Propofol maintains Th17/Treg cell balance and reduces inflammation in rats with traumatic brain injury via the miR­145­3p/NFATc2/NF­κB axis.

Propofol is a commonly used intravenous anesthetic. The aim of the study was to examine the mechanism of propofol in traumatic brain injury (TBI) by regulating interleukin (IL)­17 activity and maintaining the Th17/Treg balance. A rat model with moderate TBI was established using the weight­drop method. Rats with TBI were regularly injected with propofol and their brain injuries were monitored. The peripheral blood of rats was collected to measure the Th17/Treg ratio. MicroRNA (miR)­145­3p expression was detected in the brain tissues of rats and antagomiR­145­3p was injected into the lateral ventricles of their brains to verify the effect of miR­145­3p on brain injury. The downstream target of miR­145­3p was predicted. The targeting relationship between miR­145­3p and nuclear factor of activated T cells c2 (NFATc2) was confirmed. NFATC2 expression and phosphorylation of NF­κB pathway­related proteins were measured. Propofol alleviated brain injury in rats with TBI and maintained the Th17/Treg balance. Propofol upregulated miR­145­3p expression in rat brains, while the inhibition of miR­145­3p reversed the effect of propofol on brain injury. A binding relationship was observed between miR­145­3p and NFATc2. Furthermore, propofol decreased the phosphorylation of p65 and IκBα, and inhibited activation of the NF­κB pathway in the brains of rats with TBI. In conclusion, propofol maintained Th17/Treg balance and reduced inflammation in the rats with TBI via the miR­145­3p/NFATc2/NF­κB axis.

[Effect of hot water extract of Korean ginseng on neuroblastoma cell parthanatos].

OBJECTIVE: To explore the effect of pretreatment of neuroblastoma cells with hot water extract of Korean ginseng on MNNG-induced parthanatos and its mechanism. METHODS: Neuroblastoma SH-SY5Y cells were pretreated with 1 mg/L hot water extract of Korean ginseng before induction with 250 µmol/L MNNG for 1 h or 4 h. CCK-8 and cell flow cytometry were used to detect cell survival rate. Western blotting was used to detect the changes in poly(ADP-ribose) (PAR) expression in the treated cells. Immunofluorescence assay was used to detect nuclear distribution of apoptosis-inducing factor (AIF), and flow cytometry was used to detect the level of reactive oxygen species (ROS) in the cells. RESULTS: Compared with the blank control cells, MNNG-treated SH-SY5Y cells showed significantly decreased survival rate as the concentration of MNNG and the stimulation time increased (P < 0.05). Stimulation with MNNG also resulted in significantly increased expression of PAR protein in the cells (P < 0.05). Pretreatment of the cells with hot water extract of Korean ginseng obviously inhibited MNNG-induced cell death and significantly reduced AIF expression and nucleation in the cells (P < 0.05). MNNG stimulation significantly increased ROS level in the cells, which was decreased significantly by pretreatment of the cells with the extract (P < 0.05). CONCLUSIONS: Pretreatment with hot water extract of Korean ginseng reduces MNNG-induced parthanatos and ROS production in SH-SY5Y cells.

[Molecular mechanism underlying the inhibitory effect of propofol on lipopolysaccharide-induced pyroptosis of mouse bone marrow-derived macrophages].

OBJECTIVE: To investigate the molecular mechanism underlying the inhibitory effect of propofol on pyroptosis of macrophages. METHODS: Macrophages derived from bone marrow were extracted and divided into three groups: control group, LPS+ATP group and propofol+LPS+ATP group. The control group was not given any treatment; LPS+ATP group was given LPS 1 µg/mL stimulation for 4 h, then ATP 4 mM stimulation for 1 h; Propofol+LPS+ATP group was given propofol+LPS 1 µg/mL stimulation for 4 h, then ATP stimulation for 1 h. After treatment, the supernatant and cells of cell culture were collected. the cell activity was detected by CCK8 and flow cytometry. The inflammatory cytokines IL-1ßand IL-18 were detected by Elisa. Western blot was used to detect the expression of caspase-1 protein and TLR4 on cell membran Immunohistochemical fluorescence was used to detect apoptosis of cells. RESULTS: LPS+ATP significantly decreased the viability of the macrophages and increased the cellular production of IL-1ß and IL-18, activation of caspase-1 protein and the expression of TLR-4 on the cell membrane (P < 0.05). Treatment with propofol obviously reversed the changes induced by LPS+ATP. CONCLUSIONS: LPS+ATP can induce pyroptosis of mouse bone marrow-derived macrophages, and propofol effectively inhibits such cell death, suggesting that propofol anesthesia is beneficial during operation and helps to regulate the immune function of in patients with sepsis.

