysaccharide alleviates dextran sodium sulfate-induced inflammatory bowel disease by regulating M1/M2 macrophage polarization via the STAT1 and STAT6 pathways.

Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal Lycium barbarum L., which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways in vivo. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways.

Protective effect of the effective part of Andrographis paniculata (Burm.f.) Nees on PM2.5-induced lung injury in rats by modulating the NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata (Burm.f.) Nees, a traditional Chinese herb, has been widely used in various Asian countries as a treatment for upper respiratory tract infections for centuries. AIM OF THE STUDY: Continuous inhalation of fine particulate matter (PM2.5) may induce various respiratory diseases. This study elucidated the protective effect of the effective part of Andrographis paniculata (Burm.f.) Nees (AEP) against PM2.5-induced lung injury and detailed the underlying mechanism. MATERIALS AND METHODS: Male Wistar rats were orally administered 0.5% sodium carboxymethylcellulose (CMC-Na), andrographolide (AG) (200 mg/kg) and AEP (100 mg/kg, 200 mg/kg and 400 mg/kg) once a day for 28 days. The rats were intratracheally instilled with PM2.5 suspension (8 mg/kg) every other day beginning on the 24th day for a total of 3 times. On the 29th day, bronchoalveolar lavage fluid (BALF) was collected to analyze the levels of lactate dehydrogenase (LDH), acid phosphatase (ACP), alkaline phosphatase (AKP), total proteins (TP), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). Hematoxylin & eosin staining was conducted to evaluate the pathological changes in the lung tissues. The protein expression of NF-κB p65 in the lung tissues was analyzed by immunohistochemistry staining. Moreover, the nuclear translocation of NF-κB p65 and the phosphorylation of IκBα were analyzed by western blotting. RESULTS: PM2.5 exposure caused lung toxicity, which was characterized by pathological injury and increased levels of LDH, ACP, AKP and TP in BALF. Meanwhile, PM2.5 exposure induced lung inflammatory response, including infiltration of inflammatory cells and increased levels of inflammatory factors, such as TNF-α and IL-6 in BALF. AEP treatment significantly ameliorated the PM2.5-induced lung toxicity and the inflammatory response in rats. Moreover, AEP significantly inhibited the PM2.5-induced upregulation of NF-κB p65 protein expression, phosphorylation of IκBα and nuclear translocation of NF-κB p65 in lung tissue. Compared to AG, AEP exhibited a better ability to alleviate PM2.5-induced pathological damage and decrease the TP level in the BALF. CONCLUSION: AEP could be used to improve PM2.5-induced lung injury by modulating the NF-κB pathway, and multicomponent therapy with traditional Chinese medicine may be more effective than single-drug therapy.

Enhanced anticancer efficacy of cantharidin by mPEG-PLGA micellar encapsulation: An effective strategy for application of a poisonous traditional Chinese medicine.

Cantharidin (CTD), the main active component of a poisonous traditional Chinese medicine (PTCM) Mylabris, exhibits highly effective therapy of hepatocellular carcinoma (HCC); however, the severe toxicity of CTD on the digestive and urinary systems prevents its clinical application. Here, CTD-loaded micelles (mPEG-PLGA-CTD) were prepared for enhancement of the antitumor efficacy and reduction of the toxicity of CTD. mPEG-PLGA-CTD comprised uniform spherical particles with particle size of 25.32 ± 1.25 nm and zeta potential of -5.70 ± 0.76 mV, exhibiting good stability and biocompatibility. mPEG-PLGA-CTD showed high toxicity on HepG2 cells by improving apoptosis and inhibiting protein phosphatases 2A (PP2A) compared to the low toxicity on l-02 hepatocytes. Intravenous injection of mPEG-PLGA-CTD led to a long circulation half-life of drugs, enhanced drug accumulation in the tumor tissues, and reduced drug accumulation in the other organs (e.g., the kidney) due to the enhanced permeability and retention effect compared to injection of free CTD; more importantly, the highly efficient antitumor effect and low systemic toxicity were achieved. A micellar formulation is very useful for enhancement of therapeutic efficacy and reduction of systemic toxicity of PTCMs.

Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis.

BACKGROUND: Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its' mechanism. METHODS: Male Sprague-Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson's staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-ß1 in peritoneal fluid by ELISA. RESULTS: Compared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL, p < 0.05] and increased MTG (18.99 ± 0.86 to 10.85 ± 0.65 mmol/kg, p < 0.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33 ± 4.42 to 25.26 ± 0.32um, p < 0.05) and higher expression of a-SMA, collagen I and TGF-ß1. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-ß1 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-ß1, α-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin. CONCLUSIONS: Present results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.

Chemical constituents from Inonotus obliquus and their antitumor activities.

