Search Results (117)

Background: Varicella zoster virus (VZV) is a globally circulating pathogen that usually infects children and establishes a latent state in host nerve cells. Recurrence of latent varicella zoster virus (VZV) is often triggered by predisposing factors such as aging and immune dysfunction, which may lead to herpes zoster (HZ) and its related complications. At present, there is no specific treatment for herpes zoster or postherpetic neuralgia, so vaccination is an important preventive measure. Methods: In this study, a variety of vaccine formulations were developed by combining the gE protein with different adjuvants. Enzyme-linked immunosorbent assay (ELISA), flow cytometry, and ELISpot were used to evaluate the immune response induced by each combination of vaccines in C57BL/6 mice, and the optimal combination of adjuvants. Then, its immunogenicity was verified in SD rats and rhesus monkeys. Results: All combinations of gE/squalene oil-in-water emulsion (SWE)/CpG1018 adjuvant induced a good humoral immune response 28 days after secondary immunization. GE/SWE/CPG1018, combined with adjuvant, induced a higher cellular immune response in mice. The selected gE/SWE/CpG1018 combined with the adjuvant vaccine combination could effectively stimulate the humoral and cellular immune responses in SD rats and rhesus monkeys. Conclusions: The gE/SWE/CpG1018 combined with adjuvant vaccine may be a low-cost and highly effective vaccine candidate for the prevention of varicella zoster. Full article

Mpox virus (MPXV), a member of the Orthopoxvirus genus in the Poxviridae family, has long been endemic in Africa. The interaction between MPXV infection and peripheral immune responses is of great significance. However, the activation of signaling pathways and molecular changes in peripheral blood mononuclear cells (PBMCs) following MPXV infection remain poorly understood. This study evaluated the transcriptomic profiles of rabbit PBMCs during the mpox acute and recovery phases. The results showed that MPXV infection significantly altered the transcriptomic profiles of PBMCs. At 6 days post-infection, pathways related to pathogenic infection and IL-1 response were enriched, while at 14 days post-infection, the T cell receptor signaling pathway was enriched. During the mpox acute phase, inflammatory cytokines in serum such as IL-1α, IL-1β, IL-8, and IL-21 were upregulated, while MMP-9 and NCAM-1 were downregulated. In rabbits and rhesus monkeys, key genes upregulated in common during the mpox acute period were associated with the interferon pathway (e.g., the ISG15, OAS, and IFIT families), while downregulated genes were related to B-cell activation and differentiation (e.g., the MS4A1 and FCRL families). Additionally, rabbits developed protective immunity against reinfection, with neutralizing antibodies effectively activated. These findings provide insights into the molecular characteristics of PBMCs changes in in vivo models of MPXV infection, and offer references for the diagnosis, vaccine development, and therapeutic research of mpox. Full article

The influence of iron deficiency anemia and iron treatments on the gut microbiome was evaluated in young rhesus monkeys. First, the hindgut bacterial profiles of 12 iron-deficient anemic infants were compared to those of 9 iron-sufficient infants at 6 months of age, a time when the risk of anemia is high due to rapid growth. After this screening, the anemic monkeys were treated with either parenteral or enteral iron. Seven monkeys were injected intramuscularly with iron dextran, the typical weekly treatment used in veterinary practice. Four other anemic infants were treated with a novel oral supplement daily: yeast genetically modified to express ferritin. Fecal specimens were analyzed using 16S ribosomal RNA (rRNA) gene amplicon sequencing. Bacterial species richness in anemic infants was not different from that of iron-sufficient infants, but beta diversity and LEfSe analyses of bacterial composition indicated that the microbiota profiles were associated with iron status. Both systemic and oral iron increased alpha and beta diversity metrics. The relative abundance of Ruminococcaceae and other Firmicutes shifted in the direction of an iron-sufficient host, but many different bacteria, including Mollicutes, Tenericutes, and Archaea, were also enriched. Collectively, the findings affirm the important influence of the host’s iron status on commensal bacteria in the gut and concur with clinical concerns about the possibility of adverse consequences after iron supplementation in low-resource settings where children may be carriers of iron-responsive bacterial pathogens. Full article

