tnf - tumor necrosis factor
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Publication
Journal: International journal of molecular medicine
November/20/2019
Abstract
Nuclear receptor subfamily 4 group A member 1 (NR4A1)‑induced chondrocyte death plays a critical role in the development of osteoarthritis through poorly defined mechanisms. The present study aimed to investigate the role of NR4A1 in regulating chondrocyte death in response to tumor necrosis factor‑α (TNF‑α) and cycloheximide (CHX) treatment, with a focus on mitochondrial fission and the AMP‑activated protein kinase (AMPK) signaling pathway. The results demonstrated that NR4A1 was significantly upregulated in TNF‑α and CHX exposed chondrocytes. Increased NR4A1 triggered mitochondrial fission via the AMPK/dynamin‑related protein 1 (Drp1) pathway, resulting in mitochondrial dysfunction, and mitochondrial permeability transition pore (mPTP) opening‑related cell death. Furthermore, excessive mitochondrial fission impaired chondrocyte migration through imbalance of F‑actin homeostasis. Inhibiting NR4A1 attenuated TNF‑α and CHX‑induced mitochondrial fission and, thus, reduced mitochondrial dysfunction in chondrocytes, mPTP opening‑related cell death and migration injury. Altogether, the present data confirmed that mitochondrial fission was involved in NR4A1‑mediated chondrocyte injury via regulation of mitochondrial dysfunction, mPTP opening‑induced cell death and F‑actin‑related migratory inhibition.
Publication
Journal: The Cochrane database of systematic reviews
November/19/2019
Abstract
Adalimumab is an IgG1 monoclonal antibody that targets and blocks tumor necrosis factor-alpha, a pro-inflammatory cytokine involved in the pathogenesis of Crohn's disease (CD). A significant proportion of people with CD fail conventional therapy or therapy with biologics or develop significant adverse events. Adalimumab may be an effective alternative for these individuals.The objectives of this review were to assess the efficacy and safety of adalimumab for the induction of remission in CD.We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Register, ClinicalTrials.Gov and the World Health Organization trial registry (ICTRP) from inception to 16 April 2019. References and conference abstracts were searched to identify additional studies.Randomized controlled trials (RCTs) comparing any dose of adalimumab to placebo or an active comparator in participants with active CD were included.Two authors independently screened studies, extracted data and assessed bias using the Cochrane 'Risk of bias' tool. The primary outcome was the failure to achieve clinical remission, as defined by the original studies. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score of less than 150 points. Secondary outcomes included failure to achieve clinical response (defined as a decrease in CDAI of > 100 points or > 70 points from baseline), failure to achieve endoscopic remission and response, failure to achieve histological remission and response, failure to achieve steroid withdrawal, adverse events (AEs) and serious adverse events (SAEs), withdrawal from study due to AEs and quality of life measured by a validated instrument. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes. Data were pooled for analysis if the participants, interventions, outcomes and time frame were similar. Data were analyzed on an intention-to-treat basis. The overall certainty of the evidence was assessed using GRADE.Three placebo-controlled RCTs (714 adult participants) were included. The participants had moderate to severely active CD (CDAI 220 to 450). Two studies were rated as at low risk of bias and one study was rated as at unclear risk of bias. Seventy-six per cent (342/451) of adalimumab participants failed to achieve clinical remission at four weeks compared to 91% (240/263) of placebo participants (RR 0.85, 95% CI 0.79 to 0.90; high-certainty evidence). Forty-four per cent (197/451) of adalimumab participants compared to 66% (173/263) of placebo participants failed to achieve a 70-point clinical response at four weeks (RR 0.68, 95% CI 0.59 to 0.79; high-certainty evidence). At four weeks, 57% (257/451) of adalimumab participants failed to achieve a 100-point clinical