Interleukin Research Articles

A single bout of resistance or high-intensity interval training increases anti-cancer myokines and suppresses cancer cell growth in vitro in survivors of breast cancer.

Breast cancer is the leading cause of cancer-related death in women, highlighting the need for strategies to mitigate recurrence and mortality. We examined the effects of a single bout of resistance training (RT) versus high-intensity interval training (HIIT) on anti-cancer myokines and in vitro cancer cell suppression. Thirty-two survivors of breast cancer were randomly allocated to a single bout of RT (n = 16) or HIIT (n = 16). Blood was collected before, immediately post (0P) and 30min post (30P) exercise. We measured serum levels of decorin, interleukin 6 (IL-6), secreted protein acidic and rich in cysteine (SPARC), and oncostatin M (OSM) and cell growth of MDA-MB-231 cells in vitro using real time cellular analysis at each time point. Decorin, IL-6, and SPARC significantly increased (9 to 47%, p < 0.05) from baseline to 0P in both groups. IL-6 remained elevated in both groups at 30min post-intervention (30P), while OSM levels were elevated only in the RT group at 30P. Between groups, IL-6 was significantly increased in HIIT at 0P (p = 0.001). Cancer cell growth was significantly reduced at 0P and 30P compared to baseline in RT (20 to 21%, p < 0.05) and HIIT (19 to 29%, p < 0.05), with significantly greater effects on MDA-MB-231 cell growth reduction in favour of HIIT at 0P (p = 0.001). A single bout of RT or HIIT can increase levels of anti-cancer myokines and reduce the growth of MDA-MB-231 cells in vitro in survivors of breast cancer, potentially contributing to a lower risk of recurrence. This highlights the importance of exercise as a treatment with promising anti-cancer effects.

Nanofibrillar Cellulose Hydrogels with Anionic Surface Modifications for Modulating Macrophage Phenotype in 3D Culture.

Anti-inflammatory M2 macrophages are highly relevant in various physiological processes ranging from tissue regeneration to cancer progression. However, conventional two-dimensional (2D) in vitro cell cultures limit our understanding of macrophage phenotypes and how they can be modulated for immunotherapeutic approaches. Moreover, there is a growing demand for scalable, animal-free hydrogels to replace animal-derived materials in three-dimensional (3D) in vitro models. In this study, we explore hydrogels based on plant-derived nanofibrillar cellulose (NFC), also known as cellulose nanofibrils (CNFs) or microfibrillated cellulose (MFC), for generating 3D in vitro models of M2-like macrophages from human blood monocytes. Notably, flow cytometry analysis shows that cells cultured in 3D phosphorylated NFC hydrogels show enhanced expression of the M2 macrophage marker CD206 compared to cells cultured in other negatively charged hydrogels prepared from native NFC or NFCs with carboxylate or sulfate modifications. Furthermore, the upregulation of CD206 expression in 3D phosphorylated NFC is comparable to the induction of CD206 in interleukin 4 (IL-4)-differentiated M2a macrophages. In addition, the cells in the phosphorylated NFC hydrogel show a differential cytokine profile compared to 2D cultured cells, secreting similar levels of tumor necrosis factor α (TNF-α), but 2.6-fold higher amounts of IL-1β and 1.2-fold higher amounts of IL-10. The results suggest that the conversion of monocytes to M2-like macrophages can be controlled by the phosphorylation of NFC, a strategy which does not require the addition of polarization factors like growth factors and cytokines conventionally used to generate macrophages in vitro. The findings highlight the importance of surface chemistry in matrix-guided macrophage polarization, paving the way for xeno-free yet bioactive 3D macrophage culture scaffolds for immunological research.

Methanol Leaf Extract of Andrographis paniculata Reverses Behavioral and Neuro-biochemical Changes Induced by Chronic Restraint Stress in Mice

