Search Results (319)

Non-human primates (NHPs) are close relatives of humans and can serve as hosts for many zoonotic pathogens. They play crucial role in spreading antimicrobial resistant bacteria (AMR) to humans across various ecological niches. The spread of antimicrobial resistance in NHPs may complicate wildlife conservation efforts, as it may threaten domestic livestock, endangered species as well as human’s health. This review analyses the existing literature on the prevalence of AMR in NHP species, including Rhinopithecus roxellana, Macaca fascicularis, and Sapajus nigritus, to create awareness in all stake holders involve in the fight against AMR on the serious potential threats that these primates pose. Methods: We performed a comprehensive literature search using the PubMed (National Library of Medicine-NLM), Scopus (Elsevier), Web of Science Core Collection (Clarivate Analytics), Springer Link (Springer), and Science Direct (Elsevier) databases until January, 2025. The search strategy combined terms from the areas of non-human primates, antibiotic resistance, antimicrobial resistance, and antibacterial resistance genes (ARGs). Studies that isolated bacteria from NHPs and assessed phenotypic resistance to specific antibiotics as well as studies that identified ARGs in bacteria isolated from NHPs were included. Data were synthesised thematically across all included studies. Results: A total of 37 studies were included (explained as Cercopithecidae (n = 23), Callithrix (n = 6), Cebidae (n = 4), Hominidae (n = 3), and Atelidae (n = 1)). The results showed that the most common ARB across the various NHPs and geographical settings was Staphylococcus spp. (45.95%) and Escherichia spp. (29.73%). The tested antibiotics that showed high levels of resistance in NHPs included Tetracycline (40.54%), Ciprofloxacin (32.43%), and Erythromycin (24.34%), whereas ermC, tetA, tetM, aadA, aph (3″)-II, and qnrS1 were the most widely distributed antibiotic resistance genes in the studies. Conclusion: NHPs are potential natural reservoirs of AMR, therefore global policy makers should consider making NHPs an indicator species for monitoring the spread of ARB. Full article

Background: A spinal cord contusion injury is among the most clinically relevant models for studying pathophysiology and for developing potential therapeutic interventions for spinal cord injuries (SCI). Methods: In this study, we implemented an intra-operative ultrasound (IOU) approach to precisely locate and examine the lesion site at 5 and 10 min post-injury after a cervical hemi-contusion injury in a non-human primate (NHP) model. We assessed acute lesion progression from 5 to 10 min and then compared that to the lesion extent as measured by MRI 3 weeks later. Results: We observed a small increase in the rostrocaudal and mediolateral lesion area (mm²) from 5 to 10 min and a further 26% increase in the mediolateral lesion extent when comparing 5 and 10 min to 3 weeks post-injury. Conclusions: By enabling high-resolution ultrasound visualization of the hemicontusion lesion in vivo, this approach can provide critical insights into the early progression of SCI. It can help with further refining this preclinical SCI model and provide significant predictive value for the animals’ recovery post-injury. Full article

This review provides a mechanistic framework to strategically design nanoparticles capable of efficiently crossing the blood–brain barrier (BBB), a critical limitation in neurological treatments. We systematically analyze nanoparticle–BBB transport mechanisms, including receptor-mediated transcytosis, adsorptive-mediated transcytosis, and transient barrier modulation. Essential nanoparticle parameters (size, shape, stiffness, surface charge, and biofunctionalization) are evaluated for their role in enhancing brain targeting. For instance, receptor-targeted nanoparticles can significantly enhance brain uptake, achieving levels of up to 17.2% injected dose per gram (ID/g) in preclinical glioma models. Additionally, validated preclinical models (human-derived in vitro systems, rodents, and non-human primates) and advanced imaging techniques crucial for assessing nanoparticle performance are discussed. Distinct from prior BBB nanocarrier reviews that primarily catalogue mechanisms, this work (i) derives quantitative ‘design windows’ (size 10–100 nm, aspect ratio ~2–5, near-neutral ζ) linked to transcytosis efficiency, (ii) cross-walks human-relevant in vitro/in vivo models (including TEER thresholds and NHP evidence) into a translational decision guide, and (iii) integrates regulatory/toxicology readiness (ISO 10993-4, FDA/EMA, ICH) into practical checklists. We also curate recent (2020–2025) %ID/g brain-uptake data across lipidic, polymeric, protein, inorganic, and hybrid vectors to provide actionable, evidence-based rules for BBB design. Full article

