Tumor Necrosis Factor-alpha Research Articles (Page 1)

Sidt2 ameliorates TNF-α-induced apoptosis and inflammation by promoting autophagic flux via p65 signaling.

Diabetic nephropathy is still a chief reason for morbidity and mortality in persons with renal dysfunction. Thymoquinone, a primary constituent of black seed oil extracted from Nigella sativa, has anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. Glycine, an amino acid and neurotransmitter, participates in diverse physiological mechanisms. This study investigated the nephroprotective role of thymoquinone and glycine against streptozotocin (STZ)-induced diabetic nephropathy. Forty-two adult male Swiss albino rats were segregated into seven groups, each comprising six. These groups consisted of control normal rats; rats administered 60-mg STZ/kg (nephropathy); nephropathy rats treated with oral doses of 20-mg/kg/day thymoquinone (T20) or 30-mg/kg/day thymoquinone (T30); nephropathy rats treated with oral doses of 50-mg/kg/day glycine (G50) or 100-mg/kg/day glycine (G100); (T + G) nephropathy rats receiving combination therapy of 30-mg/kg/day thymoquinone and 100-mg/kg/day glycine. Various biochemical factors, including glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), total and myocardial creatine kinase (CK), kidney function parameters, blood electrolytes (Na, K, Cl, Ca, and P), and kidney histopathology, were assessed. The combined therapy of thymoquinone and glycine demonstrated enhanced efficacy in improving biochemical profiles, antioxidant levels, anti-inflammatory responses, and renal structure compared to monotherapies employing thymoquinone or glycine. The confluence of thymoquinone and glycine potentially operates through manifold pathways, encompassing the regulation of oxidative stress and modulation of inflammatory cascades. This study elucidates the potential synergistic benefits of integrating thymoquinone and glycine in diabetic nephropathy management, thereby heralding novel avenues for therapeutic interventions.

Front-line treatment for psoriatic arthritis (PsA) often involves the use of tumour necrosis factor alpha (TNFα) blocking medications (tumour necrosis factor alpha inhibition [TNFi]). However, more than 40% of patients exhibit inadequate responses, and there is no predictive clinical test available. Our goal is to investigate whether the response to TNFi treatment is associated with TNFα receptor 2 (TNFR2) rs1061622 polymorphic variants, TNFR2-M or TNFR2-R, in PsA. Furthermore, to elucidate the underlying mechanisms, differences in cell signalling and gene expression conferred by TNFR2-M vs TNFR2-R were examined. TNFR2 rs1061622 polymorphism status of 164 patients was assessed using restriction fragment length polymorphisms analysis. Discontinuation of the TNFi agents <12 months due to inadequate efficacy determined by chart review was the primary outcome. Human endothelial cells expressing endogenous or recombinant TNFR2-M or TNFR2-R and Jurkat T cells expressing recombinant TNFR2-M or TNFR2-R were utilised to investigate differences in cell signalling and gene expression. Patients with PsA with TNFR2-R variant had a ∼5-fold increased likelihood of discontinuing TNFi therapy <12 months, vs TNFR2-M carriers (95% CI 1.98-12.78). The cells with TNFR2-R alleles showed higher levels of proinflammatory gene expression in the absence of TNFa stimulation (P < .01). This activity of TNFR2-R was unaffected by a TNFα-neutralising antibody, whereas blocked by a Rho kinase (ROCK)-specific inhibitor. TNFR2 rs1061622 polymorphism significantly influences TNFi therapy responsiveness in PsA. The TNFα-independent, but ROCK activity-dependent gain-of-function activity conferred by TNFR2-R variant potentially serves as a mechanism underlying inadequate responses to TNFi in a subset of patients with PsA.

