Retinol palmitate protects against myocardial ischemia/reperfusion injury via reducing oxidative stress and inhibiting apoptosis.

The purpose of this study was to determine whether retinol palmitate could protect against myocardial ischemia/reperfusion (I/R) injury and explore the underlying mechanism. Retinol palmitate reduced the level of reactive oxygen species and prevented cellular apoptosis. In vivo, retinol palmitate increased superoxide dismutase (SOD) activity and reduced the level of malondialdehyde in I/R mice. Retinol palmitate also decreased myocardial infarct size and reduced cellular apoptosis by suppressing the expression of proapoptotic-related proteins and increasing that of SOD-related proteins. Our results suggest that retinol palmitate pretreatment has a protective effect against myocardial I/R injury by maintaining the balance between intracellular oxidants and antioxidants.

Inhibition of SOX15 Sensitizes Esophageal Squamous Carcinoma Cells to Paclitaxel.

BACKGROUND: SOX15 is a crucial transcription factor involved in the regulation of embryonic development and in the cell fate determination. It is also an important mediator of tumorigenesis in cancer. METHODS: Here, we sought to explore the expression patterns and biological functions of SOX15 in esophageal squamous cell carcinomas (ESCC). SOX15 was found aberrantly overexpressed in ESCC tumors. RESULTS: Experimentally, inhibition of SOX15 through RNAi suppressed cell proliferation in ESCC cells and sensitized cancer cells to paclitaxel, but not to Cisplatin. Moreover, inhibition of SOX15 significantly repressed the expression of genes associated with WNT and NOTCH signaling pathways, which may contribute to the increased sensitivity to paclitaxel. CONCLUSION: In conclusion, the current study revealed that inhibition of SOX15 in ESCC cells sensitizes the ESCC cells to paclitaxel, suggesting that the SOX15 expression level may predict the therapeutic outcomes for paclitaxel treatment for ESCC.

Saikosaponin a Inhibits Cigarette Smoke-Induced Oxidant Stress and Inflammatory Responses by Activation of Nrf2.

Saikosaponin a (SSa), a triterpenoid saponin, has numerous pharmacological properties, including anti-inflammatory and antioxidant effects. The purpose of this study was to investigate whether and how SSa protected against cigarette smoke (CS)-induced lung inflammation in mice. The mice were exposed to CS and SSa was administered by an intraperitoneal (i.p.) injection 1 h before CS treatment for 5 consecutive days. The results showed that SSa significantly inhibited CS-induced inflammatory cell infiltration, NO, TNF-α, and IL-1ß production in BALF. SSa also inhibited CS-induced MPO and MDA contents in lung tissues. Furthermore, SSa significantly inhibited CS-induced NF-κB and upregulated the expression of Nrf2 and HO-1. In conclusion, these results support a therapeutic potential for SSa in CS-induced lung inflammation.

Overexpression of microRNA-146 protects against oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis by inhibiting the NF-κB/TNF-α signaling pathway.

MicroRNA (miR) has been reported to be associated with ischemia and reperfusion (I/R) and cell apoptosis. Suppression of cell apoptosis may reduce the irreversible damage induced by reperfusion. The aims of the current study were to explore the cytoprotective effects of miR-146 against oxygen-glucose deprivation/recovery (OGD/R)-induced injury in H9c2 rat myocardial cells, as well as the underlying mechanisms. Following stimulation with OGD/R, the cells were transfected with miR-146 mimics or negative controls. The levels of miR-146 were analyzed by reverse transcription-quantitative polymerase chain reaction. Thereafter, cell viability and cell apoptosis were analyzed by MTT assay and terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling assay, respectively. In addition, the levels of tumor necrosis factor (TNF)-α were determined by ELISA and the levels of B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2 and phosphorylated (p)-nuclear factor (NF)-κB were measured by western blotting. The results demonstrated that overexpression of miR-146 significantly increased cell viability and decreased apoptosis (P<0.05). It was observed that overexpression of miR-146 statistically reduced the levels of Bax, TNF-α and p-NF-κB but markedly upregulated the levels of Bcl-2 (P<0.05). These results indicate that overexpression of miR-146 may protect against OGD/R-induced cardiomyocyte apoptosis. Overexpression of miR-146 may alleviate the irreversible injury associated with reperfusion and the effects may be achieved by inhibiting the NF-κB/TNF-α signaling pathway.

Effects of levosimendan on mortality in patients with septic shock: systematic review with meta-analysis and trial sequential analysis.

