Search Results (2,148)

Background/Objectives: Acute pancreatitis (AP) lacks disease-modifying pharmacotherapy. Neuroimmune, serotonergic, and redox-regulated pathways may modulate inflammatory amplification and acinar injury, although pharmacovigilance data link some psychotropic drug classes to AP risk. This review synthesized controlled rodent studies evaluating neuromodulatory interventions with serotonergic, stress-axis, or ferroptosis-linked targets in experimental AP. Methods: PubMed, Scopus, eLIBRARY.ru, and Elicit were searched in January 2026, supplemented by Google Scholar audit and citation chasing. Eligible studies were controlled in vivo rodent experiments using validated AP models with quantitative outcomes. Intervention timing was classified a priori as a primary analytic variable. Risk of bias was assessed with SYRCLE. A prespecified audit showed that no subset met the criteria for quantitative pooling because of heterogeneity in model class, compounds, timing, outcome definitions, units, and sampling timepoints. Mechanism-stratified qualitative synthesis was therefore performed. The protocol was registered on OSF (doi: 10.17605/OSF.IO/CZXDJ). Results: Nine studies (1992–2023) yielded 410 outcome rows across three mechanistic strands. Serotonergic modulation (5-HT₂/5-HT₂A-focused; six studies) reduced serum amylase/lipase (−37% to −65% vs. disease controls) and histological injury, with receptor-selectivity data supporting 5-HT₂A-mediated mechanisms. Stress-axis modulation with thiadiazine L-17 reduced 7-day mortality in two severe models (from 50–70% to 30%). Olanzapine attenuated ferroptosis-linked injury via off-target antioxidant activity independent of serotonergic receptors. All interventions were prophylactic, peri-induction, or very early post-induction; no delayed therapeutic-window studies were identified. Most SYRCLE domains were unclear, particularly allocation concealment and blinding-related procedures. Conclusions: Neuromodulatory pathways modulate experimental AP in rodents, but evidentiary strength differs across mechanistic strands. Inference is constrained by absent therapeutic-window testing, heterogeneous endpoints, and reporting deficits. The findings support mechanism-level target prioritization rather than clinical repurposing. Full article

Acute liver failure is often accompanied by neurological disturbances collectively referred to as hepatic encephalopathy (HE), characterized by neuroinflammation and subsequent cognitive decline. Insulin-like growth factor 1 (IGF1) is a neuroprotective peptide with anti-inflammatory properties in the brain. The role of IGF1 in cognitive deficits and neuroinflammation during HE remains largely unexplored. In C57Bl/6 mice, HE was established through an intraperitoneal injection of azoxymethane (AOM), and tissues were collected at defined time points during disease development. IGF1 expression in the cortex was downregulated following AOM administration. Central infusion of recombinant mouse IGF1 (rmIGF1) before AOM injection resulted in delayed neurological impairment, reduced microglial activation, and decreased proinflammatory cytokine and chemokine production in AOM mice. In vitro, rmIGF1 and conditioned media derived from rmIGF1-treated primary neurons attenuated phagocytic activity and C–C motif chemokine ligand 2 (CCL2) production in the microglial cell line EOC-20. Collectively, our results show that IGF1, whose levels decline during HE, alleviates neuroinflammation and improves the pathological state of AOM-treated mice through the suppression of microglial activation and the regulation of neuron–microglia paracrine communication. Full article

Background: Magnetic resonance spectroscopic imaging (MRSI) offers valuable metabolic information for assessing brain tumor progression and therapeutic response, but its performance in rodent models is often hindered by the low signal-to-noise ratio (SNR) and spatially heterogeneous spectral quality, particularly in peripheral voxels. These issues reduce the number of usable spectra available for quantitative and classifier-based analyses. To address this, we implemented a multi-voxel MRSI-semiLASER sequence—widely recommended in clinical practice—on a 7T Bruker Biospec system running ParaVision 5.1 to improve spectral homogeneity in mouse brain tumor studies. Results: Compared with the vendor CSI-PRESS sequence, MRSI-semiLASER produced more uniform spectra across the grid and achieved up to a 1.2-fold SNR increase in murine glioma, enabling a 20% reduction in slice thickness without compromising spectral quality. Importantly, the sequence produced a substantial gain in the proportion of spectra amenable to analysis, particularly in outer grid voxels that frequently fail with CSI-PRESS. The implemented MRSI-semiLASER sequence and instructions are openly available to the community. Conclusions: MRSI-semiLASER improves spectral homogeneity, increases the proportion of usable spectra, and supports higher spatial detail. These technical improvements may enhance data yield per subject and may facilitate future applications such as more robust pattern recognition workflows and greater data efficiency in longitudinal studies, although such aspects were not evaluated here. Full article

