Interleukin Research Articles

Analysis of the therapeutic role of stem cells versus selenium nanoparticles in lipopolysaccharide-induced acute lung injury in adult male albino rat: A histological, immunohistochemical and histochemical study

Pharmacological research using Lipopolysaccharide (LPS) is a reliable model of acute lung injury. This study aims to compare the therapeutic efficacy of selenium nanoparticles (SeNPs) and bone-marrow-derived mesenchymal stem cells (BMSCs) against lung damage generated by lipopolysaccharides. Fifty adult male albino rats were employed and divided into 5 groups (control group, shame control group, LPS-treated group, SeNPs-treated group, and BMSCs-treated group). Histological and immunohistochemical staining for tumor necrosis factor-alpha (TNFα), Interleukin 6 (IL-6), and Caspase 3 were carried out and followed by histomorphometric analysis. Histochemical measurements of the oxidative-antioxidative markers, superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were performed in addition to western blotting analysis to detect the antioxidative activity of Nrf2. LPS-treated group showed distorted pulmonary architecture with the upsurge in the caspase-3, TNF-α, IL-6, and MDA along with a significant decrease in GPx, SOD, and Nrf2 in the lung homogenates. These findings were relatively improved after adding SeNPs and stem cells. On comparing BMSCs and SeNPs treated group, there was a significant decrease in caspase-3, TNF-α, and IL-6 with BMSCs treatment relative to SeNPs. Treatment with selenium nanoparticles and BMSCs has improved pulmonary changes through their antioxidant and anti-inflammatory role. The level of pulmonary regeneration exerted by BMSCs is better than selenium nanoparticles so the BMSCs may be given preference for a particular course of treatment.

C-X-C chemokine receptor type 5+CD8+ T cells as immune regulators in hepatitis Be antigen-positive chronic hepatitis B under interferon-alpha treatment

BACKGROUND C-X-C chemokine receptor type 5 (CXCR5)+CD8+ T cells represent a unique immune subset with dual roles, functioning as cytotoxic cells in persistent viral infections while promoting B cell responses. Despite their importance, the specific role of CXCR5+CD8+ T cells in chronic hepatitis B (CHB), particularly during interferon-alpha (IFN-α) treatment, is not fully understood. This study aims to elucidate the relationship between CXCR5+CD8+ T cells and sustained serologic response (SR) in patients undergoing 48 weeks of pegylated IFN-α (peg-IFN-α) treatment for CHB. AIM To elucidate the relationship between CXCR5+CD8+ T cells and sustained SR in patients undergoing 48 weeks of peg-IFN-α treatment for CHB. METHODS This study enrolled 60 patients with hepatitis Be antigen (HBeAg)-positive CHB undergoing 48 weeks of peg-IFN-α treatment. Participants were assessed for eligibility based on criteria such as persistent HBsAg-positive status for at least six months, HBeAb-negative, hepatitis B virus DNA levels exceeding 2 × 104 copies/mL, and alanine aminotransferase (ALT) levels between 2 and 10 times the upper limit of normal. Blood samples were collected at baseline and at weeks 12, 24, 48, and a 24-week treatment-free follow-up (week 72) to measure serum interleukin (IL)-21 concentration via ELISA and to analyze CXCR5 and programmed death-ligand 1 (PD-L1) expression on CD8+ T cells by flow cytometry, CXCR5 is a chemokine receptor that directs immune cells to specific tissues, while PD-L1 is a protein that regulates immune responses by inhibiting T cell activity. RESULTS Patients with CHB exhibited significantly lower levels of circulating CXCR5+CD8+ T cells compared to healthy controls (P < 0.01). Notably, CXCR5+CD8+ T cells were prominently expressed in patients who achieved sustained SR compared to non-SR (NSR). A significant correlation was observed between CXCR5 and PD-L1 expression (r = -0.189, P = 0.002). However, there was no significant correlation between serum IL-21 levels and CXCR5+CD8+ lymphocytes (r = -0.03, P = 0.625) or serum ALT levels (r = 0.026, P = 0.678). CONCLUSION The enhanced expression of CXCR5+CD8+ T cells in patients achieving HBeAg seroconversion during IFN-α treatment suggests that these cells play a crucial role in antiviral immune responses against hepatitis B. This study highlights the potential of CXCR5+CD8+ T cells as immune regulators in CHB, which may inform future therapeutic strategies to optimize antiviral treatments.

Analysis of IL10 gene promoter haplotypes and changes in mRNA expression and soluble levels in patients with basal cell carcinoma.