response compared to 76% (199/263) of placebo participants (RR 0.77, 95% CI 0.69 to 0.86; high-certainty evidence). Sixty-two per cent (165/268) of adalimumab participants experienced an AE compared to 72% (188/263) of participants in the placebo group (RR 0.90, 95% CI 0.74 to 1.09; moderate-certainty evidence). Two percent (6/268) of adalimumab participants experienced a SAE compared to 5% (13/263) of participants in the placebo group (RR 0.44, 95% CI 0.17 to 1.15; low-certainty evidence). Lastly, 1% (3/268) of adalimumab participants withdrew due to AEs compared to 3% (8/268) of participants in the placebo group (RR 0.38, 95% CI 0.11 to 1.30; low-certainty evidence). Commonly reported adverse events included injection site reactions, abdominal pain, fatigue, worsening CD and nausea. Quality of life data did not allow for meta-analysis. Three studies reported better quality of life at four weeks with adalimumab (measured with either Inflammatory Bowel Disease Questionnaire or Short-Form 36; moderate-certainty evidence). Endoscopic remission and response, histologic remission and response, and steroid withdrawal were not reported in the included studies.High-certainty evidence suggests that adalimumab is superior to placebo for induction of clinical remission and clinical response in people with moderate to severely active CD. Although the rates of AEs, SAEs and withdrawals due to AEs were lower in adalimumab participants compared to placebo, we are uncertain about the effect of adalimumab on AEs due to the low number of events. Therefore, no firm conclusions can be drawn regarding the safety of adalimumab in CD. Futher studies are required to look at the long-term effectiveness and safety of using adalimumab in participants with CD.
Publication
Journal: JAAD case reports
November/13/2019
Publication
Journal: Bioscience reports
November/11/2019
Abstract
Sevoflurane was found to show protective roles in mice with asthma, however, the mechanism of which need further exploring. Aquaporins (AQPs) have been demonstrated to be involved in the pathogenesis of asthma, while endoplasmic reticulum stress has been reported to be related to many inflammatory diseases and involved in protein processing,including AQPs. This study aimed to determine the role of sevoflurane in AQPs (AQP1,3,4,5) expression in mice with allergic airway inflammation and the probable mechanism. The increased number of inflammatory cells infiltrating the lung tissue, and the elevated levels of tumor necrosis factor-α and interleukin-13 were all decreased after sevoflurane treatment (all P < 0.05). Meanwhile, mRNA levels of AQP1 and AQP5 but not AQP3 and AQP4 were decreased in OVA-induced allergic mice lung. Both the decreased mRNA expression and protein levels of AQP1 and AQP5 in allergic lung tissues were reversed by sevoflurane treatment. Furthermore, we established that sevoflurane inhibited the OVA-induced protein increase of the ER stress markers BiP and CHOP. Collectively, these findings suggested that sevoflurane modulated the expression and protein level of AOPs (AQP1, AQP5) as well as inhibited ER stress response in OVA-induced allergic airway inflammation of mice.
Publication
Journal: Molecules (Basel, Switzerland)
November/7/2019
Abstract
Glycosyltransferase-producing Leuconostoc lactis CCK940 produces CCK- oligosaccharides, gluco-oligosaccharide molecules, using sucrose and maltose as donor and acceptor molecules, respectively. In this study, the immunostimulatory activities of CCK-oligosaccharides on RAW264.7 macrophages and BALB/c mice were evaluated. CCK-oligosaccharides induced the expression of phosphorylated-p38, extracellular-signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) and upregulation of phagocytic activity in RAW264.7 macrophages, suggesting their involvement in mitogen-activated protein kinase (MAPK) signaling pathway and phagocytosis. When CCK-oligosaccharides were administered to mice intraperitoneally injected with cyclophosphamide (CY), spleen indices and expressions of interleukin (IL)-6, IL-10, and tumor necrosis factor-α increased, compared with those in only CY-treated group. These findings suggest that CCK-oligosaccharides can be used as an effective immunostimulating agent.