The global unregulated drug supply faces a critical challenge with the emergence of nitazenes, a class of novel synthetic opioids (NSOs) structurally distinct from fentanyl and associated with extreme potency and high risk of fatal overdose. First synthesised in the late 1950s, etonitazene was a target of preclinical research in rats and rhesus monkeys, but it never reached clinical trials due to an unfavourable balance between therapeutic and toxic effects. Nitazenes’ consistent reappearance began in 2019 with isotonitazene, followed by a rapid proliferation of analogues worldwide, many reported to be hundreds to thousands of times more potent than morphine and, in some cases, stronger than fentanyl. This rise is fuelled by their ease of synthesis, low production costs, and evasion of regulatory controls. Nitazenes are frequently mis-sold as counterfeit medications or adulterated into other drugs, resulting in unintentional exposure and overdose, particularly among opioid-naïve users. The primary cause of death is severe and prolonged respiratory depression. Analytical challenges are significant, as traditional screening methods are ineffective, and the low concentration in biological samples requires expensive and highly sensitive liquid chromatography mass spectrometry techniques. This perspective paper highlights critical gaps in detection, clinical management, and regulatory readiness for nitazenes. Urgent efforts are needed to improve surveillance, develop robust analytical methodologies, provide clinical guidance to nitazene intoxications, and strengthen international policy to curb their proliferation. Full article

Background/Objectives: This study aimed to develop a new attenuated live mumps vaccine strain and determine its biological properties and effectiveness. Methods: Plaque purification and amplification were performed in chicken embryo cells. Candidate live attenuated mumps MuV-365 strain sequencing was performed. After evaluating the potential neurotoxicity of the MuV-365 mumps strain, a preclinical safety evaluation of measles–mumps–rubella (MMR) live attenuated vaccine containing the MuV-365 strain was performed to support the registration and application of the MMR vaccine. Finally, mumps neutralization antibody titers and the concentration of anti-serum mumps-specific IgG were determined to evaluate the immunogenicity and efficacy of the MuV-365 strain and MMR vaccine in mice and rhesus monkeys. Results: The plaque of the PL-KUM main seed virus was screened, and strains whose sequences were highly homologous to RIT4385 (JL-5 derived) were selected to amplify. The candidate live attenuated mumps MuV-365 strain was then developed. Safety evaluation results indicated that the MuV-365 strain had no potential neurotoxicity, and the MMR vaccine containing the MuV-365 strain also showed no significant safety hazard. The immunogenicity of MuV-365 strain in BALB/c mice was not inferior to S79 and PL-KUM. After two doses of the MuV-365 strain, the concentration of anti-serum mumps-specific IgG of the MuV-365 strain was significantly higher than that of the S79 strain (p < 0.01). In rhesus monkeys, the MMR vaccine had good immunogenicity against measles and rubella after one dose, while immunogenicity against mumps improved after two doses. Conclusions: The developed MuV-365 strain was genetically stable, with adequate safety and immunogenicity. Full article

Background: In vitro blood circulation loop systems are utilized to assess the hemocompatibility and performance of medical devices that come into contact with blood, in accordance with the international standards ASTM F1830 and ASTM F1841. However, a method for evaluating the specific type of anticoagulant and the blood characteristics of each animal species is necessary to ensure consistent and reliable results. Methods: Blood was collected from healthy rabbits, pigs, rhesus monkeys, and cynomolgus monkeys to evaluate whole blood preserved in anticoagulants (ACD-A, CPDA-1, and heparin). For each sample, red blood cells were monitored over time, and their morphological characteristics were documented. Results: The morphological grade of erythrocytes gradually decreased over time. Significant differences were observed based on the type of anticoagulant used in the experiment, and variations were noted among different animal species. Conclusions: The hemocompatibility of in vitro blood circulation loop systems may vary depending on the animal species. Observing erythrocyte morphology can serve as a control measure to ensure reproducible results. Full article

Non-human primates (NHPs) are extensively utilized to investigate the neural mechanisms underlying face processing; however, measuring their brain activity necessitates a diverse array of technologies. Pupillometry emerges as a convenient, cost-effective, and non-invasive alternative for indirectly assessing brain activity. To evaluate the efficacy of pupillometry in assessing facial and emotional processing in NHPs, this study designed a face fixation task for experimental monkeys (Rhesus macaque) and recorded variations in their pupil size in response to face images with differing characteristics, such as species, emotional expression, viewing angles, and orientation (upright vs. inverted). All face images were balanced with luminance and spatial frequency. A sophisticated eye-tracking system (Eye-link 1000 plus) was employed to observe the pupils and track the viewing trajectories of monkeys as they examined images of faces. Our findings reveal that monkeys exhibited larger pupil sizes in response to carnivore faces (versus human faces, p = 0.035), negative conspecific faces (versus human faces, p = 0.018), and profile viewing angles (versus frontal view angles, p = 0.010). Notably, pupil size recorded during the 500–1000 ms post-stimulus interval was negatively correlated with their gaze durations directed at those images (r = −0.357, p = 0.016). Overall, this study demonstrates that pupillometry effectively captures subtle differences in facial and emotional processing, underscoring its potential as a valuable tool in future cognitive research and the diagnosis of disorders. Full article