Recent years have seen growing interest in the relationship between the heart and kidney disease, resulting in the general term cardiorenal syndrome (CRS) being coined for disorders involving both the heart and kidneys. However, no accurate animal model exists that can replicate the specific cardiorenal associations characteristic of the human CRS subtype. Preclinical studies published between 1990 and 2024 were identified from online electronic databases. These were reviewed and subjected to meta-analysis according to PRISMA, with the quality assessed using the SYRCLE tool. In total, the review and analysis included 251 papers discussing the rodent presentation of cardiorenal associations, expressed by various hemodynamic, echocardiographic and histopathologic parameters, and selected molecular hallmarks. A wide spectrum of invasive and non-invasive animal approaches has been proposed for CRS. Numerous approaches evoked cardiorenal impairments by elevating systemic pressure. Among the “one-hit” models, Dahl/SS and ISO-HF most commonly resulted in cardiac and renal alterations mimicking CRS-2, while DOCA-salt or STZ were the most likely to elicit cardiac injury in progression of renal failure. The clinical relevance of “two-hit” animal models of cardiorenal associations merits another study. Full article

Monkeypox (Mpox), caused by the monkeypox virus (MPXV), has re-emerged as a significant global public health concern, particularly following the 2022 outbreaks. Understanding its transmission dynamics is essential for designing effective control strategies. In this study, we develop and analyze a deterministic compartmental model that captures both human-to-human and rodent-to-human transmission pathways in order to better reflect the zoonotic nature of the disease. The model is investigated using qualitative and quantitative analytical techniques, including stability analysis, bifurcation theory, and sensitivity analysis. The basic reproduction number, $R_0$, is derived and used to determine threshold conditions for disease persistence or eradication. We show that the disease-free equilibrium is globally asymptotically stable when $R_0<1$, while an endemic equilibrium exists and is stable when $R_0>1$. Furthermore, the model exhibits backward bifurcation, indicating that reducing $R_0$ below unity may not be sufficient for disease elimination. Sensitivity analysis identifies key parameters driving transmission, particularly the rodent-to-human and human-to-human contact rates. Numerical simulations further demonstrate that reducing cross-species transmission and improving isolation of infected individuals significantly decrease disease burden. These findings highlight the complexity of Mpox transmission and emphasize that effective control requires not only lowering $R_0$, but also targeting critical transmission pathways. This study provides useful insights for public health planning by identifying priority intervention strategies such as minimizing rodent–human interactions and strengthening isolation measures. Full article

Chikungunya virus (CHIKV) pathogenesis research has long been constrained by the lack of suitable immunocompetent rodent models. Through serial passaging in A129 and C57BL/6 mice, we obtained an adapted strain (CHIKV-Adapt) harboring an E2-K200R substitution along with non-structural protein mutations. Phenotypic analysis in C57BL/6 mice, BALB/c mice, and hamster models demonstrated that compared to the wild-type virus CHIKV-Adapt induced significantly higher and more prolonged viremia, broader tissue tropism, and more severe internal joint inflammation, without exacerbating external swelling. Notably, the K200R mutation did not alter the viral replication kinetics in vitro and was predicted not to affect its binding pattern to the MXRA8 receptor. Furthermore, mice challenged 160 days after primary infection exhibited nearly complete protective immunity. These findings indicate that E2-K200R is a critical adaptive mutation that, together with accompanying non-structural mutations, significantly enhances CHIKV replication capacity and pathogenicity in immunocompetent rodents without changing its in vitro replication ability or predicted receptor-binding mode. The acquisition of this adapted strain provides a new tool for CHIKV pathogenesis research and vaccine evaluation. Full article

