Tumor Necrosis Factor-alpha Protein Research Articles

Inflammatory and Endothelial Adaptations to Aerobic and Strength Training in Hypertensive Middle‐Aged Individuals: a Controlled Randomized Clinical Trial

Hypertension is a worldwide prevalent disease, it's estimated that more than one billion of the world population is hypertensive, most of them middle‐aged productive people. Additionally, hypertension is associated with progression of the atherosclerosis and the main cause of death by myocardial infarction and stroke. This context is characterized by a marked inflammatory process that leads to an endothelial impairment. In the other hand, lifestyle modifications like physical exercise have been emerged as important non pharmacological tool to improve the treatment. However it's not fully understood how the different exercise ways, strength and aerobic exercises, can modulate inflammatory and endothelial markers in hypertensive individuals. Thus, the main goal of this study was to evaluate the inflammatory, endothelial and ambulatory blood pressure adaptations to twelve weeks of aerobic and strength training program. This study was approved by local ethic committee under the protocol: 2.199.957 and registered in the clinical trials (ID: NCT03282942) being in agreement with the Helsinki declaration. Forty‐five hypertensive middle‐aged individuals (23 women and 22 men) were randomized in three groups: aerobic training (AT: 15 individuals 47,3 ± 6,2 years); strength training (ST: 15 individuals 46,4 ± 8,1) and control group (CON: 15 individuals 45,4 ± 7,3 years). C‐reactive protein (CRP), tumor necrosis factor alpha (TNF‐a), interleukin 10 (IL‐10) and monocyte chemoattractant protein 1 (MCP‐1) were evaluated as inflammatory biomarkers. Nitrite and Nitrate (NOx) and Endothelin‐1 (ET‐1) concentrations were used to access the endothelial function. The average of 24h systolic (24hSBP), and diastolic blood pressure (24hDBP) was accessed using an automated oscillometric device. Day‐time systolic (DTSBP) and diastolic blood pressure (DTDBP), as well as night‐time systolic (NTSBP) and diastolic blood pressure (NTDBP) was also calculated. After twelve weeks of AT, ST or CON, a two‐way ANOVA founds time effects for CRP (3,1 ± 2,4 vs. 1,8 ± 0,8 mg/dl p = 0,05), IL‐10 (38,3 ± 23,5 vs. 49,5 ± 25,5 pg/ml) and MCP‐1 (121,1 ± 60,2 vs 84,5 ± 41,6 pg/ml) only in the AT groups. There are also time effects for NOx (9,9 ± 6,9 vs. 13,3 ± 3,7 μM p = 0,04) and ET‐1 (9,3 ± 8,9 vs. 6,5 ± 4 pg/ml p = 0,04) in the AT group. The 24SBP and DTSBP showed a significant decrease in the AT group (116,8 ± 8,5 vs. 109,04 ± 8,9 mmHg p = 0,005 and 121,27 ± 7,79 vs 111,46 ± 11,24 mmHg p = 0,04), while in the ST group DTSBP decreases (125,94 ± 5,2 vs 118,92 ± 6,5 mmHg p = 0,006). No changes in the CONT groups were observed, additionally no interactions between groups were found. The main feedings of the present study shows that AT can positively modulate the inflammatory profile, endothelial function and 24hSBP of middle‐aged hypertensive individuals, while ST promotes a significant improvement only in the DTSBP. Thus, we support that aerobic exercises should be emphasized as tool in the control and progression of the systemic arterial hypertension.Support or Funding InformationThis study was funded by the National Council for Scientific and Technological Development (CNPq, Brazil)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Serum fetuin-A, tumor necrosis factor alpha and C-reactive protein concentrations in patients with hereditary angioedema with C1-inhibitor deficiency