[Effect of ulinastatin on isoflurane-induced neuronal apoptosis in the hippocampus of rats].

OBJECTIVE: To investigate the effect of ulinastatin pretreatment on isoflurane-induced mitochondria-dependent neuronal apoptosis in the hippocampus of rats. METHODS: Thirty-six male SD rats were randomly assigned into control group, isoflurane group and ulinastatin group. In the latter two groups, the rats were subjected to acute exposure to 0.75% isoflurane for 6 h and pretreated with 50 000 U/kg of ulinastatin before isoflurane exposure, respectively. After the treatments, apoptosis of the hippocampal neurons was detected using TUNEL assay, and the mitochondrial membrane potential (△ ψm) was measured using JC-1 mitochondrial membrane potential kit; cytochrome C release and caspase-3 activity were examined with Western blotting, and intracellular reactive oxygen species (ROS) was detected using the fluorescent probe H2DCFDA. RESULTS: Compared with those in the control group, the rats with acute exposure to isoflurane showed markedly increased TUNEL-positive cells in the hippocampus (P < 0.05), which were obviously reduced by ulinastatin pretreatment (P < 0.05). The △ψm of the hippocampal neurons was significantly reduced after isoflurane exposure (P < 0.05), and was partly recovered by ulinastatin pretreatment (P < 0.05). Acute exposure to isoflurane resulted in obviously increased cellular ROS, cytochrome C release and caspase-3 activity in the hippocampal neurons (P < 0.05), and these changes were significantly inhibited by ulinastatin pretreatment (P < 0.05). CONCLUSIONS: Ulinastatin pretreatment provides neuroprotection against isoflurane-induced apoptosis of the hippocampal neurons in rats possibly by inhibiting mitochondria-dependent apoptosis pathway.

Dexmedetomidine protects against high mobility group box 1-induced cellular injury by inhibiting pyroptosis.

Dexmedetomidine (DEX) is a widely used clinical anesthetic with proven anti-inflammatory effects. Both high mobility group box 1 (HMGB1) and pyroptosis play an important role in the inflammatory response to infection and trauma. Thus far, there have been no studies published addressing the effect of DEX on HMGB1 and pyroptosis. In order to fill this gap in the literature, bone marrow-derived macrophages (BMDMs) were exposed to HMGB1 (4 µg/mL) with or without DEX (50 µM) pretreatment. The production of pro-inflammatory cytokines [such as tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-18], phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and P38, and the activation of caspase-1 were measured by enzyme immunosorbent assay, western blot analysis, confocal microscope, and flow cytometry, respectively. We found that DEX protected against HMGB1-induced cell death of BMDMs. In addition, DEX suppressed the generation of TNF-α, IL-1ß, and IL-18 as well as the phosphorylation of ERK1/2 and P38. Moreover, DEX inhibited caspase-1 activation and decreased pyroptosis. Taken together, these findings demonstrate the protective effect of DEX in mediating HMGB1-induced cellular injury, thus indicating that DEX may be a potential therapeutic candidate for the management of infection and trauma-derived inflammation.

A noble bimetal oxysulfide CuVOS catalyst for highly efficient catalytic reduction of 4-nitrophenol and organic dyes.

A novel copper-vanadium bimetallic oxysulfide (CuVOS) nanoparticle catalyst was successfully synthesized by a facile method. The samples were characterized by X-ray photoelectron spectrometry (XPS), X-ray diffractometry (XRD), field-emission scanning electron microscopy (FE-SEM), UV-Vis diffuse spectroscopy (DRS), Fourier transform infrared spectroscopy (FTIR), and N2 adsorption-desorption isotherms. In order to check the catalytic efficiencies toward reduction reaction, 4-nitrophenol (4-NP) and other organic dyes such as rhodamine-B (RhB), methylene blue (MB), and methyl orange (MO) were used. The results showed that the CuVOS prepared in the presence of a suitable amount of N2H4 during the synthesis of the nanoparticles exhibited the fastest reduction capabilities by using NaBH4 as a reducing agent. It was demonstrated that a 100 mL 4-NP (20 ppm) solution was completely reduced by 5 mg CuVOS-3 within 2 min. Moreover, the complete reduction of 100 mL of MO, RhB, and MB solutions of 100 ppm was also achieved by 5 mg CuVOS-3 within 2 min, 6 min, and 5 min, respectively. Hence, the CuVOS is an efficient catalyst for reducing 4-NP and organic dyes and can have great potential for industrial application.