Currently, medical science is facing several issues such as microbial growth, prevalence of infections at wound site and resistance of common pathogens of wounds such as Staphylococcus aureus and Escherichia coli against synthetic molecules. Essential oils (EOs) are considered as promising alternative to synthetic molecules owing to antibacterial, antifungal, and antiinflammatory properties. Gellan gum based composite hydrogel membranes containing essential oils of geranium and lemongrass were prepared by solution-casting inotropic gelation method for effective wound healing. Hydrogel membranes were tested for their physicochemical properties, swelling index, in vitro antioxidant, and antibacterial potential. Solid-state characterization of prepared membranes elucidated the successful encapsulation of essential oils within the hydrogel matrix without any noticeable interaction. Scanning electron microscopy revealed smooth, uniform surface of blank ((gellan gum (G2) and gellan gum/collagen (GC7)) membrane while oil encapsulated formulations (Gellan gum/geranium oil (GG4), gellan gum/lemongrass oil (GL1), gellan gum/collagen/geranium oil (GCG4), and gellan gum/collagen/lemongrass oil (GCL1)) showed heterogeneous morphology. The antioxidant activity measured by DPPH free radical scavenging indicate that the GG4, GCL1 possessed strong % inhibition due to the presence of flavonoids and phenolic components. The GG4, GCL1 formulations revealed higher antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) (14mm zone of inhibition) when compared to blank formulation by disc diffusion method. Furthermore, in-vivo study showed that GG4 & GCL1 membranes dramatically decrease the size of full-thickness wounds in rat models. Histological test revealed re-epithelialization, collagen and fibroblast formation along with angiogenesis. The findings from an ELISA further evidenced the wound healing potential of optimized membranes by the down regulation of pro-inflammatory cytokines i.e. (Interleukin-6) IL-6 and TNF-α (Tumor Necrosis Factor alpha). Thus, gellan gum based composite hydrogel membranes has great potential for effective wound healing and skin regeneration capacity.

The development and pathogenesis of rheumatoid arthritis (RA) are associated with ferroptosis. This study aims to investigate the regulatory role of ribonucleotide reductase subunit M2 (RRM2) in ferroptosis and the pathogenic phenotype of fibroblast-like synoviocytes (FLSs) in RA. Transcriptomic datasets associated with rheumatoid arthritis were analyzed to identify differentially expressed genes (DEGs), which were then intersected with known ferroptosis-related genes using a Venn diagram to determine overlapping candidates. The receiver operating characteristic (ROC) curve was utilized to evaluate the diagnostic value of key genes. The expression of RRM2 was silenced using short hairpin RNA transfection. Cell viability, motility, and invasive capacity were evaluated through the CCK-8 assay, scratch assay, Transwell, and ELISA assay, respectively. Inflammatory cytokines and ferroptosis-associated indicators were quantified using ELISA and specific biochemical detection kits. Additionally, the transcriptional and protein levels of genes linked to FLS function were analyzed. RRM2 was upregulated in tumor necrosis factor-alpha (TNF-α)-induced MH7A cells. Knockdown of RRM2 significantly inhibited TNF-α-induced cell proliferation, migration, invasiveness, and the release of pro-inflammatory cytokines in MH7A cells. Additionally, RRM2 knockdown induced ferroptosis, as evidenced by increased reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA), alongside decreased expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Further mechanistic analysis revealed that RRM2 led to nuclear factor-kappa B (NF-κB) signaling activation. RRM2 inhibits ferroptosis and enhances the pathogenic behavior of RA FLSs through activation of the NF-κB pathway, highlighting its pivotal contribution to RA development.

Hemorrhagic transformation (HT) is a severe complication occurring in ischemic stroke patients undergoing tPA thrombolytic therapy, which significantly limits its clinical applicability. The mechanism and intervention of HT is still not fully understood. In our study, we found that an increased mobilization of circulating formyl peptide receptor 1 (FPR1) expressing leucocytes into the ischemic brain after tPA treatment in mice. In Fpr1-/- mice, neutrophil mobilization and HT occurrence after tPA thrombolysis decreased. Notably, pharmacological inhibition of FPR1 using a novel antagonist T0080 effectively mitigated tPA-associated HT, concurrently reducing neutrophil infiltration into the brain and preserving blood-brain barrier (BBB) integrity. We further revealed that brain infiltration neutrophils facilitate BBB leakage and neuron death by producing cytotoxic molecules such as reactive oxygen species (ROS), matrix metalloproteinase-9 (MMP9), and tumor necrosis factor-alpha (TNF-α). Neutrophil depletion and adoptive transfer experiments in vivo with FPR1+ neutrophils demonstrate that the essential role of FPR1+ neutrophils in mediating HT post-tPA administration in mice. Collectively, these findings identify neutrophils FPR1 activation as a key mechanistic driver exacerbating HT following tPA thrombolysis in ischemic stroke.

