ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease （COPD） in rats and decipher the molecular mechanisms via the nuclear factor-kappa B （NF-κB）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups： normal control， COPD model， low-dose baicalin， medium-dose baicalin， high-dose baicalin， and budesonide. The normal control group received no treatment， whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin （HE） staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines ［interleukin （IL）-6， IL-8， IL-17， IL-22， tumor necrosis factor （TNF）-α， and transforming growth factor （TGF）-β）］， reactive oxygen species （ROS）， and vascular endothelial growth factor （VEGF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Meanwhile， the levels of IL-6， IL-17， and IL-22 in the bronchoalveolar lavage fluid （BALF） and IL-10， IL-22， and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry （IHC） was employed to detect the expression of histone deacetylase 2 （HDAC2） and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， glucocorticoid receptor （GR）， NF-κB， HDAC2， and Nrf2 in the lung tissue. Additionally， real-time PCR was conducted to assess the mRNA levels of PI3K， Akt， HDAC2， Nrf2， GR， and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding， structural disorganization， and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast， inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles， along with fibrotic narrowing of the bronchial wall. Moreover， the smooth muscle bundles of the bronchial wall were hypertrophic， with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed， leading to the formation of abnormally enlarged air-filled cavities. However， the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group， the medium- and high-dose baicalin groups showed declined ROS and VEGF levels （P<0.05）， and all the baicalin groups presented lowered levels of IL-6， IL-8， IL-17， IL-22， TGF-β， and TNF-α and elevated level of IL-10 （P<0.05）. Baicalin upregulated the protein levels of HDAC2， Nrf2， GR， PI3K， and Akt， while suppressing the protein level of NF-κB （P<0.05）. Furthermore， baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB （P<0.05）. ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2， thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.

ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease （COPD） in rats and decipher the molecular mechanisms via the nuclear factor-kappa B （NF-κB）/nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups： normal control， COPD model， low-dose baicalin， medium-dose baicalin， high-dose baicalin， and budesonide. The normal control group received no treatment， whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin （HE） staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines ［interleukin （IL）-6， IL-8， IL-17， IL-22， tumor necrosis factor （TNF）-α， and transforming growth factor （TGF）-β）］， reactive oxygen species （ROS）， and vascular endothelial growth factor （VEGF） were quantified by enzyme-linked immunosorbent assay （ELISA）. Meanwhile， the levels of IL-6， IL-17， and IL-22 in the bronchoalveolar lavage fluid （BALF） and IL-10， IL-22， and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry （IHC） was employed to detect the expression of histone deacetylase 2 （HDAC2） and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt）， glucocorticoid receptor （GR）， NF-κB， HDAC2， and Nrf2 in the lung tissue. Additionally， real-time PCR was conducted to assess the mRNA levels of PI3K， Akt， HDAC2， Nrf2， GR， and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding， structural disorganization， and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast， inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles， along with fibrotic narrowing of the bronchial wall. Moreover， the smooth muscle bundles of the bronchial wall were hypertrophic， with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed， leading to the formation of abnormally enlarged air-filled cavities. However， the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group， the medium- and high-dose baicalin groups showed declined ROS and VEGF levels （P<0.05）， and all the baicalin groups presented lowered levels of IL-6， IL-8， IL-17， IL-22， TGF-β， and TNF-α and elevated level of IL-10 （P<0.05）. Baicalin upregulated the protein levels of HDAC2， Nrf2， GR， PI3K， and Akt， while suppressing the protein level of NF-κB （P<0.05）. Furthermore， baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB （P<0.05）. ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2， thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.

To systematically review the prognostic value regarding the expression of long non-coding RNA (lncRNA) Hox transcript antisense intergenic RNA (HOTAIR) in patients with cancer. 
 Methods: Databases including The Cochrane Library, EMBASE, MEDLINE, and PubMed were searched to collect English literature on the correlation between lncRNA HOTAIR expression and overall survival in tumors. The retrieval time was from inception to September 2015. After data were extracted, a Meta-analysis was performed using RevMan 5.3 software.
 Results: A total of 17 studies were included, which was involved in 1 639 patients. The Meta-analysis showed that high expression of HOTAIR could predict poor overall survival in cancer (HR: 2.39, 95% CI 2.01-2.86, P<0.001). High expression of HOTAIR could also predict poor overall survival both in digestive tumor (HR: 2.51, 95% CI 2.02-3.11, P<0.001) and non-digestive tumor (HR: 2.17, 95% CI 1.59-2.98, P<0.001). Moreover, overexpression of HOTAIR was found to be significantly associated with recurrence-free survival.
 Conclusion: The overexpression of lncRNA HOTAIR might be associated with poor prognosis in patients with cancer.
Biomarkers, Tumor ; genetics ; Humans ; Neoplasms ; diagnosis ; genetics ; mortality ; Prognosis ; RNA, Long Noncoding ; genetics

