The prevalence of IgE positivity, environmental factors, and clinical implications associated with mite species in allergic patients in Taiwan.

BACKGROUND: Allergic diseases are a growing public health concern with increasing prevalence and severity. Allergens play significant roles in triggering immune responses and the development of allergic reactions. OBJECTIVE: Investigate the presence and clinical significance of dust mites, storage mites, and predatory mite Cheyletus eruditus(Ce) in household environments. METHODS: A survey of household dust was performed to determine mite occurrence and analyze influencing factors, an analysis of the correlation between mite species and allergic symptoms, and basophil activation triggered by mite allergens. Cross-reactivity between Ce and house dust mites was assessed. RESULTS: The high appearance rate of mite species in households of Taiwan was Dermatophagoides pteronyssinus (Dp) and D. farinae(Df). Environmental factors such as pet keeping, vacuum cleaner usage, air conditioner usage, proximity to the kitchen, cleaning frequency, and protein concentration in beds were shown to influence mite prevalence. The appearance of Dp and Df significantly increased the occurrence of airway and nasal symptoms, while the presence of Ce was strongly correlated with skin symptoms. The activation of basophils and the correlation between specific IgE levels and allergic symptoms in response to Ce exposure were demonstrated. The presence of Ce was associated with elevated levels of allergens in bedding. The IgE adsorption between mite species was demonstrated suggesting cross-reactivity between the Ce and Dp was limited. Presence of Ce is associated with elevated levels of major mite allergens in beddings. CONCLUSION: Allergenicity of Ce was confirmed by IgE reactivity and basophil activation regarding mite infestation as a potential cause of skin-related allergy.

S-Nitrosylation of Tissue Transglutaminase in Modulating Glycolysis, Oxidative Stress, and Inflammatory Responses in Normal and Indoxyl-Sulfate-Induced Endothelial Cells.

Circulating uremic toxin indoxyl sulfate (IS), endothelial cell (EC) dysfunction, and decreased nitric oxide (NO) bioavailability are found in chronic kidney disease patients. NO nitrosylates/denitrosylates a specific protein's cysteine residue(s), forming S-nitrosothios (SNOs), and the decreased NO bioavailability could interfere with NO-mediated signaling events. We were interested in investigating the underlying mechanism(s) of the reduced NO and how it would regulate the S-nitrosylation of tissue transglutaminase (TG2) and its substrates on glycolytic, redox and inflammatory responses in normal and IS-induced EC injury. TG2, a therapeutic target for fibrosis, has a Ca2+-dependent transamidase (TGase) that is modulated by S-nitrosylation. We found IS increased oxidative stress, reduced NADPH and GSH levels, and uncoupled eNOS to generate NO. Immunoblot analysis demonstrated the upregulation of an angiotensin-converting enzyme (ACE) and significant downregulation of the beneficial ACE2 isoform that could contribute to oxidative stress in IS-induced injury. An in situ TGase assay demonstrated IS-activated TG2/TGase aminylated eNOS, NFkB, IkBα, PKM2, G6PD, GAPDH, and fibronectin (FN), leading to caspases activation. Except for FN, TGase substrates were all differentially S-nitrosylated either with or without IS but were denitrosylated in the presence of a specific, irreversible TG2/TGase inhibitor ZDON, suggesting ZDON-bound TG2 was not effectively transnitrosylating to TG2/TGase substrates. The data suggest novel roles of TG2 in the aminylation of its substrates and could also potentially function as a Cys-to-Cys S-nitrosylase to exert NO's bioactivity to its substrates and modulate glycolysis, redox, and inflammation in normal and IS-induced EC injury.

Inhibition of NLRP3 Inflammasome Activation by 3H-1,2-Dithiole-3-Thione: A Potential Therapeutic Approach for Psoriasis Treatment.