To explore the therapeutic efficacy of Hypericum japonicum (HJ) and its active compounds in mitigating hepatic fibrosis by elucidating their anti-inflammatory and anti-apoptotic effects. Twenty-four mice were randomly divided into 4 groups: control group, model group, HJ-1 mg/g group, and HJ-2 mg/g group. A hepatic fibrosis model was established via carbon tetrachloride (CCl4) injection at a dose of 5 µL/g of body weight, twice weekly for 6 weeks. Subsequently, mice were gavaged with 1 mg/g or 2 mg/g HJ aqueous solution to assess its effects on liver pathological injury, liver function markers, and fibrosis markers in model mice. Integrated analyses employing network pharmacology, molecular docking, and eukaryotic transcriptomics were conducted to identify interactions between key HJ active constituents (e.g., mairin, beta-sitosterol, quercetin, kaempferol) and core targets [e.g., B-cell lymphoma-2 (Bcl-2), tumor protein p53 (TP53), tumor necrosis factor-alpha (TNF-α)], along with associated signaling pathways. Additionally, in vitro experiments were used to validate the effect of HJ active constituents on the viability of CCl4-injured HepG2 cells, expression of inflammatory cytokines, and apoptotic pathways. The study further utilized 16S rRNA amplicon sequencing to explore the modulatory effects of HJ on gut microbiota structure and function. In vivo experiments demonstrated that HJ intervention significantly ameliorated liver pathological damage, reduced liver function markers, and downregulated α -smooth muscle actin expression in mice (P<0.01). Network pharmacology and molecular docking revealed significant binding affinity between key HJ active constituents and core targets (e.g., Bcl-2, TP53, TNF-α). Eukaryotic transcriptomic analysis further identified core differentially expressed genes modulated by HJ, which were implicated in inflammatory response regulation and extracellular matrix receptor interaction pathways. Although HJ intervention did not significantly alter gut microbiota richness, it modulated metabolic and immune functions closely associated with hepatic fibrosis. In vitro, HJ active constituents significantly increased the viability of CCl4-injured HepG2 cells, downregulated TNF-α and interleukin-6 mRNA expression, and suppressed the mitochondrial apoptotic pathway via Bcl-2 regulation (P<0.01). Among the compounds, mairin demonstrated the most potent effect in reducing aspartate aminotransferase and hydroxyproline levels, while mairin and beta-sitosterol exerted anti-fibrotic effects by suppressing TNF-α and decreasing glutathione, respectively. HJ and its active ingredients elucidate the anti-inflammatory and anti-apoptotic effects in hepatic fibrosis. Further they emerge as promising candidates for targeted therapy against hepatic fibrosis.

Therapeutic stress triggers tumor STAT1 acetylation to disarm immunotherapy.

To examine changes in rheumatoid arthritis (RA) medication prescriptions during the peri-delivery period, and to explore recent RA prescription trends using a Japanese claims database. This retrospective observational cohort study used the JMDC Claims Database. We identified pregnant women with RA who delivered between April 2018 and October 2023. The outcome was the initiation or resumption of intensive treatment after delivery, defined as new or restarting of biologic disease modifying anti-rheumatic drugs (DMARDs), targeted synthetic DMARDs, oral corticosteroids (OCS), or methotrexate. We identified 229 mothers with RA and 246 deliveries. Intensive treatment was initiated in 55 (22.4%) deliveries. Continuation of the same prescription from before delivery was observed in 106 deliveries (43.1%). The most frequent new prescription postpartum was methotrexate in 18 (7.3%) deliveries. OCS were the most commonly prescribed medications throughout the observation period. Tumour necrosis factor alpha inhibitors were prescribed at similar rates as OCS before pregnancy and in the first trimester, but declined during the second and third trimesters, and returned postpartum. The number of deliveries that required intensive treatment postpartum was lower than in previous studies. Our results suggest that the latest guidelines for pregnant women with RA help control disease activity.

