Levels Of IL-12p70 Research Articles

Sex-specific functional effect of IL-12 gene polymorphisms in brain tumours

The role of the IL-12 family cytokines in brain tumourigenesis is an active area of research, but only a few studies have explored the impact of the functional IL12B polymorphisms on brain tumour (BT) risk. The present study aimed to evaluate the possible impact and functional effect of IL12B rs3212227 and rs17860508 on BT susceptibility in adults. We observed a lower frequency of the C-allele variant of the rs3212227 polymorphism among cases with primary BT compared to those with brain metastasis (BrM) and individuals with no benign or malignant tumours under allelic and dominant genetic models. The frequency of the C-allele of rs3212227 was significantly lower in primary BT cases than in controls (16% vs. 26.5% with OR = 0.529, 95%CI: 0.3–0.94, p = .029; ORadjusted=0.442; 95%CI: 0.23–0.87; p = .018). There was no significant association between rs17860508 and BT risk under all analysed genetic models after age and sex adjustment. A significantly higher IL-12p40 serum level in men with primary BT than in women (p = .0007) was found. We observed a sex-specific effect of rs3212227 polymorphism on serum IL-12p40 levels in cases with primary BT in contrast to BrM. The C-allele carriership was associated with higher IL-12p40 in women with primary BT. Serum levels of IL-23 were similar across the patients’ subgroups. The obtained results suggest that the IL12B rs3212227 polymorphism influences the risk for primary BT in contrast to rs17860508 polymorphism and shows a sex-specific functional effect on IL-12p40 levels. Also, the male gender was associated with higher IL-12p40 in cases with primary BT.

Abstract 6650: Macrophage pro-inflammatory phenotype skewing by the application of tumor treating fields (TTFields)

Abstract Introduction: Tumor Treating Fields (TTFields) are low intensity electric fields that disrupt cellular processes critical for cancer cell viability. TTFields have previously been shown to induce immunogenic cell death, promote dendritic cell maturation, and elicit a systemic anti-cancer immune response in preclinical models. The benefit of applying TTFields together with immune checkpoint inhibitors (ICI) was demonstrated in a phase 3 study in non-small cell lung carcinoma. In the current research, we investigated possible effects of TTFields on regulation of macrophage phenotype. Methods: Bone marrow-derived macrophages (BMDMs) were generated from the femurs and tibias of 5-8-week-old Balb\C mice. LPS+IFN-γ or IL-4 were applied to the BMDMs to induce polarization (M1 and M2, respectively). The BMDMs were then treated with TTFields (150 kHz, 24 h), and then examined by flow cytometry for surface expression of the macrophage biomarker F4/80 and the activation markers CD80, major histocompatibility complex class II (MHC II), inducible nitric oxide synthase (iNOS), CD206, and ARG-1. Cell supernatants were collected and analyzed by multiplexed secretion assay for secretion levels of CXCL1 (KC), IL-18, IL-23, IL-12p70, IL6, TNF-α, IL-12p40, TGF-β1, CCL22 (MDC), IL-10, IL-6, G-CSF, CCL17 (TARC), and IL-1β. Cell lysates were examined using a RhoA activation kit and Western blot to determine GEF-H1, c-Jun, and p65 phosphorylation levels. Results: BMDMs exposed to TTFields demonstrated elevated expression of the pro-inflammatory M1 markers CD80+ and MHC IIhigh, and decreased expression of the M2 markers CD206 and ARG-1. A pro-inflammatory secretion pattern was detected, with increased levels of CXCL1, IL-18, IL-23, IL-12p70, TNF-α, IL-12p40, CCL22, G-CSF, CCL17 and IL-1β. The treated cells further demonstrated RhoA activation and GEF-H1 phosphorylation, with subsequent activation of the transcription factors c-Jun and p65. Conclusions: This study reveals a novel immunomodulatory role for TTFields, promoting in vitro pro-inflammatory polarization of macrophage. Citation Format: Tal Kan, Yiftah Barsheshet, Boris Brant, Tharwat Haj Khalil, Tali Voloshin, Alexandra Volodin, Lilach Koren, Bella Koltun, Anat Klein-Goldberg, Efrat Zemer-Tov, Rom Paz, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti. Macrophage pro-inflammatory phenotype skewing by the application of tumor treating fields (TTFields) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6650.

Changes in Serum IL-12 Levels following the Administration of H1-Antihistamines in Patients with Chronic Spontaneous Urticaria.

