Protective effects of paeonol against cognitive impairment in lung diseases.

Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1ß, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.

[Efficacy of Ultrasound-Guided Peripheral Intravenous Access: A Systematic Review and Meta-Analysis].

BACKGROUND: Peripheral intravenous access is a common, invasive procedure that is performed in clinical practice. Difficult intravenous access may not only jeopardize patient safety but also increase staff stress, nursing hours, and material costs. PURPOSE: To explore the efficacy of ultrasound-guided peripheral intravenous access in difficult intravenous-access patients and in the two subgroups of adult patients and pediatric patients using systematic review and meta-analysis. METHODS: Six Chinese and English databases, including the Index to Taiwan Periodical Literature System, Airiti Library, CINAHL, Cochrane Library, PubMed/MEDLINE, and ProQuest, were searched for related articles that were published between the earliest year available and April 2016. The search was limited to studies that used randomized control trials (RCTs) or controlled clinical trials (CCTs) and the associated key words "ultrasound-guided" AND "peripheral intravenous access". The 12 articles that met these criteria were used in the analysis. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess methodological quality and RevMan 5.3 software was used to conduct the meta-analysis. RESULTS: The ultrasound-guided technique was found to improve the success rate of intravenous access significantly (OR = 3.00, p < .0001) and to decrease the number of attempts (MD = -0.61, p = .03) in the overall group of difficult intravenous-access patients. The subgroup analysis found a significantly improved success rate and decreased number of attempts in difficult intravenous-access adult patients and significantly decreased procedural times in difficult intravenous-access pediatric patients. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The ultrasound-guided technique may improve the efficacy of intravenous access by helping health care professionals visualize the peripheral veins. We suggest that patient characteristics, ultrasound accessibility, and the feasibility of staff training be assessed in order to provide ultrasound guidance that improves the efficacy of intravenous access.

[Role of macrophages in schistosome infection].

Each stage of schistosome in human body can cause disease. Pathogenic factors released by the parasites induce host immune responses and cause a series of immunopathological changes. As a major cell population in in- nate immunity, macrophages are important in the initiation and development of schistosomiasis. This paper summarizes the activation and polarization of macrophages, and the role of macrophages in schistosome immunopathology and immune evasion.

[Eukaryotic expression of SjE16, SjPPIase and SjRobl genes from Schistosoma japonicum egg and evaluation of their role in immunodiagnosis].

OBJECTIVE: To express Schistosoma japonicum egg proteins by eukaryotic system and evaluate their role in schistosomiasis immunodiagnosis. METHODS: S. japonicum egg RNA was extracted and reversed to cDNA. Egg specific or highly expressed genes: SJCHGC01695 (SjE16), SJCHGC00856 (SjlMA8), SJCHGC06249 (SjTOR), SJCHGC06324 (SjP40), SJEFTD02 (SjSLP), SJCHGC06679 (SjPPIase) and SJCHGC06529 (SjRobl), were amplified and sub-cloned to eukaryotic expression vector pPIC9K. Recombinant vectors were transformed to yeast GS115 and the recombinant yeast was induced by methanol. Proteins were purified with Ni-NTA affinity chromatography and analyzed by SDS-PAGE and Western blotting. For the detection of specific antibodies, the wells of microtiter plate were coated with soluble egg antigen (SEA), SjE16, SjPPIase and SjRobl, respectively, or combination of recombinant proteins. The specific antibody reactivity in sera from schistosome-infected mice and patients were examined by ELISA. RESULTS: The highly expressed genes from S. japonicum eggs were cloned by PCR. The recombinant proteins of SjE16, SjPPIase and SjRobl were expressed and identified by SDS-PAGE and Western blotting. Those recombinant SjE16, SjPPIase and SjRobl were recognized by IgM and IgG in schistosome-infected mouse and patient sera. The sensitivity of the three antigens in detecting IgM and IgG in acute patients were 80%, 60%, 80% and 40%, 80%, 70%, respectively, while that of the combination of SjE16 and SjRobl in detecting IgM was 100%. CONCLUSION: The above three S. japonicum egg enriched proteins were expressed using eukaryotic expression system and can be used in acute schistosomiasis diagnosis.

Clonorchis sinensis calcium-binding protein Cs16 causes acute hepatic injury possibly by reprogramming the metabolic pathway of bone marrow-derived monocytes.

