Roles of Tumor Necrosis Factor-α and Tumor Necrosis Factor-α Receptor 2 in Inflammation-Related Diseases

The aim of the present review is to provide basic knowledge about the role of tumour necrosis factor-α 1 and tumor necrosis factor-α receptor 2 in neuro-inflammation diseases. We performed an open-ended, English restricted search of PubMed, Embase, PsychINFO, Web of Science, Scopus, and the Cochrane Library for available literature from 24Feb. 2018–12 May 2021, using terms related to neuroinflammation, tumour necrosis factor-α, tumour necrosis factor II (TNFR-II), TNF-α and related diseases, TNFR-II and inflammation-related diseases, their relationships, and polymorphism. The main outcomes assessed were the presence of plaques and tangles, behaviour and cognition, reduction in brain tissue mass, and synaptic function the majority of studies were documented a beneficial effect in other areas, including the presence of plaques and tangles and synaptic function. The human studies were showed that TNF-αI was beneficial to Alzheimer's disease patients, with one being a small pilot study and the latter being an observational study, with a high risk of bias. It is concluded that the functions and mechanisms of TNF-α and TNFR-II in inflammation-related diseases will provide new viewpoints and theories in the development and treatment of these diseases. They play important roles in the pathogenesis of diseases induced by or related to inflammatory cytokines and signaling pathways.

The Impact of Lab4 Probiotic Supplementation in a 90-Day Study in Wistar Rats

The anti-inflammatory and cholesterol lowering capabilities of probiotic bacteria highlight them as potential prophylactics against chronic inflammatory diseases, particularly cardiovascular disease. Previous studies in silico, in vitro, and in vivo suggest that the Lab4 probiotic consortium may harbour such capabilities and in the current study, we assessed plasma levels of cytokines/chemokines, short chain fatty acids and lipids and faecal levels of bile acids in a subpopulation of healthy Wistar rats included in 90-day repeat dose oral toxicity study. In the rats receiving Lab4, circulating levels of pro-inflammatory interleukin-6, tumour necrosis factor-α and keratinocyte chemoattractant/growth regulated oncogene were significantly lower compared to the control group demonstrating a systemic anti-inflammatory effect. These changes occurred alongside significant reductions in plasma low density lipoprotein cholesterol and increases in faecal bile acid excretion implying the ability to lower circulating cholesterol via the deconjugation of intestinal bile acids. Correlative analysis identified significant associations between plasma tumour necrosis factor-α and the plasma total cholesterol:high density lipoprotein cholesterol ratio and faecal levels of bifidobacteria in the Lab4 rats. Together, these data highlight Lab4 supplementation as a holistic approach to CVD prevention and encourages further studies in humans.

NR4A2 expression is not altered in placentas from cases of growth restriction or preeclampsia, but is reduced in hypoxic cytotrophoblast

Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) transcripts are elevated in the circulation of individuals whose pregnancies are complicated by preterm fetal growth restriction (FGR). In this paper, we show that the cases with preeclampsia (PE) have increased circulating NR4A2 transcripts compared to those with normotensive FGR. We aimed to establish whether the dysfunctional placenta mirrors the increase in NR4A2 transcripts and further, to uncover the function of placental NR4A2. NR4A2 expression was detected in preterm and term placental tissue; expressed higher at term. NR4A2 mRNA expression and protein were not altered in placentas from preterm FGR or PE pregnancies. Hypoxia (1% O2 compared to 8% O2) significantly reduced cytotrophoblast NR4A2 mRNA expression, but not placental explant NR4A2 expression. Silencing cytotrophoblast NR4A2 expression under hypoxia (via short interfering (si)RNAs) did not alter angiogenic Placental Growth Factor, nor anti-angiogenic sFlt-1 mRNA expression or protein secretion, but increased expression of cellular antioxidant, oxidative stress, inflammatory, and growth genes. NR4A2 expression was also not altered in a model of tumour necrosis factor-α-induced endothelial dysfunction, or with pravastatin treatment. Further studies are required to identify the origin of the circulating transcripts in pathological pregnancies, and investigate the function of placental NR4A2.

Predictors of Response to Biologics in Patients with Moderate-to-severe Psoriasis: A Danish Nationwide Cohort Study

Identifying patient characteristics associated withachieving treatment response to biologics in patients with psoriasis could prevent expensive switching between biologics. The aim of this study was to identifypatient characteristics that predict the efficacy of treatment for biologics that inhibit tumour necrosis factor-α, interleukin-12/-23, and -17A. The study investigated biologic-naïve patients from the DERMBIO registry treated with adalimumab, etanercept, infliximab, secukinumab, or ustekinumab. Multivariable logistic models were conducted to assess associations between patient characteristics and treatment response. A total of 2,384 patients were included (adalimumab n = 911; etanercept n = 327; infliximab n = 152; secukinumab n = 323; ustekinumab n = 671). Smoking (odds ratio 0.74; 95% confidence interval (CI) 0.56–0.97; p = 0.03) and higher bodyweight (odds ratio 0.989; 95% CI 0.984–0.994; p < 0.001) reduced the odds of achieving response defined as Psoriasis Area and Severity Index ≤2.0 after 6 months of treatment. In conclusion, higher bodyweight and smoking were associated with a reduced probability of treatment response for tumour necrosis factor-α inhibitors, ustekinumab, and secukinumab.