Background and aimsHereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by localized, non-pitting, and transient swelling of submucosal or subcutaneous region. Human fetuin-A is a multifunctional glycoprotein that belongs to the proteinase inhibitor cystatin superfamily and has structural similarities to the high molecular weight kininogen. Fetuin-A is also known a negative acute phase reactant with anti-inflammatory characteristics. In this study we aimed to determine serum fetuin-A, C-reactive protein (CRP) and tumor necrosis factor alpha (TNFα) concentrations in patients with C1-INH-HAE during symptom-free period and during attacks and compare them to those of healthy controls. Further we analyzed possible relationship among these parameters as well as D-dimer levels which was known as marker of HAE attacks.Patients and methodsSerum samples of 25 C1-INH-HAE patients (8 men, 17 women, age: 33.1 ± 6.9 years, mean ± SD) were compared to 25 healthy controls (15 men, 10 women, age: 32.5 ± 7.8 years). Serum fetuin-A and TNFα concentrations were determined by ELISA, CRP and D-dimer by turbidimetry.ResultsCompared to healthy controls patients with C1-INH-HAE in the symptom-free period had significantly decreased serum fetuin-A 258 μg/ml (224–285) vs. 293 μg/ml (263–329), (median (25–75% percentiles, p = 0.035) and TNFα 2.53 ng/ml (1.70–2.83) vs. 3.47 ng/ml (2.92–4.18, p = 0.0008) concentrations. During HAE attacks fetuin-A levels increased from 258 (224–285) μg/ml to 287 (261–317) μg/ml (p = 0.021). TNFα and CRP levels did not change significantly. We found no significant correlation among fetuin-A CRP, TNFα and D-dimer levels in any of these three groups.ConclusionsPatients with C1-INH-HAE have decreased serum fetuin-A concentrations during the symptom-free period. Given the anti-inflammatory properties of fetuin-A, the increase of its levels may contribute to the counter-regulation of edema formation during C1-INH-HAE attacks.

TIPE2 suppresses atherosclerosis by exerting a protective effect on macrophages via the inhibition of the Akt signaling pathway.

Macrophage apoptosis and inflammation serve pivotal roles in the occurrence of atherosclerosis. However, the detailed underlying mechanism of macrophage action during atherosclerosis is poorly understood. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a well-known negative regulator of the immune response. The current study assessed the association between TIPE2 and apoptosis-associated molecules in macrophages during atherosclerosis, as well as the role of TIPE2 in macrophage inflammation. RAW264.7 macrophages were subsequently transfected with a TIPE2 expression plasmid. Following oxidized low-density lipoprotein (oxLDL) induction (100 µg/m1) for 48 h, macrophage apoptosis was assessed via Annexin V/propidium iodide dual staining. The apoptosis-associated factors and Akt signaling pathway-associated factors were also evaluated via western blot analysis. The expression of inflammatory factors was determined via a reverse transcription-quantitative polymerase chain reaction assay and western blotting. Furthermore, a transwell assay was performed to test cell invasion ability. NF-κB phosphorylation and nuclear translocation were also assessed via western blotting. The results demonstrated that TIPE2 overexpression may promote oxLDL-induced RAW264.7 macrophage apoptosis by inhibiting the protein kinase B (Akt) signaling pathway. Furthermore, it was demonstrated that TIPE2 significantly reduced oxLDL-induced tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 expression (MCP-1), and increased IL-10 expression by suppressing NF-κB phosphorylation and nuclear translocation in RAW264.7 macrophages. These results indicated that TIPE2 serves a protective role in oxLDL-induced RAW264.7 macrophages, and its mechanism may partly be exerted via the inhibition of the PI3K/Akt signaling pathway and the reduction of the macrophage inflammatory response achieved via the suppression of NF-κB signal activation.

Abstract # 2065 Markers of peripheral immune cells are increased in regions of blood-brain barrier disruption after repetitive blast injury

Cycles of blood-brain barrier (BBB) disruption have been observed in a variety of rodent brain injury models. Changes in BBB permeability are correlated with pro-inflammatory cytokine production and brain infiltration of peripheral leukocytes. Whether the influx of peripheral leukocytes through a permeable BBB affords prolonged neuroprotection, or promotes detrimental changes to the anatomical site of entry remains to be elucidated. In a mouse model of blast-induced traumatic brain injury (TBI), we observed brain-region specific BBB permeability to radiolabeled albumin at 72 h. Moreover, we measured an increase in pro-inflammatory tumor necrosis factor alpha (TNF α ) protein expression and mRNA abundance in brain regions vulnerable to BBB disruption. The nitric oxide synthase inhibitor N(G)-nitro- l -arginine methyl ester (L-NAME) attenuated TNF α levels and abrogated albumin permeability. We hypothesize that leukocyte infiltration into vulnerable brain regions after TBI may also be mediated by nitric oxide dependent mechanisms. Using flow cytometry, we measured an increase of blood-derived monocytes (Ly6C/G-high and CD45-high) and T-cells (CD3+ and CD4+) in brain regions vulnerable to BBB disruption at 72 h post-TBI. The physiological process of leukocyte infiltration could be driven by nitric oxide dependent mechanisms, which could be exploited, at the right time, to assist in chronic neurotrauma resolution.

