Search Results (119)

Apolipoprotein E (APOE) allele 4 (APOE4), one of the robust genetic risk factors for AD, has also been associated with cognitive decline in terms of memory, executive function, language, and global cognitive function. APOE genotype-stratified analysis can help to identify additional genetic loci which might be masked due to a strong effect of APOE4. We conducted a genome-wide meta-analysis in APOE2 carriers, APOE4 carriers, and APOE 3/3 homozygote groups among 2969 non-Hispanic Whites aged ≥ 65 years using slopes of decline over time across five cognitive domains (attention, language, executive function, memory, and visuospatial function) and global cognitive function. We identified novel genome-wide significant associations for decline in global cognitive function in the intergenic region between RNU7-66P/RNA5SP208 at rs116379916 (p = 1.44 × 10⁻⁹) in the APOE 3/3 group and for decline in language in the intergenic region between LINC0221/DTWD2 at rs13187183 (p = 3.79 × 10⁻⁸) in APOE4 carriers. A previously reported locus for decline in attention near RASEF at rs6559700 (p = 9.95 × 10⁻⁹) was found to be confined to the APOE 3/3 group. We also found two sub-threshold significant associations in the APOE 2 group for decline in attention (IL1RL2/rs77127114; p = 8.64 × 10⁻⁸) and decline in language (YTHDC2/KCNN2, rs116191836; p = 5.66 × 10⁻⁸). Our study points to potential biological pathways pertaining to specific domains within each APOE genotype group, and the findings suggest that immune-related pathways, plasma levels of polysaturated fatty acids, and bitter taste receptors may play roles in cognitive decline. Our findings enhance the understanding of cognitive aging and provide a framework for future studies. Full article

Long- or post-COVID-19 syndrome, which is also designated by WHO as Post COVID-19 Condition (PCC), is characterized by the persistent symptoms that remain after recovery from SARS-CoV-2 infection. A worldwide consortium of Long COVID-19 Host Genetics Initiative (Long COVID-19 HGI) identified an SNP rs9367106 (G>C; chr6:41,515,652, GRCh38, p = 1.76 × 10⁻¹⁰, OR = 1.63, 95% CI: 1.40–1.89) that is associated with PCC. Unraveling the functional significance of this SNP is of prime importance to understanding the development of the PCC phenotypes and their therapy. Here, in Silico, I explored how the risk allele of this SNP alters the functional mechanisms and molecular pathways leading to the development of PCC phenotypes. Bioinformatic methods include physical interactions using HI-C and Chia-PET analysis, Transcription Factors (TFs) binding ability, RNA structure modeling, epigenetic, and pathway analysis. This SNP resides within two long RNA genes, LINC01276 and FOXP4-AS1, and is located at ~31 kb upstream of a transcription factor FOXP4. This DNA region, including this SNP, physically interacts with FOXP4-AS1 and FOXP4, implying that this regulatory SNP could alter the normal cellular function of FOXP4-AS1 and FOXP4. Furthermore, rs9367106 is in eQTL with the FOXP4 gene in lung tissue. rs9367106 carrying DNA sequences act as distant enhancers and bind with several transcription factors (TFs) including YY1, PPAR-α, IK-1, GR-α, and AP2αA. The G>C transition extensively modifies the RNA structure that may affect the TF bindings and enhancer functions to alter the interactions and functions of these RNA molecules. This SNP also includes an ALU/SINE sequence and alteration of which by the G>C transition may prevent IFIH1/MDA5 activation, leading to suppression of host innate immune responses. LINC01276 targets the MED20 gene that expresses mostly in brain tissues, associated with sleep disorders and basal ganglia abnormalities similar to some of the symptoms of PCC phenotypes. Taken together, G>C transition of rs9367601 may likely alter the function of all three genes to explain the molecular basis of developing the long-term symptomatic abnormalities in the lungs and brain observed after COVID-19 recovery. Full article

