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A captive 17‐year‐old male cynomolgus monkey (Macaca fascicularis) developed diffuse large B‐cell lymphoma (DLBCL). This was the first report of DLBCL presenting with a mandible mass and violation of the paranasal sinus in a cynomolgus monkey. The neoplasm showed marked microscopical malignant aspects. Immunohistochemical staining showed strong positive expression of CD20. These features may contribute to the diagnosis and therapeutics of DLBCL in NHPs. [ABSTRACT FROM AUTHOR]

This review on cynomolgus monkey (Macaca fascicularis) blastoids discusses a breakthrough in modeling early non‐human primate embryogenesis, offering insights into embryonic development and implantation processes. It acknowledges ethical challenges and animal welfare considerations in developmental biology, suggests potential applications in human reproductive medicine, and highlights the need for ongoing ethical and technical refinement. [ABSTRACT FROM AUTHOR]

Background: A novel buprenorphine (BUP) extended‐release formulation (BUP‐XR) produced as a lipid‐encapsulated, low viscosity BUP suspension for subcutaneous (SC) injection to control pain was evaluated for pharmacokinetics and safety in four adult male cynomolgus monkeys. Methods: Each animal was given 0.2 mg/kg reformulated BUP‐XR SC. Clinical observations were made during the course of the study. Blood samples were obtained from each animal before BUP‐XR administration, 6, 24, 48, 72, and 96 h post‐BUP‐XR injection. Plasma levels of buprenorphine were analyzed using HPLC‐MS/MS. The PK values calculated included peak plasma concentration of the BUP analyte, time to peak plasma concentration, plasma half‐life, area under the plasma concentration–time curve, clearance, apparent volume of distribution, and elimination rate constant (Cmax, Tmax, T½, AUC0‐t, CL, Vd, and Ke, respectively). Results: Observable adverse clinical signs were not detected. BUP concentration peaked from 6 to 48 h, then declined in a linear fashion. Quantifiable plasma BUP was measured in all monkeys at all time points. Results indicate that a single BUP‐XR dose at 0.2 mg/kg can reliably provide plasma levels of BUP reported in the literature to be therapeutically relevant for up to 96 h. Conclusions: Because of the lack of any clinical observations or adverse effects at the injection site or absence of observable abnormal behaviors, it may be concluded that the use of BUP‐XR is safe and efficacious in this species of non‐human primate at the dose regimen described in this study for up to 96 h post‐administration. [ABSTRACT FROM AUTHOR]

Acute gastric dilatation (AGD) is one of the most prevalent and life-threatening diseases in nonhuman primates worldwide. However, the etiology of this syndrome has not been determined. Recently, sudden death occurred in a 7-year-old female cynomolgus monkey with a history of fecal microbiota transplantation using diarrheic stools. The monkey had undergone surgery previously. On necropsy, gastric dilatation and rupture demonstrated a tetrad arrangement on histopathologic examination. On 16S rRNA sequencing, a high population of Clostridium ventriculi was identified in the duodenum adjacent to stomach but not in the colon. This paper is the first report of Clostridium ventriculi infection in a cynomolgus macaque with acute gastric dilatation and rupture. [ABSTRACT FROM AUTHOR]

