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Background: Optimal levels and bioavailability of trace minerals (TM) in the broiler diet are important for improving performance and health status in the presence of dietary toxins., Methods: The study examines the effectiveness of advanced chelate technology-based 7-minerals (ACTM) in broilers fed aflatoxin B1 (AFB 1 )-contaminated diets, involving 768 chickens in eight treatments with six replicates, following a completely randomized design. Treatments contained (1) negative control (NC) group receiving a basal diet without AFB 1 and containing recommended inorganic TM (ITM) levels (NC + ITM), (2) positive control (PC) group receiving a basal diet with 0.5 mg AFB 1 /kg and recommended ITM levels (PC + ITM), (3) PC diet + toxin binder (ITM + TB), (4 and 5) PC diet with 50 % and 100 % ACTM instead of ITM (ACTM50 and ACTM100), (6 and 7) PC diet with 12.5 % and 25 % extra ACTM (ITM + ACTM12.5 and ITM + ACTM25), and (8) PC diet with 125 % ITM levels (ITM125)., Results: The results showed that the ACTM100 and ITM + ACTM25 treatments resulted in higher average weight gain and European production efficiency index compared to the PC + ITM treatment, but lower than the NC + ITM treatment. Key indicators of gut health, such as ileal digestibility of crude fat and phosphorus, AMEn value, duodenal villus height to crypt depth ratio, villus surface area, and gene expression of junctional adhesion molecule 2 were significantly improved in the ACTM100, ITM + BT, and NC + ITM groups compared to the PC + ITM group. Additionally, jejunal occludin expression increased in the ACTM100, ITM + ACTM25, ITM + TB treatments, and the jejunal zonula occludens-1 expression increased significantly in the ACTM100 and ITM + ACTM25 groups., Conclusion: The results indicate that completely replacing ITM with ACTM or adding ACTM supplement to ITM diets at 25 % extra commercial levels can improve growth performance, gut health, and nutrient digestibility in the presence of AFB 1 challenge. These effects are comparable to diets containing a commercial toxin binder., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Background: Organic trace minerals (TM) offer superior nutritional benefits because of their stable structure, making their addition to broiler diets potentially beneficial during challenging periods such as aflatoxin B1 (AFB1) contamination. The present study evaluated the impacts of different replacement levels of inorganic TM (ITM) with advanced chelate technology-based TM (ACTM) on the growth performance, serum biochemical parameters, antioxidant indicators, and some inflammatory and immune parameters of broilers fed diets contaminated with AFB1. A 42-day experiment involved randomly assigning 1-day-old broiler chickens (n = 480) to one of five dietary treatments, each with six replicates. The treatments were as follows: (1) NC: basal diet without AFB1 and recommended ITM levels; (2) PC: basal diet with 0.5 mg kg -1 AFB1 and recommended ITM levels; (3) TB: PC diet +1 g kg -1 toxin binder; (4) ACTM50: replacement of ITM with 50% ACTM in the PC diet; and (5) ACTM100: replacement of ITM with 100% ACTM in the PC diet., Results: Compared with PC treatment, ACTM100 treatment resulted in increased (P < 0.05) body weight gain, serum zinc and glutathione concentrations, immunoglobulin Y level, antioxidant enzyme activities, and hepatic gene expression of nuclear factor erythroid 2-related factor 2, glutathione peroxidase-1, superoxide dismutase-1 and transforming growth factor beta 1. The ACTM100 group also exhibited decreased AFB1 residue in the liver and kidney, serum alanine transaminase activity and malondialdehyde concentration, and hepatic gene expression levels of nuclear factor-kappa B and interferon-gamma (P < 0.05). These values were comparable to those recorded in the TB and NC treatments., Conclusion: In conclusion, completely replacing ITM with ACTM can benefit the metabolism and mitigate AFB1-induced immunotoxicity and oxidative damage in chickens by altering the mRNA expression of nuclear factor-kappa B and nuclear factor erythroid 2-related factor 2, and some genes downstream their signaling pathways. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The delicate balance of trace mineral supplementation is critical for optimizing rumen function and overall ruminant health. This study evaluated the solubility of an advanced chelate technology-based supplement and assessed its impact on rumen degradability and apparent total tract digestibility (ATTD) when replacing inorganic sources. The solubility of the advanced trace minerals supplement (ACTM) was assessed at pH 5 and pH 2. In situ ruminal degradability of dry matter (DM), organic matter (OM), and fiber fractions was evaluated using two fistulated rams fed diets supplemented with either ACTM or inorganic trace minerals. ATTD was determined in 6 lambs fed diets supplemented with 100% ACTM, 50% ACTM, and 50% inorganic (50% ACTM), or 100% inorganic sources in a Latin square design. Results showed solubilities ranging from 6.75% to 11.81% at pH 5, increasing to 69.24% to 80.47% at pH 2. ACTM supplementation significantly enhanced the rumen degradability of neutral detergent fiber (NDF) and acid detergent fiber (ADF) at 6 h of incubation ( p ≤ 0.05). The 100% ACTM treatment significantly decreased rumen pH ( p = 0.051) and improved DM, OM, NDF, and ADF digestibility, as well as trace mineral absorbability compared to 100% inorganic ( p ≤ 0.05). These findings highlight the potential of ACTM supplementation to enhance ruminal degradability, promote better trace mineral absorption, and improve the ATTD of nutrients compared to inorganic sources.