Background: Adeno-associated viral (AAV) vectors are the leading platform for gene therapy, but common delivery routes show limited spread to distal cortical structures, hence the utility of direct, intrathalamic infusions for broader transgene distribution. In this preliminary study, we recapitulate previous studies targeting the thalamus as a conduit to achieve cortical transgene spread and showcase novel data evaluating biodistribution of a green fluorescent protein (GFP) using cryo-fluorescence tomography (CFT). For the first time in nonhuman primates (NHPs) and coupled with magnetic resonance imaging (MRI)-guidance, we demonstrated the application of CFT as a powerful tool to map out vector distribution in the NHP brain. Methods: Briefly, a single thalamic infusion was performed in African green monkeys using ClearPoint’s navigational platform to deliver an AAV serotype 2 vector containing a GFP payload. Transgene biodistribution was assessed in the left and right hemispheres using CFT and histological analysis, respectively. Results: Infusions were successfully performed with sub-millimetric target accuracy and with minimal error, achieving ~86% thalamic coverage with the largest infusion volume. Histology confirmed the presence of the GFP transgene, with the strongest signal in the cerebral gray/white matter and internal capsule, while CFT allowed for the three-dimensional detection of the transgene starting at the site of infusion and spreading to multiple cortical regions. Conclusions: These findings suggest that by combining MRI-guided technology with CFT imaging, it is feasible to map whole-brain gene biodistribution in NHPs. This proof-of-concept study bridges the gap between cellular microscopy and MRI-guidance to provide a complete picture of disease and treatment with clinical applicability. Full article

Non-human primates (NHPs) are considered important models for the study of reproductive diseases, due to their anatomical and physiological similarities to humans. However, studies on spontaneous lesions of the reproductive system in NHPs housed in zoos remain limited compared to those in laboratory animals. In this study, we report a retrospective analysis of female reproductive pathologies in 103 necropsied non-human primates from Italian zoos between 2007 and 2024. Only adult, intact, non-pregnant females with macroscopically visible reproductive lesions were included. Histopathological examination revealed reproductive tract lesions in 15 individuals (14.6%), including both non-neoplastic (cystic endometrial hyperplasia, adenomyosis, endometriosis) and neoplastic (leiomyomas, cervical and ovarian adenocarcinomas, and metastatic tumors) conditions. Leiomyoma was the most common tumor, particularly in the genus Macaca, while rare malignant neoplasms and metastatic lesions were identified in the great apes and in the New World species. The results suggest an age-related degenerative component and highlight interspecific differences in the distribution of lesions, probably related to the reproductive physiology of the various species. These results underline the importance of systematic post-mortem surveillance to improve the management of reproductive health of these captive populations and provide comparative insights with humans. Full article

Between 2016 and 2018, the state of Minas Gerais, Brazil, experienced its most significant yellow fever (YF) outbreak in 80 years. Yellow fever virus (YFV) circulation persisted afterward, with continued non-human primate (NHP) epizootics and, recently, human cases. In June 2024, YFV RNA was detected in a dead marmoset (Callithrix penicillata) in an urban square in Belo Horizonte (BH), prompting a field investigation in an adjacent park to assess infection in potential mosquito vectors and NHPs. A total of 250 mosquitoes representing nine species were collected at ground and canopy level, of which Aedes fluviatilis and Aedes scapularis comprised 78.8% of the specimens. Haemagogus spp. and Sabethes spp. mosquitoes were not collected, possibly due to the short sampling window during the dry season. No active YFV infection was detected in any of the mosquito pools tested. Eight marmosets (Callithrix penicillata) were captured and tested for arboviral infections. Five out of eight sera, representing both adult and juvenile (less than 17 months old) animals, tested positive for anti-YFV IgM. Interestingly, two adults recaptured in later expeditions revealed seroconversion. One was IgM-positive in July 2024 but negative by September 2024, consistent with the expected decline in IgM levels. The other, initially IgM-negative (as of July 2024), tested positive in April 2025, indicating recent exposure to YFV. These findings provide evidence for the ongoing, low-level circulation of YFV among urban NHPs, posing a continued risk of viral spillover to humans. Moreover, these results highlight the importance of active surveillance in detecting recent infections that would likely be missed by passive monitoring. This integrated approach enhances our understanding of local YF epidemiology and supports early, evidence-based public health interventions to prevent future human outbreaks. Full article

