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IntroductionPeanut allergy is an immunoglobulin E (IgE) mediated food allergy. Rubia cordifolia L. (R. cordifolia), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production in vivo. This study aims to identify IgE-inhibitory compounds from the water extract of R. cordifolia and investigate the underlying mechanisms using in vitro and in vivo models.MethodsCompounds were isolated from R. cordifolia water extract and their bioactivity on IgE production was assessed using a human myeloma U266 cell line. The purified active compound, xanthopurpurin (XPP), was identified by LC-MS and NMR. Peanut-allergic C3H/HeJ mice were orally administered with or without XPP at 200µg or 400µg per mouse per day for 4 weeks. Serum peanut-specific IgE levels, symptom scores, body temperatures, and plasma histamine levels were measured at challenge. Cytokines in splenocyte cultures were determined by ELISA, and IgE + B cells were analyzed by flow cytometry. Acute and sub-chronic toxicity were evaluated. IL-4 promoter DNA methylation, RNA-Seq, and qPCR analysis were performed to determine the regulatory mechanisms of XPP.ResultsXPP significantly and dose-dependently suppressed the IgE production in U266 cells. XPP significantly reduced peanut-specific IgE (>80%, p

Abstract The pharmacokinetics (PKs) and exposure–efficacy of dupilumab have not been fully described for adults with atopic dermatitis (AD). Our objectives were to analyze the PKs and exposure–efficacy of dupilumab in adults with AD and compare the results of Japanese and overall populations. Adults with moderate‐to‐severe AD were randomly assigned to dupilumab (300 mg weekly [qw] or every 2 weeks [q2w], 200 mg q2w, 300 mg every 4 weeks [q4w], or 100 mg q4w) or placebo for 16 weeks in a randomized, double‐blind, placebo‐controlled, dose‐ranging phase IIb trial (NCT01859988). This analysis included 379 patients (58 Japanese). Functional dupilumab concentrations increased in a dose‐dependent manner; at lower concentrations, increases were greater than dose‐proportional because of nonlinear, target‐mediated clearance. Dupilumab pharmacokinetics were comparable in Japanese and non‐Japanese patients with similar body weights. Week 16 efficacy parameters, including Investigator’s Global Assessment score 0/1, greater than or equal to 75% reduction from baseline in the Eczema Area and Severity Index (EASI), and percentage change from baseline in EASI and pruritus Numerical Rating Scale, generally increased with week 16 trough concentration; the plateau of these exposure–efficacy relationships occurred for most patients at exposures associated with the 300 mg q2w and 300 mg qw regimens. Japanese ethnicity did not remain in the population PK model as covariate with or without accounting for body weight differences. In Japanese and non‐Japanese patients, efficacy responses increased with week 16 dupilumab trough concentrations in a similar manner. Dupilumab 300 mg qw and q2w regimens were recommended for further evaluation in larger phase III studies.

BackgroundGut microbiota influence food allergy. We showed that the natural compound berberine reduces IgE and others reported that BBR alters gut microbiota implying a potential role for microbiota changes in BBR function.ObjectiveWe sought to evaluate an oral Berberine-containing natural medicine with a boiled peanut oral immunotherapy (BNP) regimen as a treatment for food allergy using a murine model and to explore the correlation of treatment-induced changes in gut microbiota with therapeutic outcomes.MethodsPeanut-allergic (PA) mice, orally sensitized with roasted peanut and cholera toxin, received oral BNP or control treatments. PA mice received periodic post-therapy roasted peanut exposures. Anaphylaxis was assessed by visualization of symptoms and measurement of body temperature. Histamine and serum peanut-specific IgE levels were measured by ELISA. Splenic IgE+B cells were assessed by flow cytometry. Fecal pellets were used for sequencing of bacterial 16S rDNA by Illumina MiSeq. Sequencing data were analyzed using built-in analysis platforms.ResultsBNP treatment regimen induced long-term tolerance to peanut accompanied by profound and sustained reduction of IgE, symptom scores, plasma histamine, body temperature, and number of IgE+ B cells (p

GoalsTo assess the efficacy and safety of Chinese Medicine Prescription “W-LHIT” in subjects with simple obesity, and to explore its potential mechanism of action.MethodsThirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the “W-LHIT” capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding.Results72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment.ConclusionW-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.

