IL-17A Promotes Epithelial ADAM9 Expression in Cigarette Smoke-Related COPD.

Background: It has been reported that a disintegrin and metalloproteinase 9 (ADAM9) is involved in the pathogenesis of cigarette smoke (CS)-associated chronic obstructive pulmonary disease (COPD). But how CS exposure leads to upregulation of ADAM9 remains unknown. Methods: Patients who underwent lobectomy for a solitary pulmonary nodule were enrolled and divided into three groups: non-smokers with normal lung function, smokers without COPD and smoker patients with COPD. Immunoreactivity of interleukin (IL)-17A and ADAM9 in small airways and alveolar walls was measured by immunohistochemistry. Wild-type and Il17a -/- C57BL/6 mice were exposed to CS for six months, and ADAM9 expression in the airway epithelia was measured by immunoreactivity. In addition, the protein and mRNA expression levels of IL-17A and ADAM9 were assessed in CS extract (CSE) and/or IL-17A-treated human bronchial epithelial (HBE) cells. Results: The immunoreactivity of ADAM9 was increased in the airway epithelia and alveolar walls of patients with COPD compared to that of the controls. The expression of IL-17A was also upregulated in airway epithelial cells of patients with COPD and correlated positively with the level of ADAM9. The results from the animal model showed that Il17a -/- mice were protected from emphysema induced by CS exposure, together with a reduced level of ADAM9 expression in the airway epithelia, suggesting a possible link between ADAM9 and IL-17A. Consistently, our in vitro cell model showed that CSE stimulated the expression of ADAM9 and IL-17A in HBE cells in a dose- and time-dependent manner. Recombinant IL-17A induced ADAM9 upregulation in HBE cells and had a synergistic effect with CSE, whereas blocking IL-17A inhibited CSE-induced ADAM9 expression. Further analysis revealed that IL-17A induced c-Jun N-terminal kinase (JNK) phosphorylation, thereby increasing ADAM9 expression. Conclusion: Our results revealed a novel role of IL-17A in CS-related COPD, where IL-17A contributes to ADAM9 expression by activating JNK signaling.

Aza-BODIPY-Based Nanomedicines in Cancer Phototheranostics.

Cancer phototheranostics, composed of optical diagnosis and phototherapy (including photodynamic therapy and photothermal therapy), is a promising strategy for precise tumor treatment. Due to the unique properties of near-infrared absorption/emission, high reactive oxygen species generation, and photothermal conversion efficiency, aza-boron-dipyrromethene (aza-BODIPY), as an emerging organic photosensitizer, has shown great potential for tumor phototheranostics. By encapsulating aza-BODIPY photosensitizers within functional amphiphilic polymers, we can afford hydrophilic nanomedicines that selectively target tumor sites via an enhanced permeability and retention effect, thereby efficiently improving diagnosis and therapeutic efficacy. Herein, in this spotlight article, we attempt to highlight our recent contributions in the development of aza-BODIPY-based nanomedicines, which comprises three main sections: (1) to elucidate the design strategy of aza-BODIPY photosensitizers and corresponding nanomedicines; (2) to overview their photophysical properties and biomedical applications in phototheranostics, including fluorescence imaging, photoacoustic imaging, photodynamic therapy, photothermal therapy, and synergistic therapy; and (3) to depict the challenges and future perspectives of aza-BODIPY nanomedicines. It is believed that this Spotlight on Applications article would illuminate the way of developing new aza-BODIPY nanomedicines as well as other organic photosensitizer-based nanomedicines for future clinical translation.

Efficacy of Shenqi Pollen Capsules for High-Altitude Deacclimatization Syndrome via Suppression of the Reoxygenation Injury and Inflammatory Response.

