GTS-21 ameliorates polymicrobial sepsis-induced hepatic injury by modulating autophagy through α7nAchRs in mice.

BACKGROUND: Previous studies showed that GTS-21, a selective alpha 7 nAchR agonist, can trigger anti-inflammatory effects and improve the survival of septic animals. However, whether GTS-21 affects autophagy responses remains unclear. Here, we tested the hypothesis that GTS-21 ameliorates sepsis-induced hepatic injury by modulating autophagy in mice. METHOD: C57BL/6 male mice were randomly separated and categorized into four groups: the sham group, and CLP group subjected to caecal ligation and puncture (CLP, a model of polymicrobial sepsis). The CLP + GTS-21 group was administered GTS-21 immediately after CLP challenge. α-Bungarotoxin (an alpha 7 nAchR antagonist) was injected before CLP was performed, and then, after CLP challenge, GTS-21 was administered to α-BGT + CLP + GTS-21 group. The hepatic tissue and blood samples were harvested 6 h after the operation. RESULTS: CLP challenge increased TNF-α and IL-6 production, and hepatic enzyme alanine aminotransferase and aspartate transaminase levels. CLP also elevated the expression of hepatic LC3-II, sequestosome-1/p62, Atg7 and Atg5. The administration of GTS-21 inhibited pro-inflammatory cytokine production and hepatic enzymatic marker expression, promoted the expression of LC3-II, Atg7, Atg5, and decreased the expression of p62, which could be reversed by α-BGT treatment. CONCLUSION: Our findings suggested that α7nAchR is involved in diminishing hepatic damage by inhibiting inflammatory responses and improving autophagy in mice with polymicrobial sepsis.

SP1, MYC, CTNNB1, CREB1, JUN genes as potential therapy targets for neuropathic pain of brain.

Neuropathic pain (NP) may cause serious brain diseases, but the genes associated with the metabolic pathway and transcript factors of NP remain unclear. This study is aimed to identify the therapy target genes for NP and to investigate the metabolic pathways and transcript factors associated with NP. The differentially expressed genes of three brain tissues (nucleus accumbens, periaqueductal gray, and prefrontal cortex) dealt with NP stimulation were analyzed. Besides, The Database for Annotation, Visualization, and Integrated Discovery and Tfacts datasets were used in the analysis of the genes related to the metabolic pathway and transcript factors of the brain. Eight genes were found to coexpress in all three tissues. A functional enrichment analysis showed that the upregulated genes were mostly enriched in pathways as inflammatory response, calcium-mediated signaling, cytokine-cytokine receptor interaction, and extracellular matrix (ECM)-receptor interaction, whereas the downregulated genes were mostly enriched in pathways as phospholipid metabolic processes, positive regulation of protein kinase B signaling, and metabolism of xenobiotics by cytochrome P450. Finally, 135 and 98 transcript factors genes were upregulated and downregulated, among which SP1, MYC, CTNNB1, CREB1, JUN were identified as the most critical genes because the number of up- and downregulated gene ranked at the top. In conclusion, the pathways of immune response and cytokine-cytokine receptor interaction were determined as the main metabolic pathways of NP affecting the brain, and SP1, MYC, CTNNB1, CREB1, JUN genes were recognized as the most enriched genes in this process, which may provide evidence for the diagnosis and treatment research of neuropathic pain.

The HO-1-expressing bone mesenchymal stem cells protects intestine from ischemia and reperfusion injury.

