IL-8 Levels Research Articles

Correlation analysis of serum Rac1 level with asthma control, airway inflammatory response and lung function in asthmatic children

ObjectiveTo investigate the correlation between serum Rac1 enzyme (Rac1) level with asthma control, airway inflammatory response and lung function in asthmatic children.MethodsA retrospective analysis was performed on 79 children with asthma who were diagnosed and treated in our hospital from June 2020 to January 2023. According to the severity of the disease, the children were divided into mild group (25 cases), moderate group (30 cases) and severe group (24 cases). 36 healthy children who underwent physical examination at the same period in our hospital were selected as the control group. The state of an illness, control level, serum mRNA Rac1, inflammatory factors, and lung function of the children in two groups were compared between the control group and the observation group.ResultsThe Rac1 mRNA levels, forced vital capacity (FVC), forced expiratory volume in one second/FVC (FEV1/FVC), peak expiratory flow (PEF), and maximum mid-expiratory flow (MMEF) in the observation group were significantly lower than these in the control group (P < 0.05). The tumor necrosis factor-alpha (TNF-α), interleukin-5 (IL-5), IL-6, and IL-33 in the observation group were markedly higher than these in the control group (P < 0.05). As the state of an illness worsened, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually reduced (P < 0.05), while the levels of TNF-α, IL-5, IL-6, and IL-33 increased (P < 0.05). As the degree of disease control improved, the Rac1 mRNA levels, FVC, FEV1/FVC, PEF, and MMEF gradually elevated (P < 0.05), and the levels of TNF- α, IL-5, IL-6, and IL-33 showed the opposite trend (P < 0.05). Rac1 was negatively related to the levels of TNF-α, IL-5, IL-6 and IL-33 (P < 0.05), and positively to the levels of FVC, FEV1/FVC, PEF and MMEF (P < 0.001). Rac1 mRNA levels, FVC, FEV1/FVC, PEF and MMEF were protective factors, while TNF-α, IL-5, IL-6 and IL-33 were risk factors for the prognosis of children with asthma (P < 0.05).ConclusionChildren with asthma have obviously lower serum Rac1 mRNA levels, higher inflammatory factor levels and lower lung function. Serum Rac1 mRNA level may be associated with better asthma control, lower airway inflammatory response, better lung function and lower disease severity. It has important reference value for the evaluation of the state of an illness, efficacy and prognosis of children with bronchial asthma.

Changes and significance of Th1/Th2 and Treg/Th17 cells and their cytokines in patients with alopecia areata

BackgroundAlopecia areata (AA) is a chronic autoimmune disease. Th1/Th2 and Treg/Th17 cells and their cytokines are implicated in AA, and we explored their clinical significance in AA. MethodsAA patients and healthy people (controls) were enrolled, with their Th1/Th2/Th17/Treg cell proportion changes and serum Th1 (INF-γ)/Th2 (IL-5, IL-6)/Th17 (IL-17, IL-22)/Treg (IL-35) cytokine levels assessed. AA patients were assigned into mild, moderate and severe alopecia according to Severity of Alopecia Tool (SALT). The relationship between alopecia severity and initial onset age, disease course, family/smoking/drinking history and sleep disorders was explored. Th1/Th2 and Treg/Th17 cells and their cytokine levels in AA patients with different severity levels were compared. The correlation between cytokine levels and SALT scores was analyzed using Spearman. Additionally, the changes of serum cytokine levels in inactive/active AA patients were compared. ResultsAA patients differed from controls in family history/smoking history/drinking history/sleep disorders. Peripheral blood Th1/Th2/Th17 cell proportions and INF-γ/IL-5/IL-6/IL-17/IL-22 levels increased, while Treg cell proportions and IL-35 level dropped. With higher alopecia severity, the proportions of Th1, Th2 and Th17 cells increased, and Treg cell proportion decreased. AA patients with mild/moderate alopecia had significant differences in IL-17 level. Serum INF-γ, IL-5, IL-17 and IL-22 levels were elevated, and IL-35 level dropped in severe AA patients versus moderate AA patients. ConclusionTh1/Th2/Th17 cell proportions and serum INF-γ/IL-5/IL-6/IL-17/IL-22 levels in AA patients were up-regulated, while Treg cell proportion and IL-35 level were repressed. SALT scores were positively-correlated with serum IL-5/IL-17 levels. SALT scores were negatively-correlated with serum IL-35.

Resveratrol inhibits pancreatic cancer proliferation and metastasis by depleting senescent tumor-associated fibroblasts.