Research regarding the role of the IL-12 cytokine family in modulating immune and inflammatory responses is continuously evolving. In this study, the contribution of the p35 and p40 subunits as monomers (noted as IL-12p35 and IL-12p40) and heterodimers (noted as IL-12p70 or IL-12p35/p40) was analysed in the pathophysiology and progression of chronic spontaneous urticaria (CSU). We conducted a longitudinal, case-control study involving 42 CSU cases and 40 control cases comprising adults without associated conditions. Serial measurements were performed to assess the serum levels of IL-12p70, IL-12p35, and IL-12p40 at the onset of the disease (pre-therapy phase) and 6 weeks after the initiation of the treatment (post-therapy phase). During the pre-therapeutic phase of CSU, elevated serum levels of IL-12 cytokine subtypes were detected compared to the control group. The relationship between IL-12 profiles and the course of CSU highlighted the pro-inflammatory role of IL-12p70 and the anti-inflammatory role of IL-12p35. Significant correlations were observed between IL-12p70 levels and the duration of the disease, as well as between IL-12 and the effectiveness of H1-antihistamines. The molecular background for the pleiotropic activities mediated by IL-12-derived cytokines in patients with CSU lies in the strict regulation of the production, signalling pathways, and cytokine-specific influences on the same pathophysiological events. The results of the present study suggest that the superficial layers of the skin serve as a cellular source of IL-12, a cytokine produced through antigenic stimulation. In patients with CSU, we identified independent, additive, or divergent functions of IL-12p70, IL-12p35, and IL-12p40, all relevant to systemic inflammation. These findings prove that the prototype programming of IL-12 is abnormal in CSU.

Cytokine secretion in stem cells of cattle infected with bovine leukaemia virus.

Bovine leukaemia virus (BLV) is a Deltaretrovirus responsible for enzootic bovine leukosis, the most common neoplastic disease of cattle. It deregulates the immune system, favouring secondary infections and changes in the blood and lymphatic tissues. Blood homeostasis depends on functional haematopoietic stem cells (HSCs). Bone marrow is populated by these cells, which express CD34+ and CD35+ surface antigens and produce and release cytokines involved in the maintenance of haematopoiesis. The aim of the study was determination of the profile of cytokine production by CD34+ stem cells of cattle naturally infected with BLV. The HSCs were generated from the blood and lymphoid organs of cows infected with BLV and healthy control cows with immunomagnetic separation and anti-CD34+ monoclonal antibodies. Isolated CD34+ cells were cultivated for two weeks with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. The levels of IL-6, IL-10, IL-12p40, IL-12p70, interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α) were determined in culture fluid by flow cytometry. The expression of IL-6, IL-12p70 and TNF-α in blood HSCs was higher in BLV+ cows than in the control animals. In bone marrow HSCs of infected cows, IL-12, TNF-α and IFN-γ were more concentrated, but in these cows' spleen HSCs only expression of IL-10 was elevated. In HSCs isolated from the lymph nodes of leukaemic cows, only TNF-α secretion was lower than in control cows, the other cytokines being more potently secreted. Infection with BLV caused statistically significant differences in cytokine expression by HSC CD34+ cells.

Study on the correlation between IL-12p70, IL-17A and migraine in children.

To compare the serum levels of 12 cytokines in migraine group, encephalitis with headache symptoms group, pneumonia without headache symptoms group and migraine subgroups to explore the cytokines associated with migraine in children and their levels. A total of 44 children with migraine, 27 children in the encephalitis group with headache symptoms and 44 children in the pneumonia group without headache symptoms were selected from January 2022 to August 2023 in Hebei Children's Hospital. They were all tested for serum cytokines by immunofluorescence assay. The migraine group was further divided into subgroups according to different age, gender, course of disease, and presence of coinfection. The differences of serum cytokine levels among the above groups were compared, and the correlation analysis was carried out. Except IL-5, there were no significant differences in the expression levels of other 11 inflammatory cytokines between migraine subgroups. Compared with encephalitis with headache symptoms group and pneumonia without headache symptoms group the serum levels of IL-4, TNF-α, IL-17A, and IL-12p70 were higher in migraine group than in pneumonia group, and the levels of IL-12p70 were higher than those in encephalitis group (p < 0.05). An increase in serum IL-12p70 (OR = 1.267, 95%CI 1.054-1.523, p = 0.012) and IL-17A (OR = 1.066, 95%CI 1.016-1.119, p = 0.010) levels had a significant effect on migraine. Elevated serum levels of IL-12p70 and IL-17A may increase the risk of migraine in children, which has certain diagnostic and predictive value.

Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV.

Understanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants. We used flow cytometry to measure T cell responses following PBMC stimulation with peptide pools representing beta, delta, wild-type, and HCoV-NL63 spike proteins. Luminex bead assay was used to measure circulating plasma chemokine and cytokine levels. ELISA and MSD V-PLEX COVID-19 Serology and ACE2 Neutralization assays were used to measure humoral responses. Regardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4+ T cell responses to both HCoV-NL63 and SARS-CoV-2 than HIV-uninfected individuals. PLWH also had higher proportions of functionally exhausted (PD-1high) CD4+ T cells producing fewer proinflammatory cytokines (IFNγ and TNFα) and had elevated plasma IL-2 and IL-12(p70) levels compared to HIV-uninfected individuals. HIV status didn't significantly affect IgG antibody levels against SARS-CoV-2 antigens or ACE2 binding inhibition activity. Our results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous.

Serum levels of PDGF-CC as a potential biomarker for the diagnosis of Kawasaki disease

BackgroundKawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that predominantly affects children, and no specific diagnostic biomarkers for KD are available. Platelet-derived growth factor CC (PDGF-CC) is a peptide with angiogenic properties that has been amply demonstrated to play a critical role in the cardiovascular system. This study aimed to investigate the serum expression of PDGF-CC in children with KD and to evaluate the ability of PDGF-CC to diagnose KD.MethodsA total of 96 subjects, including 59 KD patients, 17 febrile controls (FC), and 20 healthy controls (HC), were enrolled. Serum levels of PDGF-CC were measured via enzyme-linked immunosorbent assay. The associations between PDGF-CC and clinical laboratory parameters were investigated by correlation analysis. The diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis.ResultsSerum PDGF-CC levels in the KD group were significantly higher than in the FC and HC groups. Serum PDGF-CC levels in the KD group were positively correlated with white blood cell counts, percentage of neutrophils, IL-2, IL-12p70, TNF-α, and IL-1β levels, and negatively correlated with the percentage of lymphocytes. In the analysis of ROC curves, the area under the curve was 0.796 (95% confidence interval 0.688–0.880; P < 0.0001) for PDGF-CC and increased to 0.900 (95% confidence interval 0.808–0.957; P < 0.0001) in combination with white blood cell counts and C-reactive protein.ConclusionsPDGF-CC is a potential biomarker for KD diagnosis, and the combination with white blood cell counts and C-reactive protein can further improve diagnostic performance.

Microwave ablation enhances the systemic immune response in patients with lung cancer.

Microwave ablation (MWA) is a key alternative therapy to conventional surgery for the treatment of lung cancer. In addition to eliminating local tumors, MWA may promote antitumor immunological responses, such as abscopal effects in distant lesions. However, the intensity of MWA is limited and the underlying mechanisms are not well-defined. The present study assessed the impact of MWA on immune cell subsets and cytokines in patients with lung cancer. A total of 45 patients with lung cancer who underwent percutaneous lung tumor MWA were enrolled. Peripheral blood samples were collected before and 24 h after MWA and changes in immune cell subsets [lymphocytes, CD3+, CD4+ and CD8+ T cells, B cells and natural killer (NK) cells] and serum cytokine levels (IL-1β, IL-2, IL-4-6, IL-8, IL-10, IL-12p70, IL-17A and F, IL-22, TNF-α, TNF-β and IFN-γ) were assessed by flow cytometry and ELISA. The number of total lymphocytes, CD4+ T and NK cells in the peripheral blood significantly decreased 24 h after MWA, while number of CD8+ T cells remained stable, leading to a higher proportion of CD8+ T cells. In addition, the serum levels of IL-2, IL-1β, IL-6, IL-12p70, IL-22, TNF-α and IFN-γ were significantly increased 24 h after MWA, indicating a T helper 1 type immune response. The immune response in patients with advanced stage disease was comparable with patients in the early stage group; however, the number of total lymphocytes and CD3+ T cells significantly decreased and the ratio of CD4/CD8 and IL-2 levels significantly increased. The early immune response after MWA may contribute to systemic antitumor immunity in patients with both early and advanced disease. Thus, MWA may exhibit potential as a local therapy and trigger abscopal effects in distant lesions in patients with lung cancer.

