A randomized study on the clinical and biological effects of combine therapy-hrec TNF α+MLT in patients with advanced neoplasms

In pathophysiological conditions, increased blood-borne TNF-α induces a broad range of biological effects, including activation of the hypothalamic-pituitary-adrenal axis and sympathetic drive. In urethane-anesthetized adult Sprague-Dawley rats, we examined the mechanisms by which blood-borne TNF-α activates neurons in paraventricular nucleus (PVN) of hypothalamus and rostral ventrolateral medulla (RVLM), two critical brain regions regulating sympathetic drive in normal and pathophysiological conditions. TNF-α (0.5 μg/kg), administered intravenously or into ipsilateral carotid artery (ICA), activated PVN and RLVM neurons and increased sympathetic nerve activity, arterial pressure, and heart rate. Responses to intravenous TNF-α were not affected by vagotomy but were reduced by mid-collicular decerebration. Responses to ICA TNF-α were substantially reduced by injection of the cyclooxygenase inhibitor ketorolac (150 μg) into lateral ventricle. Injection of PGE2 (50 ng) into lateral ventricle or directly into PVN increased PVN or RVLM activity, respectively, and sympathetic drive, with shorter onset latency than blood-borne TNF-α. These findings suggest that blood-borne cytokines stimulate cardiovascular and renal sympathetic responses via a prostaglandin-dependent mechanism operating at the hypothalamic level.

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Effects of Probiotic (Bacillus subtilis DE111) Supplementation on Immune Function, Hormonal Status, and Physical Performance in Division I Baseball Players

Sports ◽

10.3390/sports6030070 ◽

2018 ◽

Vol 6 (3) ◽

pp. 70 ◽

Cited By ~ 12

Author(s):

Jeremy Townsend ◽

David Bender ◽

William Vantrease ◽

Philip Sapp ◽

Ann Toy ◽

...

Keyword(s):

Body Composition ◽

Bacillus Subtilis ◽

Physical Performance ◽

Randomized Study ◽

Division I ◽

Hormonal Status ◽

Probiotic Supplementation ◽

Double Blind ◽

Significant Group ◽

Tnf Α

We sought to determine the effects of probiotic supplementation (Bacillus subtilis DE111; 1 billion CFU∙d−1) on markers of immune and hormonal status in collegiate male athletes following 12 weeks of offseason training. Twenty-five Division I male baseball athletes (20.1 ± 1.5 years, 85.5 ± 10.5 kg, 184.7 ± 6.3 cm) participated in this double blind, placebo-controlled, randomized study. Participants were randomly assigned to a probiotic (PRO; n = 13) or placebo (PL; n = 12) group. Pre- and post-training, all athletes provided resting blood and saliva samples. Circulating concentrations of testosterone, cortisol, TNF-α, IL-10, and zonulin were examined in the blood, while salivary immunoglobulin A (SIgA) and SIgM were assayed as indicators of mucosal immunity. Separate analyses of covariance (ANCOVA) were performed on all measures collected post intervention. No differences in measures of body composition or physical performance were seen between groups. TNF-α concentrations were significantly (p = 0.024) lower in PRO compared to PL, while there were no significant group differences in any other biochemical markers examined. A main effect for time was observed (p < 0.05) for increased testosterone (p = 0.045), IL-10 (p = 0.048), SIgA rate (p = 0.031), and SIgM rate (p = 0.002) following offseason training. These data indicate that probiotic supplementation had no effect on body composition, performance, hormonal status, or gut permeability, while it may attenuate circulating TNF-α in athletes.

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UVB Dose Optimization for Phototherapy in Vitamin D Deficiency : Profile Analysis of Vitamin D, TNF-α, Vascular Endothelial Growth Factor (VEGF) and Platelet Derived Growth Factor (PDGF) in Wistar Rats

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v19i4.46636 ◽

2020 ◽

Vol 19 (4) ◽

pp. 749-754

Author(s):

Cynthia Arsita ◽

Taufiqurrachman Nasihun ◽

Atina Hussaana

Keyword(s):

