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Maryam Hafizi,1 Somayeh Kalanaky,1 Saideh Fakharzadeh,1 Ehsan Janzamin,2 Tarlan Arjmandi,1 Amir Atashi,3,* Mohammad Hassan Nazaran1,* 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2Flowcyt Science-Based Company, Tehran, Iran; 3Stem Cell and Tissue Engineering Research Center, Shahroud University of Medical Sciences, Shahroud, Iran*These authors contributed equally to this workCorrespondence: Amir Atashi; Mohammad Hassan Nazaran Tel/Fax +98 23 3239 45000; +98 21 8899 2123Email atashia@shmu.ac.ir; mnazaran@nanochelatingtechnology.comBackground: Nowadays, smart synthesized nanostructures have attracted wide attention in the field of stem cell nanotechnology due to their effect on different properties of stem cells.Methods: GFc7 growth nanofactor was synthesized based on nanochelating technology as an iron-containing copper chelator nanocomplex. The effect of this nanocomplex on the expansion and differentiation of hematopoietic stem cells (HSCs) as well as its performance as a cryoprotectant was evaluated in the present study.Results: The results showed that the absolute count of CD34+ and CD34+CD38− cells on days 4, 7, 10 and 13; the percentage of lactate dehydrogenase enzyme on the same days and CD34+CXCR4 population on day 10 were significantly increased when they were treated with GFc7 growth nanofactor in a fetal bovine serum (FBS)-free medium. This medium also led to delayed differentiation in HSCs. One noticeable result was that CD34+CD38− cells cultured in an FBS medium were immediately differentiated into CD34+CD38+ cells, while CD34+CD38− cells treated with GFc7 growth nanofactor in FBS medium did not show such an immediate significant differentiation. De-freezing GFc7-treated CD34+ cells, which were already frozen according to cord blood bank protocols, showed a higher percentage of cell viability and a larger number of colonies according to colony-forming cell assay as compared to control.Conclusion: It can be claimed that treating HSCs with GFc7 growth nanofactor leads to quality and quantity improvement of HSCs, both in terms of expansion in vitro and freezing and de-freezing processes.Keywords: expansion, GFc7, human hematopoietic stem cells, nanocomplex, nanochelating technology

Saideh Fakharzadeh,1,2 Hassan Argani,1 Simin Dadashzadeh,3 Somayeh Kalanaky,2 Peyman Mohammadi Torbati,4 Mohammad Hassan Nazaran,2 Abbas Basiri5 1Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 3Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Department of Pathology, Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Urology and Nephrology Research Center, Shahid Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IranCorrespondence: Mohammad Hassan NazaranDepartment of Research and Development, Sodour Ahrar Shargh Company, Tehran, IranTel/ Fax +98 21 88992123Email mnazaran@nanochelatingtechnology.comAbbas BasiriUrology and Nephrology Research Center, Shahid Labbafinejad Hospital, Shahid Beheshti University of Medical Sciences, Tehran, IranTel/ Fax +98 21 22567222Email basiri@unrc.irBackground: One common feature of chronic diseases, such as cancer, diabetes and chronic kidney disease (CKD), is the disruption of iron metabolism and increase in labile iron pool, which can result in excessive production of harmful oxidative stress. The proper management of iron metabolism in this situation can be a valuable tool to ameliorate pathological events.Materials and Methods: In the previous studies, the anti-neoplastic effects of BCc1, a nanochelating-based nanomedicine with iron-chelating property, were demonstrated in cell culture, animal models and clinical trials. In the present study, the therapeutic effects of BCc1 in animal model of diabetic kidney disease (DKD), induced by streptozotocin injection (35 mg/kg) and high-fat diet consumption, were evaluated.Results: The results showed that BCc1 significantly decreased HOMA-IR index, uric acid, blood urea nitrogen, malondialdehyde and 8-isoprostane. In addition, it reduced urinary albumin excretion rate and albumin-to-creatinine ratio in comparison to DKD control rats. This nanomedicine had no negative impact on liver iron content, hemoglobin level, red blood cell count, hematocrit and mean corpuscular volume, while it significantly decreased aspartate aminotransferase and alanine aminotransferase compared to DKD control group. Moreover, the histopathological assessment indicated that lesser glomerular basement membrane and wrinkling, mesangial matrix expansion and pathological changes in proximal cortical tubules were seen in the kidney samples of BCc1-treated rats.Conclusion: In conclusion, BCc1 as an iron-chelating agent shows promising impacts in DKD animal model, which can ameliorate biochemical and pathological events of this disease.Keywords: BCc1, diabetic kidney disease, chronic kidney disease, nanochelating technology, iron

