Search Results (569)

Worldwide, prostate cancer (PC) has a rising incidence and is the sixth leading cause of death globally, especially with increasing cases in developing countries. Risk factors for PC include genetic predisposition, family history, race/ethnicity, and various occupational factors like diet, obesity, smoking, and transmitted diseases. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway can be activated by hormones, cytokines, and growth factors, and it plays a role in many vital biological processes such as cell growth, differentiation, immune regulation, and apoptosis. Dysregulation of JAK/STAT3 can lead to cancer, inflammation, diabetes, and neurodegenerative disorders. In cancers, including PC, STAT3 promotes cell survival, progression, angiogenesis, and metastasis. Inhibitors targeting JAK and STAT3 tested in vivo have shown potential to inhibit malignant cell growth. Additionally, flavonoids are bioactive plant compounds that are important in preventing inflammation, oxidative stress, and cancer. Research indicates that natural flavonoids can be developed into cancer-preventive and therapeutic agents. Experimental studies have demonstrated that some flavonoids can inhibit PC development. The main goal of this review is to present the incidence and risk factors of PC, the JAK/STAT3 pathway and its inhibitors, and how flavonoids may influence this pathology. Full article

The Potocki family of the Pilawa coat of arms was among the most powerful noble lineages of the former Polish–Lithuanian Commonwealth, and its history is closely intertwined with that of Poland, Lithuania, Belarus, and Ukraine. In the late seventeenth century, Feliks Kazimierz Potocki (1630–1702) founded the town of Krystynopol (now Chervonohrad), named in honor of his wife, Krystyna Lubomirska. The residence, passed down through successive generations of the Potocki family, was transformed in the mid-eighteenth century into an impressive Baroque palace-and-garden complex designed by Pierre Ricaudde Tirregaille, becoming a model example of the magnate cultural landscape on the border of present-day Poland and Ukraine. In the centuries that followed, the estate changed owners multiple times, suffered devastation during the world wars, and in the Soviet period housed the Museum of Atheism. Today, the partially restored palace accommodates a small regional museum. Although in the eighteenth century the palace was surrounded by an extensive Italian-French style garden with water canals, ponds, and fountains, the area has since been built over with public-utility buildings. This study presents a concept for the development of the surviving elements of the historical palace park. The project is based on historical analyses, field research, site inspections, interviews with museum staff and town residents, as well as a detailed dendrological inventory including an assessment of tree health. The study area covers 4.71 ha, and the current tree stand is composed mainly of Salix alba, Populus nigra, Populus alba, Betula pendula, Quercus robur, Fraxinus excelsior, Ulmus laevis, Acer negundo, and Acer pseudoplatanus. Archival sources allowed for the reconstruction of the original layout of the palace-park complex. The aim of the project is therefore to introduce new representative, educational, recreational, social, ecological, and touristic functions to the currently neglected area while respecting its historical heritage. Full article

Ormosia henryi, a rare and endemic timber tree in China, possesses exceptional economic and ecological value, but it has experienced a critical decline in wild populations. We integrated PacBio HiFi and Hi-C technologies to generate a superior, chromosome-level genome assembly, establishing a more robust genetic foundation than existing draft sequences. The resulting assembly (2.64 Gb; Contig N50 = 39.17 Mb; and Scaffold N50 = 338.40 Mb) exhibits high continuity and completeness, effectively overcoming the assembly challenges associated with high heterozygosity (1.37%) and repetitive sequence content (83.89%). Comparative genomic analysis revealed that O. henryi diverged from Lupinus albus approximately 53.82 million years ago and underwent two independent whole-genome duplication events. The historical accumulation of evolutionary resilience is reflected in the significant expansion of 276 gene families enriched in photosynthesis and phenylpropanoid biosynthesis, alongside 122 genes under positive selection involved in DNA repair and proteostasis. These genomic signatures elucidate a stable genetic foundation. While wild populations have sharply declined in recent decades, this suggests that this status underscores the overwhelming impact of intense external anthropogenic pressures, such as overexploitation and habitat fragmentation, which may have overridden the species’ inherent adaptive capacity and slow life-history strategy. This high-quality genomic resource identifies key candidate loci, such as the PIF1 helicase for growth regulation, and provides a critical framework for screening elite germplasm for population restoration. Consequently, this study establishes a theoretical and molecular basis for transitioning from fundamental research to the precision conservation and sustainable industrial application of this high-value woody species. Full article