Psoriasis is a chronic autoimmune skin disease with a significant impact on quality of life and potential for severe comorbidities. Inflammation in the skin is induced by immune cells that overexpress pro-inflammatory cytokines, with the Th17 cell playing a crucial role. NLRP3 inflammasome activation is associated with inflammatory diseases and abnormal T cell differentiation. 3H-1,2-dithiole-3-thione (D3T), isolated from cruciferous vegetables, has anti-inflammatory effects and inhibits Th17 differentiation. This study aimed to investigate how D3T reduces skin inflammation and modulates Th17 cell differentiation by inhibiting NLRP3 inflammasome activation. In an imiquimod-induced psoriasis mouse model, D3T treatment demonstrated significant reductions in ear thickness, skin redness, and scaling compared to a control group. Our study also observed decreased expression of ki-67, NLRP3 inflammasome, and cleaved caspase-1 in skin samples, reduced levels of IL-6 and IL-17A in serum samples, and inhibition of Th17 differentiation after D3T application. D3T could also inhibit the expression of NLRP3, caspase-1, and IL-1ß in TNF-α stimulated HaCaT cells. The mechanical study also revealed that D3T could inhibit NLRP3 inflammasome activation by inhibiting the JNK pathway in HaCaT cells. These results indicate that targeting NLRP3 inflammasome activation is a promising strategy in the treatment of psoriasis.

Antioxidative Activities of Micronized Solid-State Cultivated Hericium erinaceus Rich in Erinacine A against MPTP-Induced Damages.

The Lion's mane mushroom (Hericium erinaceus, HE) is a traditional medical mushroom with high nutritional and economic value. HE possesses anticancer, antimicrobial, antioxidant, immunomodulating, neurotrophic, and neuroprotective activities. The present study evaluated the protection and antioxidative activities of micronized mycelium of HE (HEM) in mice treated with 1-methyl-4-phenylpyridinium (MPTP). HEM was cultivated via solid-state fermentation and micronized using cell wall-breaking technology to increase its bioavailability when ingested. Erinacine A, the bioactive compound in the HEM, played a pivotal role in antioxidant defense. We found that micronized HEM could recover the dopamine level in the mice striatum in a dose-dependent manner that had been greatly reduced during MPTP treatment. Moreover, the malondialdehyde (MDA) and carbonyl levels were reduced in the livers and brains of the MPTP + HEM-treated groups compared with the MPTP group. Additionally, antioxidant enzyme activities, including catalase, superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G6PDH), and glutathione reductase (GRd), were elevated after the administration of HEM in MPTP-treated mice in a dose-dependent manner. Taken together, our data indicate that HEM cultivated via solid-state fermentation and processed with cell wall-breaking technology showed an excellent antioxidant efficacy.

Influence of storage conditions on the infestation of Tyrophagus putrescentiae and prevalence of mite hypersensitivity in Taiwan.

Sensitization to mites is a considerable factor in the development of allergic diseases. Because of its abundance, Tyrophagus putrescentiae (Tp) is the predominant storage mite found in home storage rooms, kitchens, and bakeries. Patients allergic to mites might exhibit a severely hypersensitive reaction upon ingesting Tp-contaminated food. The objective of this study was to investigate the rates of Tp contamination in commercial storage products from various areas, storage conditions, and environments in Taiwan. A specific antibody against Tyr p 3, the allergen on Tp, could be used as an indicator to monitor the contamination condition in storage foods. The microscopic mite examination, allergen detection by ELISA and cultured mite chemotaxis were used to evaluate the prevalence of T. putrescentiae contamination. Moreover, the IgE responses of patients allergic to mites were examined. We found that pet food and mushrooms were commonly contaminated with Tp, and this was validated through Tyr p 3 concentration and chemotaxis experiments. Tp contamination rates decreased significantly when samples were sealed and stored at a low temperature (<  4 °C), low relative humidity (RH < 60%), or for longer periods at a low temperature. The results of the clinical study indicated that the mites that elicited major positive IgE responses in allergic subjects were Dermatophagoides pteronyssinus and D. farinae. Thus, people who are sensitized to D. pteronyssinus or D. farinae might be at risk of a second anaphylactic reaction due to cross-reactivity upon ingestion of Tp-contaminated food. Accordingly, Tp contamination can be prevented by keeping food packages sealed and stored at a low temperature. This prevents the severe allergic reaction caused by the inadvertent ingestion of contaminated food-borne Tp.

