Search Results (687)

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article

Drosophila melanogaster is one of the most known and used organisms worldwide, not just to study general biology problems but above all for modeling complex human diseases. During the decades, it has become a central tool to understand the genetics of human disease, how mutations alter the behavior and health of cells, tissues, and organs, and more recently to test new compounds with a potential therapeutic use. But how did this small insect become so crucial in genetics? And how is it currently used in the study of human conditions affecting millions of people? In this review, we retrace the historical origins of its adoption in genetics laboratories and list all the advantages it provides to scientific research, both for its daily usage and for the fine tuning of gene regulation through genetic engineering approaches. We also provide some examples of how it is used to study human diseases such as cancer, neurological and infectious diseases, and its importance in drug discovery and testing. Full article

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

The yak (Bos grunniens) is a key species in high-altitude rangelands of Asia. Despite their ecological and economic importance, yak production faces persistent challenges, including low milk yields, vulnerability to climate changes, emerging diseases, and a lack of systematic breeding programs. This review presents the genomic, physiological, and environmental dimensions of yak biology and husbandry. Genes such as EPAS1, which encodes hypoxia-inducible transcription factors, underpin physiological adaptations, including enlarged cardiopulmonary structures, elevated erythrocyte concentrations, and specialized thermoregulatory mechanisms that enable their survival at elevations of 3000 m and above. Copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) present promising markers for improving milk and meat production, disease resistance, and metabolic efficiency. F1 and F2 generations of yak–cattle hybrids show superior growth and milk yields, but reproductive barriers, such as natural mating or artificial insemination, and environmental factors limit the success of these hybrids beyond second generation. Infectious diseases, such as bovine viral diarrhea and antimicrobial-resistant and biofilm-forming Enterococcus and E. coli, pose risks to herd health and food safety. Rising ambient temperatures, declining forage biomass, and increased disease prevalence due to climate changes risk yak economic performance and welfare. Addressing these challenges by nutritional, environmental, and genetic interventions will safeguard yak pastoralism. This review describes the genes associated with different yak traits and provides an overview of the genetic adaptations of yaks (Bos grunniens) to environmental stresses at high altitudes and emphasizes the need for conservation and improvement strategies for sustainable husbandry of these yaks. Full article

Mycoplasmas are known respiratory pathogens in tortoises, but few studies exist in snakes. To better understand the correlation with clinical signs and co-infections, samples from mycoplasma-positive snakes with and without clinical respiratory disease were analyzed. Oral swabs from 15 snakes (pythons n = 12, boas n = 3) were examined using polymerase chain reaction (PCR) and third-generation sequencing (TGS). Additionally, mycoplasma isolation assays were performed. Pathogens detected by PCR included Mycoplasmas (15/15, 100%), serpentoviruses (9/15, 60%), and Chlamydia sp. (2/15, 13%); those detected by TGS included Mycoplasmas (14/15, 93%), serpentoviruses (10/15, 67%), Chlamydia sp. (1/15, 7%), and 15 different bacterial species. Sequencing of the mycoplasma PCR products revealed a close genetic relationship to Mycoplasmopsis agassizii. TGS identified genetically distinct mycoplasmas and three different serpentoviruses. While mycoplasmas could not be successfully propagated, Brucella intermedia comb. nov. was identified in eight cultures. Respiratory disease in snakes is often multifactorial, involving various pathogens and environmental influences. This study demonstrates that comprehensive diagnostics are essential for understanding disease processes in snakes and improving the detection of diverse pathogens. Further research is needed to improve laboratory diagnostics for infectious diseases in reptiles and to better understand the roles of various pathogens in respiratory diseases in snakes. Full article

