Search Results (2,795)

Background: Pancreatic ductal adenocarcinoma acquired resistance to chemotherapy poses a major limitation to patient survival. Despite understanding some biological mechanisms of chemoresistance, much about those mechanisms remains to be uncovered. Mechanobiology, which studies the physical properties of cells, holds promise as a potential target for addressing the challenges of chemoresistance in PDAC. Therefore, we, here in an initial step, assessed the altered mechanobiology of PDAC cells with acquired chemoresistance to gemcitabine and paclitaxel. Methods: Five PDAC cell lines and six stably resistant subclones were assessed for force generation on elastic micropillar arrays. Those measurements of mechanical phenotype were complemented by single-cell motility and invasion in 3D collagen-based matrix assays. Further, the nuclear translocation of Yes-associated protein (YAP), as a measure of active mechanical status, was compared, and biomarkers of the epithelial-to-mesenchymal transition (EMT) were evaluated using RT-qPCR. Results: The PDAC cells with acquired chemoresistance exert higher traction forces than their parental/wild-type (WT) cells. In 2D, single-cell motility was altered for all the chemoresistant cells, with a cell-type specific pattern. In 3D, the spheroids of the chemoresistant PDAC cells were able to invade the matrix and remodel collagen more than their WT clones. However, YAP nuclear translocation and EMT were not significantly altered in relation to changes in other physical parameters. Conclusions: This is the first study to investigate and report on the altered mechanobiological features of PDAC cells that have acquired chemoresistance. A better understanding of mechanical features could help in identifying future targets to overcome chemoresistance in PDAC. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and memory loss. While the precise causes of AD remain unclear, emerging evidence suggests that messenger RNA (mRNA) dysregulation contributes to AD pathology and risk. This study examined exosomal mRNA expression profiles of 15 individuals diagnosed with AD and 15 healthy controls from Barranquilla, Colombia. Utilizing advanced bioinformatics and machine learning (ML) techniques, we identified differentially expressed mRNAs and assessed their predictive power for AD diagnosis and AD age of onset (ADAOO). Our results showed that ENST00000331581 (CADM1) and ENST00000382258 (TNFRSF19) were significantly upregulated in AD patients. Key predictors for AD diagnosis included ENST00000311550 (GABRB3), ENST00000278765 (GGTLC1), ENST00000331581 (CADM1), ENST00000372572 (FOXJ3), and ENST00000636358 (ACY1), achieving > 90% accuracy in both training and testing datasets. For ADAOO, ENST00000340552 (LIMK2) expression correlated with a delay of ~12.6 years, while ENST00000304677 (RNASE6), ENST00000640218 (HNRNPU), ENST00000602017 (PPP5D1), ENST00000224950 (STN1), and ENST00000322088 (PPP2R1A) emerged as the most important predictors. ENST00000304677 (RNASE6) and ENST00000602017 (PPP5D1) showed promising predictive accuracy in unseen data. These findings suggest that mRNA expression profiles may serve as effective biomarkers for AD diagnosis and ADAOO, providing a cost-efficient and minimally invasive tool for early detection and monitoring. Further research is needed to validate these results in larger, diverse cohorts and explore the biological roles of the identified mRNAs in AD pathogenesis. Full article

Background/Objectives: Embryo implantation is a highly complex process that requires the precise regulation of numerous molecules to be orchestrated successfully. Micro RNAs (miRNAs) are small non-coding RNAs that regulate gene expression and play a crucial role in the regulation of embryo implantation. This article aims to summarize the key findings of the literature regarding the role of miRNAs in human embryo implantation, emphasizing their involvement in critical stages such as decidualization, endometrial receptivity and trophoblast adhesion. Methods: This review includes primary research articles from the past decade. The studies utilize a range of experimental methodologies, including gene expression analysis and in vitro studies. Results: MicroRNAs, like miR-320a, miR-149, and miR30d secreted by preimplantation embryos and blastocysts significantly influence endometrial receptivity by promoting essential cellular processes, such as cell migration and trophoblast cell attachment, while others—miR17-5p, miR-193-3p, miR-372, and miR-542-3p—secreted from the endometrium regulate the decidualization phase. During the apposition and adhesion phases, miRNAs play a complex role by promoting, for example, miR-23b-3p, and inhibiting—as do miR-29c and miR-519d-3p—important biological pathways of these stages. During invasion, miR-26a-5p and miR-125-5p modulate important genes. Conclusions: This review underscores the critical impact of miRNAs in the regulation of embryo implantation and early pregnancy. The ability of miRNAs to modulate gene expression at various stages of reproduction presents promising therapeutic avenues for improving assisted reproductive technologies outcomes and addressing infertility. Further research into miRNA-based diagnostic tools and therapeutic strategies is essential to enhance our understanding of their role in reproductive health and to exploit their potential for clinical applications. Full article