Specific Immunoglobulin G4 and Immunoglobulin E Titers to Common Food Antigens in Sera of Children With Allergic Rhinitis.

CONTEXT: Allergic rhinitis is a chronic disease that usually affects children. Its etiology has been investigated for years. OBJECTIVE: The aim of the study was to evaluate the diagnostic value of immunoglobulin G4 (IgG4) against common food allergens, to determine the correlation between it and immunoglobulin E (IgE), and to evaluate the role of IgG4 (ie, whether its presence should be considered to be a significant factor that induces hypersensitivity or whether an effector role in allergic rhinitis could be attributed to it). DESIGN: This research was conducted as a randomized controlled trial. SETTING: The research team performed the study in the Department of Otolaryngology and Sleep Center, Cheng Ching General Hospital-Chung Kang Branch (Taichung, Taiwan). PARTICIPANTS: The participants were 46 patients-29 boys and 17 girls-with an average age of 8.02 ± 2.92 y-who had been diagnosed with allergic rhinitis. OUTCOME MEASURES: Blood samples were collected from the participants. The total IgE, food-specific IgE, and food-specific IgG4 in their sera were measured using the proprietary BioIC system, which is based on the principles of the enzyme-linked immunosorbent assay (ELISA). RESULTS: In terms of total IgE, 20 patients (43.5%) had a concentration of <1000 IU/mL. Regarding specific IgG4, 89.1% of patients were highly reactive to egg white IgG4, whereas >50% were highly reactive to egg yolk, milk, peanuts, almonds, wheat, and soybeans. Regression analysis to test the correlation between specific IgE and specific IgG4 revealed that egg whites, milk, peanuts, and almonds had significant correlations (P < .05). Cod, shrimp, and crab showed very significant correlations (P < .001). CONCLUSION: Total IgE varies widely in children with allergic rhinitis but remains one of the references for diagnosis. The main inhalational allergens are dust mites, followed by grass pollen, molds, German cockroach, and animal dander. Food allergy generates highly concentrated IgG4 and may play a role in children with allergic rhinitis.

An Exploratory Pilot Study of Genetic Marker for IgE-Mediated Allergic Diseases with Expressions of FcεR1α and Cε.

The high affinity immunoglobulin E (IgE) receptor-FcεR1 is mainly expressed on the surface of effector cells. Cross-linking of IgE Abs bound to FcεR1 by multi-valent antigens can induce the activation of these cells and the secretion of inflammatory mediators. Since FcεR1 plays a central role in the induction and maintenance of allergic responses, this study aimed to investigate the association of FcεR1 with the allergic phenotype of Cε expression and cytokine and histamine release from peripheral leukocytes. Peripheral leukocytes from 67 allergic and 50 non-allergic subjects were used for genotyping analysis. Peripheral mononuclear cells (PBMCs) were used for Cε expression and ELISpot analysis, while polymorphonuclear cells (PMNs) were used for histamine release. The association between genotype polymorphism of the FcεR1α promoter region (rs2427827 and rs2251746) and allergic features of Cε expression and histamine were analyzed, and their effects on leukocytes function were compared with wild type. The genotype polymorphisms of FcεR1α promoter region with CT and TT in rs2427827 and TC in rs2251746 were significantly higher in allergic patients than in non-allergic controls. Patients with single nucleotide polymorphism (SNP) of FcεR1α promoter region had high levels of total IgE, mite-specific Der p 2 (Group 2 allergen of Dermatophagoides pteronyssinus)-specific IgE and IgE secretion B cells. The mRNA expression of FcεR1α was significantly increased after Der p2 stimulation in PBMCs with SNPs of the FcεR1α promoter region. Despite the increased Cε mRNA expression in PBMCs and histamine release from PMNs and the up-regulated mRNA expression of interleukin (IL)-6 and IL-8 secretions after Der p2 stimulation, there was no statistically significant difference between SNPs of the FcεR1α promoter region and the wild type. SNPs of FcεR1α promoter region were associated with IgE expression, IgE producing B cells, and increased Der p2-induced FcεR1α mRNA expression. These SNPs may be used as a disease marker for IgE-mediated allergic inflammation caused by Dermatophagoides pteronyssinus.

