Deletion of prominin-1 in mice results in disrupted photoreceptor outer segment protein homeostasis.

AIM: To illustrate the underlying mechanism how prominin-1 (also known as Prom1) mutation contribute to progressive photoreceptor degeneration. METHODS: A CRISPR-mediated Prom1 knockout (Prom1-KO) mice model in the C57BL/6 was generated and the photoreceptor degeneration phenotypes by means of structural and functional tests were demonstrated. Immunohistochemistry and immunoblot analysis were performed to reveal the localization and quantity of related outer segment (OS) proteins. RESULTS: The Prom1-KO mice developed the photoreceptor degeneration phenotype including the decreased outer nuclear layer (ONL) thickness and compromised electroretinogram amplitude. Immunohistochemistry analysis revealed impaired trafficking of photoreceptor OS proteins. Immunoblot data demonstrated decreased photoreceptor OS proteins. CONCLUSION: Prom1 deprivation causes progressive photoreceptor degeneration. Prom1 is essential for maintaining normal trafficking and normal quantity of photoreceptor OS proteins. The new light is shed on the pathogenic mechanism underlying photoreceptor degeneration caused by Prom1 mutation.

AMPKα2 Deficiency Does Not Affect the Exercise-Induced Improvements in Glucose Tolerance and Metabolic Disorders in Mice Fed a High-Fat Diet.

Exercise can improve obesity and metabolic disorders in mice fed a high-fat diet (HFD), but the role of AMPKα2 in the process remains unclear. The aim of this study was to investigate the role of AMPKα2 in the exercise-induced improvements in glucose tolerance and metabolic turnover in obesity mice. Male wild-type mice (n=12) and AMPKα2 knockout (AMPKα2 KO) mice (n=12) were fed a HFD for 16 wk and were then randomly divided into four groups: WT HFD group (WT HF), AMPKα2 KO HFD group (AMPKα2 KO HF), WT HFD exercise group (WT HE), and AMPK HFD exercise group (AMPKα2 KO HE). The HF groups continue to be fed a HFD from 16 wk to 24 wk, and the HE groups were fed a HFD and performed exercise training. After 8 wk of exercise, all mice were placed in an energy metabolism chamber to test their metabolic turnover, include locomotor activity, food intake, oxygen consumption (VO2), carbon dioxide production (VCO2), energy expenditure (EE) and respiratory exchange ratio (RER), over a period of 3 d. Exercise improved glucose tolerance, VO2, VCO2 and EE in mice fed a HFD (p<0.05). The VO2, VCO2 and EE in AMPKα2 KO HE group were lower than these in WT HE group (p<0.05). Our findings revealed exercise improved glucose tolerance and metabolic disorders in C57 and AMPKα2 KO mice fed a HFD. AMPKα2 is not essential for exercise-induced improvements in glucose tolerance and metabolic disorders.

Split-dose 4-L polyethylene glycol regimen for patients with previous colorectal surgery in bowel preparation before colonoscopy: A randomized, controlled, single-blind study.

OBJECTIVE: We aimed to investigate the efficacy of a split-dose 4-L polyethylene glycol (PEG) regimen for the quality of bowel preparation in Asian patients with previous colorectal surgery for colorectal cancer (CRC). METHODS: This was a prospective, single-center, randomized controlled, endoscopist-blinded study. Patients with previous colorectal surgery for CRC were randomly allocated to a routine, morning-only 2-L PEG (2-MO) group or a split-dose 4-L PEG (4-SD) group. The primary outcome was a successful bowel preparation rate. Secondary outcomes were polyp detection rate (PDR), adenoma detection rate (ADR), patient compliance, satisfaction, tolerance, willingness to repeat the preparation and difficulty of the bowel preparation process. RESULTS: In total, 187 patients were included (93 in the 2-MO group, 94 in the 4-SD group) in this study. The rate of successful bowel preparation in the 4-SD group was higher than in the 2-MO group (89.4% vs 66.7%, P < 0.001) in an intention-to-treat analysis according to the Aronchick score. Patients' satisfaction with the bowel preparation process in the 4-SD group was superior to that in the 2-MO group (93.4% vs 82.2%, P = 0.021). No significant differences were detected in PDR, ADR, patient compliance, tolerance, willingness to repeat the preparation or difficulty of the bowel preparation process. CONCLUSIONS: The 4-SD PEG regimen was superior to a routine, morning-only 2-L PEG preparation for bowel preparation in an Asian population with previous colorectal surgery.

