Concentrations Of Tumor Necrosis Factor Research Articles

Effects of tumor necrosis factor on undifferentiated and syncytialized placental choriocarcinoma BeWo cells

Tumor necrosis factor (TNF) regulates trophoblast turnover during the formation of the placental syncytium and can be a potentially relevant target for adverse effects of xenobiotics. We mimicked syncytialization in vitro by stimulating BeWo cells with 50 μM forskolin. Undifferentiated and syncytialized BeWo cells were exposed to TNF (10 pg/mL–10 ng/mL) for 48 h after which cell viability, progesterone release and gene expression of a selected set of markers representative for placental function were assessed. In undifferentiated BeWo cells, high TNF levels (1–10 ng/mL) increased gene expression of TNF, NF-κB, and TNFRSF1B to maximally 99 ± 17, 2.2 ± 0.2, and 3.0 ± 0.4 of control values, respectively (p < 0.001). These effects were also found in syncytialized BeWo cells but less pronounced. Additionally, TNF may induce syncytialization in BeWo cells as it upregulated ERVW-1 expression by 1.55 ± 0.14-fold (p < 0.05). On the contrary, TNF levels of 10 and 100 pg/mL did not affect gene expression in both undifferentiated and syncytialized BeWo cells, but did enhance cell viability in syncytialised BeWo cells (p < 0.001). In conclusion, we found that high TNF levels (1–10 ng/mL) increased gene expression of TNF, NF-κB, and TNFRSF1B especially in undifferentiated BeWo cells, while physiological TNF concentrations positively affected cell viability and while there was no effect on any of the investigated functional markers.

The Effect of Hyperbaric Oxygen Therapy on Markers of Oxidative Stress and the Immune Response in Healthy Volunteers.

Hyperbaric oxygen therapy (HBOT) consists of breathing 100% oxygen under increased ambient pressure. There are indications that HBOT induces oxidative stress and activates immune pathways. However, previous research on immunological effects of HBOT has mainly been established in in vitro experiments and selected patient populations, limiting generalizability and increasing the chances of confounding by comorbidities and specific patient-related factors. More insight into the immunological effects of HBOT would aid investigation and comprehension of potentially novel treatment applications. Therefore, in this study, we investigated the effects of three 110-min HBOT-sessions with 24-h intervals on immunological parameters in healthy, young, male volunteers. Blood samples were obtained before and after the first and third HBOT sessions. We assessed neutrophilic reactive oxygen species (ROS) production, systemic oxidative stress [plasma malondialdehyde (MDA) concentrations] as well as neutrophil phagocytic activity, plasma concentrations of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and IL-10, and production of TNF, IL-6, and IL-10 by leukocytes ex vivo stimulated with the Toll-like receptor (TLR) ligands lipopolysaccharide (TLR4) and Pam3Cys (TLR2). We observed decreased neutrophilic ROS production and phagocytosis following the second HBOT session, which persisted after the third session, but no alterations in MDA concentrations. Furthermore, plasma concentrations of the investigated cytokines were unaltered at all-time points, and ex vivo cytokine production was largely unaltered over time as well. These results indicate no induction of systemic oxidative stress or a systemic inflammatory response after repeated HBOT in healthy volunteers but may suggest exhaustion of ROS generation capacity and phagocytosis.

Effects of Pyropia yezoensis enzymatic hydrolysate on the growth and immune regulation of the zebrafish

The supplemental effect of Pyropia yezoensis enzymatic hydrolysate (PYE) in fish diet was evaluated in zebrafish (Danio rerio) model. A basal diet supplemented with PYE at 0, 0.1, 1.0 and 2.0% were fed to one-month old zebrafish for 6 weeks, its growth performance and immunity index were evaluated. The increase in weight gain was significantly higher when supplementary 1% PYE which shows a positive effect on growth performance of zebrafish. In addition, crude protein content of fish body was increased in all PYE supplemental groups. The innate immune responses and activity of digestive enzymes in zebrafish were enhanced with dietary supplementation of PYE additives. Compared with the control group, lysozyme (LYZ) and interleukin-10 (IL-10) content in zebrafish intestines were up-regulated in groups fed with 0.1% and 1% PYE. The mRNA expression levels of LYZ and IL-10 in zebrafish intestines were consistent with ELISA results. The content of tumor necrosis factor (TNF-α) reduced in 1% and 2% PYE groups. Furthermore, PYE down-regulated the relative abundance of pathogenic bacteria (Aeromonadaceae) and up-regulated the relative abundance of fish probiotics (Brevibacillus) in intestinal flora. The findings in this study indicated that PYE supplementation in diet could promote growth, improve immunity and regulate intestinal flora, which made PYE considered as an potential aquatic additive.