Association of CC-chemokine ligand-2 gene polymorphisms with leprosy reactions

BackgroundC–C motif chemokine ligand 2, a gene that codes for a protein involved in inflammation. Certain SNPs in the CCL2 gene have been studied for their potential associations with susceptibility to various diseases. These SNPs may affect the production and function of the CCL2 protein, which is involved in the recruitment of immune cells to the site of inflammation. Variations in CCL2 may influence the immune response to Mycobacterium leprae infection. ObjectiveTo investigate the association of the C–C motif chemokine ligand-2 single nucleotide polymorphisms with leprosy. MethodsCCL2 single nucleotide polymorphisms were analyzed in a total of 975 leprosy patients and 357 healthy controls. Of those, 577 leprosy and 288 healthy controls were analyzed by PCR-RFLP for CCL2 -2518 A>G, 535 leprosy and 290 controls for CCL2 -362 G>C, 295 leprosy and 240 controls for CCL2 -2134 T>G, 325 leprosy and 288 controls for CCL2 -1549 A>T SNPs by melting curve analysis using hybridization probe chemistry and detection by fluorescence resonance energy transfer (FRET) technique in Realtime PCR. The levels of CCL2, IL-12p70, IFN-γ, TNF-α, and TGF-β were estimated in sera samples and correlated with CCL2 genotypes. ResultsThe frequency of the GCT (-2518 A>G, -362 G>C, -2134 T>G) haplotype is observed to be higher in leprosy patients compared to healthy controls (P = 0.04). There was no significant difference observed in genotypic frequencies between leprosy patients and healthy controls {(-2518A>G, p = 0.53), (-362 G>C, p = 0.01), (-2134 T>G, p = 0.10)}. G allele at the -2134 site is predominant in leprosy (borderline) without any reaction (8 %) compared to borderline patients with RR reactions (2.1 %) (P = 0.03). GG genotype (p = 0.008) and G allele at -2518 (p = 0.030) of the CCL 2 gene were found to be associated with patients with ENL reaction. An elevated level of serum CCL2 was observed in leprosy patients with the -2518 AA and AG genotypes (p = 0.0001). ConclusionsG allele and GG genotype at the CCL2 -2518 site are associated with a risk of ENL reactions.

Deletion of IL-27p28 induces CD8 T cell immunity against colorectal tumorigenesis

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, characterized by molecular and clinical heterogeneity. Interleukin (IL)-27, a heterodimeric cytokine composed of p28 and EBI3 subunits, has been reported to exert potent antitumor activity in several cancer models. However, the precise role of IL-27 in the pathogenesis of CRC remains unclear. Here, we show that during the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC development, IL-27p28 levels are dramatically increased in peripheral blood and tumor tissues, and the cytokine is mainly produced by tumor-infiltrating myeloid cells. IL-27p28 deficient mice display tumor resistances in both inflammation-associated CRC model and syngeneic MC38 colon cancer model. Administration with IL-27p28 neutralizing antibody also reduces the tumor formation in AOM/DSS-treated mice. Mechanically, CD8+ T cells in IL-27p28-/- mice exhibit enhanced tumor infiltration and cytotoxicity, which can be largely attributed to activation of the Akt/mTOR signaling pathway. Furthermore, selective depletion of CD8+ T cells in IL-27p28-/- mice markedly accelerate tumor growth and almost abrogate the protective effects of IL-27p28 deficiency. Most interestingly, the expression of IL-27p28 is also upregulated in tumor tissues of CRC patients and those with high expression of IL-27p28 tend to have a poorer overall survival. Our results suggest that loss of IL-27p28 suppresses colorectal tumorigenesis by augmenting CD8+ T cell-mediated anti-tumor immunity. Targeting IL-27p28 could be developed as a novel strategy for the treatment of colorectal cancers.

Association of lymphocyte subsets and cytokines with bone metabolism: a retrospective, cross-sectional study

BackgroundPrevious research has shown that lymphocytes and cytokines can mediate bone metabolism. This study explored the clinical association and predictive ability of lymphocytes and cytokines levels for bone metabolism.MethodsA total of 162 patients were enrolled in this study. The levels of N-terminal propeptide of type I procollagen (P1NP), β-collagen degradation product (β-CTX), total T lymphocytes, immature T lymphocytes, suppressor/cytotoxic T lymphocytes, helper/inducer T lymphocytes, B lymphocytes, natural killer (NK) cells, Interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), IFN-α, interleukin-1 beta (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and IL12p70 were evaluated. The relationship between these lymphocyte subsets and cytokines with bone metabolic status was examined and their predictive ability for bone metabolic status was assessed.ResultsThe principal component analysis (PCA) and correlation analysis results varied on differences in lymphocyte subsets and cytokines in various bone metabolism states. Differential analysis revealed significant differences in the absolute counts of B lymphocytes (P < 0.05), level of IL-12p70 (P < 0.05), and IL-8 (P < 0.001) at different P1NP levels. Significant differences were observed in the absolute counts of total T lymphocytes (P < 0.05), B lymphocytes (P < 0.05), the level of IL-6 (P < 0.05), the percentage of B lymphocytes (P < 0.01), and NK cells (P < 0.05) at different β-CTX levels. Furthermore, the receiver operating characteristic (ROC) curve showed that the absolute count of B lymphocytes and levels of IL-12p70 and IL-8 could be used to evaluate bone formation states, while the absolute counts of T and B lymphocytes, level of IL-6, and percentages of NK cells and B lymphocytes could be used to evaluate bone resorption states.ConclusionThe bone metabolism status changed based on the lymphocyte subsets and cytokine levels. Differentially expressed lymphocytes and cytokines could be used to distinguish bone metabolism status.