Vitamin D ◽

Growth Factor ◽

Wistar Rats ◽

Biological Effects ◽

Medical Science ◽

The Other ◽

Control Group ◽

Uvb Radiation ◽

Tnf Α ◽

Post Radiation

Background : UVB radiation responsible for the most important biological effects including Vitamin D3 synthesis and inflammation. UVB radiation are absorbed by 7-dehydrocholesterol in the plasma membrane of epidermal cells resulting in production of cis-previtamin D3. In the other hand, an exposure to UVB leads to cutaneous tissue inflammation modulates by TNF-α which also increases platelet activating factor. VEGF and PDGF induced by TNF-α during wound healing, characterized with angiogenesis and reephitalization. Furthermore, vitamin D plays a role in inflammation inhibition and upregulates growth factors. However, the study of the mechanism has not yet been thoroughly investigated. Methods: This study uses post test only group design, subjected wistar rats divided into four groups. Control group, non irradiated with UVB, and the other three groups, treated with graded UVB dose started with 1 MED (50 mJ/cm2), 2 MED (100mJ/cm2) and 3 MED (150 mJ/cm2) and investigated at 6, 12, 24 and 48 hours post UVB irradiation. Result : The serum level of vitamin D, VEGF and PDGF were increasing due to UVB dose addition. The highest level was reached at 6 hours post radiation using 3 MED, which gradually decrease up to 48 hours (p =0,000). The rise of vitamin D after UVB radiation, inhibit TNF-α induction in every dose accordant UVB dose addition and the lowest level is using 3 MED at 12 hours post radiation (p =0,000). TNF-α reach its highest level at 24 hours post radiation using 1 MED, it is related with the acute phase of inflammation. Conclusion : This study reveal that higher UVB irradiance increases vitamin D and inhibit TNF-α which also promotes VEGF and PDGF. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.749-754

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Fermentation Improves Anti-Inflammatory Effect of Sipjeondaebotang on LPS-Stimulated RAW 264.7 Cells

The American Journal of Chinese Medicine ◽

10.1142/s0192415x12500619 ◽

2012 ◽

Vol 40 (04) ◽

pp. 813-831 ◽

Cited By ~ 10

Author(s):

You-Chang Oh ◽

Won-Kyung Cho ◽

Yun Hee Jeong ◽

Ga Young Im ◽

Min Cheol Yang ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Mediators ◽

High Performance ◽

Biological Effects ◽

Inhibitory Effect ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Tnf Α ◽

Cox 2 ◽

Anti Inflammatory

Sipjeondaebotang (SJ) has been used as a traditional drug in east-Asian countries. In this study, to provide insight into the biological effects of SJ and SJ fermented by Lactobacillus, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in macrophages. The investigation was focused on whether SJ and fermented SJ could inhibit the production of pro-inflammatory mediators such as prostaglandin (PG) E2 and nitric oxide (NO) as well as the expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in LPS-stimulated RAW 264.7 cells. We found that SJ modestly inhibited LPS-induced PGE2, NO and TNF-α production as well as the expressions of COX-2 and iNOS. Interestingly, fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, fermented SJ exhibited increased inhibition of p38 MAPK and c-Jun NH2-terminal kinase (JNK) MAPK phosphorylation as well as NF-κB p65 translocation by reduced IκBα degradation compared with either untreated controls or unfermented SJ. High performance liquid chromatography (HPLC) analysis showed fermentation by Lactobacillus increases liquiritigenin and cinnamyl alcohol contained in SJ, which are known for their anti-inflammatory activities. Finally, SJ fermented by Lactobacillus exerted potent anti-inflammatory activity by inhibiting MAPK and NF-κB signaling in RAW 264.7 cells.

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Pirfenidone Blocks the In Vitro and In Vivo Effects of Staphylococcal Enterotoxin B

Infection and Immunity ◽

10.1128/iai.70.6.2989-2994.2002 ◽

2002 ◽

Vol 70 (6) ◽

pp. 2989-2994 ◽

Cited By ~ 36

Author(s):

Martha L. Hale ◽

Solomon B. Margolin ◽

Teresa Krakauer ◽

Chad J. Roy ◽

Bradley G. Stiles

Keyword(s):

