1.Angiotensin converting enzyme 2 alleviates infectious bronchitis virus-induced cellular inflammation by suppressing IL-6/JAK2/STAT3 signaling pathway.
Xiaoxia JI ; Huanhuan WANG ; Chang MA ; Zhiqiang LI ; Xinyu DU ; Yuanshu ZHANG
Chinese Journal of Biotechnology 2023;39(7):2669-2683
The goal of this study was to investigate the regulatory effect of angiotensin converting enzyme 2 (ACE2) on cellular inflammation caused by avian infectious bronchitis virus (IBV) and the underlying mechanism of such effect. Vero and DF-1 cells were used as test target to be exposed to recombinant IBV virus (IBV-3ab-Luc). Four different groups were tested: the control group, the infection group[IBV-3ab-Luc, MOI (multiplicity of infection)=1], the ACE2 overexpression group[IBV-3ab Luc+pcDNA3.1(+)-ACE2], and the ACE2-depleted group (IBV-3ab-Luc+siRNA-ACE2). After the cells in the infection group started to show cytopathic indicators, the overall protein and RNA in cell of each group were extracted. real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the mRNA expression level of the IBV nucleoprotein (IBV-N), glycoprotein 130 (gp130) and cellular interleukin-6 (IL-6). Enzyme linked immunosorbent assay (ELISA) was used to determine the level of IL-6 in cell supernatant. Western blotting was performed to determine the level of ACE2 phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). We found that ACE2 was successfully overexpressed and depleted in both Vero and DF-1 cells. Secondly, cytopathic indicators were observed in infected Vero cells including rounding, detaching, clumping, and formation of syncytia. These indicators were alleviated in ACE2 overexpression group but exacerbated when ACE2 was depleted. Thirdly, in the infection group, capering with the control group, the expression level of IBV-N, gp130, IL-6 mRNA and increased significantly (P < 0.05), the IL-6 level was significant or extremely significant elevated in cell supernatant (P < 0.05 or P < 0.01); the expression of ACE2 decreased significantly (P < 0.05); protein phosphorylation level of JAK2 and STAT3 increased significantly (P < 0.05). Fourthly, comparing with the infected group, the level of IBV-N mRNA expression in the ACE2 overexpression group had no notable change (P > 0.05), but the expression of gp130 mRNA, IL-6 level and expression of mRNA were elevated (P < 0.05) and the protein phosphorylation level of JAK2 and STAT3 decreased significantly (P < 0.05). In the ACE2-depleted group, there was no notable change in IBV-N (P > 0.05), but the IL-6 level and expression of mRNA increased significantly (P < 0.05) and the phosphorylation level of JAK2 and STAT3 protein decreased slightly (P > 0.05). The results demonstrated for the first time that ACE2 did not affect the replication of IBV in DF-1 cell, but it did contribute to the prevention of the activation of the IL-6/JAK2/STAT3 signaling pathway, resulting in an alleviation of IBV-induced cellular inflammation in Vero and DF-1 cells.
Animals
;
Chlorocebus aethiops
;
Humans
;
Interleukin-6/genetics*
;
Janus Kinase 2/pharmacology*
;
Infectious bronchitis virus/metabolism*
;
STAT3 Transcription Factor/metabolism*
;
Angiotensin-Converting Enzyme 2/pharmacology*
;
Cytokine Receptor gp130/metabolism*
;
Vero Cells
;
Signal Transduction
;
Inflammation
;
RNA, Messenger
2.Clinical characteristics of plastic bronchitis and risk factors for recurrence in children.
Xiao-Yin TIAN ; Guang-Li ZHANG ; Chong-Jie WANG ; Rui-Xue GU ; Yuan-Yuan LI ; Qin-Yuan LI ; Jian LUO ; Zheng-Xiu LUO
Chinese Journal of Contemporary Pediatrics 2023;25(6):626-632
OBJECTIVES:
To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB.
METHODS:
This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed.
RESULTS:
A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05).
CONCLUSIONS
Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.
Female
;
Male
;
Child
;
Humans
;
Child, Preschool
;
Multiple Organ Failure
;
Retrospective Studies
;
Bronchitis/etiology*
;
Dyspnea
;
Pleural Effusion
;
Pulmonary Atelectasis
;
Plastics
;
Respiratory Insufficiency
3.Efficacy of intramuscular injection of Xiyanping injection for the treatment of acute bronchitis in children: a multicenter, randomized, parallel-controlled clinical study.
