Abnormal lipid synthesis as a therapeutic target for cancer stem cells.

Cancer stem cells (CSCs) comprise a subpopulation of cancer cells with stem cell properties, which exhibit the characteristics of high tumorigenicity, self-renewal, and tumor initiation and are associated with the occurrence, metastasis, therapy resistance, and relapse of cancer. Compared with differentiated cells, CSCs have unique metabolic characteristics, and metabolic reprogramming contributes to the self-renewal and maintenance of stem cells. It has been reported that CSCs are highly dependent on lipid metabolism to maintain stemness and satisfy the requirements of biosynthesis and energy metabolism. In this review, we demonstrate that lipid anabolism alterations promote the survival of CSCs, including de novo lipogenesis, lipid desaturation, and cholesterol synthesis. In addition, we also emphasize the molecular mechanism underlying the relationship between lipid synthesis and stem cell survival, the signal trans-duction pathways involved, and the application prospect of lipid synthesis reprogramming in CSC therapy. It is demonstrated that the dependence on lipid synthesis makes targeting of lipid synthesis metabolism a promising therapeutic strategy for eliminating CSCs. Targeting key molecules in lipid synthesis will play an important role in anti-CSC therapy.

[Expression of secretoglobin family 2A member 2 in oral lichen planus lesions].

OBJECTIVE: To examine the expression of secretoglobin family 2A member 2 (SCGB2A2) (mammaglobin A, MGB1) in oral lichen planus (OLP) lesions. METHODS: Sixteen OLP patients and 10 healthy controls were included in this study. The real time reverse transcription-PCR (RT-PCR), Western blotting and immunohistochemistry (IHC) were used to determine the mRNA and protein of SCGB2A2. RESULTS: Compared with healthy controls (0.48 ± 0.09), the expression of SCGB2A2 protein in OLP lesions significantly increased (1.02 ± 0.11) (P < 0.05).However, the mRNA level of SCGB2A2 in lesions was significantly lower than that in controls (P < 0.05). CONCLUSIONS: These results suggest that SCGB2A2 may be involved in pathogenesis of OLP.

The dynamic changes of circulating OCN+ cells versus insulinlike growth factor-I during primary healing of orthognathic surgeries.

OBJECTIVE: The objective of this study was to determine the dynamic changes of circulating osteocalcin(+) (OCN(+)) cells and insulinlike growth factor-I (IGF-I) in peripheral blood during early primary repair of jaw bones in patients with orthognathic surgery. STUDY DESIGN: The expression of bone-related genes was detected by RT-PCR in circulating OCN(+) cells. The numbers of OCN(+) cells and serum level of IGF-I were determined by flow cytometry, immunocytochemical staining, and ELISA. RESULTS: OCN(+) cells significantly increased in peripheral blood, and reached the peak at 1 to 2 weeks after surgery (P < .05). IGF-I in patients significantly decreased 1 week after surgery (P < .05), and then returned gradually to the normal level. There was no significant correlation between the number of circulating OCN(+) cells and the level of IGF-I (P > .05). CONCLUSIONS: These findings suggested that circulating OCN(+) cells, at least in part, could be mobilized in response to bone injury, and contribute to bone repair in patients with orthognathic surgery.

The correlation between the severity of radiotherapy-induced glossitis andendothelial cell injury in local tissues in a rat model

Objectives: To explore the correlation between the severity of radiotherapy-induced glossitis (RTG) and endothelialcell injury in local tissues in a rat model.Study Design: The RTG animal model was designed and used by our team. The Oral mucositis index(OMI) wasdocumented daily. Immunohistochemistry (IHC) Staining of CD34 was utilized to identify endothelial cells in theRTG tissues. Apoptosis of endothelial cells in local lesions due to RTG was detected by the TUNEL assay. Thedynamic relationship between the OMI and apoptotic endothelial cells was statistically analyzed by time.Results and Conclusions: The injury and apoptosis of endothelial cells were observed 3 day post-irradiation. Thevascular lumens of the post-irradiation tongue lesions were irregular; thrombosis formation in the center of thelumens, unsmooth lumen walls and vasodilated vessels were observed. Also, endothelial cells detached from thebasal membrane and were found in the lumens. The percentages (%) of apoptotic endothelial cells were 78.3±0.31(5 day); 89.3±0.83 (8 day); 83.5±0.41 (14 day); 69.3±0.57 (21 day); and 47.3±0.59 (28 day). The OMI was correlatedwith the percentage of apoptotic endothelial cells (R0.034). Summary, endothelial cell injury was correlatedwith the pathogenic condition of RTG (AU)