Background/Objectives: Alterations in long non-protein-coding RNAs (lncRNAs) are known to influence cellular proliferation, apoptosis, and metastasis in human cancers, including renal cell carcinoma (RCC). Methods: Using pyrosequencing, we analyzed DNA methylation (DNAm) at 23 loci within the LINC00404 CpG island across 28 human cancer cell line models, 181 RCC tumor tissues, 154 paired tumor-adjacent normal tissues (adNs), and 194 metastatic tissue samples. Results: Our analysis revealed that all CpG sites exhibited tumor-specific hypermethylation (all p ≤ 1.4 × 10⁻⁵). Moreover, primary RCC tissues with distant metastases (M1) and metastatic tissue samples (Mtx) showed significant hypermethylation compared to RCC without distant metastases (M0). Notably, DNAm in Mtx displayed a significant increase in 22 CpG sites, compared to 12 CpG sites in the M1/M0 comparison, suggesting that DNAm in Mtx differs both qualitatively and quantitatively. Conclusions: Given that elevated levels of DNAm were also observed in the majority of cell line models, our findings suggest that LINC00404 may play a pivotal role in the malignant development and progression of RCC metastasis, as well as in other human cancers. Full article

T-cadherin (CDH13) is an atypical, glycosyl-phosphatidylinositol-anchored cadherin with functions ranging from axon guidance and vascular patterning to adipokine signaling and cell-fate specification. Originally identified as a homophilic cue for migrating neural crest cells, projecting axons, and growing blood vessels, it later emerged as a dual metabolic receptor for cardioprotective high-molecular-weight adiponectin and atherogenic low-density lipoproteins. We recently showed that mesenchymal stem/stromal cells lacking T-cadherin are predisposed to adipogenesis, underscoring its role in lineage choice. Emerging evidence indicates that CDH13 expression and function are fine-tuned by non-coding RNAs (ncRNAs). MiR-199b-5p, miR-377-3p, miR-23a/27a/24-2, and the miR-142 family directly bind CDH13 3′-UTR or its epigenetic regulators, affecting transcription or accelerating decay. Long non-coding RNAs (lncRNAs), including antisense transcripts CDH13-AS1/AS2, brain-restricted FEDORA, and context-dependent LINC00707 and UPAT, either sponge these miRNAs or recruit DNMT/TET enzymes to the CDH13 promoter. Circular RNAs (circRNAs), i.e.circCDH13 and circ_0000119, can add a third level of complexity by sequestering miRNA repressors or boosting DNMT1. Collectively, this ncRNA circuitry regulates T-cadherin across cardiovascular, metabolic, oncogenic, and neurodegenerative conditions. This review integrates both experimentally validated data and in silico predictions to map the ncRNA-CDH13 crosstalk between health and disease, opening new avenues for biomarker discovery and RNA-based therapeutics. Full article

Background: Intramuscular fat content is positively correlated with meat flavor and juiciness. Increasing the intramuscular fat (IMF) content of chickens while increasing their growth rate has become a hot topic in molecular breeding. The group’s previous studies showed that miR-128-3p inhibited chicken intramuscular adipocyte differentiation and lipogenesis. However, the regulatory mechanism of miR-128-3p in intramuscular preadipocytes is currently unknown. In this study, we investigated the mechanism of miR-128-3p regulation of chicken intramuscular adipocyte differentiation and deposition. Results: Transcriptome data analysis of differential LincRNAs indicated that, compared to the NC group, the mimics-treated group had seventeen significantly differentially expressed LincRNAs (p < 0.05), including six upregulated and eleven downregulated ones; the inhibitor-treated group had seventeen differentially expressed LincRNAs (p < 0.05), including eight upregulated and nine downregulated ones; and twenty-four differentially expressed LincRNAs (p < 0.05) were observed when comparing the mimics-treated group to the inhibitor-treated group, with fourteen upregulated and ten downregulated ones. Functional enrichment analysis revealed that DELincRNAs from the overexpression group (M group) and interference group (SI group) were involved in the negative regulation of metabolic processes, response to steroid hormones, and regulation of actin cytoskeleton. Furthermore, target gene prediction analysis showed that miR-128-3p can target many of the DELincRNAs, such as LincRNA-MSTRG.673.2, LincRNA-MSTRG.39.2, LincRNA-MSTRG.39.3, and LincRNA-MSTRG.14270.2. LincRNA-MSTRG.673.2 was predominantly expressed in the cytoplasm of intramuscular adipocytes. Dual luciferase reporter identified the targeting relationship between miR-128-3p and LincRNA-MSTRG.673.2. The results of subsequent functional assays demonstrated that interfering with MSTRG.673.2 has been shown to inhibit lipid deposition in intramuscular preadipocytes. Transfection experiments have shown that LincRNA-MSTRG.673.2 can affect the expression of miR-128-3p. Conclusions: This study found that LincRNA-MSTRG.673.2 promoted chicken intramuscular adipocyte differentiation by downregulating miR-128-3p. The results are noteworthy for improving chicken meat quality, molecular breeding, and lipid metabolism research. Full article