Background and Purpose: Chronic stress and behavioral activities have recently been linked with hyperglycemia. The neurobehavioral effect and neuro-biochemical changes following the administration of Andrographis paniculata leaf extract were evaluated in mice using the chronic stress paradigm. Methods: Male mice were assigned to 6 groups (n=6). Groups 1and 2 received distilled water and groups 3, 4, 5 were administered 80, 160 and 320 mg/kg of methanol extract of Andrographis paniculata (MEAP) respectively while group 6 which was the positive control was administered pioglitazone 15 mg/kg. All treatments were by the oral route. The animals were subjected to 4 cycles of restraint stress (2 h per day) in which a cycle lasted 10 days. Animals were stressed for 7 days and allowed to rest for 3 days. On the 39th day in the 4th cycle, animals were tested for neurobehavioral phenotypes: depression, anxiety and memory impairment. Blood was collected for corticosterone and insulin quantification, while the adrenal gland was weighed. Brains were collected for estimation of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, (CAT), nitric oxide (NO), reduced glutathione (GSH), tumor necrosis factor-? (TNF-?), interleukin 6 (IL-6) and acetylcholinesterase (AchE). Results: MEAP reversed hyperglycemia caused by chronic restraint stress (CRS), reduced anxiety, and memory impairment. It caused an increase in the level of SOD with a corresponding reduction in the levels of NO. Adrenal weight were not significantly changed. The levels of MDA were not significantly reduced while the levels of GSH and CAT were not significantly elevated. MEAP also reduced CRS-induced elevation in corticosterone, AChE, TNF-?, and IL-6 levels and reversed CRS-induced decrease in serum insulin levels. Conclusion: The results suggest that the extract of Andrographis paniculata reversed the complications of hyperglycemia induced by exposure to chronic stress through the modulation of antioxidant system and reduction of pro-inflammatory cytokines.

Interleukin-17 and interleukin-23 cytokine profiles in palindromic rheumatism: potential therapeutic targets and prognostic biomarkers for disease progression to rheumatoid arthritis.

Palindromic rheumatism (PR) is a rare autoimmune disorder characterized by recurrent inflammatory episodes, often progressing to more severe forms of arthritis, such as rheumatoid arthritis (RA). The interleukin (IL)-17/23 axis plays a crucial role in autoimmunity and joint inflammation; however, its involvement in PR remains unclear. This study aimed to investigate mRNA expression and serum levels of IL-17 and IL-23 in PR, RA, and healthy controls (HCs). This cross-sectional study included 20 PR patients, 40 RA patients, and 40 age- and gender-matched HCs. Serum cytokine levels and gene expression were assessed using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (qPCR). Correlations between cytokine levels, joint involvement, and disease activity were analyzed. Serum and mRNA expression levels of IL-17 and IL-23 were significantly higher in PR and RA patients compared to HCs. Notably, IL-17 and IL-23 levels were significantly higher in PR patients than RA patients, suggesting distinct inflammatory mechanisms. There was a significant positive correlation between IL-17 and IL-23 expression levels in PR and RA groups. However, no significant association was found between cytokine levels with clinical manifestations, autoantibodies and disease activity in PR and RA groups. The research findings provide valuable insights into immune imbalances and increased gene expression and protein levels of IL-17 and IL-23 in PR patients, offering potential therapeutic targets. Targeting these cytokines or their receptors may provide novel therapeutic strategies to prevent PR progression to RA. Not applicable.

Guselkumab Retention, Effectiveness, and Safety in Psoriasis: A 260-Week Real-World Multicenter Retrospective Study Exploring the Role of Concomitant PsA-IL PSO (Italian Landscape Psoriasis).

Guselkumab is a monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, approved for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis (PsA). While patients with psoriasis often achieve high clinical response rates (Psoriasis Area and Severity Index [PASI] 90 and PASI 100), the presence of PsA may influence long-term outcomes. We conducted a 260-week, multicenter, retrospective study to compare the effectiveness, safety, and drug survival of guselkumab in patients with and without concomitant PsA. A total of 1765 patients were enrolled, including 352 with a concomitant diagnosis of PsA and 1413 with isolated skin involvement. All patients were treated with guselkumab following the approved dosing schedule for moderate-to-severe plaque psoriasis for at least 1 year. Treatment effectiveness was evaluated in terms of PASI 90, PASI 100, and absolute PASI ≤ 2 at weeks 16, 28, 52, 104, 156, 204, and 260. Guselkumab drug survival was assessed using the Kaplan-Meier method at the same time points. The safety profile was evaluated by analyzing adverse events recorded in medical charts at each follow-up visit. Throughout the study period, response rates remained comparable between the two cohorts of patients, with a significant difference at 2 years of follow-up in terms of PASI 90 (80.51% versus 74.02%). Drug survival overall remained stable and similar, with 79.5% (95% confidence interval (CI) 76.9-81.9) of patients without PsA and 78.5% (95% CI 72.9-83.1) of patients with PsA still receiving guselkumab treatment after 5 years. Our results confirm the long-term effectiveness, persistence, and favorable safety profile of guselkumab in patients with moderate-to-severe psoriasis, regardless of the presence of concomitant PsA.

Pyroptosis: An Inflammatory Response to Toxic Effect of Cigarette Exposure.