A disease marker for aspirin-induced chronic urticaria.

There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (FcεRIα) and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (-344C/T) and rs2251746 (-66T/C) gene polymorphisms of FcεRIα in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (-344C>T, -66C>T) were similar to the normal controls. The allele frequency of -344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p=0.019). We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5±5.2 vs. 103.3±3.3 respectively, (p<0.05), and the percentages of histamine release were 31.3%±7.4% vs. -24.0%±17.5%, (p<0.05) respectively. Although the mean fluorescence intensity of CD203c expression and the percentage of histamine release were significantly up-regulated by aspirin, they were not affected by anti-IgE antibodies. These results suggest that a single SNP of FcεRIα (-344C>T) is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU.

Radiocontrast medium induces histamine release in association with upregulation of miR­19a­3p and miR­362­3p expression.

In Taiwan, the use of radiocontrast medium for clinical image diagnosis recently surpassed one million times and the overall prevalence of radiocontrast hypersensitivity was ~7%. A microRNA (miRNA/miRs) is a small non-coding RNA molecule that mostly plays a suppressor role in cells. However, the roles of miRNA expression in radiocontrast-induced mast cells activation remains to be elucidated. The aim of the present study was to investigate the role of miRNA on radiocontrast-induced mast cell activation. Computed tomography radiocontrast, ultravist and mouse mast cell line, P815, were used in the present study. Cell viability was detected by CCK-8 experiment. Levels of histamine and ß-hexosaminidase were measured by ELISA. miRNA expression was detected by miRNA sequencing and reverse transcription-quantitative PCR. The results showed that ultravist could increase histamine release and reduce intracellular ß-hexosaminidase levels of mast cells. A total of 102 miRNAs could be significantly upregulated by ultravist stimulation. Selected candidate miRNAs for the validation included miR-19a-3p and miR-362-3p which were also increased expression following stimulation with ultravist. In conclusion, ultravist could induce mast cell activation through upregulation of miR-19a-3p and miR-362-3p. Thus, miR-19a-3p and miR-362-3p could be promising candidates for development as novel targets for preventing radiocontrast-induced allergy in the future.

Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging.

The skin is subjected to various external factors that contribute to aging including oxidative stress from hydrogen peroxide (H2O2). This study investigated the distribution of aquaporin-8 (AQP8), a protein that transports H2O2 across biological membranes, in skin cells, and its effects in mitigating H2O2-induced oxidative damage. Human dermal fibroblasts were treated with increasing concentrations of H2O2 to evaluate oxidative damage. Cell viability, reactive oxygen species (ROS) generation, and the expression of specific genes associated with skin aging (IL-10, FPR2, COL1A1, KRT19, and Aggrecan) were evaluated and AQP8 expression was assessed via quantitative polymerase chain reaction and western blotting. Small-interfering RNA was used to silence the AQP8 gene and evaluate its significance. The results show that H2O2 treatment reduces cell viability and increases ROS generation, leading to oxidative damage that affects the expression of target molecules. Interestingly, H2O2-treated cells exhibit high levels of AQP8 expression and gene silencing of AQP8 reverses high levels of ROS and low levels of COL1A1, KRT19, and Aggrecan expression in stressed cells, indicating that AQP8 plays a vital role in preventing oxidative damage and consequent aging. In conclusion, AQP8 is upregulated in human dermal fibroblasts during H2O2-induced oxidative stress and may help prevent oxidative damage and aging. These findings suggest that AQP8 could be a potential therapeutic target for skin aging. Further research is necessary to explore the feasibility of using AQP8 as a preventive or therapeutic strategy for maintaining skin health.

Regulating TKT activity inhibits proliferation of human acute lymphoblastic leukemia cells.