Background/Objectives: Chemically induced hepatotoxicity is widely used in experimental research to model liver disease pathophysiology and to support preclinical studies. Thioacetamide (TAA) is a well-established hepatotoxic agent in conventional laboratory rodents; however, its effects in synanthropic rats—characterized by genetic heterogeneity and chronic environmental exposure—remain poorly defined. This study aimed to establish and characterize a preclinical model of TAA-induced hepatotoxicity in synanthropic rats and to assess its relevance for experimental liver disease research. Methods: Female synanthropic rats representing four phenotypic variants (albino, mottled, black, and brown; total n = 132) were housed under controlled conditions and assigned to control or TAA-treated groups. TAA was administered intraperitoneally at doses ranging from 200 to 300 mg/kg. Clinical parameters, including body weight and vital signs, were periodically monitored. Hematological profiles and serum biochemical markers of liver function were analyzed. Hepatic injury was evaluated by histopathological examination using hematoxylin–eosin staining. Statistical analyses were performed using R software, with p ≤ 0.05 considered statistically significant. Results: TAA-treated rats developed consistent clinical manifestations of hepatotoxicity, including progressive weight loss and reduced activity. Biochemical analyses revealed significant increases in serum transaminases, gamma-glutamyl transferase, and alkaline phosphatase, accompanied by alterations in hematological parameters. Histological evaluation demonstrated dose-dependent liver injury characterized by centrilobular necrosis, inflammatory infiltration, hepatocellular degeneration, and architectural disruption across all synanthropic rat variants. Conclusions: Synanthropic rats exhibit reproducible biochemical, hematological, and histopathological features of TAA-induced liver injury comparable to those reported in conventional laboratory strains. This model represents a robust preclinical approach for studying chemically induced hepatotoxicity and may provide enhanced translational relevance due to its genetic and environmental heterogeneity. Full article

Background/Objectives: Previous research demonstrates higher sodium retention with increasing levels of dietary salt in some populations. Our objective was to determine whole-body sodium retention and sodium distribution on high and low salt diets using rodent models. Methods: Whole body retention of orally dosed Na-22, a gamma emitter, was measured in female growing and adult Sprague-Dawley rats on high (3.1% by wt. of diet) and low salt (0.13% by wt. of diet) diets. In a second study, whole-body sodium retention was compared between destructive inductively coupled plasma optical emission spectroscopy (ICP-OES) and neutron activation analysis (NAA) in adult male and female C57BL/6 mice. Results: Whole body retention of Na-22 was not different due to the age of rats on a high salt diet, but rats fed the high salt diet excreted Na-22 much more rapidly than rats fed a low salt diet. In mice, neither sodium retention nor tissue distribution was affected by dietary salt. Bland–Altman analysis indicated overall agreement between NAA and ICP-OES measurements, with observed systematic positive bias. Conclusions: Dietary salt had little effect on retention in normotensive rodents and should be studied in hypertensive models. Full article

Roselle beverage residue (RBR), a by-product of Hibiscus sabdariffa L. processing, retains bioactive compounds, including soluble and insoluble dietary fiber and polyphenols. Its antihyperglycemic effect in type 2 diabetes mellitus (T2DM) has been previously demonstrated; however, its role in lipid metabolism remains unknown. This study assessed the preventive and therapeutic potential of RBR on dyslipidemia and hepatic steatosis in a rodent model of late-stage T2DM characterized by hyperglycemia and hypoinsulinemia. Male Wistar rats with T2DM induced by a high-fat and high-fructose diet combined with streptozotocin received 6% RBR supplementation as either a preventive intervention (starting at week 1 in healthy rats or week 9 in insulin-resistant rats) or a therapeutic intervention (starting at week 14 in diabetic rats). After 17 weeks, RBR supplementation significantly reduced serum triglycerides and total cholesterol, attenuating hepatic lipid accumulation regardless of the timing of intervention. Hepatic Acadm expression, involved in fatty acid β-oxidation, was significantly upregulated in rats treated with RBR from week 1 and 9, whereas no significant modulation was observed for genes related to fatty acid synthesis or uptake. These findings suggest that RBR supplementation may contribute to improving lipid metabolism and hepatic steatosis in a rat model of late-stage T2DM. Full article

