Immunophenotype and function of peripheral blood lymphocyte subsets in Chinese rhesus macaques / 中华微生物学和免疫学杂志

Objective:To provide data reference for using Chinese rhesus macaques as research model by studying the immunophenotype and function of peripheral blood lymphocytes in Chinese rhesus macaques.Methods:By optimizing antibody clones and fluorescent colors, the lymphocyte subset assay and T cell function assay panels were determined. Then the panels were used to analyze the proportion of T, B, NK and other cell subsets in peripheral blood mononuclear cells (PBMCs) in 15 healthy Chinese rhesus monkeys, and the ability of T cells to secrete cytokines after non-specific stimulation.Results:Two multi-color flow cytometry analytic panels were established. Panel 1 could simultaneously detect a variety of lymphocyte subsets, including cytotoxic T lymphocytes, follicular helper T cells, regulatory T cells, B cells and NK cells. Panel 2 could detect the functions of multiple T cell subsets and the expression of immune checkpoint moleculars. The mean percentages of T, B, NK, Tfh, Treg, CD16 + NK and CD56 + NK cells in PBMCs of the Chinese rhesus macaques were (75.32±7.73)%, (13.22±7.50)%, (0.88±0.48)%, (0.73±0.27)%, (0.75±0.43)%, (47.87±22.35)% and (10.69±12.41)%. After non-specific stimulation, the proportion of CD4 + T cells secreting IL-2 and TNF-α was higher than that of CD8 + T cells, and the proportion of CD8 + T cells secreting CD107a and IFN-γ was higher than that of CD4 + T cells, while the proportion of CD4 + and CD8 + T cells secreting IL-17A was low. Conclusions:This study established a multi-color flow detection scheme that could simultaneously detect multiple cellular surface molecules and cytokines at the single cell level and could accurately and comprehensively analyze the immune cell subsets, functions and the immune checkpoint molecules in peripheral blood of Chinese rhesus macaques, providing a new experimental method and basic data for the development of vaccines and drugs against infectious diseases.

Gene expression in rhesus macaques prefrontal cortex after multiple sevoflurane exposures / 中国临床药理学与治疗学

AIM: To analyze differentially expressed genes after multiple sevoflurane anesthesia in rhesus macaques was studied. METHODS: Rhesus macaques received three anesthetic exposures to sevoflurane on postnatal day (P) 7 and then on P21 and P35. RNA sequencing analysis was used in the studies. RESULTS: Transcriptomic analysis of differentially expressed genes (DEGs) revealed that up-regulated genes were mainly enriched in the regulation of positive regulation of gastrulation and odontogenesis, while down-regulated genes were primarily enriched in the regulation of transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding, and MAPK signaling pathway. CONCLUSION: Differentially expressed genes (DEGs) were analyzed in the prefrontal cortex of rhesus macaques after multiple sevoflurane exposures by RNA sequencing to screen essential genes for subsequent studies on neurotoxicity induced by sevoflurane, providing a solid basis for the study of the mechanism of general anesthesia.

Intermittent theta burst stimulation can improve the spatially-delayed responses of working memory / 中华物理医学与康复杂志

Objective:To observe any effect of intermittent theta burst stimulation (iTBS) on the spatially-delayed responses of working memory using cynomolgus macaques.Methods:The working memory of six male cynomolgus macaques (8-9 years old) was trained using a spatially-delayed response task. They were then randomly divided into an iTBS group and a control group, each of 3. The iTBS group was given iTBS at an intensity of 35% of the maximum output, with 2 seconds of stimulation followed by 8 seconds of rest with trains of 50Hz bursts repeated at a frequency of 5Hz over a period of 192 seconds once daily for 5 days, while the control group was given sham iTBS. Before and after the 5 days, the body weight and working memory of each animal were evaluated. The total number of effective feeding episodes, and of effective feeding episodes with short and long delay periods were recorded.Results:There was no significant change in the average body weight of either group before and after the modeling and iTBS intervention. After the intervention the number of total effective feeding cases and those with a short delay period were both significantly higher in the iTBS group than in the control group. However, no significant inter-group differences in the effective feeding cases with a long delay period were observed.Conclusions:iTBS is effective in improving the spatially-delayed responses of working memory, at least in cynomolgus macaques.