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related deaths, with notable sex-specific differences in its incidence, diagnosis, and outcomes. Our previous work identified casein kinase 2 alpha (CK2α) as being capable of impairing DNA mismatch repair (MMR) via phosphorylation of MLH1, thereby increasing the tumor mutational burden. This study aimed to investigate sex-specific differences in CK2α protein expression in CRC. Methods: Immunohistochemical (IHC) analysis was performed on 161 CRC tumors and adjacent normal tissues to quantify the CK2α protein levels. A multi-cohort meta-analysis of proteomic and clinical data was conducted to validate our findings and assess the correlations with age, sex, and relevant signaling pathways. Results: Female CRC patients exhibited significantly higher CK2α expression than male patients, which was confirmed in two independent cohorts. Additionally, CK2α expression was positively correlated with age in female but not male patients. Cross-cohort correlation analyses linked CK2α levels with key proteins involved in estrogen receptor signaling and aging, including DEAD-box helicase 5 (DDX5), histone deacetylase 1 (HDAC1), proliferating cell nuclear antigen (PCNA), prohibitin-2 (PHB2), H/ACA ribonucleoprotein complex subunit 2 (NHP2), and dual-specificity mitogen-activated protein kinase kinase 3 (MAP2K3). Conclusions: CK2α is significantly overexpressed in the tumor tissue of female CRC patients and shows a strong age-related correlation. These findings suggest a sex- and age-specific regulatory mechanism potentially influenced by estrogen signaling or menopause. Such dimorphisms underscore the need for sex-specific strategies in CRC biomarker development and therapy. Full article

The global fight against HIV/AIDS has been significantly bolstered by the development and implementation of pre-exposure prophylaxis (PrEP), yet innovation in PrEP interventions, improved adherence and greater access are still needed to maximize its benefit. Nonhuman primate (NHP) infection with simian immunodeficiency virus (SIV) has served as an instrumental animal model in advancing HIV PrEP research. This review comprehensively examines the utility of NHP models in evaluating the efficacy, pharmacokinetics, and safety of diverse PrEP strategies, including oral, injectable, implantable, and topical formulations. It discusses the development of diverse challenge models that simulate human transmission routes and the advantages of NHPs in enabling controlled and mechanistically informative studies. It also highlights the successful translation of pivotal NHP studies evaluating tenofovir-based regimens as well the long-acting agents, cabotegravir and lenacapavir, into the clinical settings, emphasizing the consistently high predictive power of the NHP models for the HIV PrEP clinical efficacy. Finally, it underscores the importance of species-specific pharmacologic considerations and the value of NHP data in informing clinical trial design. As the global community strives to end the HIV epidemic as a public health threat in the absence of an efficacious prophylactic vaccine, NHP models make a critical contribution in the development of next-generation HIV prevention tools. Full article

Background: The increasing use of food supplements (FSs) and the knowledge gaps among healthcare professionals (HPs) and non-healthcare professionals (nHPs) in Portugal regarding their influence on dietary patterns and health need investigating. This study aimed to explore FS users’ lifestyle and dietary patterns, identifying differences and how professional background influences these patterns. Methods: A cross-sectional study was conducted among 1122 Portuguese adults aged 35 ± 14.0 yrs (between 18 and 85), via snowball sampling, collecting data on sociodemographic characteristics, dietary patterns, FS use, and health attitudes. Cluster analysis (k-means) revealed four patterns: (1) professional supplement users with a healthy diet (PSHD), (2) professional non-supplement users with a less healthy diet (PnSLHD), (3) non-professional supplement users with a healthy diet (nPSHD), and (4) non-professional non-supplement users with a less healthy diet (nPnSLHD). Logistic regression assessed associations with lifestyle traits. Results: Significant sociodemographic differences existed between HPs and nHPs. Higher nutritional knowledge and nutritionist recommendations were strongly associated with a healthier diet and FS use (PSHD, nPSHD). Smoking was associated with less healthy patterns (PnSLHD, nPnSLHD). Among nHPs, males were significantly more likely to belong to the nPSHD group (OR: 1.61) compared to females (OR: 0.61). Distinct dietary and lifestyle patterns among Portuguese FS users and non-users vary by background. Conclusions: The findings suggest that FS users often maintain healthier lifestyles, indicating that FSs typically supplement rather than compensate for poor habits. Full article