High-altitude deacclimatization syndrome (HADAS) is involved in hypoxia-reoxygenation injury and inflammatory response, induced a series of symptoms, and has emerged as a severe public health issue. Here, we investigated the mechanism as well as potential means to prevent HADAS using Shenqi pollen capsules (SPCs) in subjects with HADAS in a multicenter, double-blinded, randomized, placebo-controlled study. All subjects were at the same high altitude (3650 m) for 4-8 months before returning to lower altitudes. Subjects (n = 288) in 20 clusters were diagnosed with mild or moderate HADAS on the third day of the study. We randomly allocated 20 clusters of subjects (1 : 1) to receive SPCs or a placebo for 7 weeks, and they were then followed up to the 14th week. The primary endpoints were subjects' HADAS scores recorded during the 14 weeks of follow-up. Compared with the placebo, SPC treatment significantly decreased the subjects' HADAS scores and reduced the incidence of symptom persistence. SPC therapy also reduced the serum levels of CK, CK-MB, LDH, IL-17A, TNF-α, and miR-155 and elevated IL-10 and miR-21 levels. We thus demonstrate that SPCs effectively ameliorated HADAS symptoms in these subjects via suppression of the hypoxia-reoxygenation injury and inflammatory response.

Near-infrared nanoparticles based on indocyanine green-conjugated albumin: a versatile platform for imaging-guided synergistic tumor chemo-phototherapy with temperature-responsive drug release.

BACKGROUND: The aim of this study was to develop a multifunctional theranostic agent based on BSA nanoparticles (NPs), which loaded artemisinin (ART) and co-conjugated with indocyanine green (ICG) and arginine-glycine-aspartic acid (RGD) peptide (RGD-indocyanine green-Bovine Serum Albumin-artemisinin [IBA] NPs). MATERIALS AND METHODS: The physicochemical parameters of RGD-IBA NPs were character-ized in terms of the particle size, zeta potential, morphology, entrapment efficiency, drug loading, in vitro release behavior, photothermal and photodynamic effect, and in vitro anticancer ability. In vivo fluorescence and thermal imaging as well as antitumor studies were also evaluated. RESULTS: The tumor chemotherapeutic effects of ART and the ability of fluorescence imaging, hyperthermia generation and reactive oxygen species production of ICG and tumor-targeting RGD were integrated to achieve RGD-IBA NPs for imaging-guided tumor-targeted chemotherapy/photothermal/photodynamic therapy (chemo-phototherapy). The RGD-IBA NPs showed enhanced physiological stability and photo-stability compared with free ART and ICG. In addition, they were temperature-responsive; their sizes increased with increasing temperature between 25°C and 55°C, thereby leading to drug release upon the irradiation with near infrared (NIR) laser. In vivo fluorescence images of tumor-bearing mice showed that the RGD-IBA NPs could highly and passively reach the targeted tumor region with maximum accumulation at 24 hours post-intravenous injection. The in vitro and in vivo results demonstrated that the RGD-IBA NPs not only have good biocompatibility, but also are highly efficient tumor synergistic chemo-phototherapeutic agents. CONCLUSION: Through this study, it was found that RGD-IBA NPs could potentially be a very promising tumor theranostic agent.

The Effects of Aloe vera on Wound Healing in Cell Proliferation, Migration, and Viability.

INTRODUCTION: Aloe vera is sometimes used as a folk remedy for minor wounds and burns, but its mechanisms of action in wound healing are unclear. OBJECTIVE: In this study, the authors evaluate the effects of A vera on wound healing. MATERIALS AND METHODS: In vitro analyses of cell proliferation and migration were conducted on normal human primary skin fibroblasts and keratinocytes in growth media with A vera solution and preservatives at various concentrations. Growth media with preservatives but without A vera solution served as the control. RESULTS: Aloe vera had significant stimulatory effects on cell proliferation and migration of both fibroblasts and keratinocytes. Surprisingly, A vera also exhibited strong protective effects on preservative-induced keratinocyte death. Keratinocytes in the growth media with both the preservatives and A vera had dramatically higher viability than cells in the control media without A vera. CONCLUSIONS: The results suggest A vera accelerates wound healing by promoting the proliferation and migration of fibroblasts and keratinocytes and by protecting keratinocytes from preservative-induced death.

[Nitrogen and Phosphorous Adsorption Characteristics of Suspended Solids Input into a Drinking Water Reservoir via Typhoon Heavy Rainfall].

