Tumor Necrosis Factor-alpha Levels Research Articles

The therapeutic potential of isosakuranetin against perfluorooctane sulfonate instigated cardiac toxicity via modulating Nrf-2/Keap-1 pathway, inflammatory, apoptotic, and histological profile.

Perfluorooctane sulfonate (PFOS) is a pervasive organic toxicant that damages body organs, including heart. Isosakuranetin (ISN) is a plant-based flavonoid that exhibits a broad range of pharmacological potentials. The current investigation was conducted to evaluate the potential role of ISN to counteract PFOS-induced cardiac damage in rats. Twenty-four albino rats (Rattus norvegicus) were distributed into four groups, including control, PFOS (10 mg/kg) intoxicated, PFOS + ISN (10 mg/kg + 20 mg/kg) treated, and ISN (20 mg/kg) alone supplemented group. It was revealed that PFOS intoxication reduced the expressions of Nrf-2 and its antioxidant genes while escalating the expression of Keap-1. Furthermore, PFOS exposure reduced the activities of glutathione reductase (GSR), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), Heme oxygenase-1 (HO-1) and glutathione (GSH) contents while upregulating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Besides, PFOS administration upregulated the levels of creatine kinase-MB (CK-MB), troponin I, creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Moreover, the levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were increased after PFOS intoxication. Additionally, PFOS exposure downregulated the expression of Bcl-2 while upregulating the expressions of Bax and Caspase-3. Furthermore, PFOS administration disrupted the normal architecture of cardiac tissues. Nonetheless, ISN treatment remarkably protected the cardiac tissues via regulating aforementioned dysregulations owing to its antioxidative, anti-inflammatory, and antiapoptotic properties.

Evaluating inflammatory outcomes: A systematic review and meta-analysis of aerobic versus resistance exercise interventions

Chronic inflammation is widely recognized as a crucial contributor to the onset and progression of various diseases. Physical activity serves as a nonmedicinal intervention known to influence inflammatory dynamics. The specific effects of distinct exercise types, namely aerobic and resistance training, on inflammatory indices have not been fully delineated. This systematic review with meta-analysis seeks to clarify the relative impacts of these 2 forms of exercise on markers of inflammation. An exhaustive literature review was performed across several databases, including MEDLINE, EMBASE, and the Cochrane Library, to identify randomized controlled trials that assess the impact of aerobic versus resistance training on inflammatory markers. The primary variables of interest were alterations in inflammatory indicators such as C-reactive protein, interleukin-6, and tumor necrosis factor–alpha. We synthesized the data employing a random-effect meta-analytical approach and evaluated heterogeneity using the I² statistic. The literature search culminated in 36 randomized controlled trial with a collective participant count of 3616. Data analyses revealed that aerobic training is associated with a notable decrease in levels of interleukin-6 [standardized mean difference (SMD): −0.13, 95% CI: −0.31 to −0.05] and C-reactive protein (SMD: −0.28, 95% CI: −0.47 to −0.09), whereas resistance training is linked to a significant reduction in tumor necrosis factor–alpha levels (SMD: −0.61, 95% CI: −0.87 to −0.34). The investigation indicates that both aerobic and resistance training modalities play roles in diminishing inflammatory markers, likely through different biological processes. These insights highlight the critical nature of selecting appropriate exercise modalities to manage inflammatory health issues effectively. It is imperative to conduct further studies to unravel the precise mechanisms at play and to refine exercise recommendations for tailored management of inflammation.

Effects of dietary glycerol monolaurate on growth and digestive performance, lipid metabolism, immune defense and gut microbiota of shrimp (Penaeus vannamei)

The advancement of the Penaeus vannamei industry in a sustainable manner necessitates the creation of eco-friendly and exceptionally effective feed additives. To achieve this, 720 similarly-sized juvenile shrimp (0.88 ± 0.02 g) were randomly divided into four groups in this study, with each group consisting of three replicates, each tank (400 L) containing 60 shrimp. Four experimental diets were formulated by adding 0, 500, 1000, and 1500 mg kg−1 glycerol monolaurate (GML) to the basal diet, and the feeding trial lasted for 42 days. Subsequently, a 72-h White Spot Syndrome Virus (WSSV) challenge test was conducted. Polynomial orthogonal contrasts analysis revealed that with the increase in the concentration of GML, those indicators related to growth, metabolism and immunity, exhibit linear or quadratic correlations (P < 0.05). The results indicate that the GML groups exhibited a significant improvement in the shrimp weight gain rate, specific growth rate, and a reduction in the feed conversion ratio (P < 0.05). Furthermore, the GML groups promoted the lipase activity and reduced lipid content of the shrimp, augmented the expression of triglyceride and fatty acid decomposition-related genes and lowered the levels of plasma triglycerides (P < 0.05). GML can also enhanced the humoral immunity of the shrimp by activating the Toll-like receptor and Immune deficiency immune pathways, improved the phagocytic capacity and antibacterial ability of shrimp hemocytes. The challenge test revealed that GML significantly reduced the mortality of the shrimp compared to control group. The 16S rRNA sequencing indicates that the GML group can increases the abundance of beneficial bacteria. However, 1500 mg kg−1 GML adversely affected the stability of the intestinal microbiota, significantly upregulating intestinal antimicrobial peptide-related genes and tumor necrosis factor-alpha levels (P < 0.05). In summary, 1000 mg kg−1 GML was proven to enhance the growth performance, lipid absorption and metabolism, humoral immune response, and gut microbiota condition of P. vannamei, with no negative physiological effects.

