Ghrelin promotes neural differentiation of adipose tissue-derived mesenchymal stem cell via AKT/mTOR and ß-catenin signaling pathways.

Adipose tissue-derived mesenchymal stem cells (ADSCs) are multipotent cells that can differentiate into various cell types. This study aimed to investigate the effect of ghrelin on the neural differentiation of rat ADSCs and underlying molecular mechanisms. Rat ADSCs were isolated and third-passage ADSCs were used in this study. The isolated ADSCs were characterized by flow cytometry analysis for MSCs' surface expression markers as evidenced by positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD11b/2f/c. The multilineage differentiation of ADSCs was confirmed by adipogenic, osteogenic, and neural differentiation. After induction of neurogenesis, the differentiated cells were identified by development of neuron-like morphology and expression of neural markers including glial fibrillary acidic protein, Nestin, MAP2, and ß-Tubulin III using immunofluorescence and western blot. Ghrelin concentration dependently elevated the proportion of neural-like cells and branching dendrites, as well as upregulated the expression of neural markers. Further, the expression of nuclear ß-catenin, p-GSK-3ß, p-AKT, and p-mTOR was increased by ghrelin, indicating an activation of ß-catenin and AKT/mTOR signaling after the ghrelin treatment. Importantly, inhibition of ß-catenin or AKT/mTOR signaling suppressed ghrelin-induced neurogenesis. Therefore, we demonstrate that ghrelin promotes neural differentiation of ADSCs through the activation of ß-catenin and AKT/mTOR signaling pathways.

Diagnostic performance of serum cystatin C and complement component 1q in lupus nephritis.

BACKGROUND: The information concerning non-invasive, easily obtainable, and accurate biomarkers for diagnosis of lupus nephritis (LN) is extremely limited. The aim of this study was to evaluate the diagnostic performance of cystatin C (CysC) and complement component 1q (C1q) for LN. METHODS: A case-control study that included 905 patients with systemic lupus erythematosus (SLE) without LN (group SLE), 334 patients with active lupus nephritis (group LNA), 255 patients with inactive lupus nephritis (group LNI), and 497 healthy individuals (group HC) was performed in Mianyang Central Hospital from March 2017 to December 2018. The serum levels of CysC, C1q, urea (Urea), and creatinine (Creat) were measured, and 2 estimated glomerular filtration rates (eGFRCysC and eGFRCreat) were calculated by equations which were based on serum CysC established by our group and the modification of diet in renal disease (MDRD), respectively. ANOVA analysis or Kruskal-Wallis test was used for comparing the differences among the groups, and receiver operating characteristic (ROC) curve was applied to identify the diagnostic efficiencies of individual or combined multiple indicators. RESULTS: Significantly elevated CysC and decreased C1q were observed in the LNA and LNI groups, which was in contrast to their levels in the SLE and HC groups. CysC (AUC = 0.906) or eGFRCysC (AUC = 0.907) assessed the highest diagnostic performance on LNA when detected individually, followed by C1q (AUC = 0.753). Joint utilization of C1q and CysC achieved very good performance (AUC = 0.933) which approximated to the best one observed in the combinations of C1q, Urea, CysC, eGFRCreat, and Creat (AUC = 0.975). CONCLUSION: The separately detected CysC (eGFRCysC) and C1q were superior to the conventional biomarkers Urea, Creat, and eGFRCreat in the diagnosis of LNA. Moreover, although the combined detection of Urea, Creat, C1q, CysC, and eGFRCreat had the greatest diagnostic performance, the joint utilization of CysC and C1q could be prioritized for rapid discrimination of LNA if the economic burden is taken into consideration.

Association between chromosomal aberration of exfoliated bladder cells in the urine and oxidative stress in patients with bladder transitional cell carcinoma.