Publication
Journal: Journal of food biochemistry
November/4/2019
Abstract
The current project was designed to utilize flavonoids and chlorogenic acids enriched stevia residue extract (STVRE) against hyperuricemia (HU). The in vitro results showed that STVRE potently and synergistically inhibits Xanthine oxidase (XO) with allopurinol. The AFM results predicted that STVRE compounds bind with XO and alter its structure which further prevents the entrance of substrate with XO. These in vitro results were further confirmed in fructose-PO-induced hyperuricemic mice model. The results showed that supplementation of STVRE with allopurinol significantly attenuated HU, oxidative stress, and inflammation caused by UA via inhibiting the production of uric acid and lowering cyclooxygenase-2, tumor necrosis factor-alpha, prostaglandin E2, interleukin-6, and interleukin 1-beta levels in serum and renal tissues. Moreover, STVRE and allopurinol treatment attenuated, tubular dilation, infiltration of inflammatory cells, improved structure disorder of podocyte, and foot process fusion, and decreased glomerular basement membrane thickness. These findings suggested that STVRE can be used as an antihyperuricemic agent along with allopurinol. PRACTICAL APPLICATIONS: The results of present study showed that STVRE has a beneficial effect against fructose-PO-induced hyperuricemia by decreasing uric acid level, xanthine oxidase activity, improving oxidative stress and inflammation. These findings suggested that by-product of stevia (STVRE) enriched with polyphenolic compounds can be used as a functional ingredient against hyperuricemia and related diseases.
Publication
Journal: The Journal of nutritional biochemistry
October/30/2019
Abstract
Emerging evidence shows that phytochemicals, the secondary plant metabolites present in a large variety of foods, have the potential ability in reducing the risk of cardiovascular diseases. However, the dosages of phytochemicals in the cellular and animal studies are too high to reach in humans by relevant foods or dietary supplement intake. The aims of this study were to investigate whether and how combined curcumin and luteolin synergistically inhibit tumor necrosis factor-alpha (TNF-α)-induced monocytes adhesion endothelium, a crucial step of the development of endothelial dysfunction, both in human vascular cells and mouse aortic endothelium. Our results show that combined curcumin (1 μM) and luteolin (0.5 μM) synergistically (combination index is 0.60) inhibited TNF-α-induced monocytes adhesion to human EA.hy926 endothelial cells while the individual chemicals did not have such effect at the selected concentrations. We also found that TNF-α-enhanced protein expressions of vascular cell adhesion molecule 1 (VCAM-1), monocyte chemotactic protein-1 (MCP-1) and nuclear factor (NF)-κB translocation were synergistically reduced by the combined curcumin and luteolin in EA.hy 926 cells while the individual chemical did not have this inhibitory effect. Consistently, 2 weeks dietary intake of combined curcumin (500 mg/kg) and luteolin (500 mg/kg) in C57BL/6 mice synergistically prevented TNF-α-stimulated adhesion of mouse monocytes to aortic endothelium ex vivo as well as the TNF-α-increased aortic protein expression of MCP-1 and VCAM-1. Therefore, combined curcumin and luteolin at physiological concentrations synergistically inhibits TNF-α-induced monocytes adhesion to endothelial cells and expressions of MCP-1 and VCAM-1 via suppressing NF-κB translocation into the nucleus.
Publication
Journal: Inflammatory bowel diseases
October/21/2019
Abstract
In recent years, therapeutic drug monitoring (TDM) of anti-tumor necrosis factor alpha (anti-TNFα) agents has been commonly utilized. We aimed to investigate its effect on long-term drug retention and clinical outcomes in pediatric patients with Crohn's disease (CD).The medical records of pediatric CD patients receiving anti-TNFα agents from 2007 to 2018 were reviewed retrospectively. Patients were stratified to those who initiated anti-TNFα treatment between 2007 and 2012, an era when TDM was not available (TDM-), and patients who initiated anti-TNFα treatment between 2013 and 2018, with at least 1 TDM during firstline anti-TNFα treatment (TDM+). The main outcome measures included time to first anti-TNFα discontinuation (drug retention), flares, and hospitalizations per year of first anti-TNFα treatment, treatment intensification rate, and surgical resection rate.One hundred ninety-seven patients were included (n = 98, TDM-; n = 99, TDM+; median [interquartile range] age, 12.6 [10.1-14.2] years; females 68 [35%]). Compared with the TDM- group, the TDM+ group had a longer drug retention time (mean ± SE, 45.0 ± 2.7 vs 33.5 ± 2.4 months; P = 0.001), lower hospitalization rate per patient per year (mean ± SE, 0.51 ± 0.7 vs 0.92 ± 0.81; P < 0.001), and higher treatment intensification rate (70% vs 18%; P < 0.001). Surgical resection rate was not significantly different. Analysis of the entire cohort showed a longer retention time for adalimumab vs infliximab (45.3 ± 2.8 vs 34.8 ± 2.5 months; P = 0.007).TDM-based treatment enables longer drug retention time, reflecting better utilization of anti-TNFα agents, with several additional favorable outcomes.
