ESE-1 mediates lipopolysaccharide-induced BV2 cell inflammation via upregulation of HMGB1 expression.

Microglial inflammation is characterized by an increase in proinflammatory cytokines and proinflammatory enzyme levels, facilitating inflammation-mediated neuronal apoptosis. Previous studies indicated that both high-mobility group protein B1 (HMGB1) and E26 transformation-specific sequence (ETS) transcription factor-1 (ESE-1) are involved in lipopolysaccharide (LPS)-mediated neuroinflammation. In the present study, we hypothesized that the ESE-1 modulates HMGB1 expression and is thus involved in LPS-mediated microglial inflammation. Moreover, we explored the potential mechanism by which ESE-1 modulates HMGB1 expression. Our study indicated that LPS increased proinflammatory cytokine and proinflammatory enzyme levels via upregulation of HMGB1 expression in BV2 cells. Moreover, LPS treatment increased ESE-1 expression while inhibiting sirt1 expression. Both sirt1 overexpression and si-ESE-1 treatment reversed LPSinduced HMGB1 expression and proinflammatory cytokine and proinflammatory enzyme levels. In addition, ESE-1 was found to be associated with sirt1. Also ESE-1 and sirt1 were found to be enriched with the HMGB1 promoter region. Sirt1 silencing increased the abundance of ESE-1 that occupied the HMGB1 promoter region. The present study indicated that ESE-1 associates with sirt1 to regulate HMGB1 expression, which participates in LPS-mediated inflammation in BV2 cells.

Astaxanthin prevents osteoarthritis by blocking Rspo2-mediated Wnt/ß-catenin signaling in chondrocytes and abolishing Rspo2-related inflammatory factors in macrophages.

Chondrocyte degeneration and classically activated macrophage (AM)-related inflammation play critical roles in osteoarthritis (OA). Here, we explored the effects of astaxanthin and Rspo2 on OA in vitro and in vivo. We observed that the Rspo2 gene was markedly elevated in synovial tissues of OA patients compared with healthy controls. In 2D cultures, Rspo2 and inflammatory factors were enhanced in AMs compared with nonactivated macrophages (NMs), and the protein expression levels of Rspo2, ß-catenin, and inflammatory factors were increased, and anabolic markers were reduced in osteoarthritic chondrocytes (OACs) compared to normal chondrocytes (NCs). Astaxanthin reversed these changes in AMs and OACs. Furthermore, Rspo2 shRNA significantly abolished inflammatory factors and elevated anabolic markers in OACs. In NCs cocultured with AM, and in OACs cocultured with AMs or NMs, astaxanthin reversed these changes in these coculture systems and promoted secretion of Rspo2, ß-catenin and inflammatory factors and suppressed anabolic markers compared to NCs or OACs cultured alone. In AMs, coculture with NCs resulted in a slight elevation of Rspo2 and AM-related genes, but not protein expression, compared to culture alone, but when cocultured with OACs, these inflammatory mediators were significantly enhanced at both the gene and protein levels. Astaxanthin reversed these changes in all the groups. In vivo, we observed a deterioration in cartilage quality after intra-articular injection of Rspo2 associated with medial meniscus (DMM)-induced instability in the OA group, and astaxanthin was protective in these groups. Our results collectively revealed that astaxanthin attenuated the process of OA by abolishing Rspo2 both in vitro and in vivo.

The effect of preoperative oral carbohydrate on the time to colostrum and amount of vaginal bleeding after elective cesarean section.

OBJECTIVE: To investigate the effect of oral carbohydrate at 2 h before elective cesarean section on postoperative recovery indicators such as the time to colostrum and vaginal bleeding. METHODS: Women undergoing elective cesarean section under spinal-epidural anesthesia, aged 20-40 years, with a body mass index (BMI) of 19-30 kg/m2 and an American Society of Anesthesiology (ASA) score of II were randomized to the oral carbohydrate group (the OC group), the oral placebo group (the OP group), or the control group (the C group). The OC group underwent oral carbohydrate preloading (300 mL/bottle), the OP group orally consumed 300 mL of distilled water, and the C group was forbidden from drinking or eating on the day of the operation. The time to colostrum, vaginal bleeding, time to exhaust, and complications were recorded. RESULTS: A total of 38 participants in the OC group, 37 in the OP group, and 37 in the C group completed the study. Compared with the OP group and the C group, the OC group produced colostrum significantly earlier, had a lower amount of 24-h vaginal bleeding, and had a higher 24-h consumption of analgesics. Compared with OP and OC groups, the C group took longer to exhaust. No significant intergroup difference was observed for any other indicator. CONCLUSION: Oral carbohydrates loading 2 h before elective cesarean section significantly reduces the time to produce colostrum and the amount of vaginal bleeding, which contributes to postoperative recovery.