OBJECT: Several studies have investigated a survival benefit for levosimendan treatment in patients with septic shock. However, data are conflicting. We conducted a meta-analysis to evaluate the effect of levosimendan treatment on mortality in patients with septic shock. MATERIALS AND METHODS: We searched PubMed, EMBASE and Cochrane Library Databases up to March 27, 2017, without language restrictions. We searched for terms related to septic shock, levosimendan, randomized clinical trial. Randomized controlled trials reported the effect of levosimendan on mortality were included. Moreover, we constructed the trial sequential analysis (TSA) to determine the reliability of the outcomes. Furthermore, secondary outcomes were cardiac index(CI), mean arterial pressure (MAP), blood lactate, norepinephrine dose and length of ICU stay. RESULTS: Ten studies with a total of 816 patients were included in this meta-analysis. There was no significant difference in the mortality between the levosimendan group and the standard inotropic therapy group [RR = 0.96, 95% CI (0.81-1.12), I2 = 0]. However, methods adapted from formal interim monitoring boundaries applied to TSA indicated that the cumulative evidence was unreliable and inconclusive. Blood lactate was significantly reduced in the levosimendan group while there was no difference in MAP, CI, norepinephrine dose and length of ICU stay. CONCLUSIONS: Findings from this meta-analysis demonstrated that levosimendan treatment may not reduce mortality in patients with septic shock. The result remains inclusive and further randomized controlled trials were needed to confirm these conclusions.

Effects of alliin on LPS-induced acute lung injury by activating PPARγ.

Alliin is a garlic organosulfur compound that possesses various pharmacological properties. In the present study, the protective effects and molecular mechanism of alliin on Lipopolysaccharides (LPS)-induced acute lung injury (ALI) were analyzed. LPS-induced ALI was induced in BALB/c mice by intranasal instillation of LPS. Alliin was administered intraperitoneally to mice 1 h after LPS treatment. The results showed that alliin markedly inhibited lung myeloperoxidase (MPO) activity and wet/dry (W/D) ratio induced by LPS. Alliin also inhibited TNF-α and IL-1ß in the bronchoalveolar lavage fluid (BALF) induced by LPS. Furthermore, LPS-induced lung pathological injury was attenuated by treatment of alliin. LPS-induced NF-κB activation was significantly inhibited by alliin. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) was up-regulated by treatment of alliin. Taken together, these results suggested that alliin protected against LPS-induced ALI by activating PPARγ, which subsequently inhibited LPS-induced NF-κB activation and inflammatory response. Alliin might be used as an anti-inflammatory agent in the treatment of ALI.

Effects of Angelicin on Ovalbumin (OVA)-Induced Airway Inflammation in a Mouse Model of Asthma.

Angelicin, a furocoumarin found in Psoralea corylifolia L. fruit, has been reported to have anti-inflammatory activity. The purpose of this study was to determine the protective effects of angelicin on allergic asthma induced by ovalbumin (OVA) in mice. Mice were sensitized to OVA (on days 0 and 14) and challenged with OVA three times (on days 21 to 23). Angelicin (2.5, 5, 10 mg/kg) was given intraperitoneally 1 h before OVA treatment after the initial OVA sensitization. The production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum were measured by ELISA. Lung histological changes were detected by using hematoxylin and eosin (H&E) stain. The results showed that angelicin significantly inhibited inflammatory cells infiltration into the lungs. Histological studies showed that angelicin significantly attenuated OVA-induced lung injury. Meanwhile, treatment of angelicin dose-dependently inhibited OVA-induced the production of IL-4, IL-5, and IL-13 in BALF and IgE in the serum. Furthermore, angelicin was found to inhibit airway hyperresponsiveness and NF-kB activation. In conclusion, our results suggested that angelicin inhibited allergic airway inflammation and hyperresponsiveness by inhibiting NF-kB activation.

Association between serum interleukin-35 levels and severity of acute pancreatitis.

Inflammatory cytokines have been reported to be associated with pathogenesis of acute pancreatitis. The aim of this study was to measure the serum IL-35 levels in patients with acute pancreatitis and analyze the relationship between IL-35 levels and the disease severity. Thirty-two patients with acute pancreatitis and 32 healthy control subjects were included into the study. The serum levels of IL-35 were measured by enzyme-linked immunosorbent assay upon admission and the following seven days. The relationships with severity and etiology during the clinical course were analyzed. Serum IL-35 levels in patients with acute pancreatitis at the time of admission (5.25±0.37 ng/mL) were significantly higher than those in healthy controls (1.93±0.16 ng/mL, P<0.001). Moreover, serum IL-35 levels in patients with severe attacks (7.15±0.48 ng/mL) were significantly higher than those with moderately severe attacks (5.14±0.49 ng/mL, P=0.01) and mild attacks (3.69±0.53 ng/mL, P<0.001). However, there was no significant difference of serum IL-35 levels among patients with acute pancreatitis due of alcohol, gallstone and idiopathy. In addition, the peak serum concentrations of IL-35 were on day 1 after admission. Our results demonstrate that increased serum IL-35 levels may be related to the inflammatory response in patients with acute pancreatitis, suggesting that IL-35 may be used for a potential biomarker of acute pancreatitis.

[Comparison of lumbar plexus block and epidural block for elderly patients undergoing intertrochanteric femoral fracture surgery].