Effects of bone marrow mesenchymal stem cell transplantation on thymus structure and function in the aging macaques / 中国组织工程研究

BACKGROUND: Thymus is an important central immune organ of human body, which is the place where T cells grow, develop and mature. Thymus is the first organ of senescence in human body, gradually atrophy and degeneration after puberty, followed by the gradual decline of immune function. OBJECTIVE: To investigate the effect of bone marrow mesenchymal stem cells on the structure and function of thymus in the aging macaques. METHODS: Bone marrow was collected from female macaques with an average age of 3 years by bone marrow aspiration. Bone marrow mesenchymal stem cells were obtained by differential adherent culture. Five young macaques with an average age of 3 years were used as the young group. Ten aging macaques with an average age of 25 years were randomly divided into elderly group (n=4) and elderly treatment group (n=6). The macaques in the elderly treatment group were infused with bone marrow mesenchymal stem cells (1 × 107 cells/kg) through the femoral vein, and were infused every other day for three consecutive times. Macaques of the young group and the elderly group were infused with the same volume of saline at the same time. The changes of output and secretion levels of the subgroup of thymocytes in the elderly treatment group after infusion, thymic index, thymic tissue structure and collagen fiber deposition in each group were analyzed. RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cell transplantation increased thymus index, T cell output level and reduced regulatory T cells, improved thymus secretion function, increased thymosin alpha and thymosin II secretion. The thymus parenchyma area increased; the skin and medulla junction appeared; part of the thymus tissue was regenerated and transformed to normal structure; the degree of thymus tissue fibrosis was reduced; and collagen fiber deposition was reduced. These results indicate that bone marrow mesenchymal stem cell transplantation can improve the structure and function of thymus in aging macaques.

Recent advances in myeloid-derived suppressor cell biology / 医学前沿

In recent years, studying the role of myeloid-derived suppressor cells (MDSCs) in many pathological inflammatory conditions has become a very active research area. Although the role of MDSCs in cancer is relatively well established, their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion. Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases. The following topics will be specifically focused upon: (1) definition and characterization of MDSCs; (2) whether all MDSC populations consist of immature cells; (3) technical issues in MDSC isolation, estimation and characterization; (4) the origin of MDSCs and their anatomical distribution in health and disease; (5) mediators of MDSC expansion and accumulation; (6) factors that determine the expansion of one MDSC population over the other; (7) the Yin and Yang roles of MDSCs. Moreover, the functions of MDSCs will be addressed throughout the text.

Age-related changes in the cranial thickness of Japanese macaques ( Macaca fuscata ) / Cambios relacionados con la edad en el grosor craneal de los macacos japoneses ( Macaca fuscata )

Craniometry has revealed that continuous skull expansion occurs after dental maturity in macaques and other nonhuman primates. Endocranial volume has been shown to increase with age from mid-adulthood to older age in macaques. Thus, neurocranial thickness may decrease with age, especially from mid-adulthood to older age. Here, we investigated age-related changes in the cranial thickness of Japanese macaques (Macaca fuscata). Ten cranial thickness measurements (ten neurocranial landmarks) were made using computed tomographic scans of 140 crania from adult macaques (67 males and 73 females). The cranial thickness at many sites was shown to increase in the neurocranium from young adulthood (7-9 years) to early-mid adulthood (14-19 years) in males and latemid adulthood (19-24 years) in females, while it was decreased in the oldest age group (>24 years). The cranial thickness at various sites showed a significant decrease from mid-adulthood to very old age in both sexes, although females had more sites with decreasing thickness than did males. The difference between sexes in terms of age-related changes in cranial thickness at sites on the mid-sagittal plane may be associated with the differences in the size of the projecting face and canines between males and females. The greater number of sites with decreasing thickness in females than in males may be associated with postmenopausal estrogen depletion in female macaques.

La craneometría ha revelado que la expansión continua del cráneo se produce después de la madurez dental en macacos y otros primates no humanos. Se ha demostrado que el volumen endocraneal aumenta con la edad desde mediados de la edad adulta hasta la edad más avanzada en macacos. Por lo tanto, el grosor neurocraneal puede disminuir con la edad, especialmente desde la edad adulta media hasta la edad avanzada. Aquí, investigamos los cambios relacionados con la edad en el grosor craneal de los macacos Japoneses (Macaca fuscata). Se realizaron diez mediciones del grosor craneal (considerando diez puntos de referencia neurocraneales) mediante tomografías computarizadas de 140 cráneos de macacos adultos (67 machos y 73 hembras). Se observó que el grosor craneal en muchos sitios aumentó en el neurocráneo desde la edad adulta joven (7-9 años) hasta la edad adulta media (14-19 años) en los hombres y en la edad adulta media tardía (19-24 años) en las mujeres, mientras que se redujo en el grupo de mayor edad (> 24 años). El grosor craneal en varios sitios mostró una disminución significativa desde la edad adulta media hasta la edad muy avanzada en ambos sexos, aunque las hembras tenían más sitios con grosor decreciente. La diferencia entre sexos, en términos de cambios relacionados con la edad, en el grosor craneal en los sitios en el plano mediano puede asociarse con las diferencias en el tamaño de la cara y en los caninos entre machos y hembras. El mayor número de sitios con grosor decreciente en las hembras respecto a los machos puede estar asociado con el agotamiento de los estrógenos posmenopáusicos en los macacos hembras.