Background: Gestational diabetes mellitus (GDM) is a frequent pregnancy pathology with poor maternal and fetal outcomes and risk of type 2 diabetes in later life. Despite known risk factors, such as obesity, age, and familial history, new data suggest that environmental exposure to agents, such as pesticides, can play a role in the etiogenesis of GDM. Objective: The epidemiologic, experimental, and mechanistic evidence between pesticide exposure and GDM risk is summarized here, and we concentrate on recent research (2000–2025). Methods: We conducted a literature search in PubMed, Embase, and the Cochrane Library for studies published from January 2000 to December 2025 using combinations of the terms “fertilizers”, “herbicides”, and “pesticides” with “diabetes mellitus” and “gestational diabetes”. After deduplication, 12 unique studies met inclusion criteria for qualitative synthesis (GDM endpoint or pregnancy glycemia with pesticide exposure). Results: Occupational and agricultural exposure to pesticides during first pregnancy was determined to be associated with a significantly increased risk of GDM through various epidemiologic studies. New studies have implicated new classes of pesticides, including pyrethroids and neonicotinoids, with higher GDM risk with first-trimester exposure. Experimental studies suggest that pesticides provide potential endocrine-disrupting chemicals that can induce insulin resistance through disruption of hormonal signaling, oxidative stress, inflammation, β-cell toxicity, and epigenetic modifications. However, significant limitations exist. Most of the evidence is observational, measurement of exposure is often indirect, and confounding factors are difficult to exclude. Notably, low dietary and residential exposure is not well studied, and dose–response relationships are undefined. Conclusions: New data indicate that pesticide exposure during early pregnancy and occupational exposure may increase the risk of GDM. Prospective cohort studies using biomonitoring, chemical mixture exposure, and geographic variation in pesticide exposure should be the focus of future research. Due to potential public health implications, preventive strategies to ensure the quality of nutrition and to reduce maternal exposure to pesticides during pregnancy are rational. Full article

Background and Clinical Significance: Paroxysmal extreme pain disorder (PEPD) is an extremely rare autosomal dominant sodium channelopathy caused by SCN9A gain-of-function variants. It is characterized by infantile-onset excruciating paroxysmal pain, typically in rectal, ocular, or mandibular regions, triggered by innocuous stimuli and accompanied by autonomic flares. Carbamazepine is dramatically effective in most reported cases. To date, only two genetically confirmed cases have been documented in Chinese patients, and fewer than 20 disease-causing variants are reported worldwide. We report the third Chinese case harboring a novel likely pathogenic SCN9A variant (p.Leu1623Gln), notable for its unusually severe, progressive, and carbamazepine-refractory phenotype, as well as life-threatening psychiatric sequelae, highlighting phenotypic heterogeneity and the devastating impact when standard therapy fails. Case Presentation: A Chinese male proband with positive family history presented with lifelong trigger-induced catastrophic burning and tearing pain in the perineum and lower limbs, associated with erythema, swelling, and occasional non-epileptic seizures. Attacks worsened with age despite escalating polypharmacy, including high-dose opioids, benzodiazepines, topical lidocaine and carbamazepine. Both the proband and his father developed profound psychosocial sequelae including severe depression and suicidal attempts. Next-generation sequencing in the proband revealed a novel heterozygous likely pathogenic variant NM_001365536.1 (SCN9A): c.4868T>A p.(Leu1623Gln). Conclusions: This third reported ethnic Chinese PEPD case expands the genotypic and phenotypic spectrum of SCN9A-related channelopathies, demonstrating that some variants can produce carbamazepine-refractory, progressive, and profoundly disabling disease with high suicidality risk. Early genetic diagnosis is critical in family planning and cascade testing, and has the potential in guiding targeted therapy that is under active research. Full article

