Serum Levels Of TNF-α Research Articles

CCL4 as a potential serum factor in differential diagnosis of central nervous system inflammatory diseases and gliomas.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are commonly utilized to detect brain gliomas and central nervous system inflammation diseases. However, there are instances where depending solely on medical imaging for a precise diagnosis may result in unsuitable medications or treatments. Pathological analysis is regarded as the definitive method for diagnosing brain gliomas or central nervous system inflammation diseases. To achieve this, a craniotomy or stereotaxic biopsy is necessary to collect brain tissue, which can lead to complications such as cerebral hemorrhage, neurological deficits, cerebrospinal fluid leaks, and cerebral edema. Consequently, the advancement of non-invasive or minimally invasive diagnostic techniques is currently a high priority. This study included samples from four glioma patients and five patients with central nervous system inflammatory diseases, comprising both serum and paired cerebrospinal fluid (CSF). A total of 40 human cytokines were identified in these samples. We utilized a receiver operating characteristic (ROC) analysis to assess the sensitivity and specificity for distinguishing central nervous system inflammation diseases and gliomas. Additionally, we examined the correlation of these factors between serum and CSF in the patients. Ultimately, the identified factors were validated using serum from patients with clinically confirmed gliomas and central nervous system inflammation diseases followed by detection and statistical analysis through ELISA. The levels of serum factors IL-4, IFN-α, IFN-γ, IL-6, TNF-α, CCL4, CCL11, and VEGF were found to be significantly higher in gliomas compared with inflammatory diseases of the central nervous system (p < 0.05). Furthermore, a strong correlation was observed between the levels of CCL4 in serum and CSF, with a correlation coefficient of r = 0.92 (95% CI = 0.20-0.99, p = 0.027). We gathered more clinical samples to provide further validation of the abundance of CCL4 expression. A clinical study analyzing serum samples from 19 glioma patients and 22 patients with central nervous system inflammation diseases revealed that CCL4 levels were notably elevated in the inflammatory group compared with the glioma group (p < 0.001). These results suggest that assessing serum CCL4 levels may be useful in distinguishing those patients for clinical diagnostic purposes.

Behçet's disease modifies the gingival inflammatory response.

Behçet's disease (BD) pathogenesis involves severe outcomes such as blindness, central nervous system manifestations, and deep venous thrombosis that impacts systemic and local inflammatory changes. We tested the hypothesis that BD negatively affects gingival health and increases the severity of gingivitis. The study included 37 BD patients with gingivitis without any sign of periodontitis. Systemically healthy 19 patients with gingivitis (G) and 20 periodontally and systemically healthy individuals (C) were recruited as controls. BD patients were further grouped as stable and unstable based on their responses to BD treatment. Clinical periodontal parameters were measured to determine the impact of BD on gingival health. Serum and saliva levels of ELA-2 (neutrophil elastase-2), SLPI (secretory leukocyte protease inhibitor), α1-AT (alpha1-anti-trypsin), VEGF (vascular endothelial growth factor), IL-6 (interleukin-6), IL-8 (interleukin-8), and TNF-α (tumor necrosis factor alpha) were analyzed using multiplex immunoassay to measure the systemic and local inflammatory impact of BD. Plaque index (PI), probing pocket depth (PPD), and bleeding on probing (BOP) were significantly higher in the BD group than in the controls (p<0.05). IL-6 was higher in both serum and saliva in the BD group than in the G group (p<0.05). ELA-2 levels in saliva were higher in the stable BD group than in the controls, while TNF-α and SLPI were statistically significantly higher in BD than in the control (p<0.05). Salivary α1-AT level was statistically lower in the BD group compared to the control group. Our study suggested that the gingival inflammatory profile was impaired in patients with BD.

Royal Jelly Exerts a Potent Anti-Obesity Effect in Rats by Activating Lipolysis and Suppressing Adipogenesis.