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare genetic disorder, often leading to injuries and serious infections. In 2018, we established a multidisciplinary clinic (MDC) to provide structured, proactive care. We assessed the MDC’s impact on hospitalizations, surgeries, and infection rates. Methods: A retrospective study of genetically confirmed CIPA patients, treated from 2014 to 2024. Data from electronic medical records were compared between the pre-MDC (2014–2017) and post-MDC (2018–2024) periods. The core MDC team includes an infectious disease specialist, orthopedic surgeon, and nurses. The patients are stratified according to their carriage of resistant organisms and are managed using strict infection control measures. Follow-ups are scheduled routinely or as needed. Treatment is guided by clinical findings and culture results. Results: A total of 59 patients were included in the study. The baseline age did not differ significantly between the two periods. Hospitalization rates declined by 30.7% (from 57.7 to 40.0 per 1000 days), and clinic visits decreased by 42.9% (25.5 to 14.6). Overall surgical rates remained stable (2.8 to 2.7), with a 61.9% decrease in eye surgeries and a 130.5% increase in elective tooth extractions. Infection rates increased by 52% (from 6.6 to 10.1 per 1000 days). Conclusions: The implementation of the MDC bundle led to reduced hospitalizations, clinic visits, and eye surgeries, alongside the increased use of elective tooth extractions and culture testing. Closer monitoring and early infection management contributed to fewer severe complications. These findings support the value of structured, proactive multidisciplinary care in improving outcomes for children with CIPA. Full article

Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who were hospitalized for coronavirus disease (COVID)-19 in Brazil between 2020 and 2024. Methods: We conducted a retrospective descriptive analysis using data from the Brazilian Unified Health System (SUS, which stands for the Portuguese Sistema Único de Saúde) through the Open-Data-SUS platform. Patients with a confirmed diagnosis of OI and hospitalization due to COVID-19 were included. Descriptive statistical analysis was performed to evaluate demographic, clinical, and outcome-related variables. We included all hospitalized COVID-19 cases with a confirmed diagnosis of OI between 2020 and 2024. Results: Thirteen hospitalized patients with OI and COVID-19 were identified. Most were adults (9; 69.2%), male (7; 53.8%), self-identified as White (9; 69.2%), and all were residents of urban areas (13; 100.0%). The most frequent symptoms were fever (10; 76.9%), cough (9; 69.2%), oxygen desaturation (9; 69.2%), dyspnea (8; 61.5%), and respiratory distress (7; 53.8%). Two patients had heart disease, one had chronic lung disease, and one was obese. As for vaccination status, five patients (38.5%) had been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Four patients (30.8%) required admission to an intensive care unit (ICU), and six (46.2%) required noninvasive ventilatory support. Among those admitted to the ICU, only two required invasive mechanical ventilation. The clinical outcome was death in two cases (15.4%). Both patients were male, White, and had not been vaccinated against SARS-CoV-2. One was 47 years old, was not admitted to the ICU, but required noninvasive ventilation. Despite the underlying condition most patients had favorable outcomes, consistent with an international report. Conclusions: This is the first report to describe the clinical and epidemiological profile of patients with OI hospitalized for COVID-19 in Brazil, providing initial insights into how a rare bone disorder intersects with an acute respiratory infection. The generally favorable outcomes observed—despite the underlying skeletal fragility—suggest that individuals with OI are not necessarily at disproportionate risk of severe COVID-19, particularly when appropriately monitored. The occurrence of deaths only among unvaccinated patients underscores the critical role of SARS-CoV-2 vaccination in this population. Although pharmacological treatment data were unavailable, the potential protective effects of bisphosphonates and vitamin D merit further exploration. These findings support the need for early preventive strategies, systematic vaccination efforts, and dedicated clinical protocols for rare disease populations during infectious disease outbreaks. Full article

The invention of antibacterial agents (antibiotics) was a significant event in the history of the human race, and this invention changed the way in which infectious diseases were cured; as a result, many lives have been saved. Recently, antibiotic resistance has developed as a result of excessive use of antibiotics, and it has become a major threat to world health. ARGs are spread across biomes and taxa of bacteria via lateral or horizontal gene transfer (HGT), especially via conjugation, transformation, and transduction. This review concerns transduction, whereby bacteriophages or phages facilitate gene transfer in bacteria. Bacteriophages are just as common and many times more numerous than their bacterial prey, and these phages are much more influential in controlling the population of bacteria. It is estimated that 25% of overall genes of Escherichia coli have been copied by other species of bacteria due to the HGT process. Transduction may take place via a generalized or specialized mechanism, with phages being ubiquitous in nature. Phage and virus-like particle (VLP) metagenomics have uncovered the emergence of ARGs and mobile genetic elements (MGEs) of bacterial origins. These genes, when transferred to bacteria through transduction, confer resistance to antibiotics. ARGs are spread through phage-based transduction between the environment and bacteria related to people or animals, and it is vital that we further understand and tackle this mechanism in order to combat antimicrobial resistance. Full article

