Objective: Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models. Methods: EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC. Results: FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well. Conclusion FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials.

Animals ; Dermatitis, Atopic ; Dinitrochlorobenzene ; Erythema ; Gene Expression ; Hemorrhage ; Horses ; Inflammation ; Mice ; Oligonucleotide Array Sequence Analysis ; Skin

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.
Allergens ; Analgesics ; Animals ; Antipyretics ; Asian Continental Ancestry Group ; Asthma ; Bronchial Hyperreactivity ; Cats ; Child ; Classification ; Cohort Studies ; Comorbidity ; Dermatophagoides pteronyssinus ; Disease Management ; Humans ; Methacholine Chloride ; Odds Ratio ; Ownership ; Parturition ; Phenotype ; Prevalence ; Rhinitis, Allergic ; Risk Factors ; Skin

The present study evaluated the anti-inflammatory effect of horse oil in 2, 4-dinitrochlorobenzene (DNCB)-treated BALB/c mice. After the application of DNCB, the mice showed atopic dermatitis symptoms, including severe erythema, hemorrhage, and erosion, whereas those symptoms were alleviated by treatment with horse oil. To explain the anti-dermatitis effect of horse oil, the gene expression levels in the healing process in dorsal skin were observed using a cDNA microarray. The cDNA microarray analysis revealed that the expression levels of 30 genes related to the inflammation, including Ccr1, Ccr2, Ccl20, Anxa1, and Hc genes, were up-regulated (higher than 2.0-fold) in the DNCB group compared to the levels in the control group, whereas the levels were restored to the control level in the DNCB + horse oil-treated group. In contrast, the gene expression levels of 28 genes related to inflammation, including chemokine genes Ccl5, Ccl7, Ccl8, Cxcl10, and Cxcl13 genes, were down-regulated (lower than 0.5-fold) in the DNCB group compared to the levels in the control group, whereas the levels were restored to the control level in the DNCB + horse oil-treated group. Overall, the results show that horse oil restores the expression levels of genes related to inflammation that were perturbed by DNCB treatment.

The present study evaluated the anti-inflammatory effect of horse oil in 2, 4-dinitrochlorobenzene (DNCB)-treated BALB/c mice. After the application of DNCB, the mice showed atopic dermatitis symptoms, including severe erythema, hemorrhage, and erosion, whereas those symptoms were alleviated by treatment with horse oil. To explain the anti-dermatitis effect of horse oil, the gene expression levels in the healing process in dorsal skin were observed using a cDNA microarray. The cDNA microarray analysis revealed that the expression levels of 30 genes related to the inflammation, including Ccr1, Ccr2, Ccl20, Anxa1, and Hc genes, were up-regulated (higher than 2.0-fold) in the DNCB group compared to the levels in the control group, whereas the levels were restored to the control level in the DNCB + horse oil-treated group. In contrast, the gene expression levels of 28 genes related to inflammation, including chemokine genes Ccl5, Ccl7, Ccl8, Cxcl10, and Cxcl13 genes, were down-regulated (lower than 0.5-fold) in the DNCB group compared to the levels in the control group, whereas the levels were restored to the control level in the DNCB + horse oil-treated group. Overall, the results show that horse oil restores the expression levels of genes related to inflammation that were perturbed by DNCB treatment.

Background: We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. Methods: We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. Results: Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; −0.9%, fall; −1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. Conclusion In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort.

This study was conducted to evaluate the hangover relieving effect of Sanghwang mushroom mycelium extract (SME). The extract showed 1,1-diphenyl-2-picrylhydrazyl radical scavenging effect in a concentration-dependent manner and high antioxidant capacity (56.67 ± 1.77%) when administered at 120 µg/mL. In addition, SME significantly increased (p < 0.005) the aldehyde dehydronase (ALDH) activity (126.03 ± 9.11%) when applied at 8 or 16 µL/mL. A locomotor activity test showed that the alcohol-water treated group showed significantly decreased motor activity at 90 min post-administration. However, the alcohol-SME treated group showed a 20-fold higher motor activity than that observed in the alcohol-water treated group at 90 min post-administration. Blood was harvested from each mouse at 90 min post-administration, and both alcohol and aldehyde concentrations were measured. The alcohol-SME treated group showed significantly lower (p < 0.5) alcohol (120.13 ± 12.83 µg/mL) and aldehyde (7.26 ± 1.22 µg/mL) concentrations than the values observed in the alcohol-water treated group. These results suggest that the hangover relieving effect of SME results from increased ALDH activity, which reduces the aldehyde concentration in the blood.

