WGCNA reveals a biomarker for cancer-associated fibroblasts to predict prognosis in cervical cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are crucial components of the cervical cancer tumor microenvironment, playing a significant role in cervical cancer progression, treatment resistance, and immune evasion, but whether the expression of CAF-related genes can predict clinical outcomes in cervical cancer is still unknown. In this study, we sought to analyze genes associated with CAFs through weighted gene co-expression network analysis (WGCNA) and to create a predictive model for CAFs in cervical cancer. METHODS: We acquired transcriptome sequencing data and clinical information on cervical cancer patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. WGCNA was conducted to identify genes related to CAFs. We developed a prognostic model based on CAF genes in cervical cancer using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Single-cell sequencing data analysis and in vivo experiments for validation of hub genes in CAFs. RESULTS: A prognostic model for cervical cancer was developed based on CAF genes including COL4A1 , LAMC1 , RAMP3 , POSTN , and SERPINF1 . Cervical cancer patients were divided into low- and high-risk groups based on the optimal cutoff value. Patients in the high-risk group had a significantly worse prognosis. Single-cell RNA sequencing data revealed that hub genes in the CAFs risk model were expressed mainly in fibroblasts. The real-time fluorescence quantitative polymerase chain reaction (PCR) results revealed a significant difference in the expression levels of COL4A1 , LAMC1 , POSTN , and SERPINF1 between the cancer group and the normal group ( p < 0.05). Consistently, the results of the immunohistochemical tests exhibited notable variations in COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1 expression between the cancer and normal groups ( p < 0.001). CONCLUSION: The CAF risk model for cervical cancer constructed in this study can be used to predict prognosis, while the CAF hub genes can be utilized as crucial markers for cervical cancer prognosis.

2,2',4,4',5,5'-Hexabromophenyl ether (BDE-153) causes abnormal insulin secretion and disorders of glucose and lipid metabolism in mice.

BACKGROUND: Environmental polybrominated diphenyl ether (PBDE) exposure may be associated with diabetes and obesity. 2,2',4,4',5,5'-Hexabromodiphenyl ether (BDE-153) is one of the most abundant and widely distributed homologs of PBDEs detected in humans. This study investigated the effects of BDE-153 on the expression of adipokines and glucose and lipid metabolism. METHODS: Adult male C57BL/6 mice were divided into five BDE-153 groups and one control group. After BDE-153 exposure for 4 weeks, the levels of biochemical indexes and the mRNA and protein expression levels of leptin, adiponectin, peroxisome proliferators activated receptors gamma (PPARγ), and AMPKα were measured. The histomorphological changes of liver and pancreas tissues were observed. RESULTS: After BDE-153 exposure, the weight of mice in the medium-high-dose group at different exposure times was lower than that in the control group ( p all <0.05), and the body weight decreased slightly with the increase of the dose of BDE-153. BDE-153 caused the disorder of glucose and lipid metabolism in mice, the weight of liver and pancreas increased, lipid droplets accumulated in liver cells, and the positive rate of insulin staining increased in a dose-dependent manner. BDE-153 also interfered with the expression of PPARγ, AMPKα, and adipokines. The results of restrictive cubic splines (RCS) showed that there were a nonlinear dose-response relationship between the exposure dose of BDE-153 and the expression levels of PPARγ, AMPKα, and adipokines. CONCLUSION: Our results suggest that BDE-153 may interfere with the expression of adipokines and the secretion of insulin by affecting the expression of PPARγ and AMPKα, which play a key role in glucose and lipid metabolism, leading to the occurrence of glucose and lipid metabolism disorder.

Decabromodiphenyl ether causes insulin resistance and glucose and lipid metabolism disorders in mice.

