SIRT3 promotes the invasion and metastasis of cervical cancer cells by regulating fatty acid synthase.

Sirtuin 3 (SIRT3) modulates mitochondria-localized processes and is implicated in the metabolic reprogramming of cancer cells, especially fatty acid (FA) synthesis. However, the relationship between SIRT3 and aberrant lipid synthesis in cervical cancer remains unclear. Here, we investigated the clinical relevance of SIRT3 expression in cervical squamous cell carcinoma (CSCC), cervical intraepithelial neoplasia (CIN), and normal tissues. To analyze the role of SIRT3 in CCSC in vitro, endogenous SIRT3 levels were up- and down-regulated in SiHa and C33a cells, respectively, via lentiviral-based transfection. Levels were quantified using qRT-PCR. Acetylation levels for acetyl-coA carboxylase (ACC1) were measured with the anti-acetyllysine antibody. Knockdown of SIRT3 reduced levels of cellular lipid content in cells. To investigate the role of SIRT3 in cell proliferation, nude mice were xenografted with SIRT3-overexpressing or SIRT3-knockdown CCSC cells. Overall, the results demonstrate that SIRT3 significantly contributed to the reprogramming of FA synthesis in CCSC by up-regulating ACC1 to promote de novo lipogenesis by SIRT3 deacetylation. Moreover, the findings show that the SIRT3-mediated regulation of FA synthesis played a critical role in the proliferation and metastasis of CCSC cells, suggesting that SIRT3 has therapeutic potential in CCSC treatment.

DPP3 expression promotes cell proliferation and migration in vitro and tumour growth in vivo, which is associated with poor prognosis of oesophageal carcinoma.

Dipeptidyl peptidase III (DPP3), a zinc­dependent metallopeptidase, is upregulated in a variety of malignancies. However, little is known about its roles in the pathogenesis of these malignancies. The present study was designed to investigate the roles of DPP3 in the pathogenesis and progression of oesophageal cancer (EC). The expression level of DPP3 in EC tissues and adjacent normal tissues was detected in 93 cases of tissue biopsies collected from patients diagnosed with oesophageal carcinoma by immunohistochemistry. The effect of DPP3 expression on cell proliferation, migration or apoptosis was determined in DPP3­depleted EC cells created by infection with lentivirus containing short hairpin RNA specific to the human DPP3 mRNA sequence, followed by detection at the cellular level using a Celigo cell count assay, flow cytometry, wound­healing assay and Transwell assay as well as chip screening with a Human Apoptosis Antibody Array kit, which enables the quantitative detection of 43 apoptosis­related genes. A xenograft model was applied to detect the tumour growth and invasion of DPP3­depleted cancer cells in nude mice. The results revealed that DPP3 expression was elevated in EC tissues compared with adjacent non­tumour tissues, and high DPP3 expression was significantly associated with poor prognosis. DPP3 depletion resulted in reduced cell proliferation and migration and enhanced cell cycle arrest and apoptosis of EC cells and led to the inhibition of tumour growth and invasion in a xenograft model. In addition, DPP3 depletion was associated with the upregulation of the proapoptotic proteins SMAC and p53 and the downregulation of the antiapoptotic proteins clAP­2, IGFBP­2 and TRAILR­4. Finally, DPP3 may promote cell proliferation, migration and survival of EC cells in vitro and tumour growth and invasion of oesophageal carcinoma in vivo, and thus may serve as a molecular target for tumour therapy.

Characteristics of the Intestinal Microorganisms in Middle-Aged and Elderly Patients: Effects of Smoking.