Association of serum levels of inflammatory cytokines with retinopathy of prematurity in preterm infants.

Retinopathy of prematurity (ROP) is a retinal vascular developmental disease associated with risks factors such as supplementary oxygen use or low birth weight/early gestational age. Multiple studies have reported associations between ROP and systemic inflammation. In this study, we investigated serum cytokines associated with ROP development and severity and assessed their applicability as potential biomarkers of ROP. This prospective study was conducted at an institutional referral center between 2019 and 2021. To measure the serum levels of 40 inflammatory cytokines in eligible premature patients, we collected their serum samples during the enrollment of patients or the intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents and after 2 and 4 weeks. Fifty patients were enrolled. In patients with type 1 ROP who received anti-VEGF agents (n = 22), the levels of serum intercellular adhesion molecule-1 decreased significantly (p < 0.05) at 4 weeks compared with the baseline level, whereas those of serum granulocyte-macrophage colony-stimulating factor increased significantly (p < 0.05). In patients with ROP who did not require any treatment (n = 14), no significant change was noted in the level of any of the 40 inflammatory cytokines. In control infants without ROP (n = 14), the serum levels of tumor necrosis factor-α, interleukin (IL)-15, and IL-12p40 increased significantly (p < 0.05) at 4 weeks. The changes in the levels of serum inflammatory cytokines did not vary significantly among the aforementioned three groups. A generalized estimating equation indicated that zone 1 ROP, stage 3 ROP, older postmenstrual age, respiratory distress syndrome, necrotizing enterocolitis, and sepsis were associated with the changes in serum cytokine levels. Although significant changes (compared with baseline) were observed in the serum levels of certain inflammatory cytokines in patients with type 1 ROP and infants without ROP, no significant difference in cytokine level fluctuations were noted among the three groups. Changes in serum inflammatory cytokine levels may not predict ROP development or severity. Additional comprehensive studies are warranted to establish their definitive role and significance in ROP, emphasizing the need for continued research in this area.

Influence of lactoferrin and enzymatiс hydrolysates of cow's and mare's milk proteins on anaphylactic sensitivity and cytokine profile of rats

The development of innovative ingredients of specialized formula for children with intolerance to cow's milk proteins requires accounting the influence of the protein component on the allergic sensitivity. The aim of the research was to study the effect of lactoferrin (LF) from cow colostrum, cow's milk protein hydrolysate (CMPH) and mare's milk protein hydrolysate (MMPH) on the severity of the systemic anaphylaxis reaction, the levels of specific IgG antibodies and cytokines in rats parenterally sensitized with ovalbumin (OVA). Material and methods. The experiment was carried out on 4 groups of 26 male Wistar rats, which were sensitized intraperitoneally with chicken egg OVA and a systemic anaphylaxis reaction was induced on the day 29 by intravenous administration of a challenge dose of the antigen (6 mg per kg body weight). LF, CMPH and MMPH were introduced into the diet in doses of 1.4-2 g/kg body weight per day (on an average 1.59±0.04, 1.53±0.05 and 1.48±0.05 g per kg body weight respectively). The content of IgG antibodies in the blood serum was determined by an indirect ELISA; the levels of cytokines IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12(p70), IL-13, GM-CSF, IFN-γ and TNF-α were detected by multiplex immunoassay. Results. Dietary LF did not have a significant effect on the severity of active anaphylactic shock (AAS), concentrations of antibodies and cytokines in the blood of animals. As a result of CMPH consumption, there were no significant changes in AAS severity and IgG antibodies to OVA but significant increase in TNF-α level was observed as well as a significant decrease in IL-1α (p<0.05). In animals receiving MMPH, there were also no significant changes in the severity of AAS, but a 1.9-fold decrease in the level of IgG antibodies to OVA (p<0.001) was noticed along with a significant increase in IL-12(p70) (p<0.05) and IL-10 (p<0.10) level. Conclusion. Cosumption of LF by sensitized rats didn't significantly affect their anaphylactic sensitivity and cytokine profile, while CMPH intake induced some signs of pro-inflammatory processes. Consumption of MMPH was accompanied by the formation of an anti-inflammatory cytokine profile, which corresponds to a decrease in the intensity of the humoral immune response to the model allergen. Differences in the effects of two hydrolisates, which have similar degrees of hydrolysis, may be associated with the specific composition of glycopeptides formed during the enzymatic cleavage of milk protein produced by these two species of dairy animals.