In this article, the authors summarized the RT-ABCDE strategy for the management and prevention of human diseases, which includes ReTro-ABCDE (Examination regularity, Disease and risk factor control, Changing lifestyle and reducing pathways of infection and spread, Biochemical and Antagonistic index control and therapeutic treatment as well as RT--Routine and Right Treatment). The RT-ABCDE strategy, a novel concept and an essential method, should be a routine strategy for disease control and prevention. It should be proposed and applied in both clinical and preventive medicine.
Disease ; Humans ; Life Style ; Periodicity ; Physical Examination ; Preventive Medicine ; methods ; Risk Factors

The amphiphilic polypeptide (PA) was self-assembled into three-dimensional (3-D) porous complex of hydrogel and cells with the addition of NSCs-containing DMEM/F12. Cell differentiation in the surface and that within hydrogel were described. Cells harvested from the cerebral cortex of neonatal mice were triturated and cultivated in serum-free media. 1wt% PA was added into same volume of DMEM/F12 with cell concentration of 1 x 10(5)/ml and self-supported into 3-D hydrogel-cell composition; cells suspended within hydrogel being maintained (Experiment group, EG). lwt% PA was self-assembled into two-dimensional (2-D) hydrogel films triggered by addition of DMEM/F12, and then 1 x 10(5)/ml NSCs was seeded in the surface of films (Control group, CG). Cells in EG and CG were incubated in serum-free media for two weeks and stained with immunocytochemistry methods. TEM showed that the hydrogel derived from PA was composed of network nanofibers with their diameter ranging from 3 to 5 nm and length ranging from 100 nm to 1. 5 microm. Above 50% of cells obtained were Nestin positive cells. LSCM observations demonstrated that above 90% of cells survived two days after incubation within hydrogel, and were differentiated into NF and GFAP positive cells one week after incubation, their differentiation rates were 50% +/- 4.2% and 20% +/- 2.8% respectively; however, cells in CG were also differentiated into NF and GFAP positive cells, their differentiation rates were only 40% +/- 3.4% and 31% +/- 2.3% separately. Peptide-based hydrogel was able to provide 3-D environments for cell survival and induce primarily the differentiation of NSCs into neurons. Our data indicated that peptide-directed self-assembly of hydrogels was useful and it served as the neotype nerve tissue engineering scaffolds.
Animals ; Animals, Newborn ; Cell Culture Techniques ; Cell Differentiation ; drug effects ; Cells, Cultured ; Hydrogel, Polyethylene Glycol Dimethacrylate ; chemistry ; metabolism ; Nanofibers ; chemistry ; Neural Stem Cells ; cytology ; Neurogenesis ; drug effects ; Peptides ; chemistry ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tissue Scaffolds ; chemistry

Clinical Trials as Topic ; Disease Management ; Health Services ; Humans

The RGD-containing peptide was used to modify the surface of porous PLGA-[ASP-PEG], and was incubated in the modified simulated body fluid (mSBF) for two weeks. The mineralization of PLGA-[ASP-PEG] was explored. The active peptide was used to modify PLGA-[ASP-PEG] through cross-linker (Sulfo-LC-SPDP), characterized by X-ray photoelectron spectroscopy (XPS) the peptide-modified PLGA-[ASP-PEG] (Experiment group, EG) and PLGA-[ASP-PEG] without modification (Control group, CG) were all incubated in mSBF for two weeks, confirmed by observation of Scanning electron microscope(SEM) and measurements of Energy dispersive analysis system of X-ray (EDS) and X-ray diffractometry (XRD). XPS indicated that the binding energy of sulphur in EG was 164eV, and the ratio of carbon to sulphur in EG was 99.746 : 0.1014, however, sulphur was not detected in CG; SEM analysis demonstrated that the mineralization layers were more consecutive and compact in EG than in CG. The results of EDS and XRD indicated that the main component of mineral was hydroxyapatite, and the ratio of Ca/P was 1.60 in EG, and 1.52 in CG. RGD-containing peptide provided enough functional groups for mineralization; the mineralized peptide- modified PLGA-[ASP-PEG] possessed the bonelike microstructure.
Biocompatible Materials ; chemistry ; Bone Substitutes ; Bone and Bones ; metabolism ; Calcification, Physiologic ; Lactic Acid ; chemistry ; Oligopeptides ; chemistry ; Osteogenesis ; drug effects ; Peptides ; chemical synthesis ; pharmacology ; Polyglycolic Acid ; chemistry ; Surface Properties