Interleukin-10 (IL-10) is an immunomodulatory molecule that may play an immunosuppressive role in nonmelanoma skin cancer (NMSC), specifically basal cell carcinoma (BCC). We analyzed the role of IL10 promoter variants in genetic determinants of BCC susceptibility and their association with IL10 mRNA and IL-10 serum levels. Three promoter variants (-1082 A > G, -819T > C, and -592 A > C) were examined in 250 BCC patients and 250 reference group (RG) individuals. IL10 relative gene expression was evaluated in total leucocytes in peripheral blood, and IL-10 levels were quantified in serum. The allelic and genotypic frequencies did not show significant differences between the groups. However, haplotype analysis revealed that the ATA haplotype was associated with a decreased risk of BCC (OR: 0.73, 95% CI 0.56-0.95, p = 0.02), whereas the ATC and ACA haplotypes were associated with an increased risk for the neoplasia (OR: 4.15, 95% CI 1.56-11.04, p < 0.01, and OR: 3.51, 95% CI 1.33-9.29, p < 0.01, respectively). BCC patients showed a 0.09-fold reduction in IL10 mRNA expression compared to the RG. Significant differences were in IL-10 median serum levels between the RG and BCC patients (0.4 vs 0.64pg/mL, p = 0.02). Significant median serum differences were also observed between low- and high-grade histopathological BCC (0.34 vs 1.35pg/mL, p = 0.02). The ATA, ATC, and ACA haplotypes, and serum IL-10 levels, could be markers of susceptibility to BCC in Western Mexican individuals. BCC patients had higher serum IL-10 levels than the RG, with levels increasing with the severity of lesions, confirming the role of IL-10 in immunosuppression in neoplasia.

IL-35 modulates Tfh2 and Tfr cell balance to alleviate allergic rhinitis.

Allergic rhinitis (AR) represents a persistent inflammatory condition affecting the upper respiratory tract, characterized by abnormal initiation of the immunoglobulin E (IgE)-mediated cascade. Follicular helper T (Tfh) cells and regulatory T (Tfr) cells are pivotal in orchestrating the development of IgE production in AR patients. IL-35, an anti-inflammatory cytokine, secreted by various cellular subpopulations. To investigate the interplay and underlying mechanisms between interleukin-35 (IL-35) and Tfr/Tfh2 cells in the context of AR. Experimental animal models employing BALB/c mice and IL-35-deficient mice underwent sensitization and challenge procedures utilizing ovalbumin (OVA) as the antigen in vivo. IL-35 was administered intranasally prior to OVA challenges. Nasal histopathological examination, PBMC isolation, Tfr/Tfh2 cell staining, Tfr/Tfh2 sorting and culture, and qPCR analysis as well as enzyme-linked immunosorbent assay (ELISA) were conducted for exploring the effect of IL-35 on Tfr/Tfh2 cells. Administration of IL-35 suppressed OVA-elicited allergic inflammation in murine models. IL-35 treatment led to an elevation in the proportion of peripheral blood Tfr cells and a decrease in Tfh2 cells. IL-35 also downregulated IL-4 and IL-21 protein expression by Tfh2 cells and upregulated IL-10 and transforming growth factor-β (TGF-β) production by Tfr cells. The anti-ICOS treatment abrogated the effect of IL-35 on Tfh2 and Tfr cells. Our study provided novel insights into the mechanisms of IL-35 action and its promoting effects on Tfh2 and inhibiting effects on Tfr cells by targeting key transcription factors, contributing to the understanding of the pathogenesis and treatment of AR.

Pathophysiology and Potential Clinical Significance of Il-5: A Review Article

Interleukins belong to the group of cytokines that play a key role in immune system cell signaling. Among them, Interleukin-5 (IL-5) gains paramount significance in the regulation of eosinophils, which are thinly scattered in most allergic as well as inflammatory conditions, especially asthma. A biochemical characterization of IL-5 is a prerequisite for understanding the basic aspects of its function and finding a precise treatment. Interleukin-5 (IL-5) is a critical cytokine that primarily drives the development and differentiation of eosinophils and B cells, playing a key role in the allergic response and the pathogenesis of asthma. Therefore, the knowledge of its biochemical structure is a prerequisite for any plan to develop targeted therapies for eosinophilia-related diseases. The clinical relevance of interleukins resides in their regulatory capabilities of immune responses, with an ever-growing recognition in diverse pathologies such as allergic manifestations, autoimmune diseases, or neoplastic processes. Interleukins in clinical application should be the focus of research, specifically IL-5, synthesizing observable from the latest related studies and knowledge deficits that should entice future research in the same line. This paper, therefore, gives a review based on already existing research findings concerning the biochemical structure of IL-5.

Biochemistry and Clinical Significance of Il-3: A Review Article

Interleukin-3 (IL-3) is a cytokine of many activities, centrally important for hematopoiesis and regulation of immune responses. It is produced by activated T cells and mast cells with a large influence on blood cell lineage proliferation and differentiation. Given the biochemistry of IL-3, elucidating its role in health and disease—especially immune responses and pathological conditions—is a high priority. Interleukin-3 is a cytokine profoundly important in the regulation of hematopoiesis and immune responses. The ability of this factor to modulate a wide variety of cellular responses serves to underscore its central involvement in almost all physiological as well as pathological processes. In the present article, the authors summarize recent knowledge on the mechanisms by which IL-3 exerts biological effects, with special emphasis placed on receptor signaling, downstream pathways, and functional responses.