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering. Full article

As a pivotal model organism in Lepidoptera research, the silkworm (Bombyx mori) holds significant importance in life science due to its economic value and biotechnological applications. Advancements in proteomics and bioinformatics have enabled substantial progress in characterizing the B. mori proteome. Systematic screening and identification of protein–protein interactions (PPIs) have progressively elucidated the molecular mechanisms governing key biological processes, including viral infection, immune regulation, and growth development. This review comprehensively summarizes traditional PPI detection techniques, such as yeast two-hybrid (Y2H) and immunoprecipitation (IP), alongside emerging methodologies such as mass spectrometry-based interactomics and artificial intelligence (AI)-driven PPI prediction. We critically analyze the strengths, limitations, and technological integration strategies for each approach, highlighting current field challenges. Furthermore, we elaborate on the molecular regulatory networks of Bombyx mori nucleopolyhedrovirus (BmNPV) from multiple perspectives: apoptosis and cell cycle regulation; viral protein invasion and trafficking; non-coding RNA-mediated modulation; metabolic reprogramming; and host immune evasion. These insights reveal the dynamic interplay between viral replication and host defense mechanisms. Collectively, this synthesis aims to provide a robust theoretical foundation and technical guidance for silkworm genetic improvement, infectious disease management, and the advancement of related biotechnological applications. Full article

CD226, a member of the immunoglobulin superfamily, serves as a critical regulator in various immunological processes. CD226 is expressed across immune and non-immune cells, with predominant expression being observed in natural killer (NK) cells and T cells. By engaging ligands CD155 and CD112, it orchestrates diverse signaling pathways that modulate T cell differentiation and effector functions while enhancing NK cell activation and cytotoxicity. Genetic polymorphisms and the dysregulated expression of CD226 are closely associated with susceptibility to autoimmune diseases, infectious diseases, allergic diseases, and cancer progression. Growing evidence highlight CD226’s emerging promise as a therapeutic target for immune-mediated diseases. The present work aims to review the current understanding of CD226’s role in immune responses and to comprehensively outline its multifaceted involvement in different immunological diseases, providing insights for future research to advance our mechanistic understanding of its roles in disease pathogenesis. Full article

Non-celiac villous atrophy (NCVA) is a multifaceted and under-recognized clinical entity with an etiology beyond celiac disease. This review critically examines the diverse pathophysiological mechanisms underlying NCVA, including autoimmune enteropathies, immune deficiency-related disorders, infectious processes, drug-induced trauma, and metabolic or environmental influences. A comprehensive synthesis of peer-reviewed literature, clinical studies, and case reports was conducted, adopting a multidisciplinary perspective that integrates immunologic, infectious, metabolic, and pharmacologic insights. The literature search was performed in three phases: identification of relevant studies, critical assessment of selected publications, and synthesis of key findings. Searches were carried out in PubMed, Scopus, Web of Science, and Google Scholar databases. The final search, completed in June 2025, included international, English-language articles, electronic books, and online reports. Studies were included if they addressed NCVA in the context of pathophysiology, clinical manifestations, or management strategies, with priority given to publications from the last ten years (2015–2025). The search strategy used the primary term “non-celiac villous atrophy” combined with supplementary keywords such as autoimmune enteropathy, common variable immunodeficiency, tropical sprue, drug-related enteropathy, pathophysiology, immunological mechanisms, chronic inflammation, genetic factors, environmental influences, and clinical management. Histopathological evaluations reveal that NCVA often manifests with varying degrees of villous blunting, crypt hypertrophy, and intraepithelial lymphocytosis, albeit without the gliadin-specific immune response seen in celiac disease. Various immune pathways are involved, such as autoimmune deregulation and chronic inflammatory responses, while drug-induced and environmental factors further complicate its clinical picture. These findings highlight significant diagnostic challenges and underscore the need to adapt diagnostic algorithms that combine clinical history, serologic evaluations, and histopathologic analysis. In conclusion, an in-depth understanding of the heterogeneous etiology of NCVA is critical to improving diagnostic accuracy and optimizing therapeutic strategies. Future research should prioritize the identification of specific biomarkers and the development of targeted interventions to address the unique mechanisms underlying NCVA, thereby improving patient management and outcomes. Full article