[Effect of electro-acupuncture at Zusanli acupoint on postoperative T cell immune function in rats].

OBJECTIVE: To study the effect of electro- acupuncture at Zusanli acupoint in regulating perioperative cell immune functions in rats. METHODS: Forty-two SD rats were divided into blank control group (n=6), model group (n=18), and electroacupuncture group (n=18). The rats in the latter two groups underwent thigh incision and femoral dissection under anesthesia; the rats in electro-acupuncture group received electro-acupuncture at bilateral Zusanli acupoint for 15 min before anesthesia and 1 h after the surgery. The rats in the model group and electro-acupuncture group were sacrificed at 6 h, 24 h, and 72 h after the operation and blood samples were taken from the ventricle for analyzing CD3, CD4, and CD8 T cell subpopulations and calculation of CD4/CD8 using flow cytometry. ELISA was used to detect the levels of interleukin-1 (IL-1) and IL-6. RESULTS: The CD3 T cell subpopulation was significantly lower in the model group and electro-acupuncture group than in the blank group at 6 h and 24 h after the operation. At 72 h after the operation, CD3 subpopulation levels still remained low in the model group, but recovered the control level in electro-acupuncture group. At each time point of measurement, CD3 level was significantly lower in the model group than in the electro-acupuncture group. CD4 level in the model group was significantly lowered at 6 h and 24 h after the operation, and recovered the control level at 72 h. In the electro-acupuncture group, CD4 level was significantly lowered at 6 h after the operation, but recovered the control level at 24 h. At 24 h and 72 h, the levels of CD4 were significantly lower in the model group than in the electro-acupuncture group. CD8 level underwent no significant changes after the operation in either the model group or electro-acupuncture group. CD4/CD8 was significantly lowered at 24 h and 72 h after the operation in the model group but showed no significant variation in the electro-acupuncture group. Compared with that in the control group, IL-1 level was significantly lowered in both the model group and electroacupuncture group at 6 h, 24 h, and 72 h after the operation, and was significantly lower in the model group than in the electroacupuncture group at these time points. IL-6 level increased significantly in the model group and the electro- acupuncture group at 6 h and 24 h. at 72 h, IL-6 level was obviously lowered in the electro-acupuncture group but remained elevated in the model group. CONCLUSIONS: Electro-acupuncture alleviates postoperative immune suppression and promotes recovery of the immune function in rats, suggesting a protective effect of electro-acupuncture at Zusanli acupoint on cellular immune function after surgery.

[Protective effect of dexmedetomidine against perioperative inflammation and on pulmonary function in patients undergoing radical resection of lung cancer].

OBJECTIVE: To study the protective effect of dexmedetomidine against perioperative inflammation and on pulmonary function in patients undergoing radical resection of lung cancer. METHODS: From May, 2014 to May, 2016, 124 patients with lung cancer receiving radical surgeries were randomized into experimental group (n=62) and control group (n=62). The patients in the control group received a single anesthetic agent for anesthesia, and additional dexmedetomidine was given in the experimental group. The levels of serum interleukin-1ß (IL-1ß), IL-10, and tumor necrosis factor-alpha (TNF-α) were measured before the operation (T0), at 30 min (T1) and 60 min (T2) during one lung ventilation (OLV) and at the end of operation (T3). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of malondialdehyde (MDA), myeloperoxidase (MPO) and xanthine oxidase (XOD), and the arterial oxygen partial pressure (PaO2), oxygenation index (OI), airway plateau pressure (APP) and airway resistance (AR) were also recorded. RESULTS: At the time points of T1 and T2, IL-1ß, IL-10, MDA, MPO, TNF-α, and XOD levels were significantly increased in both of the groups, but the levels of IL-1, IL-10, TNF-α and MDA were significantly lower and MPO and XOD levels significantly higher in the experimental group than in the control group (P<0.05). In both groups, PaO2 and OI decreased and APP and AR increased significantly at T1 and T2, but APP and AR were significantly lower and PaO2 and OI significantly higher in the experimental group than in the control group (P<0.05). CONCLUSION: Anesthesia with dexmedetomidine in lung cancer patients undergoing radical surgery can effectively reduce the inflammatory response of the lungs and protect the lung function of the patients.