Иммунорегулирующий потенциал омега-3 полиненасыщенных жирных кислот: использование для профилактики частой инфекционной заболеваемости у детей

В последние годы все больше исследований направлено на изучение иммуномодулирующей роли длинноцепочечных полиненасыщенных жирных кислот (ДЦПНЖК), практическое применение которых потенциально способно предотвращать развитие острых инфекционных респираторных заболеваний и аллергических состояний. Из множества ДЦПНЖК наибольший интерес вызывают омега-3-кислоты. В статье приведен обзор некоторых исследований, а также данные собственного исследования о влиянии диетической добавки, содержащей комплекс омега-3-кислот («Омегамi Розумна дитина»), на снижение заболеваемости ОРЗ детей с рекуррентными формами острой респираторной инфекционной патологии. Иммунотропное действие диетической добавки к рациону питания «Омегамi Розумна дитина» у детей характеризовалось усилением функционирования врожденного и адаптивного иммунитета, а иммунорегулирующая направленность проявилась в ограничении провоспалительной настроенности иммунной системы у детей, в виде снижения НСТ-теста, количества CD25 и уменьшения сывороточного содержания ФНО-α при отсутствии сопутствующей иммуносупрессии противомикробного защитного потенциала.

M1 Macrophage-Derived Interleukin-6 Promotes the Osteogenic Differentiation of Ligamentum Flavum Cells.

Basic experimental study. The aim of this study was to clarify the role of macrophages (Mφs) in the osteogenic differentiation of ligamentum flavum (LF) cells. Mφs and secreted factors are involved in the regulation of cell osteogenic differentiation, and play an important role in the process of heterotopic ossification. Whether Mφs are involved in the development of ossification of the ligamentum flavum (OLF) have not been reported. The expression of CD68+ Mφs in ossified LF tissue was identified by immunohistochemical staining. THP-1 cells were polarized to M1 and M2, and identified by flow cytometry and immunofluorescence. The alkaline phosphatase activity and osteogenic differentiation-related gene expression in LF cells were evaluated following incubation with each Mφs conditioned medium (CM). Enzyme-linked immunosorbent assay was used to detect the pro-inflammatory cytokines in the supernatants, and qPCR was used to detect the expression of the corresponding receptors in the LF cells after incubation with the CM. LF cells were induced with CM-M1 in the presence of neutralizing antibodies to further test whether cytokines secreted by M1 Mφs impacted their osteogenic differentiation. CD68+ Mφs were found on the OLF samples. THP-1 cells were polarized into M1 and M2, and both M1 and M2 Mφs promoted the osteogenic differentiation of LF cells. The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1 β, and IL-6 in M1 Mφ supernatants were greater than those in M2, and greater levels of these cytokine receptors were observed in LF cells induced with CM-M1 than those with CM-M2. Osteogenic differentiation of LF cells induced by CM-M1 decreased after IL-6 was neutralized; however, not after IL-1β and TNF-α were neutralized. M1 Mφ-derived IL-6 promotes the osteogenic differentiation of LF cells, which may be a pathway in which Mφs regulate the osteogenic differentiation of LF cells.

Biochemical profile in mixed martial arts athletes.

The study aimed to evaluate changes in selected biochemical indicators among mixed martial arts competitors in subsequent periods of the training cycle. The research involved 12 mixed martial arts athletes aged 25.8 ± 4.2 years competing in the intermediate category. Selected somatic indicators were measured twice. Biochemical indicators were assessed five times during the 14-week study period. Serum concentrations of testosterone, cortisol, uric acid, myoglobin, total protein, interleukin 6, and tumor necrosis factor, as well as creatine kinase activity were determined. One hour after sparring completion, there were significant increases in cortisol (by 54.9%), uric acid (22.0%), myoglobin (565.0%), and interleukin 6 (280.3%) as compared with the values before the simulated fight. The highest creatine kinase activity (893.83 ± 139.31 U/l), as well as tumor necrosis factor (3.93 ± 0.71 pg/ml) and testosterone (5.83 ± 0.81 ng/ml) concentrations (p = 0.00) were recorded 24 hours after the simulation. Systematic observation of selected blood biochemical indicators in the training process periodization in mixed martial arts helps understand adaptive, compensatory, and regenerative mechanisms occurring in training athletes.