Pancreatic cancer, a formidable gastrointestinal neoplasm, is characterized by its insidious onset, rapid progression, and resistance to treatment, which often lead to a grim prognosis. While the complex pathogenesis of pancreatic cancer is well recognized, recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts. However, their precise role in pancreatic cancer remains unknown. Resveratrol is a natural polyphenol known for its multifaceted biological actions, including antioxidative and neuroprotective properties, as well as its potential to inhibit tumor proliferation and migration. Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis. To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts. Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression of α-SMA and p16. HP-1 expression was determined using immunohistochemistry. Cells were treated with the senescence-inducing factors known as 3CKs. Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate. Western blotting was conducted to assess the expression levels of p16 and p21. Immunofluorescence was performed to assess LaminB1 expression. Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors, including IL-4, IL-6, IL-8, IL-13, MMP-2, MMP-9, CXCL1, and CXCL12. A scratch assay was used to assess the migratory capacity of the cells, whereas Transwell assays were used to evaluate their invasive potential. Specifically, we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues, linking their abundance to cancer progression. Intriguingly, Resveratrol effectively eradicated these fibroblasts and hindered their senescence, which consequently impeded pancreatic cancer progression. This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.

Reversing Pdgfrβ signaling restores metabolically active beige adipocytes by alleviating ILC2 suppression in aged and obese mice

ObjectivePlatelet Derived Growth Factor Receptor Beta (Pdgfrβ) suppresses the formation of cold temperature-induced beige adipocytes in aged mammals. We aimed to determine if deleting Pdgfrβ in aged mice could rejuvenate metabolically active beige adipocytes by activating group 2 innate lymphoid cells (ILC2), and whether this effect could counteract diet-induced obesity-associated beige fat decline. MethodsWe employed Pdgfrβ gain-of-function and loss-of-function mouse models targeting beige adipocyte progenitor cells (APCs). Our approach included cold exposure, metabolic cage analysis, and age and diet-induced obesity models to examine beige fat development and metabolic function under varied Pdgfrβ activity. ResultsAcute cold exposure alone enhanced metabolic benefits in aged mice, irrespective of beige fat generation. However, Pdgfrβ deletion in aged mice reestablished the formation of metabolically functional beige adipocytes, enhancing metabolism. Conversely, constitutive Pdgfrβ activation in young mice stymied beige fat development. Mechanistically, Pdgfrβ deletion upregulated IL-33, promoting ILC2 recruitment and activation, whereas Pdgfrβ activation reduced IL-33 levels and suppressed ILC2 activity. Notably, diet-induced obesity markedly increased Pdgfrβ expression and Stat1 signaling, which inhibited IL-33 induction and ILC2 activation. Genetic deletion of Pdgfrβ restored beige fat formation in obese mice, improving whole-body metabolism. ConclusionsThis study reveals that cold temperature exposure alone can trigger metabolic activation in aged mammals. However, reversing Pdgfrβ signaling in aged and obese mice not only restores beige fat formation but also renews metabolic function and enhances the immunological environment of white adipose tissue (WAT). These findings highlight Pdgfrβ as a crucial target for therapeutic strategies aimed at combating age- and obesity-related metabolic decline.

Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model.

Atopic dermatitis (AD), a chronic inflammatory disease, severely interferes with patient life. Human placenta extract (HPH; also known as human placenta hydrolysate) is a rich source of various bioactive substances and has widely been used to dampen inflammation, improve fatigue, exert anti-aging effects, and promote wound healing. However, information regarding HPH's incorporation in AD therapies is limited. Therefore, this study aimed to evaluate HPH's effective potential in treating AD using tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated human keratinocytes (HaCaT), immunized splenocytes, and a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. In TNF-α /IFN-γ-stimulated HaCaT cells, HPH markedly reduced the production of reactive oxygen species (ROS) and restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 1(SOD1), catalase, and filaggrin (FLG). HPH reduced interleukin (IL)-6; thymus- and activation-regulated chemokine (TARC); thymic stromal lymphopoietin (TSLP); and regulated upon activation, normal T cell expressed and presumably secreted (RANTES) levels and inhibited nuclear factor kappa B phosphorylation. Additionally, HPH suppressed the T helper 2 (Th2) immune response in immunized splenocytes. In the AD-like mouse model, it significantly mitigated the DNCB-induced elevation in infiltrating mast cells and macrophages, epidermal thickness, and AD symptoms. HPH also reduced TSLP levels and prevented FLG downregulation. Furthermore, it decreased the expression levels of IL-4, IL-5, IL-13, TARC, RANTES, and immunoglobulin E (IgE) in serum and AD-like skin lesion. Overall, our findings demonstrate that HPH effectively inhibits AD development and is a potentially useful therapeutic agent for AD-like skin disease.