IL-23 is a cytokine produced by myeloid cells that drives the T helper 17 pathway and plays an essential role in the pathophysiology of plaque psoriasis. IL-23 activation initiates a cascade of cytokines subsequently inducing the expression of many psoriasis-related proteins. This study aimed to better understand the underlying mechanisms driving the differences between IL-23 and IL-17A blockade in patients with psoriasis and their implications for durability of clinical responses. Serum and/or skin biopsies were isolated from patients treated with guselkumab or secukinumab for evaluation of potential biomarkers of pharmacodynamic response to treatment. Guselkumab treatment led to significantly greater reductions of IL-17F and IL-22 serum levels than treatment with secukinumab at weeks 24 and 48, demonstrating sustained regulation of the IL-23/T helper 17 pathway. Analyses of proteomic and transcriptomic profiles of patient sera and skin biopsies demonstrated differential regulation of proteins involved in chemokine, TNF, and relevant immune signaling pathways to a greater degree with guselkumab than with secukinumab treatment. These data provide insights into the differences between the mechanisms and impact of IL-23 and IL-17A blockade in psoriasis, with implications for efficacy observations and treatment paradigms. Trial Registration: The original study was registered at ClinicalTrials.gov (NCT03090100)., (© 2024 The Authors.)

Interleukin (IL)-23, an IL-12 cytokine family member, is a hierarchically dominant regulatory cytokine in a cluster of immune-mediated inflammatory diseases (IMIDs), including psoriasis, psoriatic arthritis, and inflammatory bowel disease. We review IL-23 biology, IL-23 signaling in IMIDs, and the effect of IL-23 inhibition in treating these diseases. We propose studies to advance IL-23 biology and unravel differences in response to anti-IL-23 therapy. Experimental evidence generated from these investigations could establish a novel molecular ontology centered around IL-23-driven diseases, improve upon current approaches to treating IMIDs with IL-23 inhibition, and ultimately facilitate optimal identification of patients and, thereby, outcomes., Competing Interests: JK served as a consultant for and/or received honoraria from AbbVie, Allergan, Almirall, Amgen, Arena, Aristea, Asana, Aurigene, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Escalier, Galapagos, Janssen, Eli Lilly, MoonLake Immunotherapeutics, Nimbus, Novartis, Pfizer, Sanofi, Sienna Biopharmaceuticals, Sun Pharmaceutical Industries, Target-Derm, UCB, Valeant, and Ventyx. KE received speaker fees from and/or served on an advisory board for AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Galapagos, Eli Lilly, Janssen, Pfizer, Novartis, Sanofi, and UCB. VK served as a consultant for iTeos; has an ownership interest in and is a member of the scientific advisory board for Tizona Therapeutics; is a cofounder of and has an ownership interest in Celsius Therapeutics; and is a cofounder of Bicara Therapeutics. CR received grant/research support and consulting fees from UCB, AbbVie, and Amgen; and received consulting fees from Eli Lilly, Pfizer, Novartis, Gilead, and Janssen. MA is a consultant or served on advisory boards for AbbVie Inc, Arena Pharmaceuticals Inc now Pfizer, Bristol Myers Squibb, Celsius Therapeutics, Eli Lilly and Company, Gilead Sciences Inc, Janssen Pharmaceuticals, Janssen Global Services, Pfizer Pharmaceutical, Prometheus Biosciences, UCB Biopharma SRL. She has received fees for lecturing from Alimentiv, Janssen Pharmaceuticals, Prime CME and WebMD Global LLC. IM received consulting fees and grant/research support from AstraZeneca, Bristol Myers Squibb, Amgen, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB; received consulting fees from AbbVie, Cabaletta, Compugen, Gilead, Pfizer, and