Bacterial isolation of oral, rectum and anus swabs from Macaca fascicularis and Macaca namestrina in Kemasul, Pahang, Malaysia

Abstract@#This study was conducted with the aim of isolating and identifying pathogenic bacterial communities from actively shedding anatomical sites of Macaca fascicularis and M. namestrina in Jambu Rias (JR) and Chemomoi (CM) in Kemasul Forest Reserve, Pahang and to determine the antibiotic susceptibility of these isolates. The findings show that M. fascicularis had higher bacterial density and ten different isolates were identified from these samples. The antibiotic susceptibility tests determined that ciproflaxin and vancomycin as most effective antibiotic towards these isolates.

Investigation of default mode networks in rhesus macaque brain with 7.0T resting-state fMRI / 中国医学影像技术

Objective To investigate default mode networks (DMN) in healthy rhesus monkey brain.Methods Under anesthesia,two healthy rhesus macaques underwent resting state fMRI at a 7.0T MR scanner.The functional images were firstly normalized to the standard rhesus monkey template 112SM-RL-T1,and the GIFT software was aplied to conduct group-level independent component analysis on all preprocessed functional images.Results The functional connectivity maps of the resting-state networks of rhesus macaques were obtained using this method.DMN bilaterally included posterior cingulate cortex,anterior cingulate cortex,medial parietal cortex,retrosplenial cortex,arcuate sulcus,ventral intraparietal area,temporoparietal area,superior temporal sulcus dorsal bank and a portion of visual cortex.Conclusion With the help of cutting-edge 7.0T fMRI technology,It was demonstrated that DMN of rhesus macaque brain highly resembled the ones in human,which could support the notion that non-primates are useful models for neuropharmacological and neurocognitive studies.

Distribution of interleukin 17 receptor mRNA in rhesus macaques / 中国免疫学杂志

Objective:To delineate the distribution and abundance of interleukin 17 receptor mRNA in normal tissues of rhesus macaques.Methods:Tissue samples were collected from different systems including lymphoid system,digestive system and genital system and the mRNA levels of IL-17RA and IL-17RC were examined by real time RT-PCR.Meanwhile the levels of IL-17RA and IL-17RC mRNA in the PBMCs of rhesus macaques,African green monkeys and cynomolgus monkeys were examined.Results:IL-17RA mRNA was expressed in all the tested tissues and the levels were significantly different among these systems (P＜0.05).IL-17RC mRNA level in the large intestine was higher than that in the small intestine.IL-17RA mRNA level in rhesus macaque PBMCs was 3 and 5 times higher than that of cynomolgus monkeys and African green monkeys respectively,while IL-17RC mRNA in the PBMCs was below the limit of detection.Conclusion:IL-17RA is widely distributed in rhesus macaques;the expression level is different among different tissues and species.

Performance of bovine-PPD based whole blood IFN-γassay for rhesus macaques / 中国比较医学杂志

Objective To assess the potential of whole blood IFN-γassay for diagnosing mycobacterium in rhesus macaques.Methods Firstly, basic serum IFN-γconcentrations of TST-negative and -positive rhesus macaques were detected.Then, heparinized whole blood from TST-negative and-positive rhesus macaques was incubated with PBS and 200 IU bovine-PPD ( tuberculin purified protein derivative ) for about 24 h, respectively.The supernatant plasma were harvested and used to determine the concentrations of IFN-γ.The results of plasma IFN-γconcentrations and stimulation index ( SI) were used to analyze the diagnostic potential of the whole blood IFN-γassay.Results The basic serum concentrations of IFN-γfor the TST-positive monkeys were significantly higher than that of the TST-negative macaques, showing a high coefficient of variation.There was no significant effect on the production of IFN-γin the TST-negative macaques.While significantly elevation of IFN-γconcentrations was found in stimulated plasma of TST-positive macaques (P<0.01).The SI of TST-positive macaques was significantly higher than the TST-negative ones.ROC curve analysis revealed that IFN-γconcentrations and SI could be used as evaluation index of whole blood IFN-γassay.Conclusions Based on a small sample experiment we have demonstrated that whole blood IFN-γassay may be one possible auxiliary diagnostic method for tuberculin skin test.

