Genes最新文献

Cardiovascular diseases represent one of the leading causes of morbidity and mortality worldwide despite tremendous advancements in therapeutic interventions. Prevention remains one of the most effective strategies to reduce individual risk. Apolipoprotein E (ApoE), through its genetic variants (ε2, ε3, ε4), is a well-known modulator of cardiovascular risk, traditionally studied for its role in lipid metabolism. However, recent evidence suggests that ApoE also influences endothelial function and thrombotic processes, opening new perspectives for an integrated approach to risk assessment. This narrative review explores the potential of using the APOE genotype as a key genetic biomarker, integrated with emerging endothelial markers (e.g., plasma levels of endothelin-1, nitric oxide, von Willebrand factor, endothelial adhesion molecules) to achieve a more accurate and personalized stratification of cardiovascular and thrombotic risk. The combined approach may overcome the limitations of traditional thrombophilia screening, which is often poorly informative when performed without clear clinical criteria, and may guide more targeted therapeutic decisions, particularly in borderline-risk individuals or those with unexplained thrombotic events. Finally, the review discusses the clinical implications, current challenges, and future perspectives for integrating this model into clinical practice within the framework of precision medicine. The early identification of genetically predisposed patients, together with functional endothelial assessment, could represent a breakthrough in modern cardiovascular prevention.

Mitochondrial dysfunction is a defining hallmark of aging that connects redox imbalance, metabolic decline, and inflammatory signaling across organ systems. The mitochondrial deacetylase SIRT3 preserves oxidative metabolism and proteostasis, yet its age-related decline transforms metabolically demanding organs into sources of pro-senescent cues. This review synthesizes evidence showing how SIRT3 loss in select "driver tissues"-notably liver, adipose tissue, vascular endothelium, bone-marrow macrophages, and ovary-initiates systemic aging through the release of cytokines, oxidized metabolites, and extracellular vesicles. We discuss molecular routes and mediators of senescence propagation, including the senescence-associated secretory phenotype (SASP), mitochondrial-derived vesicles, and circulating mitochondrial DNA, as well as sex-specific modulation of SIRT3 by hormonal and intrinsic factors. By integrating multi-tissue and sex-dependent data, we outline a framework in which SIRT3 activity defines the mitochondrial threshold separating local adaptation from systemic aging spread. Targeting SIRT3 and its NAD⁺-dependent network may offer a unified strategy to restore mitochondrial quality, dampen chronic inflammation, and therefore recalibrate the aging dynamics of an organism.

Background: Anthocyanins and proanthocyanidins (PAs), as flavonoid compounds with potent antioxidant activity, exhibit significant health-promoting and medicinal properties. Black wolfberry (Lycium ruthenicum Murr.) is renowned for its exceptional anthocyanin content; however, the regulatory mechanisms of anthocyanin biosynthesis remain poorly understood, limiting its biotechnological potential. This study aimed to elucidate the transcriptional regulatory function of LrMYB30 in anthocyanin biosynthesis in black wolfberry. Methods: The regulatory function of LrMYB30 was investigated using virus-induced gene silencing (VIGS), yeast one-hybrid assays, and dual-luciferase reporter assays in black wolfberry. Results: VIGS demonstrated that silencing LrMYB30 promoted anthocyanin accumulation while reducing PA content, establishing that the LrMYB30 transcription factor as a negative regulator of anthocyanin synthesis. Yeast one-hybrid and dual-luciferase reporter assays confirmed that LrMYB30 directly binds to and activates the promoter of LrANR, a key structural gene in PA biosynthesis. In contrast, LrMYB30 neither binds to nor suppresses the promoters of the critical anthocyanin biosynthesis genes LrUF3GT and LrDFR. Conclusions: Thus, LrMYB30 redirects the flavonoid metabolic flux from anthocyanin to PA synthesis through transcriptional activation of LrANR during later fruit development, reducing anthocyanin accumulation and delaying coloration. These findings reveal a novel regulatory mechanism in black wolfberry pigmentation and maturation, providing genetic targets for molecular breeding of high-anthocyanin cultivars.

Background: Sucrose metabolism plays a crucial role in plant responses to abiotic stresses such as drought and high temperatures, significantly influencing plant growth and yield formation. In higher plants, the second step in sucrose bioconversion involves sucrose phosphate phosphatase (SPP) hydrolyzing sucrose-6-phosphate to form sucrose. This study determined the number of SPP gene family members in upland cotton (Gossypium hirsutum), systematically analyzed their fundamental characteristics, physicochemical properties, phylogenetic relationships, chromosomal localization, and expression patterns across different tissues and under various abiotic stresses.

Methods: The SPP gene family in hirsutum was identified using Hidden Markov Models (HMMER) and the NCBI Conserved Domain Database (NCBI CDD), and its physico-chemical properties were analyzed via the SOPMA online analysis website. Phylogenetic relationships were determined using MEGA 12.0 software. Promoter regions were analyzed with PlantCARE, sequence patterns were identified via MEME, and transcriptome data were downloaded from the CottonMD database.