Human Peripheral Blood ◽

Biological Effects ◽

Interleukin 1 ◽

Staphylococcal Enterotoxin ◽

Sublethal Dose ◽

Staphylococcal Enterotoxin B ◽

Tnf Α ◽

Cytokine Levels ◽

Enterotoxin B

ABSTRACT Pirfenidone [5-methyl-1-phenyl-2-(1H)-pyridone] down-regulates expression of cytokines and other mediators involved in the onset and development of pulmonary fibrosis. Pirfenidone also inhibits production of tumor necrosis factor alpha (TNF-α) from macrophages incubated with endotoxin and protects mice against endotoxin shock. Pirfenidone's ability to reduce cytokine expression in these disorders led us to investigate the drug's effect on another cytokine anomaly, superantigen-induced shock. BALB/c mice were exposed to staphylococcal enterotoxin B (SEB) either systemically or by aerosol and subsequently potentiated with a sublethal dose of lipopolysaccharide. In these experiments, pirfenidone given 2 to 4.25 h after SEB resulted in 80 to 100% survival versus only 0 to 10% survival among untreated control animals. Relative to serum cytokine levels from controls given toxin but no drug, there was a 35 to 80% decrease in TNF-α, interleukin 1, and other proinflammatory cytokines. In vitro experiments with human peripheral blood lymphocytes revealed that pirfenidone reduced SEB-induced cytokine levels 50 to 80% and inhibited 95% of SEB-induced T-cell proliferation. Overall, these studies demonstrated the potential utility of pirfenidone as a therapeutic against septic shock and the biological effects of SEB.

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The Novel Peptide AEDPPE Alleviates Trophoblast Cell Dysfunction Associated With Preeclampsia by Regulating the NF-κB Signaling Pathway

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.738378 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yixiao Wang ◽

Yan Cao ◽

Xiaohong Ji ◽

Ting Li ◽

Lu Xue ◽

...

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Signaling Pathway ◽

Rat Model ◽

Biological Effects ◽

Cytokine Expression ◽

Cell Counting ◽

Migration And Invasion ◽

Therapeutic Effects ◽

Tnf Α

Background: Preeclampsia (PE) is a serious risk to the health of pregnant women and fetuses during pregnancy, and there is no effective treatment for this condition. Although many reports have confirmed the therapeutic effects of peptides in diseases, the role of peptides in PE remains poorly understood.Methods: A differentially expressed peptide in PE (AEDPPE) is derived from heat-shock protein beta-1 (HSPB1), amino acids 100 to 109 (DVNHFAPDEL), which we identified in a previous study. We synthesized AEDPPE and investigated its effect on HTR-8/SVneo cell function using a Cell Counting Kit-8, flow cytometric assay, and Transwell and wound-healing assays. Quantitative reverse transcription-PCR and ELISA were used to determine cytokine expression. Pull-down assay, mass spectrometry, Western blot analysis, and immunofluorescence were used to explore the potential targets and signaling pathways regulated by AEDPPE. Finally, we assessed the effect of AEDPPE in the lipopolysaccharide (LPS)-induced PE-like rat model.Results: AEDPPE significantly promoted the migration and invasion of HTR-8/SVneo cells, and it decreased the expression of interleukins 1 beta (IL-1β), interleukin 6 (IL-6), and interleukin 8 (IL-8). These functions performed by AEDPPE remained evident after injury to HTR-8/SVneo cells with tumor necrosis factor-alpha (TNF-α), and AEDPPE reversed the elevated sFlt-1/PlGF ratio induced by TNF-α. AEDPPE may exert these biological effects by binding to heat-shock protein 90β (HSP 90β) and, thus, affect the NF-κB signaling pathway. In an LPS-induced PE-like rat model, AEDPPE significantly improved PE symptoms and fetal rat outcomes.Conclusion: Our study showed that AEDPPE enhanced trophoblast migration and invasion and reduced inflammatory cytokine expression, and we hypothesized that these actions involved the NF-κB signaling pathway. The use of AEDPPE may thus develop into a novel modality in the treatment of PE.

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Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2021.688066 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qi Jiang ◽

Guocan Yang ◽

Fan Xiao ◽

Jue Xie ◽

Shengjun Wang ◽

...

Keyword(s):

Autoimmune Diseases ◽

Chemokine Receptors ◽

Inflammatory Diseases ◽

Biological Effects ◽

Cell Subset ◽

Interferon Γ ◽

Th22 Cells ◽

Tnf Α ◽

Ifn Γ

Upon antigenic stimulation, naïve CD4+T cells differentiate into different subsets and secrete various cytokines to exert biological effects. Th22 cells, a newly identified CD4+T cell subset,are distinct from the Th1, Th2 and Th17 subsets. Th22 cells secrete certain cytokines such as IL-22, IL-13 and TNF-α, but not others, such as IL-17, IL-4, or interferon-γ (IFN-γ), and they express chemokine receptors CCR4, CCR6 and CCR10. Th22 cells were initially found to play a role in skin inflammatory diseases, but recent studies have demonstrated their involvement in the development of various autoimmune diseases. Here, we review research advances in the origin, characteristics and effector mechanisms of Th22 cells, with an emphasis on the role of Th22 cells and their main effector cytokine IL-22 in the pathogenesis of autoimmune diseases. The findings presented here may facilitate the development of new therapeutic strategies for targeting these diseases.

