ABSTRACT
PURPOSE: This study aimed to investigate the impact of CC chemokine receptor 7 (CCR7) on the recruitment and polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). METHODS: We analyzed CCR7 expression pattern, clinicopathological significance, and its association with M2 macrophage infiltration in OSCC by bioinformatic methods. Small interfering RNA (siRNA) was utilized to silence CCR7 in OSCC cells. Conditioned media (CM) was harvested from transfected OSCC cells to establish a co-culture model of THP-1 derived macrophages and OSCC cells. Transwell assay and cell adhesion assay were performed to examine the effect of CCR7 on macrophages recruitment and adhesion. Cytoskeleton was labelled by phalloidin to observe macrophage morphological changes. Moreover, phenotypic alteration of macrophages was measured using quantitative real-time PCR (qRT-PCR), flow cytometry, and immunofluorescence (IF) staining. Ultimately, recombinant human CCL19 and CCL21 were added into the medium of THP-1 derived macrophages to explore their effects on polarization in vitro. RESULTS: In OSCC patients, the overexpression of CCR7 positively correlated with lymph node metastasis and M2 macrophage infiltration. Macrophage not only exhibited enhanced migration, invasion and adhesion abilities, but also appeared more spindle and branched in vitro when treated with CM from OSCC cells. However, these phenomena were abrogated with knockdown of CCR7. We also discovered that inhibition of CCR7 in OSCC cells suppressed TAMs polarization to an M2 phenotype. In addition, recombinant human CCL19 and CCL21 promoted macrophage M2-polarization in vitro. CONCLUSION: CCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.
ABSTRACT
Dynamic models of gene expression are urgently required. In this paper, we describe the time evolution of gene expression by learning a jump diffusion process to model the biological process directly. Our algorithm needs aggregate gene expression data as input and outputs the parameters of the jump diffusion process. The learned jump diffusion process can predict population distributions of gene expression at any developmental stage, obtain long-time trajectories for individual cells, and offer a novel approach to computing RNA velocity. Moreover, it studies biological systems from a stochastic dynamic perspective. Gene expression data at a time point, which is a snapshot of a cellular process, is treated as an empirical marginal distribution of a stochastic process. The Wasserstein distance between the empirical distribution and predicted distribution by the jump diffusion process is minimized to learn the dynamics. For the learned jump diffusion process, its trajectories correspond to the development process of cells, the stochasticity determines the heterogeneity of cells, its instantaneous rate of state change can be taken as "RNA velocity", and the changes in scales and orientations of clusters can be noticed too. We demonstrate that our method can recover the underlying nonlinear dynamics better compared to previous parametric models and the diffusion processes driven by Brownian motion for both synthetic and real world datasets. Our method is also robust to perturbations of data because the computation involves only population expectations.
Subject(s)
Models, Biological , Nonlinear Dynamics , Diffusion , Gene Expression , Stochastic ProcessesABSTRACT
OBJECTIVE: To observe the effects of Wentong acupuncture on bone mineral density (BMD), bone metabolism and intestinal function in elderly patients of primary osteoporosis with intestinal dysfunction. METHODS: A total of 128 elderly patients of primary osteoporosis with intestinal dysfunction were randomly divided into an observation group and a control group, 64 cases in each group. Patients in the control group were treated with oral administration of vitamin D calcium chewable tablets (0.6 g, once a day) and calcitriol capsules (0.25 µg, three times a day); the treatment was given for 6 months. On the basis of the treatment in the control group, patients in the observation group were additionally treated with Wentong acupuncture at Shenshu (BL 23), Mingmen (GV 4), Pishu (BL 20), Dachangshu (BL 25), Tianshu (ST 25) and Zusanli (ST 36), etc. for 30 min each time, once a day. After 1-week treatment, the patients took a rest for 2 days; the treatment was given for 6 months. Before and after treatment, the BMD of lumbar spine, femoral neck and femoral trochanter was detected by dual energy X-ray absorptiometry, and the serum levels of bone alkaline phosphatase (NBAP), osteocalcin (OC), matrix metalloproteinase-2 (MMP-2) and calcitonin (CT) were detected by ELISA method. The primary symptom scores of intestinal function, serum diamine oxidase (DAO) and D-lactic acid (D-Lac) levels were compared between the two groups before and after treatment, and the clinical efficacy of the two groups was evaluated. RESULTS: The total effective rate was 85.9% (55/64) in the observation group, which was higher than 71.9% (46/64) in the control group (P<0.05). After treatment, BMD were increased (P<0.05), and serum bone metabolism indexes were improved in the two groups (P<0.05); the BMD and serum bone metabolism indexes in the observation group were better than those in the control group (P<0.05). After treatment, the primary symptom scores of intestinal function, serum DAO and D-Lac levels in the observation group were decreased (P<0.05), and the indexes in the observation group were lower than those in the control group (P<0.05). CONCLUSION: The adjuvant therapy of Wentong acupuncture could increase BMD, improve bone metabolism and regulate intestinal function in elderly patients of primary osteoporosis with intestinal dysfunction.
