1.Mechanism of 2,6-DMBQ attenuates airway inflammatory responses in asthmatic mice via the mTOR signaling pathway.
Juan LI ; Shu-Fang LI ; Xiao-Man XIONG ; Qiu-Yan YANG ; Xue-Li XIE ; Yan-Li ZHANG
Chinese Journal of Contemporary Pediatrics 2025;27(4):472-479
OBJECTIVES:
To investigate the therapeutic effects and mechanisms of 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) in a mouse model of asthma.
METHODS:
SPF-grade BALB/c mice were randomly divided into 7 groups (n=8 each group): normal control group, ovalbumin (OVA) group, dimethyl sulfoxide+corn oil group, budesonide (BUD) group, and low, medium, and high dose 2,6-DMBQ groups. An asthma mouse model was established by OVA induction, followed by corresponding drug interventions. Non-invasive lung function tests were performed to measure airway hyperresponsiveness, and enzyme-linked immunosorbent assay was used to determine levels of interleukin (IL)-17, IL-10, and serum immunoglobulin E in bronchoalveolar lavage fluid. A cell counter was employed to detect eosinophil counts in bronchoalveolar lavage fluid, while hematoxylin-eosin staining and periodic acid-Schiff staining were used to assess lung tissue pathological changes. Western blot was conducted to examine the expression of proteins related to the mammalian target of rapamycin pathway (p-AKT/AKT and p-p70S6K/p70S6K), and a fully automated biochemical analyzer was used to evaluate liver and kidney functions.
RESULTS:
Compared with the normal control group, the OVA group showed increased enhanced pause values, inflammation scores from hematoxylin-eosin staining, positive area from periodic acid-Schiff staining, percentage of eosinophils, IL-17/IL-10 ratio, serum immunoglobulin E levels, and relative expression levels of p-AKT/AKT and p-p70S6K/p70S6K (P<0.05). The BUD group and the medium and high dose 2,6-DMBQ groups exhibited decreased values for these indicators compared to the OVA group (P<0.05).
CONCLUSIONS
2,6-DMBQ can inhibit the mTOR pathway to alleviate airway inflammation in asthmatic mice, possibly by mitigating the imbalance between Th17 and regulatory T cells.
Animals
;
Asthma/pathology*
;
Mice, Inbred BALB C
;
Signal Transduction/drug effects*
;
Mice
;
TOR Serine-Threonine Kinases/physiology*
;
Female
;
Benzoquinones/pharmacology*
;
Immunoglobulin E/blood*
;
Interleukin-10/analysis*
;
Interleukin-17/analysis*
;
Bronchoalveolar Lavage Fluid
;
Lung/pathology*
2.A non-invasive diagnostic model of immunoglobulin A nephropathy and serological markers for evaluating disease severity.
Qiu-Xia HAN ; Yong WANG ; Han-Yu ZHU ; Dong ZHANG ; Jing GAO ; Zhang-Suo LIU ; Guang-Yan CAI ; Xiang-Mei CHEN
Chinese Medical Journal 2019;132(6):647-652
BACKGROUND:
Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN.
METHODS:
A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was used to establish the diagnostic model.
RESULTS:
There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P < 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC + FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of I, II, III, IV, and V accounted for 2.21%, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade III being the most prevalent. The levels of urea nitrogen (UN) (13.57 ± 5.95 vs. 6.06 ± 3.63, 5.92 ± 2.97, 5.41 ± 1.73, and 8.41 ± 3.72 mmol/L, respectively) and creatinine (Cr) (292.19 ± 162.21 vs. 80.42 ± 24.75, 103.79 ± 72.72, 96.41 ± 33.79, and 163.04 ± 47.51 μmol/L, respectively) were significantly higher in grade V than in the other grades, and the levels of TP (64.45 ± 7.56, 67.16 ± 6.94, 63.22 ± 8.56, and 61.41 ± 10.86 vs. 37.47 ± 5.6 mg/d, respectively), direct bilirubin (DB) (2.34 ± 1.23, 2.58 ± 1.40, 1.91 ± 0.97, and 1.81 ± 1.44 vs. 0.74 ± 0.57 μmol/L, respectively), and IgA (310.35 ± 103.78, 318.48 ± 107.54, 292.58 ± 81.85, and 323.29 ± 181.67 vs. 227.17 ± 68.12 g/L, respectively) were significantly increased in grades II-V compared with grade I (all P < 0.05).