Suppression of inflammation by ethanol extract of Clausena lansium via modulation of TLR4/MYD88/TRAF6 signaling pathway in RAW 264.7 macrophages

The fruit and root of Clausena lansium are remedy for bronchitis in oriental traditional medicine. Extracts from Clausena lansium are reported to have antioxidant, anti-inflammatory, and anticancer activities. This study is designed to investigate whether the ethanol extract of Clausena lansium (Lour.) Skeels could inhibit the lipopolysaccharides (LPS)-induced inflammatory in RAW 264.7 macrophages and the underlining mechanisms. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) are used to detect the secretion of tumor necrosis factor alpha (TNF-α) protein and expression of TNF-α mRNA, respectively. RT-PCR and Western blotting are used to determine the mRNA and protein levels of TLR4, MYD88, and TRAF6, respectively. The extract of Clausena lansium suppressed the expression and secretion of TNF-α, which is released by RAW 264.7 cells after LPS induction. Meanwhile, the expression of TLR4, MYD88, and TRAF6 are decreased by extracts from Clausena lansium. Meanwhile, NBP2-29328, an inhibitor of MYD88, synergistically enhances the inhibiting effect of extract from Clausena lansium. The results imply that ethanol extract from Clausena lansium attenuate macrophage-mediated inflammation and TLR4/MYD88/TRAF6 pathway is its potential target.

Protective effect of citrus lemon on inflammation and adipokine levels in acrylamide-induced oxidative stress in rats

The high exposure to acrylamide (AA) due to smoking and increased consumption of processed and fast foods in recent years, has become one of the health threatening problems. This study examined the effect of lemon juice on inflammation and adipokines in acrylamide-induced oxidative stress in rats. Forty animals were divided into five groups. Toxicity was induced by AA (35mg/kg) for two weeks in all groups except normal control group. After that, lemon juice in three doses was administrated to treatment groups for 4 weeks. Serum levels of adipokines and inflammatory parameters and both serum and liver levels of oxidative stress parameters were measured. The results showed groups were received AA had significant higher levels of malondialdehyde, tumor necrosis factor alpha, leptin and C-reactive protein and lower levels of total antioxidant capacity compared to the negative control group. Lemon juice in all three doses significantly improved serum levels of TAC, MDA, TNFα and hs-CRP in treated groups. Also, 7.5 ml/kg lemon juice significantly decreased leptin levels. However, lemon juice had no significant effect on adiponectin levels. This study suggests lemon juice as a potential dietary alternative could attenuate leptin levels and manage oxidative and inflammatory damages in acrylamide- induced toxicity in rats.

Состояние липидного и углеводного обменов у детей, родившихся от матерей с гестационным сахарным диабетом

Gestational diabetes mellitus (GDM) develops in 7-18% of women worldwide. The number of pregnant with GDM is steadily increasing. GDM is more likely to develop among obese patients. Women who are obese have features of chronic low-grade inflammation, manifest by increased tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-12 (IL-12), and high sensitivity C-reactive protein (hsCRP). Obesity is characterised by insulin resistance, and down-regulation of adiponectin and up-regulation of leptin, resistin and retinol-binding protein-4 (RBP4) contribute to this. Obesity and excess gestational weight gain results in a three-fold increased risk of adverse pregnancy outcomes, including long term metabolic syndrome and endocrine diseases for baby. Offspring born from pregnancies complicated by GDM has higher body mass index (BMI) compared with non-GDM offspring and has high risk of obesity throughout all periods of childhood. GDM may have impact on genetic modifications in the offspring.