Qiang CHEN ; Xiao-Hua ZHU ; Yang LIU ; Lan LI ; Jing-Hua LUO ; Yan-Yan ZHANG ; Juan HUANG ; Xiao-Chun CAO ; Xiao-Hua SONG ; Fang-Rui WAN
Chinese Journal of Contemporary Pediatrics 2023;25(11):1107-1112
OBJECTIVES:
To study the efficacy and safety of Xiyanping injection through intramuscular injection for the treatment of acute bronchitis in children.
METHODS:
A prospective study was conducted from December 2021 to October 2022, including 78 children with acute bronchitis from three hospitals using a multicenter, randomized, parallel-controlled design. The participants were divided into a test group (conventional treatment plus Xiyanping injection; n=36) and a control group (conventional treatment alone; n=37) in a 1:1 ratio. Xiyanping injection was administered at a dose of 0.3 mL/(kg·d) (total daily dose ≤8 mL), twice daily via intramuscular injection, with a treatment duration of ≤4 days and a follow-up period of 7 days. The treatment efficacy and safety were compared between the two groups.
RESULTS:
The total effective rate on the 3rd day after treatment in the test group was significantly higher than that in the control group (P<0.05), while there was no significant difference in the total effective rate on the 5th day between the two groups (P>0.05). The rates of fever relief, cough relief, and lung rale relief in the test group on the 3rd day after treatment were higher than those in the control group (P<0.05). The cough relief rate on the 5th day after treatment in the test group was higher than that in the control group (P<0.05), while there was no significant difference in the fever relief rate and lung rale relief rate between the two groups (P>0.05). The cough relief time, daily cough relief time, and nocturnal cough relief time in the test group were significantly shorter than those in the control group (P<0.05), while there were no significant differences in the fever duration and lung rale relief time between the two groups (P>0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05).
CONCLUSIONS
The overall efficacy of combined routine treatment with intramuscular injection of Xiyanping injection in the treatment of acute bronchitis in children is superior to that of routine treatment alone, without an increase in the incidence of adverse reactions.
Humans
;
Child
;
Injections, Intramuscular
;
Cough/drug therapy*
;
Prospective Studies
;
Respiratory Sounds
;
Bronchitis/drug therapy*
;
Treatment Outcome
4.Association of temperament type and mother's emotional state with acute respiratory infection in children.
Qiong YAN ; Ting TAO ; Li Gang WANG ; Chun Lei FAN ; Wen Bin GAO
Journal of Southern Medical University 2022;42(5):747-751
OBJECTIVE:
To explore the correlation of temperament type and mother's emotional state with acute respiratory tract infections in children so as to provide evidence for comprehensive treatment of the infections.
METHODS:
A total of 200 children aged between 3 and 6 were enrolled in this study from two kindergartens of Guangzhou and Hengyang. The mothers were invited to complete a questionnaire of the children's general information followed by assessment using children's temperament scale and the Depression-Anxiety-Stress Scale.
RESULTS:
The total incidence of acute respiratory infection was significantly higher in children with a hard- to-raise temperament than the easy- to-raise children (P < 0.05); the incidences of acute rhinitis, acute pharyngitis, acute laryngitis and acute bronchitis were all significantly higher in the hard-to-raise children (P < 0.05). A significant positive correlation was identified between the total number of episodes of acute respiratory tract infection in children and their mothers' stress and anxiety levels (P < 0.01). Acute rhinitis and acute tracheitis in the children were both positively correlated with the mothers' stress scores (P < 0.05), while acute pharyngitis and acute laryngitis were positively correlated with the mothers' anxiety scores (P < 0.05), while acute bronchitis was positively correlated with the mothers' stress and anxiety scores (P < 0.05). Multiple linear regression analysis with the factors influencing the types of acute respiratory tract infections in children as the independent variables suggested that the easy-to-raise type of temperament was a protective factor against acute rhinitis in children (P < 0.05), while mothers' anxiety was a risk factor of acute laryngitis in children (P < 0.05); the mothers' stress was a risk factor for acute bronchitis in children (P < 0.05).
CONCLUSION
Acute respiratory tract infection in children is closely related to the temperament type of the children and the emotional state of the mothers, which are important therapeutic targets in comprehensive interventions of acute respiratory tract infection in children.