Background/Objective: This study examined the anti-obesity effect of royal jelly (RJ) in rats fed with a high-fat diet by targeting the major pathways involved in adipogenesis and lipolysis. In addition, it examined whether this effect is AMPK-dependent. Methods: Five groups of adult male albino rats were used (n = 6 each as 1); the control rats were fed with a normal diet (2.9 kcal), and the other groups were as follows: control + RJ (300 mg/kg), HFD (4.75 kcal), HFD + RJ (300 mg/kg), and HFD + RJ (300 mg/kg) + dorsomorphin (an AMPK inhibitor) (0.2 mg/kg). Results: RJ was administered orally to all rats. With no changes in food and energy intake, RJ significantly reduced gains in body weight, fat weight, body mass index (BMI), the Lee index, abdominal circumference (AC), and the adiposity index (AI). It also reduced fasting glucose and insulin levels, HOMA-IR, and the circulatory levels of free fatty acids (FFAs), triglycerides, cholesterol, and LDL-c in the HFD-fed rats. RJ also increased serum glycerol levels and adiponectin levels, but reduced the serum levels of leptin, IL-6, and TNF-α. Moreover, RJ reduced the secretion of IL-6 and TNF-α from isolated WAT. At the tissue level, the HFD + RJ rats exhibited a smaller adipocyte size compared to the HFD rats. At the molecular level, RJ increased the phosphorylation of AMPK, SREBP1, and ACC-1 and increased the mRNA and protein levels of HSL and ATG in the WAT of the HFD rats. In concomitance, RJ increased the mRNA levels of PGC-α1, reduced the protein levels of PPARγ, and repressed the transcriptional activities of PPARγ, SREBP1, and C/EBPαβ in the WAT of these rats. All the aforementioned effects of RJ were prevented by co-treatment with dorsomorphin. Conclusions: RJ exerts a potent anti-obesity effect in rats that is mediated by the AMPk-dependent suppression of WAT adipogenesis and the stimulation of lipolysis.

A Simple Score Scale Composed of Serum Inflammatory Factors Assists in Psoriasis Arthritis Prediction among Patients with Psoriasis Vulgaris.

Aim: To compare the levels of serum inflammatory indicators in psoriasis vulgaris patients who progress to PsA and those not, as well as to establish and validate a simple score scale for predicting PsA for psoriasis vulgaris patients. Methods: A cross-sectional study was performed at a university hospital in China to recruit five hundred and seventy-seven patients who had been diagnosed with psoriasis vulgaris for at least 10 years. After evaluation, 86 were enrolled in the PsA group, and the others were selected as the control group. Eight serum inflammatory factors were detected and compared between the two groups. A simple score scale for PsA prediction was established and validated. Results: Serum CRP, IL-6, and TNF-α levels were significantly higher in the PsA group than in the control group. A simple score scale composed of CRP, IL-6, and TNF-α was established. The sensitivity was 59.30% and the specificity was 83.50% for predicting PsA among all psoriasis vulgaris patients when the cut-off value of the total score was set as 1.8 points. The simple score scale presented a predictive value for progressing to PsA among all psoriasis vulgaris patients internally (AUC = 0.788), and the performance was also conformed in psoriasis vulgaris patients receiving topical treatment (AUC = 0.746), systemic treatment (AUC = 0.747) and biological treatment (AUC = 0.808), respectively. The predictive performance of this scale was also validated by an external retrospective cohort (AUC = 0.686). Conclusions: CRP, IL-6, and TNF-α were potential indicators to recognize PsA risk in patients with psoriasis vulgaris. A simple score scale may provide new insights for early prediction of PsA among psoriasis vulgaris patients.

Effect of chronic periodontitis on the endothelial glycocalyx of rat penile corpus cavernosum.