Anti-inflammatory and antioxidant properties of Camellia sinensis L. extract as a potential therapeutic for atopic dermatitis through NF-κB pathway inhibition

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and excessive cytokine production. This study aimed to explore the potential of Camellia sinensis L. water extract (CSE) as a treatment for AD by the impact of CSE on inflammatory responses in keratinocytes, particularly concerning the production of inflammatory cytokines and the modulation of signaling pathways relevant to AD pathogenesis. CSE was obtained via hot water extraction from Camellia sinensis L. Ultra-high-performance liquid chromatography (UPLC) analyzed catechin and caffeine content. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), polyphenol and flavonoid content were determined. 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay measured antioxidant activity. Enzyme-Linked Immunosorbent Assay (ELISA), western blotting, and Immunofluorescence (IF) assays examined cytokines, pathways, and protein localization, respectively. Molecular docking assessed compound binding with inflammation-related proteins. UPLC identified six CSE components including epigallocatechin (EGC) epicatechin (EC), caffeine (CF), catechin (C), epigallocatechin gallate (EGCG), and epicatechin gallate (ECG). CSE demonstrated a significant reduction in the production of inflammatory cytokines interleukin (IL)-2 and IL-6 in TNF-α/IFN-γ activated keratinocytes. Treatment with CSE inhibited the mitogen-activated protein kinase (MAPK) pathway, which resulted in decreased phosphorylation of p38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Exposure of TNF-α/IFN-γ- stimulated human keratinocytes (HaCaT) cells to CSE resulted in a 200 µg/mL dependent inhibition of p65 and signal transducer and activator of transcription 1 (STAT-1) translocation from the cytosol to the nucleus, as confirmed through immunofluorescence (IF) staining. Molecular docking simulations provided insights into the underlying mechanisms of CSE action, which supported its potential as a therapeutic agent for AD. CSE might be a potential candidate for its therapeutic efficacy for inflammatory skin conditions like AD. Thus, based on this evidence, the authors suggest that CSE should be studied further for its anti-inflammatory activities and topical application in the treatment of AD.

Enhancing growing rabbit heat stress resilience through dietary supplementation with natural antioxidants

Animal husbandry development is influenced by various factors, with heat stress (HS) being a significant factor. The aim of this experiment was to explore the potential of natural antioxidants such as vitamin C (VITC), vitamin E (VITE), lycopene (LYC), and allicin (AL) in enhancing growth, immune function and maintaining the redox status of fattening rabbits under HS. Male weaning rabbits (n = 150, 5 weeks of age) were randomly assigned to 5 groups. The rabbits were fed a basal diet (control group) or supplemented with 40 mg of vitamin E (VE40), 5 mg of vitamin C (VC5), 150 mg of lycopene (LYC150), or 150 mg of allicin (AL150) per kg of diet, respectively, under summer Egyptian conditions. The overall temperature humidity index (THI) value was 29.76, indicating severe HS during the experimental period. The findings indicated that all dietary supplemented groups showed significant improvements in live body weight at 8 weeks (P < 0.0001) and 11 weeks (P < 0.05) of age compared to the control group. The feed conversion ratio (FCR) was improved with all additives (P < 0.05), while feed intake and carcass traits were not affected by the treatments (P > 0.05). The AL group had the highest dressing percentage compared to the other groups (P < 0.05). Feeding stressed rabbits with antioxidant supplements resulted in a higher hemoglobin concentration compared to the control group (P < 0.05). Aspartate transaminase (AST), triglycerides, and creatinine levels were decreased with all additives as compared to the control group (P < 0.05). Total protein and albumin were significantly higher in AL group than in other groups (P < 0.05). The serum Immunoglobulin G (IgG) was significantly increased, while tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), and interferon gamma (IFN-γ) were decreased by all feed additives (P < 0.05). Immunoglobulins (IgA and IgM) did not differ among all experimental groups (P > 0.05). Serum total antioxidant capacity (TAC) and glutathione (GSH) levels were higher in all supplement groups compared to the HS group (P < 0.05). All dietary supplements significantly reduced malondialdehyde (MDA) levels in liver tissues and blood serum compared to the control group (P < 0.05). Collectively, allicin emerged as a potent shield against heat stress, bettering lycopene and vitamins E and C in safeguarding the well-being of growing rabbits.

