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The PowerPlex® 35GY System (Promega, USA) is an advanced eight-dye multiplex STR kit, incorporating twenty-three autosomal STR loci, eleven Y chromosome STR loci, one sex determining marker Amelogenin, and two quality indicators. This multiplex system includes 20 CODIS loci and up to 15 mini-STR loci with sizing values less than 250 bases. In this study, validation for PowerPlex® 35GY System was conducted following the guidelines of SWGDAM, encompassing sensitivity, precision, accuracy, concordance, species specificity, stutter, mixture, stability, and degraded DNA. The results from experiments demonstrated that the PowerPlex® 35GY System could effectively amplify DNA samples, with complete allele detection achieved at 125 pg. Moreover, over 90% of alleles from minor contributors were detected at a mixed ratio of 1:4. Additionally, the system was found to yield full profiles even in the presence of hematin, humic acid, and indigo. The PowerPlex® 35GY System demonstrated superior performance in the sensitivity and degraded DNA studies compared to a six-dye STR kit. Hence, it is evident that the PowerPlex® 35GY System is well-suited for forensic practice, whether in casework or for database samples. These findings provide strong support for the efficacy and reliability of the PowerPlex® 35GY System in forensic applications.
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Avian influenza viruses (AIVs) are the origin of multiple mammal influenza viruses. The genetic determinants of AIVs adapted to humans have been widely elucidated, however, the molecular mechanism of cross-species transmission and adaptation of AIVs to canines are still poorly understood. In this study, two H3N2 influenza viruses isolated from a live poultry market (A/environment/Guangxi/13431/2018, GX13431) and a swab sample from a canine (A/canine/Guangdong/0601/2019, GD0601) were used to investigate the possible molecular basis that determined H3N2 AIV adapting to canine. We found that GD0601 exhibited more robust polymerase activity in cells and higher pathogenicity in mice compared with its evolution ancestor H3N2 AIV GX13431. A series of reassortments of the ribonucleoprotein (RNP) complex showed that the PB2 subunit was the crucial factor that conferred high polymerase activity of GD0601, and the substitution of I714S in the PB2 subunit of GD0601 attenuated the replication and pathogenicity in mammal cells and the mouse model. Mechanistically, the reverse mutation of I714S in the PB2 polymerase subunit which was identified in AIV GX13431 reduced the nuclear import efficiency of PB2 protein and interfered with the interactions of PB2-PA/NP that affected the assembly of the viral RNP complex. Our study reveals amino acid mutation at the position of 714 in the nuclear localization signal (NLS) area in PB2 plays an important role in overcoming the barrier from poultry to mammals of the H3N2 canine influenza virus and provides clues for further study of mammalian adaptation mechanism of AIVs.
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Subtipo H3N2 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , ARN Polimerasa Dependiente del ARN , Ribonucleoproteínas , Proteínas Virales , Animales , Perros , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/fisiología , Ratones , Proteínas Virales/genética , Proteínas Virales/metabolismo , ARN Polimerasa Dependiente del ARN/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Infecciones por Orthomyxoviridae/virología , Humanos , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Transporte Activo de Núcleo Celular , Replicación Viral , Mutación , Células de Riñón Canino Madin Darby , Enfermedades de los Perros/virología , Ratones Endogámicos BALB C , Células HEK293 , Virus Reordenados/genéticaRESUMEN
OBJECTIVES: Recent studies have indicated that radiomics may have excellent performance and clinical application prospects in the differential diagnosis of benign and malignant vertebral compression fractures (VCFs). However, multimodal magnetic resonance imaging (MRI)-based radiomics model is rarely used in the differential diagnosis of benign and malignant VCFs, and is limited to lumbar. Herein, this study intends to develop and validate MRI radiomics models for differential diagnoses of benign and malignant VCFs in patients. METHODS: This cross-sectional study involved 151 adult patients diagnosed with VCF in The First Affiliated Hospital of Soochow University in 2016-2021. The study was conducted in three steps: (i) the original MRI images were segmented, and the region of interest (ROI) was marked out; (ii) among the extracted features, those features with Pearson's correlation coefficient lower than 0.9 and the top 15 with the highest variance and Lasso regression coefficient less than and more than 0 were selected; (iii) MRI images and combined data were studied by logistic regression, decision tree, random forest and extreme gradient boosting (XGBoost) models in training set and the test set (ratio of 8:2), respectively; and the models were further verified and evaluated for the differential diagnosis performance. The evaluated indexes included area under receiver (AUC) of operating characteristic curve, accuracy, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and 95% confidence intervals (CIs). The AUCs were used to assess the predictive performance of different machine learning modes for benign and malignant VCFs. RESULTS: A total of 1144 radiomics features, and 14 clinical features were extracted. Finally, 12 radiomics features were included in the radiomics model, and 12 radiomics features with 14 clinical features were included in the combined model. In the radiomics model, the differential diagnosis performance in the logistic regression model with the AUC of 0.905 ± 0.026, accuracy of 0.817 ± 0.057, sensitivity of 0.831 ± 0.065, and negative predictive value of 0.813 ± 0.042, was superior to the other three. In the combined model, XGBoost model had the superior differential diagnosis performance with specificity (0.979 ± 0.026) and positive predictive value (0.971 ± 0.035). CONCLUSION: The multimodal MRI-based radiomics model performed well in the differential diagnosis of benign and malignant VCFs, which may provide a tool for clinicians to differentially diagnose VCFs.