Phytochemical analysis and in vitro investigation of wound healing, cytotoxicity, and inflammatory response in potentially active extracts of Anogeissus dhofarica

The traditional medicine plant Anogeissus dhofarica is only found in the Jabal Fartak region of Yemen and the Dhofar region of Oman. This plant has been used traditionally for medical purposes to treat wounds, skin tanning, and sores. People use it as an antiseptic, especially women. However, this plant has not been studied in great detail, and there is no scientific proof to back up its traditional uses of it. The goal of this study was to examine the biological properties and phytochemical analysis of various extracts made from A. dhofarica leaves. The powdered leaves of A. dhofarica were extracted using the solvents ethanol (A1), methanol (A3), acetone (A5), and ethyl acetate (A8), yielding concentrations of 3, 0.3, and 0.03 mg/ml, respectively. The total phenolic and flavonoid contents, as well as the active phytochemicals, were determined using standard methods. The proliferation potential and IC50 of human dermal fibroblasts were evaluated. Cytotoxicity, wound healing activity, and the inflammatory response to the extracts were all investigated. Our results revealed that the IC50 values for plant extracts A1, A3, A5, and A8 were 9.799 ± 0.07, 5.83 ± 0.9, 8.8 ± 0.12, and 3.98 ± 0.8 mg/ml, respectively. Moreover, the cytotoxic effect of plant extracts was observed at high concentrations (p &lt;0.05). However, the lower concentration showed the least cytotoxic effect. For the inflammatory response, the secretion levels of IL-1β, IL-6, TNF-α, IL-8, and IL-12p70 were upregulated, and IL-10 was downregulated significantly (p &lt; 0.05) compared to the control. For wound healing activity, 0.3 and 0.03 mg/ml of (A8) extract and 0.03 mg/ml of (A3) and (A5) extracts showed complete closure of the scratch after 72 hours of treatment. In this study, we noticed that A. dhofarica plant extracts with a lower concentration are the most effective at healing wounds and have a minimal cytotoxic effect.

Interleukin-4 and Interleukin-17 are associated with coronary artery disease.

The present study aimed to examine the correlation between serum cytokine levels and the incidence of coronary artery disease (CAD), a leading cause of mortality globally, which is known to have a strong association with inflammatory factors. The study further sought to determine the predictors of CAD to distinguish patients with coronary artery lesions from those suspected of having CAD. In this study, 487 patients who underwent coronary angiography as a result of suspected CAD but without acute myocardial infarction (AMI) were recruited. The serum levels of the cytokines interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-α, interferon (IFN)-α, and IFN-γ were measured using a multiplexed particle-based flow cytometric assay technique. The results of the study revealed that the levels of IL-4, IL-12p70, IL-17, IFN-α, and IFN-γ in the CAD group were significantly lower compared to those in the non-CAD group. Multivariate logistic regression analysis indicated that two serum cytokines (IL-4 and IL-17), one protective factor (high-density lipoprotein cholesterol [HDL-C]), and three risk factors (sex, smoking, and diabetes) were independently predictive of CAD. The receiver operating characteristic curve analysis showed that the combined use of these predictors in a multivariate model demonstrated good predictive performance for CAD, as evidenced by an area under the curve value of 0.826. The results of the study indicated that serum IL-4 and IL-17 levels serve as independent predictors of CAD. The risk prediction model established in the research, which integrates these serum cytokines (IL-4 and IL-17) with relevant clinical risk factors (gender, smoking, and diabetes) and the protective factor HDL-C, holds the potential to differentiate patients with CAD from those suspected of having CAD but without AMI.

Treatment with Viscum album potencies induces reduction of MCP-1 and ROs levels in murine melanoma cells.

Melanoma is responsible for most skin cancer deaths. It has a high metastatic potential, complex treatment, and a hopeless prognosis. Viscum album extract (Va) is a complementary treatment in cancer, with in vitro and in vivo cytotoxic effects on different tumor types. However, its ultra-diluted homeopathic preparations' effects and mechanisms on cancer cells need further study. Thus, the aim of present work was to investigate cytokine profile and ROs production of melanoma cells after treatment with ultradiluted VA collected from host tree Abies alba (VaAa) and Quercus rubur (VaQr)during Swiss summer. For this, potencies of Va in different homeopathic scales were prepared using mother tincture (MT) from VaAa and VaQr submitted to homeopathic ethanolic maceration and then a subsequent dynamization process. Then, B16F0 melanoma cells cultivated in 24-well plates were treated with MT or 12DH, 200CH or 5LM potencies of VaAa or VaQr for 24, 48 or 72 hours. After these periods, culture supernatants were collected to assess the levels of MCP-1, INF-γ, TNF-α, IL-10, IL-12p70 and IL-6 cytokines and, ROs production. Results demonstrated significant reduction of MCP-1 and ROs levels in B16F10 melanoma cells treated with Va (VaQr, preferentially) at 12DH or 5LM potencies when compared to untreated or carboplatin-treated cells. In conclusion, we demonstrated for the first time, the in vitro effects of Va potencies prepared in different homeopathic scales in relation to cytokines and ROs production in cell melanoma cells.