Saideh Fakharzadeh,1–3 Somayeh Kalanaky,2 Maryam Hafizi,2 Mohammad Hassan Nazaran,2 Homeira Zardooz1,3 1Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 3Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Aims: Despite daily increase in diabetic patients in the world, currently approved medications for this disease, at best, only reduce its progression speed. Using novel technologies is a solution for synthetizing more efficient medicines. In the present study, we evaluated anti-diabetic effects of DIBc, a nano metal–organic framework, which is synthetized based on nanochelating technology.Methods: High-fat diet and streptozotocin-induced diabetic rats were treated by DIBc or metformin for 6 weeks.Results: DIBc decreased plasma glucose, triglyceride, cholesterol, high-density lipoprotein, and low-density lipoprotein compared with diabetic and metformin groups. In DIBc-treated rats, significant homeostasis model assessment of insulin resistance index, malondialdehyde, and tumor necrosis factor-α decrease was observed. H&E staining showed increased islet number and area in DIBc-treated rats compared with diabetic controls.Conclusion: The results showed anti-diabetic effects of nanochelating-based framework. So DIBc, as a nano structure, has the capacity to be evaluated in future studies as a novel anti-diabetic agent. Keywords: DIBc, nanochelating technology, metal organic framework, diabetes, streptozotocin, high-fat diet

Somayeh Kalanaky,1,2 Maryam Hafizi,1–3 Saideh Fakharzadeh,1 Mohammad Vasei,4 Ladan Langroudi,5 Ehsan Janzamin,6 Seyed Mahmoud Hashemi,7 Maryam Khayamzadeh,2 Masoud Soleimani,6 Mohammad Esmaeil Akbari,2 Mohammad Hassan Nazaran1 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Stem Cell Technology Research Center, Tehran, Iran; 4Department of Pathology, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 6Department of Haematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; 7Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Purpose: In spite of all the efforts and researches on anticancer therapeutics, an absolute treatment is still a myth. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In this study, for the first time, we have evaluated the anticancer effects of BCc1 nanocomplex by vitro and in vivo studies, which is designed based on the novel nanochelating technology.Methods: Human breast adenocarcinoma cell line (MCF-7) and mouse embryonic fibroblasts were used for the in vitro study. Antioxidant potential, cell toxicity, apoptosis induction, and CD44 and CD24 protein expression were evaluated after treatment of cells with different concentrations of BCc1 nanocomplex. For the in vivo study, mammary tumor-bearing female Balb/c mice were treated with different doses of BCc1 and their effects on tumor growth rate and survival were evaluated.Results: BCc1 decreased CD44 protein expression and increased CD24 protein expression. It induced MCF-7 cell apoptosis but at the same concentrations did not have negative effects on mouse embryonic fibroblasts viability and protected them against oxidative stress. Treatment with nanocomplex increased survival and reduced the tumor size growth in breast cancer-bearing balb/c mice.Conclusion: These results demonstrate that BCc1 has the capacity to be assessed as a new anticancer agent in complementary studies. Keywords: BCc1, cancer, nanotechnology, nanochelating technology, nanocomplex

Saideh Fakharzadeh,1 Mohammad Ali Sahraian,2 Maryam Hafizi,1 Somayeh Kalanaky,1 Zahra Masoumi,1 Mehdi Mahdavi,1 Nasser Kamalian,3 Alireza Minagar,4 Mohammad Hassan Nazaran1 1Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran; 2MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Pathology, Medical School of Tehran University of Medical Sciences, Tehran, Iran; 4Department of Neurology, LSU Health Sciences Centre, Shreveport, LA, USA Purpose: Currently approved therapies for multiple sclerosis (MS) at best only slow down its progression. Therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. In the present study, for the first time we evaluated the therapeutic potential of MSc1 nanocomplex, which was designed based on novel nanochelating technology. Materials and methods: MSc1 cell-protection capacity, with and without iron bond, was evaluated against hydrogen peroxide (H2O2)-induced oxidative stress in cultured rat pheochromocytoma-12 cells. The ability of MSc1 to maintain iron bond at pH ranges of 1–7 was evaluated. Nanocomplex toxicity was examined by estimating the intraperitoneal median lethal dose (LD50). Experimental autoimmune encephalomyelitic mice were injected with MSc1 14 days after disease induction, when the clinical symptoms appeared. The clinical score, body weight, and disease-induced mortality were monitored until day 54. In the end, after collecting blood samples for assessing hemoglobin and red blood cell count, the brains and livers of the mice were isolated for hematoxylin and eosin staining and analysis of iron content, respectively. Results: The results showed that MSc1 prevented H2O2-induced cell death even after binding with iron, and it preserved its bond with iron constant at pH ranges 1–7. The nanocomplex intraperitoneal LD50 was 1,776.59 mg/kg. MSc1 prompted therapeutic behavior and improved the disabling features of experimental autoimmune encephalomyelitis, which was confirmed by decreased clinical scores versus increased body mass and 100% survival probability. It did not cause any adverse effects on hemoglobin or red blood cell count. Histopathological studies showed no neural loss or lymphocyte infiltration in MSc1-treated mice, while the hepatic iron content was also normal. Conclusion: These results demonstrate that MSc1 could be a promising beneficial novel agent and has the capacity to be evaluated in further studies. Keywords: EAE, multiple sclerosis, MSc1, nanochelating technology, nanocomplex

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.)