BACKGROUND: Dextran sodium sulfate (DSS)-induced colitis mouse model is used for research of inflammatory bowel disease. The aim of this study was to establish the adequate conditions for DSS mice model, and to find useful tool to measure inflammation. METHODS: The 2.5% DSS was administered to six male C57BL/6 mice and 4% DSS to eight mice at 5 or 9 weeks of age. Each group was consisted of 6 mice with control group in which vehicle was administered instead of DSS. The mice were sacrificed on the 7th day after DSS or vehicle administration. Body weight, diarrhea, and hematochezia were recorded daily. Disease activity index (DAI) score which was composed of body weight change, diarrhea, and hematochezia was measured every day. Colon length was measured after sacrifice and colon mucosal level of interleukin 1 beta (IL-1beta) was measured by ELISA assay. Histological score was compared between ascending and descending colon in the DSS group. RESULTS: Colon length of five- and nine-week DSS group was significantly shorter than each control group but there was no statistical significance depending on DSS concentration or age. DAI score of 4% DSS group in nine-week was significantly higher than that five-week (P = 0.012) but there was no difference between 2.5% and 4% DSS group. The level of IL-1beta in DSS mice was much higher than control group (P < 0.01), but there was no difference among several DSS groups. The histological score was higher in the descending colon than in the ascending colon but there was no statistical difference between each pair of DSS groups. CONCLUSIONS: The 4% DSS mice in nine-week was adequate for DSS-induced colitis model. DAI score was useful tool and descending colon was more appropriate site for histological evaluation of colitis than ascending colon.
Animals ; Body Weight ; Body Weight Changes ; Colitis* ; Colon ; Colon, Ascending ; Colon, Descending ; Dextran Sulfate ; Dextrans* ; Diarrhea ; Enzyme-Linked Immunosorbent Assay ; Gastrointestinal Hemorrhage ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-1beta ; Male ; Mice* ; Sodium*

BACKGROUND/AIMS: Many patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin. METHODS: The clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus. RESULTS: Forty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 +/- 0.02) than in the oral responders (1.36 +/- 0.03, p < 0.01) and in non-responders (n = 141, 1.37 +/- 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR. CONCLUSIONS: A considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.
Administration, Inhalation ; Adolescent ; Adult ; Aspirin/*administration & dosage/*adverse effects ; Asthma/*physiopathology ; Asthma, Aspirin-Induced/etiology/physiopathology ; Bronchial Hyperreactivity/physiopathology ; Bronchial Provocation Tests ; Drug Hypersensitivity/etiology/physiopathology ; Female ; Humans ; Male ; Methacholine Chloride/*administration & dosage ; Retrospective Studies ; Young Adult

BACKGROUND/AIMS: The airway hyperresponsiveness (AHR) in asthma has variable and persistent components that are related to airway inflammation and remodeling, respectively. This longitudinal study examined the relationship of airway responses between exercise (reflecting variable AHR) and methacholine (reflecting persistent AHR). METHODS: The charts were reviewed of 36 young adult males who underwent both methacholine and exercise challenges at different times and were diagnosed with exercise-induced asthma. The severity of the response to each stimulus was scored (0~3). RESULTS: The mean interval between the baseline and follow-up tests was 9.8 (5~58) months. The AHR score was significantly lower with the exercise challenge than with methacholine at follow-up (1.58+/-0.16 vs 1.19+/-0.15, p<0.01), but not at baseline. Compared to baseline, the AHR score was significantly lower with exercise (1.67+/-0.13 vs 1.19+/-0.15, p<0.01), but not with methacholine, and the difference in the AHR scores between exercise and methacholine increased significantly from baseline to follow-up (0.03+/-0.13 vs 0.39+/-0.13, p<0.05). The maximum fall in the forced expiratory volume in 1 s following exercise was significantly related to methacholine AHR (r=-0.571, p<0.001). CONCLUSIONS: Exercise-induced bronchoconstriction was significantly related to methacholine AHR. However, the change in methacholine AHR in a follow-up test was significantly lower than that in the exercise response, which might have resulted from persistent worsening of the AHR with time because methacholine AHR reflects both variable and persistent AHR.
Asthma ; Asthma, Exercise-Induced ; Bronchoconstriction ; Follow-Up Studies ; Forced Expiratory Volume ; Humans ; Inflammation ; Longitudinal Studies ; Male ; Methacholine Chloride ; Young Adult