Infertility is a complex and common problem in reproductive medicine consultations. Three factors must be examined during the preconception phase: breeding management, the fertility of the bitch, and the fertility of the stud dog. Among these factors, improper breeding management remains the main cause of reproductive failure, with accurate recognition of ovulation being crucial for successful mating. Artificial insemination allows for a thorough evaluation of semen quality compared to natural mating. In addition, genetic selection, nutritional factors, and reproductive health management can either impair or improve the fertility of females and males. Idiopathic infertility can occur in bitches, but it is important to rule out other possible causes first. In bitches with irregular estrus cycles, ovarian dysfunction and endocrine imbalances should be investigated. In bitches with regular cycles, uterine disorders such as cystic endometrial hyperplasia, endometritis or congenital anomalies may be the cause. Both mating-related and chronic endometritis are recognized as contributing factors to infertility. Infectious agents, particularly Brucella spp. and Mycoplasma spp., should also be evaluated, although interpretation of Mycoplasma test results requires caution. In males presenting with poor semen quality, potential causes include infectious diseases (with brucellosis always requiring exclusion), hormonal imbalances, and the impact of exogenous treatments. The article underscores the critical role of comprehensive diagnostic protocols, proactive health surveillance, and data-driven breeding strategies in systematically addressing this multifaceted challenge. Full article

The metalloid arsenic (As) and the metals lead (Pb) and mercury (Hg), which together we call the “Toxic Triad”, are among the pollutants of greatest global concern, harming the health of millions of people and contributing to biodiversity loss. The widespread distribution of As, Pb and Hg facilitates the exposure of humans and other species to these elements simultaneously, potentially amplifying their individual toxic effects. While As, Pb and Hg are well established as toxic elements, the mechanisms by which they interact with genetic material and impact the health of various species remain incompletely understood. This is particularly true regarding the combined effects of these three elements. In this context, the objective of this work was to perform a toxicogenomic analysis of As, Pb and Hg to highlight multiple aspects of element-gene interactions, in addition to revisiting information on the genotoxicity and carcinogenicity of the Toxic Triad. By using The Comparative Toxicogenomics Database, it was possible to identify that As interacts with 7666 genes across various species, while Pb influences 3525 genes, and Hg affects 692 genes. Removing duplicate gene names, the three elements interact with 9763 genes across multiple species. Considering the top-20 As/Pb/Hg-interacting genes, catalase (CAT), NFE2 like bZIP transcription factor 2 (NFE2L2), caspase 3 (CASP3), heme oxygenase (HMOX1), tumor necrosis factor (TNF), NAD(P)H quinone dehydrogenase 1 (NQO1) and interleukin 6 (IL6) were the most frequently observed. In total, 172 genes have the potential to interact with the three elements. Gene ontology analysis based on those genes evidenced that the Toxic Triad affects several cellular compartments and molecular functions, highlighting its effect on stimulation of toxic stress mechanisms. These 172 genes are also associated with various diseases, especially those of the urogenital tract, as well as being related to biological pathways involved in infectious diseases caused by viruses, bacteria and parasites. Arsenic was the element with the best-substantiated genotoxic and carcinogenic activity. This article details, through a toxicogenomic approach, the genetic bases that underlie the toxic effects of As, Pb and Hg. Full article

The mammalian immune system, including key components such as toll-like receptors (TLRs), lymphocytes, and cytokines, plays a vital role in defending against diseases. In dogs, genetic polymorphisms and epigenetic regulation of immune-related genes contribute to breed-specific differences in susceptibility or resistance to infectious, autoimmune, and inflammatory diseases. Cytokines, essential for immune cell differentiation and activation, exhibit variable expression among breeds due to genetic factors like single-nucleotide polymorphisms (SNPs) and miRNA regulation. This variability influences immune responses not only to infections but also to chronic inflammatory conditions and cancer, providing insights for improved diagnosis, treatment, and breeding. Selective breeding has further shaped diverse immune phenotypes across breeds, especially through genetic variations in the major histocompatibility complex (MHC) region, which affect vulnerability to immune-mediated and immunodeficiency disorders. Recent studies emphasize the role of specific miRNAs in modulating immune responses during parasitic and viral infections, opening new avenues for precision veterinary medicine and immunotherapy. This review highlights the genetic and epigenetic regulation of immune genes in dogs and explores their potential applications in advancing veterinary diagnostics, therapeutics, and breeding strategies to enhance canine health. Full article