Dynamic changes of immunological and virological items in peripheral blood of Chinese-origin Rhesus macaques infected with SIVmac251 / 中华微生物学和免疫学杂志

ObjectiveTo observe the virological and immunological items in peripheral blood of Chinese-origin Rhesus macaques infected with SIVmac251.The normal levels of WBC and CD4+T cell ratio for healthy Chinese-origin Rhesus macaques that suitable for simian AIDS modeling also investigated.MethodsThirty-six Chinese-origin Rhesus macaques were intravenously infected with SIVmac251.Blood samples were collected at 10 time points respectively include 1 day before SIV infection,every week within 1-8th week and then in tenth week post infection.Blood routine,peripheral blood T lymphocyte subsets,plasma viral load were tested.ResultsThe most significant changes of the tested items were appeared in 1 or 2 weeks post SIV infection,while the WBC counts didn't show marked changes in all the time points tested.WBC counts ranged from 4×106/ml to 10×106/ml and the CD4+T cells ratio high than 25％ are the suitable levels for simian AIDS modeling.ConclusionThis research provides necessary and beneficial informations to the usage of Chinese-origin Rhesus macaques in AIDS research.

Serial passage of clade C SHIV-XJ02170 in Chinese origin Rhesus macaques / 中华微生物学和免疫学杂志

Objective To analyze the virologic and immunologic properties during SHIV-XJ02170passage in vivo and construct the clade C SHIV/Chinese origin Rhesus macaques AIDS model . Methods SHIV-XJ02170 cell-free virus tranfected in 293T was adapted by serial passage in nine Chinese-origin Rhesus macaques. CD4/CD8 ratio was detected by flow cytometry to analyze the changes in viral pathogenicity. Real-time RT-PCR and IFN-γsecreting ELISPOT methods were used to analyze changes in characteristics of virology and immunology. Results During in vivo passage, CD4/CD8 ratio did not deeply decline. However,the peak and setpoint viral load in the line 3 show a continuous upward trend. The strong humoral and cellular immune responses were induced after SHIV-XJ02170 infection. Meanwhile, there was significant positive correlation between the viral load and binding antibody titer. Conclusion There were no pathogenic viral strains, and upward trend in virulence of SHIV-XJ02170 was found during in vivo passaging. SHIVXJ02170/Chinese origin Rhesus macaques model will play an important role in effect evaluation of candidate AIDS vaccines in China.

Understanding type 2 diabetes and aging: lessons from nonhuman primates.

Background: The increase in global prevalence of obesity and diabetes, and the growth of the elderly population worldwide emphasize the biomedical research need for an animal model which exhibits close similarity to human disease and aging processes. The rhesus monkey develops obesity and type 2 diabetes spontaneously and naturally when ad libitum fed, within a lifespan which is about a third that of the human. Objective: To characterize the genetic, structural, biochemical and physiological changes occurring in monkeys who age successfully and in those who develop obesity and type 2 diabetes. Results: The rhesus monkey demonstrates the same signs and symptoms of type 2 diabetes, including macroand microvascular complications, as observed in humans. Age-related changes, potential biomarkers, and proposed biochemical pathways of aging can be readily investigated, with outcomes very similar to those in humans. Conclusion: The rhesus monkey model imparts valuable insights to normal and pathological processes accompanying aging and type 2 diabetes. It also provides a valuable tool by which to test novel therapeutic interventions which otherwise can not be performed in humans due to ethical considerations, but where results are highly translatable.

Histopathologic findings of pulmonary acariasis in a rhesus monkeys breeding unit / Aspectos histopatológicos da acaríase pulmonar em uma criação de macacos rhesus

Histological lesions in the lungs of rhesus monkeys (Macaca mulatta) related with Pneumonyssus simicola were evidenced. The most prominent pathologic alterations included numerous thin-walled cysts 1-5 mm diameter scattered throughout the lungs, bronchiolitis, peribronchiolitis where the mites were found associated with pigmented and non-pigmented materials. Our study included data from 347 rhesus monkeys submitted to necropsies during 20 years. Four adult debilitated animals were found with pulmonary acariasis which showed a very low incidence of parasite (1.2 percent) in the colony. Most of the published literature described as common and widespread pulmonary acariasis in Old World monkeys. The present study confirms the ubiquity of P. simicola in captive born and raised rhesus monkeys that would compromise experimental studies involving the respiratory system.

Foram evidenciadas lesões histológicas nos pulmões de macacos rhesus (Macaca mulatta) relacionadas ao Pneumonyssus simicola. As principais alterações incluíram numerosos cistos variando de 1-5 mm de diâmetro, com paredes finas e amplamente distribuídos nos pulmões; bronquiolite e peribronquiolite, onde os ácaros foram encontrados associados com materiais particulados pigmentados ou não. Nosso estudo incluiu dados de 347 macacos rhesus submetidos a necropsias no decorrer de 20 anos. A acaríase pulmonar foi diagnosticada em quatro animais adultos debilitados, o que representou uma incidência muito baixa do parasita (1,2 por cento) na colônia. A literatura descreve uma alta incidência de acaríase pulmonar em macacos do Velho Mundo. O presente estudo confirma a ubiqüidade do P. simicola em macacos rhesus nascidos e manejados em cativeiro, que compromete sua utilização em estudos experimentais envolvendo o sistema respiratório.