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OBJECTIVE: The aim of the study was to explore the psychological characteristics of the individuals with various suicide risks using computerized text analysis, in the hopes of a better understanding of suicide trajectories. METHODS: 627 first-time callers' records were randomly selected from Taiwan An-Shin Hotline database between 2013 and 2018. The voice records were evaluated by two psychologists to determine the levels of suicide risk (156 with uncertainty of risk, 177 with low suicidal ideation, 157 with high suicidal ideation, and 137 with suicide preparation/attempt) and transcribed into text. The Linguistic Inquiry and Word Count 2015 (LIWC2015) program combined with Chinese dictionary were then used to calculate the frequency of word categories. RESULTS: Exploratory factor analysis identified four mindsets of language characteristics, named "opposition and questioning", "active engagement", "negative rumination", and "focus on death". Psychological descriptions of the mindsets were also obtained through correlation analysis with the LIWC2015 categories and indicators. The four mindsets effectively distinguished the callers with different levels of suicide risk. CONCLUSION: The psychological characteristics of people with various suicide risks can be described and differentiated via the closed-word categories and composite indicators. These results provide useful information for practitioners and researchers.
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The objective of this study was to explore the preservation of food products through the co-fermentation of whole-plant cassava and Piper sarmentosum (PS) without additives. We assessed fermentation quality, antioxidant activity, bacterial community structure, function profile, and microbial ecological network features. Our results demonstrate that co-fermentation of whole-plant cassava with 10% PS significantly improves food quality. The co-fermented samples exhibited enhanced lactic acid concentrations and increased antioxidant activity, with reduced pH values and concentrations of acetic acid, butyric acid, and ammonia-N(NH3-N) compared to whole-plant cassava fermented alone. In addition, PS addition also optimized microbial community structure by elevating the total abundance of lactic acid bacteria and influenced bacterial predicted functions. Furthermore, our analysis of co-occurrence networks reveals that co-fermentation impacts microbial network features, including module numbers and bacterial relative abundances, leading to altered complexity and stability of the networks. Moreover, out study also highlights the impact of ferment undesirable bacteria like Pseudomonas aeruginosa and unclassified_Muribaculaceae playing crucial roles in microbial network complexity and stability. These findings provide valuable insights into the anaerobic fermentation process and offers strategies for regulating food fermentation quality.
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Objective: This study evaluates the research developments concerning Rehmanniae Radix in ovarian hypofunction diseases. It explores the processing methods of Rehmanniae Radix, the variations in its compounds before and after processing, the mechanism of Rehmanniae Radix and its active compounds in improving ovarian function, and the advancements in clinical applications of traditional Chinese medicine (TCM) compound that include Rehmanniae Radix. Methods: Comprehensive literature search was conducted using databases such as China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, National Science and Technology Library, the Pharmacopoeia of the People's Republic of China, Pubmed, and the Web of Science Database. The search utilized the following Medical Subject Headings (MeSH) and keywords: "Rehmanniae Radix," "Drying Rehmannia Root," "Rehmannia glutinosa," "Rehmanniae Radix Praeparata," "Traditional Chinese Medicine Processing," "Pharmacological Effects," "Ovarian Aging," "Diminished ovarian reserve," "Premature ovarian insufficiency," "Premature Ovarian Failure," "Ovarian hypofunction diseases". Results: The ancient Chinese medical books document various processing techniques for Rehmanniae Radix. Contemporary research has identified changes in its compounds processing and the resultant diverse therapeutic effects. When processed into Rehmanniae Radix Praeparata, it is noted for its ability to invigorate the kidney. TCM compound containing Rehmanniae Radix is frequently used to treat ovarian hypofunction diseases, demonstrating significant clinical effectiveness. The key changes in its compounds processing include cyclic dilute ether terpene glycosides, phenylethanol glycosides, sugars, and 5-hydroxymethylfurfural. Its pharmacological action is primarily linked to the improvement of granulosa cell proliferation, antioxidative and anti-aging properties, and modulation of the immune and inflammatory microenvironment. Furthermore, Rehmanniae Radix also offers therapeutic benefits for cardiovascular and cerebrovascular diseases, osteoporosis and cognitive dysfunction caused by low estrogen levels. Thereby Rehmanniae Radix mitigates both the short-term and long-term health risks associated with ovarian hypofunction diseases. Conclusion: Processed Rehmanniae Radix has shown potential to improve ovarian function, and its compound prescriptions have a definite effect on ovarian dysfunction diseases. Therefore Rehmanniae Radix was garnering interest for both basic and clinical research, with promising application prospects as a future therapeutic agent for ovarian hypofunction diseases. However, further studies on its toxicology and the design of standardized clinical trials are necessary to fully establish its efficacy and safety.