Acute and chronic response of supervised band-elastic resistance exercise in systemic cytokines levels of bipolar disorders and schizophrenia individuals: A pilot study

Despite earlier research demonstrating the immunomodulatory effects of acute and chronic exercise in many medical illnesses, there is a lack of literature evaluating the acute and chronic effects of exercise on the cytokine levels in individuals with bipolar disorder (BD) or schizophrenia (SCH). This study aims to examine the acute effects of resistance exercise on cytokines and the chronic effects of resistance exercise by 10 weeks on cytokine levels, symptoms of disease, and muscular strength in individuals with BD and SCH. The included individuals (N=10) performed a single session of band-elastic resistance exercises (six exercises, 3 sets of 12–15 repetitions, 60 seconds of interval between sets). A sub-sample (N=6) of individuals performed a supervised band-elastic resistance exercise program (2 times a week, for 10 weeks, 6 exercises, 3 sets of 12–15 repetitions, 60 seconds of interval). We verified for acute effects: IL-2 (P=0.0085) and IL-4 (P=0.0253) levels increased, while IL-6 decreased (P=0.0435), and for chronic effects: increased IL-2 and IL-4 levels (significant effect size - Pre vs Post), a decrease in disease symptoms, and an increase in muscular strength. This study adds to what is already known about how resistance exercises affect people with BD and SCH in both short-term (systemic cytokines levels) and long-term (symptoms of disease, muscular strength, and systemic cytokines levels).

Minthostachys verticillata essential oil modulates cytokine synthesis and Staphylococcus aureus internalization in MAC-T cells at least through TLR4/MyD88/NFkB pathway.

The aim of this study was to evaluate the activation pathway(s) triggered by Minthostachys verticillata essential oil (EO) in bovine mammary epithelial cells (MAC-T) challenged with a strain of bovine Staphylococcus aureus. MAC-T cells were stimulated with EO, S. aureus or pre-treated with EO and then challenged with S. aureus. Cytokine's release was measured by ELISA. The mRNA for TLR2, TLR4, NOD2, MyD88 and NFκB was quantified by RT-qPCR. S. aureus adherence and internalization was also evaluated. MAC-T cells stimulated with S. aureus synthesized high levels of IL-1ß and IL-6 were kept up to 48 h, while IL-4 levels were not altered.Cells pre-treated with EO for 2 and 6h and then challenged with S. aureus showed a significant increase of IL-1β and IL-6. However, in these cells, a decrease in IL-1ß and IL-6 levels and an increase of IL-4 values was observed from 24 h. No significant increase in the expression levels of TLR2 or NOD2 was detected in all stimulated cells. However, the expression of TLR4, MyD88 and NFκB was increased in cells stimulated with S. aureus at 2 and 6 h as well as in cells pre-treated with EO between 2 and 6h and then challenged with S. aureus. The NFκB expression levels was similar to control at 24h in all stimulated cells, although pro-inflammatory cytokine levels and TLR4 and MyD88 expression levels remained high in cells stimulated with S. aureus. This results suggested the activation of other pathways independent of MyD88 by the pathogen that involucrated the activation of others transcription factors. Pre-treatment with EO during 2, 6 and 24h did not affect S. aureus adherence but decreased its internalization. In conclusion, pre-treatment with EO increased the IL-1β and IL-6 synthesis during the first hours post-challenged with S. aureus up-regulating TLR4/MyD88/NFκB pathway. Furthermore, EO increased the IL-4 levels from 6 to 24 h down-regulating the NFκB and possibly other transcription factors activated by the pathogen, which decreased its internalization into MAC-T cells.

Immunogenicity and protective efficacy of a recombinant lactococcus lactis vaccine against HSV-1 infection

BackgroundHerpes simplex virus type 1 (HSV-1) is a major cause of viral encephalitis, genital mucosal infections, and neonatal infections. Lactococcus lactis (L. lactis) has been proven to be an effective vehicle for delivering protein antigens and stimulating both mucosal and systemic immune responses. In this study, we constructed a recombinant L. lactis system expressing the protective antigen glycoprotein D (gD) of HSV-1.ResultsTo improve the stability and persistence of antigen stimulation of the local mucosa, we inserted the immunologic adjuvant interleukin (IL)-2 and the Fc fragment of IgG into the expression system, and a recombinant L. lactis named NZ3900-gD-IL-2-Fc was constructed. By utilizing this recombinant L. lactis strain to elicit an immune response and evaluate the protective effect in mice, the recombinant L. lactis vaccine induced a significant increase in specific neutralizing antibodies, IgG, IgA, interferon-γ, and IL-4 levels in the serum of mice. Furthermore, in comparison to the mice in the control group, the vaccine also enhanced the proliferation levels of lymphocytes in response to gD. Moreover, recombinant L. lactis expressing gD significantly boosted nonspecific immune reactions in mice through the activation of immune-related genes. Furthermore, following the HSV-1 challenge of the murine lung mucosa, mice inoculated with the experimental vaccine exhibited less lung damage than control mice.ConclusionOur study presents a novel method for constructing a recombinant vaccine using the food-grade, non-pathogenic, and non-commercial bacterium L. lactis. The findings indicate that this recombinant vaccine shows promise in preventing HSV-1 infection in mice.