BACKGROUND: Decabromodiphenyl ether (BDE-209) is the most commonly used brominated flame retardant. Recently, BDE-209 has been suspected of being an environmental risk factor for metabolic diseases such as obesity, insulin resistance (IR), type 2 diabetes mellitus, and hypertension. AIM: To investigate the effects of BDE-209 on IR and glucose and lipid metabolism in C57BL/6 mice. METHODS: Adult male C57BL/6 mice were randomly divided into high, medium-high, medium, medium-low, and low dose BDE-209 groups, and a control group (n = 6 per group), which received 1000, 800, 600, 450, 300, and 0 mg/kg BDE-209, respectively. After BDE-209 exposure for 60 d, the mice were fasted overnight, and then sacrificed to obtain tissues. An automatic biochemical analyzer was used to detect serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C); enzyme-linked immunosorbent assay kits were used to detect fasting serum insulin (FINS), leptin (LEP), and adiponectin (Adp) levels; a blood glucose meter was used to detect fasting blood glucose (FBG). Morphological changes of the liver were observed by hematoxylin and eosin staining. Real-time quantitative polymerase chain reaction and Western blot were used to determine the messenger ribonucleic acid (mRNA) and protein levels, respectively, of LEP, Adp, and peroxisome proliferators activated receptor-γ (PPARγ) in mouse liver and adipose tissues. RESULTS: There was a statistically significant difference in the weight of mice in each group after 45 and 60 d of exposure (P < 0.05). After 60 d of exposure, the weight of liver and adipose tissues in the exposure groups were greater than that of the control group (P < 0.05). The liver tissue structure was disordered and the liver tissues were accompanied by local inflammatory cell infiltration in the high, medium-high, and medium dose BDE-209 groups. The levels of FINS, insulin sensitivity index, Adp, and HDL-C were decreased in the BDE-209 group compared with the control group, as were the mRNA and protein levels of Adp in liver and adipose tissues (P < 0.05). Serum level of FBG and LEP were higher in the BDE-209 group than in controls. TC, TG, and LDL-C levels as well as the mRNA and protein expression of LEP and PPARγ in liver and adipose tissues were higher than those in the control group (P < 0.05). Homeostatic assessment model of IR was higher in the medium and medium-low dose BDE-209 groups (P < 0.05). CONCLUSION: BDE-209 increases the body weight, fat and liver tissue weight, TC, TG, and LDL-C, reduces HDL-C, and causes IR in mice, which may be related to activating the PPARγ receptor.

[Comparisons of risk factors for low birth weight between Han and Uygur full-term infants].

OBJECTRIVE: To compare the differences in risk factors for low birth weight (LBW) between Han and Uygur full-term infants and to provide a basis for the prevention of LBW in newborn infants. METHODS: Eighty-seven full-term LBW infants (38 Hans and 49 Uygurs) between March 2013 and June 2014 were selected as the case group, and 186 full-term normal birth weight infants (92 Hans and 94 Uygurs) were selected as the control group. A questionnaire survey was performed to investigate the related factors for LBW. Multivariate logistic regression analysis was carried out to determine the risk factors for LBW. RESULTS: The birth weights in Uyghur LBW infants were lower than in Han ones (P<0.05). Multivariate logistic regression analysis showed that drinking (OR=2.472, P=0.015) and smoking (OR=2.323, P=0.007) by the father, pregnancy complications (OR=14.377, P<0.001), and times of pregnancy (OR=2.995, P=0.001) were the risk factors for LBW in Han infants, while drinking by the father (OR=1.968, P=0.007), times of pregnancy (OR=1.953, P=0.005), pregnancy complications (OR=10.283, P=0.002), and poor indoor environment (OR=1.367, P=0.027) were the risk factors for LBW in Uyghur infants. CONCLUSIONS: There are differences in physical growth between Han and Uygur LBW infants. Han and Uygur infants share the same traditional risk factors for LBW, such as father's harmful behaviors like drinking, times of pregnancy, and pregnancy complications, however, the indoor environment also plays a role in the occurrence of LBW in Uygur infants.