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Hydrogen peroxide (H2O2) as a reactive oxygen species produced by cellular metabolism can be used in antitumor therapy. However, the concentration of intracellular H2O2 limits its application. Some materials could enhance the concentration of intracellular H2O2 to strengthen antitumor therapy. In this review, the recent advances in H2O2-supplying materials in terms of promoting intracellular H2O2 production and exogenous H2O2 supply are summarized. Then the mechanism of H2O2-supplying materials for tumor therapy is discussed from three aspects: reconstruction of the tumor hypoxia microenvironment, enhancement of oxidative stress, and the intrinsic anti-tumor ability of H2O2-supplying materials. In addition, the application of H2O2-supplying materials for tumor therapy is discussed. Finally, the future of H2O2-supplying materials is presented. This review aims to provide a novel idea for the application of H2O2-supplying materials in tumor therapy.
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Peróxido de Hidrógeno , Neoplasias , Microambiente Tumoral , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Microambiente Tumoral/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Especies Reactivas de Oxígeno/metabolismo , Hipoxia Tumoral/efectos de los fármacosRESUMEN
It was first found that porcine pancreatic lipase (PPL) could catalyze the Knoevenagel condensation of aromatic aldehydes and ethyl acetoacetate under solvent-free conditions in this paper. Under solvent-free conditions, the highest yield of PPL catalytic reaction was 99.38%, and the Z/E selectivity of the product was 3.93. In addition, the reaction conditions were optimized, and the factors affecting the product structure were studied.
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Human cytomegalovirus (HCMV) infection in infants infected in utero can lead to a variety of neurodevelopmental disorders. However, mechanisms underlying altered neurodevelopment in infected infants remain poorly understood. We have previously described a murine model of congenital HCMV infection in which murine CMV (MCMV) spreads hematogenously and establishes a focal infection in all regions of the brain of newborn mice, including the cerebellum. Infection resulted in disruption of cerebellar cortical development characterized by reduced cerebellar size and foliation. This disruption was associated with altered cell cycle progression of the granule cell precursors (GCPs), which are the progenitors that give rise to granule cells (GCs), the most abundant neurons in the cerebellum. In the current study, we have demonstrated that MCMV infection leads to prolonged GCP cell cycle, premature exit from the cell cycle, and reduced numbers of GCs resulting in cerebellar hypoplasia. Treatment with TNF-α neutralizing antibody partially normalized the cell cycle alterations of GCPs and altered cerebellar morphogenesis induced by MCMV infection. Collectively, our results argue that virus-induced inflammation altered the cell cycle of GCPs resulting in a reduced numbers of GCs and cerebellar cortical hypoplasia, thus providing a potential mechanism for altered neurodevelopment in fetuses infected with HCMV.