Background: Melatonin is a multifunctional hormone synthesized in the pineal gland and peripheral reproductive tissues that regulates many biological processes. There is increasing evidence for a role of melatonin in oocyte maturation and embryonic development in various mammals. However, no study has reported evidence for the existence of melatonergic system, such as melatonin synthesis enzymes, melatonin membrane receptors, or melatonin binding sites in non‐human primate cumulus–oocyte complexes (COCs). Methods: Reverse transcription polymerase chain reaction (RT‐PCR) and immunocytochemistry were performed to detect transcripts and proteins of the rate‐limiting enzyme in melatonin synthesis (arylalkylamine N‐acetyltransferase, AANAT), melatonin membrane receptors (MT1 and MT2), and a melatonin binding site (NRH: quinone oxidoreductase 2, NQO2) in cynomolgus monkey COCs. Results: RT‐PCR analyses revealed the presence of AANAT, MT1, MT2, and NQO2 transcripts in granulosa cells, germinal vesicle (GV)‐ and metaphase II (MII)‐stage cumulus cells, and oocytes. Immunocytochemistry revealed the presence of AANAT, MT1, MT2, and NQO2 proteins in GV‐ and MII‐stage COCs. Conclusions: Our results provide the first evidence for the existence of the rate‐limiting enzyme required for melatonin synthesis, melatonin membrane receptors, and a melatonin binding site in non‐human primate COCs. [ABSTRACT FROM AUTHOR]

Background: Using untargeted metabolomics techniques, the goal of the study is to differentially screen serum and feces metabolite profiles of spontaneously diabetic and healthy cynomolgus monkeys, to explore potential serum and fecal biomarkers and analyze affected metabolic pathways. Methods: We adopted the diagnostic criteria for T2DM recommended by ADA for humans: FSG ≥7.0 mmol/L (126 mg/dl) and HbA1c ≥ 6.5%. The serum and feces samples from three diagnosed spontaneously T2DM cynomolgus monkeys and 11 age‐matched healthy controls were enrolled in the study. We employed LC–MS/MS‐based untargeted metabolomic methods to reveal the differential metabolite profiles of serum and feces samples between the two groups and to analyze the affected metabolic pathways in MetaboAnalyst 5.0 based on KEGG library. Results: Six and 44 differential metabolites were identified in serum and feces samples, respectively, and the corresponding affected commonly metabolic pathways involved several metabolic ways, such as arginine biosynthesis, pantothenate and CoA biosynthesis, alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, and histidine metabolism. Conclusion: The differential potential serum and feces biomarkers obtained from the LC–MS/MS based untargeted metabolomic may help to explain the potential pathophysiological mechanisms of T2DM and offer pivotal information for the early diagnosis and treatment of DM. [ABSTRACT FROM AUTHOR]

Abstract: Background: Lupus is an autoimmune disease with complex syndrome. Rodent models have limitations for recapitulating the spectrum of the disease. A more powerful translational model is desirable. Method: Lupus‐associated model in cynomolgus monkeys was induced by two intraperitoneal injections of 2, 6, 10, 14‐tetramethylpentadecane (PRISTANE). Lupus‐specific biomarkers and manifestations over a 246‐day period were observed at multilevel. To visualize and quantify kidney function in real time, contrast‐enhanced ultrasound was used. Results: The indicative biomarkers and manifestations fulfilled major diagnosis criteria according to the “Criteria of Lupus” of the American College of Rheumatology. Significant changes in time‐intensity curve parameters were observed, indicating impaired renal function and the method as a feasible, non‐invasive diagnostic method in primate model. Conclusions: We successfully induced lupus‐associated model with systemic lupus syndrome. This primate model can be a valuable translational model for further pathogenesis and symptomology studies and for exploring therapeutic candidates. [ABSTRACT FROM AUTHOR]

Background Primates exhibit substantial capacity for behavioral innovation, expanding the diversity of their behavioral repertoires, and benefiting both individual survival and species development in evolution. Novel object exploration is an integral part of behavioral innovation. Thus, qualitative and quantitative analysis of novel object exploration helps to better understand behavioral innovation. Methods To study the pattern of novel object exploration, two different sized balls were sequentially introduced to singly caged cynomolgus monkeys. Two aspects of monkeys' behaviors were analyzed: the types of motor activities in toy playing and whether there is an orderly sequence of such motor activities during novelty exploration. Results Four types of behavioral activities (oral contact, gross and fine forelimb motor, and hind limb motor) followed a pattern: first forelimb gross motor and oral contact, followed by forelimb fine motor and hind limb activities. Oral contact appeared to be an important behavior in monkeys' repertoire of novelty exploratory behaviors, both as an early appearing activity, and showing a consistent pattern of high cumulative time for two different novel objects. Conclusions These results provide a profile of novel object exploratory behaviors in cynomolgus monkeys, contributing to a better understanding of this aspect of behavioral innovation. [ABSTRACT FROM AUTHOR]