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The capability of minor quaternary benzophenanthridine alkaloids to inhibit TNF-α secretion and cyclooxygenase activity

Acta Veterinaria Brno ◽

10.2754/avb201786030223 ◽

2017 ◽

Vol 86 (3) ◽

pp. 223-230 ◽

Cited By ~ 1

Author(s):

Jan Hošek ◽

Kristýna Šebrlová ◽

Petra Kaucká ◽

Ondřej Peš ◽

Eva Táborská

Keyword(s):

Biological Effects ◽

Benzophenanthridine Alkaloids ◽

Additional Information ◽

Tnf Α ◽

Wide Range ◽

Anti Inflammatory ◽

Factor Α ◽

Relationship Of ◽

Sanguinarine And Chelerythrine

Quaternary benzophenanthridine alkaloids are known to have a wide range of biological effects, including antimicrobial, antifungal, anti-inflammatory, and antitumour activities. However, only sanguinarine and chelerythrine have been studied intensively. The aim of this study was to evaluate the anti-inflammatory potential of the five minor quaternary benzophenanthridine alkaloids sanguilutine, sanguirubine, chelirubine, chelilutine, and macarpine in vitro and to compare them with more thoroughly studied sanguinarine and chelerythrine. Before making cell-based assays, the cytotoxicity of the alkaloids was evaluated. The anti-inflammatory potential of the chosen alkaloids was evaluated as for their ability to modulate the lipopolysaccharide-induced secretion of tumour necrosis factor α (TNF-α) in the macrophage-like cell line THP-1. The cyclooxygenase (COX)-1 and COX-2 inhibitory activities were also measured. The results indicate that the presence of a methylenedioxy ring attached at carbon (C)7-C8 is important for reducing the secretion of TNF-α. Interestingly, this effect did not show a simple dependence on concentration. The selected alkaloids showed little or no anti-COX activity. The results obtained from the present experiments may provide additional information useful in understanding the structure-to-activity relationship of the quaternary benzophenanthridine alkaloids. The anti-inflammatory potential and the cytotoxic effect are driven by the presence of a methylenedioxy ring attached at C7-C8 and C2-C3, respectively.

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Molecular Mechanism of Antioxidant and Anti-Inflammatory Effects of Omega-3 Fatty Acids in Perilla Seed Oil and Rosmarinic Acid Rich Fraction Extracted from Perilla Seed Meal on TNF-α Induced A549 Lung Adenocarcinoma Cells

Molecules ◽

10.3390/molecules26226757 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6757

Author(s):

Payungsak Tantipaiboonwong ◽

Wittaya Chaiwangyen ◽

Maitree Suttajit ◽

Napapan Kangwan ◽

Sirichat Kaowinn ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Rosmarinic Acid ◽

Seed Oil ◽

Biological Effects ◽

A549 Cells ◽

Seed Meal ◽

Omega 3 ◽

Tnf Α ◽

A549 Lung ◽

Perilla Seed

Industrially, after the removal of oil from perilla seeds (PS) by screw-type compression, the large quantities of residual perilla seed meal (PSM) becomes non-valuable waste. Therefore, to increase the health value and price of PS and PSM, we focused on the biological effects of perilla seed oil (PSO) and rosmarinic acid-rich fraction (RA-RF) extracted from PSM for their role in preventing oxidative stress and inflammation caused by TNF-α exposure in an A549 lung adenocarcinoma culture model. The A549 cells were pretreated with PSO or RA-RF and followed by TNF-α treatment. We found that PSO and RA-RF were not toxic to TNF-α-induced A549 cells. Both extracts significantly decreased the generation of reactive oxygen species (ROS) in this cell line. The mRNA expression levels of IL-1β, IL-6, IL-8, TNF-α, and COX-2 were significantly decreased by the treatment of PSO and RA-RF. The Western blot indicated that the expression of MnSOD, FOXO1, and NF-κB and phosphorylation of JNK were also significantly diminished by PSO and RA-RF treatment. The results demonstrated that PSO and RA-RF act as antioxidants to scavenge TNF-α induced ROS levels, resulting in decreased the expression of MnSOD, FOXO1, NF-κB and JNK signaling pathway in a human lung cell culture exposed to TNF-α.

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