Background/Objectives: This study aimed to evaluate the relationship between sirtuin family members (SIRT1, SIRT3, and SIRT6) and Wnt/β-catenin pathways with inflammation during the rejection process following kidney transplantation, as well as to explore their potential roles as candidate biomarkers. Materials and Methods: Blood samples were collected from 35 kidney transplant rejection patients and 30 healthy controls. The gene expression levels of SIRT1, SIRT3, SIRT6, and Wnt/β-catenin pathway components were measured using real-time PCR, and miRNA and lncRNA expression levels were analyzed. Statistical analyses were performed using SPSS version 23. Results: Significant alterations in SIRT1, SIRT3, and SIRT6 expression levels were observed in rejection patients, suggesting their potential role in disease pathogenesis and as therapeutic biomarkers. Key altered genes included hsa-miR-34c-1, hsa-miR-122b-5b, MALAT1, HOTAIR, LINC00473, TUG, PVT1, SIRT1, SIRT3, SIRT6, WNT1, TCF-LEF, LRP, AXIN1, IL1B, IL6, and IFNB1, all showing significant changes. However, no significant differences were found for miRNAs such as hsa-miR-21-2, hsa-miR-155-5p, and hsa-miR-200b-3p. SIRT1 expression was significantly decreased in the cellular rejection group, with a more pronounced reduction in these patients. Significant differences in SIRT1 expression were observed with interstitial inflammation and glomerulitis. Increased inflammation severity correlated with decreased SIRT1 and increased TCF-LEF, TUG, and miR-21 levels, while tubulitis severity was associated with elevated TCF-LEF and miR-155 expression. Conclusions: Along with the activation of Wnt/β-catenin pathways and increased levels of certain miRNAs and long non-coding RNAs (lncRNAs) associated with TCF-LEF transcription factors, the observed decrease in SIRT1 expression may be related to the severity of inflammation and tubulitis. These findings suggest that SIRT1, Wnt/β-catenin pathways, and non-coding RNAs play a role in the rejection process following kidney transplantation and could be considered as potential biomarkers or therapeutic target candidates for future research. Full article