Background Biopharmaceutical development necessitates use of non-human primates in toxicology, leading to adoption of non-traditional methods including cognitive function assessment. Methods A two-object discrimination and reversal test in cynomolgus monkeys ( Macaca fascicularis) was performed using a Wisconsin General Testing Apparatus ( WGTA). Non-clinical study design and regulatory considerations dictate that infants are raised by their biological mothers until weaning at 6 months. Thirty-four animals (6-21 months of age) were trained to discriminate between two randomly selected stimulus objects to retrieve a reward. Following training, days to first reversal after interchanging the reward were measured. Results Both sexes acquired visual discrimination skills at similar rates. Trends in learning and reversals completed were uniform across age groups. Completing training early in some subjects had no impact on subsequent testing phases. Conclusions Weaned cynomolgus monkey infants can be successfully tested for cognitive abilities using the WGTA in a non-clinical laboratory setting. [ABSTRACT FROM AUTHOR]

Background Excessive weight gain has been observed in middle-aged cynomolgus monkeys. This study was designed to investigate the metabolic characteristics in overweight monkeys. Methods A total of 26 cynomolgus monkeys were grouped based on gender and body weight. Overweight was operationally defined as body weight heavier than 9.6 kg in males and 7.5 kg in females. They were monitored for glucose and insulin in fasting state, serum parameters, and somatometric measurements. Results Higher measurements of weight, body mass index ( BMI), waist, hip, and waist/hip ratio ( WHR) were the somatometric characteristics of overweight monkeys. Abdominal fat deposition was more prominent in females. Elevated total cholesterol, HDL- C, LDL- C, and fasting glucose were observed in female overweight monkeys. Impaired insulin sensitivity occurred in overweight monkeys. Conclusions Overweight could result in impaired insulin sensitivity. The metabolic changes were more prominent in female overweight monkeys. [ABSTRACT FROM AUTHOR]

Background and methods Quantitative enzyme-immunoassays of urinary and fecal immunoglobulin A (IgA), cortisol and 11-17-dioxoandrostanes (11,17-DOA), and serum cortisol in eight metabolic-cage-housed female cynomolgus monkeys were performed. The monkeys were divided into two groups, B and NB. Group B animals were blood sampled every 6 hours, whereas Group NB animals were not handled/blood sampled. Results No differences were recorded between the amounts of feces and urine excreted by the two groups. Group B animals excreted more urinary cortisol than did Group NB animals indicating that restraint-blood sampling resulted in a stress response. Excreted amounts of IgA and 11,17-DOA (urine and feces) did not differ between the groups. Conclusions Urinary cortisol was a reliable marker of the stress associated with repeated blood sampling. Declining amounts of excreted urinary cortisol indicated that cynomolgus monkeys acclimated quickly to repeated blood sampling in metabolism cages. Within and between animal variation in amounts of feces voided demonstrated the importance of expressing fecal markers as ‘amounts excreted per time unit per kg body weight’ rather than just measuring the concentrations in fecal samples. [ABSTRACT FROM AUTHOR]

