Search Results (4,126)

Per and polyfluoroalkyl substances (PFAS) are a class of synthetic, persistent environmental pollutants detected in biological systems and increasingly recognized for their harmful effects on human health. The liver, being a central organ in the metabolism of xenobiotics, is profoundly affected by these compounds and is a main target of PFAS-induced toxicity. The purpose of the present Scoping Review is to investigate the multiple and complex mechanisms behind PFAS hepatotoxicity, taking into consideration evidence from preclinical in vivo models. Using electronic databases (PubMed and Google Scholar), a total of 38 studies were found eligible to be extensively explored to gather information regarding PFAS toxicity toward hepatic lipid metabolism, oxidative stress, injury and inflammation. Moreover, the parental exposure of these chemicals on the offspring will be discussed as well. As illustrated in the proposed graphical abstract, PFAS exposure has been linked to the triggering of oxidative stress phenomena, mitochondrial dysfunction and hepatic inflammatory infiltrate with sex specific effects in rodents. The predominant effects manifest as the overproduction of reactive oxygen species (ROS), the disruption of hepatic lipid metabolism, and the activation of several nuclear transcription factors involved in lipid regulation, with PPAR-α being the most prominent. Considering their strong bioaccumulative properties and persistence in both the environment and the human body, legacy and emerging PFAS should be regarded as potent toxicants with a distinctive role in the onset of metabolic diseases and as a pressing issue to be addressed within regulatory policies. Full article

Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. Methods: We conducted a detailed analysis of preclinical data sets, Phase I–III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. Results: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 h, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved β-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. Conclusions: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders. Full article

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique extensively utilized in neuroscience and clinical medicine; however, its underlying mechanisms require further elucidation. Due to ethical safety considerations, low cost, and physiological similarities to humans, rodent models have become the primary subjects for TMS animal studies. Nevertheless, existing TMS coils designed for rodents face several limitations, including size constraints that complicate coil fabrication, insufficient stimulation intensity, suboptimal focality, and difficulty in adapting coils to practical experimental scenarios. Currently, many studies have attempted to address these issues through various methods, such as adding magnetic nanoparticles, constraining current distribution, and incorporating electric field shielding devices. Integrating the above methods, this study designs a small arc-shaped TMS coil for the frontoparietal region of rats using the inverse boundary element method, which reduces the coil’s interference with experimental observations. Compared with traditional geometrically scaled-down human coil circular and figure-of-eight coils, this coil achieves a 79.78% and 57.14% reduction in half-value volume, respectively, thus significantly improving the focusing of stimulation. Meanwhile, by adding current density constraints while minimizing the impact on the stimulation effect, the minimum wire spacing was increased from 0.39 mm to 1.02 mm, ensuring the feasibility of the coil winding. Finally, coil winding was completed using 0.05 mm × 120 Litz wire with a 3D-printed housing, which proves the practicality of the proposed design method. Full article

Polycystic ovary syndrome (PCOS) is a complex disorder characterized by reproductive abnormalities such as hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently accompanied by metabolic disturbances such as insulin resistance, obesity and dyslipidemia. Genome-wide association studies (GWASs) have identified several susceptibility loci, yet little is known about their functional implications. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) has emerged as a powerful gene editing tool in bridging this gap by allowing researchers to directly target candidate genes in ovarian and metabolic pathways. For instance, experimental models have highlighted the role of CYP17A1 and DENND1A.V2 in androgen excess, anti-Müllerian hormone (AMH) in follicular arrest, and insulin receptor substrate 1 (IRS1) and PPARγ in insulin signaling and adipogenesis. To highlight the multifactorial nature of PCOS, animal models, including zebrafish and rodents, have been used to reveal interactions between reproductive and metabolic phenotypes. Nevertheless, most studies remain restricted to single-gene models, and dual-gene models or combined gene editing and hormonal induction models remain underexplored. Future research integrating precision editing, multi-omic platforms, and patient-derived organoids may provide more accurate disease models and novel therapeutic strategies. Full article