Sepsis, a life-threatening condition resulting from a dysregulated host response to infection, is associated with high mortality and remains a major global health burden. Sepsis is characterized by an imbalance between oxidative stress and inflammation, leading to disruption of thiol-disulfide homeostasis, hematological abnormalities, cytokine dysregulation, and widespread tissue injury. An experimental sepsis model was established in thirty-two male Balb-C mice using lipopolysaccharide administration. Animals were randomized into four groups: control, vitamin E, sepsis, and sepsis plus vitamin E. Serum oxidative stress markers, thiol-disulfide parameters, and inflammatory mediators, including C-reactive protein, interleukin-40, and tumor necrosis factor-alpha, were measured. Hematological indices of systemic inflammation were evaluated (Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio), and lung, liver, and kidney tissues were examined histologically using a semi-quantitative scoring system. Lipopolysaccharide-induced sepsis caused marked disruption of thiol-disulfide balance, characterized by reduced native and total thiol levels, elevated disulfide levels, increased cytokine release, and severe histopathological injury. Vitamin E supplementation restored thiol-disulfide homeostasis, decreased oxidative stress, and attenuated systemic inflammation. In the sepsis plus vitamin E group, serum thiol levels increased significantly, while disulfide levels declined. Interleukin-40 showed a 24.2% reduction and tumor necrosis factor-alpha a 9.8% reduction compared with untreated septic animals. Histopathological analyses confirmed reduced inflammatory cell infiltration, vascular congestion, and tissue degeneration, particularly in the lungs. Vitamin E demonstrated significant protective effects against sepsis-induced oxidative and inflammatory injury by preserving thiol-disulfide homeostasis and reducing cytokine production. The more pronounced effect on interleukin-40 compared with tumor necrosis factor-alpha suggests selective modulation of inflammatory pathways and highlights interleukin-40 as a potential biomarker and therapeutic target. These findings support vitamin E as a promising adjunctive therapy in sepsis, although further studies are required to define optimal dosing strategies and assess clinical applicability.

Objective Sepsis-induced cardiotoxicity (SIC) is a critical complication characterized by inflammation, oxidative stress, and apoptosis, leading to myocardial dysfunction. The short-acting opioid analgesic remifentanil (REMI) possesses antioxidant and anti-inflammatory properties. This study aimed to evaluate the cardioprotective effects of REMI on lipopolysaccharide (LPS)-induced SIC by examining inflammation, oxidative stress, apoptosis, and mitochondrial function. Materials and methods Thirty-two female Wistar albino rats were divided into four groups: control, lipopolysaccharide (LPS), LPS + REMI, and REMI. Myocardial and aortic tissues were analyzed for histopathology, immunoexpression of Caspase-3 (Cas-3), nuclear factor kappa beta (NF-κB), and tumor necrosis factor alpha (TNF-α). Oxidative stress markers, including total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), were measured. Mitochondrial apoptosis-related gene expression of AMP-activated protein kinase (AMPK), BCL2 Associated X (BAX), B-cell lymphoma 2 (BCL-2), Sirtuin 1 (SIRT1), and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) was assessed. Results LPS administration induced severe histopathological damage, increased oxidative stress (elevated TOS and OSI), and upregulated apoptotic (Cas-3, BAX/BCL-2 imbalance) and inflammatory (NF-κB, TNF-α) markers. REMI treatment significantly alleviated myocardial and aortic injury, reducing the histopathological score. It markedly decreased Cas-3, NF-κB, and TNF-α expression, lowered TOS and OSI levels, and modulated the BAX/BCL-2. Furthermore, REMI restored the expression of AMPK, SIRT1, and PGC-1α genes, indicating a protective effect on mitochondrial biogenesis and energy metabolism. Conclusions REMI exhibits significant cardioprotective effects in LPS-induced SIC by attenuating inflammation, oxidative stress, and apoptosis while preserving mitochondrial homeostasis.

