High throughput virtual screening strategy to develop a potential treatment for bronchial asthma by targeting interleukin 13 cytokine signaling

Chronic inflammation in the airway passage leads to the clinical syndrome of pediatric asthma. Allergic reactions caused by bacterial, viral, and fungal infection lead to the immune dis-balance which primes T helper cells (Th2), a specific cluster of differentiation 4 (CD4) T cell differentiation. This favors the Th2-specific response by activating the inter-leukin 4/interleukin 13 (IL-4/IL-13) cytokine signaling and further activates the secretion of immunoglobulin E (IgE). IL-13 develops bronchial asthma by elevating bronchial hyperresponsiveness and enables production of immunoglobulin M (IgM) and IgE. The present study aims to target IL-13 signaling using molecular docking and understanding molecular dynamic simulation (MDS) to propose a compelling candidate to treat asthma. We developed a library of available allergic drugs (n=20) and checked the binding affinity against IL-13 protein (3BPN.pdb) through molecular docking and confirmed the best pose binding energy of –3.84 and –3.71 for epinephrine and guaifenesin, respectively. Studying the interaction of hydrogen bonds and Van der Walls, it is estimated that electrostatic energy is sufficient to interact with the active site of the IL-13 and has shown to inhibit inflammatory signaling. These computational results confirm epinephrine and guaifenesin as potential ligands showing potential inhibitory activity for IL-13 signaling. This study also suggests the designing of a new ligand and screening of a large cohort of drugs, in the future, to predict the exact mechanism to control the critical feature of asthma (AU)

Role of heme oxygenase-1 in sevoflurane-induced reduction of airway injury in asthmatic mice / 中华麻醉学杂志

Objective To evaluate the role of heme oxygenase-1 (HO-1) in sevoflurane-induced reduction of airway injury in asthmatic mice.Methods Forty SPF female C57BL/6 mice,aged 6-8 weeks,weighing 20-25 g,were divided into 4 groups (n=10 each) using a random number table:control group (group C),asthma group (group A),asthma plus sevoflurane group (group A+S) and asthma plus sevoflurane plus zinc protoporphyrin group (group A+S+Z).The mice were sensitized and repeatedly challenged with ovalbumin to establish the asthma model.In group A+S,3％ sevoflurane was inhaled for 1 h after every challenge.In group A+S+Z,zinc protoporphyrin 10 mg/kg was intraperitoneally injected after every challenge and before sevoflurane inhalation.The airway responsiveness were assessed at 24 h af=ter the last challenge.The bronchoalvelor lavage fluid (BALF) was collected for determination of cell type and count and concentrations of interleukin-13 (IL-13) and IL-33 (by enzyme-linked immunosorbent assay).The right lung tissues were obtained for measurement of the superoxide dismutase (SOD) activity,contents of malondialdehyde (MDA) and glutathione (GSH) and expression of HO-1 (by Western blot).Lung tissues were stained with haematoxylin and eosin and inflammatory cell infiltration was assessed and scored.Results Compared with group C,the airway responsiveness,inflammatory cell count and concentrations of IL-13 and IL-33 in BALF,and MDA content and infiltration score in lung tissues were significantly increased,the SOD activity and GSH content were decreased,and the expression of HO-1 was upregulated in group A (P＜0.05).Compared with group A,the airway responsiveness,inflammatory cell count and concentrations of IL-13 and IL-33 in BALF,and MDA content and infiltration score in lung tissues were significantly decreased,the SOD activity and GSH content were increased,and the expression of HO-1 was up-regulated in group A+S (P＜0.05),and the expression of HO-1 was down-regulated (P＜ 0.05),and no significant change was found in the other parameters mentioned above in group A+S+Z (P＞ 0.05).Compared with group A+S,the airway responsiveness,inflammatory cell count and concentrations of IL-13 and IL-33 in BALF,and MDA content and infiltration score in lung tissues were significantly increased,the SOD activity and GSH content were decreased,and the expression of HO-1 was down-regulated in group A+S+Z (P＜0.05).Conclusion HO-1 is involved in the pathophysiological mechanism by which sevoflurane attenuates airway injury in asthmatic mice.

Study on therapeutic effect of Cefoselis sulfate versus Cefepime on stroke-associated pneumonia in elderly patients / 中华老年医学杂志

Objective To explore the therapeutic effect of Cefoselis sulfate and Cefepime on the stroke-associated pneumonia in elderly patients.Methods 96 cases of stroke-associated pneumonia with positive pathogen were divided into two groups treated with Cefoselis versus Cefepime respectively.Body temperature,leukocyte count,arterial partial oxygen pressure,the serum level of C-reactive protein (CRP) and bacterial clearance rate were observed before and after the treatment.The cefoselis sulfate group (n =48) or the cefepime group (n =48) was treated with 2.0 g Cefoselis sulfate or 2.0 g Cefepime every 12 hours for 7 to 10 days.Results In post-treatment versus pretreatment,both two groups showed that clinical symptoms and inflammatory indicators were improved,and the patient's body temperature,white blood cell count and neutrophil cell count,hs-CRP and arterial partial oxygen pressure were significantly decreased (all P＜0.05).Arterial partial oxygen pressure was better in post-versus pre-treatment (P＜0.05).The total effective rate was 87.5％ in Cefoselis sulfate group and 83.3％ in cefepime group (P ＞ 0.05).The bacterial clearance rate was higher (89.6％) in Cefoselis sulfate groups than in cefepime groups (67.9％) (P＜0.05).In posttreatments of Cefoselis sulfate groups versus Cefepime groups,white blood cell count and neutrophil cell count,hs-CRP and arterial partial oxygen pressure showed no statistically significant differences (all P ＞ 0.05).Conclusions Compared with Cefepime,Cefoselis has the similar anti-infection efficacy in the treatment of stroke-associated pneumonia.While,the bacterial clearance rate and the total effective rate are better in cefoselis group than in Cefepime group.