[Sterilizing effect and residual bacteria of four different methods for sterilizing simple breathing vesicles].

OBJECTIVE: To study the effects of 4 different methods for disinfection of simple breathing vesicles and microbial residue. METHODS: The disinfection tests were divided into 4 groups: G1 group (43 cases) with 500 mg/L chlorine dioxide spray, G2 group (28 cases) with alcohol spray, G3 group (47 cases) with 50 mg/L trichloroisocyanuric acid (TCCA) immersion, and G4 group (46 cases) with 50 mg/L chlorine dioxide solution immersion. After 30 min of disinfection, each group was examined by bacterial culture and colony count. The residual bacteria were identified and typed. RESULTS: The 4 methods showed significant differences in bacterial colony count (P<0.001). The rate of bacterial residue was 0% in G1 group, 53.6% in G2 group, 27.7% in G3 group, and 21.7% in G4 group, showing significant differences between the 4 groups (P<0.001). The residual bacteria included antibiotic-resistant common opportunistic pathogen such as Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus haemolytic. CONCLUSIONS: Disinfection with 500 mg/L chlorine dioxide spray is the best for simple breathing vesicles. Prolonged immersion in TCCA may lead to the growth of drug-resistant pathogens in the breathing vesicles.

Propofol inhibits the activation of p38 through up-regulating the expression of annexin A1 to exert its anti-inflammation effect.

Inflammatory response is a kind of nonspecific immune response, with the central link of vascular response, which is mainly manifested by changes in neutrophils and vascular endothelial cells. In recent years, the in vivo and in vitro role of intravenous anesthetic propofol in inhibiting inflammatory response has been attracting more and more attention, but the anti-inflammatory mechanisms of propofol for mononuclear cells still remain undefined. In this study, proteomics analysis was applied to investigate protein expression profile changes in serum mononuclear cells following intervention of rats with endotoxemia using propofol. After two-dimensional electrophoresis and mass spectrometric identification, it has been found that the protein Annexin A1 was up-regulated in the propofol intervention group. Annexin A1 is a glucocorticoid-dependent anti-inflammatory protein. After detection using ELISA and Western blot assays, it has also been found that propofol can not only promote the expression of Annexin A1, but also inhibit the phosphorylation level of p38 and release of inflammatory factors (IL-1ß, IL-6 and TNF-α) in rats with endotoxemia. In order to further determine the role of up-regulated expression of Annexin A1 in anti-inflammation of propofol, this gene was silenced in vitro in human THP-1 cells, to detect the phosphorylation status of p38 and release of inflammatory factors. The results show that Annexin A1 can negatively regulate phosphorylation of p38 and release of IL-1ß, IL-6 and TNF-α in THP-1 cells following propofol intervention and lipopolysaccharide (LPS) stimulation. Our results clearly indicate that propofol can up-regulate Annexin A1 to inhibit the phosphorylation level of p38 and release of IL-1ß, IL-6 and TNF-α, so as to inhibit inflammatory response. Therefore, it can be speculated that Annexin A1 might be the key signaling protein in the in vivo and in vitro anti-inflammatory mechanisms of propofol.

[A proteomic study of peripheral blood mononuclear cells in patients undergoing cardiopulmonary bypass].

OBJECTIVE: To explore the effect of cardiopulmonary bypass (CPB) on the profile of protein expression in peripheral blood mononuclear cells (PBMCs). METHODS: Eleven patients undergoing cardiac surgery under cardiopulmonary bypass were enrolled in the study. Peripheral blood samples were collected before CPB (T0), 1 h after CPB (T1) and at the end of operation (T2), and PBMCs were obtained by gradient centrifugation. The profile of protein expression was analyzed using 2-D gel electrophoresis (2-DE) and mass spectrometry. The candidate proteins were further identified by Western blotting. RESULT: Compared to protein profile at T0, 12 protein spots were identified to be up-regulated in PBMCs at T1 (P <0.05), among which S100A9 reached the peak level at T1 and decreased after operation,but not returned to its initial level. CONCLUSION: Results indicate that 12 proteins are likely to be involved in CPB, however, their roles need to be elucidated.