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Neutrophils infiltration is early event of an oral mucosalxenotransplantation model

Introduction: As important effector cells of the innate immune system, neutrophils are involved in rejection of solidorgan and/or tissue transplants. But their role in rejection of oral mucosa transplantation (OMT) remains unclear. Theaim of this study is to observe the spatial-temporal change of neutrophils during acute rejection of OMT.Methods: In a rat model of oral mucosal xenotransplantation, myeloperoxidase (MPO), an indicator of influx ofneutrophils was detected by technique of ELISA on day 7 and 30 (D7, D30) of posttransplantation.Results: On D7, MPO level (6.183±0.416, ×102 ng/mg) in the OMT group was significantly higher than in trauma(0.681±0.073, ×102 ng/mg) and normal controls (0.262±0.043, ×102 ng/mg) (P<0.001, respectively), and this levelwas found to correlate with the index of submandibular lymph nodes (ILN), an indicator of inflammation of rejection(r=0.909, P<0.05). Moreover, this level was decreased significantly under FK506 treatment (2.103±0.146,×102 ng/mg, P= 0.005). On D30, MPO in the OMT group (1.063±0.096, ×102 ng/mg) was lower significantly thanthat on D7 (P<0.001), although this level was still higher that of normal controls on D30 (0.532±0.112, ×102 ng/mg, P = 0.042).Conclusion: Neutrophils infiltration was an early event of OMT, which may play important roles on acute rejectionof OMT (AU)

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The development and inflammatory featuresof radiotherapy-induced glossitis in rats

Objectives: To improve the existing animal models (mice, rats, and hamsters) for radiotherapy-induced oral mucositis(RTOM), thereby establishing a radiotherapy-induced glossitis (RTG) Sprague-Dawley (SD) rat model.Study Design: A lead device was designed to limit radiation exposure to a 1×1 cm2 area of a rat’s dorsal anteriortongue with a single 30Gy of X-ray radiation. The general conditions of the irradiated rats, such as body-weightand behavior, were observed. The oral mucositis index (OMI) of the RTG rats were measured daily. Histologicalchanges of the irradiated tongue tissues were assayed by H&E staining.Results and Conclusion: No significant changes were clinically observed 3 to 4 days after irradiation. At 5 to 6 day,punctuation and confluenced redness of the mucosa were observed. The small blood vessels became more extensive,engorged, thin vessel walls. More infiltrating cells were observable, necrosis and exfoliation of the squamouscells appeared, and the formation of an ulcerative lesion could be observed. Seven to 15 days, the exfoliated epitheliallayer was observed to have formed an ulcerative lesion, then aggravated ulcerative lesions consisting ofpseudomembranous filament exudates could be observed. The structure of the epithelium had become completelydisintegrated, forming deep, microscopic ulcerative lesions. Twenty-one days, the periphery of the ulcer wasobserved to have begun to heal, and granulation tissue could be observed at the bottom of the ulceration. At 35days after irradiation, the epithelial structure presented again, but the epithelium was very thin. An RTG animalmodel was successfully established in SD rats, which provides a new research platform for the study of RTOMpathogenesis (AU)

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[Correlation between the CD68 proportion of peripheral blood mononuclear cells and macrophage infiltration during acute rejection of rat oral mucosal xenotransplantation].

