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Objective(s): Acrylamide (ACR) induces neurotoxicity in humans and animals through different mechanisms. Sitagliptin is a type-2 diabetes medication with neuroprotective properties. The effects of sitagliptin against neurotoxicity stimulated by ACR were examined.Materials and Methods: Male Wistar rats were classified as follows: 1. Control (normal saline, 11 days, IP), 2. ACR (50 mg/kg, 11 days, IP), 3. ACR (11 days, days 11-20 normal saline), 4-7. ACR+sitagliptin (5, 10, 20, and 40 mg/kg, 11 days, IP), 8. ACR+sitagliptin (10 mg/kg, days 6-11), 9. ACR+sitagliptin (10 mg/kg, days 6-20), 10. Sitagliptin (40 mg/kg, 11 days), 11. ACR+vitamin E (200 mg/kg, IP). Finally, the gait score was evaluated. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured in cortex tissue. Also, IL-1β, TNF-α, and caspase-3 levels were assessed in the cortex by western blotting. Results: ACR caused movement disorders, triggered oxidative stress, and raised TNF-α, IL-1β, and caspase-3 cleaved levels. Supplementation of sitagliptin (10 mg/kg) along with ACR, in 3 protocols, reduced gait disorders compared to the ACR group. Receiving sitagliptin in all doses plus ACR and injection of sitagliptin (10 mg/kg) from days 6 to11 reduced the MDA level of cortex tissue. Sitagliptin (all doses) plus ACR increased the GSH level of the cortex tissue. Sitagliptin (10 mg/kg) with ACR dropped the amounts of TNF-α and caspase-3 cleaved proteins in cortex tissue but did not affect the IL-1β level.Conclusion: Sitagliptin disclosed preventive and therapeutic effects on ACR neurotoxicity. Sitagliptin possesses antioxidant, anti-inflammatory, and anti-apoptotic properties and inhibits CR neurotoxicity in rats.

BackgroundMany studies have shown that cytokines play an important role in the pathogenesis of asthma, but their biological effects on asthma remain unclear. The Mendelian randomization (MR) method was used to evaluate the causal relationship between various cytokines [such as interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), colony-stimulating factors (CSFs), transforming growth factor (TGF), etc.,] and asthma.MethodsIn this study, inverse variance weighting was used to evaluate the causal relationship between asthma and cytokines. In addition, the reliability of the results is ensured by multiple methods such as MR-Egger, weighted median, MR-Raps, MR-Presso, and RadialMR, as well as sensitivity analysis.ResultsThe results showed that none of the 11 cytokines was associated with the risk of asthma. In contrast, asthma can increase levels of IL-5 [odds ratio (OR) = 1.112, 95% confidence interval (CI): 1.009–1.224, P = 0.032] and IL-9 (OR = 1.111, 95% CI: 1.013–1.219, P = 0.025).ConclusionGenetically predicted asthma was positively associated with elevated levels of IL-5 and IL-9, indicating the downstream effects of IL-5 and IL-9 on asthma. Medical treatments can thus be designed to target IL-5 and IL-9 to prevent asthma exacerbations.

Zhenni Zhao,1 Jiawei Li,2 Jiamin Wen,2 Yanyan He,2 Zhiling Sun2 1Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, People’s Republic of China; 2School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Zhiling Sun, School of Nursing, Nanjing University of Chinese Medicine, 138 Xian Lin Road, Nanjing, People’s Republic of China, Tel +86 13813892093, Email szl@njucm.edu.cnBackground and Objective: Moxibustion is effective for low back pain (LBP), and inflammatory cytokines may play an important role in the mechanism of moxibustion treatment. The purpose of this meta-analysis was to explore the mechanism of moxibustion in LBP in terms of inflammatory cytokines.Methods: We searched China National Knowledge Infrastructure, Wanfang database, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, PubMed, and Web of Science to identify eligible randomized controlled trials (RCTs). There was no restriction on the publication date.Results: Thirty RCTs measuring interleukin (IL-) 1, IL-1β, IL-6, IL-12, IL-17, IL-23, and tumor necrosis factor (TNF-) α were included in this meta-analysis. Compared to controls: single moxibustion could effectively decrease levels IL-6 and IL-23 (SMD, − 0.71, 95% CI: − 1.25 to − 0.17, p = 0.01; SMD, − 1.61, 95% CI: − 2.20 to − 1.03, p < 0.01, respectively); combined moxibustion had significant effects on IL-1, IL-1β, IL-6, IL-12, IL-17, and TNF-α (p < 0.05). Overall, for LBP, single or combined moxibustion could effectively down-regulate levels of pro-inflammatory cytokines (p = 0.007 and p < 0.00001, respectively). For safety of moxibustion, the incidence rate of side effects was similar to that of controls (RD, − 0.01, 95% CI: − 0.02 to 0.01, p = 0.59). Sensitivity analysis showed that the pooled estimates were robust, and publication bias analysis showed there was a significant small study effect (Egger’s test p = 0.0000). High statistical heterogeneity existed between included RCTs, meta-regression showed there was no potential factor explaining the source of heterogeneity.Conclusion: For LBP, moxibustion can effectively decrease levels of IL-1, IL-1β, IL-6, IL-12, IL-17, IL-23, and TNF-α to achieve analgesia. Because the side effects of moxibustion are transient, it is relatively safe for clinical use. However, based on high heterogeneity in this meta-analysis, rigorously designed RCTs are required to further confirm the results in this review.Keywords: low back pain, moxibustion, cytokines, tumor necrosis factors, interleukins