Publication
Journal: Behavioural pharmacology
October/18/2019
Abstract
Chronic inflammation plays an important role in the mechanisms underpinning the development of anesthesia-induced cognitive dysfunction. However, less is known about how anesthesia causes inflammation. One possibility is that the inflammation is related to alteration of the activity of the alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway. This study analyzed the effect of sevoflurane administration on the cognitive function by using a novel object recognition test and Y-maze test, and on acetylcholinesterase activity and expression in hippocampal tissue by using an acetylcholinesterase assay kit and quantitative real-time PCR. This study also evaluated the effect of alpha 7 nicotinic acetylcholine receptor agonist PNU-282987 and antagonist methyllycaconitine on cognitive function and the level of hippocampal tumor necrosis factor-α in aged rats exposed to sevoflurane anesthesia. We found that 3% sevoflurane significantly impaired cognitive function and increased acetylcholinesterase activity by upregulating its expression in hippocampal tissue. Sevoflurane-induced impairment of cognitive function was significantly rescued by PNU-282987 but aggravated by methyllycaconitine. In addition to impairment of cognitive function, sevoflurane also significantly increased tumor necrosis factor-α level in plasma and hippocampal tissue. Similarly, this sevoflurane-induced change of tumor necrosis factor-α level in rats was antagonized by PNU-282987 but amplified by methyllycaconitine. In conclusion, our data show that the development of inflammation in sevoflurane-induced cognitive decline is associated with the downregulation of alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway in aged rats.
Publication
Journal: ACG case reports journal
October/16/2019
Abstract
Tumor necrosis factor-α inhibitor (TNF-α) is frequently used for Crohn's disease and other autoimmune conditions. Increased risk of infection is an accepted adverse effect of TNF-α, and routine screening for potential infections are carried out before initiation of therapy. We report the case of a patient who developed a localized painful swelling near the injection site, which was diagnosed as acute dermato-lymphangio-adenitis due to filarial infection. This adds to the limited number of case reports on parasitic complications following TNF-α therapy.
Publication
Journal: PloS one
October/4/2019
Abstract
Anti-tumor necrosis factor (Anti-TNF) therapy improves the prognosis and reduces the morbidity and mortality associated with many chronic inflammatory autoimmune diseases. However, as it is linked to an increased infection risk, appropriate vaccination is required. The study aimed at investigating the vaccination status of patients receiving Anti-TNF therapy and physicians' perceptions of and views about vaccinating these patients.A sequential explanatory mixed-methods approach was used. The study comprised a quantitative, retrospective drug utilization review for determining institutional consumption of Anti-TNF therapy and an assessment of vaccination status in patients prescribed Anti-TNF therapy to audit physicians' adherence to Anti-TNF therapy-related vaccination recommendations. Patient data from electronic medical records (EMRs) obtained from tertiary care hospitals between September 2015 and September 2017 were used. Further, a qualitative study using a phenomenographic approach with semi-structured interviews of 12 physicians was carried out to explore the physicians' perceptions, views, and recommendations of vaccinating patients who are undergoing Anti-TNF therapy and identifying factors that may cause poor adherence to vaccination recommendations.Forty-three of 310 patients receiving Anti-TNF therapy were vaccinated. Infliximab was the most frequently prescribed agent, accounting for 96.7% of total orders. Eight of the 12 physicians stated that they were aware of vaccination guidelines and seven viewed pre-Anti-TNF therapy vaccination as essential because of the high infection risk and claimed to incorporate it in their daily practice. Barriers to adherence included ignorance of recommendations, workload, vaccine unavailability, and advanced disease state.Although the recommendations published by professional medical societies emphasized the importance of vaccination before initiating Anti-TNF therapy, few patients were vaccinated. Medical administration in hospitals should develop policies, procedures, and guidelines for vaccination; implement education programs for physicians and patients and procure vaccines in a timely way to improve their use.