Cigarette smoke (CS) is a major contributor to respiratory and systemic diseases, primarily due to its ability to induce cellular damage and chronic inflammation. While apoptosis has long been recognised as the dominant form of cell death resulting from CS exposure, recent findings highlight pyroptosis-a caspase-1 (CASP-1)-dependent, pro-inflammatory form of programmed cell death-as a key pathological mechanism. Pyroptosis is characterised by gasdermin D (GSDMD) cleavage, pore formation in the cell membrane, and the release of inflammatory cytokines, particularly interleukin (IL)-1β and IL-18. This review synthesises evidence from peer-reviewed articles published between 2014 and 2024, identified through searches in PubMed, Scopus, Web of Science, and Google Scholar. Search terms included "pyroptosis", "cigarette smoke", "inflammasome", "caspase-1", and "gasdermin D". Only English-language articles from reputable, Scopus-indexed journals were included. Studies focusing on pyroptotic mechanisms, disease progression, and therapeutic interventions were prioritised. Numerous studies demonstrate that CS activates inflammasomes, triggering CASP-1 activation and GSDMD-mediated pyroptosis. This mechanism exacerbates chronic pulmonary diseases such as COPD and emphysema and also plays a role in extrapulmonary conditions including atherosclerosis, liver dysfunction, and neuroinflammation. Inhibitors of CASP-1 and inflammasome components, as well as natural bioactive compounds, have shown potential in suppressing pyroptotic pathways and alleviating CS-induced tissue damage. Pyroptosis represents a critical inflammatory pathway in CS-induced diseases. Targeting inflammasome signalling and pyroptotic mediators offers a promising strategy for therapeutic development. A deeper understanding of this cell death mechanism could inform novel interventions to combat the widespread impact of smoking-related pathology. This review elucidates the critical role of pyroptosis as a key inflammatory mechanism in response to the toxic effects of cigarette exposure. By synthesizing recent scientific evidence, it underscores the involvement of pyroptotic pathways in the pathogenesis of tobacco-related diseases, highlighting their contribution to tissue damage and disease progression. A deeper understanding of these mechanisms may facilitate the identification of novel therapeutic targets aimed at mitigating the detrimental health effects of cigarette smoke. These insights could further inform the development of preventive and therapeutic strategies to alleviate the inflammatory burden associated with chronic cigarette exposure.

Inflammation and Cognition in Bipolar Disorder: Diverging Paths of Interleukin-6 and Outcomes

Bipolar disorder (BD) may present with neurocognitive dysfunction due to inflammatory alterations through different biological pathways. However, findings are not consistent regarding the patterns of neurocognitive dysfunction and elevation of inflammatory biomarkers during the different mood phases. Therefore, we aimed to determine associations between inflammatory biomarkers, neurocognitive functioning, and clinical outcomes in patients with BD in euthymia. We conducted a cross-sectional study including 109 adults. Serum levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), neurocognitive parameters (ACER), number of suicide attempts (SA), and hospitalizations (NH) were measured. We found negative and moderate correlations between IL-6 and ACER total score, language, visuospatial abilities, and orientation/attention. There was a positive and moderate correlation between IL-6 and NH. IL-6 significantly predicted ACER total score, language, memory, orientation/attention, visuospatial abilities, and NH. Overall, IL-6 had an inverse association with neurocognition and clinical variables, whereas hs-CRP did not play a role. Here we demonstrate that IL-6 predicts neurocognitive functioning in adults with BD. BD may be a biological model for studying the relationship between inflammation and neurocognition in severe psychiatric disorders. Prospective studies at different mood phases of the disease must be conducted.

Interleukin-4 prevents increased endothelial permeability by inducing pericyte survival and modulating microglial responses in diabetic retinopathy

IntroductionRetinal vascular leakage due to increased endothelial permeability is a major contributor to the pathogenesis of diabetic retinopathy (DR) and visual impairment. Pericyte loss and microglia-mediated inflammation exacerbate this vascular dysfunction. Interleukin-4 (IL-4) is known for its anti-inflammatory and tissue-protective properties, but its role in DR remains unclear. MethodsWe evaluated IL-4 expression and signaling in the retinas of streptozotocin-induced diabetic mice. In vitro assays were conducted under high-glucose and TNF-α conditions using retinal endothelial cells, pericytes, and microglia to assess IL-4’s effects on barrier function, cell viability, and inflammatory state. Pathway-specific analyses were performed to investigate PI3K/AKT and STAT6 signaling. ResultsIL-4 expression and downstream signaling were significantly reduced in diabetic retinas. IL-4 promoted pericyte survival via PI3K/AKT activation and modulated microglial functional profiles through STAT6 signaling, favoring an anti-inflammatory phenotype. These effects contributed to restored endothelial barrier integrity and tight junction protein expression under diabetic stress conditions in vitro. ConclusionIL-4 supports retinal vascular stabilization in DR by preserving pericyte viability and modulating microglial activity. These findings highlight IL-4 as a potential therapeutic target for preventing or slowing DR progression and warrant further preclinical investigation.