The effectiveness of different education methods conducted at different times for decreasing the time required for a parturient to position herself for epidural placement.

BACKGROUND: Decreasing the anaesthesia preparation time for primiparas experiencing painful uterine contractions is clinically relevant. This prospective intervention study investigated the effect of various educational methods conducted at different times on body positioning for primiparas undergoing labour analgesia. METHODS: Ninety primiparas who were about to receive labour analgesia were randomly divided into a verbal instruction group, a photo instructions group, and an educational video group for immediate education, and 60 primiparas who were willing to receive labour analgesia but were not in labour were randomly divided into a photo instruction group and an educational video group for advance education. The times required for body positioning were compared. RESULTS: In the immediate education cohort, the body positioning time in the verbal group (50.48 ± 28.97 s) was significantly longer than those in the photo group (30.47 ± 6.94 s) and the video group (23.14 ± 9.74 s) (P = 0.00). In the advance education cohort, the time in the photo group (17.47 ± 6.48 s) was longer than that in the video group (13.71 ± 7.01 s) (P = 0.042). Whether photos or videos are used, advance education can significantly decrease body positioning time. CONCLUSIONS: Video or photo education for primiparas who are about to receive labour analgesia can decrease the body positioning time and is more effective when provided in advance.

Ropivacaine with intraspinal administration alleviates preeclampsia-induced kidney injury via glycocalyx /alpha 7 nicotinic acetylcholine receptor pathway.

Preeclampsia is characterized by hypertension and proteinuria, which is associated with kidney injury. Glycocalyx (GCX) degradation mediated endothelial injury can result in proteinuria and kidney damage. alpha 7 nicotinic acetylcholine receptor (α7nAChR) connects nervous and immune systems to respond to stress or injury. We aimed to explore the protective effect and mechanism of intraspinal analgesia on maternal kidney injury in preeclampsia. Endotoxin-induced preeclampsia rats treated with ropivacaine via intraspinal administration. Renal histopathological examination was performed, cell apoptosis in the kidney, the levels of Glycocalyx markers of Syndecan-1 and heparin sulfate (HS) in maternal serum, Syndecan-1 along with α7nAChR in the kidney were measured. Our results showed that kidney injury was obviously in preeclampsia rats with proteinuria, endothelial damage, higher apoptosis rate, increasing levels of Syndecan-1 and HS in serum, upregulated Syndecan-1 expression but downregulated α7nAChR expression in kidney. Preeclampsia rats treated with intraspinal injected ropivacaine attenuated preeclampsia-induced kidney injury as Syndecan-1 and HS were decreased in serum, Syndecan-1 expression was suppressed as well as α7nAChR was activated in the kidney. Our results suggested that Ropivacaine administered through the spinal canal may protect preeclampsia-induced renal injury by decreasing GCX and α7nAChR activation.

Ropivacaine Retards the Viability, Migration, and Invasion of Choriocarcinoma Cells by Regulating the Long Noncoding RNA OGFRP1/MicroRNA-4731-5p/HIF3A Axis.

