Increased Cellular NAD⁺ Level through NQO1 Enzymatic Action Has Protective Effects on Bleomycin-Induced Lung Fibrosis in Mice / 결핵및호흡기질환

BACKGROUND: Idiopathic pulmonary fibrosis is a common interstitial lung disease; it is a chronic, progressive, and fatal lung disease of unknown etiology. Over the last two decades, knowledge about the underlying mechanisms of pulmonary fibrosis has improved markedly and facilitated the identification of potential targets for novel therapies. However, despite the large number of antifibrotic drugs being described in experimental pre-clinical studies, the translation of these findings into clinical practices has not been accomplished yet. NADH:quinone oxidoreductase 1 (NQO1) is a homodimeric enzyme that catalyzes the oxidation of NADH to NAD+ by various quinones and thereby elevates the intracellular NAD⁺ levels. In this study, we examined the effect of increase in cellular NAD⁺ levels on bleomycin-induced lung fibrosis in mice. METHODS: C57BL/6 mice were treated with intratracheal instillation of bleomycin. The mice were orally administered with β-lapachone from 3 days before exposure to bleomycin to 1-3 weeks after exposure to bleomycin. Bronchoalveolar lavage fluid (BALF) was collected for analyzing the infiltration of immune cells. In vitro, A549 cells were treated with transforming growth factor β1 (TGF-β1) and β-lapachone to analyze the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT). RESULTS: β-Lapachone strongly attenuated bleomycin-induced lung inflammation and fibrosis, characterized by histological staining, infiltrated immune cells in BALF, inflammatory cytokines, fibrotic score, and TGF-β1, α-smooth muscle actin accumulation. In addition, β-lapachone showed a protective role in TGF-β1–induced ECM expression and EMT in A549 cells. CONCLUSION: Our results suggest that β-lapachone can protect against bleomycin-induced lung inflammation and fibrosis in mice and TGF-β1–induced EMT in vitro, by elevating the NAD+/NADH ratio through NQO1 activation.

Effect of“Warming Yang and Nourishing Qi”Acupuncture on acetylcholine receptor protein expression in neuromuscular j unction of rats with EAMG / 吉林大学学报(医学版)

Objective:To study the influence of “Warming Yang and Nourishing Qi”Acupuncture in the expression levels of acetylcholine receptor protein (AchR)in gastrocnemius neuromuscular junction (NMJ)of the rats with experimental autoimmune myasthenia gravis (EAMG),and to clarify the mechanism of “Warming Yang and Nourishing Qi”Acupucture in the treatment myasthenia gravis (MG).Methods:The female Lewis rats were used to establish the EAMG rat models immuned with AchRα1 129-145 polypeptide fragments.30 EAMG rats were selected randomly and divided into model control group, drug control group, and acupuncture treatment group (n=10),and another 10 rats purchased at the same period were used as blank control group.The rats in drug control group were treated with 1 8.5 mg · kg-1 · d-1 pyridostigmine by gavage. And the rats in acupuncture treatment group were treated with irritating by“Warming Yang and Nourishing Qi”Acupuncture.The rats in blank control group and model control group were not treated .The Lennon symptom scores of the rats in various groups were recorded.After treatment,the tissues of gastrocnemius NMJ of the rats were taken,and the AchR protein expression levels in NMJ of the rats in various groups were detected by Western blotting method. Results:Compared with blank control group,after successfully modelling,the Lennon symptom scores of the rats in model control group, drug control group and acupuncture treatment group before treatment were significantly increased (P<0.01).Compared with model control group,the Lennon symptom scores of the rats in drug control group and acupuncture treatment group after two treatment course were significantly increased (P<0.01 ). Compared with blank control group, the AchR protein expression level in gastronemus NMJ of the rats in model control group was significantly decreased (P<0.01). Compared with model control group, the AchR protein expression levels in gastronemus NMJ of the rats in acupuncture treatment group and drug control group after treatment were significantly increased (P<0.01).Conclusion:“Warming Yang and Nourishing Qi”Acupuncture has good therapeutic effect on the EAMG through increasing the NMJ AchR protein expression level of the EAMG rats.

Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies

Cisplatin is one of the most widely used and highly effective drug for the treatment of various solid tumors; however, it has dose-dependent side effects on the kidney, cochlear, and nerves. Nephrotoxicity is the most well-known and clinically important toxicity. Numerous studies have demonstrated that several mechanisms, including oxidative stress, DNA damage, and inflammatory responses, are closely associated with cisplatin-induced nephrotoxicity. Even though the establishment of cisplatin-induced nephrotoxicity can be alleviated by diuretics and pre-hydration of patients, the prevalence of cisplatin nephrotoxicity is still high, occurring in approximately one-third of patients who have undergone cisplatin therapy. Therefore it is imperative to develop treatments that will ameliorate cisplatin-nephrotoxicity. In this review, we discuss the mechanisms of cisplatin-induced renal toxicity and the new strategies for protecting the kidneys from the toxic effects without lowering the tumoricidal activity.

Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability

Hair cells at the base of the cochlea appear to be more susceptible to damage by the aminoglycoside gentamicin than those at the apex. However, the mechanism of base-to-apex gradient ototoxicity by gentamicin remains to be elucidated. We report here that gentamicin caused rodent cochlear hair cell damages in a time- and dose-dependent manner. Hair cells at the basal turn were more vulnerable to gentamicin than those at the apical turn. Gentamicin-conjugated Texas Red (GTTR) uptake was predominant in basal turn hair cells in neonatal rats. Transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) expression was confirmed in the cuticular plate, stereocilia and hair cell body of inner hair cells and outer hair cells. The involvement of TRPV1 and TRPV4 in gentamicin trafficking of hair cells was confirmed by exogenous calcium treatment and TRPV inhibitors, including gadolinium and ruthenium red, which resulted in markedly inhibited GTTR uptake and gentamicin-induced hair cell damage in rodent and zebrafish ototoxic model systems. These results indicate that the cytotoxic vulnerability of cochlear hair cells in the basal turn to gentamicin may depend on effective uptake of the drug, which was, in part, mediated by the TRPV1 and TRPV4 proteins.

Comparison of passive particle agglutination test and ELISA determination of antibody isotype on Mycoplasma pneumonia infection / 中华检验医学杂志

ObjectiveTo investigate the consistency between the results of passive particle agglutination test ( PPA ) and ELISA on Mycoplasma pneumonia ( M.pneumonia ) infection.Study the diagnostic value of both assays.Methods From November 2010 to May 2011,the serum samples of ]191 patients with respiratorysymptoms were collected fromAffiliatedHospitalof JiningMedical University.All samples were tested for antibody levels against M.pneumonia using PPA,and for IgM,IgG,IgA subclass using ELISA.The correlation between the results of two methods was evaluated by Kappa test and Spearman rank correlation analysis.The variances of the antibody subclasses among samples with different PPA titers and different age groups were analyzed by Kruskal-Wallis test.The infection status of patients was analyzed based on ELISA results and the clinical relevance of both assays was evaluated in comparison with clinical diagnosis for samples with high PPA titer.ResultsThe level of agreement between the results of PPA and ELISA was 84.3％,with Kappa value of 0.642 ( P ＜0.01 ).The prevalence of IgM and IgA antibody against M.pneumonia was significantly different among samples with various PPA titers ( P ＜0.05 ).The prevalence of IgM subclass was higher in chill and teeuager groups,while that of IgA and IgG were higher in elderly group.Antibody isotyping results suggested that 58.1％ of PPA positive samples (75 cases),especially 96.4％ of samples with high PPA titer ( 27 cases),were of current infection,which was in consistent with clinical diagnosis.ConclusionPPA showed good consistency with ELISA on diagnosis of Mycoplasma pneumonia infection.Antibody subclass determination hy ELISA indicates disease progression,thus to differentiate current infection from past.

Research and Application of New Tracheal Catheter / 医疗卫生装备

Objective To develop a new kind of tracheal catheter for large or medium -sized surgical anesthesia as a medical equipment of respiratory management,and to rescue the patients with anhelation of respiratory arrest,which is essential to first-aid treatment and will be widely used clinically.Methods The disposable non-toxic transparent plastic was adopted,which was reinforced by the spiral stainless steel wire with regular separations.The diameter of the tracheal catheter varied with the different models.The tracheal catheter was composed of the items put into the trachea when applied for anesthesia such as the inflatable bladder and liquid mouth,the ones connected with the anesthesia machine such as the ring lines regulating direction of the front end of the catheter,and the syringe adapters for the liquid and gas.Results The flexible,air-proof tracheal catheter,with its direction adjustable,injected the medicine through its front end.Conclusion The tracheal catheter can be used for intratracheal medication,and will be popularized clinically.