Background: Periodontal disease in non-human primates (NHPs) has gained relevance due to its similarities with human pathology and its potential to influence systemic health. The purpose of this study was to investigate the relationship between periodontal disease and the development of systemic conditions in NHPs, aiming to understand the mechanisms involved and their clinical significance. Methods: An integrative literature review was conducted using the PICO strategy, including observational studies, experimental research, and integrative reviews that examined periodontal disease in NHPs and its association with systemic diseases. Results: A total of eleven studies were analyzed, revealing consistent associations between periodontal disease and systemic conditions such as diabetes mellitus, cardiovascular diseases, osteoporosis, metabolic syndrome, and adverse pregnancy outcomes. The reviewed studies identified inflammatory pathways, including elevated cytokines, acute-phase proteins and immune responses, as key mediators linking periodontal disease to systemic dysfunction. Oral pathogens and chronic inflammation were shown to impact distant organs, suggesting a broader role of oral health in systemic disease. Conclusions: The findings support the hypothesis that periodontal disease in NHPs contributes to systemic disease progression and is not merely a localized condition. Full article

Background: Alzheimer’s Disease (AD) is one of the most prevalent neurodegenerative disorders and the most common form of dementia. Although current treatments examine disease progression, many have side effects and primarily target symptomatic relief as opposed to halting further neurodegeneration. Objective: The current study aims to determine the neuroprotective effects of water-soluble coenzyme Q10 (Ubisol-Q10) and an ethanolic Ashwagandha extract (E-ASH) on a transgenic mouse model of AD. Methods: A variety of immunofluorescence staining of biomarkers was conducted to assess mechanisms commonly implicated in the disease. Additionally, spatial and non-spatial memory tests evaluated cognitive functions at two timepoints throughout the progression of the disease. Results: A substantial reduction in microglial activation and amyloid-β (Aβ) plaques when treated with a combination of natural health products (NHPs), Ubisol-Q10 and E-ASH. Moreover, activation of autophagy was upregulated in both the Ubisol-Q10 and combination (Ubisol-Q10+E-ASH given as a combined “Tonic” solution) groups. Oxidative stress was decreased across treated groups, while astrocyte activation was elevated in both the E-ASH and Tonic group. The Tonic group expressed an elevation in the fluorescent intensity of neuronal nuclei (NeuN) and brain-derived neurotrophic factor (BDNF) levels. Interestingly, treatment with E-ASH and Ubisol-Q10 enhanced synaptic vesicle formation compared to controls. Pre-mortem memory tests revealed the treatments to be effective at preserving cognitive abilities. Conclusions: Based on these findings, the combination of E-ASH and Ubisol-Q10 may effectively mitigate the various mechanisms implicated in AD and ultimately prevent further disease progression. Full article

Metabolite fingerprint profiling is a robust tool for verifying suppliers of authentic botanical ingredients. While comparative studies exist, few apply identical conditions across multiple species; this study utilized a cross-species comparison to identify versatile solvents despite biochemical variability. Multiple solvents were used for sample extraction prior to analysis by proton NMR and liquid chromatography–mass spectrometry (LC-MS) for multiple botanicals including Camellia sinensis, Cannabis sativa, Myrciaria dubia, Sambucus nigra, Zingiber officinale, Curcuma longa, Silybum marianum, Vaccinium macrocarpon, and Prunus cerasus. Comparisons were normalized by total intensity; deuterated methanol aids NMR lock but is not required for LC-MS. Hierarchical clustering analysis (HCA) evaluated solvent efficacy. Methanol–deuterium oxide (1:1) was the most effective extraction method, yielding 155 NMR spectral metabolite variables for Camellia sinensis, while methanol (90% CH₃OH + 10% CD₃OD) produced 198 for Cannabis sativa and 167 for Myrciaria dubia, with 11, 9, and 28 assigned metabolites, respectively. LC-MS detected 121 metabolites in Myrciaria dubia in methanol as the most effective extraction method. Methanol (10% deuterated) is the most effective extraction method for comprehensive metabolite fingerprinting using NMR and LC-MS protocols because it provides the broadest metabolite coverage. This study advances fit-for-purpose methods to qualify suppliers of botanical ingredients in food and NHP quality control programs. Full article