CONCLUSIONS
The established diagnostic model that combined multiple factors (TC, FIB, D2, IgA, and age) might be used for IgAN non-invasive diagnosis. TP, DB, IgA, Cr, and UN have the potential to be used to evaluate IgAN disease severity.
Adult
;
Biomarkers
;
blood
;
Blood Urea Nitrogen
;
Cholesterol
;
blood
;
Creatinine
;
blood
;
Female
;
Fibrinogen
;
metabolism
;
Glomerulonephritis, IGA
;
blood
;
diagnosis
;
pathology
;
Humans
;
Immunoglobulin A
;
blood
;
Logistic Models
;
Male
;
Middle Aged
;
Multivariate Analysis
;
ROC Curve
3.Changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia.
Wei-Yin MA ; Shao PENG ; Ting ZHANG
Chinese Journal of Contemporary Pediatrics 2017;19(4):425-429
OBJECTIVETo investigate the changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia.
METHODSBlood samples were collected from 30 children with recurrent pneumonia (recurrent pneumonia group), 30 children with acute pneumonia (acute pneumonia group), and 30 healthy children (control group). Serum YKL-40 levels were measured by enzyme-linked immunosorbent assay. The correlation between serum YKL-40 level and laboratory indices related to humoral immune function was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum YKL-40 level for recurrent pneumonia.
RESULTSThe recurrent pneumonia group had a significantly higher serum YKL-40 level than the acute pneumonia and control groups (P<0.05). The acute pneumonia group had a significantly higher serum YKL-40 level than the control group (P<0.05). Serum levels of IgG and complement 4 in the recurrent pneumonia group were significantly lower than in the acute pneumonia group (P<0.05). Serum YKL-40 level was negatively correlated with serum IgG level (r=-0.309, P=0.047) and serum complement 4 level (r=-0.324, P=0.039). The area under the ROC curve of serum YKL-40 level for diagnosing recurrent pneumonia was 0.958 (95%CI: 0.921-0.994).
CONCLUSIONSHumoral immune function is low in children with recurrent pneumonia. Serum YKL-40 may be involved in the occurrence of recurrent pneumonia and can be used as a reference index for diagnosing recurrent pneumonia.
Child, Preschool ; Chitinase-3-Like Protein 1 ; blood ; Complement C4 ; analysis ; Female ; Humans ; Immunity, Humoral ; Immunoglobulin G ; blood ; Male ; Pneumonia ; immunology ; Recurrence
4.Effect of heat shock factor 1 on airway hyperresponsiveness and airway inflammation in mice with allergic asthma.
Jing WANG ; Li-Hong XIN ; Wei CHENG ; Zhen WANG ; Wen ZHANG
Chinese Journal of Contemporary Pediatrics 2017;19(2):222-228
OBJECTIVETo investigate the effect of heat shock factor 1 (HSF1) on airway hyperresponsiveness and airway inflammation in mice with asthma and possible mechanisms.
METHODSA total of 36 mice were randomly divided into four groups: control, asthma, HSF1 small interfering RNA negative control (siHSF1-NC), and siHSF1 intervention (n=9 each). Ovalbumin (OVA) sensitization and challenge were performed to induce asthma in the latter three groups. The mice in the siHSF1-NC and siHSF1 groups were treated with siHSF1-NC and siHSF1, respectively. A spirometer was used to measure airway responsiveness at 24 hours after the last challenge. The direct count method was used to calculate the number of eosinophils. ELISA was used to measure the serum level of OVA-specific IgE and levels of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), and interferon-γ (IFN-γ) in lung tissues and bronchoalveolar lavage fluid (BALF). Quantitative real-time PCR was used to measure the mRNA expression of HSF1 in asthmatic mice. Western blot was used to measure the protein expression of HSF1, high-mobility group box 1 (HMGB1), and phosphorylated c-Jun N-terminal kinase (p-JNK).
RESULTSThe asthma group had significant increases in the mRNA and protein expression of HSF1 compared with the control group (P<0.05). The siHSF1 group had significantly reduced mRNA and protein expression of HSF1 compared with the siHSF1-NC group (P<0.05). The knockdown of HSF1 increased airway wall thickness, airway hyperresponsiveness, OVA-specific IgE content, and the number of eosinophils (P<0.05). Compared with the siHSF1-NC group, the siHSF1 group had significantly increased levels of IL-4, IL-5, and IL-13 and significantly reduced expression of IFN-γ in lung tissues and BALF (P<0.05), as well as significantly increased expression of HMGB1 and p-JNK (P<0.05).
