SELENOK-dependent CD36 palmitoylation regulates microglial functions and Aß phagocytosis.

Amyloid-beta (Aß) is a key factor in the onset and progression of Alzheimer's disease (AD). Selenium (Se) compounds show promise in AD treatment. Here, we revealed that selenoprotein K (SELENOK), a selenoprotein involved in immune regulation and potentially related to AD pathology, plays a critical role in microglial immune response, migration, and phagocytosis. In vivo and in vitro studies corroborated that SELENOK deficiency inhibits microglial Aß phagocytosis, exacerbating cognitive deficits in 5xFAD mice, which are reversed by SELENOK overexpression. Mechanistically, SELENOK is involved in CD36 palmitoylation through DHHC6, regulating CD36 localization to microglial plasma membranes and thus impacting Aß phagocytosis. CD36 palmitoylation was reduced in the brains of patients and mice with AD. Se supplementation promoted SELENOK expression and CD36 palmitoylation, enhancing microglial Aß phagocytosis and mitigating AD progression. We have identified the regulatory mechanisms from Se-dependent selenoproteins to Aß pathology, providing novel insights into potential therapeutic strategies involving Se and selenoproteins.

Pretreatment of Root Canal with Photodynamic Therapy Facilitates Adhesion, Viability and Differentiation of Stem Cells of the Apical Papilla.

This study was to test the hypothesis that root canal pretreated with photodynamic therapy (PDT) would promote stem cells from the apical papilla (SCAP) adhesion, proliferation and differentiation without affecting smear layer removal and microhardness of root canal. Standardized root canals were randomized into four groups (n = 30/group): (1) sodium hypochlorite(NaOCl) group, (2) NaOCl + ethylene diaminetetraacetic acid (EDTA) group, (3) NaOCl + PDT group, (4) NaOCl + EDTA + PDT group. After treatments, smear layer removal and microhardness of root canal were evaluated. SCAP with hydroxyapatite-based scaffolds were seeded into root canals for 7 days. SCAP adhesion was observed by scanning electron microscope (SEM), and viable cells were calculated by CellTiter-Glo Luminescent kit. Platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) expression of SCAP were evaluated by Quantitative Reverse Transcriptase-Polymerase Chain Reaction. There was no significant difference in the smear layer removal and microhardness of root dentin between the groups with and without PDT treatment (P > 0.05). SCAP with elongated cytoplasmic processes and cell-cell contact were observed on the dentin surfaces treated with PDT. Elevated cell viability, PDGF and VEGF expression were found in root canal treated with PDT (P < 0.05). Under the experimental conditions, PDT could provide positive microenvironment for SCAP growth.

Pravastatin protects hyperbaric hyperoxia-induced lung injury via inhibiting inflammation in mice.

This study aimed to investigate the protective effects of pravastatin on hyperbaric hyperoxia-induced lung injury (HILI). C57BL/6 mice were randomly assigned into three groups: control group, HILI group and pravastatin (Pra) group. Mice in the HILI and Pra groups were subjected to exposure to pure oxygen at 2.5 atm abs for six hours. Mice in the Pra group were intraperitoneally treated with pravastatin at 15 mg/kg. immediately after exposure. At 24 hours, the lungs were collected for HE staining, TUNEL staining and detection of lung edema, myeloperoxidase (MPO) activity and cytokines, and bronchoalveolar lavage fluid (BALF) was harvested for cell-counting. Pravastatin treatment significantly improved the pathology of the lung after HILI (reduction in thickness of alveolar septum, attenuation of lung edema, fracturing of alveolar septa and decrease in infiltrated leukocytes); reduced the number of apoptotic cells; inhibited lung MPO activity; and regulated the balance between pro-inflammatory and anti-inflammatory cytokines. Our findings suggest that pravastatin may exert a protective effect on lung injury after hyperbaric hyperoxia exposure by inhibiting inflammation.

Hyperbaric oxygen preconditioning induces tolerance against oxidative injury and oxygen-glucose deprivation by up-regulating heat shock protein 32 in rat spinal neurons.

OBJECTIVE: Hyperbaric oxygen (HBO) preconditioning (HBO-PC) has been testified to have protective effects on spinal cord injury (SCI). However, the mechanisms remain enigmatic. The present study aimed to explore the effects of HBO-PC on primary rat spinal neurons against oxidative injury and oxygen-glucose deprivation (OGD) and the relationship with heat shock proteins (HSPs). METHODS: Primary rat spinal neurons after 7 days of culture were used in this study. HSPs were detected in rat spinal neurons following a single exposure to HBO at different time points by Western blot. Using lactate dehydrogenase release assay and cell counting kit-8 assay, the injuries induced by hydrogen peroxide (H2O2) insult or OGD were determined and compared among neurons treated with HBO-PC with or without HSP inhibitors. RESULTS: The results of Western blot showed that HSP27, HSP70 and HSP90 have a slight but not significant increase in primary neurons following HBO exposure. However, HSP32 expression significantly increased and reached highest at 12 h following HBO exposure. HBO-PC significantly increased the cell viability and decreased the medium lactate dehydrogenase content in cultures treated with H2O2 or OGD. Pretreatment with zinc protoporphyrin IX, a specific inhibitor of HSP32, significantly blocked the protective effects of HBO-PC. CONCLUSIONS: These results suggest that HBO-PC could protect rat spinal neurons in vitro against oxidative injury and OGD mostly by up-regulating of HSP32 expression.

Protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury in a rat model.

Hyperbaric oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia leads to inflammation and acute lung injury. This study aimed to investigate the protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury. Rats were intraperitoneally treated with sodium hydrosulphide (NaHS) at 28 µmol/kg immediately before hyperoxia exposure and then exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) with continuous ventilation for six hours, Immediately after hyperoxia exposure, rats were sacrificed via anesthesia. The bronchoalveolar lavage fluid (BALF) was harvested for the detection of protein concentration and IL-1 content, and the lungs were collected for HE staining, TUNEL staining and detection of wet/dry weight ratio. Our results showed hyperbaric hyperoixa exposure could significantly damage the lung (HE staining), increase the protein and IL-13 in the BALF, elevate the wet/dry Weight ratio and raise the TUNEL positive cells. However, pre-treatment with hydrogen sulfide improved the lung morphology, reduced the TUNEL positive cells and attenuated the lung inflammation (reduction in IL-13 of BALF and HE staining). Taken together, our findings indicate that hydrogen sulfide pretreatment may exert protective effects on hyperbaric hyperoxia-induced lung injury.

Heat-shock protein 70 is involved in hyperbaric oxygen preconditioning on decompression sickness in rats.

Decompression sickness (DCS) is a major concern in diving and space walk. Hyperbaric oxygen (HBO) preconditioning has been proved to enhance tolerance to DCS via nitric oxide. Heat-shock protein (HSP) 70 was also found to have protective effects against DCS. We hypothesized that the beneficial effects of HBO preconditioning on DCS was related to levels of elevated HSP70. HSPs (70, 27 and 90) expressed in tissues of spinal cord and lung in rats was detected at different time points following HBO exposure by Western blot. HSP27 and HSP90 showed a slight but not significant increase after HBO. HSP70 increased and reached highest at 18 h following exposure before decreasing. Then rats were exposed to HBO and subjected to simulated air dive and rapid decompression to induce DCS 18 h after HBO. The severity of DCS, along with levels of HSP70 expression, as well as the extent of oxidative and apoptotic parameters in the lung and spinal cord were compared among different groups of rats pretreated with HBO, HBO plus NG-nitro-l-arginine-methyl ester (l-NAME), HBO plus quercetin or normobaric air. HBO preconditioning significantly reduced the morbidity of DCS (from 66.7% to 36.7%), reduced levels of oxidation (malondialdehyde, 8-hydroxyguanine and hydrogen peroxide) and apoptosis (caspase-3 and -9 activities and the number of apoptotic cells). l-NAME or quercetin eliminated most of the beneficial effects of HBO on DCS, and counteracted the stimulation of HSP70 by HBO. Bubbles in pulmonary artery were detected using ultrasound imaging to observe the possible effect of HBO preconditioning on DCS bubble formation. The amounts of bubbles in rats pretreated with HBO or air showed no difference. These results suggest that HSP70 was involved in the beneficial effects of HBO on DCS in rats, suspected be by the antioxidation and antiapoptosis effects.

Decompression illness: clinical aspects of 5278 consecutive cases treated in a single hyperbaric unit.

BACKGROUND: Decompression illness (DCI) is a major concern in pressure-related activities. Due to its specific prerequisite conditions, DCI is rare in comparison with other illnesses and most physicians are inexperienced in treatment. In a fishery area in northern China, during the past decade, tens of thousands of divers engaged in seafood harvesting and thousands suffered from DCI. We established a hyperbaric facility there and treated the majority of the cases. METHODS AND RESULTS: A total of 5,278 DCI cases were admitted in our facility from February 2000 through December 2010 and treated using our recompression schedules. Cutaneous abnormalities, joint and muscular pain and neurological manifestations were three most common symptoms. The initial symptom occurred within 6 h after surfacing in 98.9% of cases, with an overall median latency of 62 min. The shorter the latent time, the more serious the symptoms would be (P<0.0001). Nine cases died before recompression and 5,269 were treated using four recompression schedules, with an overall effectiveness rate of 99.3%. The full recovery rate decreased with the increase of the delay from the onset of symptoms to the treatment (P<0.0001). CONCLUSIONS: DCI presents specific occurrence rules. Recompression should be administered as soon as possible and should never be abandoned irrespective of the delay. The recompression schedules used were effective and flexible for variety conditions of DCI.