Effect of sialyllactose administration on growth performance and intestinal epithelium development in suckling piglets

Sialyllactose (SL) is an abundant carbohydrate in sow’s colostrum, but decreases during the first few days of lactation. Here, we investigated its effect on growth performance and intestinal epithelium development in pigs during the suckling period. Sixteen litters of suckling piglets were divided into two groups (Control and SL group). All piglets were breast fed and the SL group was orally administrated with 4 g SL per day for 21 d. Results showed that SL administration increased the litter weight (P = 0.043) and tended to elevate the average body weight (P = 0.084) at weaning. The serum concentrations of immunoglobulin G and glutathione peroxidase were elevated, but the concentrations of tumor necrosis factor α, malondialdehyde, and diamine oxidase were decreased upon SL administration (P < 0.05). Moreover, SL administration elevated the villus height, the ratio of villus height to crypt depth, and the activities of lactase and sucrase in jejunum (P < 0.05), and decreased the total apoptotic cells in ileal epithelium (P = 0.003). The expression levels of tight-junction protein ZO-1 in the jejunum and ileum, and critical functional genes such as the glucose transporter 2, divalent metal transporter 1, and insulin growth factor 1 receptor in the jejunum were elevated by SL supplementation (P < 0.05). Importantly, SL increased butyric acid concentration, and elevated the abundances of Lactobacillus and Bifidobacterium in cecum (P < 0.05). These results suggest that SL could improve the growth performance of suckling piglets, which was associated with improved immunity and antioxidant capacity, as well as the intestinal barrier functions.

Lipoic acid alleviates LPS‑evoked PC12 cell damage by targeting p53 and inactivating the NF‑κB pathway

Lipoic acid (LA) exerts several beneficial effects including anti‑inflammatory and antioxidant activity. This research aims to explore the function and mechanisms of LA on lipopolysaccharide (LPS)‑induced PC12 cells. PC12 cells stimulated by LPS were used to mimic an in vitro inflammatory model of Parkinson's disease. Cell toxicity was determined by a cell counting kit‑8 assay after various treatments. The concentrations of tumor necrosis factor (TNF-α), interleukin (IL)‑1β and IL‑6 were analyzed by an ELISA kit. The effects of LA on cell apoptosis and cell cycle were measured by flow cytometry. The levels of α‑syn, Nurr1 and tyrosine hydroxylase (TH) were tested by immunocytochemistry and ELISA kits. Western blotting assays were used to measure the expression of NF‑κB pathway‑related proteins. In PC12 cells, 100 μmol/mL LA effectively attenuated the upregulation of TNF‑α, IL‑1β and IL‑6 triggered by LPS; inhibited the increase of cell apoptosis; and relieved the cell cycle arrest induced. Additionally, the increase in α‑syn and the decrease in Nurr1 and TH triggered by LPS were reversed by 100 μmol/mL LA. We also found that the elevated expression of p53 in LPS‑induced PC12 cells was suppressed by LA. Significantly, knockdown of p53 enhanced the ameliorative effect of LA on LPS‑triggered PC12 cell damage. The increase in levels of p‑p65 NF‑κB and p‑IκBα triggered by LPS were suppressed by LA and si‑p53 combination treatment. The results indicate that LA can attenuate LPS‑triggered inflammation and apoptosis in PC12 cells by targeting the p53/NF‑κB pathway. These findings provide a theoretical basis for the future treatment of inflammation in Parkinson's disease.

Blackberry phenolic and volatile extracts inhibit cytokine secretion in LPS-inflamed RAW264.7 cells

The anti-inflammatory activity of blackberries has been attributed to phenolic compounds, especially anthocyanins. The present study hypothesized that volatiles could contribute to anti-inflammatory activity as well. The anti-inflammatory properties of three blackberry genotypes varying in total volatile and phenolic contents were assessed by measuring concentrations of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor -α (TNF-α) within LPS-inflamed RAW264.7 murine macrophage cells after a preventive treatment of either a phenolic or a volatile extract. Extracts from blackberry genotypes A2528T, A2587T and Natchez had total phenolic contents of 4315, 3369 and 3680 µg/mL, respectively, and total volatile contents of 283, 852 and 444 ng/mL, respectively. Phenolic and volatile extracts of all genotypes significantly lowered the secretion of NO, IL-6 and TNF-α in ranges varying between 20-42%, 34-60% and 28-73% inhibition, respectively. Volatile extracts exhibited greater anti-inflammatory properties than phenolic extracts, despite being present at much lower concentrations in the berries. Further research is needed to assess bioavailability and anti-inflammatory effect of blackberry volatiles in vivo.