CONCLUSIONSKnockdown of HSF1 aggravates airway hyperresponsiveness and airway inflammation in asthmatic mice, and its possible mechanism may involve the negative regulation of HMGB1 and JNK.
Animals ; Asthma ; etiology ; Bronchial Hyperreactivity ; etiology ; immunology ; Cytokines ; biosynthesis ; DNA-Binding Proteins ; analysis ; physiology ; Eosinophils ; physiology ; Female ; HMGB1 Protein ; analysis ; Heat Shock Transcription Factors ; Immunoglobulin E ; blood ; Mice ; Mice, Inbred BALB C ; Transcription Factors ; analysis ; physiology
5.Clinical significance of fractional exhaled nitric oxide combined with in vitro allergen test in identifying children at a high risk of asthma among those with recurrent wheezing.
Wei-Peng HOU ; Ya-Jie WANG ; Li-Hong QIAO ; Hui-Li SHEN
Chinese Journal of Contemporary Pediatrics 2017;19(9):979-982
OBJECTIVETo investigate the clinical value of combined determination of in vitro allergens and fractional exhaled nitric oxide (FeNO) in indentifying children at a high risk of asthma among those with recurrent wheezing.
METHODSA total of 148 children with recurrent wheezing (0.5-6 years old) were enrolled as study subjects, and 80 healthy children who underwent physical examination were enrolled as the control group. Pharmacia UniCAP immunoassay analyzer was used to measure specific immunoglobulin E (sIgE). Nano Coulomb Nitric Oxide Analyzer was used to measure FeNO. The asthma predictive index (API) was evaluated.
RESULTSThe recurrent wheezing group had a significantly higher proportion of children with positive sIgE than the control group [68.9% (102/148) vs 11.3% (9/80); P<0.05]. The recurrent wheezing group also had significantly higher levels and positive rate of FeNO than the control group (P<0.05). The overall positive rate of API in children with wheezing was 32.4%, and the API-positive children had a significantly higher FeNO value than the API-negative children (51±6 ppb vs 13±5 ppb; P<0.05). The detection rate of API was 40.2% (41/102) in positive-sIgE children and 50.1% (38/73) in FeNO-positive children, and there was no significant difference between these two groups. The children with positive sIgE and FeNO had a significantly higher detection rate of API (81.4%) than those with positive sIgE or FeNO (P<0.05).
CONCLUSIONSCombined determination of FeNO and in vitro allergens is more sensitive in detecting children at a high risk of asthma than FeNO or in vitro allergens determination alone and provides a good method for early identification, diagnosis, and intervention of asthma in children.
Allergens ; immunology ; Asthma ; diagnosis ; Breath Tests ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulin E ; blood ; Infant ; Male ; Nitric Oxide ; analysis ; Recurrence ; Respiratory Sounds ; diagnosis
6.Standardization of Weed Pollen Extracts, Japanese Hop and Mugwort, in Korea.
Kyoung Yong JEONG ; Mina SON ; Soo Young CHOI ; Kyung Hee PARK ; Hye Jung PARK ; Chein Soo HONG ; Jae Hyun LEE ; Jung Won PARK
Yonsei Medical Journal 2016;57(2):399-406
PURPOSE: Japanese hop (Humulus spp.) and mugwort (Artemisia spp.) are notable causes of autumn pollinosis in East Asia. However, Japanese hop and mugwort pollen extracts, which are widely used for the diagnosis, have not been standardized. This study was performed to standardize Japanese hop and mugwort pollen extracts. MATERIALS AND METHODS: Allergen extracts were prepared in a standardized way using locally collected Humulus japonicus and purchased Artemisia vulgaris pollens. The immunoglobulin E (IgE) reactivities of prepared extracts were compared with commercial extracts via IgE immunoblotting and inhibition analyses. Intradermal skin tests were performed to determine the bioequivalent allergy unit (BAU). RESULTS: The IgE reactive components of the extracts via IgE immunoblotting were similar to those of commercial extracts. A 11-kDa allergen showed the strongest IgE reactivity in Japanese hop, as did a 28-kDa allergen in mugwort pollen extracts. Allergenic potencies of the investigatory Japanese hop and mugwort extracts were essentially indistinguishable from the commercial ones. Sums of erythema of 50 mm by the intradermal skin test (SigmaED50) were calculated to be 14.4th and 13.6th three-fold dilutions for Japanese hop and mugwort extracts, respectively. Therefore, the allergenic activity of the prepared extracts was 90827.4 BAU/mg for Japanese hop and 34412 BAU/mg for mugwort. CONCLUSION: We produced Japanese hop and mugwort pollen extracts using a standardized method. Standardized Japanese hop and mugwort pollen extracts will facilitate the production of improved diagnostic and immunotherapeutic reagents.