Choriocarcinoma is an aggressive gestational trophoblastic neoplasm. This study attempted to explore the biological functions and underlying mechanisms by which ropivacaine restrains the progression of choriocarcinoma. The expression of long noncoding RNA OGFRP1, microRNA-4731-5p (miR-4731-5p), and HIF3A in choriocarcinoma cells was assessed by qRT-PCR. Choriocarcinoma cells treated with ropivacaine at the concentration of 100, 500, and 1000 µM were cultured for 24, 48, and 72 h, respectively. Choriocarcinoma cell viability was evaluated by MTT assay. Transwell assay was conducted to examine choriocarcinoma cell migration and invasion. Additionally, the target relationship between OGFRP1 and miR-4731-5p or between miR-4731-5p and HIF3A was predicted by bioinformatics analysis and confirmed by dual-luciferase reporter assays. OGFRP1 and HIF3A expression were enhanced in choriocarcinoma cells, while miR-4731-5p expression was inhibited. Treatment with ropivacaine impeded choriocarcinoma cell viability, migration, and invasion. Choriocarcinoma cells treated with 1000 µM ropivacaine for 48 h were selected for subsequent experiments. OGFRP1 elevation or miR-4731-5p deficiency mitigated the reduction effect of ropivacaine on tumorigenesis of choriocarcinoma cells. Besides, miR-4731-5p was predicted as the potential OGFRP1 target by StarBase and LncBase, and HIF3A was predicted as the potential miR-4731-5p target by StarBase and TargetScan. Dual-luciferase reporter assays determined that miR-4731-5p was a target of OGFRP1 and HIF3A was a target of miR-4731-5p. Feedback experiments declared that miR-4731-5p elevation or HIF3A suppression reversed the promoting effect of OGFRP1 overexpression on the malignant behaviors of ropivacaine-treated choriocarcinoma cells. Ropivacaine constrained choriocarcinoma cell viability, migration, and invasion through modulating the OGFRP1/miR-4731-5p/HIF3A axis. Our study may provide a novel strategy for choriocarcinoma prevention and treatment.

Exosome-mediated circ_0001846 participates in IL-1ß-induced chondrocyte cell damage by miR-149-5p-dependent regulation of WNT5B.

AIMS: Osteoarthritis (OA) is the leading cause of physical disability in middle-aged and elderly people globally. Previous studies have revealed that circular RNA (circRNA) is involved in the pathogenesis of OA. In this study, we studied the role of circ_0001846 in interleukin-1ß (IL-1ß)-induced OA progression. METHODS: Twenty-one patients with OA and 17 volunteers were recruited for the collection of articular cartilage tissues. The expression of circ_0001846, microRNA-149-5p (miR-149-5p) and Wingless-type MMTV integration site family, member 5B (WNT5B) was detected by quantitative real-time polymerase chain reaction. The protein expression was determined by western blot analysis. Cell viability, apoptosis, invasion and migration were demonstrated by cell counting kit-8, flow cytometry analysis, transwell invasion and wound-healing assays, respectively. The levels of IL-6 and tumor necrosis factor-α were detected by Enzyme-linked immunosorbent assay. The interaction between miR-149-5p and circ_0001846 or WNT5B was predicted by starbase online database, and proved by dual-luciferase reporter and RIP assays. RESULTS: Circ_0001846 and WNT5B expression were upregulated, while miR-149-5p expression was downregulated in articular cartilage tissues from patients with OA and IL-1ß-treated CHON-001 cells compared with normal articular cartilage tissues or untreated CHON-001 cells. Circ_0001846 expression was increased in IL-1ß-treated CHON-001 cell exosomes. Circ_0001846 knockdown reversed IL-1ß-mediated cell proliferation, apoptosis, migration, invasion, inflammation and extracellular matrix (ECM) degradation in CHON-001 cells. Additionally, circ_0001846 participated in IL-1ß-induced chondrocyte cell damage by sponging miR-149-5p. MiR-149-5p mediated IL-1ß-induced chondrocyte cell dysfunction by targeting WNT5B. Furthermore, circ_0001846 secretion was mediated by exosomes in IL-1ß-treated CHON-001 cells. CONCLUSION: Exosome-mediated transfer of circ_0001846 modulated IL-1ß-induced chondrocyte cell damage by miR-149-5p/WNT5B axis, providing a novel avenue for the therapy of OA.

Opposing responses of the rat pulmonary artery and vein to phenylephrine and other agents in vitro.

