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Medicina (Kaunas, Lithuania) May 2024: Preeclampsia (PE) is a critical condition affecting pregnancies worldwide. Understanding its etiology, particularly the genetic factors, is vital. This study aims to...
: Preeclampsia (PE) is a critical condition affecting pregnancies worldwide. Understanding its etiology, particularly the genetic factors, is vital. This study aims to investigate the association between ACE gene polymorphisms, specifically the ACE G2350A (rs4343) variant, and the predisposition to PE, offering insights into the genetic predisposition towards this complex condition. : A case-control study was conducted with 140 participants without PE (Control Group) and 128 participants diagnosed with PE (PE Group). The study focused on comparing the prevalence of the rs4343 polymorphism between the groups. : The analysis identified a significantly reduced risk associated with the AG genotype and an insignificant increase in risk with the AA genotype. Statistically significant differences in demographic and clinical characteristics, such as BMI and marital status, were observed between the groups, suggesting a multifaceted risk profile for PE that includes genetic, environmental, and socio-economic factors. : The study highlight the significant role of genetic variations, specifically the ACE G2350A (rs4343) polymorphism, in influencing PE predisposition. It highlights the intricate interplay between genetic predispositions and other risk factors in the development of PE. Further research is encouraged to expand on these findings and explore a wider range of genetic polymorphisms and their interactions with environmental factors.
Topics: Humans; Pre-Eclampsia; Female; Pregnancy; Case-Control Studies; Adult; Genetic Predisposition to Disease; Risk Factors; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Socioeconomic Factors; Genotype; Polymorphism, Single Nucleotide
PubMed: 38929507
DOI: 10.3390/medicina60060890 -
Animals : An Open Access Journal From... Jun 2024Prion disorders are fatal infectious diseases that are caused by a buildup of pathogenic prion protein (PrP) in susceptible mammals. According to new findings, the...
First Report of Single Nucleotide Polymorphisms (SNPs) of the Leporine Shadow of Prion Protein Gene () and Absence of Nonsynonymous SNPs in the Open Reading Frame (ORF) in Rabbits.
Prion disorders are fatal infectious diseases that are caused by a buildup of pathogenic prion protein (PrP) in susceptible mammals. According to new findings, the shadow of prion protein (Sho) encoded by the shadow of prion protein gene () is associated with prion protein (PrP), promoting the progression of prion diseases. Although genetic polymorphisms in are associated with susceptibility to several prion diseases, genetic polymorphisms in the rabbit gene have not been investigated in depth. We discovered two novel single nucleotide polymorphisms (SNPs) in the leporine gene on chromosome 18 and found strong linkage disequilibrium (LD) between them. Additionally, strong LD was not found between the polymorphisms of and genes in rabbits. Furthermore, nonsynonymous SNPs that alter the amino acid sequences within the open reading frame (ORF) of have been observed in prion disease-susceptible animals, but this is the first report in rabbits. As far as we are aware, this study represents the first examination of the genetic features of the rabbit gene.
PubMed: 38929426
DOI: 10.3390/ani14121807 -
Children (Basel, Switzerland) May 2024Several single nucleotide polymorphisms (SNPs) in multiple interleukin receptor genes could be associated with asthma risk and/or phenotype. Interleukin-17 (IL-17) has...