Among pediatric blood cancers, acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy. Within ALL, T-cell acute lymphoblastic leukemia (T-ALL) accounts for 10 to 15% of all pediatric cases, and ~25% of adult cases. For T-ALL, its recurrence and relapse after treatment remain problematic. Therefore, it is necessary to develop new therapies for T-ALL. Recent studies suggested regulating energy metabolism is a novel approach to inhibit tumor growth, likely a promising treatment. Transketolase (TKT) is an important enzyme for modulating glucose metabolize in the pentose phosphate pathway (PPP). In this study, we treated T-ALL cells with different doses of niclosamide and primary T-ALL PBMCs were analyzed by RNA sequencing. T-ALL cells treated with niclosamide were analyzed with the Western blotting and TKT activity assay. Metabolism of T-ALL cells was evaluated by ATP assay and seahorse analyses. Lastly, we used a T-ALL xenograft murine model to determine effects of TKT knockdown on T-ALL tumor growth. Tumor samples were analyzed by H&E and IHC stainings. We found that niclosamide reduced T-ALL cell viability, and reduced expressions of TKT, Transketolase-Like Protein 1/2 (TKTL1/2) and transaldolase. In addition, niclosamide inhibited TKT enzyme activity, aerobic metabolism and glycolysis, finally leading to lower production of ATP. TKT knockdown inhibited tumor growth of xenograft T-ALL mice. Findings showed that niclosamide inhibits T-ALL cell growth by inhibiting TKT and energy metabolism.

Is the excellent air quality a protective factor of health problems for Taitung County in eastern Taiwan? Perspectives from visual analytics.

Taitung, an agricultural country in Eastern Taiwan, was famous for its fresh air with less industrial and petrochemical pollution. Air pollution may induce cardiovascular disease, chronic obstructive pulmonary disease (COPD), asthma, and stroke, poor air quality also resulted in a higher depression rate and less feeling of happiness; therefore, our study aims to use visualization tools to demonstrate the association between air quality index (AQI) and the among negative factors and try to find that whether Taitung got the benefit of good air quality on health issues. We retrieved data from the government of Taiwan and other open sources in the year 2019, then visual maps and generalized association plots with clusters demonstrated the relationship between each factor and each county/city. Taitung had the lowest AQI and asthma attack rate, but AQI had a negative relationship to air pollution-caused death (R = -0.379), happiness index (R = -0.358), and income (R = -0.251). The GAP analysis revealed that smoke and overweight were the nearest to air pollution causing death, also counties and cities were divided into two major clusters initially based on the air pollution-related variables. In conclusion, the World Health Organization (WHO) definition and the weight of each air pollution cause death may not be suitable for Taiwan due to too many confounding factors.

Immunomodulatory effects of modified Liu-Wei-Di-Huang-Wan Traditional Chinese medicine on allergic asthmatic mice.

BACKGROUND: Allergic asthma occurs worldwide and is particularly prevalent in westernized countries characterized by chronic airway inflammation resulting in airway hyperresponsiveness. The house dust mites (HDM) including Dermatophagoides pteronyssinus are major sources of sensitization and triggering allergic symptoms in asthmatic patients. The Der p 2 is a major allergen and the predominant source of causative respiratory disorders which induce airway inflammation and bronchial constriction in mite-allergic patients. Few studies evaluate the ameliorating effects of modified Liu-Wei-Di-Huang-Wan (modified LWDHW) on allergic asthma. METHODS: This study aimed to investigate the immunological mechanisms of modified LWDHW on the reductions of airway inflammation, signal transduction, inflammatory cytokine production, Th2 cell proliferation, and bronchial obstruction in Der p 2-induced asthmatic mice. RESULTS: At least ten active ingredients were contained in the formula of modified LWDHW- 1217A and 1217B. Results showed that the immunoglobulin generations (Der p 2 specific- IgE and IgG1), inflammatory cytokine productions (IL-5 and IL-13) in the Sera and BALF could be down-regulated, and the Th1-cytokine productions (IL-12 and IFN-γ) be increased after immunotherapy with modified LWDHW of 1217A or 1217B. The inflammatory cell infiltrations (macrophages, eosinophils, and neutrophils) in the airway and the expressions of TH2-related genes (IL-4, IL-5, and IL-13), TH2-related transcription factor (GATA-3), and neutrophil chemotactic chemokine (IL-8) in the lung tissue of asthmatic mice were significantly decreased after the immunotherapy. The Th1/Th2 polarization had been identified that the IL-4+/CD4+ T cells were downregulated and IFN-γ+/CD4+ T cells were increased. The airway hyperresponsiveness to methacholine inhalation of Penh values was significantly decreased in the treated groups. There were significant improvements in the bronchus histopathology after immunotherapy with 1217A or 1217B which were evaluated by tracheal thickness, inflammatory cell count, and tracheal rupture of mouse lung. CONCLUSION: It revealed that 1217A or 1217B could regulate the immune responses and improve pulmonary function. Data suggests that modified LWDHW of 1217A or 1217B have the potential for use as a therapeutic intervention for the treatment of mite allergen Der p 2-induced allergic asthma.