The effects of pearl oyster shell-derived bone grafts on TNF-alfa levels: An in vivo study in Cavia porcellus

Abstract Objective: This study aims to assess the effect of bone graft materials derived from pearl oyster shells on the tumor necrosis factor-alpha (TNF-α) level. Methods: This research utilized a bone graft containing hydroxyapatite Pinctada maxima (HPM) powder obtained from pearl oyster shells. Material testing was conducted on 30 male guinea pigs aged 8-10 weeks, divided into three groups: the negative control group, the group treated solely with HPM, and the group treated with HPM combined with platelet-rich fibrin (PRF). Each treatment group was observed for 7 and 14 days. The results were analyzed using One-way ANOVA with a significance level of p&lt;0.05. Results: The findings demonstrated a decrease in the average TNF-α levels across all groups. On observation days 7 and 14, the HPM group exhibited a significant difference compared to the negative control group, indicating reduced TNF-α levels. However, no significant difference was observed when comparing the HPM group with the HPM and PRF groups. Conclusions: Bone grafts derived from pearl oyster shells possess high levels of hydroxyapatite, and the addition of PRF into the bone graft effectively reduces TNF-α.

Anti-inflammatory and/or immunomodulatory activities of Uncaria tomentosa (cat's claw) extracts: A systematic review and meta-analysis of in vivo studies.

Uncaria tomentosa (Willd. ex Schult.) DC. (Rubiaceae) is traditionally used by Amazonian indigenous groups to treat inflammatory diseases. To date, there are no systematic reviews and meta-analyses on the use of U. tomentosa for inflammation control in animals supporting the traditional knowledge about this species. This study was conducted to evaluate the effect of U. tomentosa extracts in modulating inflammatory mediators and to determine which types of inflammatory diseases can be treated by this species. We conducted a systematic review and meta-analysis of preclinical studies published before 26 July 2023, identified in PubMed, Embase, and Scopus. Four independent reviewers extracted the data and assessed the risks of bias. The effects of U. tomentosa on inflammatory diseases and the inflammatory mediators involved were extracted from the studies. Standardized mean differences (SMD) and 95% confidence intervals (95%CI) of the outcomes were estimated. The meta-analyses were conducted using RevMan 5.4 (Cochrane Collaboration). This protocol was registered in PROSPERO (CRD42023450869). Twenty-four of 523 studies were included. U. tomentosa extracts decreased the cytokines interleukin (IL)-6 (SMD: -0.72, 95%CI: -1.15, -0.29, p = 0.001) and transcription factor nuclear factor kappa-B (NF-κB) (SMD: -1.19, 95%CI: -1.89, -0.48, p = 0.001). However, the extracts did not significantly alter IL-1 (SMD: -0.16, 95%CI: -0.87, +0.56, p = 0.67), IL-10 (SMD: -0.05, 95%CI:-0.35, 0.45, p = 0.80), or tumor necrosis factor-alpha (TNF-α) levels (SMD: 0.18, 95%CI: -0.25, 0.62, p = 0.41). Many extracts of stem bark, roots, and leaves of U. tomentosa, mostly aqueous and hydroethanolic, exhibited anti-inflammatory and/or immunomodulatory activities and low toxicity. The extracts decreased NF-κB and IL-6. These findings suggest that this species has the potential to treat inflammatory diseases in which these markers are increased, according to the ethnopharmacological use. These activities are not related to a specific class of compounds.

Hyposalivation in patients with psoriasis: Association with severity, inflammatory, and anti-inflammatory cytokine biomarkers of the disease.

