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Myeloid Derived Suppressor Cell (MDSC) has been raised to be a novel target for multiple cancers. However, target agents on MDSC have not display promising efficacy. One of the critical reasons shall be less optimal patient selection. In the present study, we aimed to identify clinical parameters relevant to MDSC level in hepatocellular carcinoma (HCC) patients for future MDSC targeted therapy. In the present study, a series of 55 HCC patients (testing group) and 20 healthy donors were analyzed investigating frequencies of MDSC in peripheral blood mononuclear cells (PBMC). As a result, we found that MDSC level was increased in HCC patients compared to healthy donors (10.33% vs 1.54%, p < 0.0001). The monocytes (r2 = 0.2875, p < 0.0001), neutrophils (r2 = 0.3630, p < 0.0001) and platelet counts (r2 = 0.0828, p = 0.0331) in circulation was positively associated with MDSC level. Then, the prognostic value of the above predictors was determined in a retrospective database of 255 HCC patients (validation group). The baseline characteristics of testing and validation group were similar. Multivariate analysis by Cox regression revealed that neutrophil count was an independent predictor for overall survival (OS) (p = 0.000, HR 1.065, 95% CI 1.028-1.103), with the rest parameters failed to reach a significant result. In summary, the present study firstly identified blood neutrophil counts was a predictor of MDSC level in PBMC for HCC patients. And, patients with higher neutrophil count level might be the optimal patient subgroup for MDSC targeted therapy.

The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques (Macaca leonina) are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, little is known about the composition and temporal variability of vaginal microbiota of the northern pig-tailed macaque. Here, we present a comprehensive catalog of the composition and temporal dynamics of vaginal microbiota of two healthy northern pig-tailed macaques over 19 weeks using 454-pyrosequencing of 16S rRNA genes. We found remarkably high proportions of a diverse array of anaerobic bacteria associated with bacterial vaginosis. Atopobium and Sneathia were dominant genera, and interestingly, we demonstrated the presence of Lactobacillus-dominated vaginal microbiota. Moreover, longitudinal analysis demonstrated that the temporal dynamics of the vaginal microbiota were considerably individualized. Finally, network analysis revealed that vaginal pH may influence the temporal dynamics of the vaginal microbiota, suggesting that inter-subject variability of vaginal bacterial communities could be mirrored in inter-subject variation in correlation profiles of species with each other and with vaginal pH over time. Our results suggest that the northern pig-tailed macaque could be an ideal animal model for prospective investigation of the mechanisms by which vaginal microbiota influence susceptibility and resistance to HIV-1 infection in the context of highly polymicrobial and Lactobacillus-dominated states.

The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species of Old World monkey, and we previously found that PBMCs from M. leonina were susceptible to human immunodeficiency virus type 1 (HIV-1), which may be due to the absence of a TRIM5 protein restricting HIV-1 replication. Here we investigated the infection potentials of six laboratory adapted HIV-1 strains and three primary HIV-1 isolates in PBMCs from M. leonina. The results indicate that these strains are characterized by various but low replication levels, and among which, HIV-1NL4-3 shows the highest replication ability. Based on the abundant evidence of species-specific interactions between restriction factors APOBEC3 and HIV/SIV-derived Vif protein, we subsequently examined the replication potentials of vif-substituted HIV-1 (HSIV) in M. leonina PBMCs. Notably, HSIV-vifmac and stHIV-1SV chimeras, two HIV-1NL4-3-derived viruses encoding the viral infectivity factor (Vif) protein from SIVmac239, replicated robustly in cells from M. leonina, which suggests that HSIV could effectively antagonize the antiviral activity of APOBEC3 proteins expressed in cells of M. leonina. Therefore, our data demonstrate that M. leonina has the potential to be developed into a promising animal model for human AIDS.

The pig-tailed macaque is an important non-human primate experimental animal model that has been widely used in the research of AIDS and other diseases. Pig-tailed macaques include Mentawai macaques (Macaca pagensis), Sunda pig-tailed macaques (M. nemestrina) and northern pig-tailed macaques (M. leonina). Northern pig-tailed macaques inhabit China and surrounding Southeast Asia countries. To our knowledge, no reports have been published regarding the hematology and blood chemistry parameters of northern pig-tailed macaques, which are important for the objective evaluation of experimental results. We measured and analyzed 18 hematology parameters and 13 blood chemistry parameters in juvenile (aged 2-4 years) and adult (aged 5-10 years) northern pig-tailed macaques. We found that red blood cells, hemoglobin and alkaline phosphatase values were lower in female macaques than male macaques in both juvenile and adult groups. White blood cells, lymphocyte, monocytes, platelet distribution width, cholesterol, aspartate aminotransferase and alkaline phosphatase values were higher in juvenile macaques than adult macaques, while creatinine and triglycerides values were lower in juvenile macaques. Mean corpuscular hemoglobin and creatinine values were positively correlated with weight in juvenile groups. In adult groups, mean corpuscular hemoglobin, percentage of granulocyte, hemoglobin and creatinine were also positively correlated with weight, and lymphocyte, percentage of lymphocyte, red cell distribution width, aspartate aminotransferase and cholesterol values were negatively correlated with weight. The results suggest that age, gender and weight of northern pig-tailed macaques affected their hematology and blood chemistry parameters. This hematological and blood chemistry study has great significance in biomedical research and animal models using northern pig-tailed macaque as an experimental animal.

Nonhuman primate animal models play an important role in studying HIV-1 pathogenesis, developing antiviral drugs and vaccines. Due to the lack of animals that can be directly infected with HIV-1, SIV/SHIV-infected macaques have been widely used in AIDS research. Although these models are somewhat similar to human AIDS, there are many limitations due to genetic differences between SIV/SHIV and HIV-1. Developing a suitable nonhuman primate animal model is still an important topic in HIV/AIDS research. The pigtailed macaque is the only primate in Old World monkeys that can be infected with HIV-1 and offer many benefits as HIV-1 intravenous and sexual transmission models. Here we reviewed the characteristics of pigtailed macaque models infected by SIV, HIV, SHIV, and HSIV via intravenous and mucosal routes. In addition, we briefly introduced the molecular mechanisms of viral replication in pigtailed macaque cells, and discussed the limitations and prospects of pigtailed macaque models in AIDS research.