Chronic periodontitis may induce erectile dysfunction (ED), however, the specific mechanism involved is unclear. The endothelial glycocalyx (eGlx) is a structure that can regulate endothelial nitric oxide synthase (eNOS) phosphorylation on the cavity surface of vessels. To investigate whether chronic periodontitis leads to ED by affecting the eGlx. Twenty-four 4-week-old male Sprague‒Dawley rats were randomly divided into four groups (n=6): the control group, chronic periodontitis group, chronic periodontitis + heparin group (subcutaneous heparin 200 U/kg/day, 7 days), and control + heparin group. Four weeks after the induction of periodontitis in the rats, the maximum intra-cavernous pressure/mean arterial pressure (ICPmax/MAP), serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), heparin sulfate (HS), syndecan-1 (SDC-1), heparanase (HPSE), eNOS, and phosphor-eNOS (p-eNOS) concentration were measured, and the eGlx of the penile corpus cavernosum was observed by transmission electron microscopy (TEM). Chronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF-α, and IL-6 levels, reducing the p-eNOS/eNOS ratio and the NO concentration in the penile corpus cavernosum, and resulting in the inhibition of the erectile function. Serum CRP, TNF-α, and IL-6 levels and HPSE expression in penile cavernous tissue were significantly greater in the chronic periodontitis group than in the control group and the chronic periodontitis + heparin group (P<0.05). The average thickness of the eGlx muscle in the penile corpus cavernosum in the chronic periodontitis group was significantly lower than those in the control group and chronic periodontitis + heparin group (P<0.05). The HS concentration, SDC-1 expression, p-eNOS/eNOS, NO concentration, and ICPmax/MAP in the chronic periodontitis group were significantly lower than those in the control group and chronic periodontitis+ heparin group (P<0.01). The eGlx on penile cavernosum vessels may be a new therapeutic target for the treatment of ED. This study revealed that chronic periodontitis promotes the decomposition of vascular eGlx in the rat penile corpus cavernosum, however, it is not clear whether chronic periodontitis inhibits the synthesis of eGlx. Chronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF-α, and IL-6 levels, reducing the p-eNOS/eNOS ratio and the NO concentration in penile cavernous tissue, and resulting in the inhibition of the erectile function. Heparin inhibited eGlx decomposition and improved erectile function in rats with chronic periodontitis.

Combination therapy of corylifol A and anamorelin attenuates cachexia by decreasing pro-inflammatory cytokines, inhibiting lipolysis and increasing food intake in a murine colon cancer model

PurposeIn our previous study, we found that corylifol A (CYA), an active component derived from Psoralea corylifolia L, exhibited ameliorating effects on cancer cachexia. Anamorelin (AML), a ghrelin receptor agonist, is the only approved drug for the clinical treatment of cancer cachexia. Here, we checked the combination of CYA and AML on muscle atrophy and fat lipolysis in cancer cachexia mice to explore the possible clinic therapeutic potency of the combination on cancer cachexia.MethodsC26 colon tumor-bearing mice, a well-established animal model of cancer cachexia, were used to evaluate the effects of combined therapy involving CYA and AML on cancer cachexia and compared with those of CYA or AML alone. Histological analysis was performed to assess the changes in gastrocnemius (GAS) muscle tissue and epididymal adipose tissue (eWAT) and the possible involved molecular pathways were explored using western blotting and ELISA.ResultsTreatments of CYA, AML, or CYA+AML all significantly ameliorated the body weight decrease, muscle atrophy as well as fat loss in the tumor-bearing mice. Notably, the ameliorating effects of CYA+AML on fat loss were more significant than CYA or AML alone. The eWAT weight of mice in healthy control, C26 model, C26 +CYA, C26 +AML or C26 +CYA +AML group was 0.48 ± 0.07, 0.21 ± 0.10, 0.26 ± 0.10, 0.37 ± 0.10 and 0.48 ± 0.18 g, respectively. CYA+AML could increase food intake, significantly decrease the serum levels of inflammatory cytokines (TNF-α and IL-6) and inhibit the activation (phosphorylation) of hormone-sensitive lipase (HSL) in the eWAT tissues of the C26 tumor-bearing mice. Treatment of CYA along could significantly decrease the serum TNF-α level of the C26 tumor-bearing mice. Treatment of AML alone could increase food intake but could not decrease the serum levels of inflammatory cytokines of the C26 tumor-bearing mice.ConclusionThese results suggested that the effects of CYA+AML include both the appetite-stimulating effects of AML and the anti-inflammatory effects of CYA. CYA+AML was better than CYA or AML alone in ameliorating cancer cachexia, especially fat loss, of C26 tumor-bearing mice and might be a novel and beneficial therapeutic option for cancer cachexia.