NARINGIN PREVENT CISPLATIN-INDUCED NEPHROTOXICITY BY ABROGATION OF OXIDATIVE STRESS AND INFLAMMATION IN RATS

Nephrotoxicity remains one of the most dangerous effect relevant to cisplatin use in chemotherapy. Rat injection with cisplatin in a single dose of 7 mg/kg intraperitoneally resulted in a significant increase in serum level of urea and creatinine. Also, cisplatin caused marked increase in renal content of malondialdehyde (MDA), while depletion in reduced glutathione (GSH). In addition, cisplatin administration notably increased kidney/body weight ratio, renal contents of nitric oxide (NO), tumor necrosis factor alpha(TNF-α) and cyclooxygenase-2 (COX-2) protein level as well as renal myeloperoxidase (MPO) activity. Histopathological examination confirmed the biochemical and molecular results which revealed several pathological alteration in the renal tissues following cisplatin. Oral pretreatment of rats with naringin (NAR) (80 mg/kg) for 14 days before and 7 days after cisplatin injection significantly reduced the pathological level of serum urea and creatinine and restored oxidative stress parameters. In the same manner, the inflammatory markers as well as kidney/body weight ratio show great improvement following the treatment. The histopathological examination confirms fit with the biochemical and molecular results. In conclusion, NAR showed a great protective effect against cisplatin-induced nephrotoxicity in rats via its antioxidant, anti-inflammatory roles.

Low Phytanic Acid-Concentrated DHA Prevents Cognitive Deficit and Regulates Alzheimer Disease Mediators in an ApoE-/- Mice Experimental Model.

Alzheimer’s disease (AD) is the main cause of dementia and cognitive impairment. It has been associated with a significant diminution of omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) levels in the brain. Clinical trials with DHA as a treatment in neurological diseases have shown inconsistent results. Previously, we reported that the presence of phytanic acid (PhA) in standard DHA compositions could be blunting DHA’s beneficial effects. Therefore, we aimed to analyze the effects of a low PhA-concentrated DHA and a standard PhA-concentrated DHA in Apolipoprotein E knockout (ApoE−/−) mice. Behavioral tests and protein expression of pro-inflammatory, pro-oxidant, antioxidant factors, and AD-related mediators were evaluated. Low PhA-concentrated DHA decreased Aβ, ß-amyloid precursor protein (APP), p-tau, Ca2+/calmodulin-dependent protein kinase II (CAMKII), caspase 3, and catalase, and increased brain derived neurotrophic factor (BDNF) when compared to standard PhA-concentrated DHA. Low PhA-concentrated DHA decreased interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) protein expression in ApoE−/− mice when compared to standard PhA-concentrated DHA. No significant differences were found in p22phox, inducible nitric oxide synthase (iNOS), glutathione peroxidase (GPx), superoxide dismutase 1 (SOD-1), and tau protein expression. The positive actions of a low PhA-concentrated DHA were functionally reflected by improving the cognitive deficit in the AD experimental model. Therefore, reduction of PhA content in DHA compositions could highlight a novel pathway for the neurodegeneration processes related to AD.

STAT3 and Nrf2 pathways modulate the protective effect of verapamil on lung injury of diabetic rats

We aimed to assess the protective role of verapamil, L-type calcium channel blockers, against early lung damage in diabetic rats. Lung injury has recently been recognized as a consequent complication of diabetes mellitus. Hyperglycemia induces inflammatory changes in lung tissue early in the disease. Twenty four adult male rats were grouped into control, diabetic, diabetic treated with verapamil, and verapamil control. Streptozotocin (STZ) was used to induce diabetes. Oxidative parameters and antioxidative mechanisms were assessed in lung homogenate. Tumor necrosis factor alpha (TNFα) protein was measured as a pro-inflammatory mediator. Signal transducer and activator of transcription 3 (STAT3) gene expression and nuclear erythroid factor 2 (Nrf2) immunoexpression were screened. The lung showed oxidative damage and inflammatory infiltration in STZ diabetic rats early at 2 weeks. The parameters significantly improved in lung tissue treated with verapamil. Histopathology of the lung tissue confirmed the results. Inhibition of STAT3/TNFα pathway was involved in the protection offered by verapamil. Activation of Nrf2 together with an increasing antioxidant capacity of diabetic lung significantly ameliorates the injury induced by diabetes. Verapamil afforded protection in diabetic lung injury. The protection was mediated by the anti-inflammatory and antioxidant effects of verapamil.