The aim of the study is to expound the effect of psoriasis on salivary glands by evaluating the secretion of saliva and salivary cytokine biomarkers in patients with psoriasis. This study was conducted by recruiting 120 subjects that included 60 patients diagnosed clinically with active psoriasis and 60 healthy controls who were age and gender matched to psoriatic subjects. Unstimulated whole saliva was collected from all the subjects by spitting method, and levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-2 (IL-2), and IL-10 (IL-10) were determined via enzyme-linked immunosorbent assay (BT Lab, Shanghai, China). Secretion of saliva in psoriasis patients was considerably reduced than in healthy controls. The concentrations of pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-2) were significantly increased, whereas level of anti-inflammatory cytokine (IL-10) was markedly decreased in the saliva of psoriasis patients with hyposalivation compared to healthy subjects. Our results demonstrated significant negative correlation of salivary flow rates with the disease severity. No significant correlations were obtained between salivary levels of tested cytokines and salivary flow rates in our study. Findings of the study reflect inflammation of salivary glands with reduced salivary flow rates in psoriasis patients. The inflammatory responses in salivary gland tissues by virtue of increased pro-inflammatory cytokines concentrations together with lower anti-inflammatory cytokine levels may have a role in affecting the saliva secretion in psoriasis patients. Secretion of unstimulated saliva in psoriasis patients decreases with the severity and duration of the disease.

Cytokine and Microbiome Changes in Adolescents with Anorexia Nervosa at Admission, Discharge, and One-Year Follow-Up.

Anorexia nervosa (AN) is a severe eating disorder that predominantly affects females and typically manifests during adolescence. There is increasing evidence that serum cytokine levels are altered in individuals with AN. Previous research has largely focused on adult patients, assuming a low-grade pro-inflammatory state. The serum levels of the cytokine tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and IL-15, which are pro-inflammatory, were examined in 63 female adolescents with AN and 41 age-matched healthy controls (HC). We included three time points (admission, discharge, and 1-year follow-up) and investigated the clinical data to assess whether the gut microbiota was associated with cytokine alterations. Relative to the HC group, serum levels of IL-1β and IL-6 were significantly lower during the acute phase (admission) of AN. IL-1β expression was normalised to control levels after weight recovery. TNF-α levels were not significantly different between the AN and HC groups. IL-15 levels were significantly elevated in patients with AN at all time points. We found associations between cytokines and bodyweight, illness duration, depressive symptoms, and the microbiome. In contrast to most findings for adults, we observed lower levels of the pro-inflammatory cytokines IL-1β and IL-6 in adolescent patients, whereas the level of IL-15 was consistently increased. Thus, the presence of inflammatory dysregulation suggests a varied rather than uniform pro-inflammatory state.

Dietary Cyanus depressus (M. Bieb.) Soják plant extract enhances growth performance, modulates intestinal microbiota, and alters gene expression associated with digestion, antioxidant, stress, and immune responses in rainbow trout (Oncorhynchus mykiss)

This study aimed to assess the effects of dietary Cyanus depressus (CD) extract on rainbow trout (Oncorhynchus mykiss) physiology and health. Fish with an average weight of 3.29 ± 0.34 g were allocated to four feeding groups, receiving diets containing CD extract at doses of 0 (Control), 0.5 (CD05), 1 (CD1), and 2 (CD2) g kg−1 for a period of 60 days. Results revealed significant improvements in final body weight, weight gain, and specific growth rate in groups supplemented with 1 and 2 g/kg of CD extract. Lipase activity increased notably in fish fed with CD0.5, CD1, and CD2 diets. The CD1 group exhibited the highest trypsin activity, while the groups receiving 1 g/kg and 2 g/kg of CD extract displayed the highest amylase activity. Analysis of gene expression levels for superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) showed marked increases across all groups compared to the control, with the most significant enhancement observed in fish fed with 2 g/kg of CD extract. Significant variations were observed in the expression of immunity-related genes among the treatments, with the highest expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) found in groups fed a diet enriched with CD extract. The increased activity of immune-related genes was more prominent in fish fed 2 g/kg of CD extract than in the control group. Notably, in fish fed with CD extract, heat shock protein 70 (HSP70) gene expression increased in the CD2 group, decreased in the CD05 group, and remained statistically unchanged in the CD1 group compared to the control. Additionally, supplementation with CD extract altered the composition and abundance of the intestinal microbiota in rainbow trout. In conclusion, our study suggests that Cyanusdepressus extract has significant potential for enhancing various physiological and health aspects of rainbow trout, particularly when supplemented at 2 g/kg.