Metabolic click-labeling of interleukin-10 enhances the immunomodulatory potential and wound healing properties of mesenchymal stem cell-derived extracellular nanovesicles.

Mesenchymal stem cell-derived extracellular nanovesicles (MSC-NVs) exhibit unique biological properties and tissue-regenerative effects comparable to their parent MSCs. However, despite the robust angiogenic and anti-apoptotic effects of MSC-NVs, their immunomodulatory effect is limited due to insufficient translation of anti-inflammatory cytokines from parent MSCs to isolated NVs. Hence, in this study we suggest the incorporation of interleukin (IL)-10, a key anti-inflammatory mediator in the body's immune system, on the surface of MSC-NVs via bio-orthogonal click chemistry. Metabolically engineered MSCs were serially extruded to generate azido-displaying MSC-NV-N3, followed by click chemistry-based conjugation of IL-10. Synthesized MSC-NV/IL-10 exhibited superior abilities for cell proliferation and migration of fibroblast and endothelial cells. MSC-NV/IL-10 markedly attenuated the activity of the pro-inflammatory M1 macrophage and promoted the expression of the anti-inflammatory M2 marker. We also demonstrated that MSC-NV/IL-10 induces the phenotypic transition of dendritic cells (DCs) from mature DCs to immune-tolerogenic DCs. Moreover, RNA sequencing revealed that metabolic engineering does not alter the regenerative potential or immunomodulatory functions of MSCs. In animal studies, MSC-NV/IL-10 treated mice exhibited significantly accelerated wound healing, accompanied by resolution of inflammatory responses in injured skin.

Real-world data and Mendelian randomization analysis in assessing adverse reactions of rilonacept.

Rilonacept, an interleukin-1 (IL-1) "trap," is FDA-approved for recurrent pericarditis, but research on its adverse reactions is limited due to its recent introduction. This study aimed to identify potential adverse reactions associated with rilonacept using the FDA Adverse Event Reporting System (FAERS) and to evaluate long-term effects through Mendelian randomization (MR) analysis. We analyzed all adverse event reports related to rilonacept from the FAERS database between January 2021 and June 2024. Positive signals for adverse reactions were extracted using reporting odds ratios (ROR) and information components (IC). MR analysis was conducted using genetic variants as instrumental variables to explore causal relationships between rilonacept and identified adverse reactions, with sensitivity analyses performed for robustness. A total of 419 adverse event reports were analyzed, documenting 1847 AEs. Common events included COVID-19, injection site rash, pain, and injection site reaction, categorized into 27 System Organ Classes (SOCs). Notable frequencies were found in Infections and Infestations, Nervous System Disorders, and Skin and Subcutaneous Tissue Disorders. Disproportionality analysis identified positive signals primarily in Skin and Subcutaneous Tissue Disorders, Cardiac Disorders, and Immune System Disorders, with 11 AEs showing positive signals in both Preferred Terms (PTs) and SOCs. MR analysis revealed significant associations between IL-1RN (rilonacept) and allergic urticaria (OR: 1.56), rash (OR: 0.64), and myocarditis (OR: 2.26). Rilonacept is effective for certain inflammatory conditions, but careful monitoring for adverse reactions, particularly involving the immune system, skin, and cardiac issues, is essential.

Diagnosis of infected pancreatic necrosis: A review of the role of blood biomarkers.

Infected pancreatic necrosis (IPN) is a serious and critical complication of acute pancreatitis (AP), often arising in the later stages of the disease. Early detection of high-risk individuals with IPN is essential because it may enable clinicians to implement more efficient management strategies. This review explores the key biomarkers currently used to predict and diagnose IPN. Established markers such as procalcitonin (PCT), C-reactive protein (CRP)and interleukin-6 (IL-6) play a vital role in detecting infection and inflammation. Non-invasive markers, including corticosteroid-binding globulin (CBG), neutrophil CD64 index (nCD64), soluble PD-L1 (sPD-L1)and human leukocytes antigen-DR (HLA-DR), further contribute to identifying immune suppression and infection risks. While these tools show promise, no single biomarker has proven to be sufficiently accurate. A combination of clinical assessment, imagingand multiple biomarkers is essential for a comprehensive diagnosis. This review emphasizes the need for further research to refine and validate these markers, making them more accessible and reliable for routine clinical use. By advancing our ability to identify IPN early, we can improve patient outcomes and reduce the severe impacts of this complication in individuals suffering from AP.