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Ciclo Celular , Cerebelo , Infecciones por Citomegalovirus , Modelos Animales de Enfermedad , Animales , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/patología , Ratones , Cerebelo/virología , Cerebelo/patología , Cerebelo/crecimiento & desarrollo , Cerebelo/anomalías , Femenino , Citomegalovirus , Células-Madre Neurales/virología , Muromegalovirus/fisiología , Animales Recién Nacidos , Humanos , Neuronas/virología , Factor de Necrosis Tumoral alfa/metabolismo , Discapacidades del Desarrollo , Malformaciones del Sistema NerviosoRESUMEN
The emerging evidence of human infections with emerging viruses suggests their potential public health importance. A novel taxon of viruses named Statoviruses (for stool-associated Tombus-like viruses) was recently identified in the gastrointestinal tracts of multiple mammals. Here we report the discovery of respiratory Statovirus-like viruses (provisionally named Restviruses) from the respiratory tracts of five patients experiencing acute respiratory disease with Human coronavirus OC43 infection through the retrospective analysis of meta-transcriptomic data. Restviruses shared 53.1%-98.8% identities of genomic sequences with each other and 39.9%-44.3% identities with Statoviruses. The phylogenetic analysis revealed that Restviruses together with a Stato-like virus from nasal-throat swabs of Vietnamese patients with acute respiratory disease, formed a well-supported clade distinct from the taxon of Statoviruses. However, the consistent genome characteristics of Restviruses and Statoviruses suggested that they might share similar evolutionary trajectories. These findings warrant further studies to elucidate the etiological and epidemiological significance of the emerging Restviruses.
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Genoma Viral , Filogenia , Infecciones del Sistema Respiratorio , Humanos , China/epidemiología , Genoma Viral/genética , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Sistema Respiratorio/virología , Preescolar , Adulto , Niño , ARN Viral/genética , Persona de Mediana EdadRESUMEN
Background: This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent base of tongue and floor of mouth cancer. Methods: Thirty-one patients with recurrent lingual and floor of mouth squamous cell carcinoma after surgery and radiotherapy were treated with 3DPT-guided RSBT from 2015 to 2022. Seeds were implanted through a submental approach guided by 3DPTs. Local control (LC), overall survival (OS), disease control (DC) and quality of life (QOL) were evaluated. Results: The median follow-up was 13.7 months. The 1-, 3- and 5-year LC rates were 66.1%, 66.1%, and 55.1% respectively. The 1-, 3- and 5-year OS rates were 63.4%, 33.4%, and 8.3%. The 1-, 3- and 5-year DC rates were 37.8%, 26.5%, and 21.2%. Univariate analysis showed tumor size significantly affected LC (P = 0.031). The presence of extraterritorial lesions affected DC and OS on multivariate analysis (P < 0.01). QOL improved significantly in domains of pain, swallowing, chewing, taste, and emotion after treatment compared to baseline. Four patients (13%) developed necrosis and osteoradionecrosis. Conclusions: 3DPT-guided submental RSBT provided favorable LC and QOL for recurrent tongue/floor of mouth cancer with minimal toxicity; moreover, severe toxicity should be noted.
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The objective of this study was to develop nanotechnology-mediated paclitaxel (PAC) and curcumin (CUR) co-loaded solid lipid nanoparticles (PAC-CUR-SLNs) for the treatment of lung cancer, which is a leading cause of death worldwide. Around 85 % cases of lungs cancer constitute non-small cell lung cancer (NSCLC). PAC-CUR-SLNs were prepared via high pressure homogenization. The in vitro drug release of PAC-CUR-SLNs was checked followed by their in vitro cytotoxic investigation using adenocarcinomic human alveolar basal epithelial cells (A549) cell lines. Anticancer effects along with side effects of the synergistic delivery of PAC-CUR-SLNs were studied in vivo, using BALB/c mice. PAC-CUR-SLNs were nano sized (190 nm), homogeneously disseminated particles with %IE of both PAC and CUR above 94 %. PAC-CUR-SLNs released PAC and CUR in a controlled fashion when compared with free drug suspensions. The cytotoxicity of PAC-CUR-SLNs was higher than individual drug-loaded SLNs and pure drugs. Moreover, the co-delivery displayed synergistic effect, indicating potential of PAC-CUR-SLNs in lung cancer treatment. In vivo tumor investigation of PAC-CUR-SLNs exhibited 12-fold reduced tumor volume and almost no change in body weight of BALB/c mice, when compared with the experimental groups including control group. The inhibition of tumor rate on day 28 was 82.7 % in the PAC-CUR-SLNs group, which was significantly higher than the pure drugs and monotherapies. It can be concluded that, encapsulating the co-loaded antitumor drugs like PAC-CUR in SLNs may help in improved targeting of the tumor with enhanced anticancer effect.
