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Allergic rhinitis (AR) is a common disorder of the upper airway, while asthma is a disease affecting the lower airway and both diseases are usually comorbid. Interleukin (IL)-4 and IL-13 are critical cytokines in the induction of the pathogenic Th2 responses in AR and asthma. Targeting the IL-4/IL-13 axis at various levels of its signaling pathway has emerged as promising targeted therapy in both AR and asthma patient populations. In this review, we discuss the biological characteristics of IL-4 and IL-13, their signaling pathways, and therapeutic antibodies against each cytokine as well as their receptors. In particular, the pleiotropic roles of IL-4 and IL-13 in orchestrating Th2 responses in AR and asthma patients indicate that dual IL-4/IL-13 blockade is a promising therapeutic strategy for both diseases.

Allergic rhinitis (AR) is a common allergic disease characterized by disruption of nasal epithelial barrier. In this study, we investigated the mRNA expression of zonula occludens-1 (ZO-1), ZO-2 and ZO-3 and histone deacetylase 1 (HDAC1) and HDAC2 in AR patients compared to healthy controls. RNA samples were extracted from nasal epithelial cells of house dust mites (HDMs)-sensitized AR patients and healthy controls (n = 28 in each group). The RNAs were reverse transcribed into cDNAs for measurement of ZO-1, ZO-2, ZO-3, HDAC1 and HDAC2 expression levels by quantitative PCR. The mRNA expression of ZO-1 was significantly decreased in AR patients compared to healthy controls (p = 0.010). No significant difference was observed in the expression levels of ZO-2, ZO-3, HDAC1 and HDAC2 in AR patients compared to healthy controls. We found significant associations of higher HDAC2 levels in AR patients with lower frequency of changing bedsheet (p = 0.043) and with AR patients sensitized to Dermatophagoides farinae (p = 0.041). Higher expression of ZO-2 was observed in AR patients who had pets (p = 0.007). In conclusion, our data indicated that ZO-1 expression was lower in AR patients contributing to decreased integrity of nasal epithelial barrier integrity, and HDAC2 may be involved in the pathogenesis of the disease.

Background Gouty arthritis is a disease of global burden in which defective metabolism of uric acid causes arthritis. Gouty arthritis or medications used for its treatment may lead to uric acid-associated complications such as upper gastrointestinal bleeding (UGIB) and renal impairment. Methods In this cross-sectional study with retrospective record review, 403 established gouty arthritis patients were recruited to determine the incidence of UGIB and associated factors among gout patients who were on regular nonsteroidal anti-inflammatory drugs (NSAIDs). Results The mean age of the 403 gouty arthritis patients was 55.7 years old and the majority (n = 359/403; 89.1%) were male. The incidence of UGIB among gouty arthritis patients who were on NSAIDs was 7.2% (n = 29/403). Older age (p < 0.001), diclofenac medication (p = 0.003), pantoprazole medication (p = 0.003), end-stage renal failure (ESRF) (p = 0.007), smoking (p = 0.035), hypertension (p = 0.042) and creatinine (p = 0.045) were significant risk factors for UGIB among the gouty arthritis patients in univariable analysis. Older age (p = 0.001) and diclofenac medication (p < 0.001) remained significant risk factors for UGIB among the gouty arthritis patients in multivariable analysis. Conclusions Age and diclofenac were significantly associated with UGIB among patients with gouty arthritis on regular NSAIDs, indicating that these factors increased the risks of developing UGIB in gout patients. Hence, these high-risk groups of gouty arthritis patients should be routinely monitored to avoid the potential onset of UGIB. Our data also suggest that diclofenac should be prescribed for the shortest duration possible to minimize the risk of developing UGIB in gout patients.

Allergic rhinitis (AR) is a common disease affecting 400 million of the population worldwide. Nasal epithelial cells form a barrier against the invasion of environmental pathogens. These nasal epithelial cells are connected together by tight junction (TJ) proteins including zonula occludens-1 (ZO-1), ZO-2 and ZO-3. Impairment of ZO proteins are observed in AR patients whereby dysfunction of ZOs allows allergens to pass the nasal passage into the subepithelium causing AR development. In this review, we discuss ZO proteins and their impairment leading to AR, regulation of their expression by Th1 cytokines (i.e., IL-2, TNF-α and IFN-γ), Th2 cytokines (i.e., IL-4 and IL-13) and histone deacetylases (i.e., HDAC1 and HDAC2). These findings are pivotal for future development of targeted therapies by restoring ZO protein expression and improving nasal epithelial barrier integrity in AR patients.