Observations on the efficacy of edaravone dexborneol in preventing post-stroke depression and its inflammatory mechanism: a prospective, randomized, control trial.

This study aimed to observe the effect of edaravone dexborneol (EDB) on the incidence of early post-stroke depression (PSD) and explore its inflammatory mechanisms. A prospective, randomized controlled study was conducted from January 2022 to June 2023, involving patients with acute ischemic stroke (AIS) at the Neurology Department of the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine. The control group received routine treatment, while the experimental group received routine combined EDB treatment. The main outcome measures included PSD incidence, Patient Health Questionnaire (PHQ-9) and Hamilton Depression Scale (HAMD) scores on days 14 and 30, and inflammatory factor levels on day 14. A total of 93 patients were included in the study, 51 in the experimental group and 42 in the control group. On day 14, the PSD incidence was 13.7% in the experimental group, lower than 31.0% in the control group (95%CI 0.127-0.996; p = 0.044). Compared to the control group, the experimental group showed significantly lower concentrations of pro-inflammatory cytokines IL-1β (95%CI 3.353-5.184), IL-6 (95%CI 2.694-3.426), TNF-α (95%CI 4.985-12.196), IFN-γ (95%CI 0.163-0.451), MCP-1 (95%CI 0.335-0.787), IL-17A (95%CI 0.543-1.024), and IL-23p19 (95%CI 1.677-1.959) (all p < 0.001), and higher levels of anti-inflammatory cytokines IL-4 (95%CI -1.087 to -0.941), IL-10 (95%CI -6.125 to -1.662), and IL-13 (95%CI -6.078 to -2.953) (all p ≤ 0.001). On day 30, the PSD incidence in the experimental group was 15.7%, lower than 40.5% in the control group (95%CI 0.103-0.725; p = 0.007). Compared with the control group, the experimental group had lower PHQ-9 scores on day 14 (95%CI 0.034-1.577; p = 0.041) and day 30 (95%CI 0.018-1.573; p = 0.045), and also had lower HAMD scores on day 14 (95% CI 0.281-2.856; p = 0.018) and day 30 (95% CI 0.647-3.482; p = 0.005). EDB could reduce the incidence of early PSD, reduce pro-inflammatory cytokine levels, and elevate anti-inflammatory cytokine levels, which was possibly related to the anti-inflammatory mechanism of EDB. http://www.chictr.org.cn/, identifier [ChiCTR2300067750].

SP6.6 - Examining the Immunomodulatory Effects of Fibrosis Induced by Radiation Using Adipose-derived Stem Cells

Abstract Background and Introduction Radiation-induced fibrosis (RIF) is a complication of radiotherapy in the treatment of head and neck cancer. RIF is characterised by the formation of fibrous tissue and is associated with significant morbidity. Autologous fat grafting (AFG) is a promising approach for treating RIF, and adipose-derived stem cells (ADSC) have been identified as key contributors to this therapeutic effect. Method The experimental group included subjecting human-derived fibroblasts (iHDF) to radiation, whereas the control group remained radiation-free. Both groups were then treated with ADSC-controlled medium and co-cultured with ADSC. The amounts of important immunomodulators produced by iHDF cells were then collected and evaluated using enzyme-linked immunosorbent assays (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). Results Co-cultured iHDF samples demonstrated a slight reduction in CCL2 concentrations compared to untreated iHDF samples (p = 0.0006). The iHDF co-culture samples exhibit a marginal elevation in CCL3 levels compared to the untreated iHDF samples (p = 0.0247). The co-culture samples of iHDF demonstrate a substantial and measurable elevation in IL-8 levels compared to the untreated iHDF samples (p = 0.027). The expression of Col1A1 is decreased in iHDF samples in comparison to control groups. Discussion CCL2 is implicated in the recruitment of ADSCs to specific locations. The elevated production of IL-8 in ADSC samples is associated with the pro-angiogenic characteristics of ADSC secretions, which promote healing in fibrotic tissue. Conclusion ADSCs were shown to possess anti-fibrotic properties via stimulating pro-angiogenic factors. However, experimental data indicates a concomitant elevation in pro-inflammatory factors. Further research is needed to explore the in-vivo effects of ADSC.

Causal relationship between systemic circulatory inflammatory regulators and intervertebral disc degeneration: A bidirectional 2-sample Mendelian randomization study.

