So far, there is no effective disease-modifying therapies for Alzheimer’s Disease (AD) in clinical practice. In this context, glycine-L-proline-L-glutamate (GPE) and its analogs may open the way for developing a novel molecule for treating neurodegenerative disorders, including AD. In turn, this study was aimed to investigate the neuroprotective potentials exerted by three novel GPE peptidomimetics (GPE1, GPE2, and GPE3) using an in vitro AD model. Anti-Alzheimer potentials were determined using a wide array of techniques, such as measurements of mitochondrial viability (MTT) and lactate dehydrogenase (LDH) release assays, determination of acetylcholinesterase (AChE), α-secretase and β-secretase activities, comparisons of total antioxidant capacity (TAC) and total oxidative status (TOS) levels, flow cytometric and microscopic detection of apoptotic and necrotic neuronal death, and investigating gene expression responses via PCR arrays involving 64 critical genes related to 10 different pathways. Our analysis showed that GPE peptidomimetics modulate oxidative stress, ACh depletion, α-secretase inactivation, apoptotic, and necrotic cell death. In vitro results suggested that treatments with novel GPE analogs might be promising therapeutic agents for treatment and/or or prevention of AD.

Macrophage activation syndrome (MAS) is one of the main causes of morbidity and mortality in patients with coronavirus disease 2019 (COVID‐19). This study aimed to investigate the relationship between the pentraxin 3 (PTX3) gene polymorphisms rs2305619 (281A/G) and rs1840680 (1449A/G) and the development of MAS in patients with COVID‐19. The study included a total of 94 patients aged 18–45 who were diagnosed as having COVID‐19 between June and December 2020. PTX3 281A/G and 1449A/G polymorphism frequencies were evaluated. PTX3 281A/G allele and genotype frequencies did not deviate from Hardy–Weinberg (HW) equilibrium in the MAS or non‐MAS group (χ²: 0.049, df: 2, p = 0.976, χ²: 0.430, df: 2, p = 0.806). PTX3 1449A/G allele and genotype frequencies deviated significantly from HW equilibrium in the non‐MAS group (χ²: 6.794, df: 2, p = 0.033) but not in the MAS group (χ²: 2.256, df: 2, p = 0.324). The AG genotype was significantly more frequent in the non‐MAS group, while the AA genotype was significantly more frequent in the MAS group (χ²: 11.099, df: 2, p= 0.004). Analysis of the PTX3 1449A/G polymorphism showed that individuals with the GG genotype had higher serum PTX3 levels than those with the AA and AG genotypes (p = 0.001 for both). Analysis of the PTX3 1449A/G polymorphism in patients with COVID‐19 showed that those with the AG genotype were relatively more protected from MAS compared with individuals with the AA genotype. In addition, lower serum PTX3 levels are observed in patients carrying the A allele.

Background: In obstructive sleep apnea (OSA), recurrent upper airway obstruction and apnea/hypopnea episodes result in endothelial dysfunction, which leads to the release of many proinflammatory cytokines and reactive oxygen species (ROS). ROS induces NLRP3, a protein involved in the synthesis of interleukin (IL)-1 and IL-18; vaspin is a serine protease inhibitor that has an important role in suppressing the activation of NLRP3 inflammasome. In this study, we aimed to investigate the effect of NLRP3 rs10159239 (rs9239) and vaspin rs2236242 (rs6242) single nucleotide polymorphisms (SNPs) on OSA development. Methods: This study included 220 individuals who underwent polysomnography (118 patients with OSA and 102 healthy controls). NLRP3 rs9239 and vaspin rs6242 mutation frequencies were analyzed. Results: The NLRP3 rs9239 SNP genotype analysis revealed no statistically significant differences between the OSA and control groups. In the vaspin gene analysis, the rs6242 AA genotype was significantly more frequent in the OSA group compared with the control group, while the AT genotype was more frequent in controls (P = 0.004, P = 0.02). Comparison of rs6242 allele levels showed that the A allele was significantly more frequent in OSA patients than in controls (P = 0.03). The AA genotype was significantly more frequent in patients with severe OSA than in patients with mild or moderate OSA and the control group (P = 0.001 for all). Serum vaspin levels were significantly lower in carriers of the AA genotype than those with AT and TT genotypes (P = 0.001). Conclusion: The vaspin rs6242 SNP AA genotype increased susceptibility to OSA, while the AT genotype appeared to be protective. The lower plasma vaspin levels in OSA compared with the control group and in patients with the AA genotype suggest that vaspin may be a protective biomarker for OSA.