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Background: Obstructive sleep apnea (OSA) had a high prevalence in the population. Whether OSA increases the risk of amyotrophic lateral sclerosis (ALS) is unknown. Our aim was to clarify this issue using two-sample Mendelian randomization (MR) analysis in a large cohort. Methods: Two-sample MR was used to evaluate the potential causality between OSA and ALS by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was chosen as the primary method to estimate causal association. Weighted median, weighted mode and simple mode methods were used as sensitivity analyses to ensure the robustness of the results. Results: In MR analysis, IVW mode showed genetic liability to OSA was found to be significantly associated with a higher ALS risk (OR, 1.220; 95% confidence interval, 1.031-1.443; p = 0.021). No evidence of heterogeneity and horizontal pleiotropy were suggested. Conclusion: We found potential evidence for a causal effect of OSA on an increased risk of ALS.
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Novel brominated flame retardants (NBFRs) have been developed as replacements for legacy brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs). The prevalence of NBFRs in aquatic environments has initiated intense concerns that they resemble to BFRs. To comprehensively elucidate the fate of NBFRs in aquatic environments, this review summarizes the physico-chemical properties, distribution, bioaccumulation, and fates in aquatic environments. 1,2-bis(2,3,4,5,6-pentabromophenyl) ethane (DBDPE) as the major substitute for PBDEs is the primary NBFR. The release from industrial point sources such as e-waste recycling stations is the dominant way for NBFRs to enter the environment, which results in significant differences in the regional distribution of NBFRs. Sediment is the major sink of NBFRs attributed to the high hydrophobicity. Significantly, there is no decreasing trend of NBFRs concentrations, while PBDEs achieved the peak value in 1970-2000 and decreased gradually. The bioaccumulation of NBFRs is reported in both field studies and laboratory studies, which is regulated by the active area, lipid contents, trophic level of aquatic organisms, and the log KOW of NBFRs. The biotransformation of NBFRs showed similar metabolism patterns to that of BFRs, including debromination, hydroxylation, methoxylation, hydrolysis, and glycosylation. In addition, NBFRs show great potential in trophic magnification along the aquatic food chain, which could pose a higher risk to high trophic-level species. The passive uptake by roots dominates the plant uptake of NBFRs, followed by acropetal and basipetal bidirectional transportation between roots and leaves in plants. This review will provide the support to understand the current pollution characteristics of NBFRs and highlight perspectives for future research.
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Monitoreo del Ambiente , Retardadores de Llama , Éteres Difenilos Halogenados , Hidrocarburos Bromados , Contaminantes Químicos del Agua , Retardadores de Llama/metabolismo , Retardadores de Llama/análisis , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo , Éteres Difenilos Halogenados/metabolismo , Éteres Difenilos Halogenados/análisis , Hidrocarburos Bromados/metabolismo , Hidrocarburos Bromados/análisis , BioacumulaciónRESUMEN
INTRODUCTION/AIMS: Previous studies have suggested that treatments targeting the neuromuscular junction (NMJ) may play a role in the treatment of amyotrophic lateral sclerosis (ALS). However, factors impacting repetitive nerve stimulation (RNS), a technique to evaluate NMJ function, have yet to be fully elucidated. We aimed to identify independent factors contributing to the decremental response of the accessory nerve and evaluated its value in ALS clinical practice. METHODS: A total of 626 patients who were diagnosed with ALS and underwent 3 Hz RNS tests on the accessory nerve were enrolled. Data on their clinical and electrophysiological indicators were divided into a training set (collected from June 2016 to December 2022) and a test set (collected from January to August 2023). Stepwise regression was used in independent variable selection and model building. RESULTS: Forty-two percent of patients had a decrement larger than 10% and 24% had a decrement larger than 15%. Onset age, sex, onset site, forced vital capacity (FVC) and motor unit potential (MUP) duration were independent factors contributing to the results of the RNS test. MUP duration had the greatest impact on decremental response, followed by FVC and onset age. The decremental response in females was larger than in males. Upper limb onset was found to contribute more to the decrement than lower limb or bulbar onset. DISCUSSION: In patients with ALS, NMJ safety factor is reduced during re-innervation. Decremental response is affected by multiple factors, which needs to be considered in clinical trials targeting the NMJ in these patients.
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Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Estimulación Eléctrica/métodos , Unión Neuromuscular/fisiopatología , Electromiografía/métodosRESUMEN
Mitochondrial DNA (mtDNA) G-quadruplexes (G4s) have important regulatory roles in energy metabolism, yet their specific functions and underlying regulatory mechanisms have not been delineated. Using a chemical-genetic screening strategy, we demonstrated that the JAK/STAT3 pathway is the primary regulatory mechanism governing mtDNA G4 dynamics in hypoxic cancer cells. Further proteomic analysis showed that activation of the JAK/STAT3 pathway facilitates the translocation of RelA, a member of the NF-κB family, to the mitochondria, where RelA binds to mtDNA G4s and promotes their folding, resulting in increased mtDNA instability, inhibited mtDNA transcription, and subsequent mitochondrial dysfunction. This binding event disrupts the equilibrium of energy metabolism, catalyzing a metabolic shift favoring glycolysis. Collectively, the results provide insights into a strategy employed by cancer cells to adapt to hypoxia through metabolic reprogramming.