A pilot study of non-invasive diagnostic tools to detect Helicobacter pylori infection and peptic ulcer disease.

Helicobacter pylori (H. pylori) infection can lead to various digestive system diseases, making accurate diagnosis crucial. However, not all available tests are equally non-invasive and sensitive. This study aimed to compare the efficacy of non-invasive and invasive diagnostic tools for H. pylori infection and assess their correlation with esophagogastroduodenoscopic (EGD) findings. The study utilized the Campylobacter-Like Organism (CLO) test, serum anti-HP IgG blood test, and C-13-urea breath test (UBT) to diagnose H. pylori infection. A total of 100 patients with peptic ulcer symptoms, including 45 males and 55 females, were recruited for the study. Symptomatic patients between the ages of 20-70, eligible for EGD examination, were enrolled. Each diagnostic test and any combination of two positive tests were considered the reference standard and compared against the other diagnostic methods. Additionally, the relationship between these diagnostic tests and EGD findings was evaluated. Among the participants, 74.0% were diagnosed with peptic ulcer disease through EGD. The UBT demonstrated the highest Youden's index, ranging from 58 to 100%, against all the non-invasive tests. The IgG blood test displayed the highest sensitivity at 100%, with a specificity of 60-70%. On the other hand, the CLO test exhibited the highest specificity at 100% and a sensitivity of 50-85%. Furthermore, only the CLO test showed a significant association with esophageal ulcers (p-value = 0.01). The IgG blood test holds promise as a primary screening tool due to its exceptional sensitivity. While the UBT is relatively expensive, its non-invasive nature and high sensitivity and specificity make it a potential standalone diagnostic test for H. pylori infection. Moreover, the noteworthy negative correlation between the CLO test and esophageal ulcers provides evidence of the differing effects of H. pylori infection on antral-predominant and corpus-predominant gastritis.

A pilot study of digital bedside cards in the emergency room of a medical centre in Taiwan.

The emergency room (ER) digital bedside card is a simple and important invention. It can be directly connected to the hospital information system to display important patient information in real time, reduce the workload of ER staff, improve their satisfaction, and provide useful information for patients and their families. We conducted a prospective study of ER staff using questionnaires and conducted Wilcoxon signed-rank test to compare before and after ER digital bedside card implementation in the Tamsui MacKay Memorial Hospital. Sixty participants of the ER staff joined the study before and after digital card implementation. After the ER digital bedside card was set up, the number of round trips from the nursing station to the ER bedside and the number of common questions asked by patients and their family members were significantly reduced. The cards reduced the response time for frequently asked questions by patients and their family members and significantly improved the satisfaction of ER staff. Our study showed that ER digital bedside cards reduced the workload of ER staff, provided patients and their families with useful information, and greatly improved ER staff satisfaction. This marks an important milestone in the future development of smart ER.