Measurement of Salivary Tumor Necrosis Factor- alpha (TNF- α) in Periodontitis Patients with or without Diabetes Mellitus

Introduction: Tumor necrosis factor-alpha (TNF-α) is a proinflammatory mediator considered to be a soluble mediator released from immunocompetent cells. It exercises a wide range of proinflammatory and immunomodulatory effects in different cell populations, such as stimulating prostaglandin synthesis, promoting tumors in a variety of cancers, producing proteases, and activating osteoclastic function and therefore bone resorption. Its myriad functions suggest that TNF-α plays an important role in mediating the immune-inflammatory responses initiated by infection or other types of damage.&#x0D; Aim: The aim of the present study is to evaluate the concentrations of Tumour Necrosis Factor- alpha (TNF- α) in the saliva of periodontitis patients with or without diabetes mellitus.&#x0D; Materials and methods: A total of 30 participants were taken and divided into 3 groups with each group consisting of 10 saliva samples from patients with clinically healthy gingiva and patients with chronic periodontitis with diabetes mellitus and periodontitis patients only. Saliva sample was collected and salivary TNF- α was done using Enzyme Linked Immunosorbent Assay (ELISA). Statistically analyses was done by one way ANOVA test&#x0D; Results: Salivary TNF- α concentration in periodontal health, periodontitis with diabetes mellitus (P+DM), Periodontitis only (P) were analysed. Salivary TNF- α concentration was found to be significantly higher (p&lt;0.05) in periodontitis with diabetes mellitus (49±3.5 pg/ml) when compared with periodontitis only (29±3.6 pg/ml) and also when compared with healthy controls (17±1.4 pg/ml).&#x0D; Conclusion: The present study showed elevated TNF- α in periodontitis patients with diabetes mellitus when compared to patients with periodontitis only and normal healthy patients. Further studies are required in a large scale to substantiate the role of TNF-α in the progression of periodontal diseases.

Effect of Ethanolic Extract of Xylopia aethiopica Fruit on Cadmium-induced Inflammatory Changes and Dyslipidemic Rats

The extensive utilization of cadmium (Cd) in industry is a major cause of environmental health menace to humans and animals. This study was to investigate the protective effects of Xylopia aethiopica fruit ethanol extract (XAFEE) on cadmium-induced inflammation and dyslipidemia in male albino rats. Thirty albino rats weighing 120–180 g were randomly selected into six groups (n = 5). A: control rats (administered distilled water only), B: Cd alone group (10 mg/ kg bw), C: Cd + 150 mg/kgbw XAFEE, D: Cd + 300 mg/kgbw XAFEE, E: 150 mg/kgbw XAFEE and F: 300 mg /kgbw XAFEE group. After 2-week acclimatization and 21 days of the experiment, blood sample was collected via cardiac puncture. Changes in tumor necrosis factor (TNF-α), interleukin 10 (IL-10), total cholesterol (TC), triacylglycerol (TAG), phospholipids and free fatty acids (FFAs) concentrations in serum were determined. The results of the present study indicated that Cd exposure remarkably increased (p &lt; 0.05) the TC, TAG, phospholipids, FFAs and TNF-α concentrations, and significantly decreased IL-10 concentration (p &lt; 0.05) compared with control. These findings suggest that inflammatory changes and alterations in lipid metabolism might be one of the mechanisms underlying the subtle effects of Cd-induced inflammation and dyslipidemia. XAFEE expressed protective role against the toxic influence of Cd on affected parameters. The results raised the possibility of Xylopia aethiopica fruit being considered as a condiment in soup, local drinks, supplements or herbs preparations in areas where people have chances to Cd exposure, occupationally or environmentally.