The enteric nervous system (ENS), frequently referred to as the “second brain,” is integral to maintaining gastrointestinal and systemic homeostasis. The structural and functional homeostasis of the ENS is crucial for both local intestinal processes (digestion, immunity) and systemic physiological equilibrium via the gut–brain axis, directly influencing overall health and disease. In recent years, dietary substances have attracted increasing scholarly attention for their potential to modulate the ENS, attributed to their safety and accessibility. This review commences with a systematic exploration of the anatomical structure of the ENS, including the myenteric and submucosal plexuses, its cellular constituents such as enteric neurons and enteric glial cells, and its core physiological functions, encompassing the regulation of gastrointestinal motility, the secretion–absorption balance, and the maintenance of immune homeostasis. Subsequently, it delineates the classification, distribution, and properties of essential dietary components, encompassing polyphenols, short-chain fatty acids, amino acids and their derivatives, as well as prebiotics and probiotics. Additionally, it examines the mechanisms through which these substances modulate the physiological functions of the ENS, including the regulation of intestinal motility, support for neuronal survival and network integrity, and the maintenance of neuro-immune homeostasis. The review concludes by highlighting current limitations—including reliance on rodent models, unclear human ENS mechanisms, and imprecise interventions—and proposes future directions focused on precision medicine, clinical translation, and advanced tools like single-cell sequencing and targeted delivery systems. Full article

Colorectal cancer (CRC) is the third most common cancer worldwide, imposing a significant burden on public health. Despite the use of various therapeutic strategies, the prognosis for patients with metastatic and drug-resistant CRC remains poor, which underscores the need for further investigations into cancer mechanisms to develop more effective treatments. Rodents, particularly mice, are the most frequently used animal models for CRC research. However, as the demand for more precise simulations and higher ethical standards in animal experimentation grows, the applicability of rodent models may face increasing limitations. This review highlights a variety of non-rodent animals, including model organisms such as zebrafish (Danio rerio), fruit flies (Drosophila melanogaster), and Caenorhabditis elegans (C. elegans), as well as the chorioallantoic membrane (CAM) model and mammals such as rabbits (Oryctolagus cuniculus), dogs (Canis lupus familiaris), and pigs (Sus scrofa domesticus), which have been utilized in CRC research. Each of these alternatives offers specific advantages in certain areas of cancer research. Their use has enabled new insights into the mechanisms of carcinogenesis, metastasis, and drug resistance in CRC, as well as the development of novel therapies. Full article

Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with neurodevelopmental toxicity, yet the effects of exposure during adolescence and adulthood remain underexplored. This scoping review evaluates the neurotoxic outcomes of post-weaning PCB exposure in rodent models. A comprehensive literature search was conducted across PubMed, Embase, and Scopus. Studies were screened according to PRISMA guidelines. Articles were included if they reported neurotoxic or behavioral outcomes in mice or rats exposed to PCBs during post-weaning stages. Thirty-five studies met the inclusion criteria, encompassing a variety of PCB congeners and mixtures administered via oral, inhalation, or intraperitoneal routes. Reported neurotoxic outcomes included histological and morphological brain changes, oxidative stress, disrupted calcium signaling, altered neurotransmitter systems, apoptosis, and gene expression alterations. These outcomes were assessed using diverse methodological approaches, including immunohistochemistry, biochemical assays, and gene expression profiling. Behavioral outcomes affected by PCB exposure included locomotion, anxiety-like behavior, learning and memory, motor coordination, and cognitive flexibility. Effects were often exposure-specific and sex-dependent, with limited female-focused studies and integrative molecular-behavioral assessments. These findings highlight the broad neurotoxic potential of PCBs following adolescent or adult exposure and underscore the need for further mechanistic, sex-specific research to inform health risk assessment and regulatory policy. Full article

Nonhuman primates are often considered as the best animal models for studying human ophthalmological diseases, but the metabolomic composition of primate ocular tissues remains largely unknown. In this work, we performed NMR-based quantitative metabolomic analysis of crab-eating macaque (Macaca fascicularis) serum, aqueous (AH) and vitreous (VH) humors, and lens. We determined the concentrations of a total 94 compounds in these tissues, 13 of which play important cytoprotective roles. The obtained metabolomic profiles represent the baseline metabolomes of blood and eye tissues characteristic of young healthy M. fascicularis adults. The obtained data indicate that antioxidants ascorbate and ergothioneine are actively pumped from blood into AH with the use of specific transporters, and there is an active transport against the concentration gradient of amino acids from AH into the lens. The comparison of metabolomic profiles of M. fascicularis and human ocular tissues shows a very high degree of similarity at the qualitative level, while the quantitative compositions of cytoprotective compounds (antioxidants, osmolytes, and ultraviolet filters) in M. fascicularis and human lenses differ. Despite these differences, from the metabolomic viewpoint, M. fascicularis are much better models of human diseases than rodents, which are often used in studies of eye disorders. Full article