Effects of Local Nasal Immunotherapy with FIP-fve Peptide and Denatured Tyrophagus putrescentiae for Storage Mite-Induced Airway Inflammation.

Allergic diseases are affecting public health and have increased over the last decade. Sensitization to mite allergens is a considerable trigger for allergy development. Storage mite-Tyrophagus putrescentiae shows great significance of allergenic potential and clinical relevance. The fungal immunomodulatory peptide FIP-fve has been reported to possess immunomodulatory activity. We aimed to determine whether T. putrescentiae-induced sensitization and airway inflammation in mice could be downregulated by FIP-fve in conjunction with denatured T. putrescentiae (FIP-fve and DN-Tp). Immune responses and physiologic variations in immunoglobulins, leukocyte subpopulations, cytokine productions, pulmonary function, lung pathology, cytokines in CD4+ and Treg cells were evaluated after local nasal immunotherapy (LNIT). After the LNIT with FIP-fve and DN-Tp, levels of specific IgE, IgG1, and IgG2a in the sera and IgA in the bronchoalveolar lavage fluid (BALF) were significantly reduced. Infiltrations of inflammatory leukocytes (eosinophils, neutrophils, and lymphocytes) in the airway decreased significantly. Production of proinflammatory cytokines (IL-5, IL-13, IL-17F and IL-23) and chemokine (IL-8) were significantly reduced, and Th1-cytokine (IL-12) increased in the airway BALF after LNIT. Pulmonary functions of Penh values were significantly decreased after the methacholine challenge, which resulted in a reduction of airway hypersensitivity after LNIT. Bronchus pathology showed a reduction of inflammatory cell infiltration and epithelium damage after LNIT. The IL-4+/CD4+ T cells could be downregulated and the IFN-γ+/CD4+ T cells upregulated. The Treg-related immunity of IL-10 and Foxp3 expressions in CD4+CD25+ cells were both upregulated after LNIT. In conclusion, LNIT with FIP-fve and DN-Tp had an anti-inflammatory effect on mite-induced airway inflammations and possesses potential as an immunomodulatory therapy agent for allergic airway diseases.

Niclosamide suppresses T­cell acute lymphoblastic leukemia growth through activation of apoptosis and autophagy.

T­cell acute lymphoblastic leukemia (T­ALL) is a common pediatric malignancy, characterized by the abnormal presence of immature T­cell progenitors. Conventional treatments for T­ALL fail to prevent or cure the disease, with a high­risk of recurrence after the first remission. Thus, medical options are in demand to develop novel therapies for patients suffering with T­ALL. Niclosamide, a traditional oral anti­helminthic drug, has been reported to be a potential anticancer agent that regulates intracellular signaling pathways. Few studies have yet investigated the effects of niclosamide on the development of T­ALL. Here, the present study aimed to investigate the anti­leukemia effects of niclosamide on T­ALL. We first hypothesized that the suppressive effects of niclosamide on the tumor growth of T­ALL are exerted by regulating autophagy and apoptosis. Following niclosamide treatment, T­ALL cell viability was evaluated using MTT assay, and apoptosis with Annexin V/propidium iodide staining. In T­ALL cells treated with niclosamide, changes in apoptosis­ and autophagy­related proteins were analyzed by western blotting. In addition, in an in vivo model, T­ALL xenograft mice were used to study the anti­leukemia effects of niclosamide. The results showed that niclosamide significantly reduced the viability of Jurkat and CCRF­CEM T­ALL cells in both a dose­ and time­dependent manner. Niclosamide significantly activated the early and late phases of apoptosis in Jurkat (at 2 µM) and CCRF­CEM cells (at 1 µM). Furthermore, niclosamide upregulated protein expression of cleaved caspase­3 and LC3B, while downregulated those of Bcl­2 and p62, in a dose­dependent manner in both Jurkat and CCRF­CEM cells. The in vivo results showed that niclosamide treatment significantly suppressed tumor growth and the disease progression in T­ALL xenograft mice by activating cleaved caspase­3 and LC3B. We conclude that niclosamide plays an anti­leukemia role, and that it represents a novel approach for the treatment of T­ALL.