Keratinocytes contribute to the recruitment and M1 polarisation of macrophages during C. albicans colonisation

Candida albicans (C. albicans) is an opportunistic human fungal pathogen that colonises the skin. Both keratinocytes and macrophages play crucial roles in host defence against C. albicans. However, the interaction of keratinocytes with macrophages during C. albicans colonisation has not been well studied. In this study, macrophages were cultured in conditioned medium from keratinocytes treated with heat-inactivated C. albicans (CM-C. albicans), macrophage migration and polarised activation and were then assessed by a Transwell assay, flow cytometry, quantitative real-time PCR (qPCR), Western blot and an enzyme-linked immunosorbent assay (ELISA). The results showed that CM-C. albicans-stimulated macrophages display significantly increased migration and phagocytosis, and they display an upregulation of proinflammatory cytokines (tumour necrosis factor alpha (TNF-a), interleukin (IL)-12 and nitric oxide (NO)). Markers characteristic of M1macrophages,such as human leukocyte antigen (HLA)-DR, CD86 and inducible nitric oxide synthase (iNOS), are upregulated, whereas markers of M2macrophages,such as mannose receptor (MR) and Arginase1(Arg1), are not affected. Additionally, the levels of TNF-a, IL-12 and monocyte chemotactic protein 1 (MCP-1) in CM-C. albicans are markedly upregulated, whereas the levels of IL-4 and IL-10 are not affected. And the CM-C. albicans-induced M1macrophage polarisation, proinflammatory cytokine production and phagocytosis could be blocked by an anti-TNF-a neutralising antibody. This study showed that keratinocytes may promote macrophage recruitment and M1polarisation during C. albicans colonisation at least in part by secreting TNF-a.

Blockade of NEAT1 represses inflammation response and lipid uptake via modulating miR-342-3p in human macrophages THP-1 cells.

Atherosclerosis has been recognized as a chronic inflammation process induced by lipid of the vessel wall. Oxidized low-density lipoprotein (ox-LDL) can drive atherosclerosis progression involving macrophages. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in atherosclerosis development. In our current study, we focused on the biological roles of lncRNA NEAT1 in atherosclerosis progress. Here, we found that ox-LDL was able to trigger human macrophages THP-1 cells, a human monocytic cell line, apoptosis in a dose-dependent and time-dependent course. In addition, we observed that NEAT1 was significantly increased in THP-1 cells incubated with ox-LDL and meanwhile miR-342-3p was greatly decreased. Then, NEAT1 was silenced by transfection of small interfering RNA (siRNA) of NEAT1 into THP-1 cells. As exhibited, CD36, oil-red staining levels, total cholesterol (TC), total cholesterol (TG) levels and THP-1 cell apoptosis were obviously repressed by knockdown of NEAT1. Furthermore, inhibition of NEAT1 contributed to the repression of inflammation in vitro. Interleukin 6 (IL-6), IL-1β, cyclooxygenase-2 (COX-2) and tumour necrosis factor-alpha (TNF-α) protein levels were remarkably depressed by NEAT1 siRNA in THP-1 cells. By using bioinformatics analysis, miR-342-3p was predicted as a downstream target of NEAT1 and the correlation between them was confirmed in our study. Moreover, overexpression of miR-342-3p could also greatly suppress inflammation response and lipid uptake in THP-1 cells. Knockdown of NEAT1 and miR-342-3p mimics inhibited lipid uptake in THP-1 cells. In conclusion, we implied that blockade of NEAT1 repressed inflammation response through modulating miR-342-3p in human macrophages THP-1 cells and NEAT1 may offer a promising strategy to treat atherosclerotic cardiovascular diseases.

Serum Tumor Necrosis Factor Alpha and High Sensitive C-Reactive protein as Biomarkers in Periodontitis in Iraqi Patients with Osteoarthritis