One of the most frequent reasons behindrespiratory failure is acute lung injury (ALI). In response to endoplasmic reticulum stress (ERS), the protein known as stimulator of interferon genes (STING) triggers strong lung inflammatory reactions and damage. The current study evaluated the possible influence of platelet-rich plasma (PRP) on ALI through altering the cyclic GMP-AMP synthase (cGAS)-triggered STING/ERS/TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3)/nuclear factor kappa B (NF-κB) pathway. Twenty-one adult male Wistar rats were arbitrarily divided into three sets of seven: (1)control(CTRL); (2) ALI, in whichthe rats were givenintraperitoneal (i.p.) lipopolysaccharide (LPS) at 10mg/kg once; and (3) ALI + PRP, in which, at 1 week after i.p. LPS injection, rats were injected (i.p.) with PRP every 3days for 4weeks. At the end of the experiment, blood samples and lung tissues were evaluated at biochemical, molecular, and histological levels. PRP caused downregulation of the cGAS-induced STING/ERS/TBK1/IRF3/NF-κB signaling pathway and lessened lung inflammatory and apoptotic insults. This was evident on microscopic examination of lung tissue with significantly decreased immunoreactivity of lung tissue caspase 3, NF-κB, and tumor necrosis factor-alpha. PRP is a promising biological therapeutic regimen against ALI.

Prospective cohort study. To evaluate the impact of smoking on intervertebral disc degeneration (IDD) by analyzing inflammatory and anti-inflammatory biomarkers-interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and alpha-1 proteinase inhibitor (A1PI, also known as AAT)-in disc tissue samples from smokers and nonsmokers undergoing microdiscectomy. IDD is a leading cause of chronic lower back pain and disability, often requiring surgical intervention. Smoking is a well-established risk factor, promoting oxidative stress, inflammation, and impaired tissue repair. However, few studies have directly compared biochemical changes in surgically removed disc tissue from smokers and nonsmokers. Sixty-seven patients undergoing microdiscectomy for lumbar disc herniation were enrolled, with 34 classified as smokers and 33 as nonsmokers. Intervertebral disc tissue was collected intraoperatively and analyzed through enzyme-linked immunosorbent assay (ELISA) to quantify IL-1β, IL-6, TNF-α, and AAT levels. Independent t tests and Mann-Whitney U tests were applied for group comparisons. Receiver Operating Characteristic (ROC) curves assessed biomarker diagnostic accuracy. Smokers were significantly younger ( P <0.001) and had lower BMI ( P =0.031) than nonsmokers. Levels of IL-1β ( P <0.001), IL-6 ( P <0.001), and TNF-α ( P <0.001) were significantly higher in smokers, while AAT levels were lower ( P <0.001). ROC analysis showed high discriminatory power for IL-1β (AUC=0.912), IL-6 (AUC=0.899), TNF-α (AUC=0.895), and AAT (AUC=0.881) in identifying smoking-related disc degeneration. Smoking increases inflammatory activity and reduces anti-inflammatory protection in intervertebral discs, accelerating degeneration. Elevated IL-1β and TNF-α are reliable biomarkers of smoking-related inflammation, while reduced AAT indicates compromised protective mechanisms. These results support smoking cessation as a preventive strategy and highlight biomarker-based approaches for early detection and targeted therapy in IDD.

Background: Alopecia is a condition with partial or complete hair loss, leading to psychological distress. Current treatments, such as minoxidil and finasteride, have limited efficacyand side effects. Recent studies suggest that mesenchymal stem cells (MSCs)-derived exosomes offer regenerative potential by modulating inflammation and enhancing hair follicle regeneration, though optimal dosage remains unclear. Tumor necrosis factor-alpha (TNF-α) inhibits hair follicle growth, while vascular endothelial growth factor (VEGF) promotes hair regrowth. This study evaluates exosome therapy from hypoxia (Hypo-Exo)-treated MSCs in modulating TNF-α and VEGF in a fluconazole-induced alopecia-like model..Materials and methods: An experimental post-test only control group design was used with 30 male Wistar rats, divided into five groups: Healthy group, 0.9% NaCl-treated group, 5% Minoxidil-treated group, 100 μg/mL Hypo-Exo MSCs-treated group, and 200 μg/mL Hypo-Exo MSCs-treated group. TNF-α and VEGF levels were analyzed using ELISA on day 14 post-treatment. Results: The highest TNF-α level was found in the 0.9% NaCl-treated group (307.46 ± 20.68 pg/mL) and significantly reduced (p&lt;0.05) in 100 μg/mL Hypo-Exo MSCs-treated group (65.38±15.05 pg/mL) and 200 μg/mL Hypo-Exo MSCs-treated group (37.16±7.14 pg/mL). VEGF levels were the highest in the 200 μg/mL Hypo-Exo MSCs-treated group (189.11±9.75 pg/mL) and 100 μg/mL Hypo-Exo MSCs-treated group (158.50±5.33 pg/mL), compared to the 0.9% NaCl-treated group (69.60±15.39 pg/mL). Conclusion: Hypo-Exo MSCs significantly reduced TNF-α and increased VEGF levels, supporting their potential as a novel regenerative therapy for alopecia. Keywords: alopecia, TNF-α, VEGF, exosome, hypoxia, mesenchymal stem cells