Modified and alternative bone cements can improve the induced membrane: Critical size bone defect model in rat femur

BackgroundAs a two-stage surgical procedure, Masquelet's technique has been used to care for critical-size bone defects (CSD). We aimed to determine the effects of modified and altered bone cement with biological or chemical enriching agents on the progression of Masquelet's induced membrane (IM) applied to a rat femur CSD model, and to compare the histopathological, biochemical, and immunohistochemical findings of these cements to enhance IM capacity. MethodsThirty-five male rats were included in five groups: plain polymethyl methacrylate (PMMA), estrogen-impregnated PMMA (E+PMMA), bone chip added PMMA (BC+PMMA), hydroxyapatite-coated PMMA (HA) and calcium phosphate cement (CPC). The levels of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) were analyzed in intracardiac blood samples collected at the end of 4 weeks of the right femur CSD intervention. All IMs collected were fixed and prepared for histopathological scoring. The tissue levels of rat-specific Transforming Growth Factor-Beta (TGF-β), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) were analyzed immunohistochemically. ResultsSerum levels of BALP and OC were significantly higher in E+PMMA and BC+PMMA groups than those of other groups (P = 0.0061 and 0.0019, respectively). In contrast, TNF-α levels of all groups with alternative bone cement significantly decreased compared to bare PMMA (P = 0.0116). Histopathological scores of E+PMMA, BC+PMMA, and CPC groups were 6.86 ± 1.57, 4.71 ± 0.76, and 6.57 ± 1.51, respectively, which were considerably higher than those of PMMA and HA groups (3.14 ± 0.70 and 1.86 ± 0.69, respectively) (P < 0.0001). Significant increases in TGF-β and VEGF expressions were observed in E+PMMA and CPC groups (P = 0.0001 and <0.0001, respectively) whereas Runx2 expression significantly increased only in the HA group compared to other groups (P < 0.0001). ConclusionsThe modified PMMA with E and BC, and CPC as an alternative spacer resulted in a well-differentiated IM and increased IM progression by elevating BALP and OC levels in serum and by mediating expressions of TGF-β and VEGF at the tissue level. Estrogen-supplemented cement spacer has yielded promising findings between modified and alternative bone cement.

Downregulation of miR-181c-5p in Alzheimer’s disease weakens the response of microglia to Aβ phagocytosis

Alzheimer’s disease (AD) is an age-associated neurodegenerative disease. Recently, studies have demonstrated the potential involvement of microRNA-181c-5p (miR-181c-5p) in AD. However, the mechanism through which miR-181c-5p is responsible for the onset and progression of this disease remains unclear, and our study aimed to explore this problem. Differential expression analysis of the AD dataset was performed to identify dysregulated genes. Based on hypergeometric analysis, AD differential the upstream regulation genes miR-181c-5p was found. We constructed a model where SH-SY5Y and BV2 cells were exposed to Aβ1-42 to simulate AD. Levels of tumor necrosis factor-alpha, interleukin-6, and IL-1β were determined using enzyme-linked immunosorbent assay or reverse transcription quantitative polymerase chain reaction. Phosphorylation levels of p-P38 and P38 were detected by Western blot. The level of apoptosis in BV2 cells under Aβ1-42 stress was exacerbated by miR-181c-5p mimic. Downregulated miR-181c-5p impaired the phagocytosis and degradation of Aβ by BV2 cells. The release of proinflammatory cytokines in BV2 cells with Aβ1-42 stress was alleviated by miR-181c-5p upregulation. Additionally, miR-181c-5p downregulation alleviated the phosphorylation of P38 in Aβ1-42-induced SH-SY5Y cells. In conclusion, miR-181c-5p improves the phagocytosis of Aβ by microglial cells in AD patients, thereby reducing neuroinflammation.

Attenuated adiponectin, omentin, increased interleukin-6 and tumor necrosis factor-alpha levels with altered cognition and depression in non-Hodgkin lymphoma patients: A case-control study