In the context of the development of intervertebral disc degeneration (IDD), inflammatory mediators play a pivotal role. Nevertheless, due to the influence of the inflammatory microenvironment, the causal relationship between specific inflammatory mediators and the development of IDD remains uncertain. The understanding of the causal relationship between inflammatory mediators and IDD is of great importance in preventing and delaying disc degeneration in the future. We utilized genetic data concerning systemic circulating inflammatory regulators obtained from a Genome-Wide Association Study (GWAS) analyzing 41 serum cytokines in a cohort of 8293 individuals from Finland. The genetic data for IDD were derived from the most recent GWAS summary statistics conducted within the FinnGen consortium, encompassing 37,636 IDD cases and 270,964 controls. Our analysis employed bidirectional 2-sample Mendelian randomization (MR) techniques, which included several MR methods such as MR Egger, weighted median, inverse variance weighted, weighted mode, and simple mode. Additionally, the MR-PRESSO method was employed to identify horizontal pleiotropy, heterogeneity was quantified using the Cochran Q statistic, and MR-Egger intercept analysis was performed to assess pleiotropy. We established causal relationships between 3 specific inflammatory factors and IDD. Elevated levels of MIP-1β (OR = 0.956, 95% CI: -0.08 to -0.006; P = .02) and IFN-G (OR = 0.915, 95% CI: -0.16 to -0.02; P = .01) expression were associated with a reduced risk of IDD. Conversely, genetic susceptibility to IDD was linked to a decrease in IL-13 levels (OR = 0.967, 95% CI: -0.063 to -0.004; P = .03). In this study, we have identified inflammatory factors that exhibit a causal relationship with the onset and progression of IDD, as supported by genetic predictions.

Comprehensive modulatory effects of whole grain consumption on immune-mediated inflammation in middle-aged and elderly community residents: A real-world randomized controlled trial

Background and aimsWhole grain consumption is widely recognized as a vital component of a balanced diet. Dietary fiber has been well-documented to play a crucial role in these health benefits attributed to whole grain intake. However, population-based evidence directly linking whole grain consumption to anti-inflammatory effects, especially in the context of immune-mediated inflammation, remains limited. We hypothesized that whole grain consumption promotes health by modulating immune-mediated inflammation. Methods and resultsThis study was designed as a real-world, population-based randomized controlled trial. We compared the effects of whole grain versus refined grain consumption on immune-mediated inflammation through staple food substitution, while participants maintained their usual dietary practices. The results demonstrated that whole grain consumption significantly reduced circulating levels of pro-inflammatory cytokines IL-22 and IL-23 compared to refined grain consumption. These reductions were associated with optimized short-chain fatty acid profiles and changes in CD4+ T cell subset distributions. ConclusionsThe findings suggest that the anti-inflammatory effects of whole grain consumption in middle-aged and elderly populations are mediated by targeting specific CD4+ T cell subsets, in addition to modulating both upstream short-chain fatty acid composition and downstream expression of the pro-inflammatory cytokines IL-22 and IL-23.

Investigation of pre and postoperative Th1/Th2 cytokine balance and novel cytokines in colorectal cancer patients

Colorectal cancer (CRC) is a major health problem worldwide and is usually detected in advanced stages, although it is highly treatable with early detection. The aim of this study was to examine the serum levels of various cytokines involved in the pathogenesis of CRC. The study included 29 patients and 30 healthy volunteers. Blood samples were collected twice from the patient group, before and after surgery, and these samples were evaluated for interleukin (IL) 4, 10, 23r, 37, 38, 40 and interferon (IFN) gamma levels. The results showed that IL-4 and IL-38 levels were significantly lower in the preoperative serum samples of the patient group compared to the control group (p < 0.001 and p = 0.01, respectively), while IL-4, IL-10, IL-38 and IL-40 levels increased significantly in the postoperative period (p = 0.004, p = 0.02, p = 0.03 and p = 0.004, respectively). These findings may contribute to the development of immunotherapy agents in the treatment of CRC. However, comprehensive studies on larger patient groups are needed to fully understand the role of cytokines in CRC pathogenesis.

Saffron (Crocus sativus) and its constituents in ovalbumin-induced asthma model: a preclinical systematic review and meta-analysis.