Background: Low birth weight in newborns is of multifactorial origin (fetal, maternal, placental, and environmental factors), and in one-third of cases, the cause is of unknown origin, with high infant morbidity and mortality. The main treatment for regaining weight and height in children with low birth weight is the application of growth hormones. However, their role as a protective factor to prevent an increase in body composition and the development of metabolic diseases is still poorly understood. Methodology: A case–control study was conducted in a cohort of patients consulted at the CES Pediatric Endocrinology Clinic, Medellín, Colombia, between 2008 and 2018. We evaluated sociodemographic and clinical variables. Additionally, the identification of differential patterns of genomic methylation between cases (treated with growth hormone) and controls (without growth hormone treatment) was performed. The groups were compared using Fisher’s exact test for qualitative variables and Student’s t-test for the difference in means in independent samples. The correlation was evaluated with the Pearson coefficient. Results: Regarding clinical manifestations, body mass index (BMI) was higher in children who did not receive growth hormone treatment, higher doses of growth hormone treatment helped reduce body mass index (R: −0.21, and p = 0.067), and the use of growth hormone was related to a decrease in triglyceride blood concentrations (p = 0.06); these results tended towards significance. Regarding genome-wide methylation patterns, the following genes were found to be hypermethylated: MDGA1, HOXA5, LINC01168, ZFYVE19, ASAH1, MYH15, DNAJC17, PAMR1, MROCKI, CNDP2, CBY2, ZADH2, HOOK2, C9orf129, NXPH2, OSCP1, ZMIZ2, RUNX1, PTPRS, TEX26, EIF2A4K, MYO1F, C2orf69, and ZSCAN1. Meanwhile, the following genes were found hypomethylated: C10orf71-AS1, ZDHHC13, RPL17, EMC4, RPRD2, OBSCN-AS1, ZNF714, MUC4, SUGT1P4, TRIM38, C3, SPON1, NGF-AS1, CCSER2, P2RX2, LOC284379, GGTA1, NLRP5, OR51A4, HLA-H, and TTLL8. Conclusions: Using growth hormone as a treatment in SGA newborns helps regain weight and height. Additionally, it could be a protective factor against the increase in adolescent body composition. Full article

Despite the growing popularity of women’s basketball in recent years, scientific literature on the subject remains significantly less extensive compared to its male counterpart. The main objective of this research was to analyze successful offensive actions and patterns during critical moments in the Women’s EuroLeague. The sample consisted of 377 technical–tactical actions corresponding to plays with score differences of three points or less (one-possession games) in the final minute and overtime periods of the Women’s EuroLeague during the 2021/22 and 2022/23 seasons. This study was based on an observational design, utilizing the LINCE PLUS software together with a customized observation tool. Descriptive statistics and chi-square (χ²) tests were carried out using SPSS version 25, while T-Pattern detection was performed through Theme 5 software. A threshold for statistical significance was established at p < 0.05. The findings indicated that home teams achieved a higher percentage of successful plays compared to visiting teams. Most successful patterns occurred during the final phase of possession (8”–0”), regardless of game location or team result. Additionally, layups, plays involving shots after on-ball screen, and actions following personal fouls demonstrated the highest success rates. The practical implications discussed in this research provide valuable insights for coaches to optimize offensive strategies during high-pressure moments in elite women’s basketball. Full article

Objective: This study aims to develop a prognostic model based on senescence-related long non-coding RNAs (lncRNAs) to predict the prognosis of patients with colon cancer and enhance their survival rates. Method: Differential expression analysis and Pearson correlation were employed to identify senescence-related lncRNAs in colon cancer. A risk prognosis model was constructed using univariate Cox regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The reliability of this model was validated through survival analysis, receiver operating characteristic (ROC) curves, bar charts, and calibration curves. Additionally, the relationship between the prognostic model, immune microenvironment, and drug sensitivity was explored. Results: A risk prognosis model comprising eight senescence-related lncRNAs (LINC02257, AL138921.1, ATP2B1-AS1, AC005332.7, AC007728.3, AC018755.4, AL390719.3, and THCAT158) was successfully established, demonstrating strong performance in predicting the overall survival rates of colon cancer patients (AUC = 0.733). A significant correlation was observed between the senescence-related lncRNA prognostic model and the tumor microenvironment, immune cell infiltration, and drug sensitivity (p < 0.05). Conclusions: The senescence-related lncRNA prognostic model developed in this work can accurately forecast the prognosis of colon cancer patients, offering new insights for personalized treatment approaches in colon cancer. Full article