Anemonin suppresses sepsis‐induced acute lung injury by inactivation of nuclear factor‐kappa B and activation of nuclear factor erythroid 2‐related factor‐2/heme oxygenase‐1 pathway

AbstractSepsis‐induced acute lung injury (ALI) is a common acute and severe reason of death in the intensive care unit. Although the pathogenesis is complicated and multifactorial, elevated inflammation and oxidative stress are considered as fundamental mechanisms for the progression of ALI. Anemonin is a natural compound with diverse biological properties including anti‐inflammatory and anti‐oxidative effects. To identify whether anemonin has protective effects on sepsis‐induced ALI, a mouse sepsis‐induced ALI model and cellular models using the mouse alveolar macrophage MH‐S cells and mouse lung epithelial MLE‐12 cells were established. Our results showed that anemonin reduced lipopolysaccharide (LPS)‐induced mortality, and improved sepsis‐induced ALI in the mouse model, as shown by improved histopathological changes, decreased lung wet/dry weight ratio, and myeloperoxidase activity. Anemonin alleviated LPS‐induced secretion of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6) in bronchoalveolar lavage fluid samples, as well as reversed the LPS‐caused increase in malondialdehyde (MDA) content and decrease in activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in lung tissues. In the cellular model, anemonin inhibited the LPS‐induced inflammatory responses and oxidative stress in MH‐S and MLE‐12 cells. In addition, anemonin inhibited LPS‐induced nuclear factor‐kappa B (NF‐κB) pathway, while enhancing the activation of nuclear factor erythroid 2‐related factor‐2 (Nrf2) in lung tissues, MH‐S, and MLE‐12 cells. NF‐κB inhibition enhanced the anti‐inflammatory and anti‐oxidative effects of anemonin, while Nrf2 knockdown attenuated these effects of anemonin, implying the critical roles of NF‐κB and Nrf2. These results indicated that anemonin suppressed sepsis‐induced acute lung injury by inhibition of NF‐κB and activation of Nrf2/heme oxygenase‐1 pathway, suggesting that anemonin might be developed as a new therapeutic agent for the treatment of sepsis‐induced ALI.

Epcoritamab-Induced fatal pleural effusion in diffuse large B-Cell lymphoma: a case report and literature review.

Epcoritamab, a bispecific T-cell engager (BiTE) antibody targeting CD3 and CD20, has shown significant efficacy in treating refractory diffuse large B-cell lymphoma (DLBCL). However, its use can lead to severe side effects, such as tumor flare. Here, we report the case of an 84-year-old male with relapsed DLBCL who developed fatal unilateral pleural effusion following Epcoritamab treatment. Initially, the patient showed a favorable response, but later developed significant pleural effusion with elevated interleukin-6 (IL-6) levels, indicating a severe inflammatory response. This suggests that Epcoritamab directly affected the pleural lesions and caused a local cytokine release syndrome (L-CRS). Despite aggressive management, including Tocilizumab and Dexamethasone, the patient's condition worsened, leading to his death. This case underscores the importance of regular lab tests and imaging follow-ups to monitor and manage severe inflammatory reactions based on tumor location. Comprehensive monitoring protocols are needed to mitigate risks associated with novel immunotherapies. To our knowledge, this is the first reported case of fatal unilateral pleural effusion in a patient with relapsed DLBCL following Epcoritamab treatment.

The effect of high-fiber diet based on gut microbiota in patients with chronic heart failure.

Objective: This research explored the effect of high-fiber diet based on gut microbiota on chronic heart failure (HF) patients. Methods: Chronic HF patients, who had undergone a dietary survey indicating a daily dietary fiber intake of less than 15g/d were divided into the control and study groups (n = 50). In addition to conventional heart failure treatment, the study group received dietary guidance, while the control group did not receive any dietary guidance and maintained their usual low-fiber dietary habits. After one year intervention, the daily dietary fiber intake, abundance of gut microbiota, plasma trimethylamine N-oxide (TMAO), albumin (ALB), prealbumin (PA), transferrin (TF), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), left ventricular ejection fraction (LVEF), left ventricular end-diastolic index (LVEDVI), and left ventricular end-systolic volume index (LVESVI), Barthel index (BI), and 6 min walking distance (6 MWD) were compared. Results: After intervention, in both groups, the daily dietary fiber intake increased, abundance of Firmicutes, Proteobacteria, Actinobacteria, Fusobacteria decreased and that of Bacteroides increased; the plasma TMAO decreased; serum ALB, PA, and TF levels increased; serum CRP, TNF-α, IL-6, and IL-8 levels decreased, and the change was greater in the study group; LVEF elevated, LVEDVI and LVESVI reduced, and the differences between both groups were not significant; BI and 6 MWD elevated, and the study group was higher than the control group. Conclusion: High-fiber diet positively regulates the composition of gut microbiota, nutritional status and microinflammatory level in chronic HF patients, thereby improving patients' quality of life.