Early neurological deterioration is associated with poor functional outcomes in stroke patients, but the underlying mechanisms remain unclear. This study aims to understand the progression of stroke-related brain damage using a rhesus monkey model with ischemic occlusion. Multiparameter MRI was used to monitor the progressive evolution of the brain lesion following stroke. Resting-state functional MRI, dynamic susceptibility contrast perfusion MRI, diffusion tensor imaging, and T1- and T2-weighted scans were acquired prior to surgery and at 4–6 h, 48 h, and 96 h following the stroke. The results revealed a sudden increase in infarction volume after the hyper-acute phase but before 48 h on diffusion-weighted imaging (DWI), with a slight extension by 96 h. Lower relative cerebral blood flow (CBF) and time to maximum (Tmax) prior to the stroke, along with a progressive decrease post-stroke, were observed when compared to other stroke monkeys in the same cohort. Functional connectivity (FC) in the ipsilesional secondary somatosensory cortex (S2) and primary motor cortex (M1) exhibited an immediate decline on Day 0 compared to baseline and followed by a slight increase on Day 2 and a further decrease on Day 4. These findings provide valuable insights into infarction progression, emphasizing the critical role of collateral circulation and its impact on early neurological deterioration during acute stroke. Full article

Early life adversity (ELA) is a known risk factor for psychopathology, including stress-related anxiety and depressive disorders. The underlying mechanisms and developmental changes remain poorly understood. A likely underpinning is the impact of ELA on the development of stress response systems, including the hypothalamic–pituitary–adrenal (HPA) axis. Our group studied a translational ELA model of spontaneous infant maltreatment by the mother in rhesus macaques, where we used a cross-fostering design to randomly assign infant macaques to either Control or Maltreating (MALT) foster mothers at birth to examine the impact of adverse caregiving on the development of the HPA axis, while controlling for the confounding effects of heritable and prenatal factors. We previously reported higher levels of plasma and hair cortisol (CORT) across the first 6 postnatal months (equivalent to the first 2 years of life in humans) in the MALT than in the Control infants. Here, we followed the same cohort of infants longitudinally to assess the long-term developmental impact of this adverse experience on HPA axis function during the juvenile (12, 18 months) and late adolescent (~5 years) periods. For this, we collected measurements of diurnal CORT rhythm and glucocorticoid negative feedback using the dexamethasone suppression test (DST). At 12 months, we found higher diurnal CORT secretion in MALT females compared to Control females, and impaired negative feedback in response to the DST in both sexes in the MALT group. However, ELA group differences in the HPA axis function disappeared by 18 months and late adolescence, while sex differences in diurnal CORT rhythm emerged or became stronger. These results suggest that infant maltreatment causes dysregulation of the HPA axis during the first year of life, with HPA axis function normalizing later, during the pre-pubertal juvenile period and adolescence. This suggests that the impact of maltreatment on HPA axis function may be transient, at least if the adverse experience stops. Our findings are consistent with human evidence of recalibration/normalization of HPA axis function during adolescence in children that switch from adverse/deprived environments to supportive adoptive families. This research has broad implications regarding the biological processes that translate ELA to psychopathology during development and the pathways to resiliency. Full article