During typhoon "Mujigae" in October 2015, water samples and surface sediments were collected from Gaozhou Reservoir, a drinking water reservoir, for simulation and analysis of the kinetics of suspended solids adsorption to nitrogen and phosphorus and the adsorption isotherms of suspended solids with different particle sizes and different concentrations. The results showed no obvious nitrogen adsorption of suspended solids of Gaozhou Reservoir. However, the adsorption effect to phosphorus by suspended solids was significant and the equilibrium time of phosphorus adsorption was 10 hours. The adsorption capacity of phosphorus increased with the decrease of sediment particle size when particle sizes were less than 0.25 mm, whereas it increased with the increase of suspended solids concentration when the concentration was in the range of 0.2-2.0 kg·m-3. The adsorption isotherm of suspended solids to phosphorus conformed to the Langmuir and Freundlich models, and the maximum adsorption capacity increased with the decrease of suspended solids particle sizes, which increased with the increase of suspended solids concentrations. The maximum adsorption capacity of suspended solids to phosphorus was 0.073-1.776 mg·g-1. These results indicated that the increase of suspended solids concentration due to the heavy rainfall of the typhoon promoted the adsorption of suspended solids to phosphorus, which reduced eutrophication in Gaozhou Reservoir.

[Eutrophication and Characteristics of Cyanobacteria Bloom in the Summer in Guishi Reservoir].

Large-scale cyanobacteria bloom occurred in the summer of 2014 in the Guishi Reservoir that is an important drinking water source for Hezhou City. The dynamic change regularity, external pollution sources, and the phytoplankton community characteristics during the bloom were investigated to evaluate the eutrophication in the reservoir and to present effective prevention and control measures. The results showed that nitrogen and phosphorus concentrations increased year by year; water quality on some sites has been out of class Ⅱ of national water quality standards; and the main pollution source was the agricultural non-point sources. Phytoplankton cell density was in the range of 8.60×106-5.36×108 cells·L-1 and chlorophyll a concentrations reached 74.48 µg·L-1 during the bloom. The dominant species was Microcystis wesenbergii whose density reached 5.36×108 cells·L-1. The cell density decreased over time and concentrated on the surface and at the depth of 2 m underwater. The total phytoplankton cell density was strongly correlated to total phosphorus, total nitrogen, nitrate nitrogen, and the permanganate index, and was inversely correlated to transparency. The water in the Guishi Reservoir was not polluted by microcystic toxins. Moreover, Guishi Reservoir is in a meso-eutrophic state; therefore, the prevention and control of the cyanobacteria bloom should focus on weather conditions and on reducing the input of nitrogen and phosphorus to keep the nutrient levels low.

[Phytoplankton community structure and eutrophication risk assessment of Beijiang River].

To study the distribution of phytoplankton and water quality of Beijiang River, the community structure of phytoplankton was investigated and analyzed in wet and dry seasons. The results showed that a total of 74 species belonging to six phyla, 29 family and 48 genera of phytoplankton were identified, including 58 species of five phyla, 23 family and 41 genera in wet season and 59 species of six phyla, 26 family and 40 genera in dry season. Phytoplankton community structure in Beijiang River was represented by Bacillariophyta, Chlorophyta and Cyanophyta. Bacillariophyta dominanted the phytoplankton, and the dominant species were Aulacoseira granulate, Fragilaria virescens, Surirella biseriata, Nitzschia amphibia, Navicula simplex, Cyclotella meneghiniana, Synedra ulna, Gomphonema angustatum and Cymbella tumida. There was little difference in phytoplankton density between both seasons with the mean values being 3.54 x 10(5) and 4.87 x 10(5) cells L(-1) in dry and wet seasons, respectively. Based on the RDA results, DO, permanganate index, nitrogen and phosphorus were the important environmental factors affecting the distribution of phytoplankton in Beijiang River. The water quality of Beijiang River was classified as oligo-mesotrophic level even if this river was subjected to nitrogen and phosphorus pollution mainly from agricultural non-point source.

[Therapeutic efficacy of Traditional Vein Chemotherapy and Bronchial Arterial Infusion Combining with CIKs on III Stage Non-small Cell Lung Cancer.].