This study was conducted to assess the involvement of two lizard species: the sand lizard (Lacerta agilis) and the common lizard (Zootoca vivipara), and their Ixodes ricinus ticks, in the circulation spirochetes of the Borrelia burgdorferi s.l. complex. Lizards were captured at three study sites in suburban areas of western Poland. Common lizards were less abundant and occurred only at one site. A total of 1129 ticks were collected from 167 sand lizards and 164 individuals from 42 common lizards. Biopsies of the distal part of the lizard tail were taken from 172 animals. All samples that tested positive by real-time PCR underwent subsequent nested PCR targeting the flaB gene, followed by sequencing. At least 6.3% of I. ricinus ticks (MIR) from L. agilis, and 6.1% from Z. vivipara, were infected. Borrelia lusitaniae was the most prevalent genospecies in L. agilis-derived ticks, accounting for 73.2% of all infected samples, followed by B. burgdorferi s.s. (23.0%). Conversely, this latter species prevailed (90%) over B. lusitaniae (10%) in tick samples from Z. vivipara. Therefore, we believe that sand lizards are competent reservoir hosts for B. lusitaniae, while the role of Z. vivipara for this species is unclear. The high prevalence of B. burgdorferi s.s. was also found in infected larval samples (40.7%) and biopsies (60%) of L. agilis. Thus, in our opinion, these two lizard species could be another group of reservoir hosts for this human pathogen, along with birds and rodents. Full article

Ischemia–reperfusion is a rapidly evolving cascade that involves a variety of metabolic shifts whose precise timing and sequential order are still poorly understood. Clarifying these dynamics is critical for understanding the core injury trajectory of stroke and for refining time-delimited therapeutic interventions. More broadly, continuous in situ monitoring of the middle-cerebral-artery occlusion process at the system level has not yet been achieved. Here, we report the first single-subject high-resolution spatiotemporal resolution metabolic maps of the ultra-early phase of ischemic stroke in a rodent model. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging mapped a metabolic abnormality area in the ischemic hemisphere that propagates from the striatum to the cortex. Microdialysis probes were then stereotaxically implanted within this metabolic abnormality area, capturing 10,429 metabolites that resolved into 16 temporally distinct trajectories aligned with probe insertion, ischemic injury, and reperfusion injury. Analysis of specific metabolic pathways mainly revealed that the delayed clearance of metabolic waste (urea and tryptamine) during early reperfusion, the transient attenuation of the citrate-to-oxaloacetate buffering gradient within the TCA cycle, and the accumulation of extracellular branched-chain amino acids all play crucial roles in shaping the injury trajectory. Simultaneously, the depletion of cellular repair mechanisms (pyrimidine synthesis) in the early phase of reperfusion also warrants our attention. These findings provide novel insights into the molecular basis and mechanisms of ischemia–reperfusion and offer a comprehensive resource for further investigation. Full article

Quantifying sex-specific dietary differences in small mammals reveals the internal resource allocation mechanisms within a species and provides new insights for ecosystem management and conservation practices. The plateau pika (Ochotona curzoniae) and plateau zokor (Eospalax baileyi) are dominant small mammals that exhibit distinct lifestyles and social structures on the Qinghai-Tibetan Plateau. Despite the fact that the diets of both species have been extensively studied, sex-specific dietary differences have rarely been investigated. This study employed DNA metabarcoding combined with a self-constructed plant DNA barcode database to analyze the diet composition and trophic niche of male and female plateau pika and plateau zokor during the growing season. The results showed that male and female plateau pika consumed 39 and 37 plant species, respectively, and male and female plateau zokor consumed 38 and 39 plant species, respectively. With respect to the plateau pika, males showed a significantly higher intake of Phlomoides umbrosa than females (p < 0.05), whereas females consumed a significantly greater proportion of tuberous plants (p < 0.05). Females also exhibited a significantly greater dietary diversity and trophic niche breadth than males. But there was no significant difference in dietary diversity and trophic niche breadth between the sexes in the plateau zokor. In conclusion, our results show that dietary differences between males and females depend on each species’ lifestyle. Social, surface-living pikas show apparent sex-based differences, while solitary, underground-living zokors do not. Full article