Allergens/*analysis/*immunology
;
Antibody Specificity
;
*Artemisia
;
Bronchial Hyperreactivity/blood/immunology
;
Cross Reactions
;
Enzyme-Linked Immunosorbent Assay
;
Humans
;
Immunoblotting
;
Immunoglobulin E/blood/*immunology
;
Pollen/*chemistry/*immunology
;
Reference Standards
;
Republic of Korea
;
Rhinitis, Allergic, Seasonal
7.Correlations between the CagA Antigen and Serum Levels of Anti-Helicobacter pylori IgG and IgA in Children.
Ji Hyun SEO ; Chun Woo LIM ; Ji Sook PARK ; Jung Sook YEOM ; Jae Young LIM ; Jin Su JUN ; Hyang Ok WOO ; Hee Shang YOUN ; Seung Chul BAIK ; Woo Kon LEE ; Myung Je CHO ; Kwang Ho RHEE
Journal of Korean Medical Science 2016;31(3):417-422
We tested correlations between anti-Helicobacter pylori IgG and IgA levels and the urease test, anti-CagA protein antibody, degree of gastritis, and age. In total, 509 children (0-15 years) were enrolled. Subjects were stratified as 0-4 years (n = 132), 5-9 years (n = 274), and 10-15 years (n = 103) and subjected to the urease test, histopathology, ELISA, and western blot using whole-cell lysates of H. pylori strain 51. The positivity rate in the urease test (P = 0.003), the degree of chronic gastritis (P = 0.021), and H. pylori infiltration (P < 0.001) increased with age. The median titer for anti-H. pylori IgG was 732.5 IU/mL at 0-4 years, 689.0 IU/mL at 5-9 years, and 966.0 IU/mL at 10-15 years (P < 0.001); the median titer for anti-H. pylori IgA was 61.0 IU/mL at 0-4 years, 63.5 IU/mL at 5-9 years, and 75.0 IU/mL at 10-15 years (P < 0.001). The CagA-positivity rate was 26.5% at 0-4 years, 36.5% at 5-9 years, and 46.6% at 10-15 years for IgG (P = 0.036), and 11.3% at 0-4 years, 18.6% at 5-9 years, and 23.3% at 10-15 years for IgA (P < 0.001). Anti-H. pylori IgG and IgA titers increased with the urease test grade, chronic gastritis degree, active gastritis, and H. pylori infiltration. Presence of CagA-positivity is well correlated with a high urease test grade and high anti-H. pylori IgG/IgA levels.
Adolescent
;
Antibodies, Bacterial/*blood
;
Antigens, Bacterial/*analysis/immunology
;
Bacterial Proteins/*analysis/immunology/metabolism
;
Blotting, Western
;
Child
;
Child, Preschool
;
Chronic Disease
;
Enzyme-Linked Immunosorbent Assay
;
Female
;
Gastritis/pathology
;
Helicobacter Infections/blood/microbiology/*pathology
;
Helicobacter pylori/isolation & purification/*metabolism
;
Humans
;
Immunoglobulin A/*blood
;
Immunoglobulin G/*blood
;
Infant
;
Infant, Newborn
;
Male
;
Severity of Illness Index
;
Urease/metabolism
8.A Korean patient with Guillain-Barré syndrome following acute hepatitis E whose cholestasis resolved with steroid therapy.