Exploring the beneficial effects of GHK-Cu on an experimental model of colitis and the underlying mechanisms

IntroductionUlcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by mucosal damage and impaired epithelial barrier function. While glycyl-l-histidyl-l-lysine-copper (GHK-Cu) exhibits known anti-inflammatory properties, its therapeutic mechanisms in UC remain undefined. This study was designed to systematically evaluate the therapeutic potential of GHK-Cu in a dextran sulfate sodium (DSS)-induced murine model of UC, with particular emphasis on elucidating its regulatory effects on the NAD-dependent deacetylase sirtuin-1 (SIRT1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.MethodsUC was induced in BALB/c mice with 3% DSS for 14 days. The protein expression levels of tight junction associated protein-1 (ZO-1), Occludin, inflammatory factors interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, SIRT1, STAT3, p-STAT3, and retinoic acid receptor-related orphan receptor gamma t (RORγt) were detected by Western blot. Histopathological changes were evaluated by Hematoxylin and Eosin (H&amp;amp;E) and Alcian blue-periodic acid-Schiff (AB-PAS). Network pharmacology and molecular docking were used to predict the core targets of GHK Cu in the treatment of UC. An in vitro UC model was also established in mouse peritoneal macrophages (MPMs) using lipopolysaccharide (LPS), and a co culture model was constructed using mouse colonic epithelial cells (MCECs) and MPMs to examine the role of GHK Cu in promoting mucosal healing. STAT3 was silenced by gene transfection technology to verify the core role of STAT3 in GHK Cu treatment of UC.ResultsGHK-Cu alleviated weight loss, improved the disease activity index (DAI), reduced colonic edema and shortening, attenuated inflammatory damage, increased goblet cell numbers, suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and promoted mucosal repair. Additionally, a co-culture system of MCECs and MPMs revealed that GHK-Cu facilitated MCECs healing, impaired by DSS, by upregulating ZO-1 and Occludin expression. Subsequently, network pharmacology and molecular docking identified SIRT1 as a potential target of GHK-Cu. Results showed that GHK-Cu upregulated SIRT1 protein expression and suppressed the expression of phosphorylated p-STAT3 in colon tissue and MCECs of the co-culture model. Our findings revealed that after transfection with STAT3-targeting siRNA (siSTAT3), the stimulant effect of GHK-Cu on the healing of MCECs and the effect on the protein expression of ZO-1 and Occludin is canceled. Nevertheless, after transfection with siSTAT3, it could inhibit the expression of inflammatory factors in conjunction with GHK-Cu. Furthermore, we found that GHK-Cu could inhibit RORγt expression in the colon tissue of UC mice.DiscussionThis study found that GHK-Cu demonstrated significant therapeutic effects in DSS-induced UC in mice. GHK-Cu may promote mucosal healing and enhance tight junction protein expression by regulating the SIRT1/STAT3 pathway. In addition to suppressing p-STAT3 expression, GHK-Cu may utilize additional pathways to inhibit inflammatory factors. Furthermore, GHK-Cu may reduce the number of Th17 cells. In summary, GHK-Cu may treat UC by acting on the SIRT1/STAT3 pathway.

Association of peripheral inflammatory cytokines with motor and non-motor symptoms in patients with Parkinson’s disease and type 2 diabetes mellitus

ObjectiveThis pilot study aims to investigate the association between peripheral inflammatory cytokines and motor and non-motor symptoms in patients with both Parkinson’s disease (PD) and type 2 diabetes mellitus (T2DM) and the underlying mechanisms.MethodsSixty patients with PD were divided into two groups depending on whether they also had T2DM, resulting in a PD group (21 cases) and a PD–T2DM group (39 cases). Thirty healthy volunteers from the physical examination centre were enrolled as the control group. Peripheral blood was collected from all patients.ResultsPatients with PD–T2DM had higher Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III scores; total MDS-UPDRS scores; Parkinson’s Disease Questionnaire-39 (PDQ-39) scores; and interleukin (IL)-6, IL-1β, tumour necrosis factor alpha (TNF-α) and IL-4 levels than patients with PD (p &amp;lt; 0.05). In the PD group, IL-4 levels correlated with UPDRS II (r = 0.337), Non-Motor Symptom Scale (r = 0.354), Hamilton Depression Scale (r = 0.420) and PDQ-39 (r = 0.423) scores (p &amp;lt; 0.05). A multivariate regression revealed IL-6 independently predicted lower UPDRS III scores (β = −0.497, p = 0.018), TNF-α correlated with PD duration (β = 0.689, p &amp;lt; 0.001) and IL-1β correlated with PDQ-39 scores (β = 0.462, p = 0.002) in patients with PD–T2DM. Adjusted models explained up to 52.3% of variance (adjusted R2). In the PD group, age-adjusted correlations confirmed IL-4 was associated with UPDRS II (r = 0.321, p = 0.047) and PDQ-39 (r = 0.418, p = 0.009), and interferon gamma (IFN-γ) was associated with Scales for Outcomes in Parkinson’s Disease-Autonomic Questionnaire (SCOPA-AUT; r = −0.564, p = 0.001). Negative correlations were identified between IL-6 and UPDRS III scores (r = −0.497) and IFN-γ and SCOPA-AUT scores (r = −0.588; p &amp;lt; 0.05).ConclusionThese pilot findings suggest peripheral inflammatory cytokines can be considered biomarkers in patients with PD–T2DM. The underlying mechanism by which T2DM worsens the motor and non-motor symptoms of PD may involve increased inflammation.