OBJECTIVE: To investigate the role of the dynamic process of peripheral blood CD68 mononuclear cells proportion and macrophages inflitration and possible correlation between them during acute rejection of rat oral mucosal xenotransplantation. METHODS: Thirty-six female wistar rats were divided into three groups randomly, including xenotransplantation group (n = 15), trauma control group (n = 12) and normal control group (n = 9). The rat oral mucosa xenotransplantation model was established. The flow cytometry was used to evaluate the peripheral blood CD68 mononuclear cell and immunohistochemical assay performed to detect the macrophages infiltration one week (W1), two weeks (W2) and four weeks (W4) after xenotransplantation. RESULTS: The peripheral blood CD68 mononuclear cells percentage of each xenotransplantation group presented a rise and fall tendency at the three time points, and the peak value appeared at W4 (43.1%), and the nadir at W2 (10.4%). The macrophage counts achieved peak value in xenotransplantation group at W1 [580.0(195.5) cell/high power field], and then reduced with time. CONCLUSIONS: The mononuclear cells and macrophage were capable of recognizing the xenograft and directly participated the acute rejection of rat oral mucosal xenotransplantation. The peripheral blood mononuclear cells percentage could reflect macrophage infiltrating condition at the early stage of the acute rejection.

Neutrophils infiltration is early event of an oral mucosal xenotransplantation model.

INTRODUCTION: As important effector cells of the innate immune system, neutrophils are involved in rejection of solid organ and/or tissue transplants. But their role in rejection of oral mucosa transplantation (OMT) remains unclear. The aim of this study is to observe the spatial-temporal change of neutrophils during acute rejection of OMT. METHODS: In a rat model of oral mucosal xenotransplantation, myeloperoxidase (MPO), an indicator of influx of neutrophils was detected by technique of ELISA on day 7 and 30 (D7, D30) of posttransplantation. RESULTS: On D7, MPO level (6.183±0.416, x102 ng/mg) in the OMT group was significantly higher than in trauma (0.681±0.073, x102 ng/mg) and normal controls (0.262±0.043, x102 ng/mg) (P<0.001, respectively), and this level was found to correlate with the index of submandibular lymph nodes (ILN), an indicator of inflammation of rejection (r=0.909, P<0.05). Moreover, this level was decreased significantly under FK506 treatment (2.103±0.146, x102 ng/mg, P=0.005). On D30, MPO in the OMT group (1.063±0.096, x102 ng/mg) was lower significantly than that on D7 (P<0.001), although this level was still higher that of normal controls on D30 (0.532±0.112, x102 ng/mg, P=0.042). CONCLUSION: Neutrophils infiltration was an early event of OMT, which may play important roles on acute rejection of OMT.

The development and inflammatory features of radiotherapy-induced glossitis in rats.

OBJECTIVES: To improve the existing animal models (mice, rats, and hamsters) for radiotherapy-induced oral mucositis (RTOM), thereby establishing a radiotherapy-induced glossitis (RTG) Sprague-Dawley (SD) rat model. STUDY DESIGN: A lead device was designed to limit radiation exposure to a 1x1 cm2 area of a rat 's dorsal anterior tongue with a single 30 Gy of X-ray radiation. The general conditions of the irradiated rats, such as body-weight and behavior, were observed. The oral mucositis index (OMI) of the RTG rats were measured daily. Histological changes of the irradiated tongue tissues were assayed by H &E staining. RESULTS AND CONCLUSION: No significant changes were clinically observed 3 to 4 days after irradiation. At 5 to 6 day, punctuation and confluenced redness of the mucosa were observed. The small blood vessels became more extensive, engorged, thin vessel walls. More infiltrating cells were observable, necrosis and exfoliation of the squamous cells appeared, and the formation of an ulcerative lesion could be observed. Seven to 15 days, the exfoliated epithelial layer was observed to have formed an ulcerative lesion, then aggravated ulcerative lesions consisting of pseudomembranous filament exudates could be observed. The structure of the epithelium had become completely disintegrated, forming deep, microscopic ulcerative lesions. Twenty-one days, the periphery of the ulcer was observed to have begun to heal, and granulation tissue could be observed at the bottom of the ulceration. At 35 days after irradiation, the epithelial structure presented again, but the epithelium was very thin. An RTG animal model was successfully established in SD rats, which provides a new research platform for the study of RTOM pathogenesis.