BACKGROUND: Different from current cognition, our study demonstrated that adrenergic receptors agonist phenylephrine significantly relaxed isolated pulmonary artery but constricted pulmonary veins. Through comparing differences in the effects of commonly used vasoactive drugs on pulmonary artery and veins, the study aimed to improve efficiency and accuracy of isolated pulmonary vascular experiments, and to provide experimental basis for clinical drug use. METHODS: The contractile responses of pulmonary arteries and veins from twelve-week-old Male Sprague-Dawley rats to phenylephrine, arginine vasopressin (AVP), U46619, endothelin-1, and potassium chloride (KCl) were recorded, as well as the relaxation in response to phenylephrine, AVP, acetylcholine. To further explore the mechanism, some vessels was also pre-incubated with adrenergic receptors antagonists propranolol, prazosin and nitric oxide synthesis inhibitor N[gamma]-nitro-L-arginine methyl ester (L-NAME) before addition of the experimental drugs. RESULTS: Phenylephrine constricted pulmonary veins directly, but constricted pulmonary artery only after incubation with propranolol or/and L-NAME. The pulmonary artery exhibited significant relaxation to AVP with or without L-NAME incubation. AVP more clearly constricted the veins after incubation with L-NAME. Changes in vascular tension also varied from pulmonary artery to veins for KCl stimulation. Different from phenomena presented in veins, acetylcholine did not relax pulmonary artery preconstricted by KCl, U46619, and endothelin-1. CONCLUSIONS: According to the results, phenylephrine, KCl, AVP, and acetylcholine could be used to distinguish pulmonary arteries and pulmonary veins in vitro. This also suggested that the pulmonary arteries and pulmonary veins have great differences in physiology and drug reactivity.

A Randomized Controlled Comparison of Epidural Analgesia Onset Time and Adverse Reactions During Labor With Different Dose Combinations of Bupivacaine and Sufentanil.

OBJECTIVES: The purpose was to compare the effects of 3 different dose combinations of bupivacaine and sufentanil on the onset of analgesia and the occurrence of side effects. MATERIALS AND METHODS: One hundred sixty-nine pregnant women were randomly assigned to 3 groups: the B1S5 group received 0.1% bupivacaine+5 µg sufentanil in 15 mL; the B125S5 group received 0.125% bupivacaine+5 µg sufentanil in 15 mL; and the B1S10 group received 0.1% bupivacaine+10 µg sufentanil in 15 mL. The primary outcome was the analgesic onset time, and the secondary outcomes were mode of delivery, patient satisfaction, maternal and neonatal side effects (pruritus, hypotension, sedation, motor block, decreased fetal heart rate, fever, and interference with breastfeeding). RESULTS: The median (inter-quartile range) time to achieve effective analgesia was significantly faster in the B125S5 group than in the B1S5 group (10 [11-14 {4-30}] min vs. 15 [17-20 {5-30}] min, P<0.001). There was no significant difference in the analgesia onset time between the B1S10 and B125S5 groups (10 [11-14 {4-30}] min vs. 12 [13-15 {3-30}] min, P=0.202). Pruritus, hypotension, motor block, maternal satisfaction, delivery mode, decreased fetal heart rate, total bupivacaine dose and breastfeeding scores were not significantly different among the 3 groups except the sufentanil dosage and incidence of mild drowsiness and fever (the B1S10 group had significantly higher fever than the other groups). DISCUSSION: The B125S5 combination may be superior to the B1S5 and B1S10 combinations as an initial dose for epidural analgesia to achieve rapid effective analgesia with minimal side effects.

Ketamine inhibits LPS-mediated BV2 microglial inflammation via NMDA receptor blockage.

Microglial inflammation leads to the upregulation of proinflammatory cytokine and proinflammatory enzyme expression, resulting in inflammation-induced neuronal cell apoptosis. Ketamine, an anesthetic mostly used in critical patients, has been reported to possess neuroprotective effects. However, the potential mechanism is still not well understood. In the present study, we investigated how ketamine attenuates lipopolysaccharide (LPS)-mediated BV2 cell inflammation. LPS upregulated proinflammatory cytokine and proinflammatory enzyme expression, increased NF-κB phosphorylation and nuclear translocation, and augmented calcium (Ca2+ )/calmodulin-dependent protein kinase II (CaMK II) phosphorylation and Ca2+ levels in BV2 cells. Ketamine could reverse these LPS-induced effects. Furthermore, AP5, an inhibitor of NMDA receptors, inhibited LPS-induced inflammatory effects in BV2 cells, which was similar to the effects of ketamine. Moreover, these effects of ketamine against LPS-mediated inflammation in BV2 cells could be reversed by D-serine, an activator of NMDA receptors. The present study suggests that ketamine, by inhibiting NMDA receptors, attenuating Ca2+ levels, and inhibiting CaMK II phosphorylation, NF-κB phosphorylation and nuclear translocation, may ameliorate LPS-mediated inflammation in BV2 cells.