Effects of echinacoside on the regulation of mitochondrial fission induced by TBK1/Drp1 in rheumatoid arthritis.

Dysregulated mitochondrial fission in synovial tissue is a key contributor to the progression of rheumatoid arthritis (RA), and echinacoside (ECH) has been shown to modulate this process in a mouse model of RA. This study aimed to investigate the effects of echinacoside (ECH) on the proliferation and inflammatory response of human fibroblast-like synoviocytes (MH7A cells), and to elucidate the potential underlying mechanisms. The expression and co-localization of TANK-binding kinase 1 (TBK1) and phosphorylated dynamin-related protein 1 (p-Drp1) in synovial tissues from patients with and without RA were analyzed. MH7A cells were exposed to either ECH or 0.1% dimethyl sulfoxide (DMSO). Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) assay and reactive oxygen species (ROS) expression was detected with dichlorofluorescin (DCFH) staining. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), cyclooxygenase (COX)-2, IL-1β, TANK-binding kinase 1 (TBK1), and Drp1 and the oxidative stress markers NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) were measured using quantitative real-time polymerase chain reaction (qPCR). The mitochondrial morphology was detected with transmission electron microscopy (TEM), and the expression levels of p-TBK1 (S172), TBK1, p-Drp1 (S616), p-Drp1 (S637), and Drp1 were assessed using western blotting. Compared to tissue from non-RA patients, RA synovial tissue exhibited higher expression and co-localization of TBK1 and phosphorylated Drp1 (p-Drp1). Following ECH treatment, MH7A cell proliferation and inflammatory cytokine secretion were reduced, while the expression of antioxidant stress markers was significantly increased. Furthermore, ECH treatment led to reduced levels of ROS, mitochondrial fragmentation and dysregulated mitochondrial fission in MH7A cells, along with decreased expression of p-TBK1 (Ser172) and p-Drp1 (Ser616), while p-Drp1 (Ser637) levels were increased. Echinacoside regulates abnormal mitochondrial fission via the TBK1/Drp1 pathway, reducing the proliferation and inflammatory response of MH7A cells.

Efficacy and safety of anamorelin in patients with metastatic urothelial carcinoma receiving systemic chemotherapy: a randomized controlled study.

Cancer cachexia reduces chemotherapy efficacy in patients with metastatic urothelial carcinoma (mUC). Anamorelin improves cancer cachexia by increasing serum insulin-like growth factor 1 (IGF-1). The aim of this study was to evaluate the efficacy and safety of anamorelin in patients with mUC. A total of 38 patients with mUC who received platinum-based chemotherapy were enrolled in an interventional prospective study. Patients were randomized to anamorelin (Ana; n=20) or control (n=18) groups. The primary endpoint was the change in prealbumin. Secondary endpoints were changes in albumin, IGF-1, body weight, skeletal muscle mass index (SMI), interleukin-6 (IL-6) and median overall survival (mOS). Changes in prealbumin, albumin, body weight, and SMI were similar between groups. Compared to control, serum IGF-1 levels in the anamorelin-treated group were higher after 1-week (p<0.05). Changes in IGF-1 and SMI positively correlated in the anamorelin group (R=0.61, p<0.05). When the anamorelin group was divided into two groups by the median serum IGF-1 level after 1-week (Ana-IGF-1 high and Ana IGF-1 low groups), the SMI in the latter group showed a decreased tendency (p=0.14). The Ana-IGF-1 low group showed significantly higher IL-6 levels (p<0.05) at baseline and significantly shorter mOS compared to the Ana-IGF-1 high group (p<0.05). Treatment-related adverse events were comparable between the two groups (any grade: 100% vs. 100%; grade ≥3: 88.9% vs. 90.0%). Anamorelin was well tolerated in patients with mUC. A higher serum IGF-1 level might be associated with anamorelin efficacy; however, a larger study is needed to confirm this.

Loss of NR2F6 Protects from Salmonella Typhimurium Infection.

