Protective effect of hydrogen sulfide is mediated by negative regulation of epigenetic histone acetylation in Parkinson's disease.

Introduction: Derangements in monoaminergic transmission in the substantia nigra with disturbed signaling in the hypothalamic-pituitary-adrenal axis are the major characteristics of Parkinson's disease (PD). It has been reported that the administration of hydrogen sulfide (H2S) is in practice to treat PD because of its redundant nature in regulating various neuronal signals. Hence, the current investigation was performed to evaluate the hypothesis that H2S might exert protective action via the inhibition of epigenetic histone acetylation. Material and methods: To test this notion, 6-hydroxydopamine (6-OHDA) was used to induce PD and sodium hydrogen sulfide (SHS) was used as a H2S donor and tubastatin A (TSA) was tested in an in vivo rat model to delineate the signaling mechanism. Results: Induction of PD in rats demonstrated elevated oxidative stress with an evidenced decrease in antioxidant enzymes, while elevated pro-inflammatory cytokines and inflammatory mediators were observed in the striatum of PD rats compared to controls. On the other hand, elevated (p < 0.01) levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), mRNA transcript of HDAC-2, -3, -4, -6 and total histone deacetylase (HDAC) were found with reduced levels of histone acetyltransferase (HAT) in the brain tissues of PD induced rats. Conclusions: Diversely, H2S exposure reversed these alterations with reduced HDAC activity. Further, PD rats treated with HDAC inhibitor showed a dramatic upsurge in the level of tyrosine hydroxylase, with a decreased level of glial fibrillary acidic protein, α-synuclein, tumor necrosis factor α, and other cytokines. Thus the results of the study suggest that H2S exerts protection via inhibition of HDAC.

BIS feedback closed-loop target-controlled infusion of propofol or etomidate in elderly patients with spinal surgery.

OBJECTIVE: To investigate the safety of etomidate anesthesia induction combined with Bispectral index (BIS) feedback closed-loop target-controlled infusion of propofol for spinal surgery in elderly patients. METHODS: Clinical data of 90 elderly patients who underwent elective spinal surgery were retrospectively analyzed. The patients were assigned to an etomidate group (n=48) and a propofol group (n=42) according to the different anesthesia methods. The etomidate group was anesthetized with etomidate combined with BIS feedback closed-loop target-controlled infusion, and the propofol group was anesthetized with closed-loop target-controlled infusion induced by propofol. The mean arterial pressure (MAP) and heart rate (HR) of the two groups were statistically analyzed 5 min after admission to the operating room (T0), the moment of the intubation (T1), 3 min after intubation (T2), 1 min before prone position (T3), 3 min after prone position (T4), the end of suture skin (T5) and 3 min after supine position (T6). In addition, the vasoactive drug application, awakening time, tracheal tube extraction time and incidence of postoperative complications were compared between the two groups. RESULTS: There were significant changes in MAP and HR from T0 to T1 in both groups (MAP: etomidate group t=5.677, P<0.001, propofol group t=8.093, P<0.001; HR: etomidate group t=2.731, P=0.008, propofol group t=3.967, P<0.001). MAP changes in etomidate group from T0 to T1 were less (MAP: t=4.236, P<0.001; t=2.082, P=0.040), and there was no significant difference in HR between the two groups (P>0.05). There were fewer patients receiving vasoactive drugs in the etomidate group (χ2=5.070, P=0.024), but no significant difference was found in the incidence of complications between the two groups, χ2=3.670, P=0.055. CONCLUSION: Compared to propofol, the application of etomidate combined with BIS feedback closed-loop target-controlled infusion in spinal surgery anesthesia for elderly patients can keep hemodynamics in a stable state, without affecting postoperative resuscitation, showing high safety, so it is worthy of clinical application.

The clinical effect of nursing intervention in the operating room on the prevention of orthopedic wound infections.