Impact of Nanoparticles on Oxidative Stress and Inflammatory Pathways in Human Prostate Cancer

Prostate cancer is one of the most prevalent cancers among men and is fueled by oxidative stress and inflammation that drive tumor progression and resistance to therapy. Production of reactive oxygen species (ROS) and pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) establish a pro-tumor microenvironment. Iron oxide nanoparticles are believed to be promising micro/nano therapy agents because NPs such as ferric oxide (Fe2O3) play a critical role in antioxidant and anti-inflammatory events. Herein, we examine influences of NPs on oxidative stress and inflammatory pathways in prostate cancer models. NP treatment was used for cells exposed to oxidative and inflammatory stressors. We measured a variety of key markers including ROS, MDA, GSH, and activities of antioxidant enzymes (catalase [CAT] and superoxide dismutase [SOD]). The levels of inflammatory cytokines were determined by widely used biochemical methods and spectrophotomedically. This resulted in significant reduction in ROS and MDA (oxidative damage markers) and significant elevation in the reduced GSH levels and these results were supported by the increased levels of antioxidant enzymes namely catalase (CAT) and superoxide dismutase (SOD) activity in NP-treated. Moreover, NPs also inhibited inflammation by downregulating the release of cytokines, such as TNF-α and IL-6. These effects suggest that NPs are capable of restoring oxidative homeostasis and suppressing inflammation, ultimately leading to a more tumor-hostile microenvironment. Abstract Nanoparticles that alleviate oxidative stress and overwrite inflammation pathways synergistically offer two critical blockade points in prostate cancer therapy to counter plasma phase-induced cellular malfunctions required for tumor progression. These results reinforce the prospect of NP as complements to cancer therapy. Optimizing NP formulations could improve their efficacy and safety for potential clinical applications in the future and provide new approaches for improving prostate cancer treatment. CuO NPs with Anti-cancer Effect on Prostate Cancer: In Vivo Study Oxidative Stress along with Inflammation as Potential Pathogenesis Prostate Cancer Responsive Ferric Oxide Nanoparticles Release ROS Assist in Treating Prostate Cancer.

Association between inflammatory biomarkers and the cognitive response to a multidomain intervention: secondary longitudinal analyses from the MAPT study.

The aim of this study is to evaluate the association of systemic inflammation measured by plasma biomarkers with the change in cognitive function among participants from the Multidomain Alzheimer Preventive Trial (MAPT) exposed to the multidomain intervention (MI). Secondary analysis of the MAPT longitudinal data. MAPT is a randomized, placebo-controlled trial with 3 interventional groups (omega-3 only, MI only, omega-3 plus MI) and a control group. We tested the association of the change in cognitive function with inflammatory biomarkers (tumoral necrosis factor receptor-1 (TNFR1), monocyte chemoattractant protein-1 (MCP1), Growth Differentiation Factor-15 (GDF15), Interleukin-6 (IL6) and C reactive protein (CRP)) using mixed-effects models. A subgroup analysis was performed in those exposed to the MI. The response to the MI was defined as the change in the composite cognitive score over the 2-year clinical follow-up period. by modeling the response to the intervention and identifying "good responders", i.e., those in the 5th quintile of response at the end of the intervention period (2years after the measurement of inflammatory markers). We included 1,527 participants (mean age 75.3, SD = 4.4; 64% female). Higher levels of GDF15 and TNFR1 were associated with a worse trajectory in the cognitive composite score in adjusted models. "Good responders" had an estimated mean change in the composite score of 0.051 (SD 0.062) over two years of intervention, compared to -0.136 (SD = 0.111) for the "not-good responders". Higher IL6 levels were associated with a decreased likelihood of being a "good responder" (OR = 0.22, p = 0.018, 95% CI 0.06; 0.78), with similar results for CRP (OR = 0.48, p = 0.009, 95% CI 0.28; 0.84). Higher inflammation was associated with a worse cognitive trajectory among nondemented participants and a lower likelihood of being classified as a "good responder" in those receiving a MI. Further confirmation of these findings could lead to the use of systemic inflammation as inclusion or stratification criteria in prevention trials.

Clinical characteristics of bullous pemphigoid patients of different ages and the possible mechanism.