Nuclear receptors regulate key functions of mononuclear phagocytes and are critical components of the innate immune system, acting as regulators of organ health and disease. In healthy mice, the loss of the nuclear orphan receptor NR2F6 alters tissue-resident macrophage populations in the liver, lung, and spleen. In response to Salmonella Typhimurium infection, Nr2f6-deficient mice exhibit improved clinical outcomes, characterized by reduced weight loss, bacterial loads in the spleen and liver, and decreased plasma pro-inflammatory cytokines. Despite unchanged basal iron metabolism in the spleen and liver, iron regulatory proteins and the interleukin (IL)-6-hepcidin axis are altered in Nr2f6-deficient mice during Salmonella infection, reducing hypoferremia. Transcriptomic analysis of splenic red pulp macrophages reveals significant alterations of phagocytosis-related genes, including upregulation of signal-regulatory protein alpha (Sirpa). In vitro, phagocytosis of red blood cells, regulated by the inhibitory CD47-Sirpα axis, and Salmonella Typhimurium phagocytosis are significantly impaired in Nr2f6-deficient splenic macrophages. Blocking Sirpα in vitro restores the phagocytic activity of Nr2f6-deficient macrophages to wild-type levels. In vivo, Salmonella Typhimurium loads are partially increased post-infection in anti-Sirpα treated Nr2f6-deficient mice. These findings uncover a previously unrecognized role of NR2F6 in host-pathogen interactions, positioning it as a potential therapeutic target for infectious diseases.

Case Report: Intra-articular injection of tocilizumab for arthritis treatment in chronic graft-vs.-host disease

BackgroundChronic graft-vs.-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplantation. It is a leading cause of long-term morbidity, non-relapse mortality, and impaired health-related quality of life. cGVHD is a multifactorial syndrome that can manifest with articular involvement. Approximately 50% of cGVHD survivors do not respond to glucocorticoid therapy used for arthritis. Subsequently, we shall present a case of a juvenile patient with arthritis and cGVHD, who responded well to intra-articular injection of tocilizumab, after bone marrow transplantation.Case pressentationA male adolescent with acute myeloid leukemia successfully underwent marrow stem cell transplantation. However, he developed arthritis in the elbow and knee joints and had difficulty walking more than 3 months after transplantation. He was administered anti-rejection drugs with cyclosporine, ruxolitinib, and methylprednisolone by his physician, which did not work. He was subsequently treated with intravenous tocilizumab under the supervision of his rheumatologist. Although his clinical symptoms showed remission at early stages, his knee joints were more swollen, and he could not stand after being infected with COVID-19. Both of his knee joints was injected with tocilizumab at 0, 2, 4, 6, 7, 11, and 19 weeks. Interleukin (IL)-6 levels in the peripheral blood continuously decreased. After treatment for 4 months, the patient could walk a few hundred meters with minimal exertion.ConclusionAn intra-articular injection of tocilizumab could be a viable treatment option for arthritis; however, large-scale clinical trials are warranted to confirm its efficacy.

Anti-cancer effects of genistein supplementation and moderate-intensity exercise in high-fat diet-induced breast cancer via regulation of inflammation and adipose tissue metabolism in vivo and in vitro

BackgroundBreast cancer represents a significant global health concern and is influenced by a range of environmental factors. Increased fat intake and physical inactivity contribute to elevated body fat levels and are strongly linked to breast cancer incidence. Genistein (GEN), isoflavone in soy-derived foods, demonstrates anti-estrogenic properties and anti-cancer effects by regulating various mechanisms such as apoptosis. Regular physical activity prevents the progression and development of cancer by releasing various myokine signaling molecules from the muscles. This study aimed to explore the potential anti-cancer effects of combining GEN supplementation with regular moderate-intensity exercise on breast cancer.MethodsFemale BALB/c mice aged 5 weeks were divided into five groups and received GEN, moderate-intensity exercise, or a combination of both throughout the experiment. After 8 weeks of treatment, mammary tumor cells were inoculated into mammary fat pads. Anti-cancer effects of these treatments on apoptosis, macrophage polarization, and adipose tissue wasting mechanisms in breast tumors were analyzed. In addition, U937, a human monocytic leukemia cell line, was treated with phorbol-12-myristate-13-acetate and interleukin (IL)-4 to induce an M2 macrophage phenotype and analyzed markers for M2 polarization.ResultsModerate-intensity exercise alone or in conjunction with GEN proved effective in retarding tumor initiation and growth, leading to reduced tumor volume compared to GEN supplementation alone. The combined regimen enhanced the expression of apoptosis markers and augmented the proportion of M1 macrophages while diminishing M2 macrophages. In vitro, treatment with GEN and myokines suppressed markers of M2 macrophage polarization and expression of the JAK1/STAT6 signaling pathway. Furthermore, the study suggested that the combined intervention of GEN supplementation and moderate-intensity exercise prevented adipose tissue wasting by regulating adipogenesis, lipolysis, and systemic inflammation in subcutaneous fat.ConclusionsThe potential anti-cancer effects of GEN supplementation and regular moderate-intensity exercise on breast cancer are mediated through the induction of apoptosis and inhibition of macrophage polarization. They also exert a protective effect on adipose tissue wasting.