The invasion of blackchin tilapia in Thailand is a critical ecological threat affecting native biodiversity and destabilizing ecosystems. It is also resulting in significant ecological and socio-economic impacts. Originally from West Africa and introduced globally for aquaculture, blackchin tilapia thrive in Thailand’s brackish and freshwater ecosystems because of their high reproductive rates, environmental adaptability, and trophic plasticity. This review evaluates potential solutions for the invasion of blackchin tilapia in Thailand from a scientific perspective. The successful invasion of blackchin tilapia in Thailand can be attributed to several key factors, including late detection of the species, the delayed government response, the absence of effective management strategies, and the species’ high invasive potential. Given its wide distribution, large population size, and high reproductive rate, the eradication of the entire blackchin tilapia population is unlikely. Management efforts should focus on containment and impact reduction. Early detection and monitoring at the invasion front remain crucial to limit the species’ spread. Developing an online platform for tracking invasive species would aid these efforts. Public education and outreach are essential for promoting responsible behaviors for preventing further spread. Encouraging the utilization of blackchin tilapia as a food source and for commercial purposes could help suppress its population while supporting local economies. Biological control and other potentially harmful strategies should be avoided unless supported by strong scientific evidence to ensure minimal risks to ecosystems. Scientific research into controlling blackchin tilapia should be encouraged to develop suitable strategies, including using sterile triploid tilapia. The “polluter pays” policy should be implemented to cover the costs associated with invasive species. Coordinated efforts between researchers, policymakers, and the public are crucial for formulating effective management strategies to promote a balance between economic benefits and long-term environmental sustainability. Full article

This study evaluated the potential of using dogs’ apparent age, judged from photographs, as a non-invasive tool for assessing their welfare. Traditional welfare assessment methods often rely on behavioral and physiological indicators, which can be resource-intensive and invasive. This research explored whether apparent age, a measure used in humans to predict health and longevity, can also serve as an indicator of welfare in dogs by investigating its association with relative telomere length (RTL), a biomarker of biological aging. Photographs of 60 domestic dogs were evaluated by canine specialists and general volunteers via the citizen science platform Zooniverse. Participants estimated the age of 20 dogs from three different age categories: young (0–2 years), adult (2–5 years), and senior (6+ years). The accuracy of these predictions was compared to the dogs’ chronological ages and RTLs. Generalized linear models were used to assess factors influencing prediction accuracy, including the dogs’ age, sex, and origin. Results indicated that both specialists and volunteers reliably estimated the age of senior dogs, with no significant differences in accuracy between groups. Dogs with accurate apparent age estimates had RTLs matching their chronological age, while those with premature aging signs had shorter RTLs. This suggests apparent age could be a practical, non-invasive welfare assessment tool, offering a potentially accessible method for new welfare assessment protocols. Full article

The origins of multiple sclerosis (MS) have been a subject intriguing researchers and scholars for generations. The multifactorial etiological nature of the disease continues to be studied as a complex combination of genetic aspects and environmental or external risk elements contributing to the development of the disease. Descriptions of symptoms or clinical disorders suggestive of MS affecting historical figures or prominent individuals (i.e., Lidwina of Schiedam, Heinrich Heine, Augustus d’Este) did not provide clues on the origin of the disease, except for the observation that all these early possible cases were white European individuals. MS was initially framed as a neurological entity and named in the 19th century by the historical participation of the French masters Cruveilhier, Vulpian, and Charcot, among others, but the question of how the disease originated was not addressed until Charles Poser raised his conjecture on the origins of MS in two historical essays (1994 and 1995), raising the question if the Viking voyages and invasions from the 8th to the 11th century carried the Scandinavian MS genetic risk factor to Europe and the rest of the known world at that time. Poser did not have the benefit of access to ancient molecular DNA data and based his theoretical postulation on interesting historical and archeological observations. A series of studies and opinions published in 2024, utilizing sophisticated genetic analyses and genome identification, archeological DNA analysis, and other advanced techniques and biological computation, distinctly demonstrate the installation of HLA-DRB1*15:01 (class II allele) in Europe (with a higher prevalence in Scandinavia) following the massive Yamnaya pastoralists migration from the Pontic Steppe in Eurasia to western Europe (~5000 to 2500 BCE). The data suggest HLA-DRB1*15:01, the strongest genetic association with MS, underwent an evolutive switch (“thrifty drift”) from immune protector against novel zoonotic diseases appearing among the early pastoralists of the Yamnaya civilization to an autoimmune deleterious reactor to molecular mimicry and self-antigens, enabled by lifestyle changes and reduction of pastoralism once communities settled in Europe after the migration from the Pontic Steppe. This writer offers a new perspective on the origins of MS through a phase 1, the ancient east to west migration in the late Bronze Age, consolidating the HLA-DRB1*15:01 haplotype in Europe, and phase 2, the additional dissemination of the genetic MS risk through the Viking invasions, reinforcing inheritability by enabling a homozygous dominant inheritance. Full article