Depression is a common mental disorder during gestation, posing potential risks to fetal development and leading to behavioral and psychiatric alterations in offspring. Pharmacological intervention, particularly with selective serotonin reuptake inhibitors (SSRIs), is often necessary. This study investigated the effects of fluoxetine (F) on behavioral and memory changes in rodent offspring following maternal gestational and lactation treatment, as well as potential alterations in hippocampal cellularity compared to control (C) progeny. Methodologies included the Morris water maze, elevated plus maze, activity monitoring, parental behavior assessments, and isotropic fractionation for the quantification of hippocampal cells and neurons. Results indicated that maternal fluoxetine exposure significantly affected the body mass, brain weight, and hippocampal metrics of the offspring, aligning with the ‘selfish brain’ hypothesis. Notably, dams treated with fluoxetine showed reduced parental care, leading to offspring with increased activity levels but no changes in anxiety-like behaviors. However, while there was a decline in learning and memory retention, as assessed by the Morris water maze, working and reference memory did not differ significantly from those of controls. This study establishes an association between fluoxetine treatment, increased hippocampal neuron density, and behavioral changes related to memory and hyperactivity, with implications for understanding behavioral disorders and informing future therapeutic interventions. Full article

Background/Objectives: Sclerostin is a glycoprotein produced by osteocytes that regulates osseous remodeling, particularly in the context of orthodontic tooth movement. The purpose of the current systematic review is to assess the effect of orthodontic tooth movement (OTM) on sclerostin expression (SE) in the alveolar bone matrix (ABM). Methods: Indexed databases including PubMed, Embase and Web of Science were searched without time and language restrictions up to and including March 2025. Results: Seven studies performed on 8- to 12-week-old male rodents were included. The magnitude of orthodontic forces ranged from 10–120 g. Distalization and mesialization of the maxillary first molar were performed in one and six studies, respectively. In two studies, SE was increased on the compression and tension sides during OTM. In one study, SE is increased and decreased on the compression and tension sides, respectively; and another reported no difference in SE on the compression and tension sites during OTM. Two studies did not report data on SE on the control-sites (sites unexposed to OTM). Sample-size estimation was not performed in any of the included studies. All studies had a high risk of bias (RoB) and low certainty of evidence (CoE). Conclusions: Sclerostin may play a regulatory role in ABM during OTM. However, current evidence is limited by methodological inconsistencies, high RoB, and low CoE. Well-designed, power-adjusted studies using standardized protocols are required to establish reproducible findings and assess the translational potential of SE in orthodontics. Full article

Contact dermatitis (CD) is a common inflammatory skin condition with irritant etiology or a delayed-type hypersensitivity called allergic contact dermatitis (ACD). Contact hypersensitivity (CHS) is a widely used rodent model of ACD and similarly consists of two phases: sensitization and elicitation. To trigger CHS, low-molecular-weight haptens, such as DNFB or TNCB, are commonly applied. However, the characterization of the induced immune response remains incomplete. Our aim was to characterize the immune response after first and repeated exposures to model haptens. First exposure to DNFB or TNCB led to significant ear swelling, with DNFB causing a more pronounced effect. DNFB enhanced neutrophil infiltration, whereas TNCB led to macrophage, dendritic cell, and helper T cell accumulation. Repeated DNFB exposure did not aggravate edema significantly, while TNCB re-exposure enhanced edema formation and induced neutrophil granulocyte, dendritic cell, and helper and cytotoxic T cell accumulation. Our results demonstrate that a hapten-specific immune response is induced during both phases of CHS. A detailed understanding of allergen-specific immune responses is crucial for the appropriate selection of the model and for gaining deeper insight into the mechanisms of inflammatory skin diseases. These findings may contribute to the targeted selection of haptens. Full article

The structure and assembly mechanism of wild animal gut microbiota represent persistent research hotspots. Among, the impact of geographic factors on the bacterial co-occurrence network characteristics and assembly mechanism of the gut microbiome remains unclear. Therefore, this study analyzed the gut microbiome of Niviventer confucianus and Apodemus agrarius from Anhui and Hubei provinces. The same alpha diversity pattern was found in the gut microbiome of species from the same region. The gut microbiome of the two rodent species in Anhui region exhibited “small world” characteristics, such as nodes with more local connections to allow interaction information (such as metabolites) to rapidly spread throughout the entire microbial community. In addition, dispersal limitations and heterogeneous selection accounted for higher proportions of the gut microbiome in the rodents from the Anhui and Hubei regions, respectively. The higher proportion of heterogeneous selection may exacerbate selection pressure in the Hubei region. Multiple regression on distance matrices analysis revealed that geographic region exerted a limited but significant influence (0 < R² < 0.2, * p < 0.05) on the gut microbiome, surpassing the effects of host phylogeny, gender, and weight. Nevertheless, the roles of regional factors—such as environmental microbes, pollutants, and diet—remain unexamined, and their potential as key drivers of microbiota variation in these rodents warrants further investigation. Full article