Sevoflurane Alters Serum Metabolites in Elders and Aging Mice and Increases Inflammation in Hippocampus.

Purpose: Postoperative cognitive dysfunction (POCD) is a central nervous system complication that occurs after anesthesia, particularly among the elderly. However, the neurological pathogenesis of postoperative cognitive dysfunction remains unclear. The aim of this study was to evaluate the effects of sevoflurane exposure on serum metabolites and hippocampal gene expression in elderly patients and aging mice by metabolomics and transcriptomic analysis and to explore the pathogenesis of sevoflurane induced POCD. Patients and Methods: Human serum samples from five patients over 60 years old were collected before sevoflurane anesthesia and 1 hour after anesthesia. Besides, mice aged at 12 months (n=6 per group) were anesthetized with sevoflurane for 2 hours or with sham procedure. Subsequently, serum and hippocampal tissues were harvested for analysis. Further investigation into the relationship between isatin and neuroinflammation was conducted using BV2 microglial cells. Results: Sevoflurane anesthesia led to the activation of inflammatory pathways, an increased presence of hippocampal astrocytes and microglia, and elevated expression of neuroinflammatory cytokines. Comparative analysis identified 12 differential metabolites that exhibited changes in both human and mouse serum post-sevoflurane anesthesia. Notably, isatin levels were significantly decreased after anesthesia. Notably, isatin levels significantly decreased after anesthesia, a factor known to stimulate proliferation and proinflammatory gene expression in microglia-the pivotal cell type in inflammatory responses. Conclusion: Sevoflurane-induced alterations in serum metabolites in both elderly patients and aging mice, subsequently contributing to increased inflammation in the hippocampus.

Obesity induced disruption on diurnal rhythm of insulin sensitivity via gut microbiome-bile acid metabolism.

The disruption of the diurnal rhythm has been recognized as a significant contributing factor to metabolic dysregulation. The important role of gut microbiota and bile acid metabolism has attracted extensive attention. However, the function of the gut microbiota-bile acid axis in regulating the diurnal rhythms of metabolic homeostasis remains largely unknown. Herein, we aimed to investigate the interplay between rhythmicity of host metabolism and gut microbiota-bile acid axis, as well as to assess the impact of obesity on them. We found that high fat diet feeding and Leptin gene deficiency (ob/ob) significantly disturbed the rhythmic patterns of insulin sensitivity and serum total cholesterol levels. The bile acid profiling unveiled a conspicuous diurnal rhythm oscillation of ursodeoxycholic acid (UDCA) in lean mice, concomitant with fluctuations in insulin sensitivity, whereas it was absent in obese mice. The aforementioned diurnal rhythm oscillations were largely desynchronized by gut microbiota depletion, suggesting the indispensable role of gut microbiota in diurnal regulation of insulin sensitivity and bile acid metabolism. Consistently, 16S rRNA sequencing revealed that UDCA-associated bacteria exhibited diurnal rhythm oscillations that paralleled the fluctuation in insulin sensitivity. Collectively, the current study provides compelling evidence regarding the association between diurnal rhythm of insulin sensitivity and gut microbiota-bile acid axis. Moreover, we have elucidated the deleterious effects of obesity on gut microbiome-bile acid metabolism in both the genetic obesity model and the diet-induced obesity model.

[Expression and significance of basic fibroblast growth factor and transforming growth factor-beta 1 in mucoepidermoid carcinoma with different malignant degree].

OBJECTIVE: To study the expression and significance of basic fibroblast growth factor(bFGF)and transforming growth factor-beta 1 (TGF-beta1) in mucoepidermoid carcinomas with different malignant degree. METHODS: Using immunohistochemistry (IHC) staining technique, bFGF and TGF-beta1 proteins in the mucoepidermoid carcinoma tissues with different malignant degree, including well-differentiated, moderately differentiated and poorly differentiated mucoepidermoid carcinoma, and normal salivary gland tissue were detected. RESULTS: The positive rate of bFGF and TGF-beta1 in normal salivary glands were apparently lower than those in malignant mucoepidermoid carcinomas (P<0.05). The positive rate of bFGF in moderately and poorly differentiated mucoepidermoid carcinoma was higher than that in the well-differentiated carcinoma (P <0.05). However, the positive expression of bFGF showed no relationship between the moderately and poorly differentiated mucoepidermoid carcinomas. The positive rate of TGF-beta1 in moderately and poorly differentiated mucoepidermoid carcinomas was lower than that in the well-differentiated carcinoma (P<0.05). The positive expression of TGF-beta1 showed no relationship between the moderately and poorly differentiated mucoepidermoid carcinomas. The expression of bFGF and TGF-beta1 showed negative correlation (r=- 0.471, P=0.0003). CONCLUSION: The expression of TGF-beta1 may inhibit the development of the mucoepidermoid carcinoma, contrariwise, the expression of bFGF may prompt the development of the mucoepidermoid carcinoma. The expression of bFGF and TGF-beta1 has a negative correlation.

[Facial multiple malignant proliferating tricholemmoma: a case report].

Malignant proliferating tricholemmoma is a very rare dermatic annexal tumor originated from outer root sheath cells. In this article, a case of facial multiple malignant proliferating tricholemmoma was reported, and its clinical pathologic features, differential diagnosis, treatment methods and histogenesis were discussed by reviewing relevant literatures.

The expression profile of microRNAs in a model of 7,12-dimethyl-benz[a]anthrance-induced oral carcinogenesis in Syrian hamster.