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid malignancy, and its progression is closely associated with patient outcomes. This study investigated the role of the long non-coding RNA LINC02560 in the pathogenesis and aggressiveness of PTC through cell culture, transfection, RT-qPCR, Western blot analysis, and various functional assays, such as MTT, EdU, colony formation, wound healing, and Transwell migration assays. Our results revealed a significant upregulation of LINC02560 in PTC tissues, correlating with poor prognosis in affected patients. Functional analyses demonstrated that silencing of LINC02560 markedly inhibited the proliferation, migration, and invasion of the PTC cell lines, KTC-1, and BCPAP, whereas overexpression promoted these aggressive traits. Mechanistically, LINC02560 acted as a competitive endogenous RNA, sponging miR-505-5p and alleviating its suppression on PDE4C degradation, thereby activating the P-AKT and epithelial–mesenchymal transition (EMT) signaling pathways. Additionally, HNF4α was identified as a transcription factor capable of enhancing the expression of LINC02560. In conclusion, our findings elucidate the critical HNF4α/LINC02560/miR-505-5p/PDE4C axis in PTC pathology, presenting this regulatory network as a promising biomarker combination and potential therapeutic target to improve patient outcomes and survival rates, warranting further clinical investigation to validate these insights and support the development of targeted therapies in PTC management. Full article

Pancreatic (PC), colorectal (CRC), hepatocellular (HCC), and gallbladder (GC) cancers together account for nearly 20% of all cancer cases. However, specific biomarkers and therapeutic targets for these cancers are lacking. Diagnosing these cancers early and providing timely, appropriate treatment to improve patient outcomes is crucial. In this context, previous studies, including ours, have highlighted the potential of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), in diagnosing and prognosis of various cancers. This review focuses on the mechanistic role of the recently identified lncRNA LINC00261 in PC, CRC, HCC, and GC. Our comprehensive literature analysis revealed that LINC00261 functions as a tumor suppressor, and its reduced expression is associated with larger tumor size, advanced tumor-node-metastasis (TNM) stages, lymphatic metastasis, and poorer overall survival rates. Additionally, we discovered that LINC00261 acts as a molecular sponge for miRNAs, such as miR-550a-3p, miR-23a-3p, miR-148a, miR-324-3p, and miR-105-5p, regulating critical cancer-related signaling pathways, including PI3K/Akt/mTOR, Protein kinase B, and Mammalian target of rapamycin (mTOR). Further bioinformatic analysis revealed that LINC00261 regulates key cellular processes, such as protein-DNA complex formation, ribonuclease complex activity, histone deacetylase complexes, and nuclear matrix interactions. Overall, we believe that LINC00261 holds significant promise as a future biomarker and, when combined with existing treatment strategies, may enhance cancer patient care and survival. Full article

In elite basketball, closely contested games are often decided in the last minute, where a single possession can significantly alter the outcome. The objective of this study was to analyze the offensive patterns and effectiveness of successful play sequences executed during the last minute and overtime periods of the 2022–2023 EuroLeague men’s basketball season. Specifically, we examined how offensive strategies varied based on score conditions and team status (winning, losing, or tied) in games with a score difference of three points or fewer, representing a maximum one-possession margin. The sample consisted of 709 technical–tactical actions performed in one-possession games during the last minute and overtime periods of the men’s EuroLeague 2022–2023 season. An observational methodology was employed using the LINCE PLUS software with a purpose-designed observational instrument. Descriptive analyses and chi-square (χ²) tests were conducted using SPSS 25, and T-Pattern analysis was performed with Theme 6 software. Statistical significance was set at p < 0.05. The results showed that teams leading at the start of the possession executed a higher number of successful actions, primarily through free throws drawn from fouls committed by the opposing team. Additionally, plays involving few or no passes, executed within the first 17 s of possession, and completed by point guards or centers, were associated with higher success rates. While less frequent, fast breaks proved to be more effective than set offenses. Furthermore, the study highlights the role of elite playmakers in late-game situations, as their ability to read defenses and create scoring opportunities plays a crucial role in determining offensive success. The practical implications of this study can assist coaches in optimizing offensive strategies during high-pressure moments in elite men’s basketball by refining late-game decision-making and tactical planning. Full article