Several single nucleotide polymorphisms (SNPs) in multiple interleukin receptor genes could be associated with asthma risk and/or phenotype. Interleukin-17 (IL-17) has been implicated in tissue inflammation and autoimmune diseases. As no previous studies have uncovered the potential role of () gene variants in asthma risk, we aimed to explore the association of four SNPs (i.e., rs4819554A/G, rs879577C/T, rs41323645G/A, and rs4819555C/T) with asthma susceptibility/phenotype in our region. TaqMan allelic discrimination analysis was used to genotype 192 individuals. We found that the rs4819554 G/G genotype significantly reduced disease risk in the codominant (OR = 0.15, 95%CI = 0.05-0.45, < 0.001), dominant (OR = 0.49, 95%CI = 0.26-0.93, = 0.028), and recessive (OR = 0.18, 95%CI = 0.07-0.52, < 0.001) models. Similarly, rs879577 showed reduced disease risk associated with the T allele across all genetic models. However, the A allele of rs41323645 was associated with increased disease risk in all models. The G/A and A/A genotypes have higher ORs of 2.47 (95%CI = 1.19-5.14) and 3.86 (95%CI = 1.62-9.18), respectively. Similar trends are observed in the dominant 2.89 (95%CI = 1.47-5.68, = 0.002) and recessive 2.34 (95%CI = 1.10-4.98, = 0.025) models. For the rs4819555 variant, although there was no significant association identified under any models, carriers of the rs4819554*A demonstrated an association with a positive family history of asthma (71.4% in carriers vs. 27% in non-carriers; = 0.025) and the use of relievers for >2 weeks (52.2% of carriers vs. 28.8% of non-carriers; = 0.047). Meanwhile, the rs4819555*C carriers displayed a significant divergence in the asthma phenotype, specifically atopic asthma (83.3% vs. 61.1%; = 0.007), showed a higher prevalence of chest tightness (88.9% vs. 61.5%; = 0.029), and were more likely to report comorbidities (57.7% vs. 16.7%, = 0.003). The most frequent haplotype in the asthma group was ACAC, with a frequency of 22.87% vs. 1.36% in the controls ( < 0.001). In conclusion, the studied variants could be essential in asthma susceptibility and phenotype in children and adolescents.
PubMed: 38929236
DOI: 10.3390/children11060657 -
Antioxidants (Basel, Switzerland) Jun 2024Oxidative stress can damage tissues and cells, and their resilience or susceptibility depends on the robustness of their antioxidant mechanisms. The latter include small... (Review)
Review
Oxidative stress can damage tissues and cells, and their resilience or susceptibility depends on the robustness of their antioxidant mechanisms. The latter include small molecules, proteins, and enzymes, which are linked together in metabolic pathways. Red blood cells are particularly susceptible to oxidative stress due to their large number of hemoglobin molecules, which can undergo auto-oxidation. This yields reactive oxygen species that participate in Fenton chemistry, ultimately damaging their membranes and cytosolic constituents. Fortunately, red blood cells contain robust antioxidant systems to enable them to circulate and perform their physiological functions, particularly delivering oxygen and removing carbon dioxide. Nonetheless, if red blood cells have insufficient antioxidant reserves (e.g., due to genetics, diet, disease, or toxin exposure), this can induce hemolysis in vivo or enhance susceptibility to a "storage lesion" in vitro, when blood donations are refrigerator-stored for transfusion purposes. Ergothioneine, a small molecule not synthesized by mammals, is obtained only through the diet. It is absorbed from the gut and enters cells using a highly specific transporter (i.e., SLC22A4). Certain cells and tissues, particularly red blood cells, contain high ergothioneine levels. Although no deficiency-related disease has been identified, evidence suggests ergothioneine may be a beneficial "nutraceutical." Given the requirements of red blood cells to resist oxidative stress and their high ergothioneine content, this review discusses ergothioneine's potential importance in protecting these cells and identifies knowledge gaps regarding its relevance in enhancing red blood cell circulatory, storage, and transfusion quality.
PubMed: 38929156
DOI: 10.3390/antiox13060717 -
Antioxidants (Basel, Switzerland) Jun 2024Glutathione (GSH), a prominent antioxidant in organisms, exhibits diverse biological functions and is crucial in safeguarding cells against oxidative harm and upholding... (Review)
Review
Glutathione (GSH), a prominent antioxidant in organisms, exhibits diverse biological functions and is crucial in safeguarding cells against oxidative harm and upholding a stable redox milieu. The metabolism of GSH is implicated in numerous diseases, particularly in the progression of malignant tumors. Consequently, therapeutic strategies targeting the regulation of GSH synthesis and metabolism to modulate GSH levels represent a promising avenue for future research. This study aimed to elucidate the intricate relationship between GSH metabolism and ferroptosis, highlighting how modulation of GSH metabolism can impact cellular susceptibility to ferroptosis and consequently influence the development of tumors and other diseases. The paper provides a comprehensive overview of the physiological functions of GSH, including its structural characteristics, physicochemical properties, sources, and metabolic pathways, as well as investigate the molecular mechanisms underlying GSH regulation of ferroptosis and potential therapeutic interventions. Unraveling the biological role of GSH holds promise for individuals afflicted with tumors.