Four new lanostane-type triterpenes (inonotusanes D-G, 1-4), including a 24,25,26,27-tetranorlanostane, together with 11 known compounds (5-15), including 7 lanostane derivatives, 2 steroids and 2 aromatic compounds, were isolated from the sclerotia of Inonotus obliquus. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRMS. To our knowledge, 1 is the first 24,25,26,27-tetranorlanostane-type triterpenoid from fungus, and this is the first time that 31-member lanostane-type triterpenes, 5 and 6, have been isolated from the sclerotia of I. obliquus instead of from its submerged culture. 7 and 8 are also new isolates of this genus. Compounds 1, 8, 12 and 13 exhibited strong cytotoxicity against the 4T1 (mouse breast cancer) cell line, with IC50 9.40, 7.79, 9.06 and 9.31 µM, respectively. 8, 12 and 13 also exhibited strong cytotoxicity against the the MCF-7 (human breast cancer) cell line, with IC50 8.35-9.01 µM.

Craniofacial reconstruction evaluation by geodesic network.

Craniofacial reconstruction is to estimate an individual's face model from its skull. It has a widespread application in forensic medicine, archeology, medical cosmetic surgery, and so forth. However, little attention is paid to the evaluation of craniofacial reconstruction. This paper proposes an objective method to evaluate globally and locally the reconstructed craniofacial faces based on the geodesic network. Firstly, the geodesic networks of the reconstructed craniofacial face and the original face are built, respectively, by geodesics and isogeodesics, whose intersections are network vertices. Then, the absolute value of the correlation coefficient of the features of all corresponding geodesic network vertices between two models is taken as the holistic similarity, where the weighted average of the shape index values in a neighborhood is defined as the feature of each network vertex. Moreover, the geodesic network vertices of each model are divided into six subareas, that is, forehead, eyes, nose, mouth, cheeks, and chin, and the local similarity is measured for each subarea. Experiments using 100 pairs of reconstructed craniofacial faces and their corresponding original faces show that the evaluation by our method is roughly consistent with the subjective evaluation derived from thirty-five persons in five groups.

[Effects of control-releasing arsenic trioxide-eluting stent on intimal smooth muscle cells and type III collagen in canine coronary artery post-stent model].

OBJECTIVE: To study the safety and efficacy of control-releasing arsenic trioxide (As2O3)-eluting stent on intimal smooth muscle cells (SMC) and type III collagen (CIII) in canine coronary artery post-stent model. METHODS: Twenty-four experimental canines were equally divided into 4 groups, the three tested groups were deployed by stents with different dosage of As2O3 (1.6 microg/mm2, 2.4 microg/mm2 and 3.2 microg/mm2 in low, median and high dose groups, respectively) and coated with polybutyl methacrylate/nano silica and poly-lactide-coglycolide in mild oversizing (stent/vessel ratio of 1.3:1) in left anterior descending (LAD) or circumflex coronary arteries (LCX), while the control group only by simple coated stent without As2O3. The effect was assessed 4 weeks after stent implantation in terms of vascular histomorphology, and changes of SMC and C III expressions were detected using immunohistochemical analysis. RESULTS: Subintimal hemorrhage, medial/adventitial necrosis, thrombosis and inflammatory cell infiltration were not found and integral endothelium could be seen under screening electron microscopy in all groups. Positive expression of SMC and CIII in the tested groups, especial in the high dose As2O3 group, was more weaker than that in control group. Histo-morphological analysis showed that the neo-genetic intimal area and vascular stenosis were lower, but the mean luminal diameter was larger in the three tested groups than that in the control group (P < 0.01). Comparisons of various indices between tested groups treated by different doses of As2O3 showed that the difference between high/median dose vs. low dose was significant (P < 0.01), but that between high dose vs. median dose was insignificant (P > 0.05). CONCLUSION: Control-releasing As2O3-eluting stent shows a reliable and safe effect in preventing and treating post-stent restenosis by its dose-dependent inhibition on expressions of SMC and CIII to suppress the neo-genesis of intimal hyperplasia.

[Effect of zedoary turmeric oil-eluting stents for post-stenting restenosis prevention and treatment].

OBJECTIVE: To investigate the effect and safety of Zedoary Turmeric Oil (ZTO)-eluting stents for post-coronary stenting restenosis prevention and treatment in the experimental dogs. METHODS: Bare stents, stents coated with polybutyl methacrylate/Nano silica, and stents eluted with 100 microg ZTO were randomly deployed in canine anterior descending or circumflex coronary artery. Four weeks after stent implantation, the dogs were sacrificed and the vascular histomorphologic changes in the stenting segment analyzed. RESULTS: Thickened intima could be seen under light microscope in the bare or coated stents, but thinner in ZTO-duting stent, with no sub-intimal hemorrhage, medial or adventitial necrosis, wall adhesive thrombus, or infiltration of inflammatory cells. Scanning electric microscopy showed the intima was intact. Histomorphologic analysis showed that the thickness and area of neo-intima, and the lumen stenosis percent in artery stented with ZTO eluting stents were significantly lower than those stented with bare or coated stents (P <0.01), and thus the lumen cavity was expanded (P < 0.01), while no statistic significant difference between polymer and bare stents was found (P > 0.05). CONCLUSION: ZTO-eluting stent is available and safe, and it could significantly inhibit the growth of neo-intimal in canine coronary mode after stenting, showing a restenosis preventive and treatment effect.