1,2,3,4,6-Penta-O-galloyl-d-glucose Interrupts the Early Adipocyte Lifecycle and Attenuates Adiposity and Hepatic Steatosis in Mice with Diet-Induced Obesity.

Phytochemicals that interrupt adipocyte lifecycle can provide anti-obesity effects. 1,2,3,4,6-penta-O-galloyl-d-glucose (PGG) is a tannin with two isomers that occurs widely in plants and exhibits various pharmacological activities. The aim of the investigation is to comprehensively examine effects of PGG isomer(s) on adipocyte lifecycle and diet-induced obesity. Human mesenchymal stem cells (hMSC), 3T3-L1 fibroblasts, and H4IIE hepatoma cells were used to determine the effects of PGG isomers on cell viability and adipogenesis. Mice with diet-induced obesity were generated from male C57/BL6 mice fed with a 45% high fat diet. Oral administration of ß-PGG (0.1 and 5 mg/kg) lasted for 14 weeks. Viability was reduced by repeated PGG treatment in hMSC, preadipocytes, and cells under differentiation. PGG mainly induces apoptosis, and this effect is independent of its insulin mimetic action. In vivo, administration of ß-PGG attenuated shortening of the colon, hyperlipidaemia, fat cells and islet hypertrophy in DIO mice. Hepatic steatosis and related gene expression were improved along with glucose intolerance. Increased serum adiponectin, leptin, and glucagon-like peptide-1 levels were also observed. In conclusion, repeated PGG treatment interrupts the adipocyte lifecycle. PGG administration reduces adiposity and fatty liver development in DIO mice, and therefore, PGG could aid in clinical management of obesity.

The association between serum testosterone and mortality among elderly men on hemodialysis.

OBJECTIVES: This study examines the associations between total testosterone levels and dialysis mortality. METHODS: Elderly men who initiate hemodialysis in Taoyuan General Hospital from January 2012 to June 2017 were enrolled. We reviewed clinical characteristics and biochemical data from start of dialysis and followed over a 5-year period after dialysis. Body composition parameters were assessed 3-6 months after dialysis. Skeletal muscle mass index (SMMI) was defined by skeletal muscle mass divided by squared height. We defined those with lowest tertile of testosterone values as low testosterone group. Adjusted hazard ratios (aHRs) and 95% confidence interval (95% CI) for mortality and cumulative survival curves were evaluated by Cox hazards model and Kaplan-Meier method. The discriminative power of SMMI and testosterone levels was calculated according to the area under the curve and the receiver operating characteristic curve (AUROC). RESULTS: From a total of 137 elderly hemodialysis patients, the range of lowest, middle, and highest tertile of testosterone values was <6.25 nmol/L, 6.25-10.5 nmol/L, and >10.5 nmol/L. After multivariate adjustment other than SMMI, total testosterone levels at baseline were a significant predictor for mortality aHR(95% CI): 0.79 (0.70-0.91). The unadjusted and adjusted c-statistics of SMMI vs testosterone values to predict overall were 770 (0.688-0.852) vs 0.779 (0.691-0.866) and 855 (0.812-0.886) vs 0.812 (0.744-0.856) (Ps < .05), whereas the capacity of c-statistics was similar (χ2  = 0.143 and 2.709, Ps > .05). CONCLUSIONS: Total testosterone value was a predictor for mortality. It was noninferior to SMMI in predicting dialysis mortality.

Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO.

BACKGROUND: The accumulation of soluble oligomeric amyloid-ß peptide (oAß) proceeding the formation of senile plaques contributes to synaptic and memory deficits in Alzheimer's disease. Our previous studies have indentified scavenger receptor A (SR-A), especially SR-A type I (SR-AI), as prominent scavenger receptors on mediating oAß clearance by microglia while glycan moiety and scavenger receptor cysteine-rich (SRCR) domain may play the critical role. Macrophage receptor with collagenous structure (MARCO), another member of class A superfamily with a highly conserved SRCR domain, may also play the similar role on oAß internalization. However, the role of N-glycosylation and SRCR domain of SR-AI and MARCO on oAß internalization remains unclear. RESULT: We found that oAß internalization was diminished in the cells expressing SR-AI harboring mutations of dual N-glycosylation sites (i.e. N120Q-N143Q and N143Q-N184Q) while they were normally surface targeted. Normal oAß internalization was observed in 10 SR-AI-SRCR and 4 MARCO-SRCR surface targeted mutants. Alternatively, the SRCR mutants at ß-sheet and α-helix and on disulfide bone formation obstructed receptor's N-glycosylation and surface targeting. CONCLUSION: Our study reveals that N-glycan moiety is more critical than SRCR domain for SR-A-mediated oAß internalization.

Incidence and mortality of postoperative acute kidney injury in non-dialysis patients: comparison between the AKIN and KDIGO criteria.

OBJECTIVES: This retrospective study determines whether the kidney disease: improving global outcomes (KDIGO) criteria are superior to acute kidney injury network (AKIN) criteria in detecting non-dialysis AKI events and predicting mortality in chronic kidney disease (CKD) patients after surgery. METHODS: Surgical patients who were admitted to the intensive care unit were enrolled. Non-dialysis AKI cases were defined using either KDIGO or AKIN creatinine criteria and stratified by CKD stages. The adjusted hazard ratios (AHRs) for in-hospital mortality are compared to those without AKI. The cumulative survival curves and the predictability for mortality are accessed by Kaplan-Meier method and calculating the area under the curve (AUC) for the receiver operating characteristic (ROC) curve, respectively. RESULTS: From a total of 826 postoperative patients, the overall in-hospital mortality rate was 11.6% (96 cases) and that for AKI according to KDIGO and AKIN criteria was 30.0% (248 cases) and 31.0% (256 cases). The cumulative survival curve stratified by CKD and AKI stages were comparable between KDIGO and AKIN criteria. The discriminative power for mortality stratified by CKD stages for KDIGO and AKIN criteria are as followed: all subjects: 0.678 versus 0.670 (both ps <0.001); non-CKD: 0.800 versus 0.809 (both ps <0.001); early-stage CKD: 0.676 versus 0.676 (both ps <0.001); late-stage CKD: 0.674 versus 0.660 (ps were <0.001 and 0.003). CONCLUSION: The KDIGO criteria are superior to AKIN criteria in predicting mortality after surgery, especially in those with advanced CKD.

Tension pneumocephalus as a complication of hyperbaric oxygen therapy in a patient with chronic traumatic brain injury.

Although hyperbaric oxygen therapy has not been accepted as a standard therapy for traumatic brain injuries, it has been used, along with rehabilitative exercises, for traumatic brain injuries, and the standard protocol has a low risk of complications. We report a case of chronic traumatic brain injury that progressed to tension pneumocephalus after hyperbaric oxygen therapy. The patient was a 25-yr-old man who presented with left occipital bone fracture and subarachnoid and subdural hemorrhage after being hit by a car. He underwent craniectomy to remove the hematoma and cerebrospinal fluid diversion with a ventriculoperitoneal shunt for the treatment of hydrocephalus. Fifteen months after the trauma, the patient received hyperbaric oxygen therapy to promote functional recovery. Tension pneumocephalus developed after the first session of hyperbaric oxygen therapy, and immediate burr hole drainage followed by ligation of the ventriculoperitoneal shunt was performed. The patient's consciousness recovered gradually, and he was discharged home. We suggest that patients with unrepaired skull base fracture and cerebrospinal fluid diversion should be carefully evaluated before receiving hyperbaric oxygen therapy.