OBJECTIVE: To study the preventive effect of operating room nursing intervention on surgical incision infections in elderly patients undergoing orthopedic surgery. METHODS: Altogether, 128 orthopedic patients were divided into an observation group and a control group according to the nursing method each patient underwent, with 64 patients in each group. RESULTS: The grade A incision healing rate in the observation group was significantly higher than the rate in the control group (P<0.01). The eating and getting out of bed times, and the lengths of the hospital stays in the observation group were significantly shorter than the corresponding times in the control group (P<0.01). The incidences of postoperative wound infections in the observation group (0 cases) was significantly lower than the incidences in the control group (14 cases, accounting for 21.88%), and the difference was statistically significant (P<0.001). After the nursing, the prognoses and quality of life scores of the patients in the observation group were better than they were in the control group, and the differences were statistically significant (P<0.01). Our investigation indicated that, after the treatment, the overall patient satisfaction rate in the observation group (98.44%) was significantly higher than the patient satisfaction rate in the control group (84.38%), and the difference was statistically significant (χ2=27.349, P=0.000). CONCLUSION: Operating room nursing intervention can effectively prevent postoperative wound infections and promote incision healing, so it is worthy of application.

Senescence marker protein 30 confers neuroprotection in oxygen-glucose deprivation/reoxygenation-injured neurons through modulation of Keap1/Nrf2 signaling: Role of SMP30 in OGD/R-induced neuronal injury.

Senescence marker protein 30 (SMP30) is a senescence marker molecule and identified as a calcium regulatory protein. Currently, SMP30 has emerged as a cytoprotective protein in a wide range of cell types. However, the role of SMP30 in regulating neuronal survival during cerebral ischemia/reperfusion injury remains unclear. In the present study, we aimed to investigate the biological function and regulatory mechanism of SMP30 on neuronal survival using a cellular model induced by oxygen-glucose deprivation/reoxygenation (OGD/R). The results showed that SMP30 expression was significantly decreased by OGD/R exposure in neurons. Functional experiments demonstrated that SMP30 overexpression significantly rescued the decreased cell viability and attenuated the apoptosis and reactive oxygen species generation in OGD/R-exposed neurons. By contrast, SMP30 knockdown exhibited the opposite effect. Mechanism research revealed that SMP30 overexpression contributed to the activation of nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response element (ARE) signaling associated with downregulation of Kelch-like ECH-associated protein (Keap1). Keap1 overexpression or Nrf2 silencing significantly reversed SMP30-mediated neuroprotection against OGD/R-induced injury. Overall, these findings demonstrate that SMP30 overexpression protects neurons from OGD/R-induced apoptosis and oxidative stress by enhancing Nrf2/ARE antioxidant signaling via inhibition of Keap1. These data highlight the importance of the SMP30/Keap1/Nrf2/ARE signaling axis in regulating neuronal survival during cerebral ischemia/reperfusion injury.

Trigonelline protects hippocampal neurons from oxygen-glucose deprivation-induced injury through activating the PI3K/Akt pathway.

Trigonelline is a plant alkaloid that has generated interest for its neuroprotective roles in brain pathology. However, the protective effect of trigonelline on cerebral ischemia/reperfusion (I/R) injury and the potential mechanism have not been fully evaluated. Our results showed that trigonelline pretreatment ameliorated oxygen-glucose deprivation/reperfusion (OGD/R)-induced hippocampal neurons injury. The OGD/R-caused reactive oxygen species (ROS) generation and decreased concentrations of superoxide dismutases (SOD) and glutathione peroxidase (GPx) were markedly attenuated by trigonelline. In addition, the increased levels of TNF-α, IL-6 and IL-1ß in OGD/R-induced hippocampal neurons were significantly decreased by trigonelline pretreatment. Trigonelline also suppressed caspase-3 activity and bax expression, and induced bcl-2 expression in OGD/R-induced hippocampal neurons. Furthermore, trigonelline induced the activation of PI3K/Akt pathway in hippocampal neurons exposed to OGD/R condition. Inhibition of PI3K/Akt signaling reversed the protective effects of trigonelline on OGD/R-induced hippocampal neurons injury. Taken together, these findings indicated that trigonelline protected hippocampal neurons from OGD/R-induced injury, which was mediated by the activation of PI3K/Akt signaling pathway.