This study examines the impact of Kosovo’s matrimonial property and inheritance laws on intergenerational inheritance and family connections. It explores how the division of property during marriage or upon divorce influences inheritance outcomes and the continuity of family lineage. The research employs a comparative approach, including genealogical case studies, to analyze these effects. Findings demonstrate that legal provisions significantly influence the preservation of family property and help prevent intra-family disputes. Well-structured laws ensuring the participation of children and the surviving spouse promote gender and social equality, respect heirs’ rights, and support economic sustainability. Comparative experiences from Germany and France offer practical examples for harmonizing property management in Kosovo. Additionally, the study highlights the importance of accurate property data and the use of genealogical records to maintain continuity in material inheritance and the construction of family history. Overall, matrimonial property and inheritance laws are more than legal instruments; they uphold social order and safeguard families’ material legacies. The study concludes with concrete recommendations for policy and legal practices that address communities’ real needs while acknowledging family history. Full article

Introduction: Cardiomyopathies (DCM, HCM, and ACM) and primary arrhythmogenic disorders (BrS, LQTS, and CPVT) represent the most common causes of sudden cardiac death (SCD) in young individuals. Systematic genome-wide single-nucleotide polymorphism (SNP) analyses and genome-wide association studies (GWASs) have enabled the identification of numerous genetic variants associated with cardiovascular diseases. Body: Genetic testing for cardiomyopathies and inherited channelopathies primarily involves panel testing of genes with definitive and strong evidence of disease association; genes supported by moderate evidence may also be considered. Cardiomyocytes express a variety of proteins implicated in the pathogenesis of genetic cardiomyopathies, including sarcomeric, cytoskeletal, desmosomal, and nuclear envelope proteins. Inherited cardiac channelopathies result from mutations in genes encoding cellular components that influence calcium ion availability or affect membrane ion channels, including sodium, potassium, and calcium channels. Common variants associated with SCD are found in genes encoding cardiac ion channels (e.g., SCN5A, KCNQ1, and KCNH2), calmodulin (CALM2), sarcomeric proteins (MYH7, MYBPC3, TTN, and TNNI3), and desmosomal proteins (RyR2 and DES). Conclusions: This review demonstrates that specific genetic variants are significantly associated with an increased risk of SCD. The evidence underscores the importance of genetic screening and early intervention in individuals with a family history of SCD or other risk factors for inherited cardiac disorders predisposing to SCD. Future research should focus on gene-specific management strategies for familial cardiomyopathies and inherited channelopathies, with the goal of improving targeted genetic therapies and reducing the burden of sudden cardiac death. Full article

Background/Objectives: Pathogenic and likely pathogenic variants in the BRCA1 and BRCA2 genes are associated with a significantly increased risk of breast and/or ovarian cancer. We investigated genetic variants in a cohort of 450 unaffected individuals with a family history of breast and/or ovarian cancer, involving at least one first-degree relative. Methods: Next-generation sequencing (NGS) was used to analyze the coding regions of these two genes, with copy number variation (CNV) analysis. Results: A total of 16 unique to our cohort variants classified as pathogenic or likely pathogenic were identified in 22 patients, including one novel loss-of-function variant in BRCA1 gene. Furthermore, we identified a deletion of exon 21 in the BRCA1 gene in two patients. Conclusions: These results emphasize the difficulties involved in molecular diagnostics and indicate the need for further research into new predictive models for patients with hereditary breast and ovarian cancer. Full article

This study focuses on the genetic and clinical characterization of Monogenic Forms of Diabetes (MFD), which are frequently underdiagnosed or misclassified due to clinical similarities with type 1 and type 2 diabetes. Researchers performed Exome Sequencing on 11 Tunisian patients suspected of having MFD. The pathogenicity of genetic variants was assessed using filtering and bioinformatics prediction tools. The ORVAL online tool was used to predict the likelihood of combinations of pathogenic variants. Sanger sequencing confirmed likely pathogenic predicted variants in patients and assessed familial segregation. We identified 15 potentially pathogenic variants in 14 genes linked to MFD, including MODY-3, and isolated diabetes with low penetrance for Wolfram syndrome. Additionally, syndromic forms such as partial familial lipodystrophy types 2 and 4, and Wolfram syndrome were detected. Five patients exhibited characteristics of unspecified MFD. This study underscores the importance of genetic screening in individuals with diabetes who have a family history of the disease, particularly those with associated comorbidities. Our findings emphasize the crucial role of genetic testing in refining diabetes classification, leading to more accurate diagnoses. Therefore, integrating genetic research into clinical practice is essential to improving healthcare outcomes for patients with diabetes. Full article