Bullous pemphigoid (BP) is an acquired autoimmune bullous disease that often occurs in elderly patients. Some BP patients with early age of disease onset were observed to have difficulty in receiving applicable disease control. It remains challenging for clinicians to choose the appropriate treatment for these patients. This study aimed to analyze the differences between patients of different ages at disease onset and further explore the possible mechanism of these differences between patients of different ages. A total of 215 BP patients seen at the dermatology department of Peking Union Medical College Hospital between January 2009 and September 2020 were included. The patients were allocated to five groups according to the age at disease onset. Clinical data were collected through medical records and telephone follow-up interviews. Analyses of anti-BP180 antibody subclasses, anti-BP230 antibodies, complement fixation, serum cytokine levels, and single nucleotide polymorphisms (SNPs) were conducted. Nearly 52% of patients under 60 were misdiagnosed on their first visit, often presenting with oral mucosal involvement. The anti-BP180 immunoglobulin (Ig) E titers and C3 deposition increased in patients under 60 (p = 0.044 and p = 0.014, respectively), while the anti-BP230 IgG titers decreased (p = 0.043). The hospitalization rate of patients under 50 was significantly higher than that of patients aged 80 and older (p < 0.001). The patients under 60 had a significantly higher serum concentration of interleukin (IL)-13, tumor necrosis factor (TNF)-α, and interferon gamma (IFN-γ) (p < 0.005, respectively). We observed significant differences in the distribution of genotypes or alleles of TNF-α rs1799964, TNF-α rs1800630, and IFN-γ rs2069705. Approximately one-third of the elderly patients suffered from neurological diseases. Elderly patients usually presented with peripheral eosinophilia (p = 0.013). No significant difference was identified in the recurrence rate and complement-activating capacity among the age groups. In conclusion, the early age of BP onset was associated with a more severe clinical presentation, higher titers of anti-BP180 IgE, lower titers of anti-BP230 IgG, and significantly higher serum concentrations of IL-13, TNF-α, and IFN-γ. It may also be associated with the presence of SNPs of cytokines, including TNF-α rs1799964, TNF-α rs1800630, and IFN-γ rs2069705 variants.

Nerve-Derived Extracellular Matrix Promotes Neural Differentiation of Bone Marrow Stromal Cells and Enhances Interleukin-4 Efficacy for Advanced Nerve Regeneration.

Facilitating neuronal differentiation of stem cells and microenvironment remodeling are the key challenges in cell-based transplantation strategies for central nervous system regeneration. Herein, the study harnesses the intrinsic pro-neural differentiation potential of nerve-derived extracellular matrix (NDEM) and its specific affinity for cytokines to develop an NDEM-gelatin methacryloyl(gelMA)-based bifunctional hydrogel delivery system for stem cells and cytokines. This system promotes the neural differentiation of bone marrow stromal cells (BMSCs) and optimizes the therapeutic index of Interleukin-4 (IL-4) for spinal cord injury (SCI) treatment. It is observed that incorporating NDEM into the hydrogel system intrinsically promotes BMSC differentiation into neuron-like cells and effectively regulates IL-4 release kinetics to match the neural reconstructing timeframe. Further analysis reveals that trace amounts of endogenous basic fibroblast growth factor (bFGF) detected in NDEM exhibit a potent effect in promoting neural differentiation. The sustained release of IL-4 from the NDEM significantly encourages macrophage polarization toward the M2 phase, optimizing the transplant microenvironment throughout the reconstruction process. This study demonstrates an NDEM-based optimization strategy for hybrid hydrogel to achieve synchronized delivery of stem cells and cytokines in regenerative medicine applications.

Warm and humid environment induces gut microbiota dysbiosis and bacterial translocation leading to inflammatory state and promotes proliferation and biofilm formation of certain bacteria, potentially causing sticky stool

Background and aims of the studyFluctuations in environmental temperature and humidity significantly affect human physiology and disease manifestation. In the Lingnan region of China, high summer temperatures and humidity often cause symptoms like diminished appetite, sticky tongue coating, sticky stool, unsatisfactory defecation, lethargy, and joint heaviness. These are referred to as “Dampness Syndrome” in Traditional Chinese Medicine (TCM). Thick and greasy tongue fur and sticky feces are characteristic symptoms of “Dampness Syndrome” and serve as crucial diagnostic indicators in TCM for assessing health conditions. However, the specific mechanisms that lead to these symptoms, such as sticky feces and thick and greasy tongue fur, have not been fully elucidated. Understanding these external symptoms is essential, as they reflect internal health status.Warm, humid environments favor microorganism growth, potentially disrupting gut microbiota and bacterial translocation, which could induce an immune-inflammatory response. The primary objective of this study is to explore the potential significant role of immune response products in influencing the proliferation and biofilm formation of gut microbiota, which may subsequently lead to changes in fecal characteristics. MethodsIn this study, mice were exposed to a controlled warm and humid environment (25 ± 3 °C with 95% humidity) for 16 days to simulate conditions associated with “Dampness Syndrome.” After this period, Huoxiang Zhengqi Water, a traditional remedy, has been administrated for four days. On the one hand saliva and tongue coating samples were also taken from human subjects with “Dampness Syndrome” for microorganism culturing and to assess biofilm formation, on the other hand the co-culture products of a macrophage cell line RAW264.7 and Candida albicans and the effect of tumor necrosis factor-α (TNF-α) were evaluated for their impact on the proliferation and biofilm-forming abilities of different bacterial strains. ResultsCompared to a control group, the treatment group exhibited significant changes in gut microbiota, including increased biofilm formation, which was mitigated by Huoxiang Zhengqi Water. In the model group, fungal translocation was observed, potentially triggering an inflammatory response. Intraperitoneal injections of various bacterial strains in mice reproduced the sticky stool characteristics. Both mice and human subjects with “Dampness Syndrome” displayed elevated serum levels of inflammatory cytokines TNF-α and interleukin-17 A (IL-17A). Interestingly, Saliva samples from individuals with “Dampness Syndrome” showed elevated TNF-α levels, accompanied by thick and greasy tongue fur. Culturing samples from the tongue coating of individuals in the “Dampness Syndrome” group revealed an increased biofilm formation capability. C. albicans co-cultured with RAW264.7 cells increased TNF-α secretion, and the supernatant promoted pathogenic bacterial proliferation and biofilm formation. TNF-α specifically enhanced biofilm formation in microorganism like C. albicans and Staphylococcus aureus, with minimal effect on beneficial bacteria like Lacticaseibacillus paracasei and Lactiplantibacillus plantarum in the tested conditions.ConclusionsThese findings provided new insights into the biological mechanisms of ‘Dampness Syndrome’ and support the therapeutic role of Huoxiang Zhengqi Water in treating symptoms associated with microbial dysbiosis and inflammation. Additionally, they indicate that TNF-α seems to have selective effects in promoting the proliferation and biofilm formation of different microbial species.