Human activities significantly influence the changes in wildlife habitats and biodiversity, highlighting the necessity to enhance public knowledge, perceptions, and practices (KPP) to mitigate their consequences. Previous research suggests that many people in Bangladesh do not consider wildlife and biodiversity conservation a crucial issue. However, enhancing their KPP could be essential in developing effective and sustainable conservation efforts in Bangladesh. So, the current study aimed to evaluate the public’s KPP of wildlife conservation and biodiversity management in Bangladesh. A total of 3060 individuals’ data were collected from various sociodemographic backgrounds using a structured questionnaire followed by statistical analyses including Pearson’s chi-square, Spearman’s correlation, and logistic regression analysis, which were performed to assess the correlations and trends among variables using STATA and SPSS. The results revealed a significant heterogeneity in KPP across different sociodemographic groups. Importantly, the younger respondents (ages 21–30) indicated a high level of KPP, and respondents without formal education and belonging to older ages demonstrated markedly low levels of KPP. In the country’s divisional levels, respondents from Khulna and Rangpur revealed the highest and lowest KPP levels, respectively. Our study also revealed that students represented the major occupational demographic and displayed moderate levels of KPP. Notably, respondents highlighted the decline or absence of several wild animal species, including black bears, deer, vultures, wild cats, hanuman monkeys, and rhesus monkeys, from their local areas over the past decades. Public opinion on wildlife protection revealed 78.6% and 73.4% disapproving of hunting rejection and wildlife trading, respectively. Nonetheless, a lack of knowledge remained, as 16.89% of respondents were unaware of measures to alleviate human-wildlife conflict. The correlation analysis indicated a favorable association among KPP components, especially between knowledge and perception (correlation coefficient = 0.438), underscoring the essential influence of awareness on conservation actions. This study offers critical insights for developing interventions to enhance KPP among local communities and stakeholders, hence promoting sustainable wildlife conservation and biodiversity management in Bangladesh. Taken together, the findings provide baseline data for safeguarding biodiversity and fostering long-term wildlife sustainability in Bangladesh. Full article

The seasonal variations that occur in the gut microbiota of healthy adult rhesus monkeys kept in outdoor groups under conventional rearing patterns and how these variations are affected by environmental variables are relatively poorly understood. In this study, we collected 120 fecal samples from 30 adult male rhesus monkeys kept in outdoor groups across four seasons and recorded the temperature and humidity of the housing facilities, as well as the proportions of fruit and vegetables in their diet. A 16S rRNA sequencing analysis showed that the alpha diversity of the gut microbiota of the rhesus monkeys was higher in winter and spring than in summer and autumn. A principal coordinate analysis (PCoA) further demonstrated notable seasonal variations in the composition and functionality of the gut microbiota in the rhesus monkeys. The phyla Firmicutes and Bacteroidetes and the genus Prevotella 9 were the significantly dominant groups in all 120 fecal samples from the rhesus monkeys. A linear discriminant analysis (LDA) effect size (LEfSe) analysis (LDA > 4) indicated that at the phylum level, Firmicutes was significantly enriched in winter, Bacteroidetes was significantly enriched in summer, and Proteobacteria and Campylobacter were significantly enriched in spring. At the genus level, Helicobacter and Ralstonia were significantly enriched in spring; Prevotella 9, Streptococcus, and Prevotella were significantly enriched in summer; and UCG_005 was significantly enriched in autumn. The beneficial genera Lactobacillus, Limosilactobacillus, and Ligilactobacillus and the beneficial species Lactobacillus johnsonii, Limosilactobacillus reuteri, Ligilactobacillus murinus, and Lactobacillus amylovorus all showed the same seasonal trend; namely, their average relative abundance was markedly greater during the winter months compared to other seasons. Compared with other seasons, carbohydrate metabolic function was significantly upregulated in winter (p < 0.01), amino acid metabolic function was relatively increased in spring, and energy metabolic function and the metabolic function of cofactors and vitamins were significantly downregulated in winter and relatively upregulated in summer. A variance partitioning analysis (VPA) and redundancy analysis (RDA) showed that the proportions of fruits and vegetables in the diet, but not climatic factors (temperature and humidity), significantly influenced the seasonal changes in the gut microbiota. These variations were related to changes in the proportions of fruits and vegetables. This research presents novel findings regarding the influence of external environmental factors on the gastrointestinal environment of rhesus monkeys. Full article

The rhesus monkey (Macaca mulatta) is a non-human primate with a genome that is 93.5% identical to that of humans. Both species, therefore, have numerous phenotypical similarities in common. Consequently, this non-human primate is regularly studied in biomedical research. Not only does the rhesus monkey play an important role as an animal model for studying human disease, but it is also often featured in zoos, and there are substantial feral populations that live in Asia. Since they are exploited as research subjects, their appropriate housing and husbandry and the validation of obtained research data benefit from the comprehension of the rhesus monkey anatomy. Unexpectedly, the number of anatomical documents on the rhesus monkey are largely outnumbered by publications on the anatomy of domestic animals. In addition, the limited number of available anatomical books and atlases are, unfortunately, outdated, e.g., by presenting black-and-white photographs and using archaic nomenclature, or failing to cover the in-depth anatomy of various anatomical systems. Since state-of-the-art data on the rhesus monkey anatomy are requested by biomedical researchers and veterinarians responsible for the daily care of these captive animals, the present study describes the musculature of the foot of the rhesus monkey. It builds on a recently published manuscript on the topographical anatomy of the pelvic limb of this non-human primate. Full-color anatomical (stereomicroscopic) photographs are taken during layer-by-layer dissections of the feet of three rhesus monkeys. All the muscles, from the superficial to the deepest layer, are described using veterinary anatomical nomenclature and annotated on multipaneled figures. Although the foot musculature of the rhesus monkey largely parallels that of its human counterparts, the small number of dissimilarities should be recognized when extrapolating these research data. In addition, a solid understanding of the rhesus monkey anatomy by veterinarians can be valuable during medical interventions, such as surgery for foot injuries. Full article