Chronic d-galactose (d-gal) treatment is a model to induce accelerated aging-like phenotypes in rodents. However, the sex differences in behavioral and musculoskeletal manifestations of this model are not well understood. Heme oxygenase-1 (HO-1) is a cytoprotective protein that may have anti-aging properties. The goal of this study was to better understand the sex differences in the behavioral and musculoskeletal effects of chronic d-gal treatment in C57BL/6J mice, as well as the role of HO-1 induction or inhibition. Eight-week-old male and female mice received daily saline or d-gal injections (500 mg/kg, s.c.) for 12 weeks. After this time, mice in the d-gal group were randomized into three groups (n = 6/group/sex): d-gal, d-gal + cobalt protoporphyrin (CoPP) (5 mg/kg, s.c. weekly), and d-gal + zinc deutroporphyrin bisglycol (ZnBG) (42 mg/kg, i.p. triweekly) for a period of 4 weeks. Open-field, novel-object recognition, Barnes maze, grip strength, micro-computed tomography (µ-CT), histology, and protein analysis were performed. Chronic d-gal treatment resulted in a sexual dimorphic response, with female mice being more prone to develop deficits in both short- and long-term spatial memory as well as in non-spatial memory. Male mice exhibited deficits only in long-term spatial memory when treated chronically with d-gal. Inhibition of HO-1 was protective in both females and males. Chronic d-gal treatment did not accelerate the development of osteoporosis or sarcopenia in either males or females. Our results demonstrate a sexual dimorphic response to the chronic effects of d-gal treatment on aging, with greater effects in females than in males, which is dependent on HO-1. Full article

Background: Incorporating sex as a biological variable (SBV) is recognized as essential for improving the reliability, reproducibility, and generalizability of pharmacological research. This principle is codified in international policies and guidelines, yet implementation remains uneven, especially in phytomedicine. Phytomedicines are a major component of healthcare worldwide, with 65% of the global population relying on them in both regulated and traditional contexts. Globally, phytomedicines are used by males, females, intersex and non-cis gender persons, all of whom may present specific safety and efficacy considerations and warrant full inclusion in pre-clinical to clinical research pipelines. However, in contemporary settings, phytomedicine lags in SBV best practices relative to Western allopathic standards for research design. Methods: We conducted a non-systematic review and in silico data mining to quantify sex/gender representation in recent preclinical and clinical phytomedicine studies, complemented by targeted case studies of sexually dimorphic safety/efficacy. We also summarize the historical role of women and gender-diverse people as users and providers within Traditional and Integrative Medical Systems (TIMSs). Results: Across rodent and human studies, females are under-represented relative to males, and sex is rarely reported for cell lines. Intentional inclusion of intersex and other gender-diverse populations is largely absent. Case studies illustrate plausible sex-associated differences in pharmacokinetics, pharmacodynamics, and adverse event profiles. TIMSs historically address women’s health needs and include substantial participation by female practitioners; however, contemporary SBV practices remain less standardized than in Western allopathic pipelines. Conclusions: SBV integration in phytomedicine is needed to strengthen safety, efficacy, and regulatory-grade evidence. Practical barriers include legacy datasets without sex metadata, limited intersex animal models, and uneven resources across settings. We outline feasible, stepwise practices to improve SBV adoption in a manner compatible with TIMS contexts and recommend expanding current guidelines to better support diverse research environments while maintaining scientific rigor. Full article

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness characterized by disrupted physiologic vascularization followed by pathologic neovascularization, classically organized around the insulin-like growth factor-1 (IGF-1)–vascular endothelial growth factor (VEGF) axis in the retina. Increasing evidence suggests that early-life gut dysbiosis may act as an upstream modifier of this biphasic process. In this review, we synthesize human cohort studies, multi-omics analyses, and experimental animal models examining associations between the neonatal gut microbiome and ROP. Preterm infants who develop severe ROP demonstrate enrichment of facultative anaerobes and reduced acquisition of obligate anaerobes, alongside altered predicted metabolic capacity. Microbiome-derived metabolites, including short-chain fatty acids, bile acid derivatives, and lipid mediators, have been shown in experimental systems to influence systemic IGF-1 production, hypoxia-inducible factor-1α stabilization, and VEGF signaling. Rodent oxygen-induced retinopathy models offer a translation framework to assess the functional link between microbial perturbation and retinal angiogenic responses. Collectively, these findings support a conceptual microbiome–IGF-1–VEGF–retina axis in which early intestinal dysbiosis may modulate inflammatory tone, metabolic signaling, and retinal vascular development. Although current evidence remains largely associative, integrating microbiome profiling with mechanistic and longitudinal studies may clarify potential causal pathways and identify novel biomarkers or preventive strategies for severe ROP. Full article