Roles of HDAC2 and HDAC8 in Cardiac Remodeling in Renovascular Hypertensive Rats and the Effects of Valproic Acid Sodium.

Recent studies indicate that histone deacetylases (HDACs) activity is associated with the development and progression of cardiac hypertrophy. In this study, we investigated the effects of a HDACs inhibitor, valproic acid sodium (VPA), on cardiac remodeling and the differential expression of HDACs in left ventricles (LVs) of renovascular hypertensive rats. Renovascular hypertension was induced in rats by the two-kidney two-clip (2K2C) method. Cardiac remodeling, heart function and the differential expression of HDACs were examined at different weeks after 2K2C operation. The effects of VPA on cardiac remodeling, the expressions of HDACs, transforming growth factor-beta 1 (TGF-ß1) and connective tissue growth factor (CTGF) in LV were investigated. The expressions of atrial natriuretic factor, ß-myosin heavy chain, HDAC2 and HDAC8 increased in LV of 2K2C rats at 4, 8, 12 weeks after operation. Cardiac dysfunction, cardiac hypertrophy and fibrosis were markedly attenuated by VPA treatment in 2K2C rats. Further studies revealed that VPA inhibited the expressions of HDAC2, HDAC8, TGF-ß1 and CTGF in LV of 2K2C rats. In summary, these data indicate that HDAC2 and HDAC8 play a key role in cardiac remodeling in renovascular hypertensive rats and that VPA attenuates hypertension and cardiac remodeling. The effect of VPA is possibly exerted via decreasing HDAC2, HDAC8, TGF-ß1 and CTGF expressions in LV of 2K2C rats.

Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1 receptor.

1. This study examined whether Paeoniflorin (PF), the major active components of Chinese herb Paeoniae alba Radix, has neuroprotective effect in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). 2. Subcutaneous administration of PF (2.5 and 5 mg kg(-1)) for 11 days could protect tyrosine hydroxylase (TH)-positive substantia nigra neurons and striatal nerve fibers from death and bradykinesia induced by four-dose injection of MPTP (20 mg kg(-1)) on day 8. 3. When given at 1 h after the last dose of MPTP, and then administered once a day for the following 3 days, PF (2.5 and 5 mg kg(-1)) also significantly attenuated the dopaminergic neurodegeneration in a dose-dependent manner. Post-treatment with PF (5 mg kg(-1)) significantly attenuated MPTP-induced proinflammatory gene upregulation and microglial and astrocytic activation. 4. Pretreatment with 0.3 mg kg(-1) 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor (A1AR) antagonist, 15 min before each dose of PF, reversed the neuroprotective and antineuroinflammatory effects of PF. 5. In conclusion, this study demonstrated that PF could reduce the MPTP-induced toxicity by inhibition of neuroinflammation by activation of the A1AR, and suggested that PF might be a valuable neuroprotective agent for the treatment of PD.

Effects of paeoniflorin on the cerebral infarction, behavioral and cognitive impairments at the chronic stage of transient middle cerebral artery occlusion in rats.

In the present study, the effects of paeoniflorin (PF), a characteristic monoterpene glucoside isolated from Paeoniae Radix, on cerebral infarction, neurological symptoms, tongue protrusion (TP) and performance in the water maze were examined at the chronic stage (4 weeks) of transient cerebral ischemia using a rat middle cerebral artery occlusion (MCAO) model. One-day (10 mg/kg, twice, s.c.) or seven-day (2.5-10 mg/kg, twice a day, s.c.) injection of PF significantly reduced the infarct volume as well as ameliorated the deficits in neurological symptoms caused by transient MCAO at chronic stage. Transient MCAO also induced impairments in TP and performance in the water maze. Treatment with PF was able to reverse or alleviate these impairments. These results indicate that PF may be effective for treatment of stroke.