With the online wildlife trade and the demand for viral videos increasing, the trade in primates on TikTok is becoming more prevalent. Despite wildlife trading being banned on most social media platforms, the trade in primates persists. TikTok’s policies ban the sale of live animals, and specific terms related to wildlife trading are banned; however, these search-term bans are easy to get around, and sellers are still prolific on the site. This study documented primates for sale on TikTok using the search term “for sale monkey” over a four-month period (from mid-July to mid-November 2023) with the aim of determining how widespread primate trade is on TikTok, the legality of advertisements, and which countries advertise the most primates for sale. In total, 43 individual advertisements were identified, spanning six different genera of primates and five different countries. Spider monkeys, rhesus macaques, and common marmosets were found to be the most commonly advertised species on TikTok. All the spider monkeys were advertised from the USA, while the majority of the marmosets were advertised from the UK, and all of the rhesus macaques were advertised from Pakistan. The USA was the only country identified in this study that advertised a range of species, and the only species found in this study that was not advertised in the USA was the mona monkey. In total, 44% of all species recorded were classified as either Endangered or Critically Endangered, and it was found that Endangered species were more frequently sold illegally than non-Endangered species. The findings of this study underline a need for stricter primate legislation and wildlife law enforcement, especially if the UN’s sustainable development goals are to be achieved by 2030. They also show a need for TikTok to broaden their restrictions on wildlife trading on their app. Full article

Background. Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted live attenuated influenza vaccine (LAIV) of H3N2 subtype, which expressed SARS-CoV-2 immunogenic T-cell epitopes. A cassette encoding fragments of S and N proteins of SARS-CoV-2 was inserted into the influenza NA gene using the P2A autocleavage site. In this study, we present the results of preclinical evaluation of the developed bivalent vaccine in a non-human primate model. Methods. Rhesus macaques (Macaca mulatta) (n = 3 per group) were immunized intranasally with 7.5 lg EID₅₀ of the LAIV/CoV-2 bivalent vaccine, a control non-modified H3N2 LAIV or a placebo (chorioallantoic fluid) using a sprayer device, twice, with a 28-day interval. The blood samples were collected at days 0, 3, 28 and 35 for hematological and biochemical assessment. Safety was also assessed by monitoring body weight, body temperature and clinical signs of the disease. Immune responses to influenza virus were assessed both by determining serum antibody titers in hemagglutination inhibition assay, microneutralization assay and IgG ELISA. T-cell responses were measured both to influenza and SARS-CoV-2 antigens using ELISPOT and flow cytometry. Three weeks after the second immunization, animals were challenged with 10⁵ PFU of Delta SARS-CoV-2. The body temperature, weight and challenge virus shedding were monitored for 5 days post-challenge. In addition, virus titers in various organs and histopathology were evaluated on day 6 after SARS-CoV-2 infection. Results. There was no toxic effect of the immunizations on the hematological and coagulation hemostasis of animals. No difference in the dynamics of the average weight and thermometry results were found between the groups of animals. Both LAIV and LAIV/CoV-2 variants poorly replicated in the upper respiratory tract of rhesus macaques. Nevertheless, despite this low level of virus shedding, influenza-specific serum IgG responses were detected in the group of monkeys immunized with the LAIV/CoV-2 bivalent but not in the LAIV group. Furthermore, T-cell responses to both influenza and SARS-CoV-2 viruses were detected in the LAIV/CoV-2 vaccine group only. The animals were generally resistant to SARS-CoV-2 challenge, with minimal virus shedding in the placebo and LAIV groups. Histopathological changes in vaccinated animals were decreased compared to the PBS group, suggesting a protective effect of the chimeric vaccine candidate. Conclusions. The candidate bivalent vaccine was safe and immunogenic for non-human primates and warrants its further evaluation in clinical trials. Full article