PubMed: 38929136
DOI: 10.3390/antiox13060697 -
International Journal of Environmental... Jun 2024The hypothesis that physiological changes in women can affect periodontal tissues is the subject of this study, and inflammatory markers such as matrix...
The hypothesis that physiological changes in women can affect periodontal tissues is the subject of this study, and inflammatory markers such as matrix metalloproteinase-8 can measure susceptibility to inflammation. The study aimed to analyze MMP-8 levels in periodontal sites of postpartum women and women without a history of pregnancy, comparing health parameters and periodontal disease. This is a case-control study with 40 participants, 20 cases (women in the postpartum period) and 20 controls (women without any pregnancy), who underwent clinical periodontal examination and the collection of crevicular gingival fluid. The ELISA test was used to detect MMP-8 levels. Postpartum women had worse periodontal parameters, such as bleeding index on probing, number of sites with CAL ≥ 3, and fewer teeth present. In the group of women without a history of pregnancy, a significantly lower MMP-8 level was observed in healthy sites and a higher one was observed in periodontal pockets ( < 0.01). In contrast, in postpartum women, MMP-8 levels were elevated in both healthy sites and periodontal pockets ( > 0.01). The MMP-8 levels in gingival fluid appear to be related to periodontal clinical parameters and may be a possible marker of enzymatic changes involved in periodontal tissue destruction in postpartum women.
Topics: Humans; Female; Matrix Metalloproteinase 8; Adult; Case-Control Studies; Postpartum Period; Gingival Crevicular Fluid; Pregnancy; Periodontal Diseases; Biomarkers; Young Adult
PubMed: 38928985
DOI: 10.3390/ijerph21060739 -
International Journal of Environmental... May 2024The effects of exposure to airborne particulate matter with a size of 10 μm or less (PM) on C57BL/6 mouse corneas, their response to (PA) infection, and the protective...
The effects of exposure to airborne particulate matter with a size of 10 μm or less (PM) on C57BL/6 mouse corneas, their response to (PA) infection, and the protective effects of SKQ1 were determined. C57BL/6 mouse corneas receiving PBS or SKQ1 were exposed to control (air) or PM for 2 weeks, infected, and the disease was documented by clinical score, PMN quantitation, bacterial plate count, RT-PCR and Western blot. PBS-treated, PM-exposed corneas did not differ at 1 day postinfection (dpi), but exhibited earlier (3 dpi) corneal thinning compared to controls. By 3 dpi, PM significantly increased corneal mRNA levels of several pro-inflammatory cytokines, but decreased IL-10, NQO1, GR1, GPX4, and Nrf2 over control. SKQ1 reversed these effects and Western blot selectively confirmed the RT-PCR results. PM resulted in higher viable bacterial plate counts at 1 and 3 dpi, but SKQ1 reduced them at 3 dpi. PM significantly increased MPO in the cornea at 3 dpi and was reduced by SKQ1. SKQ1, used as an adjunctive treatment to moxifloxacin, was not significantly different from moxifloxacin alone. Exposure to PM increased the susceptibility of C57BL/6 to PA infection; SKQ1 significantly reversed these effects, but was not effective as an adjunctive treatment.
Topics: Animals; Mice, Inbred C57BL; Pseudomonas Infections; Particulate Matter; Pseudomonas aeruginosa; Mice; Cornea; Disease Susceptibility; Cytokines; Female; Air Pollutants
PubMed: 38928968
DOI: 10.3390/ijerph21060722 -
Diagnostics (Basel, Switzerland) Jun 2024It was demonstrated that differentiated thyroid cancer (DTC) patients may develop multiple primary tumors (MPT) during follow-up. Many studies showed an association...
PURPOSE
It was demonstrated that differentiated thyroid cancer (DTC) patients may develop multiple primary tumors (MPT) during follow-up. Many studies showed an association between reduced telomere length and cancer phenotype; in particular, the short telomeres were associated with the development of a primary tumor. However, the role of altered telomere length in MPT development has not yet been demonstrated. The aim of this study was to evaluate the possible correlation between a short telomere length in blood leukocytes and the risk of developing MPT in DTC patients.