Peculiarities of cytokine and chemokine content in blood serum of children with psoriasis vulgaris

Psoriasis is a chronic auto-inflammatory skin disease with a hereditary predisposition due to the activation of T-lymphocytes and the synthesis of pro-inflammatory cytokines. The pathogenesis involves populations of Th1 and Th17 lymphocytes that produce TNFa, IFNy, IL-17, IL-21 and IL-23. The aim of the study was to identify the features of the content of cytokines and chemokines in the blood serum of children with psoriasis. 88 children with psoriasis of varying severity were examined. The level of circulating cytokines was determined by the multiplex method on the Bio-plex 200 device using the MILLIPLEX MAP Human Th17 kit. In children with psoriasis, increased levels of IL-23, IL-22, IL-12p70, IL-27, IL-17E, IL-17F and TNFa were detected. The consistency of the functioning of the cytokine network in children with psoriasis was shown, which was expressed in the high strength of the connection between cytokines of the IL-17 family and cytokines of the IL-12 family, between IL-31 and IL-33, as well as in significant correlations between GM-CSF and cytokines IL-2, IL-5, IL-9, IL-10, IL-15 and TNFa. In children with psoriasis, the dependence of the level of IL-17A, TNFa, IL-2, IL-6, IL-9, CCL20/MIP3a with the severity of the disease according to PASI was revealed. The study confirmed the pathogenetic role of the cytokine network in the development and maintenance of an inflammatory response in children with psoriasis. The data obtained substantiate the need for targeted anti-cytokine therapy. The level of proinflammatory cytokines in children with psoriasis can be used as an additional laboratory criterion for the severity of the condition and monitoring the effectiveness of therapy.

Higher Nrf2 Level is Correlated with Metabolic Parameters in Type 2 Diabetes Mellitus

BACKGROUND: Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder associated with oxidative stress and chronic inflammation. Understanding the regulatory mechanisms related to the role of nuclear factor erythroid 2 (Nrf2), a master regulator of cellular antioxidant defenses, in individuals with T2DM, is essential. Therefore, in-depth investigation regarding the associations between Nrf2 levels, and metabolic parameters, such as waist circumference, fasting glucose levels, HbA1C, and serum inflammatory markers expressions is needed to elucidate the mechanisms driving T2DM and its metabolic disturbances.METHODS: This was a cross-sectional study including 90 T2DM and 25 healthy subjects. Nrf2 level; serum inflammatory markers levels, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-α2, IFN-g, monocyte chemoattractant protein (MCP)-1, IL-10, IL-12p70, IL-17A, IL-18 and IL-23; as well as waist circumference; fasting glucose levels; and HbA1C were measured. Nrf2 concentrations in peripheral blood mononuclear cells were determined using enzyme-linked immunosorbent assay (ELISA), while serum inflammatory markers concentrations were quantified with flowcytometry.RESULTS: Nrf2, TNF-α, and IL-17A levels were significantly higher in the T2DM group, while IL-1β, IFN-α 2, IL-10, IL-12p70, and IL-23 levels were elevated in healthy controls Nrf2 exhibited positive correlations with waist circumference, fasting glucose, HbA1C, and TNF-α. Conversely, an inverse correlation of Nrf2 was observed with IL-1β, IL-12p70 and IL-17A.CONCLUSION: Correlations between Nrf2 and metabolic clinical parameters suggest its role in regulating glucose metabolism and adiposity. Elevated Nrf2 levels observed in T2DM patients may present novel therapeutic avenues for enhancing endogenous antioxidant defenses.KEYWORDS: type 2 diabetes mellitus, Nrf2, oxidative stress, inflammation, metabolic regulation, therapeutic strategies

Unveiling COVID-19 Secrets: Harnessing Cytokines as Powerful Biomarkers for Diagnosis and Predicting Severity.