IntroductionFood allergy is a significant public health problem with limited treatment options. As Food Allergy Herbal Formula 2 (FAHF-2) showed potential as a food allergy treatment, we further developed a purified version named EBF-2 and identified active compounds. We investigated the mechanisms of EBF-2 on IgE-mediated peanut (PN) allergy and its active compound, berberine, on IgE production.MethodsIgE plasma cell line U266 cells were cultured with EBF-2 and FAHF-2, and their effects on IgE production were compared. EBF-2 was evaluated in a murine PN allergy model for its effect on PN-specific IgE production, number of IgE+ plasma cells, and PN anaphylaxis. Effects of berberine on IgE production, the expression of transcription factors, and mitochondrial glucose metabolism in U266 cells were evaluated.ResultsEBF-2 dose-dependently suppressed IgE production and was over 16 times more potent than FAHF-2 in IgE suppression in U266 cells. EBF-2 significantly suppressed PN-specific IgE production (70%, p

Introduction: Cytochrome P450 (CYP) 3A4 is a major drug metabolizing enzyme for corticosteroids (CS). Epimedium has been used for asthma and variety of inflammatory conditions with or without CS. It is unknown whether epimedium has an effect on CYP 3A4 and how it interacts with CS. We sought to determine the effects of epimedium on CYP3A4 and whether it affects the anti-inflammatory function of CS and identify the active compound responsible for this effect.Methods: The effect of epimedium on CYP3A4 activity was evaluated using the Vivid CYP high-throughput screening kit. CYP3A4 mRNA expression was determined in human hepatocyte carcinoma (HepG2) cells with or without epimedium, dexamethasone, rifampin, and ketoconazole. TNF-α levels were determined following co-culture of epimedium with dexamethasone in a murine macrophage cell line (Raw 264.7). Active compound (s) derived from epimedium were tested on IL-8 and TNF-α production with or without corticosteroid, on CYP3A4 function and binding affinity.Results: Epimedium inhibited CYP3A4 activity in a dose-dependent manner. Dexamethasone enhanced the expression of CYP3A4 mRNA, while epimedium inhibited the expression of CYP3A4 mRNA and further suppressed dexamethasone enhancement of CYP3A4 mRNA expression in HepG2 cells (p < 0.05). Epimedium and dexamethasone synergistically suppressed TNF-α production by RAW cells (p < 0.001). Eleven epimedium compounds were screened by TCMSP. Among the compounds identified and tested only kaempferol significantly inhibited IL-8 production in a dose dependent manner without any cell cytotoxicity (p < 0.01). Kaempferol in combination with dexamethasone showed complete elimination of TNF-α production (p < 0.001). Furthermore, kaempferol showed a dose dependent inhibition of CYP3A4 activity. Computer docking analysis showed that kaempferol significantly inhibited the catalytic activity of CYP3A4 with a binding affinity of −44.73kJ/mol.Discussion: Inhibition of CYP3A4 function by epimedium and its active compound kaempferol leads to enhancement of CS anti-inflammatory effect.

The notion of 'mental health literacy' has been proposed as a way of improving mental health problem recognition, service utilisation and reducing stigma. Yet, the idea embodies a number of medical-model assumptions which are often at odds with diverse communities' spiritual traditions and local belief systems. Twenty participants were recruited to this study consisting of mental health service users (N = 7), family carers (N = 8) and community members (N = 5) in a temple town in Kerala, South India participated in semi-structured interviews exploring the variety of beliefs and practices relating to mental health. Our findings indicate that the issue may be better understood in terms of multiple mental health literacies which people deploy in different circumstances. Even those sceptical of traditional and spiritual approaches are knowledgeable about them, and the traditional practices themselves often involve detailed regimes of activities aimed at effecting an improvement in the person's mood or condition. Therefore, we argue it is appropriate to consider mental health literacy not as a unitary universal phenomenon but instead as a mosaic of different literacies which may be deployed in different settings and in line with different experiences and which may operate in synergy with each other to enable treatment but also facilitate a sense of meaning and purpose in life., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Current technological developments in medical imaging are primarily focused on increasing the integration of artificial intelligence (AI) into all medical imaging modalities. They are already considered capable of handling tasks such as image reconstruction, processing (denoising, segmentation), analysis, and predictive modeling. The purpose of this study is to assess the awareness (knowledge, attitudes, and practices) of radiologists and radiologic technologists regarding AI in medical imaging., Materials and Methods: This cross-sectional, qualitative study focuses on radiologists and radiologic technologists in Saudi Arabia, Sudan, and Yemen. A self-administered questionnaire based on published studies was used to collect primary data. Version 25.0 of IBM SPSS Statistics (IBM Corp., Armonk, NY) was used for the statistical analysis. The demographics were summarized as frequency and percentage. Independent samples t-tests and ANOVA tests were used to evaluate and compare the degree of AI awareness among the study groups., Results: A total of 210 individuals completed the survey. According to demographic information, there were 134 (63.8%) radiologic technologists and 76 radiologists (36.2%). Of the participants, 131 (62%) were male, while 79 (37.6%) were female. A total of 130 (61.9%) of the targeted respondents had a positive attitude, 105 (50%) had appropriate practice, and 122 (58.1%) of them were informed (knowledgeable) about AI in medical imaging. There was a significant difference in knowledge awareness between radiologists and radiologic technologists (p-value: <0.05). Radiologists were more knowledgeable than radiologic technologists, and females were more knowledgeable than males (p-value: 0.049). For attitude awareness, there were no significant differences regarding specialization, gender, age, academic qualification, and experience (p-value > 0.05). Regarding practice awareness, it turned out that females are more knowledgeable than males (p-value: 0.007). Additionally, it was discovered that significant differences indicated that bachelor's degree holders have a higher level of practice awareness than diploma holders (p-value: <0.05)., Conclusion: Significant differences between the respondent's knowledge awareness regarding specialization, gender, and experience are linked with relatively sufficient AI-basic knowledge and positive attitude awareness among radiologists and radiologic technologists. Only half of the study participants had appropriate practical awareness; therefore, additional training could enhance practical awareness., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alsultan et al.)