Allergic rhinitis (AR) is a common disorder of the upper airway, while asthma is a disease affecting the lower airway and both diseases are usually comorbid. Interleukin (IL)-4 and IL-13 are critical cytokines in the induction of the pathogenic Th2 responses in AR and asthma. Targeting the IL-4/IL-13 axis at various levels of its signaling pathway has emerged as promising targeted therapy in both AR and asthma patient populations. In this review, we discuss the biological characteristics of IL-4 and IL-13, their signaling pathways, and therapeutic antibodies against each cytokine as well as their receptors. In particular, the pleiotropic roles of IL-4 and IL-13 in orchestrating Th2 responses in AR and asthma patients indicate that dual IL-4/IL-13 blockade is a promising therapeutic strategy for both diseases. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a common allergic disease characterized by disruption of nasal epithelial barrier. In this study, we investigated the mRNA expression of zonula occludens-1 (ZO-1), ZO-2 and ZO-3 and histone deacetylase 1 (HDAC1) and HDAC2 in AR patients compared to healthy controls. RNA samples were extracted from nasal epithelial cells of house dust mites (HDMs)-sensitized AR patients and healthy controls (n = 28 in each group). The RNAs were reverse transcribed into cDNAs for measurement of ZO-1, ZO-2, ZO-3, HDAC1 and HDAC2 expression levels by quantitative PCR. The mRNA expression of ZO-1 was significantly decreased in AR patients compared to healthy controls (p = 0.010). No significant difference was observed in the expression levels of ZO-2, ZO-3, HDAC1 and HDAC2 in AR patients compared to healthy controls. We found significant associations of higher HDAC2 levels in AR patients with lower frequency of changing bedsheet (p = 0.043) and with AR patients sensitized to Dermatophagoides farinae (p = 0.041). Higher expression of ZO-2 was observed in AR patients who had pets (p = 0.007). In conclusion, our data indicated that ZO-1 expression was lower in AR patients contributing to decreased integrity of nasal epithelial barrier integrity, and HDAC2 may be involved in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Background: Gouty arthritis is a disease of global burden in which defective metabolism of uric acid causes arthritis. Gouty arthritis or medications used for its treatment may lead to uric acid-associated complications such as upper gastrointestinal bleeding (UGIB) and renal impairment. Methods: In this cross-sectional study with retrospective record review, 403 established gouty arthritis patients were recruited to determine the incidence of UGIB and associated factors among gout patients who were on regular nonsteroidal anti-inflammatory drugs (NSAIDs). Results: The mean age of the 403 gouty arthritis patients was 55.7 years old and the majority (n = 359/403; 89.1%) were male. The incidence of UGIB among gouty arthritis patients who were on NSAIDs was 7.2% (n = 29/403). Older age (p < 0.001), diclofenac medication (p = 0.003), pantoprazole medication (p = 0.003), end-stage renal failure (ESRF) (p = 0.007), smoking (p = 0.035), hypertension (p = 0.042) and creatinine (p = 0.045) were significant risk factors for UGIB among the gouty arthritis patients in univariable analysis. Older age (p = 0.001) and diclofenac medication (p < 0.001) remained significant risk factors for UGIB among the gouty arthritis patients in multivariable analysis. Conclusions: Age and diclofenac were significantly associated with UGIB among patients with gouty arthritis on regular NSAIDs, indicating that these factors increased the risks of developing UGIB in gout patients. Hence, these high-risk groups of gouty arthritis patients should be routinely monitored to avoid the potential onset of UGIB. Our data also suggest that diclofenac should be prescribed for the shortest duration possible to minimize the risk of developing UGIB in gout patients. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a common disease affecting 400 million of the population worldwide. Nasal epithelial cells form a barrier against the invasion of environmental pathogens. These nasal epithelial cells are connected together by tight junction (TJ) proteins including zonula occludens-1 (ZO-1), ZO-2 and ZO-3. Impairment of ZO proteins are observed inARpatients whereby dysfunction of ZOs allows allergens to pass the nasal passage into the subepithelium causing AR development. In this review, we discuss ZO proteins and their impairment leading to AR, regulation of their expression by Th1 cytokines (i.e., IL-2, TNF-α and IFN-γ), Th2 cytokines (i.e., IL-4 and IL-13) and histone deacetylases (i.e., HDAC1 and HDAC2). These findings are pivotal for future development of targeted therapies by restoring ZO protein expression and improving nasal epithelial barrier integrity in AR patients. [ABSTRACT FROM AUTHOR]