Comprehensive profiling of Rhodiola rosea roots and corresponding products: phytochemical insights and modulation of neuroinflammation in BV2 microglial cell model

IntroductionRhodiola rosea L., mainly known within the medicinal plant industry as golden root, Arctic root, or rose root, derives its name from its economic significance, distinctive morphology, and restricted geographical distribution. Extracts from Rhodiola rosea roots/rhizomes are widely used across Europe and Asia as ingredients of traditional herbal medicines and dietary supplements, with numerous claims regarding their adaptogenic effects. With the growing demand for pharmaceutical products that relieve stress-related fatigue and exhaustion, driven by technological advancements and increasing psychophysical challenges, R. rosea has become a highly sought-after resource. However, this heightened demand has also increased the risk of adulteration and the proliferation of low-quality products on the market. The reproducible efficacy and quality of R. rosea preparations are largely dependent on the variable content of key active compounds, such as rosavin, which directly influence product quality. The rapid expansion of the dietary supplement market, coupled with insufficient quality verification of products entering the market, underscores the need for rigorous identification and quality assessment of these products.MethodsThis study aimed to perform a phytochemical analysis of 13 dietary supplements claiming to contain R. rosea using HPTLC and LC-MS techniques and to correlate these findings with their anti-inflammatory activity in an LPS-stimulated BV2 microglial cell model, in vitro.ResultsOur study indicates that nearly 60% of the tested preparations did not contain the declared amount of Rhodiola rosea roots/rhizomes or the characteristic marker compounds associated with this species. Furthermore, rosavin was detected in only 9 out of the 13 analyzed products, with 4 of these containing only trace amounts of this marker compound. Misidentification of R. rosea was most frequently observed among tablet and capsule formulations, whereas products in the form of cut raw material exhibited the highest quality. Moreover, rosavin significantly and dose-dependently inhibited the secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide (LPS)-stimulated microglial cells.DiscussionThe identification of R. rosea in only 40% of the preparations underlines that rigorous control and standardisation of herbal supplements are crucial to understanding their therapeutic activity and preventing adulteration.

Green silver nanoparticles ameliorate diet-induced obesity through antioxidant and anti-inflammatory properties

This study aims to evaluate the anti-obesity effect of silver nanoparticles biosynthesized in Aloe vera leaf extract (AV-AgNPs) administrated to Sprague Dawley rats that fed with high-fat diet (HFD) for up to 12 weeks. AV-AgNPs were recognized by transmission electron microscopy (TEM) and dynamic light scattering. The in vitro study investigated the antioxidant ability, effects on coagulation time, anti-inflammatory, cytotoxicity of AVLE and AV-AgNPs and cytokinesis-block micronucleus (CBMN) assay for genotoxic effects. When the in vivo experiment is completed, different parameters such as body weight, fasting plasma glucose (FPG), serum lipid levels, white adipose tissue (WAD) oxidative stress markers and adipokines were evaluated. Green AV-AgNPs were spherical with sizes of 19.4–25.9 nm as revealed using TEM. The sizes and zeta potentials of AV-AgNPs presented particle stability up to 70 days. AV-AgNPs had a high in vitro antioxidant and anti-inflammatory abilities with no significant effects on partial thromboplastin time and the prothrombin time. In vitro CBMN assay indicated no significant genotoxic effects of AVLE or AV-AgNPs at low concentration (25 µg/ml). AV-AgNPs and AVLE showed significant decline in body FPG and lipid profile in HFD-fed rats with no apparent effects on normal pellet diet (NPD)-fed ones. In addition, oxidative stress markers, size of subcutaneous adipocytes and micro-vesicular steatosis of hepatocytes in the HFD group were significantly reduced after AVLE and AV-AgNPs administration. Finally, WAD analysis of M2 interleukin (IL)-4 and IL-10 was significantly elevated with AVLE and AV-AgNPs supplementation. Further, both significantly lowered M1 pro-inflammatory cytokines as tumor necrosis factor-α (TNF-α), IL-1β and IL-6 in the WAD of HFD-fed group. In terms of body weight, adiposity and hepatic steatosis, the anti-obesity properties of AV-AgNPs were significant (34.4–35.17% weight reduction) compared to whole AVLE (13.9–18.36% weight reduction). The biochemical and immunological effects were comparable and mediated by amelioration of oxidative stress and induction M2 polarization in WAD.