The aim of the current study was to investigate the chromosomal aberrations of exfoliated bladder cells in the urine and blood oxidative stress in patients with bladder transitional cell carcinoma (BTCC). A total of 40 healthy controls and 246 patients with BTCC were recruited. Abnormal levels of CSP3, CSP7, CSP17 and GLPp16 were detected by fluorescence in situ hybridization (FISH) in exfoliated bladder cells in the urine of patients with BTCC. Serum total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were measured. Significant differences were observed in the abnormal CSP3, CSP7, CSP17, GLPp16 signals and FISH positive rate between patients with BTCC and healthy controls (P<0.001). Serum TOS, TAS and OSI were also significantly different between the two groups (P<0.001). The clinical stage of BTCC was not associated with abnormal CSP3, CSP7, CSP17, GLPp16 or FISH positive rate and oxidative stress (P>0.05). A Gamma rank correlation analysis revealed an association between the pathological grade of BTCC with abnormal CSP3, CSP7 and CSP17 as well as FISH positive rate (P<0.001). In addition, the clinical stage of BTCC was associated with serum TOS, TAS and OSI (P<0.001). Evaluation of the association between chromosomal aberrations and oxidative stress revealed that abnormal CSP3, CSP7 and CSP17 were positively associated with serum TOS and OSI (P<0.001), abnormal CSP7 and CSP17 were negatively associated with serum TAS (P<0.001), but abnormal GLPp16 was not associated with serum TOS, TAS or OSI (P>0.05). Therefore, the chromosomal aberrations of exfoliated bladder cells in the urine are associated with blood oxidative stress in patients with BTCC, and these factors may contribute to the occurrence and development of BTCC.

Role of Cystatin C and glomerular filtration rate in diagnosis of kidney impairment in hepatic cirrhosis patients.

Hepatic cirrhosis is often accompanied by functional kidney impairment, which may be reversed if early treatment is promptly administered. This study aimed to investigate the role of Cystatin C and Cystatin C estimated glomerular filtration rate in the diagnosis of kidney impairment in patients with hepatic cirrhosis.Four hundred sixty five patients with hepatic cirrhosis were recruited. Serum creatinine and Cystatin C were determined, and their estimated glomerular filtration rates were calculated.The area under the receiver-operating characteristic curve (area under curve [AUC]) of Cystatin C and Cystatin C estimated glomerular filtration rate was significantly larger than that of serum creatinine and serum creatinine estimated glomerular filtration rate, respectively (P = .000). When the optimal cut-off value and upper reference limit were used, similar sensitivity, misdiagnosis rate, and diagnostic consistency were only observed in Cystatin C estimated glomerular filtration rate (P > .05).Cystatin C and Cystatin C estimated glomerular filtration rate are superior to serum creatinine and serum creatinine estimated glomerular filtration rate in diagnosis of secondary kidney impairment, and Cystatin C estimated glomerular filtration rate has a better performance as compared with Cystatin C. However, it is not a measured parameter, and thus the lab should determine its own optimal cut-off value.

Analysis of the diagnostic efficiency of serum oxidative stress parameters in patients with breast cancer at various clinical stages.

BACKGROUND: Reactive oxygen species (ROS) are balanced through enzymatic mechanisms and exogenous antioxidants; imbalance results in oxidative stress (OxS). It is known that OxS plays an important role in the occurrence, development, and metastasis of breast cancer. The present study aimed to assess serum total oxidant status (TOS), total antioxidant status (TAS), and oxidant stress index (OSI) in patients at different clinical stages of breast cancer and to evaluate their diagnostic accuracy. METHODS: Serum TOS, TAS, and OSI were determined in 91 patients with breast cancer at different stages, 51 patients with benign breast tumors, and 35 healthy adults. RESULTS: Significant differences in serum TOS (F=104.384, p=0.000), TAS (F=18.247, p=0.000), and OSI (F=62.598, p=0.000) were observed among the 3 groups (benign breast tumor patients, breast cancer patients, and healthy women). Of the enrolled breast cancer patients, significant differences were also observed among different tumor stages, with TOS and OSI gradually increasing as the disease progressed, while TAS diminished. Receiver operating characteristic curve analysis revealed that the area under the ROC curve for OSI (AUCOSI) was significantly higher than AUCTAS (z=2.344, p=0.019) in distinguishing breast cancer from control groups (including disease control and the healthy control). The AUCOSI (z=4.700, p=0.001) or AUCTOS (z=4.700, p=0.001) was significantly higher than AUCTAS in distinguishing breast cancer from the healthy control. The AUCOSI (z=5.907, p=0.000) or AUCTOS (z=5.667, p=0.000) was significantly higher than AUCTAS in distinguishing benign breast tumors from the healthy control. CONCLUSION: Oxidative stress parameters might serve as important indexes for monitoring breast cancer occurrence and progression. The combined evaluation of TOS, TAS, and OSI could be more beneficial for clinical assessment.