Sung Bok JI ; Sang Soo LEE ; Hee Cheul JUNG ; Hong Jun KIM ; Hyun Jin KIM ; Tae Hyo KIM ; Woon Tae JUNG ; Ok Jae LEE ; Dae Hyun SONG
Clinical and Molecular Hepatology 2016;22(3):396-399
Autochthonous hepatitis E virus (HEV) is an emerging pathogen in developed countries, and several cases of acute HEV infection have been reported in South Korea. However, there have been no reports on HEV-associated Guillain-Barré syndrome (GBS) in Korea. We recently experienced the case of a 58-year-old Korean male with acute HEV infection after ingesting raw deer meat. Persistent cholestasis was resolved by the administration of prednisolone. At 2.5 months after the clinical presentation of HEV infection, the patient developed weakness of the lower limbs, and was diagnosed with GBS associated with acute hepatitis E. To our knowledge, this is the second report on supportive steroid therapy for persistent cholestasis due to hepatitis E, and the first report of GBS in a Korean patient with acute HEV infection.
Acute Disease
;
Alanine Transaminase/blood
;
Antibodies, Viral/blood
;
Aspartate Aminotransferases/blood
;
Bilirubin/analysis
;
Cholestasis/*drug therapy
;
Guillain-Barre Syndrome/complications/*diagnosis
;
Hepatitis E/*diagnosis/etiology
;
Hepatitis E virus/immunology
;
Humans
;
Immunoglobulin M/blood
;
Liver/pathology
;
Male
;
Middle Aged
;
Prednisolone/therapeutic use
;
Republic of Korea
;
Steroids/*therapeutic use
9.Abnormalities in Chromosomes 1q and 13 Independently Correlate With Factors of Poor Prognosis in Multiple Myeloma.
Miyoung KIM ; Young Su JU ; Eun Jin LEE ; Hee Jung KANG ; Han Sung KIM ; Hyoun Chan CHO ; Hyo Jung KIM ; Jung Ah KIM ; Dong Soon LEE ; Young Kyung LEE
Annals of Laboratory Medicine 2016;36(6):573-582
BACKGROUND: We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. METHODS: The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. RESULTS: MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. CONCLUSIONS: This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis.
Adolescent
;
Adult
;
Aged
;
Aged, 80 and over
;
Calcium/blood
;
*Chromosome Aberrations
;
Chromosomes, Human, Pair 1
;
Chromosomes, Human, Pair 13
;
Chromosomes, Human, Pair 4
;
Creatine/blood
;
Female
;
Hemoglobins/analysis
;
Humans
;
Immunoglobulin A/blood
;
Immunoglobulin G/blood
;
Karyotyping
;
Male
;
Middle Aged
;
Multiple Myeloma/*diagnosis/genetics/mortality
;
Multivariate Analysis
;
Prognosis
;
Survival Rate
;
Young Adult
10.Analysis of allergens characteristic in 1172 patients with allergic rhinitis in Changzhou area.
Mei SHI ; Lina YAO ; Xiaojun YANG ; Jian CHEN ; Lirong ZHANG ; Jing SUN ; Xiaopeng XU
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2016;30(1):54-57
OBJECTIVE:
To determine the distribution of allergens in patients with allergic rhinitis during from 2008 to 2015 in Changzhou area.
METHOD:
Allergy Screen method was used to detect the specifical-allergen IgE levels of 1172 patients with allergic rhinitis. Among the patients, the distribution of all allergens was analyzed. The positive rate was compared with age, gender, season and so on.
RESULT:
The most common allergens in allergic rhinitis patients in Changzhou were dust mite, fungus, house dust, milk, dander of dog, weed mixture, farina and dander of cat. The more higher positive rates of dust mite, fungus, house dust, milk, dander of dog, dander of cat, eggs were found in teenager group than adult group (P < 0.05). There were more higer positive rates of weed mixture, farina, cashew, cockroaches and crab in teenager group than adult group (P < 0.05). There was no significant difference of positive rate between female group and male group. There was significant difference of variation with seasons.
CONCLUSION
Dust mite, fungus and house dust were the most common allergens among patiens with allergic rhinitis in Changzhou area. The positive rates of allergens varied with ages and seasons.
Adolescent
;
Adult
;
Allergens
;
analysis
;
Animals
;
Cats
;
China
;
Dogs
;
Dust
;
Eggs
;
Female
;
Humans
;
Immunoglobulin E
;
blood
;
Male
;
Pollen
;
Pyroglyphidae
;
Rhinitis, Allergic
;
diagnosis
;
Seasons

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