Background and purposeImmune dysfunction is one of the risk factors which plays an important role in the development of non-Hodgkin lymphoma (NHL), and inflammation may be involved in its etiology. Minimal data is available on the effect of cytokine levels on neurobehavioral function in lymphoma before the initiation of chemotherapy. Therefore, we aimed to explore the risk of NHL by assessment of cytokine and adipokine levels and their correlation with neurobehavioral changes. MethodsThis case-control study enrolled 62 subjects (age-sex matched: 31 cases and 31 controls). Neurobehavioral assessment was done using Montreal Cognitive Assessment questionnaire (MoCA) and Patient Health Questionnaire (PHQ-9). EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) was used to assess quality of life. Questionnaire assessment and sample collection were done after the patient enrolment and before first cycle of chemotherapy. ResultsMean age of NHL patients and healthy controls was 51.9 ± 11.8 and 50 ± 10.9 years, respectively. NHL patients showed significantly higher levels of IL-6 (0.77 ± 0.11) and TNF- α (1.47 ± 1.31) than controls (0.55 ± 0.4 and 0.66 ± 0.89, respectively) with p-value<0.005. Also, NHL patients showed significantly lower levels of adiponectin (0.31 ± 0.24) and omentin (0.46 ± 0.1) than controls (0.42 ± 0.13 and 0.53 ± 0.11, respectively) with p-value<0.005. Lower MoCA and EORTC QLQ C-30 scores and higher PHQ-9 scores were observed in NHL patients in comparison to healthy control. ConclusionOur results showed that adiponectin, omentin IL-6 and TNF-α may be used as pre-diagnostic markers of NHL risk. Neurobehavioral changes observed in NHL patients may alter the quality of life.

Recombinant Klotho protein protects pulmonary alveolar epithelial cells against sepsis-induced apoptosis by inhibiting the Bcl-2/Bax/caspase-3 pathway.

Inflammation-induced apoptosis of alveolar type II epithelial cells is a primary contributor to sepsis-induced acute respiratory distress syndrome (ARDS). Klotho is a single-pass transmembrane protein with anti-inflammatory and anti-apoptotic effects. However, the role and mechanism of Klotho in the development of ARDS remains unknown. This study aimed to investigate the effect of Klotho on sepsis-induced apoptosis in human pulmonary alveolar epithelial cells (HPAEpiCs) together with the potential mechanism. Cecal ligation and puncture (CLP) were performed to generate an in vivo sepsis model, and HPAEpiCs were treated with lipopolysaccharide (LPS) to mimic sepsis in vitro. Both models were administered recombinant Klotho protein. The morphology of the lung tissue was observed, and apoptotic cells and cell viability were detected. Interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA), while the expression of Bcl-2, Bax and cleaved caspase-3 was detected with western blotting. Klotho reversed the CLP-induced decrease in mouse survival in vivo (p < 0.001) and increased inflammatory cell infiltration and inflammatory substance exudation in the lung tissue of mice with sepsis (both p < 0.001). Klotho also suppressed apoptosis (p < 0.001) as demonstrated by IL-1β, IL-6 and TNF-α expression (all p < 0.001), and Bcl-2/Bax/caspase-3 pathway activation (p < 0.001). Klotho pretreatment significantly prevented LPS-induced apoptosis in vitro (p < 0.001), as demonstrated by IL-1β, IL-6 and TNF-α upregulation (all p < 0.001); and Bcl-2/Bax/caspase-3 pathway activation in HPAEpiCs (p < 0.001). This study demonstrated that Klotho can ameliorate acute lung injury (ALI) induced by sepsis by inhibiting inflammatory responses and exerting anti-apoptotic effects by suppressing Bcl-2/Bax/caspase-3 pathway activation.

Influence of administration timing of San-Huang-Xie-Xin-Tang treatment on attenuating Salmonella enterica serovar Typhimurium infection.

Salmonella infections are a serious global health concern, particularly in developing countries, and are further exacerbated by the emergence of antibiotic resistance. San-Huang-Xie-Xin-Tang (SHXXT), a traditional herbal medicine with potent anti-inflammatory properties, has recently gained attention as an alternative treatment. Our study emphasizes on the importance of precise timing in accordance with traditional Chinese medicine principles. A mouse infection model was established while different administration times of SHXXT were recorded for the body weight, clinical scores, bacterial counts in blood, and organs. Additionally, cytokine levels, fatty acids, and amino acids in the serum were also monitored. We found that administering SHXXT 1 day after Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection (T1 group) leads to positive outcomes. This includes restoration of body weight, improved clinical scores, and reduced bacterial counts in blood and vital organs. Interferon-gamma levels remained consistently high across all treatment groups 6 days post-infection. However, the T1 group showed exclusive suppression of serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). The timing of administration significantly influenced serum fatty acid concentrations, countering Salmonella-induced disruptions, aligning with TNF-α and IL-1β levels. SHXXT had also restored amino acid profiles disrupted by the infection, with notable effects when administered at the correct timing. Our research highlights SHXXT's potential in treating S. Typhimurium infection, emphasizing the importance of precise timing in line with traditional Chinese medicine principles for effective treatment at different disease stages.

The Impact of Exercise on Interleukin-6 to Counteract Immunosenescence: Methodological Quality and Overview of Systematic Reviews.