Fritillaria cirrhosa D. Don Alleviates Inflammatory Progression and Suppresses M1 Polarization of Macrophages in Chronic Obstructive Pulmonary Disease

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive and largely irreversible disease. Current therapeutic approaches for COPD are limited in terms of slowing disease progression and suppressing pulmonary inflammation. Therefore, this study aimed to identify a method for alleviating inflammation in COPD. Methods: A COPD-like mouse model was established and treated with or without Fritillaria cirrhosa D. Don (hereinafter referred to as Fritillaria). The expression levels of inflammatory cytokines in mouse serum were detected by using enzyme-linked immunosorbent assay (ELISA). Additionally, lung tissue was analyzed by hematoxylin-eosin staining and immunohistochemistry analysis, respectively. MLE-12 cells were exposed to cigarette smoke extract (CSE) and treated with or without Fritillaria. The MTT assay was conducted to assess cell viability. The activation of NF-κB p65 was determined by Western blotting (WB). Finally, flow cytometry was applied to analyze the M1 macrophage percentage. Results: The results displayed that Fritillaria downregulated the levels of IL-1β, IL-6, IL-8, and TNF-α in the COPD-like mouse serum and MLE-12 cells. Fritillaria alleviated the inflammatory response in lung tissue of COPD-like mice. The cell viability of MLE-12 cells considerably decreased when exposed to CSE, which could be restored by adding Fritillaria. The Fritillaria reduced the activation of the pro-inflammatory factor NF-κB p65 and inhibited M1 polarization of macrophages, thereby mitigating the inflammatory response. Conclusion: In conclusion, Fritillaria exhibits beneficial effects in suppressing pulmonary infection-related inflammation in both the COPD-like mouse model and in vitro cell experiments.

Baicalin relieves complement alternative pathway activation-induced lung inflammation through inhibition of NF-κB pathway

IntroductionAcute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation.MethodsActivation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue.ResultsBaicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue.ConclusionBaicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI.

Putative role of 6-chogaol against tramadol-induced hepatotoxicity in albino rats via anti-inflammatory, antifibrotic, and antiapoptotic effects

Tramadol is a commonly used drug to relieve pain and avoid premature ejaculation in males with hepatotoxic effects, and 6-chogaol has potent anti-inflammatory and hepatoprotective properties.The work impetus is probing the hepatoprotective mechanisms of 6-chogaol against tramadol hepatoxicity. Twenty adult male rats were enrolled to obtain four equal groups [control group (G1), 6-chogaol group (G2), tramadol group (G3), and 6-chogaol+tramadol group (G4)]. Liver specimens were excised and processed to evaluate hepatocyte injury through histopathological (HP), immunohistochemical (IHC), flow cytometry, and biochemical investigations. The HP study exhibited hepatic injury in G3 hepatocytes (inflammatory cell infiltration, hepatic fibrosis, and disturbed liver structure). The IHC study showed a significant rise in caspase-3 and reduced PCNA immuno-expression (IE). Likewise, the flow cytometry and biochemical experiments exhibited a substantial elevation of apoptotic hepatocytes and the serum levels of IL-1β, IL-6, TNF-α, ALP, ALT, and AST in G3. In contrast, G4 rats significantly improved in all HP, IHC, flow cytometry, and biochemical parameters. Collectively, tramadol intake exerted harmful toxic effects on hepatocytes, whereas 6-Shogaol hampered these changes and served as a natural hepatoprotective agent. Therefore, we advise concurrent intake of 6-Shogaol supplement with tramadol to preserve the integrity of hepatic tissues.

Bifidobacterium regulates premature infant gut metabolites, reducing serum inflammatory factors: a randomised controlled trial.