Background Prostate-specific antigen (PSA) is an invaluable tumor marker for the detection of early prostate cancer, and can be a target for active immunotherapy of prostate cancer. We wanted to assess the usefulness of the cynomolgus monkey ( Macaca fascicularis) as a relevant animal model to evaluate PSA-specific therapies. Methods RNA was isolated from the prostate of cynomolgus monkeys, and PSA gene products were amplified by reverse transcriptase-polymerase chain reaction using primers from conserved regions of human and rhesus monkey ( Macaca mulatta) PSA genes. These amplified products were then sequenced. Results The cynomolgus PSA amino acid sequence is 89.7% identical to the human PSA gene, and 99.2% identical to the rhesus PSA amino acid sequence. Like the human and rhesus PSA genes, an open-reading frame of 261 amino acids was identified for the cynomolgus gene. Expression of the cynomolgus PSA gene appears to be restricted to the prostate, as it is in humans. Conclusions The high identity between human and cynomolgus PSA sequences suggests that the cynomolgus monkey should be studied further for its potential as a large animal model to evaluate PSA-specific therapies. [ABSTRACT FROM AUTHOR]

Indicators of transport stress were investigated in blood parameters of five male cynomolgus monkeys obtained from abroad. They underwent air and ground travel-related stress in transport cages for a 15-hour transit time. On arrival, hematological parameters of white blood cell count, red blood cell count, hemoglobin concentration, and hematocrit values were within the limits of reference range, indicating that these parameters were not typical changes derived from transport stress loading. An increase in neutrophil-to-lymphocyte (N/L) ratio with a marked increase in neutrophils and a decrease in lymphocytes was observed on arrival, and the increased N/L ratio returned approximately to the normal level 1 week after arrival. The serum cortisol level markedly increased on the day of arrival and it returned to normal 1 week after arrival. These findings indicate that the transport process was stressful for animals, showing increases in N/L ratio as well as cortisol level. Thus, it is possible that an increase in N/L ratio may be utilized as an indirect indicator of transport stress in newly acquired cynomolgus monkeys, as it has the similar pattern of change in cortisol with an increased cortisol level on the day of arrival. [ABSTRACT FROM AUTHOR]

To establish reproductive biological techniques in mammals, it is important to understand the growth environment of the embryo. Oviduct epithelial cells are in close proximity to the embryo during pre-implantation development. We, therefore, established an immortalized oviduct epithelial cell line from the cynomolgus monkey, evaluated the usefulness of these cells as feeder cells for embryo culture, and investigated the gene expression of several growth factors and cytokines in the cells. The immortalized cells were positive for the anti-cytokeratin antibody, as determined by immunocytochemistry, indicating that they are epithelial. They also expressed oviductin, which is specific to oviduct epithelial cells, glyceraldehyde-3-phosphate dehydrogenase (control), leukemia inhibitory factor, vascular endothelial growth factor, epidermal growth factor, insulin-like growth factor 1, transforming growth factor beta-2, and interleukin 4. Mouse embryo development was improved when the immortalized cells were used as feeder cells. This cell line is also useful for studying the factors secreted by oviduct epithelial cells. [ABSTRACT FROM AUTHOR]

The effects of ketamine anesthesia on both hematological and serum biochemical variables were investigated in 19 male and 15 female cynomolgus monkeys. Blood samples were obtained from the cephalic vein within 30 minutes of an intramuscular injection of ketamine hydrochloride (10 mg/kg). Ketamine anesthesia caused a reduction in leukocyte counts and a significant reduction in lymphocytes percentages. Ketamine anesthesia also increased the serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine phosphokinase (CPK), but reduced the serum concentrations of glucose, inorganic phosphate, sodium and potassium. The alterations of hematological and serum biochemical values will be discussed. These alterations should be considered when designing studies for and interpreting data from cynomolgus monkeys. [ABSTRACT FROM AUTHOR]

Strees sensitive molecules exhibit great variation in concentration in the circulation and it may often be advantageous to quantify these in urine or feces rather than in serum or plasma. We advocate that all urine-or feces-should be collected, and that excretion of stress sensitive molecules should be expressed as amounts excreted per time unit per kg body-weight, rather than being expressed as concentrations in samples. Urine and feces excretion varies significantly within and between animals over time, which may render simple concentration measures of molecules of little biological relevance. [ABSTRACT FROM AUTHOR]