Esmolol upregulates the α7 nAChR/STAT3/NF-κB pathway by decreasing the ubiquitin and increasing the ChAT+CD4+ T lymphocyte to alleviate inflammation in septic cardiomyopathy.

Esmolol has been demonstrated to mitigate inflammation damage and T lymphocyte apoptosis in septic cardiomyopathy. It has been established that the activation of α7 nicotinic acetylcholine receptor (nAChR) by cluster of differentiation 4(CD4) + T lymphocytes expressing choline acetyltransferase (ChAT) can prevent excessive inflammation and reduce splenocyte apoptosis in septic cardiomyopathy. Given the similar anti-inflammatory effects, we hypothesized that esmolol might be associated with α7 nAChR and thereby exert its cardioprotective functions. In the cecal ligation puncture (CLP)-induced rat septic cardiomyopathy model, esmolol was found to attenuate myocardial injury as evidenced by Hematoxylin and Eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, and the reduced concentration of interleukin (IL)-1, IL-6, and Tumor Necrosis Factor (TNF)-α detected by enzyme-linked immunosorbent assay (ELISA). Western blotting (WB) revealed that esmolol enhanced the expression of α7 nAChR, elevated the level of Phosphorylated-Signal transducer and activator of transcription 3 (P-STAT3)/STAT3, and decreased the level of Nuclear factor-κB (NF-κB), which led to the reduction of plasma IL-1, IL-6, and TNF-α. Methyl lycaconitine Citrate (MLA, an α7 nAChR inhibitor) suppressed the level of P-STAT3/STAT3, while stattic (a STAT3 inhibitor) inhibited the level of P-STAT3/STAT3 and up-regulated the expression of NF-κB. Real-time quantitative PCR (RT-qPCR) results indicated no significant difference in the mRNA level of α7 nAChR, but immunofluorescence and WB results verified the upregulation of α7 nAChR by esmolol and the reduction of ubiquitin induced by esmolol. In the spleen, esmolol decreased splenocyte apoptosis and increased the expression of α7 nAChR as shown by immunofluorescence. In isolated CD4+ T cells obtained through magnetic cell separation, esmolol enhanced the expression of ChAT mRNA. In conclusion, esmolol upregulates α7 nAChR by decreasing ubiquitin and increasing ChAT+CD4+ T lymphocytes and then increases the P-STAT3/STAT3 which inhibits NF-κB thus alleviating inflammation in septic cardiomyopathy.

Investigation of the preventive effect of methylsulfonylmethane on alveolar bone loss and oxidative stress in a rat model of periodontitis

BackgroundTo investigate the preventive efficacy of methylsulfonylmethane (MSM) on alveolar bone destruction in rats with periodontitis.MethodsTwenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-MSM. Periodontitis was induced by placing 4.0 silk sutures in the subparamarginal position on the necks of the mandibular first molars and applying the suture for 5 weeks. The Ep-MSM group was given 500 mg/body weight/day MSM intraperitoneally for 35 days. At the end of the study, bilateral mandibular samples were taken. Periodontal bone loss was measured through histologic sections. Histomorphometric and immunohistochemical (receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin (OPG)) evaluations were performed on right mandibular tissue samples, and biochemical (interleukin (IL)-1 beta (β)/IL-10, malondialdehyde (MDA), glutathione (GSH), oxidative stress index (OSI)) evaluations were performed on left mandibular tissue samples.ResultsNo significant difference was found between the groups in IL-1β and IL-1β/IL-10 values ​​(p > 0.05). A significant decrease in IL-10 levels was observed in the Ep-MSM and Ep groups compared with the control group (p < 0.05). MDA levels significantly increased in the Ep and Ep-MSM groups compared with the control group, and GSH levels significantly decreased in the Ep group compared with the other groups (p < 0.05). OSI values ​​were significantly higher only in the Ep group (p < 0.05). RANKL levels showed a significant increase in the Ep group compared with the other groups. OPG levels were significantly increased only in the Ep-MSM group (p < 0.05).ConclusionsThe results of this study may suggest that MSM has preventive effects on alveolar bone loss and oxidative stress.