Nd-Fe-B Magnets: The Gradient Change of Microstructures and the Diffusion Principle after Grain Boundary Diffusion Process.

The diffusion of Tb in sintered Nd-Fe-B magnets by the grain boundary diffusion process can significantly enhance coercivity. However, due to the influence of microstructures at different depths, the coercivity increment and temperature stability gradually decreases with the increase of diffusion depth, and exhibit good corrosion resistance at a sub-surface layer (300-1000 µm). According to the Electron Probe Micro-analyzer (EPMA) test results and the diffusion mechanism, the grain boundary and intragranular diffusion behavior under different Tb concentration gradients were analyzed, and the diffusion was divided into three stages. The first stage is located on the surface of the magnet, which formed a thick core-shell structure and a large number of RE-rich phases. The second stage is located in the sub-surface layer, forming a uniform and continuous RE-rich phase and thin core-shell structure. The third stage is located deeper in the magnet, and the Tb enrichment only existed at the triangular grain boundary.

Gremlin2 Regulates the Differentiation and Function of Cardiac Progenitor Cells via the Notch Signaling Pathway.

BACKGROUND/AIMS: The transplantation of cardiac progenitor cells (CPCs) improves neovascularization and left ventricular function after myocardial infarction (MI). The bone morphogenetic protein antagonist Gremlin 2 (Grem2) is required for early cardiac development and cardiomyocyte differentiation. The present study examined the role of Grem2 in CPC differentiation and cardiac repair. METHODS: To determine the role of Grem 2 during CPC differentiation, c-Kit+ CPCs were cultured in differentiation medium for different times, and Grem2, Notch1 and Jagged1 expression was determined by RT-PCR and western blotting. Short hairpin RNA was used to silence Grem2 expression, and the expression of cardiomyocyte surface markers was assessed by RT-PCR and immunofluorescence staining. In vivo experiments were performed in a mouse model of left anterior descending coronary artery ligation-induced MI. RESULTS: CPC differentiation upregulated Grem2 expression and activated the Notch1 pathway. Grem2 knockdown inhibited cardiomyocyte differentiation, and this effect was similar to that of Notch1 pathway inhibition in vitro. Jagged1 overexpression rescued the effects of Grem2 silencing. In vivo, Grem2 silencing abolished the protective effects of CPC injection on cardiac fibrosis and function. CONCLUSIONS: Grem2 regulates CPC cardiac differentiation by modulating Notch1 signaling. Grem2 enhances the protective effect of CPCs on heart function in a mouse model of MI, suggesting its potential as the rapeutic protein for cardiac repair.

Inflammatory biomarkers of coronary heart disease.

Coronary heart disease (CHD) is one of the leading causes of death worldwide. CHD is characterized by formation of arterial plaques which are mainly comprised of lipids, calcium and inflammatory cells. These plaques narrow the lumen of coronary arteries leading to episodic or persistent angina. Rupture of these plaques leads to the formation of thrombus, which as a result of cessation of blood flow, causes myocardial infarct and death. CHD is exacerbated by risk factors including obesity, diabetes mellitus, and hypertension. Diagnosis is established by the level of blood cholesterol, triglycerides and lipoproteins Inflammation is considered significant in the pathogenesis of CHD and for this reason, severity and prognosis of CHD is assessed by the levels of inflammatory biomarkers, including interleukin-6, C-reactive protein (CRP), complement, CD40 and myeloperoxidase (MPO).

Inflammatory biomarkers of coronary heart disease.

Coronary heart disease (CHD), characterized by inflammation and accumulation of plaques mainly comprised of lipids, calcium and inflammatory cells in the walls of coronary arteries. CHD is exacerbated by specific cardiovascular risk factors, such as obesity, diabetes mellitus, and hypertension. The current review focuses on the critical role of traditional inflammatory biomarkers, including interleukin-6, C-reactive protein (CRP), complement, CD40 and myeloperoxidase (MPO), in the pathogenesis of CHD.