Animal and human studies have demonstrated that the saffron and the active components of saffron, including crocin, crocetin, and safranal, possess anti-inflammatory, antioxidant, and immunomodulatory properties. In this meta-analysis, the preclinical evidence and potential mechanism of saffron were explored in an animal model of ovalbumin-induced asthma. Studies related to saffron and its constituents in an animal model of ovalbumin-induced asthma from the beginning to March 2024 were searched from Scopus, PubMed, and Web of Science databases. The methodological quality of the studies was evaluated using the 15-item CAMARADES checklist. Data analysis was performed using STATA software version 17. Thirteen studies with 536 animals (268 animals in the intervention group and 268 animals in the ovalbumin-induced group) were analyzed. The meta-analysis findings demonstrated that saffron and its constituents played a significant role in reducing total WBC, eosinophil, lymphocyte, and monocyte counts. Moreover, saffron showed a significant decrease in the levels of IL-4, IL-5, IL-13, IgE, histamine, endothelin, nitric oxide, and nitrite. Moreover, saffron was found to elevate EC50 thresholds and lower maximum response rates in experimental animals. The analysis revealed a significant identification of modulation in endoplasmic reticulum (ER) stress markers and miRNAs pathways. Saffron and its components may impact ovalbumin-induced asthma model in animals through anti-inflammatory, antioxidant, and immunomodulatory pathways, as well as improving pulmonary function and modulating ER stress markers and miRNAs pathways. As a result, saffron should be considered for further clinical trials in individuals suffering from asthma.

Glatiramer acetate in situ forming gel, a new approach for multiple sclerosis treatment.

Glatiramer acetate (GA), a commonly used treatment for multiple sclerosis (MS), requires long-term frequent injections to ensure its effectiveness. This often leads to adverse effects, patient noncompliance, and economic inefficiency. In this study, poloxamer, as a thermosensitive polymer modified by chitosan (CS) and hyaluronic acid (HA), was employed to prepare an in situ forming prolonged release formulation of GA to overcome the problems derived from frequent repeated injections and to enhance the patient compliance. The sol-gel formulation was produced through a cold method and optimized using design of experiments. The final product was characterized in terms of gelation time (GT), rheological behaviors, morphological properties, assay, and drug release kinetics. The in vitro release rate of GA during the first 24 h was quite rapid, but then it continued at a slower rate of 0.05 mg ml-1h-1. The in vivo analysis after the subcutaneous injections showed lower levels of IL-5, IL-13, and uric acid (UA) in mice treated with the gel formulation compared with those receiving free GA in the first few days. However, after 10 days, significantly higher concentrations were detected, which continued to increase slowly. It can be concluded that the designed thermosensitive sol-gel formula is capable of extending the effectiveness of GA and can be considered as a promising sustained release formulation for the treatment of MS.

Changes in Circulating CD44+CD62L− Treg Subsets and CD44−CD62L+ Treg Subsets Reflect the Clinical Status of Patients with Allergic Rhinitis

Introduction: This study clarified the expression changes and clinical significance of CD44+CD62L− Treg and CD44−CD62L+ Treg subsets in the peripheral blood of patients with allergic rhinitis (AR). Methods: The peripheral blood of 39 patients with AR and 42 healthy controls was collected. Clinical data, such as sex, age, IgE titer, allergen screening information and visual analogue scale (VAS) score, were recorded. Changes in serum IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ were detected using the cytometric bead array method. Flow cytometry was used to detect the proportions of Th1, Th2, Th17, TFH, and Th9 cells and the proportions of CD44+CD62L− Treg and CD44−CD62L+ Treg subsets. Correlation analysis was performed between the CD44+CD62L− Treg subsets and the CD44−CD62L+ Treg subsets with clinical indicators (VAS score, total IgE titer), cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ), and Th1/Th2/Th17/TFH/Th9 cell proportions. Results: Compared to the control group, the proportion of total Treg cells and CD44+CD62L− Treg cells in the AR group decreased, and the proportion of CD44−CD62L+ Treg cells increased (p < 0.05). The proportions of CD44+CD62L− Treg cells significantly negatively correlated with Th2 cells (R = −0.5270, p < 0.05) and positively correlated with Treg cytokine IL-10 (R = 0.6447, p < 0.05). In addition, CD44+CD62L− Treg cells negatively correlated with the VAS score (R = −0.4956, p < 0.05), total IgE level (R = −0.4177, p < 0.05) and Th2 cytokine IL-6 level (R = −0.3034, p < 0.05) but positively correlated with the Th1 cytokine IL-2 (R = 0.4331, p < 0.05). In contrast, the proportion of CD44+CD62L− Treg cells significantly positively correlated with the Th2 cells (R = 0.6187, p < 0.05). Moreover, the proportion of CD44−CD62L+ Treg cells positively correlated with the VAS score (R = 0.4060, p < 0.05), total IgE level (R = 0.5224, p < 0.05) and Th2 cytokine IL-4 (R = 0.2647, p < 0.05) and IL-6 levels (R = 0.3824, p < 0.05) but negatively correlated with Th1 cytokine IL-2 (R = −0.3451, p < 0.05) and IL-10 (R = −0.3277, p < 0.05). Conclusion: A greater proportion of CD44+CD62L− Tregs correlated with better reversal of the Th1/Th2 imbalance and milder clinical symptoms in AR patients. The presence of more CD44−CD62L+ Tregs correlated with a weaker immunosuppressive effect on Th2 cells and more severe clinical symptoms in AR patients. These findings provide new perspectives for the treatment and disease monitoring of AR.