Publication
Journal: The New England journal of medicine
September/25/2019
Abstract
Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking.In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52.A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P = 0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years.In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. (Funded by Takeda; VARSITY ClinicalTrials.gov number, NCT02497469; EudraCT number, 2015-000939-33.).
Publication
Journal: PharmacoEconomics
September/25/2019
Abstract
Vedolizumab (VDZ) was approved by the Japanese Ministry of Health, Labor and Welfare in 2018 for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The comparative cost-effectiveness of VDZ compared with other biologics is unknown in Japan. This information could be useful for decision makers at the time of repricing biologics for the treatment of patients with moderate-to-severe UC.The aim was to assess the cost-effectiveness of VDZ versus other branded biologics for the treatment of patients with moderate-to-severe UC who were anti-tumor necrosis factor (TNF)-naïve, from the Japanese public healthcare payer perspective.A hybrid decision tree/Markov model was developed to predict the number of patients who achieved response and remission at the end of the induction phase and sustained it during the maintenance phase, translating this into quality-adjusted life-years (QALYs) and costs. Treatment-related adverse events, discontinuation and surgery, and their impact on QALYs and costs were also modeled. A systematic literature review and network meta-analysis were conducted to estimate the comparative efficacy of each treatment versus placebo. Rates of adverse events, surgery, surgery complications, and utilities were from the literature. Costs (2018 Japanese yen) were obtained from the Japanese National Health Insurance drug price list and medical fee table and local claims databases. Clinical and economic outcomes were projected over a lifetime and discounted at 2% annually.Over a lifetime, VDZ yielded greater QALYs and cost savings compared with golimumab and was cost-effective compared with adalimumab and infliximab (incremental cost-effectiveness ratios ¥4,821,940 and ¥4,687,692, respectively). Deterministic and probabilistic analyses supported the robustness of the findings in the base-case analysis, indicating that VDZ was either dominant or cost-effective in most scenarios and replications. The main limitations of this analysis include excluding tofacitinib and infliximab biosimilar as comparators, health-state utility estimates were obtained from population studies in the United Kingdom, and the impact of subsequent (i.e., second-line) biologic treatment was not evaluated.Our analysis suggests that VDZ is dominant or cost-effective compared with other branded biologics for the treatment of anti-TNF-naïve patients with moderate-to-severe UC in Japan.
Publication
Journal: Gut and liver
September/18/2019
Abstract
Studies on long-term outcomes of adalimumab therapy in non-Caucasian patients with ulcerative colitis (UC) are lacking.We analyzed long-term outcomes of Korean UC patients treated with adalimumab at the Asan Medical Center, Seoul, Korea.Between July 2013 and October 2018, adalimumab therapy was started in a total of 100 patients with UC (65 males [65.0%]; median age, 39.5 years [interquartile range, 23.3 to 49.8 years]; and median disease duration, 3.0 years [interquartile range, 1.0 to 7.0 years]). The median duration of adalimumab therapy was 13.5 months (interquartile range, 4.0 to 32.0 months). Eight of 100 patients (8.0%) received induction therapy only, four (4.0%) of whom ultimately underwent colectomy. Of 92 patients who received adalimumab maintenance therapy, 30 (30.0%) stopped adalimumab therapy due to loss of response, and one patient (1.0%) was lost to follow-up. Among the 92 patients who received adalimumab maintenance therapy, the cumulative proportions of patients remaining on adalimumab maintenance therapy were 70.0% at 1 year and 48.9% at 5 years. High partial Mayo score after 8 weeks of adalimumab therapy (hazard ratio [HR], 1.217; 95% confidence interval [CI], 1.040 to 1.425; p=0.014) and a history of exposure to two biologic agents before adalimumab therapy (HR, 4.722; CI, 1.033 to 21.586; p=0.045) were predictors of adalimumab discontinuation.Long-term outcomes of adalimumab therapy in Korean UC patients appear to be comparable to those in previously published Western studies. Furthermore, previous exposure to multiple biologic agents before adalimumab therapy and disease activity after 8 weeks of adalimumab therapy were predictors of adalimumab discontinuation.