Analyse the effects of Bifidobacterium BB-12 on intestinal metabolites and serum inflammatory factors in premature infants. 71 premature infants at gestational age of ≤32 weeks were randomly divided into the probiotic (n = 36) and control (n = 35) groups. Faecal and blood samples were collected from the two groups of premature infants at the 2nd and 4th week of life for intestinal metabolite detection and assessment of the level of the serum inflammatory markers TLR4, NF- κ B, IL-1β, and TNF- α. Compared to the control group, the probiotic group contained more amino acids, these elements were enriched on multiple amino acid metabolic pathways, and the probiotic group showed significantly lower levels of the serum inflammatory markers TLR4, NF-κB, IL-1β, and TNF-α. Finally, the probiotic group showed a lower incidence of feeding intolerance. The administration of Bifidobacterium BB-12 is associated with increasing the levels of glutamine, glutamic acid, and kynurenine in the gut of premature infants, and associated with reducing the levels of TLR4 and NF-κB in the serum, further decreasing the secretion of the pro-inflammatory factors IL-1β and TNF-α, and alleviating systemic inflammatory reactions, thereby reducing the incidence of feeding intolerance. 1. The use of Bifidobacterium BB-12 in premature infants can increase the levels of amino acids in the intestine. 2. Increases in Bifidobacterium BB-12 may decrease the serum levels of TLR4, NF-κB, IL-1β, and TNF-α. 3. Kynurenine may improve the prognosis of preterm infants by reducing inflammation. 4. Bifidobacterium BB-12 may improve the feeding tolerance of premature infants, thus reducing the incidence of feeding intolerance.

The effect of vitamin C on the recovery of activity and survival of autografted ovaries through inhibition of oxidation and inflammation

Ovarian tissue autografting is a valuable clinical option to help restore fertility in women with cancer. However, many follicles are lost due to ischemia-reperfusion (IR) injury, which depletes follicles after grafting. We aimed to investigate the effect of vitamin C, an antioxidant with anti-apoptotic and anti-inflammatory properties, on improving the structure and function of autografted ovaries in mice. Thirty-six female NMRI mice (4–5 weeks old) were divided into three groups of 12: control (no grafting), autograft + vitamin C (50 mg/kg/day intraperitoneally), and autograft + saline (100 µl/day/animal, intraperitoneally). After the ovarian autografting and before the start of the experiment, each group was further divided into 7-day and 28-day subgroups. Seven days after ovary autografting, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and inflammatory factors were measured. On day 28, ovarian histology, DNA fragmentation, and estradiol and progesterone levels were assessed. Results were analyzed using one-way ANOVA and Tukey’s test, with significance set at p<0.05. In the autograft + vitamin C group, there were significant increases in the mean total volume of the ovary, cortex (p<0.05), medulla, number of follicles, and levels of IL-10, progesterone, estradiol, and TAC (p<0.001), compared to the autograft group. Conversely, the rate of apoptosis and serum levels of MDA, IL-6, and TNF-α were notably reduced in the autograft + vitamin C group (p<0.001). These results suggest that vitamin C can significantly enhance the recovery of autografted ovaries through its antioxidant, anti-inflammatory, and anti-apoptotic effects.

Preoperative gut microbiota of POCD patients induces pre- and postoperative cognitive impairment and systemic inflammation in rats

BackgroundPostoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD.MethodsHerein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1.ResultsBased on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-α and IL-1β in the serum, increased levels of TNF-α and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-α in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-α, IL-1β and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus.ConclusionsOur findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD.

THE THERAPEUTIC POTENTIAL OF PRECONDITIONED MESENCHYMAL STEM CELLS IN ATHEROSCLEROSIS

Atherosclerosis (AS) is a multifactorial and inflammatory disease the cause of which is the formation of lipid and cholesterol plaques on the inner wall of blood vessels. Experimental and clinical studies have shown that the pathogenesis of atherosclerosis is, in particular, connected with inflammatory reactions. Recent studies reported that preconditioned mesenchymal stem cells (MSCs) possess an enhanced immunomodulatory potential. The purpose of the study was to investigate the therapeutic potential of preconditioned MSCs in the development of atherosclerosis. MSCs were isolated from the compact bone of mice by standard protocol. The characterization was conducted using flow cytometry, CFU assay and three-lineage differentiation. Cells were preconditioned with different combinations of cytokines and the optimal concentrations were determined by ELISA and by analysis of co-culturing with lymphocytes. The cytokine-preconditioned MSCs were administrated to mice with induced atherosclerosis. The lipids analysis, measuring of mouse spleens’ weights, ELISA and histological analysis of the aorta sections were done after 8-th weeks. We isolated MSCs and then confirmed the possession of the immunomodulatory properties. Preconditioning with the TNF-α cytokine effectively increased the immunomodulatory properties of MSCs compared to untreated MSCs in vitro. The results of in vivo study that the use of TNF-α-preconditioned MSCs reduced the development of atherosclerosis in mice compared to untreated MSCs: it increased the level of Treg cells in the spleen of mice; significantly reduced the levels of TNF-α and IFN-γ in blood serum; significantly reduced the spleen weights of mice; slightly decreased the total cholesterol levels and also increased HDL levels. Administration of TNF-α-preconditioned MSCs reduced the size of atherosclerotic plaques in the aorta of mice. The results of this study demonstrated the effect of cytokine-preconditioned MSCs in the inhibition of the development of atherosclerosis in a mouse model. However, for application as a therapy for suffered patients additional studies are needed. Besides, using of TNF-α preconditioned MSCs can be considered in other preclinical studies of the different diseases.