The mechanism by which intestinal flora metabolites regulate ILC2s transformation and intestinal immunity through the metabolite-sensitive receptor Ffar2.

The objective of this article was to investigate how the metabolites produced by the intestinal flora regulate the transformation of ILC2s and intestinal immunity via the receptor Ffar2, which is sensitive to metabolites. Forty male C57BL/6 mice with wild-type characteristics (6-7 weeks in age) and 20 FFAR2-/- mice were acquired from The Jackson Laboratory. The mice were kept in a controlled environment without any disease-causing agents, with the help of air conditioning and a 12-hour cycle of light and darkness. Throughout the experiment, every mouse was provided with unrestricted availability of both food and water. All protocols were performed following the Regulations of Animal Welfare and the recommendations for Animal Testing. According to the research protocol, the mice were categorized into three groups, each consisting of 20 mice. FFAR2-/- mice in the FFAR2-/- group were reared in conventional environments. Male C57BL/6 mice with wild-type characteristics were reared in conventional conditions in the wild-type group. In the group where wild-type mice were inhibited with Ffar2, a total of 20 mice with the wild-type phenotype were chosen to receive intraperitoneal injection of an FFAR2 antagonist at a dosage of 5 mg/kg per day for a continuous period of 3 weeks. qRT-PCR was used to detect the expression of FFAR2 mRNA in the mucosal tissue of the mouse colon. High-throughput sequencing was used to conduct an examination of metabolites in the intestinal tract of mice. Flow cytometry was used to test the quantity of ILC2s. ELISA was used to measure the levels of IL-5 and IL-13 in cellular mouse intestinal mucosal tissues. Flow cytometry was used to detect the quantity of CD4+ and CD8+ T cells. CCL20 and CCL25 expression was analyzed by Western blotting. The level of FFAR2 mRNA expression was higher in the wild-type group than the FFAR2-/- group (P < 0.05), while it was lower in the wild-type + Ffar2 inhibition group than the wild-type group (P < 0.05). No variations were observed in the composition of metabolites and levels of major SCFAs in the gut microbiota of mice across all groups (P > 0.05). The quantity of CRTH2+ and ST2+ cells in the wild-type category exceeded that in the FFAR2-/- category (P < 0.05), whereas the quantity of CRTH2+ and ST2+ cells in the wild-type + Ffar2 inhibition category was lower than that in the wild-type category (P < 0.05). The concentrations of IL-5 and IL-13 were higher in the wild-type group compared with the FFAR2-/- group (P < 0.05), while the wild-type + Ffar2 inhibition group exhibited lower levels of IL-5 and IL-13 than the wild-type group (P < 0.05). The count of CD4+ T cells and CD8+ T cells in the wild-type group showed an increase in comparison to the FFAR2-/- group (P < 0.05), whereas the count of CD4+ T cells and CD8+ T cells in the wild-type + Ffar2 inhibition group exhibited a decrease in comparison to the wild-type group (P < 0.05). The levels of protein expression for CCL20 and CCL25 were higher in the wild-type group compared with the FFAR2-/- group (P < 0.05), whereas the wild-type + Ffar2 inhibition group exhibited lower protein expression of CCL20 and CCL25 than the wild-type group (P < 0.05). Ffar2 has a significant regulatory function in the conversion of ILC2s, consequently impacting the immune response in the intestines. Ffar2, a crucial receptor for metabolites produced by the intestinal flora, plays a vital function in controlling the conversion of ILC2s and the overall immune response in the intestines.

The influence on the structure and allergenicity of milk β-lactoglobulin by methylglyoxal during thermal processing

This study aims to investigate the effects of the typical glycation intermediate methylglyoxal (MGO) on the structure and allergenicity of milk β-lactoglobulin (βLG) during thermal processing. Structural changes were assessed using SDS-PAGE, intrinsic fluorescence, circular dichroism, and HPLC-MS/MS. Allergenicity was evaluated through in vitro and in vivo experiments. The conformational changes of βLG significantly were induced by MGO during heat treatment, with a 41.3% decrease in α-helix content and a 25.4% increase in random structure. Furthermore, the lysine, arginine, aspartic acid, and histidine residues in βLG were modified by MGO, which may disrupt or mask allergenic epitopes. Additionally, MGO treatment resulted in a reduction of 41.1% and 26.8% in the pro-inflammatory mediators histamine and β-hexosaminidase in KU812 cells, respectively. Additionally, cytokine levels of IL-4 and IL-13 were reduced by 26.3% and 21.75%, respectively. In mouse experiments, compared to the βLG group, the MGO-βLG group showed a 2–4 fold decrease in IgE, IgG, and IgG1 levels. After reacting with βLG, MGO can reduce serum histamine release by up to 73.9% and mast cell protease-1 (MCP-1) release by 40.8%. These results indicate that the typical glycation intermediate MGO can modify the allergenic epitopes of milk βLG during thermal processing, thereby affecting its allergenicity. This study provides a reference for elucidating the natural rules of allergenicity changes during milk thermal processing.