The impact of ambroxol on the anti-inflammatory effect of azithromycin in lung tissue

The aim of this study was to compare the effects of two different doses of ambroxol (AMB) co-administered with azithromycin (AZIT) on the concentrations of bronchoalveolar lavage fluid (BALF) cytokines and serum biochemical parameters in an lipopolysaccharide (LPS)-induced acute lung injury mouse model. A total of 78 male Swiss albino mice were used for this investigation. After six mice had been separated as the control group (0 hours), the remaining animals were divided into the following three equal groups: LPS, LPS+AZIT+AMB30 and LPS+AZIT+AMB70. LPS, AZIT and AMB were administered intraperitoneally. BALF and serum samples were collected before (0 hour) and after applications at 4, 8, 16 and 24 hours under general anaesthesia, and then all mice were euthanised by cervical dislocation. Concentrations of tumor necrosis factor (TNF)α, interleukin (IL)-6 and IL-10 in BALF and aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine concentrations in serum were determined. Elevated TNFα and IL-6 concentrations in the LPS group were prevented at 8 and 16 hours in LPS+AZIT+AMB30 group. In addition, both treatment groups inhibited elevated IL-6 concentrations in the LPS group at 16 hours. LPS+AZIT+AMB30 and LPS+AZIT+AMB70 increased IL-10 concentrations at 16 and 4 hours, respectively. LPS caused significant elevations in urea concentrations at all sampling times and statistical fluctuations in other parameters at different sampling times. The increased ALP concentration in LPS group decreased in the treatment groups at 8 hours. In conclusion, the combination of low-dose AMB and AZIT may achieve beneficial effects in pulmonary infections by influencing the cytokine network.

Weilan gum oligosaccharide ameliorates dextran sulfate sodium‑induced experimental ulcerative colitis.

Ulcerative colitis (UC) is a global disease, characterized by periods of relapse that seriously affects the quality of life of patients. Oligosaccharides are considered to be a prospective strategy to alleviate the symptoms of UC. The present study aimed to evaluate the effect of weilan gum oligosaccharide (WLGO) on a mouse UC model induced by dextran sulfate sodium (DSS). WLGO structural physical properties were characterized by electrospray mass spectrometry and fourier tansform infrared spectroscopy. MTT assays were performed to evaluate the non-toxic concentration of WLGO. RT-qPCR and ELISAs were conducted to determine the levels of inflammatory factors. The clinical symptoms and mucosal integrity of the DSS-induced UC model were assessed by DAI and histological assessment. LPS-induced Caco-2 cells and DSS-induced UC mice were used to explore the effects of WLGO on UC. Treatment of the mice with 4.48 g/kg/day WLGO via gavage for 7 days significantly relieved the symptoms of DSS-induced UC model mice, whereas significant effects were not observed for all symptoms of DSS-induced UC in the WLGO-low group. The disease activity index score was decreased and the loss of body weight was reduced in DSS-induced UC model mice treated with WLGO. Moreover, colonic damage and abnormally short colon length shortenings were relieved following WLGO treatment. WLGO treatment also reduced the concentration and mRNA expression levels of proinflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor α, in DSS-induced UC model mice and lipopolysaccharide-treated Caco-2 cells. These results indicated that WLGO may be an effective strategy for UC treatment.

Anti-Osteogenic Effect of Danshensu in Ankylosing Spondylitis: An in Vitro Study Based on Integrated Network Pharmacology

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by abnormal bone metabolism, with few effective treatments available. Danshensu [3-(3,4-dihydroxy-phenyl) lactic acid) is a bioactive compound from traditional Chinese medicine with a variety of pharmacologic effects. In the present study, we investigated the pharmacologic effect and molecular mechanism of Danshensu in AS. Potential targets of Danshensu were identified in four drugs-genes databases; and potential pharmacologic target genes in AS were identified in three diseases-genes databases. Differentially expressed genes related to AS were obtained from the Gene Expression Omnibus database. Overlapping targets of Danshensu and AS were determined and a disease–active ingredient–target interaction network was constructed with Cytoscape software. Enrichment analyses of the common targets were performed using Bioconductor. To test the validity of the constructed network, an in vitro model was established by treating osteoblasts from newborn rats with low concentrations of tumor necrosis factor (TNF)-α. Then, the in vitro model and AS fibroblasts were treated with Danshensu (1–10 μM). Osteogenesis was evaluated by alkaline phosphatase staining and activity assay, alizarin red staining, quantitative PCR, and western blotting. We identified 2944 AS-related genes and 406 Danshensu targets, including 47 that were common to both datasets. The main signaling pathways associated with the targets were the c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways. A low concentration of TNF-α (0.01 ng/ml) promoted the differentiation of osteoblasts; this was inhibited by Danshensu, which had the same effect on AS fibroblasts but had the opposite effect on normal osteoblasts. Danshensu also decreased the phosphorylation of JNK and ERK in AS fibroblasts. There results provide evidence that Danshensu exerts an anti-osteogenic effect via suppression of JNK and ERK signaling, highlighting its therapeutic potential for the treatment of AS.