Core microbe Bifidobacterium in the hindgut of calves improves the growth phenotype of young hosts by regulating microbial functions and host metabolism

BackgroundThe growth and health of young ruminants are regulated by their gut microbiome, which can have lifelong consequences. Compared with subjective grouping, phenotypic clustering might be a more comprehensive approach to revealing the relationship between calf growth state and core gut microbes. However, the identification of beneficial gut bacteria and its internal mechanisms of shaping host phenotype differentiation remains unclear.ResultsIn this study, calves were divided into two clusters, cluster1 and cluster2, based on 29 phenotypic indicators using cluster analysis. Calves in cluster2 showed better growth performance, including higher body weight (BW), average daily gain (ADG), and dry matter intake (DMI), as well as better serum indicators with a high level of total superoxide dismutase (T-SOD), interleukin-6 (IL-6), and insulin-like growth factor-1 (IGF-1) compared to those in cluster1. Multi-omics was used to detect microbial features among calves in different phenotypic clusters. Distinct differences were observed between the two clustered gut microbiomes, including microbial diversity and composition. The close relationships between growth performance, blood metabolites, and microbiome were also confirmed. In cluster2, Bifidobacterium members were the dominant contributors to microbial metabolic functions with a higher abundance. Furthermore, pathways involved in carbohydrate degradation, glycolysis, and biosynthesis of propionate and proteins were active, while methane production was inhibited. In addition, the diversity and richness of hindgut resistome in cluster2 were lower than those in cluster1. The isolation and culture of Bifidobacterium strain, as well as the mice experiment, indicated that B. longum 1109 from calf feces in cluster2 could promote the growth of young hosts, enhance their blood immunity and antioxidation, and improve the development of hindgut.ConclusionsIn summary, cluster analysis has proved to be a feasible and reliable approach for identifying phenotypic subgroups of calves, prompting further exploration of host-microbiome interactions. Bifidobacterium as a core microbe in the hindgut of calves may play a crucial probiotic role in host phenotypic differentiation. This study enhances our comprehension of how gut core microbe shapes the host phenotype and provides new insights into the manipulation of beneficial gut colonizers to improve the growth performance and productivity of young ruminants.EbRLLe7F-yvVZ5Dd-FAxmeVideo

Characterization for the Similarity Assessment Between the Proposed Biosimilar SB17 and Ustekinumab Reference Product Using State-of-the-Art Analytical Methods.

SB17 is being developed as a biosimilar to ustekinumab reference product (RP), a human monoclonal antibody (IgG1 kappa immunoglobulin) that binds to the common p40 subunit of cytokines interleukin (IL)-23 and IL-12. Binding to this subunit prevents interaction with their receptor, resulting in modulation in the immune system responses that play a key role in inflammatory disease. The objective of this study was to demonstrate structural, physicochemical, and biological similarity between ustekinumab RP and SB17 using various state-of-the-art analytical methods. Comprehensive analytical characterization was conducted by the quality range and side-by-side comparison approach for SB17 versus the European Union (EU) and US ustekinumab RP using various analytical methods. Comparisons included purity, product-related impurity, charge heterogeneity, primary structure, posttranslational modification, higher-order structure, quantity, Fab-related biological activities (potency and binding activity), and Fc-related biological activities. On the basis of the analytical similarity assessment, the structural, physicochemical, and biological characterization results demonstrated that SB17 is comparable to the ustekinumab RP. In the structural aspects, it was confirmed that there is no clinically meaningful difference between posttranslational modification profiles and higher-order structures of SB17 compared with the ustekinumab RP. Product-related impurities in the form of aggregates were also confirmed to be similar. SB17 has lower acidic and basic variants compared with ustekinumab RP, owing to the difference in the producing cell line. Ustekinumab RP is expressed in an Sp2/0 cell line, whereas SB17 is expressed in CHO cell line. However, the difference between SB17 and ustekinumab RP in the charge variants is not considered to be clinically meaningful, since equivalent biological activity was observed. In the case of mechanism of action (MoA)-related biological activities, SB17 is highly similar to the EU and US ustekinumab RP with respect to overall critical and noncritical quality attributes analyzed. Moreover, similarity or lack of activity in Fc-related biological activities was also confirmed. On the basis of these results, SB17 is expected to have comparable safety and efficacy as compared with ustekinumab RP. In summary, the overall analytical characterization and similarity assessment results show that SB17 is comparable to the EU and US ustekinumab RP in terms of structural, physicochemical, biophysical, and biological attributes.