Investigation of Folate-Functionalized Magnetic-Gold Nanoparticles Based Targeted Drug Delivery for Liver: In Vitro, In Vivo and Docking Studies.

Magnetic nanoparticles used for targeted drug administration present a promising approach in cancer treatment owing to its notable advantages, such as targeted and enhanced encapsulation ability and improved bio protection compared with conventional drug delivery methods. Au shell-iron core nanoparticles (Fe3O4@Au) were manufactured by a chemical process, coated with dextran to encapsulate curcumin, and functionalized for precision drug delivery using folic acid to combat liver cancer. Dynamic light scattering, scanning electron microscopy, transmission electron microscopy, vibrational spectroscopy, and magnetometry were applied to assess the synthesis of the Fe3O4@Au-DEX-CU-FA compound. The mean size, zeta potential, and polydispersity of Fe3O4@Au-DEX-CU-FA were 63.3 ± 2.33 nm, -68.3 ± 1.78 mV, and 0.041 ± 0.008, respectively. Molecular docking models were created to examine the relationship between Fe3O4@Au-CU and BCL-XL, BAK, and to identify potential binding sites. The loading efficiency and release profile tests examined the medication delivery system's ability. MTT assay was subsequently utilized to determine the optimal dosage and therapeutic efficacy of Fe3O4@Au-DEX-CU-FA on cancer SNU-449 and healthy THLE-2 cell lines. Flow cytometry demonstrated that Fe3O4@Au-DEX-CU-FA effectively induced cancer cell death. Fe3O4@Au-DEX-FA showed a regulated release profile of free curcumin at 37 °C and pH values of 7.4 and 5.4. Real-time PCR revealed increased BAK expression and decreased BCL-XL expression. Nude tumor-bearing mice were used for in vivo experiments. Fe3O4@Au-DEX-CU-FA treatment dramatically reduced the swelling size compared with free CU and control treatments. It also resulted in a longer lifespan, expanded splenocyte proliferation, increased IFN-γ levels, and decreased IL-4 levels. The regular cells showed no cytotoxic effect compared with the cancer type, confirming that Fe3O4@Au-DEX-CU-FA maintained its potent anticancer actions. The data suggests that Fe3O4@Au-DEX-CU-FA possesses a promising potential as a therapeutic agent for combating tumors.

Clinical characteristic, laboratory biomarkers, treatment regimen and psychiatry problems predictors of outcomes of alopecia areata: a prospective study

Background Alopecia areata (AA) has multiple aetiology such as genetic and environmental triggers. Aims To assess the recovery rate of AA and examine the associated psychiatric problems. Additionally, the relationship between clinical, psychiatric, and laboratory biomarkers and alopecia outcomes were investigated, along with potential risk factors that could aid in treating alopecia. Patients and methods A prospective cohort research included 42 AA patients and 45 healthy controls. Group A (active disease), group B (inactive disease), and group C (healthy control) were based on illness outcomes after 3 months of treatment. The Severity of Alopecia Tool (SALT), treatment regimens, laboratory investigation Interleukins 19 and 33 (IL-19 and IL-33), Symptom Checklist 90, and post-traumatic stress disorder Checklist for DSM-5 (PCL-5) were evaluated. Results After 3 months of therapy, the incidence of inactive AA was found to be 57.14%. Being females with family history of dermatitis were highly related with active illness, while smoking and unmarried patients were associated with inactive disease. After 3 months of treatment, active illness had the highest mean IL-33 and IL-19 levels. Conclusion The active disease group exhibited the highest mean IL-33 and IL-19 levels at baseline following three months of treatment. Our patients had 7.1% somatization, 7.1% obsessive-compulsive symptoms, 4.8% depression, 4.8% anxiety, 15.9% anger-hostility, 35.7% phobic-anxiety, 26.2% paranoid ideation, 4.8% psychoticism, and 61.9% post-traumatic stress disorder. AA outcomes were linked to females, a family history of dermatological disorders, smoking, being single, and higher mean IL-33 and IL-19 levels. Psychosis was highly linked with active AA. Only khellin and Ultraviolet A improved AA results.