Celastrol Loaded Nanoparticles With ROS-Response and ROS-Inducer for the Treatment of Ovarian Cancer.

Ovarian cancer is a gynecological cancer from which it is difficult to be completely cured. It is common to use regimens as an effective treatment for ovarian cancer, but these inevitably bring serious side effects. New treatment strategies and special drugs are needed to improve the prognosis of patients. Celastrol is a natural product, isolated from traditional medicine, that has been proven to be curative for inflammation and cancers. However, the non-targeting and low solubility of celastrol limit its clinical application. We prepared celastrol-loaded nanoparticles for the efficient treatment of ovarian cancer via oxidative stress amplification. In this work, a tumor-targeted, ROS-sensitive nanoparticle was designed, synthesized, and assembled into a drug delivery system that used celastrol. Folic acid (FA) groups on the surface of nanoparticles guide them to actively target the surface of the tumor cell membrane. Thioketal (TK) bonds in nanoparticles can be oxidized and broken into -SH within the ROS level of tumor tissues, which causes the breaking of the PEG hydrophilic shell layer of nanoparticles and promotes the release of celastrol. The released celastrol further stimulated the production of ROS and amplified the intracellular ROS level to promote the apoptosis of tumor cells, thus achieving a therapeutic effect on the celastrol treated ovarian cancer.

Tetramethylpyrazine Attenuated Sevoflurane-Induced Neurotoxicity by Enhancing Autophagy through GPR50/CREB Pathway in SH-SY5Y Cells.

Tetramethylpyrazine has shown neuroprotective and axonal outgrowth-promoting effects and can improve cognitive deficit in a rat model of chronic hypoperfusion. However, the role of tetramethylpyrazine in sevoflurane-induced neurotoxicity is still vague. Therefore, this study was designed to investigate the effects and mechanisms of tetramethylpyrazine on sevoflurane-induced autophagy, apoptosis, and the expression of BACE1 and A[Formula: see text] in SH-SY5Y cells. We measured the expression levels of the apoptosis protein markers Bax and Bcl-2, autophagy protein markers Atg5 and LC3-II, BACE1, and A[Formula: see text] in SH-SY5Y cells after sevoflurane treatment and determined the effects of tetramethylpyrazine on sevoflurane-induced expression of these proteins after silencing GPR50 or Atg5 with siRNA in vitro. We found that exposure to 3.4% sevoflurane for 6 h decreased the expression of autophagy protein markers and increased the expression of the apoptosis protein markers, BACE1, and A[Formula: see text] in SH-SY5Y cells. The number of red puncta (autolysosomes) and yellow puncta (autophagosomes) in each SH-SY5Y cell decreased after transient transfection with the mRFP-GFP-LC3 expression plasmid. Silencing of GPR50 decreased the expression of pCREB, Atg5, and LC3-II, while silencing of Atg5 increased the expression of BACE1 and A[Formula: see text] in SH-SY5Y cells. Our results demonstrate that tetramethylpyrazine attenuated sevoflurane-induced neurotoxicity by enhancing autophagy through the GPR50/CREB pathway in SH-SY5Y cells.

The Effects of Leukocyte Filtration on Cell Salvaged Autologous Blood Transfusion on Lung Function and Lung Inflammatory and Oxidative Stress Reactions in Elderly Patients Undergoing Lumbar Spinal Surgery.

BACKGROUND: This study was designed to investigate the effects of leukocyte filtration of autologous salvaged blood on lung function, lung inflammatory reaction, and oxidative stress reaction in elderly patients undergoing lumbar spinal surgery. MATERIALS AND METHODS: Sixty elderly patients undergoing lumbar spinal surgery were randomly divided into 2 groups: Leukocyte Filter group and Control group. Serum levels of inflammatory markers including white blood cell and polymorphonuclear count, neutrophil elastase, serum surfactant protein A, methane dicarboxylic aldehyde, superoxide dismutase, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and respiratory function markers including dynamic respiratory system compliance, oxygenation index, and respiratory index were measured immediately before induction of anesthesia (T0), immediately before blood transfusion (T1), and 1 (T2), 6 (T3), and 12 hours (T4) after end of blood transfusion. RESULTS: The Leukocyte Filter group had higher dynamic respiratory system compliance at T2, oxygenation index at T2 and T3, respiratory index and superoxide dismutase at T2, T3, and T4 than those in the Control group (P<0.05). The Leukocyte Filter group had lower white blood cell, polymorphonuclear count, neutrophil elastase, serum surfactant protein A, methane dicarboxylic aldehyde, IL-6, IL-8, and tumor necrosis factor-α at T2, T3, and T4 than those in the Control group (P<0.05). There were no significant differences in adverse reactions related specifically to blood transfusion or postoperative respiratory complications within 72 hours. CONCLUSIONS: Salvaged autologous blood leukocyte filtration can improve ventilation, promote gas exchange and oxygenation, and inhibit lung inflammatory and oxidative stress reactions in elderly patients undergoing lumbar spinal surgery.

Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia.

SPECIFIC AIM: Cerebral injury caused by hypoperfusion during the perioperative period is one of the main causes of disability and death in patients after major surgery. No effective protective or preventative strategies have been identified. This study was designed to evaluate the effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. METHODS: Sixty ASA (American Society of Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip replacement surgery, were enrolled in the study. They were randomly allocated to receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D group n=30) after induction of anesthesia. Blood samples were collected from radial artery and jugular venous bulb catheters for blood gas analysis and determination of glucose and lactate concentrations preoperatively, before surgical incision, at the end of surgery, and on post-op day 1. Arterial O2 content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated. RESULTS: There were no significant differences in CaO2 or Da-jvGlu during surgery between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at the end of surgery (T2) and on post-op day 1 (T3) than those in the control group (p<0.05). CONCLUSION: Ginkgo biloba extract can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and help maintain the balance between cerebral oxygen supply and consumption. It has no effect, however, on cerebral glucose metabolism in elderly patients with known, pre-existing cerebral ischemia.

[Effects of hyperbaric oxygen on the acute lung injury induced by oleic acid in rats].

OBJECTIVE: To explore the effect of hyperbaric oxygen (HBO) on acute lung injury (ALI) induced by oleic acid (OA) in rats. METHODS: Eighty healthy Sprague-Dawley (SD) rats were randomly divided into four groups. In OA group (n=30), ALI was produced by injection of OA 0.15 ml/kg through tail vein. Ten rats were randomly selected and sacrificed after injection of OA at the time of 4 hours, 3 days, and 7 days, respectively. In OA plus HBO group (n=20), rats received HBO intervention in a special box with oxygen of 2.5 atm (1 atm=101.325 kPa) for 90 minutes. Ten rats were randomly respectively sacrificed at 3 days and 7 days. In simple HBO group, 20 rats were sacrificed at 3 days and 7 days of HBO intervention, respectively. Other 10 rats were assigned as control group. Blood, lung specimens were collected after sacrifice. Serum contents of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-6 were measured. Gross changes and pathological findings of the left lung were recorded. The wet to the dry weigh (W/D) of the right lung was determined. RESULTS: Partial pressure of oxygen in arterial blood (PaO2, mm Hg, 1 mm Hg=0.133 kPa) fell from 107.70+/-5.37 to 57.40+/-2.63 in OA group. Congestion, bleeding and edema could be seen grossly. They could also be found under microscope with disappearance of normal structure, and accumulation of fluid in interstitium with inflammatory cell infiltration and hyaline membrane formation were also found. Lung W/D ratio was increased as compared with the control group (6.94+/-0.44 vs. 4.59+/-0.44, P<0.05). A marked increase was found in serum TNF-alpha, IL-1 beta, IL-6 levels [TNF-alpha (microg/L): 18.52+/-1.20 vs. 5.27+/-0.61, IL-1 beta (microg/L): 13.73+/-1.37 vs. 6.13+/-1.51, IL-6 (microg/L): 14.51+/-1.21 vs. 11.14+/-0.89]. After HBO therapy for 3 days and 7 days, PaO2 (mm Hg, 3 days: 79.20+/-1.68 vs. 59.00+/-2.70, 7 days: 94.30+/-3.77 vs. 74.00+/-3.85) and lung W/D (3 day: 7.43+/-0.73 vs. 9.82+/-0.99, 7 days : 6.75+/-1.14 vs. 8.77+/-1.60) of HBO group were ameliorated to varying degrees compared with OA model group (P<0.05 or P<0.01). HBO therapy for 3 days could lower levels of IL-1 beta (microg/L) in the serum (6.46+/-1.99 vs. 9.09+/-1.09, P<0.05). CONCLUSION: It is suggested that HBO treatment for ALI in rats had effects of improving arterial blood gases and the lung water transport, and inhibiting inflammatory mediators production.