Veronicastrum sibiricum (L.) Pennell, a species within the Plantaginaceae family, has a history of traditional application in addressing conditions such as abdominal pain, common cold, sore throat, parotitis, rheumatic discomfort, and snakebite. The plant produces diverse bioactive constituents, including phenylpropanoids, essential oils, flavonoids, and terpenoids. Terpenoids, generated via terpene synthases (TPSs), are of particular interest due to their pharmacological properties. Nevertheless, TPS enzymes in V. sibiricum have not been thoroughly investigated. In this research, a transcriptomic strategy was employed to isolate and profile TPS genes from V. sibiricum. Sequencing of the transcriptome produced 107,929 unigenes, among which 42,976 were functionally annotated using public databases. KEGG pathway examination revealed 264 genes associated with terpenoid metabolism, including 12 putative VsTPS genes harboring characteristic TPS domains. From these, VsTPS1 was successfully cloned. Functional characterization established that VsTPS1 operates as a bifunctional enzyme: in vitro, it catalyzes the conversion of FPP to (E)-nerolidol and, to a lesser extent, GPP to linalool. When expressed transiently in Nicotiana benthamiana, however, only (E)-nerolidol was detected, supporting its cytosolic localization and substrate specificity toward FPP. Accordingly, this sesquiterpene synthase was redesignated VsNES1. Co-expression of VsNES1 with HMGR in N. benthamiana markedly increased (E)-nerolidol yields, illustrating an effective strategy for heterologous production. These findings deepen our understanding of the TPS family in medicinal plant V. sibiricum and enable future biotechnological exploitation of terpenoid production in heterogenous plant cells. Full article

Background: Colorectal cancer (CRC) is a leading cause of cancer death, and the incidence and mortality rates among young adults are rising. Although a subset of CRC cases presents with a family history, suggesting a hereditary component, the specific genetic underpinnings remain incompletely understood, particularly in early-onset CRC (EOCRC). This study aimed to discover novel risk genes for EOCRC using exome sequencing and gene-based rare variant burden testing. Methods: Our cohort consisted of 212 European-ancestry cases (174 diagnosed with CRC and 38 with significant polyps) from the South Australian Young Onset Colorectal Polyp and Cancer Study (SAYO) and 31,699 unaffected controls from the Simons Foundation Powering Autism Research for Knowledge (SPARK) cohort. After filtering for ancestry, relatedness, variant quality, and population allele frequency, we performed gene-set and individual-gene burden tests using predicted deleterious missense and loss-of-function variants. Statistical significance was assessed using permutation-corrected binomial testing. An independent validation was conducted in the UK Biobank. Results: Loss-of-function variants in known CRC tumor suppressor genes were significantly enriched in SAYO cases. Gene-level analyses identified MEIKIN as a novel EOCRC susceptibility candidate (p value = 1.0 × 10⁻⁷), with supporting enrichment of deleterious missense and loss-of-function variants in distal colon cancer cases from the UK Biobank. Additional genes (STK25, PGBD4, DIRAS3, ATG3, RPS6KA4, and DDX42) demonstrated borderline significance, implicating pathways related to kinetochore assembly, autophagy regulation, and immune signaling. Both predicted gain-of-function and loss-of-function variants contributed to the EOCRC risk, supporting heterogeneous mechanisms of CRC pathogenesis. Conclusions: This study identified novel candidate risk genes for EOCRC, underscoring the role of rare variants and expanding our understanding of the genetic architecture of CRC. Future studies should include functional validation and replication studies on other ancestries to confirm and extend these results. Full article