The chemical constituents from 95% ethanol extract of Dendropanax proteus rhizomes and their anti-inflammatory activities were investigated. These compounds in 95% ethanol extract of D. proteus rhizomes were isolated and purified by silica gel column chromatography, medium-pressure liquid chromatography, preparative liquid chromatography, etc. Their structures were elucidated based on the spectral data and physicochemical properties. All the compounds were tested for their ability to inhibit lipopolysaccharide (LPS) induced nitric oxide production in the murine microglia BV2 cell line. Nine compounds were isolated from the ethyl acetate fraction of 95% ethanol extract of D. proteus rhizomes, and identified as (-)-syringaresinol (1), (+)-(7S,8S)-1',4-dihydroxy-3,3',5'-trimethoxy-7',8,9'-trinor-8,4'-oxyneoligna-7,9-diol (2), erythro-guaiacylglycerol-β-O-4'-coniferyl ether (3), threo-guaiacylglycerol-β-O-4'-coniferyl ether (4), coniferyl alcohol (5), 7-O-ethylguaiacylglycerol (6), vanillin (7), syringaldehyde (8), and excoecanol B (9). Compounds 2 and 4 showed neuritis inhibitory activity against microglial inflammation factor, their half inhibitory concentrations (IC₅₀) were 5.85, 7.29 μmol ·L^-1, respectively. Compounds 1-6,8-9 are isolated from this plant for the first time, compounds 2 and 4 exhibit the potent inhibitory activity.

To establish rat model of lung ischemia/reperfusion (IR) in vivo, and to explore the effects of acidification pretreatment for respiratory acidosis on the expression of matrix metalloproteinase-9 (MMP-9) and the possible mechanisms.
 Methods: A total of 36 male Sprague-Dawley rats were divided into a sham group (S group), a IR group, and an experiment group (RA group) (n=12 in each group). The rat left lung hilum in the S group was dissociated, followed by perfusion without ischemia. After the left lung hilum in the IR group was blocked for 45 min, the rats were followed by reperfusion for 180 min. After left lung hilum in the RA group was dissociated, the respiratory parameters were adjusted so that pressure of end tidal carbon dioxide (PETCO2) reached 56-65 mmHg (1 mmHg=0.133 kPa) for 5 min, then the rats was subjected to IR. Lung tissue wet/dry (W/D) and lung permeability index (LPI) were calculated, while the lung histopathology was observed and the MMP-9 protein expression were measured.
 Results: Compared with the control group, the W/D and LPI in the IR group and the RA group increased after reperfusion (both P<0.05), and the levels of W/D and LPI in the group RA were lower than that in the IR group (P<0.05). LPI and pathology scores were significantly lower in the RA group than those in the IR group (both P<0.01). After IR, the expression of MMP9 in the lung tissues in the IR group and the RA group increased significantly (both P<0.01). The expression of MMP-9 protein in the RA group was significantly lower than that in the IR group (P<0.01).
 Conclusion: After lung IR injury, the expression of MMP-9 protein, vascular permeability and inflammatory exudation is increased. The acidification pretreatment for respiratory acidosis can inhibit the expression of MMP-9 protein and reduce inflammatory exudation after lung IR, showing a protective effect on lung IR injury.
Acidosis, Respiratory ; drug therapy ; prevention & control ; Animals ; Gene Expression Regulation, Enzymologic ; drug effects ; Lung ; enzymology ; Lung Injury ; enzymology ; Male ; Matrix Metalloproteinase 9 ; genetics ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; prevention & control

OBJECTIVETo observe the effects of low-intensity pulsed ultrasound (LIPUS) pretreatment on pulmonary expression of high mobility group box-1 (HMGB1) in a rat model of lung ischemia-reperfusion (IR).

METHODSThirty-two male SpragueDawley rats weighing 250-300 g were randomly divided (=8) into sham-operated group, lung IR group, LIPUS pretreatment group and pretreatment with α7-nicotinic cholinergic receptor (α7nAChR) antagonist group. In the sham-operated group, the left pulmonary hilum was dissociated without occlusion; in the other 3 groups, the left pulmonary hilum was occluded for 45 min followed by reperfusion for 180 min; LIPUS pretreatment for 30 min and intraperitoneal injection of methyllycaconitine (2 mg/kg), an α7nAChR antagonist, were administered before the operation. The wet/dry weight ratio (W/D) and pulmonary permeability index (LPI) of the lung tissue were measured, and the lung histopathology was observed and scored. The contents of interleukin-1 (IL-1) and IL-6 in the lung tissues were measured using ELISA, and the pulmonary expression of HMGB1 protein was detected using immunofluorescence assay and Western blotting.

RESULTSCompared with those in the sham-operated group, the W/D of the lung tissue, LPI, pathological scores, IL-1 and IL-6 contents in the lung tissue, and pulmonary HMGB1 expression all significantly increased in the other 3 groups ( < 0.05). LIPUS preconditioning significantly lowered the W/D values, LPI, pathological score, IL-1 and IL-6 contents and HMGB1 expression in the lung tissues following lung IR, and these effects were significantly inhibited by administration of methyllycaconitine.

CONCLUSIONSLIPUS preconditioning can reduce lung IR injury possibly by activating α7nAChR-dependent cholinergic anti-inflammatory pathway to reduce lung tissue HMGB1 expression.