Introduction: Clonorchis sinensis infection results in various complications in the liver and biliary systems and is a neglected tropical disease in Eastern Asia. In this study, we report that C. sinensis calcium-binding protein Cs16 activates host immune cells and induces immunopathology in liver. Methods: Immunohistochemistry was used to detect the localization of Cs16 in C. sinensis adult worms. ELISA was used to detect the serum levels of anti-Cs16 IgG antibody in infected humans and mice. Bile duct injection model was used to figure out the role of Cs16 in vivo. RT-qPCR and ELISA were used to detect the cytokine production from Cs16-treated BMMs in vitro. Seahorse assay was used to detect the metabolic pathway of Cs16-treated BMMs in vitro. Result: Cs16 localizes in the tegument and gut of C. sinensis. Humans and mice with C. sinensis infection exhibited increased levels of anti-Cs16-specific antibody. Using the bile duct injection technique, we found that Cs16 induced obvious inflammation and hepatic necrosis in vivo. Cs16 treatment caused the upregulation of inflammatory cytokines in innate immune cells. Moreover, Cs16-treated monocytes relied more on the glycolytic metabolic pathway. Discussion: Our findings suggest that Cs16 is a potential pathogenic factor derived from C. sinensis adult worm. By reprogramming the metabolic pathway of innate immune cells, Cs16 triggers pro-inflammatory responses in the liver, and therefore, Cs16 is a potential target for the prevention and treatment of clonorchiasis.

Diltiazem inhibits breast cancer metastasis via mediating growth differentiation factor 15 and epithelial-mesenchymal transition.

Migration and metastasis commonly happen to triple-negative breast cancer (TNBC) patients with advanced diseases. In many studies, it has been suggested that epithelial-mesenchymal transition (EMT) is one of the key mechanisms triggering cancer metastasis. Accumulating evidence has proven that calcium channel blockers mediate cell motility. Therefore, we attempt to investigate the effects of diltiazem, which has been selected from several FDA-approved clinical calcium channel blockers, on EMT in TNBC. By using both mouse and human TNBC cell lines, we found that diltiazem decreases colony formation and cell migration in breast cancer cells. The expression of epithelial markers such as E-cadherin and ZO-1 were increased dose-dependently by diltiazem, while mesenchymal markers such as Snail and Twist were decreased. In addition, we found that the expression of growth differentiation factor-15 (GDF-15) was also increased by diltiazem. Administering recombinant GDF-15 also reverses EMT, inhibits colony formation and migration in breast cancer cells. Moreover, treatment with diltiazem in tumor-bearing mice also decreases cancer metastasis and nodule formation, with more GDF-15 expression in diltiazem-treated mice than saline-treated mice, respectively. These findings suggest that diltiazem regulates EMT and cell motility through elevating GDF-15 expression in breast cancers in vitro and in vivo.

Cardamonin attenuates phorbol 12-myristate 13-acetate-induced pulmonary inflammation in alveolar macrophages.

Pulmonary inflammation involves complex immune responses in which alveolar macrophages release pro-inflammatory proteins and cytokines. Cardamonin is a spice component that exerts anti-inflammatory and anti-oxidative properties against pulmonary inflammation. Herein, the aim of this research is to investigate the effects of cardamonin on pulmonary inflammation and its mechanism. Pulmonary inflammation in mice was induced by intratracheal administration of PMA. PMA-stimulated acute fibrosis, pulmonary edema, and inflammatory responses were ameliorated by oral administration of cardamonin in vivo. In MH-S alveolar macrophages, PMA-induced pro-inflammatory responses, including iNOS, COX-2, MMP-9 and cytokines expressions were reduced by cardamonin. The anti-oxidative Nrf2/HO-1 axis was also provoked by cardamonin in MH-S alveolar macrophages. In addition, MMP-9 expression induced by PMA is also decreased by the down-stream metabolites of HO-1, indicating that HO-1 expression partially contributes to the anti-inflammatory effect exerted by cardamonin. In this study, cardamonin demonstrates anti-inflammatory and anti-oxidative effects on PMA-induced pulmonary inflammation and activating Nrf2/HO-1 axis in alveolar macrophages. Cardamonin also ameliorates pulmonary inflammation, rapid fibrosis in vivo, suggesting powerful health benefits.

Clonorchis sinensis infection modulates key cytokines for essential immune response impacted by sex.

Infection with helminths can modulate the host immune response, which ultimately shape morbidity and mortality of the associated diseases. We studied key cytokines for essential immune response in sera from 229 southeastern China individuals infected with Clonorchis sinensis and 60 individuals without C. sinensis infection, and measured serum specific IgG and IgE against worms in these people. Individuals infected with C. sinensis had significantly higher antigen-specific IgG and IgE levels, which were positively correlated with egg counts in feces. However, less enhancement of IgE antibody was observed in females when compared to males with similar infection levels. C. sinensis infection caused diminished Th1 cytokines (IL-1ß, IL-2, IL-12p70, IFN-γ and TNF-α), Th2 cytokine (IL-4), as well as Th17 cytokine (IL-17A) in sera, which showed decreasing trend by infection intensity. Notably, these phenotypes were more significant in females than those in males. Although C. sinensis infection is associated with the development of hepatobiliary diseases, there was no significant correlation between the dampened cytokine profiles and the hepatobiliary morbidities. Our study indicates C. sinensis infection is strongly related to the immune suppression in human. Sex differences shape the immune milieus of clonorchiasis. This study provides a better understanding of how worms affect immune responses and cause a long-term immune alternation in humans with C. sinensis infection.