Concurrent ozone and high temperature exacerbates nasal epithelial barrier damage in allergic rhinitis mice: Insights from the nasal transcriptome and nasal microbiota

The global ambient temperature has been rising in recent decades and high temperature is usually accompanied by ozone (O3) pollution. Environmental change is an underlying factor for the increased prevalence of respiratory allergic disease. However, the potential mechanisms are complex and remain elusive. This study was performed to reveal toxic effects and molecular mechanisms of O3 or/and high temperature induced allergic rhinitis (AR) deterioration. The results indicated that O3 and high temperature co-exposure exacerbated rhinitis symptoms, destroyed ultrastructure of nasal mucosa and down-regulated the expression of nasal epithelial barrier structural proteins ZO-1 and occludin. Moreover, the levels of total protein and lactate dehydrogenase (LDH) in nasal lavage fluid and the levels of IL-1β and TNF-α in serum also exhibited a significant upward trend. Transcriptomic analysis revealed that immune and inflammatory signaling pathways such as IL-17 signaling pathway was involved in the combined toxicity of O3 and high temperature. Microbiome examination showed that Prevotella and Elizabethkingia were linked to nasal injury. What’s more, spearman correlation analysis revealed correlations among nasal microbiota dysbiosis, inflammation and injury. To sum up, the present study assessed the combined toxicity of O3 and high temperature and found potential mechanisms, which provided important experimental evidence for making preventive intervention strategies and protecting vulnerable populations.

Analyze interleukin-1β, interleukin-6, and tumor necrosis factor-α levels in dry eye and the therapeutic effect of cyclosporine A.

Dry eye is a common eye disease. Artificial tears supplements are widely used for the treatment of dry eyes. However, multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears, which may affect the therapeutic effect. To analyze the characteristics of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A. A total of 124 dry eye patients treated at The First People's Hospital of Xining from April 2020 to April 2022 were selected as the observation group, while 20 healthy individuals served as the control group during the same period. Levels of inflammatory markers, including IL-1β, IL-6, and TNF-α, were analyzed. The observation group was further divided into a study group and a control group, each consisting of 62 patients. The control group received artificial tears, whereas the study group received a combination of artificial tears and cyclosporine A. Inflammatory markers, Schirmer's test (SIT), tear break-up time (TBUT), corneal fluorescein staining (CFS), National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) scores, and adverse events (AEs) were compared between the two groups. The observation group exhibited significantly elevated serum levels of IL-1β, IL-6, and TNF-α in comparison to the healthy group. Following treatment, the study group demonstrated substantial reductions in IL-1β, IL-6, and TNF-α levels relative to the control group. Moreover, after treatment, the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group. Additionally, significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia, foreign body sensation, fatigue, red eye, and burning sensation within the study group. Furthermore, post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group (P < 0.05). It is noteworthy that significant AEs were reported in both groups throughout the treatment period. Cyclosporine A combined with artificial tears is effective in treating dry eye, yielding enhanced outcomes by improving SIT and TBUT levels, reducing CFS scores, and ameliorating vision-related quality of life.

Exploring the Mechanism of Modified Zexie Decoction Against Metabolic Associated Fatty Liver Disease Based on Network Pharmacology and Experimental Validation.