Introduction: Smoking affects the occurrence and development of many diseases. We attempt to study the structure of intestinal flora in the middle-aged and elderly population as well as how smoking affects the intestinal flora. Methods: We collected population information, biochemical indicators, and patient feces from 188 middle-aged and elderly male patients, and their feces were tested for the 16S rRNA gene of intestinal flora. Results: We performed a cluster analysis on the intestinal structure of the included population and found that there was a significant difference in the number of smokers between each group (p = 0.011). Subsequently, the microbiological diversity analysis of current smokers and nonsmokers was carried out. The results indicated that there was a significant difference in species composition between the two groups (p = 0.029). Through the analysis on LEfSe differential bacteria, it was found that in current smoking patients, the abundances of the genus Bifidobacterium and the genus Coprobacillus were less, while the abundances of the genera Shigella, Paraprevotella, Burkholderia, Sutterella, Megamonas, and p-75-a5 under the family level of Erysipelotrichaceae were slightly high. We analyzed the correlation between the abundances of these eight different bacteria and clinical indicators. The results revealed the following: the abundance of the genus Bifidobacterium was negatively correlated with fasting blood glucose (r = -0.198, p = 0.006) and positively correlated with uric acid (r = 0.207, p = 0.004) and total bilirubin (r = 0.175, p = 0.017); Shigella bacteria were positively correlated with fasting blood glucose (r = 0.160, p = 0.028) and uric acid (r = 0.153, p = 0.036) levels; the genus Paraprevotella and BMI (r = -0.172, p = 0.018) are negatively correlated; the abundance of the genus Burkholderia was positively correlated with γ-glutamyltransferase (r = 0.146, p = 0.045) levels; Sutterella was correlated with fasting blood glucose (r = 0.143, p = 0.05) and creatinine level (r = -0.16, p = 0.027), which was positively correlated with fasting blood glucose and negatively correlated with creatinine. Conclusions: In middle-aged and elderly patients with cardiovascular disease, smoking can reduce the abundance of Bifidobacterium, while the abundances of some negative bacteria such as Burkholderia, Sutterella, and Megamonas increase.

Gut Microbiome-Based Diagnostic Model to Predict Diabetes Mellitus.

The aim of this study was to determine the diversity of intestinal microflora and its correlation with clinical parameters in diabetic patients and healthy subjects and to assess the importance of intestinal flora in patients with diabetes. Forty-four patients with diabetes were included. The control group included 47 healthy people. Their data, biochemical indicators and results from 16S rRNA sequencing of their fecal samples were collected. Compared with the healthy population, the intestinal flora of the diabetic patients was obviously abnormal. Within the diabetes group, the abundances of the genera Faecalibacterium, Prevotella, and Roseburia were higher, and the abundances of the genera Shigella and Bifidobacterium were lower. In the correlation analysis between bacteria and clinical indicators, it was found that the genera Veillonella and unclassified_Enterobacteriaceae were negatively related to blood glucose, while the genera Phascolarctobacterium, unidentified_Bacteroidales and Prevotella were significantly positively correlated with fasting blood glucose. Twelve microbial markers were detected in the random forest model, and the area under the curve (AUC) was 84.1%. This index was greater than the diagnostic effect of fasting blood glucose. This was also supported by the joint diagnostic model of microorganisms and clinical indicators. In addition, the intestinal flora significantly improved the diagnosis of diabetes. In conclusion, it can be concluded from these results that intestinal flora is essential for the occurrence and development of diabetes, which seems to be as important as blood glucose itself.Abbreviations: PCoA: principal coordinate analysis; NMDS: non econometric multidimensional scaling analysis; LEfSe: linear discriminant analysis effect size; LDA: linear discriminant analysis; POD: probability of disease; BMI: body mass index; DCA: decision curve analysis.

Gut Microbiota Characterization in Patients with Asymptomatic Hyperuricemia: probiotics increased.

Asymptomatic hyperuricemia (AH) is an early stage of gout. Emerging evidence shows that the intestinal microbiota is related to gout. However, the relationship between AH and the intestinal microbiota is poorly understood. Therefore, the aim of the current study was to explore the possible correlation between AH and intestinal flora. We compared the intestinal microbial communities of AH (45 cases) and healthy subjects (45 cases) by 16S rRNA gene sequencing and clustering analysis on the incorporated population. Intestinal-type clustering can be divided into two groups, and significant differences in the proportion of AH are found among different bowel types. Alpha diversity indices were higher in the AH group than in the control group, and beta diversity indices also showed significant differences. A total of 19 genera were found different between the AH group and the control group. Compared with the control group, some probiotics are increased in the AH population. Two groups were ranked by importance of bacteria. We found the different bacteria partially coincided with the important bacteria, and the joint diagnosis level of the important bacteria was good. Conclusion: There were significant differences in the composition of intestinal biota between AH patients and healthy subjects. Some probiotics increased in AH.