Familial Mediterranean fever (FMF) is the most prevalent autoinflammatory disease. Typical findings are recurrent fever attacks with serositis, skin rash, and synovitis. FMF is caused by mutations in the MEFV gene, encoding pyrin protein. Pyrin functions in innate immunity and triggers inflammation via inflammatory mediators’ production and acts as the primary regulatory component of the inflammasome. On the other hand, various miRNAs play crucial roles in the pathogenesis of different types of cancers and immune‐related and neurodegenerative diseases. However, their association with FMF is still unclear. Therefore, in this study, we assessed the roles of selected thirteen miRNAs associated with immune functions. We recruited genetically diagnosed 28 FMF patients and 28 healthy individuals. The expression profiling of the miRNAs was determined by qRT‐PCR and normalized to SNORD61. Our analysis revealed that miR‐34a‐5p, miR‐142‐3p, miR‐216a‐5p, miR‐340‐5p, miR‐429, and miR‐582‐5p were upregulated, whereas miR‐107, miR‐569, and miR‐1304‐5p were downregulated in the FMF patients. Among them, miR‐107 was found to be the most remarkable in M694V homozygous mutants compared to other homozygous mutants. During clinical follow‐up of the patients with M694V mutation, which is closely related to amyloidosis, evaluation of mir‐107 expression might be crucial and suggestive. Our results showed that miRNAs might serve a function in the pathogenesis of FMF. Further studies may provide novel and effective diagnostic and therapeutic agents that target examined miRNAs. Targeting miRNAs in FMF seems to be promising and may yield a new generation of rational therapeutics and diagnostic or monitoring tools enabling FMF treatment.

The sweet taste and bitter taste genes are thought to have an influence on obesity and caries, which are chronic diseases. The aim of the study was to investigate the effects of the polymorphisms of TAS2R38 (the bitter taste gene) and TAS1R2 (the sweet taste gene), which are the most important members of the taste gene family, on the dental status of obese and normal-weight children. The study included 78 healthy children and 100 children diagnosed with obesity (5-16 years old). The anthropometric measurements and dental status of the children were evaluated. The decayed, missing and filled permanent/primary teeth (DMFT/dmft) index was determined using the standard methods recommended by the World Health Organization (WHO). Blood samples were collected from all subjects and were analyzed via the polymerase chain reaction (PCR) test, with the use of specific primers for the genetic analysis. Five single-nucleotide polymorphisms (SNPs) of the TAS2R38 and TAS1R2 genes were investigated. The truncated Poisson and truncated negative binomial modeling approaches were used with regard to the data. The DMFT/dmft scores were low in obese children and high in children who did not sense the bitter taste (non-tasters). While obese non-taster children had increased DMFT/dmft scores, normalweight non-taster children had decreased DMFT/dmft scores. The alanine, valine and isoleucine (AVI) as well as proline, alanine and valine (PAV) haplotypes of the TAS2R38 gene are associated with the DMFT/dmft index and obesity. This study showed that the DMFT/dmft scores were decreased in obese children. According to the haplotype analysis of the TAS2R38 gene, the DMFT/dmft scores were increased in non-tasters. When differentiating obese nontasters and control non-tasters, DMFT/dmft increased in obese non-taster patients, while it decreased in control non-taster patients.