Diketopiperazine gels: New horizons from the self-assembly of cyclic dipeptides

Cyclodipeptides (CDPs) or 2, 5-diketopiperazines (DKPs) can exert a variety of biological activities and display pronounced resistance against enzymatic hydrolysis as well as a propensity towards self-assembly into gels, relative to the linear-dipeptide counterparts. They have attracted great interest in a variety of fields spanning from functional materials to drug discovery. This concise review will analyze the latest advancements in their synthesis, self-assembly into gels, and their more innovative applications

Variation in the CXCR1 gene (IL8RA) is not associated with susceptibility to chronic periodontitis

<p>Abstract</p> <p>Background</p> <p>The chemokine receptor 1 CXCR-1 (or IL8R-alpha) is a specific receptor for the interleukin 8 (IL-8), which is chemoattractant for neutrophils and has an important role in the inflammatory response. The polymorphism rs2234671 at position Ex2+860G > C of the <it>CXCR1 </it>gene causes a conservative amino acid substitution (S276T). This single nucleotide polymorphism (SNP) seemed to be functional as it was associated with decreased lung cancer risk. Previous studies of our group found association of haplotypes in the <it>IL8 </it>and in the <it>CXCR2 </it>genes with the multifactorial disease chronic periodontitis. In this study we investigated the polymorphism rs2234671 in 395 Brazilian subjects with and without chronic periodontitis.</p> <p>Findings</p> <p>Similar distribution of the allelic and genotypic frequencies were observed between the groups (p > 0.05).</p> <p>Conclusions</p> <p>The polymorphism rs2234671 in the <it>CXCR1 </it>gene was not associated with the susceptibility to chronic periodontitis in the studied Brazilian population.</p

Expression of interferon-γ, interferon-α and related genes in individuals with Down syndrome and periodontitis

AbstractBackgroundRecently, attenuation of anti-inflammatory and increase of pro-inflammatory mediators was demonstrated in individuals with Down syndrome (DS) in comparison with euploid patients during periodontal disease (PD), suggesting a shift to a more aggressive inflammation in DS.AimTo determine the influence of DS in the modulation of interferons (IFNs) signaling pathway in PD.Materials and methodsClinical periodontal assessment was performed and gingival tissue samples obtained from a total of 51 subjects, including 19 DS individuals with PD, 20 euploid individuals with PD and 12 euploid individuals without PD. Expression levels of interferon-gamma (IFNG) and interferon-alpha (IFNA), and their receptors IFNGR1, IFNGR2, IFNAR1 and IFNAR2, the signaling intermediates Janus kinase 1 (JAK1), signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF1) were determined using real time quantitative polymerase chain reaction (qPCR).ResultsClinical signs of periodontal disease were markedly more severe in DS and euploid patients with PD in comparison to euploid and periodontally healthy patients. There was no difference on mRNA levels of IFNA, IFNG, INFGR2, IFNAR1 and IFNAR2 between DS and euploid individuals, even though some of these genes are located on chromosome 21. STAT1 and IRF1 mRNA levels were significantly lower in DS patients in comparison with euploid individuals with PD. In euploid individuals, PD was associated with an increased expression of IFNGR1, IFNGR2, IFNAR1, STAT1 and IRF1.ConclusionsReduced expression of STAT1 and IRF1 genes indicate an impaired activation of IFNs signaling in individuals with DS and PD. Expression of IFNA, IFNG and IFN receptors was not altered in DS patients, indicating that indirect mechanisms are involved in the reduced activation of IFN signaling

Diabetes and Increased Lipid Peroxidation are Associated with Systemic Inflammation Even in Well-Controlled Patients