Background/Objectives: Liposomes and niosomes are established drug delivery systems, some of which have received FDA approval and demonstrated therapeutic efficacy. This study investigates a novel niosome formulation, utilizing two natural food-derived components, as a cost-effective alternative to traditional nanocarriers. The active pharmaceutical ingredient, calcium fructoborate (CF), possesses notable anti-inflammatory properties. The study aims to evaluate the efficacy of this novel natural niosome (NN) system, in comparison to existing nanocarrier formulations, in an ischemia–reperfusion (I/R) pain model. Methods: An acute ischemia/reperfusion injury model was employed to induce pain in 36 rats. The efficacy of the following treatments was assessed: standard CF, liposomal CF, niosomal CF, and natural niosomal CF. Efficacy was determined by quantifying the treatments’ ability to mitigate inflammation and oxidative stress in the kidneys, lungs, heart, and liver, and by evaluating potential organ damage through histopathological analysis. Results: The NN treatment significantly reduced malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels in the kidneys and liver compared to the other treatments (p &lt; 0.05). In the kidney, NN treatment also significantly decreased creatinine levels relative to the other treatments (p &lt; 0.01). The histopathological analysis of kidney tissue revealed that NN treatment attenuated tubular dilation, interstitial inflammation, and epithelial thinning. In the heart, liposomal treatment significantly increased MDA levels (p &lt; 0.05) and decreased sialic acid levels (p &lt; 0.05); however, no significant differences were observed in troponin levels (p &gt; 0.05). In the lung, no significant differences in MDA, lactate, TNF-α, or sialic acid levels were detected among the treatment groups (p &gt; 0.05). Conclusions: The natural niosome drug delivery system demonstrates potential as a therapeutic intervention for protecting and improving kidney and liver health. While liposomal treatment exhibited some adverse effects, it effectively suppressed inflammation. This study provides a foundation for future research and positions the NN drug delivery system as a promising, cost-effective alternative for inflammation-associated pathologies.

Background: Centaurium erythraea Rafn. (C. erythraea) is a medicinal plant traditionally used in European folk medicine for the treatment of wounds, skin inflammations, and other dermatological conditions, in addition to its well-documented systemic antioxidant and anti-inflammatory effects. However, its topical applications remain insufficiently investigated, particularly using plant material collected from Romania. The purpose of this study was to prepare different ointment formulations containing C. erythraea Rafn. extract obtained from the aerial parts of the plant, using various excipients, and to evaluate their in vitro and in vivo efficacy. Methods: The phytochemical profile of C. erythraea extract was characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The lyophilized extract was pre-dissolved in different solubilizing agents—Transcutol® P (diethylene glycol monoethyl ether), Capryol® 90 (propylene glycol monocaprylate), or a combination of both—and then incorporated into five ointment formulations. Texture analysis and an in vitro membrane diffusion study were performed. The antioxidant capacity of the formulations was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) assays. Anti-inflammatory activity was evaluated in vitro using tumor necrosis factor-alpha (TNF-α)-induced interleukin-1 beta (IL-1β) production in human keratinocyte (HaCaT) cells, and in vivo using a carrageenan-induced rat paw edema model. Results: LC–MS/MS identified 18 polyphenolic compounds, with hyperoside (3.78 ± 0.05 µg/mL), protocatechuic acid (1.13 ± 0.06 µg/mL), chlorogenic acid (1.07 ± 0.06 µg/mL), and quercetin (0.53 ± 0.03 µg/mL) as the principal constituents. The formulation containing both Transcutol® P and Capryol® 90 exhibited the most pronounced antioxidant activity (65% DPPH inhibition; 69.71 ± 0.83 mg gallic acid equivalent/mL) and significantly reduced IL-1β levels by 45.7% compared to the inflamed control. In vivo, this formulation showed comparable anti-edematous effects to a methylprednisolone ointment. Furthermore, it demonstrated the highest skin permeation efficiency, with a quercetin diffusion coefficient of 35.12 × 10−5 cm2/min. Conclusions: These findings highlight the therapeutic potential of C. erythraea extract from aerial parts in topical formulations and underscore the enhancing role of Transcutol® P and Capryol® 90 in improving both the pharmacodynamic and pharmacokinetic properties of bioactive compounds.