The risk of Aspergillus flavus contamination is expanding with global warming. Targeting the pathogenicity of A. flavus at its source and diminishing its colonization within the host may be a potential control strategy. Oxidative stress transcription factor AtfA plays a pivotal role in A. flavus pathogenicity by combating reactive oxygen species (ROS) generated by host immune cells. This study employed chromatin immunoprecipitation sequencing to elucidate the binding sites and epigenetic mechanisms of AtfA under oxidative stress. Among the total 1022 identified potential AtfA-binding peaks, a 10-bp region predominated by 5′-DRTGTTGCAA-3′, which is highly similar to the AP-1 binding motif was predicted. The significantly regulated genes exhibited a variety of biological functions, including regulation of filamentous growth, response to extracellular stimulus, and regulation of gene expression. Moreover, AtfA indirectly influenced these processes via the MAPK signaling pathway, carbon metabolism, and fatty acid metabolism in response to oxidative stress. The absence of atfA contributed to the decrease in the growth and development, sporulation, AFB₁ biosynthesis, and invasion ability of A. flavus under oxidative stress. These findings suggest that AtfA is critical to overcome oxidative stress induced by the host immune cells during the infection, providing a novel target for early prevention of A. flavus contamination. Full article

Background: Long non-coding RNAs (lncRNAs) are pivotal mediators during the development of carcinomas; however, it remains to be investigated whether lncRNAs are implicated in oral squamous cell carcinoma (OSCC). Methods: In this study, quantitative real-time PCR was conducted for detecting the expression of LINC01614 in OSCC cell lines. The biological functions of LINC01614 were assessed by loss- and gain-of-function experiments conducted both in vivo and in vitro. Cellular proliferation, migration, and invasion were investigated herein, and dual luciferase reporter assays were additionally performed to explore the relationships among LINC01614, miR-138-5p, and Forkhead box C1 (FOXC1). Results: The research presented herein revealed that OSCC cells express high levels of LINC01614. Functional experiments employing cellular and animal models demonstrated that LINC01614 knockdown repressed the malignant phenotypes of OSCC cells, including their growth, invasiveness, and migration. Further investigation revealed that LINC01614 absorbs miR-138-5p miRNA by functioning as a competing endogenous RNA to downregulate the abundance of FOXC1. Conclusions: The findings revealed that LINC01614 contributes to the progression of OSCC by targeting the FOXC1 signaling pathway. The study provides insights into a novel mechanistic process to regulate the development of OSCC, and established a possible target for the therapeutic management of OSCC. Full article

Entomopathogenic fungi (EPFs) are capable of infecting a variety of insect pests and are widely used as biopesticides worldwide. This study intended to isolate indigenous EPFs from cadavers of Protaetia brevitarsis and investigate their effects on the fall armyworm Spodoptera frugiperda (FAW), a globally widespread invasive pest. Morphological and molecular analyses confirmed four native EPF strains all belong to Beauveria bassiana. Pathogenicity tests showed they were virulent toward FAW 1st instar larvae. The application of EPFs either by dipping or spraying significantly increased the larval mortalities compared to the control group, with corrected mortalities ranging from 92% to 73% after dipping in a fungal suspension of 10⁸ conidia/mL, and those ranging from 76% to 35% after spraying with a fungal suspension of 10⁷ conidia/mL. Our findings revealed the infectivity of four strains to FAW larvae significantly changed in a dose- and time-dependent manner. In addition, the combination use of the local B. bassiana strain and parasitoid Microplitis prodeniae resulted in a significantly enhanced S. frugiperda 3rd instar larval mortality compared to a single inoculation with one of them, suggesting an apparent synergistic effect for the joint application of these two biological control agents. The mortality inflicted by B. bassiana was probably promoted by the release of parasitoids, since the parasitoids’ movements and attacks could strengthen the fungal distribution and infection processes. This study underscores the potential of the combination use of EPFs and parasitoids against S. frugiperda early-instar larvae, and provides insights into the consequences of integrating these EPFs into integrated pest management systems. Full article