Timeouts are a widely supported strategy in the literature, recognized for directly influencing team performance during basketball games. This study aimed to analyze and define the successful patterns of actions after timeouts (ATOs) during critical moments in the 2022/23 EuroLeague season. The sample was drawn from the last two minutes and overtime of 169 games with a final point difference of 10 points or fewer, totaling 365 ATOs. An observational methodology was used, applying the LINCE PLUS software version 2.1.0 and an ad hoc observational instrument. Descriptive analysis and chi-square tests (χ²) were conducted using SPSS 25.0, and T-pattern analysis was performed with Theme 6 software. Statistical significance was set at p < 0.05. Teams in the lead often concluded successful plays through free throws following opponent fouls, while teams trailing behind attempted to close the gap by committing fouls to force free throws in defense and scoring two-point baskets on offense. The findings offer insights into ATOs strategies that can support coaches and technical staff in training and adapting these actions to meet competition demands during critical game moments. These results may assist in enhancing team performance and decision-making under high-stakes conditions. Full article

Background: Pickleball has experienced remarkable growth in recent years, yet studies exploring its specific characteristics are scarce. This investigation provides a detailed notational analysis of women’s singles pickleball, evaluating the technical and tactical performance indicators in the game. Method: An observational methodology was used to analyze all points from five PPA Tour tournaments. The matches were recorded and coded using LINCE PLUS software, version 2.1.0, with a category system designed for this sport. A descriptive analysis was conducted with IBM SPSS version 25.0, and Theme 6.0 Edu software was used to detect gameplay patterns. The statistical significance was set at p < 0.05. Results: The findings indicate that serving players have a slight advantage, winning 55.1% of points. Most of the points were resolved through unforced errors, accounting for 63.7% of the total, primarily from forehand strokes in short rallies and backhand strokes in medium rallies. The most frequent hitting zones for point termination were near the non-volley zone (35.8%) and behind the baseline (38.6%). Conclusions: This study provides a deeper understanding of performance in women’s pickleball, highlighting technical and tactical patterns that offer guidelines for optimizing strategies and techniques in the sport. Full article

Osteoarthritis (OA), particularly in the knee and hip, poses a significant global health challenge due to limited therapeutic options. To elucidate the molecular mechanisms of OA and identify potential biomarkers and therapeutic targets, we utilized genome-wide association studies (GWAS) and cis-miRNA expression quantitative trait loci (cis-miR-eQTL) datasets to identify miRNAs associated with OA, revealing 16 that were linked to knee OA and 21 to hip OA. Among these, hsa-miR-1303 was significantly upregulated in both knee and hip OA (IVW: p = $6.8164\times {10}^{-36}$ and $4.7919\times {10}^{-2}$ respectively, OR > 1) and identified as a key factor in disease progression. Hsa-miR-1303 potentially regulates 30 genes involved in critical signaling pathways, such as the neurotrophin signaling pathway, and interacts with competing endogenous RNAs (ceRNAs) like circ_0041843 and LINC01338, thereby influencing key regulatory proteins such as SUMO2 and PARP1. Pharmacologically, hsa-miR-1303 targets nine druggable genes, including NRAS, H2AZ1, and RPS3, which have implications for drugs like cantharidin and diindolylmethane, potentially critical for developing novel OA treatments. Conversely, hsa-miR-125a-5p and hsa-miR-125b-5p, which are downregulated in both knee and hip OA, are associated with pathways such as HIF-1 and JAK-STAT, which modulate apoptotic signaling and transcriptional regulation. These miRNAs also interact with ceRNAs such as circ_0000254 and SPACA6P-AS, impacting proteins like STAT3, MCL1, and TRAF6. A drug interaction analysis identified 47 potential treatments, including Resveratrol and Acetaminophen, suggesting new therapeutic possibilities for OA management. This study not only highlights the role of miRNAs like hsa-miR-1303 and hsa-miR-125 in OA but also opens avenues for miRNA-based therapeutic development. Full article