Acute myocardial infarction is a leading cause of morbidity and mortality, with ischaemia-reperfusion (I/R) injury exacerbating myocardial damage. Vagus nerve stimulation (VNS) has been reported to exert cardioprotective effects, but its efficacy in preconditioning against I/R injury requires further investigation. We evaluated the cardioprotective effects of VNS preconditioning in a rat model of acute myocardial infarction with induced I/R injury. Sixty rats were randomized into Pre-VNS, Control and Sham groups. The Pre-VNS group received 1 week of low-level cervical VNS before induction of I/R injury; stimulation was deactivated 30 min before ischaemia. Survival, echocardiographic function, reperfusion arrhythmias, arrhythmia inducibility, infarct size, apoptosis and inflammatory cytokines were assessed. Survival did not differ significantly between Pre-VNS and Control groups (75.0%vs. 65.0%, p=0.497). However, Pre-VNS animals exhibited preserved cardiac function, with higher ejection fraction and fractional shortening (p<0.001). VNS preconditioning reduced the incidence of reperfusion arrhythmia during left anterior descending coronary artery ligature release (p=0.006) and decreased the arrhythmia index on programmed stimulation (p=0.003). Infarct size and cardiomyocyte apoptosis were significantly attenuated (p<0.001), accompanied by markedly lower serum interleukin-1β, interleukin-6 and tumour necrosis factor-alpha levels (p<0.001). VNS preconditioning effectively mitigates I/R injury by improving cardiac function, reducing infarct size and arrhythmias, and attenuating inflammatory and apoptotic responses.

In recent years, monoclonal antibodies targeting key cytokines underlying the occurrence of psoriatic skin lesions and joint involvement, i.e., Tumor Necrosis Factor-alpha (TNF-α), Interleukin 17 (IL-17), Interleukin 12 (IL-12), and Interleukin 23 (IL-23), have become more commonly used in the therapy of psoriasis. Due to the high effectiveness, a favorable safety profile, and growing availability of biological treatment methods, the number of patients receiving chronic monoclonal antibody therapy is increasing each year. However, the factors affecting the effectiveness of biological drugs are not fully recognized. The study aimed at analyzing the clinical profile of patients and non-specific inflammatory markers in terms of the response to the psoriasis treatment with IL-17, IL-23, IL-12/23, and TNF-α inhibitors. The analysis involved 185 patients receiving biological therapy in the Department of Dermatology and Venereology at the Medical University of Lodz, which resulted in a total of 222 treatment cycles (TC). The super-response was defined as 100% reduction in the Psoriasis Area and Severity Index (PASI 100), at week 16 (±4 weeks) of therapy. Our study indicates that the chance of achieving a super-response was higher among younger patients with no psoriatic lesions on palms and soles, not suffering from non-alcoholic fatty liver disease, previously treated with methotrexate, and characterized by a higher level of derived Neutrophil-to-Lymphocyte Ratio (dNLR) at the beginning of treatment.