Background The effect of the interaction between type 2 diabetes and dyslipidemia on inflammation and lipid peroxidation (LPO) has not been assessed. Aim To investigate whether diabetes coupled with dyslipidemia alters oxidative metabolism leading to increased LPO products and inflammatory status. Methods 100 patients were divided into four groups based upon diabetic and dyslipidemic status: poorly controlled diabetes with dyslipidemia (DM-PC/D), well-controlled diabetes with dyslipidemia (DM-WC/D), normoglycemic individuals with dyslipidemia (NG/D), and normoglycemic individuals without dyslipidemia (NG/ND). Plasma was evaluated for an LPO product (MDA), antioxidant levels and inflammatory cytokines. Results Diabetics presented significantly higher levels of LPO (p \u3c 0.05) and the DM-PC/D had higher levels of proinflammatory cytokines and MDA in the plasma in comparison with normoglycemics (p \u3c 0.05). Interestingly IL1-β, IL-6, and TNF-α in DM-WC/D were not statistically different from those in DM-PC/D. Normoglycemic individuals with dyslipidemia presented significantly increased levels of IL-6 and TNF-α when compared to normoglycemic without dyslipidemia (p \u3c 0.05). MDA levels were also positively correlated with the presence of DM complications (r = 0.42, p \u3c 0.01). Conclusions These findings show that dyslipidemia is associated with an increased inflammatory status, even in well-controlled diabetics and in normoglycemics. Our results suggest that lipid metabolism and peroxidation are important for the development of inflammation, which is elevated in several complications associated with diabetes

TNFA and IL10 Gene Polymorphisms are not Associated with Periodontitis in Brazilians

IL-10 and TNF-α are cytokines that have complex and opposing roles in the inflammatory responses. G/A polymorphisms at position –1082 of IL10 and –308 of TNFA genes have been reported to influence the expression of IL-10 and TNF-α, respectively. The aim of this study was to investigate the association between the IL10 (-1082) and TNFA (- 308) gene polymorphisms with different clinical forms or severity of periodontitis in a sample of Brazilian individuals. DNA was obtained from oral swabs of 165 Brazilian individuals, which were divided into three groups: individuals with chronic periodontitis, aggressive periodontitis and individuals without clinical evidence of periodontitis. Evaluation of IL10 and TNFA polymorphisms was performed by RFLP analysis. Statistical analysis of data was performed using the χ2 likelihood ratio and Fisher`s exact test. No significant differences in the genotype and allele distribution of either IL10 or TNFA were observed among individuals with different clinical forms or with different degrees of severity of periodontitis. Moreover, combined analysis of IL10 and TNFA polymorphisms did not show any association with periodontal status. As conclusion, the IL10 and TNFA gene promoter polymorphisms investigated are not associated with different clinical forms of periodontitis or with severity of the disease in the Brazilian population polymorphisms

Different contribution of BRINP3 gene in chronic periodontitis and peri-implantitis: A cross-sectional study

Background: Peri-implantitis is a chronic inflammation, resulting in loss of supporting bone around implants. Chronic periodontitis is a risk indicator for implant failure. Both diseases have a common etiology regarding inflammatory destructive response. BRINP3 gene is associated with aggressive periodontitis. However, is still unclear if chronic periodontitis and peri-implantitis have the same genetic background. The aim of this work was to investigate the association between BRINP3 genetic variation (rs1342913 and rs1935881) and expression and susceptibility to both diseases. Methods: Periodontal and peri-implant examinations were performed in 215 subjects, divided into: healthy (without chronic periodontitis and peri-implantitis, n = 93); diseased (with chronic periodontitis and peri-implantitis, n = 52); chronic periodontitis only (n = 36), and peri-implantitis only (n = 34). A replication sample of 92 subjects who lost implants and 185 subjects successfully treated with implants were tested. DNA was extracted from buccal cells. Two genetic markers of BRINP3 (rs1342913 and rs1935881) were genotyped using TaqMan chemistry. Chi-square (p<0.05) compared genotype and allele frequency between groups. A subset of subjects (n = 31) had gingival biopsies harvested. The BRINP3 mRNA levels were studied by CT method (2δδCT). Mann-Whitney test correlated the levels of BRINP3 in each group (p<0.05). Results: Statistically significant association between BRINP3 rs1342913 and peri-implantitis was found in both studied groups (p<0.04). The levels of BRINP3 mRNA were significantly higher in diseased subjects compared to healthy individuals (p<0.01). Conclusion: This study provides evidence that the BRINP3 polymorphic variant rs1342913 and low level of BRINP3 expression are associated with peri-implantitis, independently from the presence of chronic periodontitis

The magneto-electric properties of RMnO3 compounds

The RMnO3 compounds adopt the orthorhombic perovskite crystal structure for large rare earth ions R, and a hexagonal crystal structure for small rare earth ions. In both crystal structures, the rare earth ions occupy non-centered positions which can result in long-range dipolar order at low temperature. Consequently, these materials exhibit coexistence of magnetic and electric ordering. The crystal packing and chemical bonding of these open-shell systems provides information about mechanisms of magneto-ferroelectric ordering and magneto-electric coupling