Publication
Journal: Cureus
September/13/2019
Abstract
Severe alcoholic hepatitis (SAH) is associated with significant morbidity and mortality, yet the treatment options available are very limited. Past studies have evaluated the efficacy of infliximab in such patients; however, they were limited by sample size. Our aim was to perform a systematic review of these studies to assess the role of infliximab in patients with SAH. We conducted a literature search using electronic database engines including Ovid, PubMed, Scopus, MEDLINE and Cochrane Library from inception to October 2018 to identify published articles addressing outcomes in patients treated for alcoholic hepatitis with infliximab. The primary outcome reviewed was one-month mortality. Secondary outcomes included rate and type of infection; cause of mortality; levels of aspartate aminotransferase, alanine aminotransferase, bilirubin and tumor necrosis factor-α; and Maddrey discriminant function. Five studies including two randomized controlled trials and three case series were included in our analysis with a total sample size of 70 patients. One-month mortality ranged from 10% to 17% in patients who received a single dose of infliximab with or without prednisone compared to 38% in patients who received three doses of infliximab in combination with prednisone. A single dose of infliximab was associated with an infection rate of 10% to 26% in contrast to an 89% rate with three doses of infliximab. Infliximab, when used in a single dose, could potentially be an alternative agent for the management of SAH in a large group of patients who have contraindications such as gastrointestinal bleeding, uncontrolled diabetes or an active hepatitis infection. It might also have a role in the prevention of hepatorenal syndrome. There is a need for larger trials to evaluate the role of infliximab in a cohort of patients who are not candidates for prednisolone therapy.
Publication
Journal: Pediatric research
September/7/2019
Abstract
To examine which inflammatory markers are associated with bone mass and whether this association varies according to muscular fitness in children with overweight/obesity.Plasma interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), epidermal growth factor, vascular endothelial growth factor A (VEGF), and C-reactive protein were analyzed in 55 children aged 8-11 years. A muscular fitness score was computed. Bone mineral content (BMC) of the total body-less head (TBLH) and lumbar spine (LS) were assessed using dual-energy x-ray absorptiometry.IL-6 (β = -0.136) and VEGF (β = -0.099) were associated with TBLH BMC, while TNF-α (β = -0.345) and IL-1β (β = 0.212) were associated with LS BMC (P < 0.05). The interaction effect of muscular fitness showed a trend in the association of VEGF with TBLH BMC (P = 0.122) and TNF-α with LS BMC (P = 0.057). Stratified analyses by muscular fitness levels showed an inverse association of VEGF with TBLH BMC (β = -0.152) and TNF-α with LS BMC (β = -0.491) in the low-fitness group, while no association was found in the high-fitness group.IL-6, VEGF, TNF-α, and IL-1β are significantly associated with bone mass. Higher muscular fitness may attenuate the adverse effect of high VEGF and TNF-α on bone mass.
Publication
Journal: The British journal of dermatology
September/5/2019
Abstract
Psoriasis is a chronic, inflammatory, immune-mediated disease, characterized by erythematous scaly plaques occurring in about 2-3% of the population. TNF- α plays a role not only in the inflammatory cascade but also in body weight homeostasis which could be disrupted by TNF-α inhibitors, such as adalimumab, infliximab, and etanercept, used for treatment of moderate-severe psoriasis. The goal of this study is to determine the association between the use of TNF-α inhibitors and weight gain in patients with plaque psoriasis based on available clinical trials. This article is protected by copyright. All rights reserved.
Publication
Journal: Acta pharmacologica Sinica
August/24/2019
Abstract
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the death receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of cancer cells. TRAIL gene transfection can produce a "bystander effect" of tumor cell killing and provide a potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed.