This study evaluated the methodological quality of published systematic reviews on randomized and non-randomized clinical trials to synthesize evidence on the association between IL-6, immunosenescence, and aerobic and/or resistance exercise. The Preferred Reporting Items for Overviews of Systematic Reviews (PRIO-harms) guideline was used, with registration number CRD42022346142-PROSPERO. Relevant databases such as Cochrane Library, PubMed, Web of Science, Scopus, and Google Scholar were searched using English Medical Subject Headings terms. Inclusion criteria were systematic reviews analyzing aerobic exercise, resistance exercise, or a combination of both and assessing IL-6 as a biomarker of cellular immunosenescence in humans. The Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) was employed. Out of 742 identified articles, 18 were eligible, and 13 were selected for analysis. Sample sizes ranged from 249 to 1421 participants, mostly female, with ages ranging from 17 to 95 years. Aerobic exercise was the most studied type (46.15%), followed by combined exercise (38.46%) and resistance exercise (15.38%). Aerobic exercise showed a statistically significant reduction in IL-6, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α) levels. Among the 13 reviews analyzed using AMSTAR-2, 8 were rated as critically low quality, and 5 were classified as low quality. Aerobic exercise has anti-inflammatory properties and the potential to modulate IL-6, CRP, and TNF-α levels in immunosenescence. However, the limited methodological quality of the analyzed systematic reviews highlights the urgent need for robust, high-quality studies to improve access to information and facilitate evidence-based decision-making in healthcare.

Artichoke Leaf Extract Effectiveness on the Skin Aging Exposome: Efficacy and Safety Results of a Split-Face Study

The skin is a barrier organ subjected to lifelong exposure to internal and external factors influencing both its biological response and appearance. A randomized split-face study was carried out on 22 adult female outdoor workers using an artichoke leaf extract (CynageTM). The product’s efficacy was measured before and after 28 days of use. The following skin parameters were measured: wrinkle depth, skin roughness, and radiance, to assess the product’s effect on the skin appearance; Ferric Reducing Antioxidant Power (FRAP), to assess the total antioxidant capacity; and tumor necrosis factor-alpha (TNF-α) levels, to assess the anti-inflammatory efficacy. These parameters were also integrated by the evaluation of the subjective perception of product efficacy. After 28 days of product use, the skin’s appearance improved as follows: wrinkle depth and skin roughness decreased by 5.2% and 7.0%, respectively, while the skin radiance increased by 19.0%. The total antioxidant capacity of the skin increased by 20.2%. The skin’s TNF-α levels decreased by 8.2%. The product efficacy was also perceived by the subjects participating in the study. The product was well tolerated. Our findings demonstrate the active role of the ingredient in decreasing the skin damage induced by the exposome.

Mitochondrial Fragmentation Increases with Aging in Rats

The diaphragm muscle (DIAm) is the major pump muscle for breathing. Neural control of the DIAm involves recruitment of phrenic motor neurons (PhMNs) comprising motor units that vary in their mechanical and fatigue properties. Smaller PhMNs innervating fatigue resistant DIAm fibers are highly active being recruited during breathing, while larger PhMNs are infrequently recruited during more forceful expulsive behaviors. Previously, we found that to support their higher activity levels, smaller PhMNs have higher mitochondrial volume density and are less fragmented compared to larger PhMNs. With aging, larger PhMNs are more vulnerable and ~30% are lost, and those surviving display greater mitochondrial fragmentation. We also found that older rats exhibit elevated levels of the proinflammatory cytokine tumor necrosis factor alpha (TNFa), which in other tissue has been linked to mitochondrial fragmentation via activation of the IRE1a S724-mediated endoplasmic reticulum (ER) stress pathway. Accordingly, we hypothesized that in 24-month-old rats, increased TNFa levels activate the pIRE1aS724-mediated ER stress pathway, leading to XBP1s splicing, which transcriptionally increases expression of cyclin-dependent kinases (CDK1 and CDK5) that mediate phosphorylation of DRP1 at Serine 616 (pDRP1S616), and ultimately mitochondrial fragmentation. We found that serum TNFa levels increased ~3.5 fold in 24-month rats compared to 6-month rats. Consistent with elevated TNFa, we found increased pIRE1aS724 and XBP1s splicing in the cervical ventral horn of 24-month rats. In retrogradely labeled PhMNs, we found XBP1s was localized to the nucleus, consistent with transcriptional activation of gene expression. Bioinformatic analysis and ChIP assay confirmed XBP1s binding to the CDK1 and CDK5 promoter regions in rat cervical ventral horn. Both CDK1 and CDK5 mRNA and protein were elevated in the cervical ventral of 24-month rats. In aged rats, pDRP1S616 phosphorylation increased with a corresponding increase in mitochondrial fragmentation. Our results support our hypothesis that chronic inflammation (elevated TNFa levels) in older rats activate the pIRE1aS724-mediated ER stress pathway, leading to XBP1s splicing, which transcriptionally targets CDK1 and CDK5 expression mediating pDRP1S616 phosphorylation and mitochondrial fragmentation. Research Supported by NIH R01 grant AG44615. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Exercise role on inflammatory and MCH-1 plasticity markers in severely contused spinal cord injured rodents