BACKGROUND: The therapeutic efficacy of late lung-cancer was very poor, and cytokine-induced killer cells (CIK) were paid more attention to treat non-small cell lung cancer (NSCLC). The aim of this study is to get insight into the role of bronchial arterial infusion bronchial arterial infusion (BAI) plus CIK about NSCLC by comparing therapeutic efficacy among BAI, traditional vein chemotherapy and BAI plus CIK, for late NSCLC. METHODS: A total of 120 patients were enrolled in this study, dividing randomly into three groups: bronchial arterial infusion (BAI), traditional vein chemotherapy and BAI plus CIK. Clinical effects and side effects were estimated after two period of therapy. RESULTS: The effective rate (CR+PR%) of combined group is higher than the traditional vein chemotherapy group (66.67%, n=39) and there are significant differences (Chi-square=4.721, P=0.03); The side effect of rate of BAI plus CIK group is significantly lower than the traditional vein chemotherapy group, and so did the non-bone marrow inhibition side effects (P<0.05). The tumor progression rate (PD%) of bronchial arterial infusion (BAI) group is higher than combined group (Chi-square=4.287, P=0.038). There was no difference between the traditional vein chemotherapy group and combined group (Chi-square=0.082, P=0.775). CONCLUSIONS: Bronchial Artery Infusion combined with cytokine-induced killer cells is an ideal, safety, effective comprehensive treatment method for late stage lung cancer.

Transgenic maize plants expressing a fungal phytase gene.

Maize seeds are the major ingredient of commercial pig and poultry feed. Phosphorus in maize seeds exists predominantly in the form of phytate. Phytate phosphorus is not available to monogastric animals and phosphate supplementation is required for optimal animal growth. Undigested phytate in animal manure is considered a major source of phosphorus pollution to the environment from agricultural production. Microbial phytase produced by fermentation as a feed additive is widely used to manage the nutritional and environmental problems caused by phytate, but the approach is associated with production costs for the enzyme and requirement of special cares in feed processing and diet formulation. An alternative approach would be to produce plant seeds that contain high phytase activities. We have over-expressed Aspergillus niger phyA2 gene in maize seeds using a construct driven by the maize embryo-specific globulin-1 promoter. Low-copy-number transgenic lines with simple integration patterns were identified. Western-blot analysis showed that the maize-expressed phytase protein was smaller than that expressed in yeast, apparently due to different glycosylation. Phytase activity in transgenic maize seeds reached approximately 2,200 units per kg seed, about a 50-fold increase compared to non-transgenic maize seeds. The phytase expression was stable across four generations. The transgenic seeds germinated normally. Our results show that the phytase expression lines can be used for development of new maize hybrids to improve phosphorus availability and reduce the impact of animal production on the environment.

Sickle cell bone disease: response to vitamin D and calcium.

Bone disease with osteoporosis and osteomalacia are common in sickle cell disease (SCD). Some patients have vitamin D deficiency and low bone mineral density (BMD). The role of vitamin D and calcium supplementation to restore bone health in SCD has not been well studied. In 14 adults with SCD, we measured 25(OH)D (25-hydroxyvitamin D) and BMD at the femoral neck, lumbar spine, and distal third of the ulna plus radius, along with markers of bone resorption (CTx; C-terminal component of pro-collagen type I) and bone formation (osteocalcin) before and after 12 months of vitamin D(2) and calcium carbonate treatment. Pretreatment, all patients were vitamin D deficient with a mean 25(OH)D level of 11.6 [corrected] +/- 4 [corrected] ng/ml, had low BMD at the lumbar spine (L-spine), 0.87 +/- 0.11 g/cm(2) (mean Z-score of -2.6 3 +/- 0.71 SD and T score of -2.31 +/- 0.75 SD), femoral neck, 0.8 +/- 0.18 g/cm(2) (mean Z-score -1.36 +/- 0.84, T-score -1.14 +/- 0.75), and the distal radius and ulna, 0.6 +/- 0.17 g/cm(2) (mean Z-score -1.18 +/- 0.79, T-score -1.01 +/- 0.74) and had elevated CTx (0.87 +/- 0.5 ng/ml) and osteocalcin levels (12.3 +/- 3.7 ng/mul). After treatment, all patients corrected their 25(OH)D level (34.6 [corrected] +/- 11 [corrected] ng/ml) (P < 0.001) with a 3.6% +/- 3.9% increase in BMD at the L-spine (P = 0.009), 4.6% +/- 8.5% increase at the femoral neck (P = 0.05) and 6.5% +/- 12.6% increase at the distal radius plus ulna (P = 0.09). CTx, osteocalcin, and PTH(i) levels were unchanged. Treatment of adult SCD with vitamin D and calcium can restore 25(OH)D levels to normal and improve BMD, but, markers of bone resorption remained unchanged. Screening for vitamin D deficiency and BMD in SCD patients seems warranted.