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Journal of Clinical Medicine Jun 2024Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of... (Review)
Review
Advances in perinatal intensive care have significantly enhanced the survival rates of extremely low gestation-al-age neonates but with continued high rates of bronchopulmonary dysplasia (BPD). Nevertheless, as the survival of these infants improves, there is a growing awareness of associated abnormalities in pulmonary vascular development and hemodynamics within the pulmonary circulation. Premature infants, now born as early as 22 weeks, face heightened risks of adverse development in both pulmonary arterial and venous systems. This risk is compounded by parenchymal and airway abnormalities, as well as factors such as inflammation, fibrosis, and adverse growth trajectory. The presence of pulmonary hypertension in bronchopulmonary dysplasia (BPD-PH) has been linked to an increased mortality and substantial morbidities, including a greater susceptibility to later neurodevelopmental challenges. BPD-PH is now recognized to be a spectrum of disease, with a multifactorial pathophysiology. This review discusses the challenges associated with the identification and management of BPD-PH, both of which are important in minimizing further disease progression and improving cardiopulmonary morbidity in the BPD infant.
PubMed: 38929946
DOI: 10.3390/jcm13123417 -
Journal of Personalized Medicine May 2024COVID-19 is a systemic disease caused by the etiologic agent SARS-CoV-2, first reported in Hubei Province in Wuhan, China, in late 2019. The SARS-CoV-2 virus has evolved...
COVID-19 is a systemic disease caused by the etiologic agent SARS-CoV-2, first reported in Hubei Province in Wuhan, China, in late 2019. The SARS-CoV-2 virus has evolved over time with distinct transmissibility subvariants from ancestral lineages. The clinical manifestations of the disease vary according to their severity and can range from asymptomatic to severe. Due to the rapid evolution to a pandemic, epidemiological studies have become essential to understand and effectively combat COVID-19, as the incidence and mortality of this disease vary between territories and populations. This study correlated epidemiological data on the incidence and mortality of COVID-19 with frequencies of important SNPs in GWAS studies associated with the susceptibility and mortality of this disease in different populations. Our results indicated significant correlations for 11 genetic variants (rs117169628, rs2547438, rs2271616, rs12610495, rs12046291, rs35705950, rs2176724, rs10774671, rs1073165, rs4804803 and rs7528026). Of these 11 variants, 7 (rs12046291, rs117169628, rs1073165, rs2547438, rs2271616, rs12610495 and rs35705950) were positively correlated with the incidence rate, these variants were more frequent in EUR populations, suggesting that this population is more susceptible to COVID-19. The rs2176724 variant was inversely related to incidence rates; therefore, the higher the frequency of the allele is, the lower the incidence rate. This variant was more frequent in the AFR population, which suggests a protective factor against SARS-CoV-2 infection in this population. The variants rs10774671, rs4804803, and rs7528026 showed a significant relationship with mortality rates. SNPs rs10774671 and rs4804803 were inversely related to mortality rates and are more frequently present in the AFR population. The rs7528026 variant, which is more frequent in the AMR population, was positively related to mortality rates. The study has the potential to identify and correlate the genetic profile with epidemiological data, identify populations that are more susceptible to severe forms of COVID-19, and relate them to incidence and mortality.
PubMed: 38929800
DOI: 10.3390/jpm14060579 -
Journal of Personalized Medicine May 2024Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for...
Coronary artery disease (CAD) stands as the most predominant type of cardiovascular disease (CVD). Polygenic risk scores (PRSs) have become essential tools for quantifying genetic susceptibility, and researchers endeavor to improve their predictive precision. The aim of the present work is to assess the performance and the relative contribution of PRSs developed for CVD or CAD within a Greek population. The sample under study comprised 924 Greek individuals (390 cases with CAD and 534 controls) from the THISEAS study. Nine PRSs drawn from the PGS catalog were replicated and tested for CAD risk prediction. PRSs computations were performed in the R language, and snpStats was used to process genotypic data. Descriptive characteristics of the study were analyzed using the statistical software IBM SPSS Statistics v21.0. The effectiveness of each PRS was assessed using the PRS R metric provided by PRSice2. Among nine PRSs, PGS000747 greatly increased the predictive value of primary CAD risk factors by 21.6% (-value = 2.63 × 10). PGS000012 was associated with a modest increase in CAD risk by 2.2% (-value = 9.58 × 10). The remarkable risk discrimination capability of PGS000747 stands out as the most noteworthy outcome of our study.
PubMed: 38929788
DOI: 10.3390/jpm14060565 -
Life (Basel, Switzerland) Jun 2024Pomegranate fruit dry rot is caused by , also referred as . In order to decipher the induced responses of mature pomegranates inoculated with the pathogen, an RNA-seq...
Pomegranate fruit dry rot is caused by , also referred as . In order to decipher the induced responses of mature pomegranates inoculated with the pathogen, an RNA-seq analysis was employed. A high number of differentially expressed genes (DEGs) were observed through a three-time series inoculation period. The transcriptional reprogramming was time-dependent, whereas the majority of DEGs were suppressed and the expression patterns of specific genes may facilitate the pathogen colonization at 1 day after inoculation (dai). In contrast, at 2 dai and mainly thereafter at 3 dai, defense responses were partially triggered in delay. Particularly, DEGs were mainly upregulated at the latest time point. Among them, specific DEGs involved in cell wall modification and degradation processes, pathogen recognition and signaling transduction cascades, activation of specific defense and metabolite biosynthesis-related genes, as well in induction of particular families of transcriptional factors, may constitute crucial components of a defense recruiting strategy employed by pomegranate fruit upon challenge. Overall, our findings provide novel insights to the compatible interaction of pomegranates- and lay the foundations for establishing integrated pest management (IPM) strategies involving advanced approaches, such as gene editing or molecular breeding programs for disease resistance, according to European Union (EU) goals.
PubMed: 38929736
DOI: 10.3390/life14060752 -
Medicina (Kaunas, Lithuania) May 2024Primary open angle glaucoma (POAG) is defined as a "genetically complex trait", where modifying factors act on a genetic predisposing background. For the majority of... (Review)
Review
Primary open angle glaucoma (POAG) is defined as a "genetically complex trait", where modifying factors act on a genetic predisposing background. For the majority of glaucomatous conditions, DNA variants are not sufficient to explain pathogenesis. Some genes are clearly underlying the more "Mendelian" forms, while a growing number of related polymorphisms in other genes have been identified in recent years. Environmental, dietary, or biological factors are known to influence the development of the condition, but interactions between these factors and the genetic background are poorly understood. Several studies conducted in recent years have led to evidence that epigenetics, that is, changes in the pattern of gene expression without any changes in the DNA sequence, appear to be the missing link. Different epigenetic mechanisms have been proven to lead to glaucomatous changes in the eye, principally DNA methylation, post-translational histone modification, and RNA-associated gene regulation by non-coding RNAs. The aim of this work is to define the principal epigenetic actors in glaucoma pathogenesis. The identification of such mechanisms could potentially lead to new perspectives on therapeutic strategies.
Topics: Humans; Epigenesis, Genetic; DNA Methylation; Glaucoma, Open-Angle; Glaucoma; Genetic Predisposition to Disease
PubMed: 38929522
DOI: 10.3390/medicina60060905 -
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