Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma / 中西医结合学报

OBJECTIVE@#Although there have been improvements in targeted therapy and immunotherapy, the majority of lung adenocarcinoma (LUAD) patients still lack effective therapies. Consequently, it is urgent to screen for new diagnosis biomarkers and pharmacological targets. Junctional adhesion molecule-like protein (JAML) was considered to be an oncogenic protein and may be a novel therapeutic target in LUAD. Kaempferol is a natural flavonoid that exhibits antitumor activities in LUAD. However, the effect of kaempferol on JAML is still unknown.@*METHODS@#Small interfering RNA was used to knockdown JAML expression. The cell viability was determined using the cell counting kit-8 assay. The proliferation of LUAD cells was evaluated using the 5-ethynyl-2'-deoxyuridine incorporation assay. The migration and invasion of LUAD cells were evaluated by transwell assays. Molecular mechanisms were explored by Western blotting.@*RESULTS@#JAML knockdown suppressed proliferation, migration and invasion of LUAD cells, and JAML deficiency restrained epithelial-mesenchymal transition (EMT) via inactivating the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Using a PI3K activator (740Y-P), rescue experiments showed that phenotypes to JAML knockdown in LUAD cells were dependent on the PI3K/AKT/mTOR pathway. Kaempferol also inhibited proliferation, migration and invasion of A549 and H1299 cells and partially suppressed EMT through the PI3K/AKT/mTOR pathway. Knockdown of JAML ameliorated the inhibitory effect of kaempferol on LUAD cells. Kaempferol exerted anticancer effects by targeting JAML.@*CONCLUSION@#JAML is a novel target for kaempferol against LUAD cells. Please cite this article as: Wu Q, Wang YB, Che XW, Wang H, Wang W. Junctional adhesion molecule-like protein as a novel target for kaempferol to ameliorate lung adenocarcinoma. J Integr Med. 2023; 21(3): 268-276.

Effects of Ligustrazine on Airway Inflammation in A Mouse Model of Neutrophilic Asthma / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of ligustrazine (LTZ) on airway inflammation in a mouse model of neutrophilic asthma (NA).</p><p><b>METHODS</b>Forty healthy C57BL/6 female mice were randomly divided into 4 groups using a random number table, including the normal control, NA, LTZ and dexamethasone (DXM) groups, with 10 rats in each group. The NA mice model was established by the method of ovalbumin combined with lipopolysaccharide sensitization. At 0.5 h before each challenge, LTZ and DXM groups were intraperitoneally injected with LTZ (80 mg/kg) or DXM (0.5 mg/kg) for 14 d, respectively, while the other two groups were given the equal volume of normal saline. After last challenge for 24 h, the aerosol inhalation of methacholine was performed and the airway reactivity was measured. The bronchoalveolar lavage fluid (BALF) was collected. The Wright-Giemsa staining was used for total white blood cells and differential counts. The levels of cytokines interleukin (IL)-17 and IL-10 were detected by enzyme-linked immunosorbent assay. The pathological change of lung tissue was observed by hematoxylin eosin staining.</p><p><b>RESULTS</b>The airway responsiveness of the NA group was signifificantly higher than the normal control group (P<0.05), while those in the LTZ and DXM groups were signifificantly lower than the NA group (P<0.05). The neutrophil and eosinophil counts in the LTZ and DXM groups were signifificantly lower than the NA group (P<0.05), and those in the LTZ group were signifificantly lower than the DXM group (P<0.05). There were a large number of peribronchiolar and perivascular inflammatory cells in fifiltration in the NA group. The airway inflflammation in the LTZ and DXM groups were signifificantly alleviated than the NA group. The infifiltration in the LTZ group was signifificantly reduced than the DXM group. Compared with the normal control group, the IL-17 level in BALF was signifificantly increased and the IL-10 level in BALF was signifificantly decreased in the NA group (P<0.05). LTZ and DXM treatment signifificantly decreased IL-17 levels and increased IL-10 levels compared with the NA group (P<0.05), and the changes in the above indices were more signifificant in the LTZ group (P<0.05).</p><p><b>CONCLUSION</b>LTZ could alleviate the airway inflflammation in the NA mice model through increasing the IL-10 level and decreasing the IL-17 level.</p>

Research on morbidity and relative factors of cough variant asthma among patients with chronic cough syndrome / 中华流行病学杂志

Objective To study the morbidity of cough variant asthma (CVA) among patients with chronic cough syndrome and its relative risk factors. Methods Patients were recruited with detailed history on their illness. Data were collected on physical examination, chest X-ray, eosinophil cell counts, pulmonary ventilation with histamine stimulating test and bronchi dilation test. According to available data, diagnosis of CVA was confirmed and the relative factors Questionnaire form was completed for each patient. Results Among 473 patients with chronic cough, 95 (44 male and 51 female) were confirmed to be CVA (20.08%). Analysis of the relative factors suggested that CVA was associated with multiple factors. Morbidity of CVA was associated with season, personal histories on allergy and family history on asthma, CVA could be induced by upper respiratory tract infection, inhale of oil vapor, acrimony air, over-burdened physical exercises etc. Conclusion For patients with chronic cough symptom, clear diagnosis of CVA, avoid of passable risk factors and timely medical intervention when necessary, would be helpful in controlling clinical courses and improving the prognosis of the disease.

Effect of ligustrazine injection on levels of interleukin-4 and interferon-gamma in patients with bronchial asthma / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effect of ligustrazine injection (LI) on serum levels of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) in patients with bronchial asthma and determine the mechanism of action of LI in preventing and treating asthma.</p><p><b>METHODS</b>Sixty-eight patients with mild or moderate bronchial asthma were assigned to two groups equally according to their sequence number, odd or even. The conventional treatment was administered to both groups, and LI was given to the treatment group by ultrasonic spray inhalation twice a day but not to the control group. The therapeutic course for all was 2 weeks. Further, 30 healthy subjects who had no history of smoking were enrolled as the normal control group. The clinical condition scores, frequency of attacks and dosage of Terbutaline inhaled were scored and recorded on the first day of hospitalization (before treatment) and after treatment. At the same time, the indexes of lung function, including forced expiratory volume in one second (FEV1), forced expiratory volume in one second to forced vital capacity ratio (FEV1%) and the peak expiratory flow (PEF) were determined before treatment. The levels of IL-4 and IFN-gamma in peripheral blood were detected by ELISA before and after treatment, and compared with that of the healthy control group.</p><p><b>RESULTS</b>After treatment, the clinical condition scores were found to be lower, indexes of lung function were elevated, but serum level of IL-4 and ratio of IL-4/IFN-gamma were reduced in both groups, showing significant differences as compared to those before treatment (P<0.05). However, the changes in all the indexes were more significant in the treatment group than in the control group, also showing statistical significance (P<0.05). No significant difference was revealed when IFN-gamma levels were compared before and after treatment in both groups, though a lowering trend could be seen, significant difference could not be found in the comparison of IFN-gamma levels between groups after treatment (P>0.05).</p><p><b>CONCLUSION</b>LI shows good clinical effect in treating bronchial asthma, and its mechanism might be related to the suppression of the synthesis of IL-4, thus leading to the inhibition of TH2 cell subset preponderant response and immune equilibrium regulation.</p>