Protective Effects of Ozone Oxidative Postconditioning on Long-term Injury After Renal Ischemia/Reperfusion in Rat.

BACKGROUND: Renal ischemia/reperfusion (I/R) injury can cause serious kidney damage (eg, acute aortic injury, chronic fibrosis). Some postconditioning treatments have been reported to protect from I/R effects. However, their mechanisms remain unclear. Here, we focused on potential protective effects of ozone on tubulointerstitial fibrosis after renal I/R injury in rats. METHODS: Adult male rats were randomly divided into 4 groups with (1) sham-without I/R; (2) I/R-by clamping renal pedicle for 45 minutes; (3) I/R with ozone oxidative postconditioning (OzoneOP) following a 10-day reperfusion; and (4) I/R with oxygen oxidative postconditioning (OxygenOP) following a 10-day reperfusion. The kidneys were collected at 2 time points post I/R 10 days (at early phase) and 12 weeks (at late phase) and then analyzed for renal function, tissue fibrosis, and serum creatinine and urea nitrogen levels by staining and colorimetric methods. Additionally, expression levels of related fibrotic factors, such as α-smooth muscle actin, transforming growth factor ß1, and phospho-Smad2, were assayed by immunochemistry staining. RESULTS: OzoneOP treatment downregulated the α-smooth muscle actin, transforming growth factor ß1, and phospho-Smad 2 protein expression in rats subjected to I/R at 10 days and 12 weeks. Moreover, it improved renal dysfunction and attenuated the patchy tubulointerstitial fibrosis. CONCLUSION: Ourdata indicate that I/R-induced renal damage might cause severe tubulointerstitial fibrosis at the late phase, and OzoneOP treatment may inhibit this fibrotic development.

MicroRNA-147 negatively regulates expression of toll-like receptor-7 in rat macrophages and attenuates pristane induced rheumatoid arthritis in rats.

Background/Introduction: Aberrant expression of Toll like receptors (TLR) plays a vital role in pathogenesis of rheumatoid arthritis (RA). Micro RNAs (miRs) could play important role in the related signaling pathways. The present study was undertaken to establish the link between miR-147 and TLR-7 in rat macrophages (in vitro) and in pristane (PS) induced arthritic rats. METHODOLOGY: Dual luciferase assay was done to confirm the interaction between miR-147 and TLR-7. The effect of miR-147 on regulation of TLR-7 was done by RT-qPCR and Immunoblotting studies in rat macrophages (ATCC® CRL-2192TM) after treating them with miR-147 mimics and inhibitors. R-848 (Imiquimod) was used as TLR-7 stimulant, the mRNA and protein expression levels of IFN-ß and TNF-α were recorded to determine the regulation of TLR-7. The levels of miR-147 and TLR-7 were evaluated during induction of rat bone marrow derived macrophage in the PS induced rat macrophages and spleens of methotrexate exposed rats. The miR-147 mimics was injected intraperitoneal to the PS treated rats and the severity of arthritis was studied. RESULTS: The study confirmed TLR-7 mRNA as the potential target of miR-147 in rats. Alterations in miR-147 by transfecting mimics or inhibitors in ATCC® CRL-2192TM cells exhibited suppression and amelioration of TLR-7 and cytokine expression. The alteration in expression of miR-147 was inversely correlated with expression of TLR-7 during bone marrow derived macrophages induction in PS exposed cells and spleens. The abnormal expression was reversed in spleens of methotrexate treated arthritic rats. The treatment of miR-147 mimic caused suppression in expression of TLR-7 and improved the severity of arthritis in PS induced arthritic rats. CONCLUSIONS: MiR-147 inversely regulates the TLR-7 signaling by targeting TLR-7 itself both in vivo and in vitro. The study provides a novel approach for conditions involving abnormal TLR-7 expression in arthritis.