The red imported fire ant (RIFA, Solenopsis invicta Buren) represents a significant invasive pest in China, exerting extensive negative impacts on ecosystems. The invasion of RIFA not only poses a severe threat to biodiversity within the environment; inappropriate controlling measures can also adversely affect community dynamics. Therefore, while implementing effective management strategies to control the proliferation of RIFA populations, it is imperative to evaluate the potential effects of these measures on the structure of local biological communities to safeguard native biodiversity. This study employs a “two-step method” using dust and bait formulations, respectively, to control RIFA while conducting ecological monitoring to further assess the impact of RIFA population decline on ant communities. The results of RIFA management showed that after post-treatment periods of 28 days, 35 days, and 60 days, the worker ant reduction rates for the three insecticides—0.5% beta-cypermethrin dust, 1.0% hydramethylnon bait, and 0.1% indoxacarb bait—reached approximately 72%, with their efficacy ranked as follows: 1.0% hydramethylnon bait > 0.1% indoxacarb bait > 0.5% beta-cypermethrin dust. By the 60th day of the experiment, the ant nest reduction rates reached their highest values—66.84% for 0.5% beta-cypermethrin dust, 77.89% for 1.0% hydramethylnon bait, and 87.52% for 0.1% indoxacarb bait—with the latter performing the best. Meanwhile, the occurrence level of RIFAs in all three pesticide treatment areas decreased from level III to level I 60 days post-treatment. Following the application of these three insecticides, the RIFA population significantly decreased, leading to an increase in species richness within the ant community. The reduction in RIFA numbers had a positive impact on the restoration of ant community diversity, as evidenced by significant improvements in both diversity and evenness indices. Notably, 0.1% indoxacarb bait was particularly effective in enhancing the ant community diversity and species richness, while 1.0% hydramethylnon bait was more effective in improving community evenness. These findings indicate that the controlling strategy used in this study not only effectively manages RIFA populations but also promotes recovery and contributes to the ecological balance of local ant communities, providing an important reference for future biodiversity conservation efforts. Full article

Background/Objectives: Bladder cancer (BC) is a highly heterogeneous disease, presenting clinical challenges, particularly in predicting patient outcomes and selecting effective treatments. Molecular subtyping has emerged as an essential tool for understanding the biological diversity of BC; however, its implementation in clinical practice remains limited due to the high costs and complexity of genomic techniques. This review examines the role of immunohistochemistry (IHC) as a surrogate marker for molecular subtyping in BC, highlighting its potential to bridge the gap between advanced molecular classifications and routine clinical application; Methods: We explore the evolution of taxonomic classification in BC, with a particular focus on cytokeratin (KRT) expression patterns in normal urothelium, which are key to identifying basal and luminal subtypes. Furthermore, we emphasise the need for consensus on IHC markers to reliably define these subtypes, facilitating wider and standardised clinical use. The review also analyses the application of IHC in both muscle-invasive (MIBC) and non-muscle-invasive bladder cancer (NMIBC), with particular attention to the less extensively studied NMIBC cases. We discuss the practical advantages of IHC for subtyping, including its cost effectiveness and feasibility in standard pathology laboratories, alongside ongoing challenges such as the requirement for standardised protocols and external validation across diverse clinical settings; Conclusions: While IHC has limitations, it offers a viable alternative for laboratories lacking access to advanced molecular techniques. Further research is required to determine the optimal combination of markers, establish a consensus diagnostic algorithm, and validate IHC through large-scale trials. This will ultimately enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes. Full article

