Adiponectin Ameliorated Pancreatic Islet Injury Induced by Chronic Intermittent Hypoxia through Inhibiting the Imbalance in Mitochondrial Fusion and Division.

Objective This study aimed to assess the protective value of adiponectin (APN) in pancreatic islet injury induced by chronic intermittent hypoxia (CIH). Methods Sixty rats were randomly divided into three groups: normal control (NC) group, CIH group, and CIH with APN supplement (CIH+APN) group. After 5 weeks of CIH exposure, we conducted oral glucose tolerance tests (OGTT) and insulin released test (IRT), examined and compared the adenosine triphosphate (ATP) levels, mitochondrial membrane potential (MMP) levels, reactive oxygen species (ROS) levels, enzymes gene expression levels of Ant1, Cs, Hmox1, and Cox4i1 which represented mitochondrial tricarboxylic acid cycle function, the protein and gene expression levels of DRP1, FIS1, MFN1, and OPA1 which represented mitochondrial fusion and division, and the protein expression levels of BAX, BCL-2, cleaved Caspase-3, and cleaved PARP which represented mitochondrial associated apoptosis pathway of pancreatic islet. Results OGTT and IRT showed blood glucose and insulin levels had no differences among the NC, CIH and CIH+APN groups (both P>0.05) at 0 min, 20 min, 30 min, 60 min, 120 min. However, we found that compared to NC group, CIH increased the ROS level, reduced ATP level and MMP level. The islets of CIH exposed rats showed reduced gene expression levels of Ant1, Cs, Hmox1, and Cox4i1, decreased protein and gene expression levels of MFN1 and OPA1, increased protein and gene expression levels of DRP1 and FIS1, increased protein expression levels of cleaved Caspase-3 and cleaved PARP, with lower ratio of BCL-2/BAX at protein expression level. All the differences among three groups were statistically significant. APN treated CIH rats showed mitigated changes in the above measurements associated with islet injuries. Conclusion APN may ameliorate the pancreatic islet injury induced by CIH via inhibiting the imbalance in mitochondrial fusion and division.

Altered amplitude of low-frequency fluctuation in basal ganglia correlates to pulmonary ventilation function in COPD patients: A resting-state fMRI study.

INTRODUCTION: Patients under chronic obstructive pulmonary disease (COPD) has been reported to be associated with a higher prevalence of cognitive impairment (CI). However, it is still largely unknown whether the aberrant resting-state spontaneous neuronal activity pattern reflected by the amplitude of low-frequency fluctuation (ALFF) analysis will be associated with the CI in COPD patients. MATERIALS: A total of 28 COPD patients and 26 healthy controls were enrolled in this study. Of all the subjects, structural and functional MRI data, spirometry tests performance and neuropsychological assessments of different cognitive domains were collected. Voxel-based two-sample t tests were used to detect brain regions showing differences in the ALFF value between COPD patients and healthy controls. An additional fMRI runs with supplementary oxygen delivery were employed to explore the impact of elevated partial pressure of oxygen (PaO2 ) or moderate hyperoxia on ALFF in COPD patients and healthy controls respectively. RESULTS: More extensive white matter lesion was detected in COPD patients. COPD patients exhibit decreased ALFF value in bilateral basal ganglia areas and right thalamus, and aberrant ALFF value is correlated with PaO2 and pulmonary ventilation function (FEV1%pred). COPD patients performed worse in the Digit Span Test (reverse), Digit Symbol Substitution Test, Trail-making test (A and B) than controls. After supplementary oxygen inhalation, the ALFF value of basal ganglia and right thalamus significantly increased in the controls, but not in the COPD patients. CONCLUSIONS: COPD patients mainly exhibit impaired executive function but not long-term memory in cognitive function assessment. Aberrant ALFF alteration in the deep brain may be directly related to lower PaO2 in COPD patients.

The prognostic impact of serum bilirubin in stage IV colorectal cancer patients.

BACKGROUND: Bilirubin played a great role in antioxidation and anticancer and has been considered as a promising prognostic factor of non-liver disease-related death in various cancers. The aim of this study was to assess the prognostic value of pre-treatment serum bilirubin in stage IV CRC patients. METHODS: Serum bilirubin including TBIL, DBIL, and IBI which were tested at pre-treatment were investigated in 154 stage IV CRC patients in Zhongda Hospital, Nanjing, China, from July 2005 to July 2011. X-tile program was used to determine the optimal cut-off values of these three biomarkers. Kaplan-Meier analysis, univariate, and multivariate cox regression as well as time-dependent ROC curve analysis were performed to evaluate the relations between serum bilirubin and survival outcomes. RESULTS: We got the results that the optimal cut-off points of serum TBIL, DBIL, and IBI levels were 12.9, 6.1, and 4.8 µmol/L, respectively. Univariate analysis showed that elevated TBIL, DBIL, and CEA were significantly associated with poor 5-year OS in stage IV CRC patients. Multivariate cox analysis indicated that the high DBIL (HR=1.603, 95%CI=1.053-2.442, P<.028) and CEA (HR=1.785, 95%CI=1.123-2.837, P=.014) could be identified as independent factors for poor OS. Furthermore, time-dependent ROC curves demonstrated that high DBIL had similar prognostic efficacy as elevated CEA for poor OS (AUC=0.63 and 0.61, respectively). CONCLUSIONS: Pre-treatment elevated TBIL and DBIL levels were associated with poor OS in stage IV CRC patients. Moreover, DBIL could be considered as an independent prognostic biomarker for OS. Furthermore, DBIL had similar prognostic efficacy as CEA for OS.