Background: Irradiation-induced injury is a common fallout of radiological/nuclear accidents or therapeutic exposures to high doses of radiation at high dose rates. Currently, there are no prophylactic drugs available to mitigate radiation injury as a result of exposure to lethal doses of ionizing radiation. Gamma-tocotrienol (GT3) of vitamin E is a promising radioprotector under advanced development which has been tested for efficacy in both murine and nonhuman primate (NHP) models. Previously, we have demonstrated that GT3 has radioprotective efficacy in intestinal epithelial and crypt cells, and restores transcriptomic changes in NHPs with a supralethal dose of 12 Gy total-body irradiation (TBI). Methods: In this study, we evaluated the effect of 12 Gy partial-body irradiation (PBI) or TBI on metabolomic changes in serum samples and the extent to which GT3 was able to modulate these irradiation-induced changes. A total of 32 nonhuman primates were used for this study, and blood sample were collected 3 days (d) prior to irradiation, and 4 h, 8 h, 12 h, 1 d, 2 d, and 6 d post-irradiation. Results: Our results demonstrate that exposure to a supralethal dose of radiation induces a complex range of metabolomic shifts with similar degrees of dysregulation in both partial- and total-body irradiated animals. The C21-steroid hormone biosynthesis and metabolism pathway was significantly dysregulated in both PBI and TBI groups, with minimal protection afforded by GT3 administration. Conclusions: GT3 offered a differential response in terms of protected metabolites and pathways in either group that was most effective at the early post-irradiation time points. Full article

In Brazil, Plasmodium infections in non-human primates (NHPs) have been associated with P. simium and P. brasilianum, which are morphologically and genetically similar to the human-infecting species P. vivax and P. malariae, respectively. Surveillance and monitoring of wild NHPs are crucial for understanding the distribution of these parasites and assessing the risk of zoonotic transmission. This study aimed to detect the presence of Plasmodium spp. genetic material in Platyrrhini primates from 47 municipalities in the states of Bahia and Minas Gerais. The animals were captured using Tomahawk-type live traps baited with fruit or immobilized with tranquilizer darts. Free-ranging individuals were chemically restrained via inhalation anesthesia using VetBag^® or intramuscular anesthesia injection. Blood samples were collected from the femoral vein. A total of 298 blood and tissue samples were collected from 10 primate species across five genera: Alouatta caraya (25), Alouatta guariba clamitans (1), Callicebus melanochir (1), Callithrix geoffroyi (28), Callithrix jacchus (4), Callithrix kuhlii (31), Callithrix penicillata (175), Callithrix spp. hybrids (15), Leontopithecus chrysomelas (16), Sapajus robustus (1), and Sapajus xanthosthernos (1). Molecular diagnosis was performed using a nested PCR targeting the 18S small subunit ribosomal RNA (18S SSU rRNA) gene, followed by sequencing. Of the 298 samples analyzed, only one (0.3%) from Bahia tested positive for Plasmodium brasilianum/P. malariae. This represents the first detection of this parasite in a free-living C. geoffroyi in Brazil. These findings highlight the importance of continued surveillance of Plasmodium infections in NHPs to identify regions at risk for zoonotic transmission. Full article

While viral pathogens are often subdivided into neurotropic and non-neurotropic categories, systemic inflammation caused by non-neurotropic viruses still possesses the ability to alter the central nervous system (CNS). Studies of CNS disease induced by viral infection, whether neurotropic or not, are presented with a unique set of challenges. First, because brain biopsies are rarely necessary to diagnose viral-associated neurological disorders, antemortem tissue samples are not readily available for study and human pathological studies must rely on end-stage, postmortem evaluations. Second, in vitro models fail to fully capture the nuances of an intact immune system, necessitating the use of animal models to fully characterize pathogenesis and identify potential therapeutic approaches. Non-human primates (NHP) represent a particularly attractive animal model in that they overcome many of the limits posed by more distant species and most closely mirror human disease pathogenesis and susceptibility. Here, we review NHP infection models of viruses known to infect and/or replicate within cells of the CNS, including West Nile virus, the equine encephalitis viruses, Zika virus, and herpesviruses, as well as those known to alter the immune status of the brain in the absence of significant CNS penetrance, including human immunodeficiency virus (HIV) in the current era of combination antiretroviral therapy (cART) and the coronavirus of severe acute respiratory syndrome (SARS)-CoV−2. This review focuses on viruses with an established role in causing CNS disease, including encephalitis, meningitis, and myelitis and NHP models of viral infection that are directly translatable to the human condition through relevant routes of infection, comparable disease pathogenesis, and responses to therapeutic intervention. Full article