The correlation between the severity of radiotherapy-induced glossitis and endothelial cell injury in local tissues in a rat model.

OBJECTIVES: To explore the correlation between the severity of radiotherapy-induced glossitis (RTG) and endothelial cell injury in local tissues in a rat model. STUDY DESIGN: The RTG animal model was designed and used by our team. The Oral mucositis index(OMI) was documented daily. Immunohistochemistry (IHC) Staining of CD34 was utilized to identify endothelial cells in the RTG tissues. Apoptosis of endothelial cells in local lesions due to RTG was detected by the TUNEL assay. The dynamic relationship between the OMI and apoptotic endothelial cells was statistically analyzed by time. RESULTS AND CONCLUSIONS: The injury and apoptosis of endothelial cells were observed 3 day post-irradiation. The vascular lumens of the post-irradiation tongue lesions were irregular; thrombosis formation in the center of the lumens, unsmooth lumen walls and vasodilated vessels were observed. Also, endothelial cells detached from the basal membrane and were found in the lumens. The percentages (%) of apoptotic endothelial cells were 78.3 ± 0.31 (5 day); 89.3 ± 0.83 (8 day); 83.5 ± 0.41 (14 day); 69.3 ± 0.57 (21 day); and 47.3 ± 0.59 (28 day). The OMI was correlated with the percentage of apoptotic endothelial cells (R=0.67, P=0.034). Summary, endothelial cell injury was correlated with the pathogenic condition of RTG.

Differential gene expression profiles of whole lesions from patients with oral lichen planus.

BACKGROUND: The molecular biological properties of oral lichen planus (OLP) are largely unknown. The aim of this study was to identify the genes responsible for its pathogenesis at the genome scale using DNA microarray technology. METHODS: The RNA samples extracted from the specimens of nine OLP patients and nine controls were analyzed with Affymetrix GeneChip. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis was applied to confirm GeneChip results. RESULTS: A total of 985 differentially expressed genes (629 up-regulated and 356 down-regulated) were identified. These genes were involved in many function classifications and biochemical pathways. The results of quantitative RT-PCR analysis of FOXP3, VEGFA, ANGPT1, MMP1, and SCGB2A2 were consistent with their changes demonstrated by GeneChip. CONCLUSIONS: This study showed the gene expression profiles of OLP, which were quite distinct from that of healthy controls. These results presented a global view of physiopathologic processes in lesions, which will give important clues to understand pathogenesis and identify new therapeutic targets of OLP.

Simultaneous detection of IFN-gamma and IL-4 in lesional tissues and whole unstimulated saliva from patients with oral lichen planus.

BACKGROUND: Although the roles of interferon (IFN)-gamma and interleukin (IL)-4 in oral lichen planus (OLP) have been described extensively in past decades, the available results are controversial. Moreover, few studies have utilized simultaneous detection of cytokines in local tissues and saliva to determine whether salivary cytokines could reflect the fact of local lesions. METHODS: IFN-gamma and IL-4 were determined simultaneously in lesions and whole unstimulated saliva (WUS) from OLP patients with various clinical forms. RESULTS: In OLP lesions, both IFN-gamma and IL-4 in erythematous/ulcerated OLP were higher significantly than that in control specimens. In WUS, however, only IFN-gamma of erythematous/ulcerated OLP was increased compared with control. Remarkably, IFN-gamma and IL-4 in WUS showed a more significant correlation to those in local tissues of all subjects. CONCLUSION: These results indicate that both IFN-gamma and IL-4 may play more important role in pathogenesis of erythematous/ulcerated OLP, and changes of these proinflammatory cytokines in WUS may reflect the status of the OLP lesion.