Bronchitis
;
Child
;
Child, Preschool
;
Female
;
Humans
;
Laryngitis
;
Mothers/psychology*
;
Pharyngitis
;
Rhinitis
;
Temperament
5.The potential inhibitory impact of curcumin, epigallocatechin gallate and their combinations on infectious bronchitis virus in vivo
Fadwa Amin ; Sabry Tamam ; Abdou Allayeh ; Mai Raslan
Malaysian Journal of Microbiology 2022;18(1):47-57
Aims:
Infectious bronchitis virus (IBV) is a highly contagious, acute viral respiratory disease that mostly affects chickens. The poultry sector has suffered enormous losses as a result of IBV. Currently, live attenuated vaccines are routinely used to prevent and control IBV. However, due to the enormous genetic variety, vaccinations are becoming ineffective, with low cross-protection effects among vaccine serotypes. The present study aimed at investigating the possible antiviral effects of curcumin, epigallocatechin gallate (EGCG) and their mixtures against IBV in vivo.
Methodology and results:
Curcumin, EGCG and their combinations were administered to infected and uninfected chicken groups and viral load titers were determined by real-time PCR. The clinical symptoms of both the negative and positive control groups were also compared. Finally, the trachea tissues of each group were examined histopathologically. According to our findings, the viral titer and the clinical signs dropped significantly during the pretreatment infection procedure. Curcumin, EGCG and their combinations also show significant antiviral activities.
Conclusion, significance and impact of study
This study clearly shown that natural compounds and their combinations, such as curcumin or/and ECGC can reduce viral pathogenicity in vivo, suggesting that they might have therapeutic implications in the poultry sector.
Infectious bronchitis virus--physiology
;
Curcumin
;
Catechin
6.Preventive and therapeutic effects and mechanism of Xiaoer Feike Granules on chronic bronchitis induced by lipopolysaccharide in rats.
Qiong ZAN ; Rong HU ; Xian-Qin LUO
China Journal of Chinese Materia Medica 2021;46(8):2112-2118
The aim of this paper was to investigate the preventive and therapeutic effects of Xiaoer Feike Granules(XEFK) on chronic bronchitis in rats and its mechanism. Except for 10 rats in the blank group, the remaining 50 of the 60 SD rats were used to establish a model of chronic bronchitis induced by LPS. On the 22 nd day, the model rats were randomly divided into 5 groups according to their body weight, and administrated with purified water, Keteling Capsules 0.11 g·kg~(-1), XEFK 3.2, 1.6 and 0.8 g·kg~(-1)(the dosing concentrations were 0.32, 0.16, 0.08 g·mL~(-1), respectively). These rats took the corresponding drug orally once a day, for consecutive 21 days. The rats were anesthetized 1 hour after the last administration, and the lavage bronchus and alveoli were collected. Then, after the fixation of the smear, neutrophils were counted microscopically, and the contents of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and malondialdehyde(MDA) in the bronchoalveolar lavage fluid(BALF) were detected by colorimetric method. Flow cytometry was used to detect the content changes of T cell subsets CD4~+, CD8~+, CD4~+/CD8~(+ )in serum. Hemorheology related indexes were detected by automatic hemorheology. Enzyme-linked immunosorbent assay(ELISA) was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-2, IL-6 and IL-10 in serum. The expression of TNF-α and IL-10 mRNA in lung was detected by Real-time quantitative PCR(RT-qPCR). HE staining was used to observe the pathological changes in the bronchitis tissues. Compared with the model group, XEFK high and medium dose groups could significantly reduce the contents of neutrophils and MDA in bronchial lavage fluid, and increase the activities of GSH-Px and SOD in BALF, and repair the chronic inflammatory cell infiltration and lymphoid tissue hyperplasia in the bronchial mucosal layer and submucosal layer. The high-dose group could reduce the plasma viscosity of rats, but there was no statistical difference in other hemorheological indexes. CD4~+, CD8~+, CD4~+/CD8~+, IL-2 and IL-10 contents in each dose group were significantly increased, and TNF-α, IL-1β and IL-6 contents were significantly decreased in serum. Each dose group could significantly down-regulate the expression level of TNF-α mRNA in the lung and increase the expression of IL-10 mRNA. XEFK could reduce lipid peroxidation, increase the content of peripheral blood T cell subsets, regulate the release and secretion of inflammatory factors, and repair the morphological and pathological changes of bronchial tissue. Its mechanism might be related to the improvement of inflammatory response and the enhancement of immune function.