Background/Objectives: Fucoidan is a sulfated long-chain polysaccharide found mainly in sea cucumbers and brown algae. Studies suggest that fucoidan may play a role in treating various diseases, including metabolic syndrome and diabetes mellitus. The purpose of the current study was to investigate the effects of fucoidan isolated from brown algae on diabetic hyperglycemia and dyslipidemia. Methods: Two databases, PubMed and Embase, were searched to identify peer-reviewed articles written in English and published up to 30 June 2025. Studies reporting blood glucose and serum/plasma lipid levels of diabetic rodents treated with fucoidan or vehicle were included in the meta-analysis. Results: Forty-seven studies reported blood glucose levels. The pooled effect size for blood glucose levels was −2.26 (95% CI: −2.78 to −1.75), with substantial heterogeneity. Subsequent analyses showed that diabetic dyslipidemia was markedly improved in the fucoidan-treated group compared with the control. Conclusions: Fucoidan treatment could improve hyperglycemia and dyslipidemia in diabetic rodents. Full article

N-Lactoyl-phenylalanine (Lac-Phe), identified in 2022 as an exercise-inducible signaling metabolite, is formed by carnosine dipeptidase 2 via conjugation of lactate and phenylalanine. Its circulating levels rise sharply after intense exercise in mice, humans, and racehorses, reflecting increased glycolytic flux. Beyond exercise, Lac-Phe also rises with feeding and metformin, positioning it as a potential integrator of energy intake, expenditure, and metabolic homeostasis. Centrally, Lac-Phe may contribute to appetite suppression by inhibiting hypothalamic orexigenic agouti-related protein neurons, primarily observed in obese rodent models, while sparing anorexigenic pro-opiomelanocortin neurons, thereby reducing food intake, promoting weight loss, and improving glucose tolerance in obese models without altering energy expenditure. Peripherally, it drives anti-inflammatory M2 macrophage polarization, ameliorating colitis and aiding recovery after spinal cord injury via NF-κB suppression and reactive oxygen species reduction. As a biomarker, Lac-Phe may offer advantages over lactate in reflecting mitochondrial dysfunction in conditions such as MELAS, sepsis, and NADH-reductive stress; however, these observations derive mainly from small-scale or exploratory studies and require prospective validation. Recent studies from 2024 to 2025 further reveal its partial and context-dependent role in mediating metformin’s effects, intensity- and sex-dependent responses, renal clearance via SLC17A1/3 transporters, and links to exercise-induced redox adaptations. The first human phase I trial (NCT06743009), launched in 2025, is assessing the metabolic effects of Lac-Phe in obesity. This Perspective summarizes Lac-Phe biosynthesis, physiological mechanisms, including its emerging but largely correlative connections to redox homeostasis, and therapeutic promise, underscoring its potential relevance for exercise-mimicking strategies in metabolic, inflammatory, and redox-related disorders. Full article

The discovery of the glymphatic system (GS) transformed understanding of central nervous system homeostasis by revealing a brain-wide network that facilitates cerebrospinal and interstitial fluid exchange along perivascular pathways. This system clears metabolic waste and maintains the precise ionic environment required for neuronal function through the coordinated action of astrocytic aquaporin-4 channels and intact perivascular architecture. Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, alters physiological barriers through pathological angiogenesis, compression of perivascular spaces, depolarization of aquaporin-4 at astrocytic endfeet, and obstruction of venous and lymphatic drainage. This narrative review synthesizes current experimental and clinical literature identified through targeted searches of PubMed and Scopus to examine interactions between glioblastoma, glymphatic system dysfunction, and tumor microenvironmental changes. To minimize selection bias, studies were categorized according to evidence source and experimental design. Evidence from rodent models and advanced imaging demonstrates as tumor growth impairs glymphatic function, the resulting dysfunction promotes tumor progression by enabling accumulation of pro-tumorigenic growth factors, inflammatory mediators, and acidic metabolites, while elevated interstitial fluid pressure limits drug delivery. Impaired antigen drainage further diminishes immune surveillance, contributing to the immunosuppressive microenvironment that limits immunotherapy efficacy. A critical evaluation of these mechanisms highlights how the glymphatic system influences disease progression and suggests novel avenues for diagnostic imaging and therapeutic intervention. Although significant challenges remain in modeling human fluid dynamics, understanding these hidden networks offers a promising frontier for strategies aimed at restoring cerebral clearance and improving clinical outcomes. Full article