Publication
Journal: Molecular genetics & genomic medicine
August/23/2019
Abstract
Hepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor-α (TNF-α) antagonists showed the importance of this cytokine in HBV infection control. Here, we investigated the influence of TNF-α promoter polymorphisms on susceptibility to chronic HBV infection (CHB), liver injury progression and outcomes.A total of 231 patients with CHB constituted the study group and 100 healthy volunteers-the local control group. TNF-α -1031T/C, -863C/A, -857C/T, -308G/A, and -238G/A were genotyped using MALDI-TOF mass spectrometry.TNF-α -1031C and -863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF-α -1031C and -863A variant alleles had lower baseline levels of serum HBV DNA and lower liver necroinflammatory activity than dominant homozygotes. A -857CT genotype predisposed to higher necroinflammatory activity. No associations between TNF-α variants and liver fibrosis were found.This study indicates that TNF-α -863A and -1031C alleles are associated with increased susceptibility to CHB in individuals from northern Poland. The same variants determine the course of CHB, lowering viremia and reducing necroinflammatory activity of the liver.
Publication
Journal: The British journal of dermatology
August/17/2019
Abstract
NCSTN encodes nicastrin, one of the three subunits of γ-secretase, a transmembrane endoprotease complex that catalyzes the cleavage of many transmembrane proteins including Notch receptors.1 In 2010, mutations in genes encoding γ-secretase subunits (NCSTN, PSENEN and PSEN1) were reported in cases of hidradenitis suppurativa (HS).2 It has been demonstrated that tumor necrosis factor-α and interleukin (IL) -10 levels are elevated in patients with HS with NCSTN mutations,1 although other reports found no elevation3 or found decreases.
Publication
Journal: Drug design, development and therapy
August/15/2019
Abstract
Psoriasis is a chronic immune-mediated skin disease affecting multiple systems, and tumor necrosis factor-α (TNF-α) plays a significant role in the initiation and progression of the disease process. Psoriasis has a high prevalence rate in the Western world, especially in the USA and Australia; in China, although the prevalence rate is much lower, there is still a large number of patients suffering from psoriasis and its comorbidities. As TNF-α is thought to be crucial in the pathogenesis of psoriasis, specific therapy blocking TNF-α may be beneficial in the treatment of this disease. Infliximab, a murine-human monoclonal antibody, is highly efficacious in the treatment of moderate-to-severe psoriasis, with better skin clearance and faster onset of action than topical medications such as methotrexate, narrow-band ultraviolet B, and calcipotriol. Lack of adherence to infliximab therapy is mainly due to loss of response (LOR) over time and adverse events, particularly because infusion reactions are usually encountered. Anti-infliximab antibody is thought to be responsible for the LOR and infusion reactions. However, the mechanism underlying the formation of anti-infliximab antibody and its side effects remains unclear. Further studies identifying patients at risk for LOR will probably help clinicians to select the right patients for anti-TNF-α therapy and to increase the durability of the treatment. This review discusses the efficacy of infliximab as demonstrated by various clinical trials, LOR to infliximab, combatting LOR, as well as the adverse events usually faced during the use of infliximab therapy and the infliximab biosimilar Remsima®. We hope that we can discover a better way to use infliximab in the therapy of psoriasis from the current research data.
Publication
Journal: Journal of clinical medicine
August/10/2019
Abstract
Background and Aims: It is not known whether inflammatory bowel disease (IBD) enhances the risk of Parkinson's disease (PD) or whether PD diagnosis is the result of increased health care use. We determined the risk of developing PD among patients with IBD in terms of health care and medication use. Methods: A nationwide population-based study was conducted using claims data from the Korean National Health care Insurance service. From 2010 to 2013, patients with Crohn's disease (CD) and ulcerative colitis (UC) were identified through both International Classification of Disease, Tenth Revision (ICD-10) and national rare intractable disease (RID) registration program codes. We compared 38,861 IBD patients with age and sex-matched non-IBD individuals at a ratio of 1:3. Patients with newly diagnosed PD were identified through both ICD-10 and RID codes. Results: The incidence of PD among patients with IBD was 49 per 100,000 person-years. The risk of developing PD in patients with IBD was significantly higher than controls even after adjustment for health care use (adjusted hazard ratio (aHR), 1.87; P < 0.001). Compared to controls, the risk of PD was significantly higher in patients with CD (aHR, 2.23; P = 0.023) and UC (aHR, 1.85; P < 0.001). Corticosteroid use showed a preventive effect on developing PD in patients with CD (aHR 0.08; P < 0.001), but not UC (aHR, 0.75; P = 0.213). Among 2110 patients receiving anti-tumor necrosis factor (anti-TNF), none of the treated patients experienced PD during 9950 person-years. Conclusion: Patients with IBD are at an increased risk of PD, regardless of health care use. Corticosteroid and anti-TNF use may prevent PD in patients with IBD.