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) is an age-associated cardiometabolic disease associated with metabolic and inflammatory changes in cardiac tissue, pulmonary circulation and right ventricular dysfunction. Elevated tumour necrosis factor α (TNFα) levels are predictive of the risk of morbidity events in HFpEF. TNF-mediated metabolic responses may have a critical impact on both cardiac and pulmonary pathobiology. We therefore investigated the influence of TNF-deficiency on metabolism and the severity of HFpEF and its consequences in a gender-specific manner. Methods Meta-inflammatory HFpEF was induced in a mouse model by the combination of metabolic (high-fat diet [HFD]) and hypertensive stress (inhibition of constitutive NO synthase by Nω-nitro-1-arginomethyl ester (L-NAME) via drinking water) over a period of 15 weeks. The control group consisted of TNF+/+ and TNF-/- mice that received a normal chow diet. The phenotypic severity was determined by weight analyses, determination of insulin resistance and morphometric, echocardiographic and haemodynamic measurements of cardiopulmonary parameters. Left ventricular hypertrophy was quantified as the ratio of the wet weight of the left ventricle including septum to tibia length (LV+S/tibia). Right ventricular systolic pressure (RVSP) was measured using a Millar pressure catheter inserted into the right ventricle. Results TNF-/- mice of both male (22.43±2.97 vs. 24.82±1.66g, p&amp;lt;0.05) and female (16.71±1.07 vs. 17.98±2.56g, p&amp;lt;0.01) sexes had slightly lower baseline weights than age-matched TNF+/+ control mice. Under HFpEF conditions (HFD + L-NAME), the weight gain of female animals increased equally in both genotypes (TNF-/-: +17.23±0.79g; TNF+/+: +17.37±2.91g, n.s.). In contrast, male TNF-/- mice showed a significantly lower weight increase compared to TNF+/+ mice (TNF-/-: +12.33±0.67g vs. TNF+/+: +21.38±0.93g; p&amp;lt;0.001). In addition, the glucose tolerance test in male mice in the HFpEF group also revealed a significant difference between TNF-/- (403.7±42.2 mg/dl) and TNF+/+ mice (549.0±39.0 mg/dl, p&amp;lt;0.01), while no difference between the genotypes was detected in female mice. Male TNF+/+ animals, but not TNF-/- mice, exhibited the features of HFpEF with left ventricular hypertrophy, as well as echocardiographic signs of diastolic LV dysfunction under HFD+L-NAME. In contrast, female TNF-/- and TNF+/+ mice developed comparable HFpEF. With regard to RVSP and Fulton index (RV/LV+S), there were no significant differences between the respective groups for both sexes. Conclusion Male TNF-deficient mice were protected from obesity, insulin resistance and HFpEF under conditions of meta-inflammatory stress. Under the given experimental conditions, TNFα has a decisive influence on the degree of metabolic changes and HFpEF, especially in males. The molecular basis of these gender-specific differences is the subject of further investigations.

Ethnopharmacological relevance Heart failure (HF) is a major global health challenge. Traditional therapies have limitations, while recent studies highlight plant extracts’ potential due to their medicinal properties and milder side effects. Objective This study conducts a systematic review and network meta-analysis (NMA) to assess the therapeutic effects of plant extracts on patients with heart failure, providing robust evidence for clinical practice. Materials and methods A comprehensive search of databases, including PubMed, Embase, and Cochrane Library, was performed. Studies were screened using predefined criteria to extract data and assess quality. Network meta-analysis enabled direct/indirect comparisons of multiple plant extracts’ efficacy in heart failure intervention. Results A total of 20 studies encompassing 2,077 patients were incorporated into the analysis. Astragalus extract demonstrated the highest efficacy in enhancing the 6-min walk test (6-MWT) score (surface under the cumulative ranking curve [SUCRA]: 90.70%) and reducing tumor necrosis factor-alpha (TNF-α) levels (SUCRA: 74.4%). Shenfu extract exhibited superior efficacy in decreasing B-type natriuretic peptide (BNP) values (SUCRA: 68.2%) and enhancing the quality of life (QL) (SUCRA: 77.0%). Red ginseng extract was more effective in improving left ventricular ejection fraction (LVEF) (SUCRA: 77.9%), while Ginkgo biloba extract showed greater efficacy in ameliorating New York Heart Association (NYHA) functional classification (SUCRA: 76.5%). Despite these findings, heterogeneity and methodological issues in the studies warrant further high-quality, large-scale randomized controlled trials (RCTs) to validate the results and determine the optimal plant extract use in heart failure treatment. Conclusion Astragalus extract, red ginseng extract, Ginkgo biloba extract, Terminalia arjuna extract, and Shenfu extract have demonstrated significant efficacy in heart failure management in the study for the selection of optimal plant extracts based on enhanced indicators of cardiac function outcomes. Continued research through rigorous randomized controlled trials is essential to substantiate and refine the current evidence.