Oxycodone versus sufentanil in adult patient-controlled intravenous analgesia after abdominal surgery: A prospective, randomized, double-blinded, multiple-center clinical trial.

BACKGROUND: A randomized controlled trial was performed to compare analgesic effects and adverse effects of oxycodone and sufentanil in patient-controlled intravenous analgesia (PCIA) after abdominal surgery under general anesthesia. METHODS: Adult patients undergoing elective abdominal surgery were randomly allocated into oxycodone and sufentanil groups according to the randomization sequence. Study personnel, health-care team members, and patients were masked to the group assignment throughout the study period. Oxycodone (0.1 mg/kg for endoscopy; 0.15 mg/kg for laparotomy) or sufentanil (0.1 µg/kg for endoscopy; 0.15 µg/kg for laparotomy) was administrated at the end of surgeries. Postoperative pain was controlled using PCIA. Bolus dose was 2 mg and 2 µg for oxycodone and sufentanil group, respectively. The lockout time was 5 minutes for all patients, and there was no background infusion for oxycodone group, whereas 0.02 µg/kg/h background infusion was administrated in sufentanil group. The primary outcomes were the total analgesic doses in PCIA, effective bolus times, the length of first bolus since patients returning to ward from postanesthesia care unit (PACU), rescue analgesic rate in PACU, numeric rating scales, functional activity scores, and patients' satisfaction scores. RESULTS: A total of 200 patients were screened, and 175 patients were enrolled. Patients were randomly assigned to oxycodone (n = 87) and sufentanil (n = 88) groups. Both oxycodone and sufentanil PCIA provided adequate postoperative pain relief. Patients in oxycodone group showed a shorter consciousness recovery time after surgery. The major adverse effect in patients from oxycodone group was nausea/vomiting, whereas multiple adverse complications including nausea/vomiting, pruritus, and respiratory depression were observed in patients from sufentanil group. Patients from oxycodone group showed significantly reduced analgesic drug consumption (calculated as equivalent dose of morphine), functional activity scores, and patient satisfaction scores. DISCUSSION: Compared with sufentanil PCIA, oxycodone PCIA showed better analgesic effects, lower incidence of adverse complications, and less analgesic drug consumption during postoperative pain management.

Evaluation of Anti-Nociceptive and Anti-Inflammatory Effect of Luteolin in Mice.

Flavonoids are polyphenolic compounds that not only impart coloration to plants and fruits, but also protect plants from pathogens, radiation, etc. They serve as a nutrient to plants and possess immense anti-oxidant properties. Research has shown that they exhibit anti-inflammatory, anti-cancer, and neuroprotective properties in both in vitro and in vivo analyses. Luteolin is one such flavonoid belongs to the group of flavones present in herbs such as thyme, chamomile, celery, and green pepper. The epidemiological data on luteolin consumption show that luteolin has anti-inflammatory activity and protects from diseases associated with inflammation. The present study assessed the anti-nociceptive properties of luteolin, a potent anti-inflammatory agent, in mice. The results demonstrated that luteolin produces a significant and dose-dependent increase in hot plate latency and tail withdrawal time. It also reduced the number of abdominal constrictions and paw licking induced by acetic acid and glutamate, respectively. Luteolin inhibited the nociceptive responses in both phases of formalin test. The anti-inflammatory property of luteolin was also confirmed with different anti-inflammatory mice models induced by carrageenan and air pouch. Behavioral changes in luteolin-treated mice were assessed with open-field test to confirm the muscle relaxant property. The results of the current study from various pain and inflammatory models confirms that luteolin possess potent anti-nociceptive and anti-inflammatory properties and can thus be used as a drug in pain management.