Animals
;
Bronchitis, Chronic/drug therapy*
;
Drugs, Chinese Herbal/pharmacology*
;
Glutathione Peroxidase
;
Lipopolysaccharides
;
Lung
;
Rats
;
Rats, Sprague-Dawley
;
Tumor Necrosis Factor-alpha
7.Effect of fresh Phragmitis Rhizoma on airway inflammation in chronic bronchitis based on TGF-β signaling pathway.
Li-Hua CAO ; Yuan-Yuan ZHAO ; Jin-Xin MIAO ; Ming BAI ; Le KANG ; Ming-San MIAO ; Xiu-Min LI
China Journal of Chinese Materia Medica 2021;46(22):5887-5894
This study aims to explore the mechanism of fresh Phragmitis Rhizoma against chronic bronchitis airway inflammation. The SD rats of SPF grade were divided into control group, model group, Guilongkechuanning group(GLKCN, 1.125 g·kg~(-1)), high-dose fresh Phragmitis Rhizoma group(LG-HD, 15 g·kg~(-1)), and low-dose fresh Phragmitis Rhizoma group(LG-LD, 7.5 g·kg~(-1)). The chronic bronchitis models of rats in other groups except the control group were induced by the modified smoking method. From the 15 th day of modeling, the rats were given corresponding agents by gavage for 20 consecutive days. After the last administration, the rats were sacrificed for sample collection. Enzyme-linked immunosorbent assay(ELISA) was employed to detect serum transforming growth factor-β(TGF-β) and interleukin-6(IL-6) levels. The protein expression of TGF-β, IL-1β and IL-6 in lung tissue was detected by immunohistochemical method. Masson staining was performed to detect collagen fibers and muscle fibers in lung tissue, and HE staining to detect the pathological changes of lung tissue. Human bronchial epithelial(16 HBE) cells were cultured in vitro, and CCK-8(cell counting kit-8) method was used to detect the cytotoxicity of cigarette smoke extract(CSE) and fresh Phragmitis Rhizoma. After the exposure of 16 HBE cells to 3.5% CSE and appropriate concentration(800, 400 μg·mL~(-1)) of fresh Phragmitis Rhizoma for 24 h, quantitative real-time PCR was conducted to determine the mRNA levels of TGF-β and IL-1β, and Western blot was employed to determine the protein levels of TGF-β and IL-6 in the cells. The rat model of chronic bronchitis induced by smoking was successfully established. Fresh Phragmitis Rhizoma reduced serum TGF-β and IL-6 levels, down-regulated the protein levels of TGF-β, IL-1β, and IL-6 in lung tissue, and alleviated pathological changes and fibrotic lesions in lung tissue. Moreover, it down-regulated the CSE-induced protein expression of TGF-β and IL-6 as well as the mRNA level of TGF-β in 16 HBE cells. These results indicated that fresh Phragmitis Rhizoma could prevent airway inflammation from chronic bronchitis and promote cell repair by inhibiting the TGF-β signaling pathway.
Animals
;
Bronchitis, Chronic/genetics*
;
Drugs, Chinese Herbal/pharmacology*
;
Inflammation
;
Lung
;
Poaceae/chemistry*
;
Rats
;
Rats, Sprague-Dawley
;
Rhizome
;
Signal Transduction
;
Transforming Growth Factor beta/genetics*
8.Clinical features of severe type 7 adenovirus pneumonia: an analysis of 45 cases.
Xin-Ping ZHANG ; Mei-Yu YANG ; Xiong ZHOU ; Jian-She CAO ; Zi-Li CAI ; Xia-Yan KANG ; Bo XIE ; Ying LIU ; Jie HE ; Zheng-Hui XIAO
Chinese Journal of Contemporary Pediatrics 2020;22(5):429-434
OBJECTIVE:
To study the clinical features of severe type 7 adenovirus pneumonia in children.
METHODS:
A retrospective analysis was performed for the clinical data of children who were diagnosed with severe type 7 adenovirus pneumonia from February to June, 2019.