PATIENTS AND METHODS
We retrospectively evaluated 167 DTC patients followed up for a median of 13.6 years. Our control group was represented by 105 healthy subjects without any thyroid disease or present or past history of tumors. Our study groups, age-matched, were evaluated for the relative telomere length measured in leukocytes of peripheral venous blood.
RESULTS
The relative telomere length (RTL) was significantly different in healthy subjects compared to the total group of differentiated thyroid cancer patients [ < 0.0001]. Shorter telomeres length was observed in DTC patients with ( = 32) and without ( = 135) MPT compared to healthy subjects ( < 0.0001 and = 0.0002, respectively). At multivariate analysis, the parameters independently associated with the presence of MPT were RTL [OR: 0.466 (0.226-0.817), = 0.018] and the familial DTC [OR: 2.949 (1.142-8.466), = 0.032].
CONCLUSIONS
The results of this study suggest a role of the relative telomere length in predicting MPT development in DTC patients. Our results contribute to increasing the knowledge of the genetic mechanisms underlying MPT development in DTC patients, considering relative telomere length as a possible prognostic marker.
PubMed: 38928626
DOI: 10.3390/diagnostics14121210 -
International Journal of Molecular... Jun 2024Genetic insights help us to investigate disease pathogenesis and risk. The ABCA1 protein encoded by is involved in transporting cholesterol across the cell membrane....
Genetic insights help us to investigate disease pathogenesis and risk. The ABCA1 protein encoded by is involved in transporting cholesterol across the cell membrane. Genetic variations in the gene are well documented; however, their role in the development of diabetic dyslipidemia still needs to be explored. This study aimed to identify the associations of rs757194699 (K1587Q) and rs2066714 (I883M) with dyslipidemia in type 2 diabetes and performed molecular simulations. In our case-control study, 330 individuals were divided equally into a diabetic dyslipidemia cases and a healthy controls. Allele-specific polymerase chain reaction and restriction fragment length polymorphism were performed to screen selected variants of the gene. Sanger sequencing was also performed to find genetic mutations in exon 5 of the gene. The C allele of rs757194699 was observed at a high frequency in cases compared to controls and followed the overdominant genetic model ( < 0.0001, OR:3.84; CI:1.67-8.82). The frequency of G allele of rs2066714 was significantly higher in cases compared to controls and followed the genetic model of codominant (< 0.0001, OR: 39.61; CI:9.97-157.32), dominant ( < 0.0001,OR:59.59; CI:15.19-233.81), overdominant (< 0.0001, OR:9.75; CI:3.16-30.11), and log-additive (< 0.0001, OR:42.15; CI:11.08-160.40). In silico modeling and docking revealed that rs2066714 and rs757194699 produced deleterious conformational changes in the ABCA1 protein, resulting in alterations in the binding of the apoA1 protein. There were no genetic variations found in exon-5 in Sanger sequencing. The G allele of rs2066714 and C allele of rs757194699 in the gene were found to be risk alleles in the development of dyslipidemia in type 2 diabetes. These polymorphisms could alter the binding site of ABCA1 with apoA1 thus disturbs the reverse cholesterol transport.
Topics: Humans; Diabetes Mellitus, Type 2; ATP Binding Cassette Transporter 1; Dyslipidemias; Genetic Predisposition to Disease; Male; Female; Middle Aged; Polymorphism, Single Nucleotide; Case-Control Studies; Alleles; Gene Frequency; Aged; Molecular Docking Simulation
PubMed: 38928502
DOI: 10.3390/ijms25126796 -
International Journal of Molecular... Jun 2024Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most...
Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of (), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV by analyzing the differential expression of both alleles compared with the homozygous control group using RT-qPCR, and we describe the isoforms produced by the wild-type and alleles using nanopore long-sequencing. Using the Kruskal-Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV and identifying which of them has developed cancer.
Topics: Humans; BRCA1 Protein; Female; Alleles; Hereditary Breast and Ovarian Cancer Syndrome; Middle Aged; Genetic Predisposition to Disease; Adult; Founder Effect; Exons; Breast Neoplasms; Heterozygote; Mutation; Mexico; Ovarian Neoplasms; Clinical Relevance
PubMed: 38928478
DOI: 10.3390/ijms25126773