Sanofi; serves as a shareholder of Compugen and Causeway Therapeutics, and as a board member for National Health Service Greater Glasgow and Clyde; and is a trustee for Versus Arthritis. ME, AF, SF, JS, Y-WY, and DC are employees of Janssen and hold stock in Johnson & Johnson. Box 1Questions to consider for future investigation to advance the science of IL-23 and approaches to IL-23 inhibitor therapy.A multiomics approach to advancing the science of IL-23 Are there any trends in the literature that identify how the IL-23/IL-17 axis may function and drive nuanced effects in different cell types or tissues?Does the impact of this pathway change over time or with progression of disease, identifying an ideal timeframe or context in the course of disease to initiate IL-23 inhibitor treatment?Are there any differences in biomarker profiles between inadequate responders and responders to therapy that may be used to predict clinical outcomes?What is the epigenetic profile of IL-23 signaling in various immune and non-immune cell types and how may this impact disease pathogenesis, disease progression, or response to treatment?What post-translational modifications of downstream cytokines/effector molecules are associated with IL-23 signaling?What are the functional consequences of changes in multiomics profiles and associated changes in immune cell populations over the course of disease and in response to treatment?“Broad sweep” of IL-23 receptor–expressing cells Which cells express the IL-23 receptor in healthy and inflamed tissues in humans?What is the role of IL-23 receptor signaling in diverse T-cell targets?How may a comprehensive assessment of IL-23 receptor expression across cell types and tissues identify new disease states that may be treatable through targeted intervention with IL-23 inhibition?How does IL-23 receptor expression change at various timepoints and tissue types across IMIDs and in response to treatment with IL-23 blockade?Is the IL-23 receptor coexpressed with other molecules of interest (ie, other cytokines or receptors) that may help to explain differences between currently available therapies and help design future treatments?Gaps in understanding IL-23 signaling and cellular activity Are there different nuances to IL-23 signaling in different cell types or tissues that may have functional consequences impacting disease pathogenesis or response to treatment?Do these signaling nuances change over the course of disease progression, and normalize with treatment with an IL-23 inhibitor?What is the role of STAT3 and STAT4 signaling in the context of IL-23 receptor signaling in Treg cells?What is the relationship between tissue-specific microbiota and IL-23 receptor signaling?Durability of response What is the effect of targeting IL-23p19 on TRM cells and the ratio of TRM/Treg cells across IMIDs?What are the mechanisms underlying the long-lasting effects of targeting IL-23p19?Can early intervention with IL-23 blockade after recent onset of disease modify the course of disease progression by suppressing TRM cells?Future IL-23 inhibitor molecules What molecular attributes of IL-23 inhibitors may be relevant for optimizing inhibition of IL-23 across IMIDs?Are there therapeutic advantages in targeting the IL-23 receptor versus IL-23p19 subunit directly in treating IMIDs?Combination therapy What potential therapeutic benefits may derive from combining IL-23 inhibition with blockade of another complementary inflammatory disease-driving pathway in treating IMIDs?What complementary pathway(s) would be optimal for blockade in combination with IL-23 inhibition for treatment of given IMIDs?IL, interleukin; STAT, signal transducer and activator of transcription; Treg, regulatory T., (Copyright © 2024 Krueger, Eyerich, Kuchroo, Ritchlin, Abreu, Elloso, Fourie, Fakharzadeh, Sherlock, Yang, Cua and McInnes.)