Results: This study identified four members of the hirsutum SPP gene family, with amino acid lengths ranging from 335 to 1015, molecular weights between 38.38 and 113.28 kDa, and theoretical isoelectric points (pI) between 5.39 and 6.33. These genes are localized across four chromosomes. The SPP gene family in hirsutum exhibits closer phylo-genetic relationships with SPP genes in Arabidopsis thaliana and Chenopodium quinoa. Their promoter regions are rich in cis-elements associated with multiple abiotic stress resistance functions, and their expression patterns vary across different tissues and under different abiotic stress conditions.

Conclusions: The GhSPP gene may play an important role in the growth and development of upland cotton and its responses to salt stress and drought. Therefore, it could be considered as a candidate gene for future functional analysis of cotton resistance to salt and drought stress.

Background: Snipe eels (family Nemichthyidae) are a group of pelagic fishes with unique specializations; yet, species within this study are not well-studied due to a lack of molecular data. As typical mesopelagic-to-bathypelagic fishes, snipe eels exhibit extreme body elongation, reduced skeletal ossification, and highly specialized beak-like jaws that facilitate survival in deep-sea midwater environments. Methods: The complete mitochondrial genome of the deep-sea eel Nemichthys curvirostris (Anguilliformes: Nemichthyidae) was sequenced and annotated, representing the first mitogenomic resource for this species. The phylogenetic position of N. curvirostris was also explored. Results: The circular genome of N. curvirostris was determined to be 16,911 bp in length and contained 37 genes, including 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and a single control region, with an overall A + T bias of 56.67%. The maximum-likelihood phylogeny inferred from concatenated mitochondrial protein-coding genes recovered a well-supported monophyletic Nemichthys clade, with N. curvirostris positioned as the sister taxon to N. scolopaceus. The genera Avocettina and Labichthys were recovered as sister taxa, and Nemichthys clustered within a broader clade alongside them. The COX1 haplotype phylogeny showed that the two public database sequences (HQ563894.1 and MN123435.1) appeared as long, isolated branches outside the main N. curvirostris lineage, with COX1 genetic distances from typical N. curvirostris haplotypes reaching 12-13%, far exceeding the expected range of intraspecific variation. Conclusions: This mitogenome provides a valuable molecular resource for phylogenetic, evolutionary, and population genetic studies of deep-sea Anguilliformes.

Background: The 17q12 recurrent deletion syndrome is a genomic disorder encompassing a 1.4 to 1.5 Mb region that includes the HNF1B gene, and it manifests with remarkable phenotypic variability. Renal anomalies, endocrine and metabolic disturbances, and neurodevelopmental or psychiatric disorders are recurrent features, although penetrance and severity differ widely between patients.

Methods: We reviewed the literature on the molecular basis, clinical presentation, diagnostic approaches, and management of 17q12 deletion syndrome, and we illustrate the variability of this condition through two contrasting paediatric cases.

Results: The cases concern three siblings harbouring the same familial deletion, who nevertheless exhibited striking intrafamilial variability, ranging from renal and neurodevelopmental features to multisystemic involvement. These cases exemplify both extremes of the syndrome and highlight the challenges of clinical prognostication.

Conclusions: The review and cases emphasise the importance of early genetic testing in paediatric renal anomalies, the necessity of multidisciplinary surveillance even in asymptomatic individuals, and the relevance of 17q12 deletion as a model of variable expressivity in genomic medicine.

Background and Clinical Significance: Methyltransferase-like protein 5 (METTL5) is a conserved RNA methyltransferase responsible for catalyzing the N6-methyladenosine (m6A) modification of 18S ribosomal RNA, a process critical for ribosome biogenesis and translational regulation. Biallelic variants in METTL5 have been linked to autosomal recessive intellectual developmental disorder-72 (MRT72), typically presenting with microcephaly, intellectual disability, and speech delay. However, the association between METTL5 and isolated attention-deficit/hyperactivity disorder (ADHD) remains underexplored. Case Presentation: We report a 14-year-old Qatari female, born to consanguineous parents, who presented with microcephaly, speech delay, learning difficulties, and inattentive-type ADHD. Trio-based whole-genome sequencing identified a novel homozygous METTL5 variant (c.617G > A; p. Arg206Gln), with both parent's heterozygous carriers. The variant is extremely rare (gnomAD MAF: 0.0000175) and predicted to be deleterious (CADD: 23.7; SIFT: damaging; PolyPhen-2: probably damaging). Structural modeling localized the change within the SAM-dependent catalytic domain, predicting protein destabilization (ΔΔG = +1.8 kcal/mol). The affected residue is highly conserved (ConSurf score: 8), and protein-protein interaction analysis linked METTL5 with METTL14, METTL16, and ZCCHC4, key regulators of rRNA methylation. Conclusions: In silico evidence suggests that the p. Arg206Gln variant disrupts METTL5 function, likely contributing to the observed neurodevelopmental phenotype, including ADHD. This expands the clinical spectrum of METTL5-related disorders and supports its inclusion in neurodevelopmental gene panels.