An experimental model of the epithelial to mesenchymal transition and pro-fibrogenesis in urothelial cells related to bladder pain syndrome/interstitial cystitis.

BackgroundSuitable in vitro models are needed to investigate urothelial epithelial to mesenchymal transition (EMT) and pro-fibrogenesis phenotype in bladder pain syndrome/interstitial cystitis (BPS/IC). This study is to establish a novel experimental BPS/IC cell model and explore how different concentrations of tumor necrosis factor (TNF)-α influence the EMT and pro-fibrogenesis phenotype of urothelial cells.MethodsSV-HUC-1 urothelial cells were cultured with 2, 10, or 50 ng/mL TNF-α to mimic chronic inflammatory stimulation. The EMT and pro-fibrogenesis phenotype, including production of collagen I and pro-fibrosis cytokines, were estimated after 72 h of culture.ResultsThe bladder urothelial cells of BPS/IC exhibited upregulated vimentin, TNF-α and TNF receptor, downregulated E-cadherin, and increased collagen I. Higher concentrations of TNF-α (10 and 50 ng/mL) produced an obvious mesenchymal morphology, enhanced invasion and migratory capacity, increased expression of vimentin, and decreased expression of E-cadherin. Collagen I was increased in cells treated with 2 and 10 ng/mL TNF-α after 72 h. Secretion of interleukin (IL)-6 and IL-8 was promoted with 10 and 50 ng/mL TNF-α, while that of IL-1β or transforming growth factor-β was unaffected. Slug and Smad2 were upregulated by TNF-α after 72 h. The Smad pathway was activated most strongly with 10 ng/mL TNF-α and Slug pathway activation was positively correlated with the concentration of TNF-α.ConclusionsSustained 10 ng/mL TNF-α stimulation induced the EMT and pro-fibrogenesis phenotype resembling BPS/IC in SV-HUC-1 cells. Minor inflammatory stimulation induced the pro-fibrogenesis phenotype while severe inflammatory stimulation was more likely to produce significant EMT changes. Different degrees of activation of the Slug and Smad pathways may underlie this phenomenon.

Tributyrin supplementation in pasteurized waste milk: Effects on growth performance, health, and blood parameters of dairy calves

This study evaluated the effects of incremental tributyrin supplementation in pasteurized waste milk on growth performance, health, and blood metabolism of dairy calves before and after weaning. Forty-eight newborn female Holstein dairy calves (39.6 ± 2.75 kg; mean ± standard deviation) were blocked by age and randomly assigned to 3 treatments: pasteurized waste milk (1) without supplementation, (2) with 1 g/L of tributyrin products (unprotected solid powder; containing 35% tributyrin), or (3) with 2 g/L of tributyrin products. The calves were weaned on d 56 and were raised until d 77. Data were analyzed for the preweaning, postweaning, and overall periods. The results showed that starter intake and hay intake were not different among treatments in any period of the trial, but the crude protein intake tended to increase linearly with tributyrin supplementation during the overall period. Although tributyrin supplementation had no effects on body weight during preweaning and overall periods, body weight increased linearly with tributyrin supplementation postweaning. The average daily gain tended to increase linearly during postweaning and overall periods. No effects were observed on feed efficiency in any period. A positive linear relationship between body length and tributyrin supplementation was observed during the postweaning period, but no differences were found for the other body structural measurements in any period. The results of diarrhea showed that tributyrin concentration had a negative linear relationship with diarrhea frequency during preweaning and overall periods. The rectal temperature did not differ among treatments in any period, but a treatment × week effect for rectal body temperature was observed. For blood metabolism, tributyrin supplementation had no effects on insulin, growth hormone, total protein, albumin, or globulin. No differences were found in serum amyloid A concentration in any of the periods, yet haptoglobin concentration decreased linearly with increasing tributyrin concentration during postweaning and overall periods. Endothelin concentration showed a tendency to decrease linearly during preweaning and postweaning periods and decreased linearly with tributyrin supplementation during the overall period. An increasing tributyrin concentration was associated with a negative linear relationship with IL-1β concentration during the preweaning period, and no differences were found in the other periods. The concentration of IL-6 and tumor necrosis factor α were not different among treatments in any of the periods. These data suggest that increasing the concentration of tributyrin in pasteurized waste milk could increase growth performance and health of dairy calves, and incremental tributyrin supplementation could linearly reduce haptoglobin, endothelin, and IL-1β concentrations, indicating a positive effect of tributyrin on alleviating oxidative stress and inflammatory status of dairy calves. Calves fed pasteurized waste milk supplemented with tributyrin products (containing 35% tributyrin) at 2 g/L compared with 1 g/L of milk had more improved growth and health.