Introduction: The side effects of anti-cancer chemotherapy remain a concern for patients. So, designing alternative medications seems inevitable. In this research, the immunological mechanisms of BCc1 nanomedicine on tumor-bearing mice were investigated., Methods: BALB/c mice underwent tumor transplantation and were assigned into four groups. Group 1 was orally administered with PBS buffer, Group 2 was orally administered BCc1 10 mg/kg, and Group 3 was orally administered BCc1 40 mg/kg daily, respectively. In addition, a group of mice was administered Cyclophosphamide, 20 mg/kg daily. The weight and tumor volume of mice were evaluated bi-weekly. After 24 days of treatment, cytokines and CTL assay in the spleen cell and the tumor were assessed. Furthermore, the spleen, liver, kidney, lung, gut, and uterine tissue were stained with hematoxylin and eosin. Finally, the tumor samples were stained and analyzed for FOXP3. The survival rate of mice was recorded., Results: The results confirmed the histological safety of BCc1. This nanomedicine, especially BCc1 10 mg/kg, led to a strong IFN-γ response and suppressed TGF-β cytokine. The frequency of Treg in the tumor tissue of BCc1 nanomedicine groups was decreased. In addition, nanomedicine repressed tumor volume and tumor weight significantly, which was comparable to Cyclophosphamide. These immunologic events increased the survival rate of BCc1-treated groups. The results indicate that BCc1 nanomedicine can suppress tumor growth and thereby increase the survival rate of experimental mice., Conclusion: It seems a modulation in the tumor microenvironment and polarization toward a Th1 response may be involved. So, BCc1 nanomedicine is efficient for human cancer therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In the severe forms of COVID-19 and many other infectious diseases, the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as IL-6 and TNF-α play a key role in the development of this serious process. Selenium and iron are two important trace minerals, and their metabolism is tightly connected to immune system function. Numerous studies highlight the role of selenium and iron metabolism changes in the procedure of COVID-19 inflammation. The immunomodulator effect of nanomedicines that are synthesized based on nanochelating technology has been proved in previous studies. In the present study, the effects of the combination of BCc1(with iron-chelating property) and Hep-S (containing selenium) nanomedicines on mentioned cytokines levels in hospitalized moderate COVID-19 patients were evaluated., Methods: Laboratory-confirmed moderate COVID-19 patients were enrolled to participate in a randomized, double-blind, placebo-controlled study in two separate groups: combination of BCc1 and Hep-S (N = 62) (treatment) or placebo (N = 60) (placebo). The blood samples were taken before medications on day zero, at discharge, and 28 days after consumption to measure hematological and biochemical parameters and cytokine levels. The clinical symptoms of all the patients were recorded according to an assessment questionnaire before the start of the treatment and on days 3 and discharge day., Results: The results revealed that consumption of the nanomedicines led to a significant decrease in the mean level of IL-6 cytokine, and at the end of the study, there was a 77% downward trend in IL-6 in the nanomedicine group, while an 18% increase in the placebo group (p < 0.05). In addition, the patients in the nanomedicines group had lower TNF-α levels; accordingly, there was a 21% decrease in TNF-α level in the treatment group, while a 31% increase in this cytokine level in the placebo was observed (p > 0.05). On the other hand, in nanomedicines treated groups, clinical scores of coughing, fatigue, and need for oxygen therapy improved., Conclusions: In conclusion, the combination of BCc1 and Hep-S inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology and presents a promising view for immunomodulation that can manage CSS., Trial Registration: Iranian Registry of Clinical Trials RCT20170731035423N2 . Registered on June 12, 2020., (© 2023. The Author(s).)

Background: Palmoplantar pustulosis (PPP) is a chronic inflammatory condition characterized by sterile pustules on the palms and soles. This study evaluated the epidemiology of PPP using claims and electronic health record (EHR) databases., Methods: Patients coded for PPP in the United States (US) and Japan from 2016 to 2020 were identified. Several PPP definitions were evaluated; the specific definition (≥ 2 visits coded for PPP, the second 31-730 days after diagnosis) was chosen for characterizing PPP epidemiology. Baseline characteristics and pre- and post-diagnosis treatments were summarized. Prevalence and incidence rates were analyzed by calendar year, sex, age, and database., Results: Prevalence and incidence of PPP were higher in Japan than the US. PPP prevalence increased over time. PPP occurred predominantly in adulthood and was more common among women. Features of metabolic syndromes, anxiety, and depression were more common among US PPP patients. Consistently high baseline use of anti-bacterial, anti-inflammatory/anti-rheumatic, and obstructive airway disease treatments was observed among PPP patients. Potential miscoding or misclassification of PPP limited this analysis. Prevalence estimates from databases may differ from field- and population-based approaches., Conclusions: The burden of PPP was greater in Japan than in the US. Additional studies are needed to further elucidate PPP epidemiology worldwide., (© 2023. The Author(s).)