The incidence of metabolic-associated fatty liver disease (MAFLD) increases annually. Modified Zexie Decoction (MZXD) can treat this disease; however, their mechanisms of action are uncertain. This study evaluated the mechanisms of MZXD against MAFLD based on network pharmacology, molecular docking, and in vivo experiments. The main active compounds, targets and signaling pathways of MZXD against MAFLD were obtained using network pharmacological analysis. Underlying mechanisms were validated by molecular docking and in vivo assays. Forty-one active ingredients and 197 intersection targets were identified. The main active ingredients include quercetin, luteolin, isorhamnetin, 3-methylhexane, and 3β- acetoxyatractylone. The main targets were TP53, JUN, HSP90AA1, MAPK1, MAPK3, AKT1, NF-κB p65, TNF, ESR1, FOS, and IL-6. The pathway enrichment analysis indicated that MZXD was related to the IL-17, TNF, and PI3K-AKT signaling pathways. Molecular docking suggested that these active ingredients bound strongly to TNF, IL-6, and NF-κB p65, which are integral components of the TNF pathway. In the rat MAFLD model, MZXD attenuated high-fat diet( HFD)-induced liver injury and lipid accumulation, decreased the serum levels of the inflammatory mediators TNF-α, IL6, and IL-1β, and inhibited the protein expression of TNF-α, IL6, p- IKB-α and p-NF-κB p65. Furthermore, immunohistochemistry results showed that MZXD attenuated the F4/80 staining intensity of the liver compared with the model group. Collectively, our results suggested that MZXD could improve MAFLD by downregulating TNF/NF-κB signaling mediated macrophage activation.

Terminalia Chebula Extract Replacing Zinc Oxide Enhances Antioxidant and Anti-Inflammatory Capabilities, Improves Growth Performance, and Promotes Intestinal Health in Weaned Piglets.

This study aimed to assess the effects of substituting zinc oxide with terminalia chebula extract (TCE) on growth performance, antioxidant capacity, immune function, and intestinal health in weaned pigs. Initially, 72 weaned Duroc × Landrace × Large White piglets, 28 days old with an initial weight of 7.43 ± 0.14 kg, equally divided by gender, were randomly assigned into three groups, with six replicates and four piglets per replicate. They were fed a basal diet (CON group), a diet containing 2 g/kg zinc oxide (ZnO group), or 2 g/kg TCE (TCE group) for a duration of 28 days. Subsequently, to further confirm the most appropriate levels of TCE in piglets, 96 piglets of the same breeds and age, with an initial weight of 7.42 ± 0.12 kg, also equally divided by gender, were randomly assigned into four groups, each with six replicates and four piglets per replicate, and fed a basal diet (CON group), or diets supplemented with 1 g/kg TCE (LTCE group), 2 g/kg TCE (MTCE group), or 4 g/kg TCE (HTCE group) for a duration of 28 days. The results demonstrated that both TCE and ZnO reduced diarrhea rates (p = 0.001) and enhanced average daily gain (ADG) (p = 0.014) compared to the control group. TCE at 1 g/kg and 4 g/kg reduced the feed to gain ratio (p = 0.050). Dietary supplementing with TCE and ZnO increased serum total antioxidant capacity (T-AOC) (p = 0.020). Various doses of TCE also increased jejunal IgA (p = 0.000) levels and IL-10 expression (p = 0.004), and decreased the levels of TNF-α in both serum (p = 0.043) and jejunal mucosa (p = 0.000). Notably, TCE reduced the crypt depth (CD) of the duodenal (p = 0.007) and increased the villus height (VH) of the ileal (p = 0.045), and with increased dosage, there was a rise in the villus height to crypt depth ratio (VH:CD) in the duodenum (p = 0.000) and jejunum (p = 0.001). Higher abundances of Lactobacillaceae (p = 0.000) and lower levels of Streptococcaceae (p = 0.000) and Peptostreptococcaceae (p = 0.035) in cecal contents were fed the ZnO and TCE pigs compared with CON pigs. Therefore, TCE was firstly presented as being able to replace zinc oxide, improve intestinal morphology, and enhance antioxidant and immune functions, thus safeguarding intestinal mucosal health and promoting piglet growth.

Hesperidin Helps Improve the Intestinal Structure, Maintain Barrier Function, and Reduce Inflammation in Yellow-Feathered Broilers Exposed to High Temperatures.