BACKGROUND: Non-coding RNA molecules, such as microRNAs, may play an important role in carcinogenesis. Recent studies have indicated that microRNAs are involved in initiation and progression of various malignancies. However, little work has been done to compare the microRNA expression patterns in oral cancer. In this study, we constructed an animal model of oral squamous cell carcinoma to investigate expression profiles of microRNAs in oral carcinogenesis. METHODS: The animal model of oral squamous cell carcinoma was conducted by tri-weekly (Monday, Wednesday, and Friday) painting with 5% DMBA in acetone. Six Syrian hamsters, including three from the treated group and three from the control group, were used as a training group for microRNA microarray analysis. All microarray data were analyzed by Significance Analysis of Microarrays (SAM) and CLUSTER 3.0 software, and this result was further confirmed by qRT-PCR assay. RESULTS: Seventeen microRNAs were differentially expressed in oral squamous cell carcinoma. Five microRNAs (hsa-miR-21, hsa-miR-200b, hsa-miR-221, hsa-miR-338, and mmu-miR-762) were significantly upregulated and twelve microRNAs (hsa-miR-16, hsa-miR-26a, hsa-miR-29a, hsa-miR-124a, hsa-miR-125b, mmu-miR-126-5p, hsa-miR-143, hsa-miR-145, hsa-miR-148b, hsa-miR-155, hsa-miR-199a, and hsa-miR-203) were down-regulated in cancer tissues. The expression levels of hsa-miR-21 and hsa-miR-16 seen with Stem-loop qRT-PCR were also seen in microarray analysis in all samples. CONCLUSION: Our findings identified specific microRNA expression in oral squamous cell carcinoma and suggested that microRNAs have a role in oral carcinogenesis.

Correlation between the expression of thrombospondin-1 and neovascularization in mucoepidermoid carcinoma.

BACKGROUND: Researchers have recently demonstrated that thrombospondin-1 (TSP-1) has an important function in regulating neovascularization. Whether it inhibits or accelerates neovascularization, however, is still controversial. We found few reports about the correlation between TSP-1 and vascularization in mucoepidermoid carcinoma. In this research, the distribution and expression of TSP-1 in mucoepidermoid carcinoma were investigated. We also analyzed (1) the correlation between the expression of TSP-1 and microvessel density (MVD), as an indicator of neovascularization activity, and (2) the effect of TSP-1 on neovascularization and tumor growth in the subcutaneous xenotransplanted model of mucoepidermoid carcinoma. METHOD: (1) The sites and intensity of expression of TSP-1 and the MVD were analyzed in 45 cases of mucoepidermoid carcinoma after surgery by the method of streptavidin-peroxidase (SP) immunohistochemistry; and (2) recombinant human thrombospondin-1 (rhTSP-1) was injected twice a week for five consecutive weeks around the tumor in the subcutaneous xenotransplanted tumor model of mucoepidermoid carcinoma in nude mice. Each week, the tumor size was measured, in order to draw the growth curve of the xenotransplanted tumor model of mucoepidermoid carcinoma, and MVD was measured. RESULTS: (1) The positive expression of TSP-1 protein was 57.78% (26/45). Most positive staining for TSP-1 was found in the cytoplasm of the cancer cells, while some staining occurred in the extracellular matrix. The mean MVD in 45 cases of mucoepidermoid carcinoma was 58.17 +/- 19.77 per 100 visual fields. Tumors with a high expression of TSP-1 showed a low MVD value, and the TSP-1 immunocompetence and microvessel density showed a significant negative correlation (r(s) = -0.947, P < 0.001). (2) The xenotransplanted tumors with the injection doses of 1.25, 0.75 and 0.25 microg/ml respectively were 36.97%, 53.36% and 73.61% of the size of the control group ((451 +/- 92), (651 +/- 113), (898 +/- 86) and (1220 +/- 157) mm(3) respectively, F = 53.167, P < 0.001), and their weights were respectively 35.14%, 51.35% and 70.27% of the control group ((1.3 +/- 0.5), (1.9 +/- 0.5), (2.6 +/- 0.3), and (3.7 +/- 0.7) g respectively, F = 62.669, P < 0.001). Their MVDs were 25.00%, 45.93%, and 72.20% respectively of the control group and concentration dependent (15.43 +/- 3.45, 28.35 +/- 4.24, 44.57 +/- 3.35 and 61.73 +/- 5.43 per 100 visual fields respectively, F = 54.582, P < 0.001). CONCLUSIONS: The TSP-1 has a higher expression in mucoepidermoid carcinoma and the expression has a significant negative correlation with neovascularization. The TSP-1 inhibits neovascularization and tumor growth, and it might be a new biological therapy for treatment of patients with mucoepidermoid carcinoma.

[Correlation between the expression of thrombospondin-1 and the angiogenesis in mucoepidermoid carcinoma].

OBJECTIVE: To study the relationship between the expression of thrombospondin-1 (TSP-1) and the angiogenesis in mucoepidermoid carcinoma. METHODS: Immunohistochemistry were applied to detect the expression of TSP-1 and the value of microvessel density (MVD) in 45 mucoepidermoid carcinoma patients. RESULTS: Positive expressions of TSP-1 protein were detected in 26 of the 45 (57. 78%) cases. Most positive staining for TSP-1 was observed in the cytoplasm of the cancer cells, some of those were in the extracellular matrix. The mean MVD in 45 cases with mucoepidermoid carcinoma was 60. 68 +/- 19.84 vessels per 100 field of vision. Tumors with a high expression of TSP-1 showed a low value of MVD and the correlation between TSP-1 immunocompetence and microvessel density was highly significant (r(s) = -0.942, P < 0.001). CONCLUSION: The TSP-1 is expressed in most mucoepidermoid carcinoma and were associated with neovascularization. TSP-1 is likely to inhibit the extensive neovascularization and increased TSP-1 expression might inhibit angiogenic phenotype in mucoepidermoid carcinoma.