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that causes substantial physical, emotional and psychological burdens. Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin-23, has demonstrated high levels of efficacy in the treatment of inflammatory diseases, including psoriasis and psoriatic arthritis., Objective: To evaluate the effect of guselkumab on the treatment of HS, a phase 2, multicentre, randomized, placebo-controlled, double-blind, proof-of-concept study was conducted., Methods: Patients ≥18 years of age with moderate-to-severe HS for ≥1 year were randomized to (1) guselkumab 200 mg by subcutaneous (SC) injection every 4 weeks (q4w) through Week 36 (guselkumab SC); (2) guselkumab 1200 mg intravenously (IV) q4w for 12 weeks, then switched to guselkumab 200 mg SC q4w from Weeks 12 through 36 (guselkumab IV); or (3) placebo for 12 weeks, with re-randomization to guselkumab 200 mg SC q4w at Weeks 16 through 36 (placebo → guselkumab 200 mg) or guselkumab 100 mg SC at Weeks 16, 20, 28 and 36 and placebo at Weeks 24 and 32 (placebo → guselkumab 100 mg). End points included HS clinical response (HiSCR) and patient-reported outcomes., Results: Although guselkumab SC or guselkumab IV resulted in numerically higher HiSCR versus placebo at Week 16 (50.8%, 45.0%, 38.7%, respectively), statistical significance was not achieved. Numerically greater improvements in patient-reported outcomes were also observed for guselkumab SC and guselkumab IV versus placebo at Week 16. Through Week 40, no clear differences to suggest a dose response were observed for HiSCR and patient-reported outcomes., Conclusions: Despite modest improvements, the primary end point was not met and the overall findings do not support the efficacy of guselkumab in the treatment of HS., Clinicaltrials: gov: NCT03628924., (© 2023 Janssen Research & Development, LLC and The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Despite the great success of vaccines in various infectious diseases, most current vaccines are not effective enough, and on the contrary, clinically approved alum adjuvants cannot induce sufficient immune responses, including a potent cellular immune response to confer protection. In this study, we used Nanochelating Technology to develop novel nanoadjuvants to boost the potency of the alum-adjuvanted inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. BALB/c mice were immunized twice over 2 weeks with different doses of adjuvanted-vaccine formulations and immune responses were assessed. The analysis results of IFN- γ and IL-17 cytokines demonstrated the effectiveness of the nanoadjuvants produced by the Nanochelating Technology in shifting the alum-based vaccine toward a stronger Th1 pattern. In addition, these nanoadjuvants improved IL-2 cytokine response, which shows the efficacy of these novel formulations in inducing specific T lymphocyte proliferation. Using these nanoadjuvants increased IL-10 cytokine secretion that may be representative of a better immunoregulatory impact and may also potentially prevent immunopathology responses. Moreover, specific IgG titer analysis revealed the potency of these nanoadjuvants in improving humoral immune responses. The enzyme-linked immunosorbent assay of receptor-binding domain (RBD)-specific IgG response showed that the developed novel formulations induced strong IgG responses against this protein. This study shows that the nanostructures produced by the Advanced Nanochelating Technology have potent adjuvant effects on alum-based SARS-CoV-2 vaccines to not only compensate for alum weakness in inducing the cellular immune responses by smart regulation of the immune system but also significantly improve the humoral and cellular immune responses simultaneously.

Listener behavior has been shown to influence speaker behavior. However, little is known about the extent to which listener behavior can influence countertherapeutic outcomes. This study evaluated the influence of listener interest on the topics presented by adult participants conversing with an experimenter acting as an individual who exhibited restricted interests. Each session consisted of a 5-min conversation, during which the participant was instructed to talk about 3 topics. We compared the duration of topic presentation across phases in which the experimenter behaved as an interested listener for 1 topic or for all 3 topics. Results showed that topic presentation was controlled by listener interest and all participants reported that the simulation was believable, acceptable, and useful. Although preliminary, these findings have implications for understanding possible undesirable interactions between individuals diagnosed with autism spectrum disorder who exhibit restricted interests and their peers or caregivers., (© 2022 The Authors. Journal of Applied Behavior Analysis published by Wiley Periodicals LLC on behalf of Society for the Experimental Analysis of Behavior (SEAB).)