Berberine Alleviates Ischemic Brain Injury by Enhancing Autophagic Flux via Facilitation of TFEB Nuclear Translocation.

Berberine has been demonstrated to alleviate cerebral ischemia/reperfusion injury, but its neuroprotective mechanism has yet to be understood. Studies have indicated that ischemic neuronal damage was frequently driven by autophagic/lysosomal dysfunction, which could be restored by boosting transcription factor EB (TFEB) nuclear translocation. Therefore, this study investigated the pharmacological effects of berberine on TFEB-regulated autophagic/lysosomal signaling in neurons after cerebral stroke. A rat model of ischemic stroke and a neuronal ischemia model in HT22 cells were prepared using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD), respectively. Berberine was pre-administered at a dose of 100[Formula: see text]mg/kg/d for three days in rats and 90[Formula: see text][Formula: see text]M in HT22 neurons for 12[Formula: see text]h. 24[Formula: see text]h after MCAO and 2[Formula: see text]h after OGD, the penumbral tissues and OGD neurons were obtained to detect nuclear and cytoplasmic TFEB, and the key proteins in the autophagic/lysosomal pathway were examined using western blot and immunofluorescence, respectively. Meanwhile, neuron survival, infarct volume, and neurological deficits were assessed to evaluate the therapeutic efficacy. The results showed that berberine prominently facilitated TFEB nuclear translocation, as indicated by increased nuclear expression in penumbral neurons as well as in OGD HT22 cells. Consequently, both autophagic activity and lysosomal capacity were simultaneously augmented to alleviate the ischemic injury. However, berberine-conferred neuroprotection could be greatly counteracted by lysosomal inhibitor Bafilomycin A1 (Baf-A1). Meanwhile, autophagy inhibitor 3-Methyladenine (3-MA) also slightly neutralized the pharmacological effect of berberine on ameliorating autophagic/lysosomal dysfunction. Our study suggests that berberine-induced neuroprotection against ischemic stroke is elicited by enhancing autophagic flux via facilitation of TFEB nuclear translocation in neurons.

[Greenlight photoselective vaporization prostatectomy versus thulium laser vaporesection of the prostate for aged high-risk BPH patients with the prostate heavier than 80 g].

OBJECTIVE: To compare the effects of greenlight photoselective vaporization prostatectomy (PVP) and thulium laser vaporesection of the prostate (TmLRP) in the treatment of aged high-risk BPH patients with the prostate weighing > 80 g. METHODS: We included in this study 118 high-risk BPH patients aged 62-96 (mean 76) years with the prostate heavier than 80 g, 82 treated by PVP and the other 36 by TmLRP. Then we compared the operation time, intraoperative bleeding, complications, short-term effectiveness, and surgical cost between the two groups. RESULTS: All the patients tided over the perioperative period without blood transfusion and serious complications. The mean operation time, postoperative bladder irrigation time and surgical cost were significantly less in the TmLRP than in the PVP group (P < 0.05). Both the procedures remarkably improved the international prostatic symptom score (IPSS), quality of life (QOL), post void residual urine (PVR) and Qmax of the patients (P < 0.05), but with no significant differences between the two groups (P > 0.05). CONCLUSION: Both PVP and TmLRP are effective and safe for the treatment of aged high-risk BPH patients with the prostate heavier than 80 g, but the latter is superior for its shorter operation time and lower surgical cost.