Background/Objectives: Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of misfolded alpha-synuclein protein in the brain. Mutations in the glucocerebrosidase 1 (GBA1) gene have been identified as a significant genetic risk factor for both PD and DLB. GBA1 encodes for the lysosomal enzyme glucocerebrosidase, which is responsible for the breakdown of glucosylceramide (GC). Deficiencies in glucocerebrosidase activity lead to the accumulation of glucosylceramide within lysosomes, contributing to lysosomal dysfunction and impaired protein degradation. The aim of this narrative review is to update the underlying mechanisms by which GBA1 mutations contribute to the pathogenesis of PD and DLB. Methods: A comprehensive literature search was conducted across four major electronic databases (PubMed, Web of Science (Core Collection), Scopus, and Embase) from inception to 8 November 2025. The initial search identified approximately 1650 articles in total, with the number of hits from each database being as follows: PubMed (~450), Web of Science (~380), Scopus (~520), and Embase (~300). Results: The mechanism by which mutations in the GBA1 gene contribute to PD involves both loss-of- function and gain-of-function pathways, which are not mutually exclusive. Typically, GBA1 mutations lead to a loss of function by reducing the activity of the GCase enzyme, impairing the autophagy- lysosomal pathway and leading to α-synuclein accumulation. However, some mutant forms (GBA1L444P) of the GCase enzyme can also acquire a toxic gain of function, contributing to α-synuclein aggregation through mechanisms like endoplasmic reticulum stress and misfolding. While Venglustat effectively reduced GC levels, a key marker associated with GBA1-PD, the lack of clinical improvement led to the discontinuation of its development for this indication. Conclusions: GBA1-mediated lysosomal and lipid dysregulation represents a key pathogenic axis in PD and DLB. Understanding these mechanisms provides crucial insight into disease progression and highlights emerging therapeutic strategies-such as pharmacological chaperones, substrate reduction therapies, and gene-targeted approaches-aimed at restoring GCase function and lysosomal homeostasis to slow or prevent neurodegeneration.

Head and neck cancer represents a heterogeneous group of malignancies. Oral squamous cell carcinoma (OSCC) is the most prevalent form of head and neck cancer, with a rising incidence in recent years. Risk factors for developing OSCC include exposure to carcinogens, such as alcohol and tobacco products, that can lead to molecular alterations in the oral mucosa and progression from premalignant lesions to invasive phenotypes. Despite the relative curative potential of localized OSCC, the overall prognosis of OSCC has not significantly improved for decades due to a frequently delayed diagnosis and limited targeted treatment options. There remains a need to better characterize the molecular biomarkers of OSCC progression, especially in dysplastic mucosal lesions, before their malignant transformation. In this review, we discuss several molecular biomarkers highly implicated in OSCC tumorigenesis that have demonstrated correlation with clinicopathological parameters and clinical outcomes. These biomarkers are typically involved in vital pathways of carcinogenesis, including cell cycle control, growth factor signaling, and stress responses. They include ubiquitous cancer biomarkers such as p53 and PTEN, as well as those more specific to OSCC, such as DJ-1 and Cornulin. Collectively, we envision that a diverse panel of these biomarkers can provide the greatest clinical benefit in enhancing early detection and prognostic accuracy, while some individual biomarkers may also serve as therapeutic targets for personalized approaches to head and neck cancers.

Background/objectives: Tropoelastin is a highly hydrophobic extracellular matrix protein responsible for the extensibility and elastic recoil of various organs. The Windkessel effect in blood vessels dampens pressure variations during the cardiac cycle to provide continuous perfusion of tissues, such as the fragile gill capillaries in fish. The teleost-specific whole-genome duplication was followed by structural and functional divergence of the duplicated tropoelastins, of which ElnB confers the uniquely low stiffness of the bulbus arteriosus.

Methods: We have examined the diversity of tropoelastins in all major fish clades by searching for tropoelastin (eln) genes in the sequenced genomes. Duplication of eln genes in tetraploid salmonids and cyprinids was examined by maximum likelihood phylogenetic analysis, and cardiac eln expression in rainbow trout was quantified by qPCR.

Results: The tetraploid salmonid genomes harbor two elna genes but a single elnb, except for the tandem duplicated elnb genes in sockeye salmon and lake whitefish, while the tetraploid common carp possesses four elna and elnb genes on separate chromosomes. Rainbow trout showed strong elastin staining in the larval bulbus and ventral aorta, and the bulbar expression of elnb was 15 times higher than the ventricular levels in juvenile fish. The expression of elna1 and elna2 was also significantly higher in the bulbus, and together their transcript levels were almost similar as the elnb levels. The overall hydrophobicity of the fish tropoelastins differed considerably among the species ranging from 28.6% in Emerald rockcod ElnB to 56.3% in lesser devil ray Eln, but showed no significant difference with the tetrapods examined, except for the lower hydrophobicity of teleost ElnB.

Conclusions: The inclusion of tetrapods in the analysis revealed a positive relationship between ventral aortic blood pressure and tropoelastin hydrophobicity.