Forsythoside A Alleviates Imiquimod-Induced Psoriasis-like Dermatitis in Mice by Regulating Th17 Cells and IL-17A Expression.

Psoriasis is a recurrent inflammatory skin disease characterized by redness and scaly skin lesions with itchy or painful sensations. Forsythoside A, one of the main active compounds isolated from the fruit of Forsythia suspensa, has been widely applied to treat inflammatory diseases in the clinical use of traditional oriental medicine. However, the effect of forsythoside A on psoriasis remains unclear. This study aimed to explore the therapeutic effects and immune regulation of forsythoside A on psoriasis. C57BL/6 mice were divided into six groups and treated with imiquimod cream on their shaved back skin to induce psoriasis-like dermatitis. Different doses of forsythoside A (5 mg/kg, 10 mg/kg, or 20 mg/kg) were administered to the respective treatment groups. Skin redness, scaling, and ear thickness were measured; keratinocyte proliferation and inflammatory cytokine expression were detected by hematoxylin-eosin and immunohistochemical staining. Th17 cells in the inguinal lymph nodes were detected by flow cytometric analysis. IL-17A levels were measured using ELISA. The results showed that forsythoside A relieved psoriatic skin symptoms such as skin redness, thickness, scaling, and reduced epidermal thickening. The expression of IL-6, IL-17, and Ki-67 was downregulated in the forsythoside-A-treated groups. Th17 cell expression in inguinal lymph nodes and IL-17A secretion was suppressed by forsythoside A. In conclusion, forsythoside A was found to alleviate imiquimod-induced psoriasis-like dermatitis in mice by suppressing Th17 development and IL-17A secretion. These findings demonstrate the feasibility of forsythoside A in treating human psoriasis.

Mechanisms of Tumor Necrosis Factor-Alpha Inhibitor-Induced Systemic Lupus Erythematosus.

Systemic lupus erythematosus induced by biologics mainly results from tumor necrosis factor-alpha remains unclear. The objectives of the study were to investigate the mechanisms of tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus. Peripheral blood mononuclear cells obtained from thirteen psoriasis patients were cultured and treated with the following: untreated control, Streptococcus pyogenes with or without different biologics. The supernatants were collected for cytokines assay. Analysis of cytokine expression revealed that IL-2 and IL-10 levels decreased only in the TNF-α inhibitor-treated groups but not in the groups treated with biologics involving IL-17, IL-12/IL-23 or IL-23 inhibitor mechanisms (p < 0.001, p < 0.05). The IFN-γ/IL-13 ratio increased significantly in patients with SLE inducing biologics to S. pyogenes induction only compared with non-SLE inducing biologics to S. pyogenes induction only (p = 0.001). IL-2 and IL-10 depletion and a shift to the Th-1 pathway in the innate response are the correlated mechanism for tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus.

Elevated alanine aminotransferase is associated with biphasic insulin secretion in the healthy elderly Han Chinese population.

OBJECTIVE: To evaluate the relationship between alanine transaminase (ALT) level and biphasic insulin secretion (BPIS) in healthy elderly Han Chinese individuals. METHODS: This cross-sectional study enrolled healthy elderly participants aged ≥60 years that were part of a health examination programme. In order to explore the correlation and severity of the clinical condition, those with any possible confounding factors known to affect insulin secretion or liver function were excluded from the study. BPIS was calculated using an equation developed previously by this research team. RESULTS: This study enrolled 39 845 healthy elderly individuals (19 058 males and 20 787 females). Participants were stratified into four quartile groups according to their ALT level. In both males and females, the increasing ALT quartiles (ordinal variable) were associated with greater values of log-transformed first-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS). The correlation and the linear regression model showed that increasing ALT level was significantly correlated with higher log-transformed FPIS and SPIS. CONCLUSIONS: ALT was positively correlated with BPIS in a healthy elderly population in both men and women. Elevated ALT may serve as an indicating factor for developing metabolic syndrome and type 2 diabetes mellitus in healthy elderly individuals.