Influence of different menstrual phases on the Bispectral Index during dexmedetomidine sedation.

To investigate the influence of different menstrual phases on the Bispectral Index (BIS) during dexmedetomidine (Dex) sedation, 40 patients with regular menstrual cycle, American Society of Anesthesiologists I-II, aged 18-40 years, undergoing selective gynecologic laparoscopic surgery, were enrolled. According to different menstrual phases and the serum progesterone concentration, they were divided into two groups: the follicular phase group (Group F) and the luteal phase group (Group L), and each group had 20 patients. Before anesthesia induction, patients were infused with an initial loading dose of Dex (1 µg/kg) for 10 minutes and then 0.5 µg/kg/h for 20 minutes. BIS and the changes in hemodynamic and respiratory parameters were recorded within those 30 minutes. Time to lower BIS to 70 and 60 in Group L was shorter than that in Group F (9.4 ± 1.3 minutes vs. 11.3 ± 2.1 minutes, p = 0.005; 11.3 ± 2.4 minutes vs. 14.0 ± 3.6 minutes, p = 0.021). The number of patients whose BIS reached 50 in Group L was greater than that in Group F (15 vs. 8, p < 0.05). The lowest BIS value in the Group L was lower than that in Group F (46.8 ± 6.3 vs. 55.3 ± 5.5, p = 0.006), and the heart rate of patients in both groups showed a decrease (p < 0.05). The sedative effect of Dex was more significant in patients during the luteal phase than during the follicular phase.

Immunofluorescence laser confocal expression and localization study of rat nerve growth guidance cues Netrin-1 and Slit2 after spinal cord injury.

OBJECTIVE: To observe the expression and distribution of adult rat axon guidance cues Netrin-1 and Slit2 at different time points after spinal cord injury and to investigate the guidance mechanism of regenerated axons. METHODS: Twenty adult Sprague Dawley (SD) rats were divided randomly into five groups with 4 in each. Four groups of them were used to make Allen's spinal cord punch models and we took materials randomly from one of them on the 2nd, 4th, 7th and 14th day respectively after operation. The left one group was taken as the control group. Immunofluorescence laser confocal scan was used to examine the co-expression and localization of Netrin-1 and Slit2 proteins in the injured site of the spinal cord. RESULTS: Within two weeks after SCI, the expression of Netrin-1 and Slit2 proteins increased temporarily and there was co-expression of them on the neuron plasma membrane. CONCLUSIONS: Synchronous high expression and co-expression of axon attractant Netrin-1 and repellent Slit2 are found in the adult rat injured spinal cord in the damaged local and vicinity parts, and probably, they act as the key regulators of axon guidance regeneration.

Reconstruction of finger pulp defect with reversed fasciocutaneous island flap from same finger.

OBJECTIVE: To investigate the clinical curative effect of reconstruction of finger pulp defect by anastomosis of reversed fasciocutaneous island flap with dorsal branch of the digital nerve of the same finger. METHODS: The restoration of finger pulp defect with fasciocutaneous island flap from the same finger was conducted in 25 cases (30 fingers) from January 2002 to June 2003. Nine patients (11 fingers) whose flaps with dorsal branch of the digital nerve anastomosed with the digital inherent nerve around the surface of the wound were Group A and the others were Group B. The follow-up was carried out at 3 and 9 months after the operation to observe the shape of finger pulp and the sense restoration between two groups. RESULTS: All flaps of 25 cases (30 fingers) survived. Three months after operation, the patients had fully grown finger pulps and recovered the superficial sensation and tactile sense of finger pulps. The two point discrimination on average was 5.00 mm+/-0.23 mm in Group A and 6.00 mm+/-0.30 mm in Group B. The difference between two groups was highly significant. Nine months later, their senses of finger pulps between two groups were recovered basically. CONCLUSIONS: The reversed fasciocutaneous island flap from the same finger is the first choice to reconstruct the finger pulp defect, and the anastomosis of dorsal branch of the digital nerve shall be determined according to the specific condition.