RESULTS:
Among the 45 children, the male/female ratio was 3:2 and the median age was 14 months. All children had repeated fever, cough, and pulmonary moist rales, and the mean duration of fever was 14±4 days. The median time from fever to dyspnea was 8 days, and the time from fever to mechanical ventilation was 11.6±2.5 d. There was no significant increase in white blood cell count, with neutrophils as the main type. There were slight reductions in hemoglobin and albumin, while platelet and fibrinogen remained normal. There were increases in aspartate aminotransferase, lactate dehydrogenase, procalcitonin, and C-reaction protein. The detection rate of mixed pathogens was 84%. Effusion in both lungs was the major change on chest imaging (64%). Bronchoscopic manifestations were endobronchitis, tracheomalacia, and plastic bronchitis. The incidence rate of respiratory complications was 100%, and extrapulmonary complications mainly involved the circulatory system (47%), digestive system (36%), and nervous system (31%). Among the 45 children, 16 were administered with 400 mg/kg intravenous immunoglobulin (IVIG) daily for 5 days, with a mean duration of fever of 16±5 days, and 29 were administered with 1 g/kg IVIG daily for 2 days, with a mean duration of fever of 13±4 days; there was a significant difference in the mean duration of fever between the two groups (P=0.046). The overall mortality rate was 11%.
CONCLUSIONS
Severe type 7 adenovirus pneumonia in children has severe conditions, with a high incidence rate of complications and a high mortality rate, so it should be diagnosed and treated as early as possible.
Adenoviridae
;
Bronchitis
;
Female
;
Fever
;
Humans
;
Infant
;
Male
;
Pneumonia, Viral
;
Retrospective Studies
9.Clinical Characteristics of Chronic Cough in Korea
Tai Joon AN ; Jin Woo KIM ; Eun Young CHOI ; Seung Hun JANG ; Hwa Young LEE ; Hye Seon KANG ; Hyeon Kyoung KOO ; Jong Min LEE ; Sung Kyung KIM ; Jong Wook SHIN ; So Young PARK ; Chin Kook RHEE ; Ji Yong MOON ; Yee Hyung KIM ; Hyun LEE ; Yong Hyun KIM ; Je Hyeong KIM ; Sang Haak LEE ; Deog Kyeom KIM ; Kwang Ha YOO ; Dong Gyu KIM ; Ki Suck JUNG ; Hui Jung KIM ; Hyoung Kyu YOON ;
Tuberculosis and Respiratory Diseases 2020;83(1):31-41
bronchitis were less frequently observed. Following the KATRD cough-management guidelines, 91.2% of the subjects improved after 4 weeks of treatment. Responders were younger, had a longer duration of cough, and an initial impression of CVA. In univariate and multivariate analyses, an initial impression of CVA was the only factor related to better treatment response.CONCLUSION: The causes of chronic cough in Korea differed from those reported in other countries. The current Korean guidelines proved efficient for treating Korean patients with chronic cough.]]>
Asthma
;
Bronchitis
;
Cohort Studies
;
Cough
;
Diagnosis
;
Disease Management
;
Eosinophils
;
Epidemiology
;
Female
;
Gastroesophageal Reflux
;
Humans
;
Korea
;
Lung Diseases
;
Multivariate Analysis
;
Observational Study
;
Pregnant Women
;
Retrospective Studies
;
Tuberculosis
10.Genomic characteristics of natural recombinant infectious bronchitis viruses isolated in Korea
Hyun Woo MOON ; Haan Woo SUNG ; Hyuk Moo KWON
Korean Journal of Veterinary Research 2019;59(3):123-132
Two infectious bronchitis virus (IBV) K046-12 and K047-12 strains were isolated and the nearly complete genomes of them were sequenced. Sequence comparisons showed that the K046-12 genome was most similar to Korean IBV strains, and the K047-12 genome was most similar to QX-like IBV strains. Phylogenetic analysis showed that nearly all K046-12 and most K046-12 genes were placed in the same cluster as Korean IBV isolates, but the S1 region was placed in the same cluster as Mass-type IBVs. For K047-12, nearly all K047-12 and most K047-12 genes were located in the same cluster as QX-like IBVs, but the M region was located in the same cluster as Korean IBV isolates with K047-12. Recombination analysis confirmed that K046-12 is a recombinant strain with the primary parental sequence derived from Korean IBVs and minor parental sequence derived from Mass-type IBV, and K047-12 is a recombinant strain with the major parental sequence derived from QX-IBV and minor parental sequence derived from Korean IBVs. This study showed that new IBV recombinants are constantly generated among various IBVs, including those used for vaccination. Therefore, genetic analysis of new virus isolates should be performed for effective infectious bronchitis control and appropriate vaccine development.
Bronchitis
;
Genome
;
Humans
;
Infectious bronchitis virus
;
Korea
;
Parents
;
Recombination, Genetic
;
Vaccination


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