Coastal wetlands face threats from climate change-induced flooding and biological invasions. Plants respond to these stressors through changes in their phytochemical metabolome, but it is unclear whether stressors affecting one tissue compartment (e.g., leaves) create vulnerabilities in others (e.g., roots) or elicit similar responses across tissues. Additionally, responses to multiple simultaneous stressors remain poorly understood due to the focus on individual metabolites in past studies. This study aims to elucidate how the phytochemical metabolome of three Phragmites australis (Cav.) lineages, common in the Mississippi River Delta, responds to flooding and infestation by the non-native scale insect Nipponaclerda biwakoensis (Kuwana). Among these lineages, one is non-native and poses a threat to North American wetlands. Results indicate that metabolomic responses are highly specific, varying with lineage, tissue type, stressor type, and the presence of multiple stressors. Notably, the non-native lineage displayed high chemical evenness, while the other two showed stressor-dependent responses. The 10 most informative features identified by a machine learning model showed less than 1% overlap with known metabolites linked to water and herbivory stress, underscoring gaps in our understanding of plant responses to environmental stressors. Our metabolomic approach offers a valuable tool for identifying candidate plant genotypes for wetland restoration. Full article

Extracellular vesicles (EVs) are a population of nanoscale particles surrounded by a phospholipid bilayer, enabling intercellular transfer of bioactive molecules. Once released from the parental cell, EVs can be found in most biological fluids in the human body and can be isolated from them. For this reason, EVs have significant diagnostic potential and can serve as an excellent source of circulating disease biomarkers. Protein glycosylation plays a key role in many biological processes, and aberrant glycosylation is a hallmark of various diseases. EVs have been shown to carry multiple glycoproteins, but little is known about the specific biological roles of these glycoproteins in the context of EVs. Moreover, specific changes in EV glycosylation have been described for several diseases, including cancers and metabolic, cardiovascular, neurological or kidney diseases. Urine is the richest source of EVs, providing almost unlimited (in terms of volume) opportunities for non-invasive EV isolation. Recent studies have also revealed a pathological link between urinary EV glycosylation and urological cancers, as well as other pathologies of the urinary tract. In this review, we discuss recent research advances in this field and the diagnostic/prognostic potential of urinary EV glycosylation. In addition, we summarize common methods for isolating EVs from urine and techniques used to study their glycosylation. Full article

Elevated brain iron levels are characteristic of many neurodegenerative diseases. As an iron chelator with short biological half-life, deferiprone leads to agranulocytosis and neutropenia with a prolonged therapeutic course. Its inclusion in sustained-release dosage forms may reduce the frequency of administration. On the other hand, when administered by an alternative route of administration, such as the nasal route, systemic exposure to deferiprone will be reduced, thereby reducing the occurrence of adverse effects. Direct nose-to-brain delivery has been raised as a non-invasive strategy to deliver drugs to the brain, bypassing the blood–brain barrier. The aim of the study was to develop and characterize nanocomposite microspheres suitable for intranasal administration by combining nano- and microparticle-based approaches. Nanoparticles with an average particle size of 213 ± 56 nm based on the biodegradable polymer poly-ε-caprolactone were developed using the solvent evaporation method. To ensure the deposition of the particles in the nasal cavity and avoid exhalation or deposition into the small airways, the nanoparticles were incorporated into composite structures of sodium alginate obtained by spray drying. Deferiprone demonstrated sustained release from the nanocomposite microspheres and high iron-chelating activity. Full article

Biological control of undesirable organisms and pathogens often involves the introduction of alien species into new regions. However, alien species themselves pose a potential threat to local ecosystems and economies. The Eastern mosquitofish Gambusia holbrooki is recognised as a dangerous invasive species, but despite this, it is still used for biological control of mosquito larvae, a potential vector of malaria plasmodium transmission to humans, on the Black Sea coast of the Caucasus. We focused on the species composition of helminths in this fish species. We detected adult nematodes Pseudocapillaria (Pseudocapillaria) tomentosa and cestodes Schyzocotyle acheilognathi (formely Bothriocephalus acheilognathi). The above nematode was observed for the first time in fish of the genus Gambusia. Importantly, the cestode S. acheilognathi, which we found in G. holbrooki, is the most successful invasive alien parasite species in freshwaters of the planet and is extremely hazardous to natural ecosystems and aquaculture as it can cause mass mortality of young fish. Thus, the current practice of transferring mosquitofish between water bodies on the Black Sea coast of the Caucasus to control mosquito larvae may contribute to the undesirable spread of a harmful quarantine fish parasite. Full article