To investigate the possible protective effect of hesperidin on intestinal damage caused by high-temperature heat stress in yellow-feathered broilers, 960 broilers aged 21 days were randomly divided into four groups: HT, HT300, HT450, and HT600, with each group receiving different amounts of hesperidin supplementation (0, 300, 450, and 600 mg/kg). The dietary supplementation of hesperidin could mitigate the elevation of corticosterone (CORT) and adrenocorticotropic hormone (ATCH) levels in serum from yellow-feathered broilers induced by heat stress. The supplementation of 300 mg/kg and 450 mg/kg of hesperidin reduced crypt depth and increased the V/C ratio in the small intestine compared to the HT group. The dietary supplementation of hesperidin decreased endotoxin and D-lactic acid levels in the blood, and dietary supplementation of 300 mg/kg of hesperidin increased the expression of claudin-1 and ZO-1 mRNA in the jejunum compared with the HT group. Furthermore, the dietary supplementation of 300 mg/kg of hesperidin decreased serum IL-1β and IL-6 levels. In comparison, supplementation with 300 mg/kg and 450 mg/kg of hesperidin decreased serum TNF-α levels in yellow-feathered broilers compared to the HT group. Moreover, the dietary supplementation of hesperidin decreased NF-κB mRNA levels. Overall, these data suggest that dietary supplementation with hesperidin potentially improves intestinal injury caused by heat stress in yellow-feathered broilers.

Diagnostic value and correlation analysis of serum cytokine levels in patients with multiple system atrophy.

The association between cytokines in peripheral blood and clinical symptoms of multiple system atrophy (MSA) has been explored in only a few studies with small sample size, and the results were obviously controversial. Otherwise, no studies have explored the diagnostic value of serum cytokines in MSA. Serum cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α), were measured in 125 MSA patients and 98 healthy controls (HCs). Correlations of these serum cytokines with clinical variables were analyzed in MSA patients. Diagnostic value of cytokines for MSA was plotted by receiver operating curves. No significant differences were found in sex and age between the MSA group and the HCs. TNF-α in MSA patients were significantly higher than those in HCs (area under the curve (AUC) 0.768), while IL-6 and IL-8 were not. Only Hamilton Anxiety Scale (HAMA) has a positive correlation between with TNF-α in MSA patients with age and age at onset as covariates. Serum IL-6 was associated with HAMA, Hamilton Depression Scale (HAMD), the Unified MSA Rating Scale I (UMSARS I) scores, the UMSARS IV and the Instrumental Activity of Daily Living scores. However, IL-8 was not associated with all clinical variables in MSA patients. Regression analysis showed that HAMA and age at onset were significantly associated with TNF-α, and only HAMA was mild related with IL-6 levels in MSA patients. Serum TNF-α and IL-6 levels in MSA patients may be associated with anxiety symptom; however, only TNF-α was shown to be a useful tool in distinguishing between MSA and HCs.

Diagnostic value of miR-34a in Mycoplasma pneumoniae pneumonia in children and its correlation with rehabilitation effect

BackgroundMycoplasma pneumoniae pneumonia (MPP) is responsible for 20 to 40% of all cases of pneumonia acquired by children and shows an increasing incidence year by year. The aim of this study was to investigate the expression of miR-34a in children with MPP and its diagnostic value, and further explore the relationship between miR-34a and the rehabilitation effect of children with MPP.MethodsThe expression level of miR-34a was detected by RT-qPCR, and the clinical value of miR-34a was analyzed by ROC analysis. In addition, the levels of IL-6, IL-18 and TNF-α in serum of children with MPP were detected by ELISA kit, and the correlation with miR-34a was analyzed.ResultsElevated levels of miR-34a were observed in the serum of children with MPP, and significantly higher expression levels were observed in children with severe symptoms and poor rehabilitation. The study suggested that miR-34a has potential as a diagnostic marker for MPP in children, helping to distinguish between mild and severe cases and predicting rehabilitation from MPP in children. In addition, miR-34a expression was positively correlated with IL-6, IL-8, and TNF-α levels.ConclusionsmiR-34a is closely related to MPP in children and miR-34a may be used as a clinical biomarker for MPP in children.