BackgroundPhysical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer.MethodsIn this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1:1:1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor necrosis factor-alpha receptor 2 (sTNFαR2). Mixed models for repeated measures were used to test the hypothesis that exercise was associated with dose-response reductions in inflammation; exploratory analyses examined treatment effects by cancer stage.ResultsIn the overall population, aerobic exercise was not associated with dose-response reductions in hs-CRP, IL6, or sTNFαR2. Cancer stage modified the association between randomized group and hs-CRP (P=0.022) and IL6 (P

Mice bearing sarcoma implants (S.37) obtained from the National Câncer Institute received sublethal dosage of Serrata Marcenscens polysaccharide (as obtained from Dr. Shear). The cytotoxic like action, characterized by hemorrhage and necrosis in the tumor mass has been investigated, as to its relationship to an anaphylactic action, or as due to an increased capillary fragility. Results are herewith reported.

Case report of three patients with inflammatory bowel disease who underwent treatment with biology therapy and developed respectively: non-Hodgkins lymphoma, colorectal adenocarcinoma, and cholangiocarcinoma after long-term follow-up. They demonstrated that data are currently inconclusive about the development of long-term anti-TNF neoplasias.

ABSTRACT Objective: To study the relationship between the pre and post chemotherapy (CT) serum levels of alkaline phosphatase (AP) and lactate dehydrogenase (LDH), and the percentage of tumor necrosis (TN) found in specimens after the pre surgical CT in patients with osteosarcoma. Methods: Series of cases with retrospective evaluation of patients diagnosed with osteosarcoma. Participants were divided into two groups according to serum values of both enzymes. The values of AP and LDH were obtained before and after preoperative CT. The percentage of tumor necrosis (TN) of surgical specimens of each patient was also included. Results: One hundred and thirty seven medical records were included from 1990 to 2013. Both the AP as LDH decreased in the patients studied, being the higher in pre CT than post CT. The average LHD decrease was 795.12U/L and AP decrease was 437.40 U/L. The average TN was 34.10 %. There was no statistically significant correlation between the serums values and the percentage of tumoral necrosis. Conclusion: The serum levels values of AP and LDH are not good predictors for the chemotherapy-induced necrosis in patients with osteosarcoma. Level of Evidence IV, Case Series.

Abstract Objectives To determine whether Tumor Necrosis Factor alpha (TNFα) –308 G/A polymorphism is associated with oral lichen planus (OLP). Material and Methods A systematic electronic search of the literature was conducted to identify all published studies on the association between TNFα –308 G/A polymorphism and OLP. All case-control studies evaluating the TNFα –308 G/A polymorphisms in OLP were selected. A meta-analysis of the studies that fulfilled the inclusion criteria was performed. Odds ratios (OR) with 95% confidence intervals (CI) were also calculated. Results Seven studies comprising 450 OLP cases and 867 controls were included in the meta-analysis. In the pooled analysis, TNFα –308 G/A polymorphism was associated with OLP with random effects and OR of 2.33 (95%CI=1.07-5.11; p=0.03), assuming a dominant mode of inheritance (AA+GA vs. GG). In the subgroup analysis by ethnicity, TNFα –308 G/A was associated with a significantly increased odds ratio of OLP in mixed ethnicity (OR=5.22; 95%CI=1.93-14.15; p=0.001), but not in Asians (OR=1.57; 95%CI=0.54-4.54; p=0.41) or Caucasians (OR=1.45; 95%CI=0.19-11.22; p=0.72). For subgroup analysis based on HCV (hepatitis C virus) infection status, significant increased risk of OLP was found among patients with mixed HCV infection status (OR=3.77; 95%CI=1.07-13.2; p=0.038), but not in patients without HCV infection (OR=2.09; 95%CI=0.63-6.91; p=0.22) and patients with HCV infection (OR=0.48; 95%CI=0.13-1.69; p=0.25). Conclusion Our results suggest that –308 G/A polymorphism in TNFα is a potential genetic marker for OLP.

Objectives Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease. Cytokines play an important role in the pathogenesis and disease progression of OLP. Various reports have implicated cytokine gene polymorphisms in susceptibility to develop some immune mediated conditions including OLP. The purpose of this study was to investigate the association of tumor necrosis factor (TNF)-α, TNF-β and interleukin (IL)-10 gene polymorphisms with the OLP risk. Material and Methods Forty two unrelated patients with OLP and 211 healthy volunteers were genotyped for TNF-α (-308 G/A), TNF-β (+252A/G), IL-10 (-1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. Results The frequencies of allele A and genotype GA of TNF-α (-308G/A) were significantly higher while allele G and GG genotypes were lower in OLP patients as compared to the controls (P0.05). However, haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10 were more prevalent in OLP patients when compared to controls indicating its possible association with OLP susceptibility. Conclusion It is concluded that TNF-α (-308G/A), TNF-β (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A) polymorphisms are associated with the susceptibility of OLP, thus giving additional support for the genetic basis of this disease.

Aim. The results of investigation of 78 patients in acute period of brain ischemic aterotrombotic stroke are given in the article. Methods and results. It was revealed that development of brain ischemic aterotrombotic stroke is accompanied with elevation of TNF-α (Δ%=419,8; p

Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A) is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01). Next, we characterized the compound’s growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01). The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.