Huangkui Capsule Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Macrophage Activation by Suppressing Inflammation and Oxidative Stress in Mice.

Background Huangkui capsule (HKC) comprises the total flavonoid extract of flowers of Abelmoschus manihot (L.) Medicus. This study aimed to explore the effects of HKC on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and LPS-stimulated RAW 264.7 cells. Methods Enzyme-linked immunosorbent assay, histopathology, spectrophotometry, and quantitative real-time polymerase chain reaction were used for the assessments. Statistical analysis was performed using a one-way analysis of variance. Results LPS significantly increased lung inflammation, neutrophil infiltration, and oxidative stress and downregulated lung miR-451 expression. Treatment with HKC dramatically, reduced the total cell count in the bronchoalveolar lavage fluid (BALF), and inhibited myeloperoxidase activity in the lung tissues 24 h after LPS challenge. Histopathological analysis demonstrated that HKC attenuated LPS-induced tissue oedema and neutrophil infiltration in the lung tissues. Additionally, the concentrations of tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 in BALF and IL-6 in the plasma reduced after HKC administration. Moreover, HKC could enhance glutathione peroxidase and catalase activities and upregulate the expression of miR-451 in the lung tissues. In vitro experiments revealed that HKC inhibited the production of nitric oxide, TNF-α, and IL-6 in LPS-induced RAW 264.7 cells and mouse primary peritoneal macrophages. Additionally, HKC downregulated LPS-induced transcription of TNF-α and IL-6 in RAW 264.7 cells. Conclusions These findings suggest that HKC has anti-inflammatory and antioxidative effects that may protect mice against LPS-induced ALI and macrophage activation.

Імунологічні особливості перебігу хронічного гастродуоденіту в дітей на тлі лямбліозу

У статті проаналізовано імунологічні особливості перебігу хронічної гастродуоденальної патології в дітей на тлі лямбліозу. Мета дослідження: виділити характерні імунологічні критерії перебігу хронічної гастродуоденальної патології на тлі лямбліозу в дітей. Матеріали й методи. Обстеженi 54 дитини з ураженням слизової оболонки шлунка та дванадцятипалої кишки. Залежно від інвазування лямбліями усі діти були поділені на дві групи: І — 28 осіб з діагностованим лямбліозом, ІІ — 26 пацiєнтiв без інвазії. До групи контролю увійшли 24 практично здоровi дитини. Усім дітям проводили визначення концентрації iнтерлейкiну-4 (ІЛ-4) та фактора некрозу пухлини α (ФНП-α) у сироватці крові, паразитологічне дослідження калу. Результати. Інфікування H.pylori підтверджено в 18 (33,3 %) дітей. Частота інфікування H.pylori у хворих обох груп не відрізнялася: у І групі — 9 (32,1 ± 8,9 %), у ІІ — 9 (34,6 ± 9,5 %) випадків (р &gt; 0,05). Установлено, що вміст ІЛ-4 у обстежених дітей (8,0 ± 0,5 пг/мл) був вищим за показники контрольної групи, тоді як рівень ФНП-α (2,7 ± 0,7 пг/мл) — не відрізнявся. У дітей iз супутнім лямбліозом виявлено вищу концентрацію ІЛ-4 (9,2 ± 0,9 пг/мл) порівняно з пацієнтами без інвазування (6,7 ± 0,3 пг/мл). На рівень ІЛ-4 впливало поєднання лямблій та H.pylori. Максимальні показники ІЛ-4 спостерігалися при моноінвазії лямбліями і були вірогідно вищими за такi при моноінфекції H.pylori, а при поєднанні інфікуванні паразитами з H.pylori вміст ІЛ-4 знижувався, тоді як рiвень ФНП-α не відрізнявся. Вища концентрація ФНП-α спостерігалася в дітей із гіперацидністю, вона також зростала із тривалістю хвороби.