In coronavirus disease (COVID-19), inflammation takes center stage, with a cascade of cytokines released, contributing to both inflammation and lung damage. The objective of this study is to identify biomarkers for diagnosing and predicting the severity of COVID-19. Cytokine levels were determined in the serum from venous blood samples collected from 100 patients with COVID-19 and 50 healthy controls. COVID-19 patients classified based on the Modified Early Warning (MEWS) score. Cytokine concentrations were determined with a multiplex ELISA kit (Bio-Plex Pro™ Human Cytokine Screening Panel). The concentrations of all analyzed cytokines were elevated in the serum of COVID-19 patients relative to the control group, but no significant differences were observed in interleukin-9 (IL-9) and IL-12 p70 levels. In addition, the concentrations of IL-1α, IL-1β, IL-1ra, IL-2Rα, IL-6, IL-12 p40, IL-18, and tumor necrosis factor alpha (TNFα) were significantly higher in symptomatic patients with accompanying pneumonia without respiratory failure (stage 2) than in asymptomatic/mildly symptomatic patients (stage 1). The study revealed that IL-1ra, IL-2Rα, IL-6, IL-8, IL-12 p40, IL-16, and IL-18 levels serve as potential diagnostic biomarkers in COVID-19 patients. Furthermore, elevated IL-1α levels proved to be valuable in assessing the severity of COVID-19.

Potential Predictive Biomarkers for the Development and Outcomes of Inhibitors in Hemophilia A Patients

Introduction Inhibitor development poses a significant challenge in the treatment of hemophilia A (HA). Approximately 30% of HA patients develop inhibitors in response to FVIII infusion therapy. While the risk is highest early in treatment days, patients are at risk throughout their lifetime. Regardless of certain known risk factors, the lack of biomarkers for inhibitor development hampers efforts to prevent their occurrence. Since inflammation is a well-known risk factor, one of our goals is to identify potential biomarkers among inflammatory cytokines. Another focus is glycosylation-related biomarkers, which has drawn great attention in biomarker discovery of various diseases including cancers. By analyzing the association of cytokines and plasma glycosylation with inhibitor formation, this research aims to provide valuable references for clinical care. Methods Plasma samples from 60 HA patients, and 23 healthy donors were analyzed to detect the levels of G-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL12p70, IP-10 and TNF. The HA samples were divided into inhibitor negative (InhNeg, BU &amp;lt; 0.6, n = 26) and inhibitor positive (InhPos, BU ≥ 0.6, n = 34) groups. A predictive model of inhibitor development was established using logistic regression analysis. To investigate the correlation between cytokine levels and high inhibitor titers, the inhibitor-positive samples were further categorized into good risk (&amp;lt; 10 BU, n = 14) and poor risk (≥ 10 BU, n = 20) groups based on immune tolerance induction therapy prognosis. Total plasma N-glycans were released, methylated, and analyzed by using MALDI-TOF MS/MS. A synthesized N-glycan was spiked in to quantify each glycoform. The study evaluated the correlation between HA sample groups and various glycosylation ratios, including for sialylation, core-fucosylation, galactosylation and galactose. The cut-off value of each glycosylation ratio was based on the median of the inhibitor-negative group. Results The adjusted odds ratio of inhibitor development for elevated G-CSF, IL-6 and decreased IL-10 were 2.84 (95% CI: 1.45-8.48; p = 0.021), 1.50 (95% CI: 1.14-2.42; p = 0.069), and 0.28 (95% CI: 0.10-0.61; p = 0.006), respectively in HA patients. Among InhPos HA patients, the levels of G-CSF, IL-2, IL-6, IL-8, and IL-10 in poor risk group were significantly higher than in good risk group (p-value &amp;lt; 0.05, ANOVA). Since aging also causes glycosylation changes, we analyzed adult (≥ 18 years old, n = 31) and pediatric (&amp;lt; 18 years old, n = 17) HA patients separately. Among analyzed glycan ratios, 80% of adult HA patients with inhibitors had a higher core-fucosylation ratio. All pediatric patients with inhibitors had significant lower sialylation and higher galactosylation ratios. Strikingly, pediatric patients with inhibitors exhibited around 2-fold higher core-fucosylation than those without inhibitor. Conclusion Our finding of elevated levels of G-CSF and IL-6 along with decreased levels of IL-10 associated with the presence of inhibitors, suggests the potential for prediction of inhibitor development. Moreover, high levels of G-CSF, IL-2, IL-6, IL-8 and IL-10 in patients with high inhibitor titers (≥ 10 BU, poor risk group) but not in good risk group imply they could be explored in future studies as prognostic factors in immune tolerance therapy. Glycan ratios can also hold promise as biomarkers including higher core-fucosylation in adult patients. Additionally, significant lower sialyation, higher galactosylation and core-fucosylation ratios indicate higher possibility of inhibitor development in pediatric patients.