Background: Periodontitis (PD) is well-known chronic disease affecting the periodontal ligament and alveolar bone, Osteoarthritis (OA) is a chronic joint disease with compound reasons characterized by synovial inflammation, subchondral bone remodeling, also the formation of osteophytes, that cause cartilage degradation. Chronic periodontitis and osteoarthritis are considered widely prevalent diseases and related to tissue destruction due to chronic inflammation in general health and oral health. The aim of this study is todetermine the association of chronic periodontitis and osteoarthritits in patients by analysing tumor necrosis factor alpha TNFα and high sensitive c-reactive protein (hsCRP) in the serum. Materials and Method: A total of 80 patients of both sexes aged 35-50 years ,30 patients with osteoarthritis and moderate chronic periodontitis (CP+OA), 30 patients of both sexes aged 35-50 years with moderate chronic periodontitis alone (CP). And control group (C) of 20 healthy patients with healthy periodontium participated in this cross sectional study. we excluded the postmenopausal and pregnant woman from female patient and smoker patient also. All patients are free of medication and have good general health with no history of systemic disease. Participants with OA have documentation or radiographic imaging, consistent with degenerative arthritis in the absence of an inflammatory condition. Venous blood samples were drawn from each subject using pyrogen-free heparinized collection tubes. Tubes were centrifuged according to the manufacturer’s guidelines, then stored at -15°C till analyse. serum TNFα and hs CRP were measured using an enzyme-linked immunosorbent assay (ELISA). Results: A non-significant differences between studied group regarding serum level of hsCRP and TNF-α, as well as, the result revealed that the median of serum levels of hsCRP were little higher in chronic periodontitis with osteoarthritis group than chronic periodontitis group and control groups represent as 0.31, 0.29, and 0.24. Similarly, the medium serum level of TNFα was higher in chronic periodontitis with OAthan in other two groups (10.615, 10.533, and 9.682 respectively). The age and gender showed a non-significant difference between the groups Conclusion: The present study revealed that there’s a strong positive correlation between serum levels of hsCRP and TNFα in patients of all groups but there is no correlation between Osteoarthritis and chronic periodontitis.

Adipokine and cytokine levels in patients with adrenocortical cancer, subclinical Cushing's syndrome and healthy controls

IntroductionIn recent years researchers have focused at hormonal activity in Cushing’s syndrome (CS) in connection with metabolic disorders and the role of adipokines and cytokines secreted by the adipose tissue. The aim of the study was to investigate levels of adipokines and cytokines in patients with: subclinical CS (SCS) – in relation to hormonal parameters of hypercortisolemia, and, adrenocortical cancer (ACC). Materials and methodsThe study included 20 SCS as well as 7 ACC patients, and 18 healthy participants. Hormonal activity and serum concentrations of adiponectin, leptin, resistin, tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), and monocyte chemoattractant protein 1 (MCP1), were analyzed. ResultsIn SCS patients compared to healthy volunteers a trend toward higher concentrations of all pro-inflammatory cytokines was noted, however, statistically significant differences were only found for TNFα and IL6 (p = 0.047 and p = 0.028, respectively). Adiponectin concentrations were significantly lower in the SCS group (p = 0.006). Serum adipokine and cytokine levels were independent of the presence of diabetes mellitus (DM) and hypertension (HT) in the SCS group. A significant correlation was found between subclinical glucocorticoid secretion and IL6 concentration (Pearson’s r = 0.517, p = 0.02). Acquired results were independent of BMI. In ACC patients compared to controls higher IL6, TNFα and MCP1 levels were recorded. ConclusionIt is possible that higher adipokine and pro-inflammatory cytokine concentrations as well as lower anti-inflammatory adiponectin concentrations comprise an additional risk factor of metabolic and cardiovascular diseases in SCS patients. It seems that at least among patients with SCS adipokine and cytokine secretion is independent of hormonal activity (except for IL6).

Pathogenetic mechanisms of biological agents in managing of relapsing polychondritis

Relapsing polychondritis (RPC) is an autoimmune disease characterized by the inflammation of cartilaginous tissues and other proteoglycan rich tissues. A concomitant disease, particularly myelodysplasia or systemic autoimmune disease can be detected in one-third of the patients with RPC. Unlike adults in children, RPC is less often associated with other autoimmune diseases. The diagnosis of RPC is established using the criteria of Mc Adam (1976) or Damiani (1979). The basis of the pathogenesis of RPC is an autoimmune reaction, which is initially directed against cartilage and then spreads to non-cartilaginous tissues. One of the elements in the pathogenesis of RPC is the mechanical trauma of cartilage, resulting in the release of pro-inflammatory cytokines (tumor necrosis factor alpha, interferon-γ, interleukin-8, and macrophage inflammatory protein 1) and local inflammation followed by the formation of autoantibodies in a patient with a genetic predisposition. In the treatment of RPC, steroids, non-steroidal anti-inflammatory drugs, colchicine are used and, if they are ineffective, immunosuppressants are prescribed. The most effective anti-cytokine drugs used in the treatment of RPC are tumor necrosis factor-alpha (TNF-α) inhibitors, IL-1 receptor antagonists, an inhibitor of the costimulatory pathway of T-lymphocyte activation, monoclonal antibodies against the IL-6 receptor. Given the fact that management of these patients is very complex, the aim of the study is to review available data on pathogenetic mechanisms of biological agents in managing of relapsing polychondritis.