Serum Soluble Tumor Necrosis Factor Receptors 1 and 2 Are Early Prognosis Markers After ST-Segment Elevation Myocardial Infarction.

Background: As inflammation following ST-segment elevation myocardial infarction (STEMI) is both beneficial and deleterious, there is a need to find new biomarkers of STEMI severity.Objective: We hypothesized that the circulating concentration of the soluble tumor necrosis factor α receptors 1 and 2 (sTNFR1 and sTNFR2) might predict clinical outcomes in STEMI patients.Methods: We enrolled into a prospective cohort 251 consecutive STEMI patients referred to our hospital for percutaneous coronary intervention revascularization. Blood samples were collected at five time points: admission and 4, 24, 48 h, and 1 month after admission to assess sTNFR1 and sTNFR2 serum concentrations. Patients underwent cardiac magnetic resonance imaging at 1 month.Results: sTNFR1 concentration increased at 24 h with a median of 580.5 pg/ml [95% confidence interval (CI): 534.4–645.6]. sTNFR2 increased at 48 h with a median of 2,244.0 pg/ml [95% CI: 2090.0–2,399.0]. Both sTNFR1 and sTNFR2 peak levels were correlated with infarct size and left ventricular end-diastolic volume and inversely correlated with left ventricular ejection fraction. Patients with sTNFR1 or sTNFR2 concentration above the median value were more likely to experience an adverse clinical event within 24 months after STEMI [hazards ratio (HR): 8.8, 95% CI: 4.2–18.6, p < 0.0001 for sTNFR1; HR: 6.1, 95% CI: 2.5 –10.5, p = 0.0003 for sTNFR2]. Soluble TNFR1 was an independent predictor of major adverse cardiovascular events and was more powerful than troponin I (p = 0.04 as compared to the troponin AUC).Conclusion: The circulating sTNFR1 and sTNFR2 are inflammatory markers of morphological and functional injury after STEMI. sTNFR1 appears as an early independent predictor of clinical outcomes in STEMI patients.

Hypoxia-inducible transcription factor-1\u03b1 inhibition by topotecan protects against lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes

BackgroundMyocarditis, an inflammatory disease of the myocardium, is a serious hazard to human life due to the expansion of inflammatory lesions in the myocardium. The aim of this study was to investigate the role of hypoxia-inducible transcription factor (HIF)-1α and its inhibitor topotecan in the pathogenesis of myocarditis.MethodsH9c2 cardiomyoblasts was stimulated with lipopolysaccharide (LPS) to simulate myocarditis model in vitro. The levels of myocardial damage markers were determined using commercially available kits. Western blotting was used to evaluate HIF-1α expression after LPS challenge. Then, after HIF-1α silencing, the contents of inflammatory factors were determined with enzyme-linked immunosorbent assay (ELISA). Cell viability was tested by means of a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed by flow cytometry, and the expression of apoptotic proteins was examined using western blot analysis. Subsequently, HIF-1α was overexpressed and topotecan was employed to treat H9c2 cells under LPS exposure condition. The biological functions were detected again.ResultsLPS significantly elevated the levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I) in supernatant of H9c2 cell lysates. Additionally, LPS led to the notably upregulated expression of HIF-1α. HIF-1α-knockdown markedly decreased the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 compared with the LPS-induced group. Moreover, the cell viability was conspicuously enhanced and cell apoptotic ratio was remarkably reduced, accompanied by downregulated expression of Bax, Bim, caspase 3 and caspase 9 after HIF-1α silencing. Consistently, HIF-1α gain-of-function significantly promoted the production of inflammatory cytokines and cell apoptosis, which was partially counteracted by topotecan administration.ConclusionTo conclude, these findings demonstrated that HIF-1α inhibition by topotecan ameliorates LPS-induced myocarditis in vitro, providing a new approach in the treatment of myocarditis.