Publication
Journal: Fish & shellfish immunology
August/2/2019
Abstract
Radix Bupleuri extract (RBE) is one of the most popular oriental herbal medicines, which has anti-oxidative and anti-inflammatory properties. However, its protective effects and underlying molecular mechanisms on oxidative damage in tilapia are still unclear. The aims of the study were to explore the anti-oxidative, anti-inflammatory and hepatoprotective effects of RBE against oxidative damage, and to elucidate underlying molecular mechanisms in fish. Tilapia received diet containing three doses of RBE (0, 1 and 3 g/kg diet) for 60 days, and then were given an intraperitoneal injection of H2O2 or saline. Before injection, RBE treatments improved growth performance and partial anti-oxidative capacity in tilapia. After oxidative damage, RBE pretreatments were able to signally reduce the higher serum aminotransferases, alkaline phosphatase (AKP) and liver necrosis. In serum and liver, the abnormal lipid peroxidation level and antioxidant status induced by H2O2 injection were restored by RBE treatments. Furthermore, RBE treatments activated erythroid 2-related factor 2 (Nrf2) signaling pathway, which promoted the gene expression of heme oxygenase 1 (HO-1), NAD(P) H:quinone oxidoreductase 1 (NQO-1), glutathione-S-transferase (GST) and catalase (CAT). Meanwhile, RBE treatments reduced inflammatory response by inhibiting TLRs-MyD88-NF-κB signaling pathway, accompanied by the lower interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-8 mRNA levels. In addition, RBE treatments upregulated complement (C3) gene expression and downregulated heat shock protein (HSP70) gene expression. In conclusion, the current study suggested that RBE pretreatments protected against H2O2-induced oxidative damage in tilapia. The beneficial activity of RBE may be due to the modulation of Nrf2/ARE and TLRs-Myd88-NF-κB signaling pathway.
Publication
Journal: Pakistan journal of medical sciences
August/2/2019
Abstract
To observe the effect of intravenous infusion of immune globulin in the treatment of children with severe pneumonia.Ninety-eight children with severe pneumonia who received treatment in our hospital between April 2015 and December 2016 were selected, and they were grouped into a control group and an treatment group, 49 each group. The control group received conventional treatment. The treatment group was additionally treated with immune globulin on the basis of conventional treatment. The humoral immune indicators were detected using immunoturbidimetric assay, and the inflammatory reaction indicators were detected using enzyme-linked immunoabsorbent kit. The overall efficacy, clinical symptoms, humoral immunity and inflammatory response were compared between the two groups.The total effective rate of the treatment group was significantly higher than that of the control group (P<0.05). The cough, rale and fever of the treatment group disappeared faster than those of the control group, the relief of cardiac failure was also faster in the treatment group (P<0.05). The immunoglobulin G (Ig G), Ig A and Ig M of patients in the two groups compared before treatment, and no significant difference was found (P>0.05). The Ig G level of the treatment group was higher than that of the control group after treatment (P<0.05). The comparison of Ig A and Ig M between the two groups indicated no significant difference (P>0.05). The two groups had no significant differences in the content of tumor necrosis factor (TNF)-α, C-reactive protein (CRP), soluble intercellular adhesion molecule (SICAM)-1 and interferon (IFN)-γ (P>0.05) before treatment, but the content of the treatment group was significantly higher than that of the control group (P<0.01).Immunoglobulin was significantly effective in the adjuvant treatment of children with severe pneumonia, and it can rapidly improve the improvement of symptoms, enhance immune function and inhibit inflammatory reaction; therefore it is worth promotion.
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