Approximately 17,500 new cases of Spinal cord Injury (SCI) occur annually in the United States. Growing evidence suggests that mobilizing the body following SCI through physical therapy regimens can help patients regain locomotor function. The immune response and the role of inflammation following SCI represents an important factor contributing to plasticity and recovery of function post-injury. The immune response uses both pro and anti-inflammatory factors to facilitate healing at the primary and secondary injury. In the severe case of SCI, inflammation can lead to maladaptive plasticity and that can hinder locomotor recovery. Pro-inflammatory cytokines such as Tumor necrosis factor alpha (TNF-a) can enhance the C-fiber activation in the dorsal horn resulting in sensitization and maladaptive plasticity. Exercise can also be pro-inflammatory. Exercise has been shown to decrease TNF-a levels and increases Interleukin-10 (IL-10) in human skeletal muscle. Bodyweight treadmill training in SCI animal has shown improvements in locomotor function. Interleukin-10 (IL-10), demonstrates potent anti-inflammatory effects in which it down-regulates TNF-alpha and its secondary effects. In addition, major histocompatibility complex class I proteins (MHC1), play a vital role in maintaining the structural integrity of neurons which is critical for fostering an environment for spinal plasticity to occur. In this study, we focus on the role of training paradigms to be used to facilitate locomotor recovery in spinally contused rats. The Body-Weight Supported Treadmill Training (BWSTT) and circular Bodyweight-Supported Ambulatory Rodent Trainer (cBART) both represent locomotor training for SCI animals. Mid-thoracic spinal cord contusion was performed, and the animals were allowed to recover for two weeks. The contused BWSTT alone, or cBART alone or combined BWSTT and cBART training groups were initiated at beginning of the third week for a total of 8-weeks of training. Controls include contused rats that received no training, and intact group (SHAM). At 10 weeks, the spinal cord was dissected for qPCR study. We measure the levels of TNF-alpha, MHC1, and IL-10 in the thoracic segment above the injury site, the injury site, Lumbar 1-3 and Lumbar 3-5 segment. Results show that in the cBART trained group, the MHC-1 expression in the L3-L5 segment was significantly greater when compared to the contused injury with no training intervention. No training effect was realized in MHC-1 in the L1-L3 trained groups. The training paradigms did not modulate TNF-a levels in the lumbar spinal cord segments. Lastly, IL-10 expression was undetectable in all the spinal cord segments. In this severe spinal cord contused model, we were only able to show modulation in the MHC-1 expression in the trained lumbar segment as function of exercise. Additional work will be required to consider the intensity of locomotor training and the severity of spinal cord contusion impact on these plasticity markers. Future understanding of these mechanisms may be useful in developing better locomotor training methods and drug targets for facilitation of recovery following SCI. CSULA RSCA 2020 MINI Grant- Dr. Joseph CSULA MORE Programs Offce, MBRS-URISE (1734GM145503) Bridges to Doctorate 5T23GM146700 NIH R25HD097701-04 - Dr. Ray De Leon. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Changes of Inflammatory Cytokines after 4-week and 8-week Aerobic Exercise in Hispanic Obese Females