The role of mesenchymal stem cells in chemotherapy-induced gonadotoxicity

BackgroundThe therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) against cisplatin-induced nephrotoxicity has been reported, however, its efficacy in gonadotoxicity still has not been addressed. Herein, we investigated the effect of BM-MSCs in cisplatin-induced testicular toxicity and its underlying mechanism of action.MethodsThirty male Sprague–Dawley rats were divided into a control group: injected with phosphate-buffered saline (PBS) intraperitoneal (ip), a cisplatin group: injected with a single dose of 7 mg/kg cisplatin ip to induce gonadotoxicity and a BM-MSCs group: received cisplatin ip followed by BM-MSCs injection 1 day after cisplatin. In testicular tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) levels were assessed. Additionally, gene expressions of inducible nitric oxide synthase (iNOS), caspase-3, and p38 mitogen-activated protein kinase (MAPK) were measured. The testicular tumor necrosis factor alpha (TNF-α) protein contents and Bcl-2 associated X protein (BAX) expression were determined. Histopathology of testicular tissues was examined.ResultsCisplatin injection showed a significant decrease in GSH and SOD testicular levels besides a significant increase of MDA and TNF-α testicular levels and upregulation of testicular gene expressions of iNOS, caspase-3, and p38-MAPK in comparison to the control group. Moreover, a marked increase in BAX protein expression was observed in the cisplatin group when compared with the control one. Histopathological examination exhibited significant seminiferous tubules atrophy in cisplatin-treated rats.ConclusionsThe BM-MSCs injection significantly repaired the testicular injury and improved both biochemical and histopathological changes. The MSCs mitigated the gonadotoxicity induced by cisplatin through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

Effects of a 6-week, whole-body vibration strength-training on depression symptoms, endocrinological and neurobiological parameters in adolescent inpatients experiencing a major depressive episode (the \u201cBalancing Vibrations Study\u201d): study protocol for a randomized placebo-controlled trial

BackgroundModerate to vigorous endurance and strength-training exercise was suggested as a treatment option for major depression. However, there is little evidence to support this suggestion in adolescent patients. The present study investigates the effects of a whole-body vibration strength-training intervention on symptoms in medication-naïve adolescent inpatients experiencing a major depressive episode. Potential underlying endocrinological and neurobiological mechanisms are explored.Methods/designA double-blinded randomized controlled trial is conducted at the University Hospital of Cologne in Germany, comparing a 6-week, whole-body vibration strength-training with a 6-week placebo-intervention, as add-on therapy to inpatient treatment as usual. Forty-one subjects (13–18 years of age) will be included in each of the two groups. The study is powered to detect (α = .05, β = .2) a medium effect size difference between the two groups (d = .5) in terms of patients’ change in the Children’s Depression Rating Scale raw-score, from baseline until the end of the intervention. As secondary endpoints, the effects of exercise treatment on patients’ cortisol awakening response as well as on brain-derived neurotrophic factor, insulin-like growth factor 1 and inflammatory markers (tumor necrosis factor-alpha, interleukin-6 and C-reactive protein) serum levels will be assessed.DiscussionThis study will provide evidence on the effectiveness of whole-body vibration strength-training as an add-on therapy in adolescent inpatients experiencing a major depressive episode. After completion of data collection, the present study will be the largest randomized controlled trial so far to investigate the effectiveness of an exercise intervention in inpatient adolescents suffering from a major depressive episode. Moreover, the present study may help to determine the underlying mechanisms of potential anti-depressant effects of exercise in depressed adolescent inpatients.Trial registrationDRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00011772. Registered on 20 March 2017.

Correlations between resistance training-induced changes on phase angle and biochemical markers in older women.