Background: The concept of stigma has been widely used to understand patterns of discrimination and negative ideas surrounding people with mental health problems, yet we know little of the specific nuances of how this might operate beyond the 'Global North'., Aim: This paper aims to explore the notion of stigma in an Indian context by considering the lived experience of patients, carers and community members., Methods: A sample of 204 participants, representing mental health patients, informal carers and community members was recruited from urban and rural areas in Kerala, India. Participants took part in interviews where they were encouraged to talk about their experiences of mental ill health, attitudes towards these problems, barriers encountered and sources of support., Results: Experiences akin to the experience of stigma in Europe and the United States were elicited but there were important local dimensions specific to the Indian context. The difficulties faced by people with diagnoses of mental disorders in finding marriage partners was seen as an important problem, leading to marriage proposals being refused in some cases, and secrecy on the part of those with mental health problems. Rather than the 'self-stigma' identified in the US, participants were more likely to see this as a collective problem in that it could reflect badly on the family group as a whole rather than just the sufferer., Conclusions: In the Indian context, the idioms of stigma emphasised impairments in marriage eligibility and the implications for the family group rather than just the self.

The fundamental role of epigenetic regulatory mechanisms involved in neuroplasticity and adaptive responses to traumatic brain injury (TBI) is gaining increased recognition. TBI-induced neurodegeneration is associated with several changes in the expression-activity of various epigenetic regulatory enzymes, including histone deacetylases (HDACs). In this study, PET/CT with 6-([ 18 F]trifluoroacetamido)-1- hexanoicanilide ([ 18 F]TFAHA) to image spatial and temporal dynamics of HDACs class IIa expression-activity in brains of adult rats subjected to a weight drop model of diffuse, non-penetrating, mild traumatic brain injury (mTBI). The mTBI model was validated by histopathological and immunohistochemical analyses of brain tissue sections for localization and magnitude of expression of heat-shock protein-70 kDa (HSP70), amyloid precursor protein (APP), cannabinoid receptor-2 (CB2), ionized calcium-binding adapter protein-1 (IBA1), histone deacetylase-4 and -5 (HDAC4 and HDAC5). In comparison to baseline, the expression-activities of HDAC4 and HDAC5 were downregulated in the hippocampus, nucleus accumbens, peri-3rd ventricular part of the thalamus, and substantia nigra at 1-3 days post mTBI, and remained low at 7-8 days post mTBI. Reduced levels of HDAC4 and HDAC5 expression observed in neurons of these brain regions post mTBI were associated with the reduced nuclear and neuropil levels of HDAC4 and HDAC5 with the shift to perinuclear localization of these enzymes. These results support the rationale for the development of therapeutic strategies to upregulate expression-activity of HDACs class IIa post-TBI. PET/CT (MRI) with [ 18 F]TFAHA can facilitate the development and clinical translation of unique therapeutic approaches to upregulate the expression and activity of HDACs class IIa enzymes in the brain after TBI., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction Otitis media is one of the most common causes of infection in preschool children. The most damaging complication of otitis media is temporary or permanent hearing loss. This study aimed to determine the important risk factors for otitis media. Methods In this case-control study, 625 children aged six months to seven years were examined from winter to spring 2020, and 53 children with otitis media were allocated to the case group and the same number to the control group. The chi-square test was used to identify the risk factors affecting otitis media, and the risk factors were compared between the case and control groups. Logistic regression was used to investigate the relationship between the incidence of otitis media and risk factors. Results Bivariate analysis revealed the following primary risk factors for otitis media: using pacifiers or bottle feeding, working mother, seasonal rhinitis, allergic rhinitis, tonsillopharyngitis, rhinorrhea, and adenoid hypertrophy (P<0.05). In logistic regression analysis, using pacifiers or bottle feeding (odds ratio [OR]=0.156, P=0.000), working mother (OR=0.226, P=0.000), seasonal rhinitis (OR=0.175, P=0.000), allergic rhinitis (OR=5.20, P=0.000) and adenoid hypertrophy (OR=1.57, P=0.000) were identified as the most important risk factors. Conclusion Adenoid hypertrophy and allergic rhinitis increased the risk of otitis media more than the other risk factors. Therefore, pediatricians should increase their awareness of the existence of these risk factors in a patient, and take the appropriate diagnostic steps and implement therapeutic care to prevent language and speech complications., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Hardani et al.)