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OBJECTIVES: Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, yet there are currently no disease-modifying treatments. Disrupted miRNA expressions may lead to dysregulation of target mRNAs and dysfunction involved in DM1 pathogenic mechanism. METHODS: We used microarray platforms to examine the miRNA/mRNA expression profiles in skeletal muscle biopsies derived from DM1 patients and matched controls. Bioinformatics analysis and dual-luciferase reporter assay were conducted to provide insight into miRNA-mRNA regulatory networks altered in DM1. RESULTS: Twenty-three differentially expressed miRNAs and 135 differentially expressed genes were identified. qPCR confirmed that miR-3201, myogenic factor 5 (MYF5), myogenic differentiation 1 (MYOD1), CUGBP, Elav-like family member 1 (CELF1), and CELF2 were significantly up-regulated, while miR-196a, miR-200c, and miR-146a were significantly down-regulated. Enriched functions and pathways such as multicellular organismal development, RNA splicing, cell differentiation, and spliceosome are relevant to DM1. The miRNA-mRNA interaction network revealed that miR-182, miR-30c-2, and miR-200c were the critical nodes that potentially interacted with hub genes. Luciferase reporter assay confirmed the direct interaction between miR-196a and CELF2. CONCLUSION: Those results implied that the observed miRNA/mRNA dysregulation could contribute to specific functions and pathways related to DM1 pathogenesis, highlighting the dysfunction of miR-196a and CELF2.
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MicroARNs , Músculo Esquelético , Distrofia Miotónica , ARN Mensajero , Humanos , Distrofia Miotónica/genética , Distrofia Miotónica/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Adulto , Masculino , Femenino , Persona de Mediana Edad , Perfilación de la Expresión GénicaAsunto(s)
Adhesión Celular , Neoplasias del Colon , Neoplasias Hepáticas , Proteínas Asociadas a Pancreatitis , Humanos , Neoplasias del Colon/patología , Neoplasias del Colon/metabolismo , Neoplasias del Colon/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Línea Celular Tumoral , Proteínas Asociadas a Pancreatitis/metabolismo , Proteínas Asociadas a Pancreatitis/genética , Animales , Regulación Neoplásica de la Expresión Génica , RatonesRESUMEN
Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which leads to muscle weakness and eventual paralysis. Numerous studies have indicated that mitophagy and immune inflammation have a significant impact on the onset and advancement of ALS. Nevertheless, the possible diagnostic and prognostic significance of mitophagy-related genes associated with immune infiltration in ALS is uncertain. The purpose of this study is to create a predictive model for ALS using genes linked with mitophagy-associated immune infiltration. Methods: ALS gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Univariate Cox analysis and machine learning methods were applied to analyze mitophagy-associated genes and develop a prognostic risk score model. Subsequently, functional and immune infiltration analyses were conducted to study the biological attributes and immune cell enrichment in individuals with ALS. Additionally, validation of identified feature genes in the prediction model was performed using ALS mouse models and ALS patients. Results: In this study, a comprehensive analysis revealed the identification of 22 mitophagy-related differential expression genes and 40 prognostic genes. Additionally, an 18-gene prognostic signature was identified with machine learning, which was utilized to construct a prognostic risk score model. Functional enrichment analysis demonstrated the enrichment of various pathways, including oxidative phosphorylation, unfolded proteins, KRAS, and mTOR signaling pathways, as well as other immune-related pathways. The analysis of immune infiltration revealed notable distinctions in certain congenital immune cells and adaptive immune cells between the low-risk and high-risk groups, particularly concerning the T lymphocyte subgroup. ALS mouse models and ALS clinical samples demonstrated consistent expression levels of four mitophagy-related immune infiltration genes (BCKDHA, JTB, KYNU, and GTF2H5) with the results of bioinformatics analysis. Conclusion: This study has successfully devised and verified a pioneering prognostic predictive risk score for ALS, utilizing eighteen mitophagy-related genes. Furthermore, the findings indicate that four of these genes exhibit promising roles in the context of ALS prognostic.