Recent studies have insuffcient data to support the effects of exercise on inflammatory cytokines independent from weight loss. Thus, a reduction in fat mass is required to induce decreases in markers of pro-inflammatory cytokines. PURPOSE: Changes in inflammatory cytokines following 4-weeks and 8-weeks of aerobic exercise were measured in this study to find if exercise is an independent determinant on changes in inflammatory cytokines in middle-aged Hispanic obese females. Methods: 35 obese females were randomly assigned to either exercise (EX, N=16) or control (CON, N=19) group. The exercise group performed moderate intensity aerobic exercise on the treadmill for 60 minutes at 55% of VO2max for 8 weeks (3 days/week). Body composition measurement with dual-energy X-ray absorptiometry and blood collection were conducted before and after the 4th week and 8th week of the intervention (PRE, 4W, and 8W). Blood samples were used to measure levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and adiponectin. Two-way repeated measures ANOVA and Tukey post hoc tests were used for data analysis. RESULTS: Following 8 weeks of aerobic exercise intervention, participants had significantly reduced body mass index (34.2±4.6 mean±SD → 33.7±4.7, P=.035), %body fat (42.1±5.2% → 41.4±5.3, P=.014) and TNF-α (4.57±.24pg/mL mean±SE → 4.14±.31, P=.019) as compared to PRE. EX also observed a decrease in TNF-α (4.57±.24 → 4.29±.28, P=.033) when changes in body weight and %body fat were not observed after 4 weeks of aerobic exercise. CRP and adiponectin were unaltered in EX. CON showed no significant changes in any variables at 4W and 8W. CONCLUSION: It is suggested reductions in inflammatory cytokines are associated with fat loss; however, significant change in TNF- α at 4W when no change in %body fat is observed this indicates that moderate aerobic exercises may reduce level of inflammation independent from fat loss. This change is further improved when fat loss occurs at 8W. Therefore, it is plausible that moderate aerobic exercises may independently reduce risks of obesity-associated disorders in middle-aged Hispanic obese females. Results of this study suggest that longer periods of exercise training with fat loss may be required to induce significant changes in CRP and adiponectin in middle-aged obese females. TAMIU University Research Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The possible cardioprotective effect of ghrelin during experimental endotoxemia in mice.

This study aimed to evaluate the cardioprotective effects of ghrelin in septic mice, focusing on its anti-inflammatory and antioxidant properties. Thirty-five male Swiss mice (8-12 weeks old, 23-33g) were randomly assigned to five groups (n = 7 each): (1) Normal, fed usual diets, (2) Sham, subjected to anesthesia and laparotomy, (3) Sepsis, subjected to cecal ligation and puncture, (4) Vehicle, given an equivalent volume of intraperitoneal saline injections immediately after cecal ligation and puncture, and (5) Ghrelin-treated, administered 80 µg/kg ghrelin intraperitoneal injections immediately following cecal ligation and puncture. Serum levels of tumor necrosis factor-alpha (TNF-α), macrophage migration inhibitory factor (MIF), toll-like receptor 4 (TLR4), and 8-epi-prostaglandin F2 alpha (8-epi-PGF2α) were measured. The extent of cardiac damage was also evaluated histologically. The mean serum levels of TNF-α, MIF, TLR4, and 8-epi-PGF2α levels were significantly higher in the sepsis and vehicle groups than in the normal and sham groups. The levels were significantly lower in the ghrelin-treated group than in the vehicle and sepsis groups. Histological analysis revealed normal myocardial architecture in the normal and sham groups, whereas the sepsis and vehicle groups had severe myocardial injury. The ghrelin-treated group displayed histological features similar to the sham group, indicating reduced myocardial damage. Ghrelin ameliorated sepsis-induced cardiotoxicity in mice by exhibiting strong anti-inflammatory and antioxidant effects. These findings suggest that ghrelin may be a promising therapeutic candidate for the prevention of sepsis-induced cardiotoxicity.

Assessment of salivary tumor necrosis factor-alpha level in the initial stages of treatment with fixed appliances and clear aligners.

To assess and compare the tumor necrosis factor-alpha (TNF-α) levels in saliva samples during the initial stages of orthodontic treatment with fixed orthodontic appliances (FAs) and clear aligners (CAs). This longitudinal study comprised 40 patients (22 males, 18 females, mean age 22 ± 7 years) who were categorized into two equal-sized groups. Group A comprised 20 patients treated with FA, and Group B comprised 20 patients treated with CA. Unstimulated saliva was collected before the intiation of treatment and then collected again after the placement of the FA/CA at 24 hrs, 7th day, and on the 21st day in both groups. TNF-α levels were determined through ELISA. The data were subjected to statistical analysis. For intragroup comparison of TNF-α at different time points, the Wilcoxon matched-pairs signed-rank test was used, and for intergroup comparison of FAs and CAs at different time points, the Mann-Whitney U test was used. TNF-α levels in the saliva increased significantly at 24 hours, followed by a decline on the 7th day and 21st day in both groups. Changes in TNF-α levels were significantly higher in the FA group than those in the CA group at different time points. This study showed that the salivary TNF-α levels increased significantly during the initial stages of FA and CA treatment at different time points. The mean salivary TNF-α level in both FA and CA groups increased significantly at 24 hours, followed by a decline on the 7th day and then on the 21st day. There was a significant difference between the FA and CA treatment, where the CAs showed a significantly low level of TNF-α in saliva at different intervals of time when compared to the FAs.