Madagascar is one of the world’s most prominent biodiversity hotspots and is characterized by exceptionally high amphibian diversity, with 429 currently described, mostly endemic species. However, cytogenetic research on Malagasy amphibians has been conducted only intermittently over the years. Previous studies, mostly using conventional staining and banding methods and often confined to single taxa or isolated families, have provided only partial insights into the karyotype evolution and genome organization of the major Malagasy clades. In this contribution, we present the first comprehensive synthesis of all available cytogenetic data on Malagasy anurans, including chromosome number and morphology, heterochromatin distribution, and chromosomal markers across the major endemic Malagasy families. By integrating and comparing results from decades of scattered studies, this review reveals consistent patterns of chromosomal diversification and identifies evolutionary trends associated with speciation and adaptive radiation in Malagasy amphibians. Overall, native Malagasy amphibian species can be subdivided into two main karyotype groups: the first includes karyotypes with only biarmed chromosomes (Heterixalus, Ptychadena, Boophis, Mantella, and Guibemantis), while the second comprises karyotypes with one or more uniarmed elements (Gephyromantis, Mantidactylus, and Microhylidae). The localization of NORs follows a diverse pattern, often varying even among closely related species. Heterochromatin distribution and composition also appear to be species-specific and thus taxonomically informative. Beyond summarizing existing knowledge, this work establishes a unified framework for interpreting chromosome evolution within the unique biogeography and evolutionary history of Madagascar. Our synthesis provides essential baseline data for future molecular, genomic, and conservation studies, thereby enhancing our understanding of the mechanisms that have generated and maintained the island’s extraordinary amphibian diversity. Full article

Childhood emotional neglect and parental overprotection are two subtle yet influential caregiving patterns that shape emotional, relational, and self-regulatory development. Though they are often examined separately, emerging research suggests that they may act independently and together to increase vulnerability to disordered eating. This narrative review synthesizes contemporary theoretical and empirical contributions to clarify how emotional neglect and overprotection affect pathways related to emotion regulation, attachment processes, and self-concept development. The review introduces the concept of complementarity, explaining how these patterns may co-occur within the same family system or fluctuate among individual caregivers. This creates developmental contexts marked by emotional deprivation and restricted autonomy. Based on this synthesis, the manuscript presents an integrative framework that considers distinct and shared mechanisms connecting caregiving experiences to maladaptive eating patterns. Developmental and clinical implications are discussed, emphasizing the importance of assessing relational histories, supporting emotional clarity, and promoting autonomy in intervention planning. The limitations of the narrative approach and directions for future research are outlined, including the need for longitudinal designs, more precise measurement of caregiving dimensions, and a more systematic investigation of the interactive effects of emotional neglect and overprotection. Full article

Objective: We assess the prevalence of myopia and its associated factors among schoolchildren in Madrid, Spain, where school-based data using cycloplegic refraction are currently scarce. Methods: A cross-sectional study was conducted in 39 randomly selected schools in Madrid, targeting children in the second (6–7 years) and sixth grades (11–12 years). Parents completed questionnaires detailing family ocular history, the child’s lifestyle, and screen time. Socio-economic status was inferred from the Human Development Index of school districts. Children were examined using a two-stage approach: initial screening with visual acuity testing and Plusoptix photorefraction (myopia screening cut-off ≤ 0.00 D spherical equivalent), followed by confirmatory cycloplegic autorefraction (three drops of cyclopentolate 1% administered at 10 min intervals), with myopia defined as spherical equivalent ≤ −0.50 D. Statistical analyses included chi-square tests and logistic regression models to evaluate associated factors. Results: Of 3680 children invited, 2489 (67.6%) were examined. Myopia prevalence was 6.5% in second grade and 18.7% in sixth grade. Family history of myopia was a significant risk factor (OR 2.04; 95% CI: 1.53–2.70; p < 0.001 for both parents). Outdoor activity during weekends was associated with lower myopia prevalence (OR 0.50; 95% CI: 0.37–0.66; p < 0.01 for 2–6 h). Screen time was not a significant factor in multivariate analysis. Conclusions: This large school-based study using cycloplegic refraction provides more accurate prevalence data for Spanish schoolchildren. It confirms family history as a major risk factor and highlights the association of outdoor activities with lower prevalence of myopia. These results underline the need for preventive measures and suggest areas for future interventional research. Full article

Despite extensive and multigenerational efforts by the three federally recognized Cherokee tribes to educate the larger public about the sovereign right and authority of Cherokee governments to determine affiliation, well over a million unaffiliated and unsubstantiated American claimants still declare Cherokee heritage in official records, deforming public understanding and reinforcing dangerously anti-Native racial logics. This article considers the problems associated with the “Cherokee” population categories in the 2020 U.S. census, its relationship to genealogical stereotypes in mainstream family history research, its dangers to Cherokee nationhood, and its consequences for Indian Country as a whole. Full article