The main purpose of this study was to investigate the effects of 12weeks of resistance training (RT) on phase angle (PhA), inflammatory and oxidative stress biomarkers, and to evaluate whether these RT-induced adaptations are related to PhA changes. Fifty-one older women (70.6±5.1years; 26.9±4.2kg/m2 ) were randomly allocated into a training group (TG) that performed 12-week RT or a nonexercising control group (CG). The PhA (Xitron), body composition (DXA), and blood sample measurements (after a 12hours fast) were performed before and after the intervention. The TG showed a significant (P<.05) increase in PhA (TG: +7.4±5.9% vs CG: -3.6±8.8%), and interleukin-10 (IL-10; TG: +51.8±71.1% vs CG: -46.6±38.0%), and a decrease in tumor necrosis factor alpha (TNF-α; TG: -15.2±11.1% vs CG: +6.9±17.7%), interleukin-6 (IL-6; TG: -17.9±17.8% vs CG: +6.1±24.8%), and C-reactive protein (CRP; TG: -24.1±19.9% vs CG: +43.8±31.1%). Moreover, TG upregulated catalase (TG: +11.4±15.0% vs CG: -6.7±10.2%). Changes in TNF-α (r=-.71), CRP (r=-.65), lower advanced oxidation protein products (r=-.55), and catalase (r=+.73) after RT were correlated with changes in PhA (P<.05). These results suggest that RT improves PhA, inflammatory and oxidative stress biomarkers, and the changes in inflammatory and oxidative damage markers are correlated with changes in PhA.

Tumor necrosis factor-alpha protein concentrations in bronchoalveolar lavage fluid from healthy horses and horses with severe equine asthma

The objective of this study was to determine if TNF-α protein concentration differs in bronchoalveolar lavage fluid (BALF) obtained from healthy horses, horses with naturally occurring exacerbations of severe equine asthma and horses in remission from severe equine asthma. Tumor necrosis factor-alpha (TNF- α) protein concentrations were determined in BALF by commercial equine ELISA. Horses with naturally occurring exacerbation of severe equine asthma were found to have significantly lower BALF TNF-α protein concentrations than healthy horses (p = 0.0026). There was no significant difference in BALF TNF-α concentration between horses in exacerbation and remission from disease, but there was a decrease in median TNF-α concentration between healthy horses and horses with clinical exacerbation of severe equine asthma. These findings suggest, that similar to human asthma, the role of TNF-α in chronic lower airway inflammation of horses may differ between disease phenotypes and disease state. Furthermore, the method with which TNF-α is measured (mRNA expression vs. protein concentration) may affect results when studying the role of TNF-α in horses with severe equine asthma.

Markers of Inflammation and Monoamine Metabolism Indicate Accelerated Aging in Bipolar Disorder.

Background: A mild pro-inflammatory status accompanies bipolar disorder (BD). Inflammation can cause a shift in monoamine metabolism, thereby activating more cytotoxic pathways. The extent to which low-grade inflammation in BD interacts with monoamine metabolism and how this accords to aging and clinical course is unknown.Objectives: We evaluated the presence of alterations in inflammation and monoamine metabolism in BD throughout different mood states and the role of aging therein.Methods: Sixty-seven patients with BD were included during an acute mood episode, either depressive (n = 29), (hypo)manic (n = 29), or mixed (n = 9). Plasma levels of inflammatory markers [tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-y), interleukin-6 (IL-6), and C-reactive protein (CRP)] and markers of monoamine metabolism (neopterin, tryptophan, kynurenine, phenylalanine, and tyrosine) were measured repeatedly during a follow-up of 8 months. Levels in patients were compared to controls (n = 35) and correlated to HDRS-17 and YMRS scores. Spearman correlations and linear mixed model analysis were used for statistical analysis.Results: Forty-nine patients and 30 controls (age range: 22–62 years) completed the study. No significant differences in inflammatory markers were found between patients and controls overall. Tryptophan, tyrosine, and phenylalanine levels were lower in patients. In both patients and controls, markers of inflammation correlated only weakly with markers of monoamine metabolism, but correlations representative for activity of cytotoxic pathways in monoamine metabolism were more pronounced in patients. In patients, but not in controls, older age was associated with increases in inflammatory markers (IL-6, CRP, neopterin) and the kynurenine/tryptophan ratio. None of the biological markers correlated significantly with mood symptom severity.Conclusion: Our data suggest an increased susceptibility of patients with BD to develop a pro-inflammatory state and to shift monoamine metabolism toward more cytotoxic pathways. These findings are in support of the theory of neuroprogression and accelerated aging in BD. Since associations between biological markers and clinical characteristics are limited, it remains to be determined if alterations in biological markers are due to a disease effect or rather are a consequence of confounding factors.