OBJECTIVE: To compare the anesthesia efficacy, hemodynamics, recovery of passage of gas by anus and bladder function in elderly patients with operation of intertrochanteric femoral fracture with epidural or lumbar plexus block. METHODS: Sixty patients with intertrochanteric femoral fracture, aged 65-97, were randomly divided into 3 equal groups: lumbar plexus group (Group A, undergoing posterior lumbar plexus block) and epidural group (Group B, undergoing epidural block at L(1-2) interspace). The block onset time, anesthesia efficacy, transfusion amount during operation, blood pressure and heart rate change 1 h after anesthesia, and recovery after anesthesia were observed. RESULTS: The block onset time on femoral nerve, lateral cutaneous nerve of thigh, obturator nerve, and saphenous nerve of Group A were (2.7 +/- 2.0) min, (3.1 +/- 3.4) min, (3.5 +/- 3.3) min, and (3.7 +/- 3.1) min respectively, all significantly shorter than those of Group B [(13.5 +/- 2.1) min, (13.5 +/- 2.1) min, (13.5 +/- 2.1) min, and (13.5 +/- 2.1) min respectively, all P < 0.01]. The duration of postoperative analgesia of Group A was (420 +/- 152) min, significantly longer than that of Group B [(204 +/- 44) min, P < 0.05]. There were no significant differences in the change of blood pressure and heart rate between these 2 groups. The blood pressure decreased significantly 10 - 60 min after anesthesia in Group B, and remained stable in Group A. The transfusion amount of Group A was (773 +/- 353) ml, significantly fewer than that in Group B [(1483 +/- 444) ml, P < 0.01]. Passage of gas by anus started (1.1 +/- 0.6) h after operation in Group A, a time significantly shorter than that in Group B (5.9 +/- 1.2) h, P < 0.01). Urinary retention was seen in 8 patients of Group B, however, no patient in Group A showed incidence of urinary retention (P < 0.01). Forty-eight patients, 20 in Group A and 28 in Group B got excellent anesthesia effect, and 12 of them, 10 in Group A and 2 in Group B, got relatively good anesthesia (P < 0.05). CONCLUSION: Both lumbar plexus block and epidural block provide satisfactory anesthetic efficacy for operation of intertrochanteric femoral fracture in elderly patients. Epidural block provide better efficacy, and lumbar plexus block shows faster recovery of digestive system and urinary system after operation.

[Determination of median effective dose of lidocaine to control the onset time of sciatic nerve blockade using up-and-down sequential method].

OBJECTIVE: To determine the median effective dose (ED50) of 2% lidocaine to control the onset time of sciatic nerve blockade within 15 min by using 2% lidocaine and 0.75% ropivacaine 10 ml. METHODS: Fifty patients underwent sciatic nerve blockade and lumbar plexus blockade for operations of unilateral lower extremities. 2% lidocaine was allocated into 7 ranks in geometric proportion between 4.2 ml and 12.5 ml. The observed index was the blockade onset time less than 15 min of the lateral cutaneous branch of sural nerve, fibular nerve, and rami calcanei medicales nervi tibialis. The ED50 of 2% lidocaine was determined respectively in the patients in which dorsiflexion or plantarflexion was elicited by in up-and-down sequential method. RESULTS: Combined with ropivacaine, the values of ED50 of 2% lidocaine in the patients in which dorsiflexion and plantarflexion were elicited by up-and-down sequential method were 6.88 ml and 6.19 ml respectively when the onset time of blockade of sciatic nerve was within the range of 15 min. CONCLUSION: The dosage to elicit plantarflexion is similar to the dosage to elicit dorsiflexion in sciatic nerve blockade.

[Efficacy of axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture technique].

OBJECTIVE: To investigate the clinical effects and safety of the technique of axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture. METHODS: Eighty patients scheduled for elective operation were randomly divided into 2 equal groups to undergo axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture technique (Group U) or nerve stimulator-guided brachial plexus blocking (Group N). The main branches of brachial plexus (radial, median, ulnar, and musculocutaneous nerves) were localized by ultrasound-guided or nerve stimulator-guided techniques. In Group U 8 ml of mixed anesthetic solution containing isovolumetric 0.75% ropivacaine and 2% lidocaine was injected into the 4 main branches of brachial plexus, with a total volume of 32 ml. The ultrasonic manifestations of the brachial plexus and its surrounding tissues were observed. The values of diameter and depth of the 4 nerves and the distance of the musculocutaneous nerve to the midpoint of axillary artery were measured. The manipulation time, onset time, maintaining time, efficacy of blocking, and incidence of complication were recorded. RESULTS: The manipulation time of Group U was 5.2 +/- 2.1 min, significantly shorter than that of Group N (14.6 +/- 3.2 min, P = 0.000), The onset times of the median, radial, and ulnar nerves of Group U were 3.3 +/- 1.9 min, 3.0 +/- 1.7 min, and 3.4 +/- 1.9 min respectively, all significantly shorter than those of Group N (4.6 +/- 2.0 min, 7.3 +/- 7.4 min, and 6.4 +/- 6.1 min respectively, P < 0.01 or P < 0.05). The anesthetic success rate of Group U was 100%, significantly higher than that of Group N (77.5%, P = 0.005). The rate of accidental puncture to blood vessel of Group U was 0, significantly lower than that of Group N (40%, P = 0.000). CONCLUSION: With significantly higher anesthetic success rate, shorter manipulation time and onset time, and lower complication rate, the technique of axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture is a safe and reliable blocking method in comparison with the nerve stimulator-guided method.