BACKGROUND: Bone mesenchymal stromal cells (BMSC) showed protective potential against intestinal ischemia. Oxygenase-1(HO-1) could alleviate oxidative stress. In the present study, we constructed HO-1-expressing BMSC and detected the effects of it on survival, intestinal injury and inflammation following intestinal ischemia and reperfusion injury (I/R). METHODS: In this experiment, eighty adult male mice were divided into Sham, I/R, I/R + BMSC, I/R + BMSC/HO-1 groups. Mice were anesthetized and intestinal I/R model were established by temporarily occluding the superior mesenteric artery for 60 min with a non-crushing clamp. Following ischemia, the clamp was removed and the intestines were allowed for reperfusion. Prior to abdominal closure, BMSC/ HO-1 (2 × 106 cells) or BMSC (2 × 106 cells) were injected into the peritoneum of I/R mice respectively. Mice were allowed to recover for 24 h and then survival rate, intestinal injury and inflammation were determined. Reactive oxygen species (ROS) was assayed by fluorescent probe. TNFα and IL-6 were assayed by ELISA. RESULTS: BMSC/HO-1 increased seven day survival rate, improved intestinal injury and down-regulated inflammation after intestinal I/R when compared with sole BMSC (p < 0.05 respectively). Multiple pro-inflammatory media were also decreased following application of BMSC/HO-1, when compared with sole BMSC (p < 0.05) respectively, suggesting that BMSC /HO-1 had a better protection to intestinal I/R than BMSC therapy. CONCLUSION: Administration of BMSC/HO-1 following intestinal I/R, significantly improved intestinal I/R by limiting intestinal damage and inflammation.

Effect of epidural analgesia in trial of labor after cesarean on maternal and neonatal outcomes in China: a multicenter, prospective cohort study.

BACKGROUND: The trial of labor after cesarean section (TOLAC) is a relatively new technique in mainland of China, and epidural analgesia is one of the risk factors for uterine rupture. This study aimed to evaluate the effect of epidural analgesia on primary labor outcome [success rate of vaginal birth after cesarean (VBAC)], parturient complications and neonatal outcomes after TOLAC in Chinese multiparas based on a strictly uniform TOLAC indication, management and epidural protocol. METHODS: A total of 423 multiparas undergoing TOLAC were enrolled in this study from January 2017 to February 2018. Multiparas were divided into two groups according to whether they received epidural analgesia (study group, N = 263) or not (control group, N = 160) during labor. Maternal delivery outcomes and neonatal characteristics were recorded and evaluated using univariate analysis, multivariable logistic regression and propensity score matching (PSM). RESULTS: The success rate of VBAC was remarkably higher (85.55% vs. 69.38%, p < 0.01) in study group. Epidural analgesia significantly shortened initiating lactation period and declined Visual Analogue Score (VAS). It also showed more superiority in neonatal umbilical arterial blood pH value. After matching by PSM, multivariable logistic regression revealed that the correction of confounding factors including epidural analgesia, cervical Bishop score at admission and spontaneous onset of labor were still shown as promotion probability in study group (OR = 4.480, 1.360, and 10.188, respectively; 95%CI = 2.025-10.660, 1.113-1.673, and 2.875-48.418, respectively; p < 0.001, p = 0.003, and p < 0.001, respectively). CONCLUSIONS: Epidural analgesia could reduce labor pain, and no increased risk of postpartum bleeding or uterine rupture, as well as adverse effects in newborns were observed. The labor duration of multiparas was increased, but within acceptable range. In summary, epidural analgesia may be safe for both mother and neonate in the three studied hospitals. TRIAL REGISTRATION: Chineses Clinical Trial Register, ChiCTR-ONC-17010654. Registered February 16th, 2017.

XIST accelerates neuropathic pain progression through regulation of miR-150 and ZEB1 in CCI rat models.

LncRNAs are reported to participate in neuropathic pain development. LncRNA X-inactive specific transcript (XIST) is involved in the progression of various cancers. However, the role of XIST in neuropathic pain remains unclear. In our present study, we established a chronic constriction injury (CCI) rat model and XIST was found to be greatly upregulated both in the spinal cord tissues and in the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic pain behaviors including mechanical and thermal hyperalgesia. Moreover, decrease of XIST repressed neuroinflammation through inhibiting COX-2, tumor necrosis factor (TNF)-α and IL-6 and in CCI rats. Previously, miR-150 has been reported to restrain neuropathic pain by targeting TLR5. Currently, miR-150 was predicted to be a microRNA target of XIST, which indicated a negative correlation between miR-150 and XIST. miR-150 was remarkably decreased in CCI rats and overexpression of miR-150 can significantly suppress neuroinflammation-related cytokines. Furthermore, ZEB1 was exhibited to be a direct target of miR-150 and we found it was overexpressed in CCI rats. Silencing ZEB1 was able to inhibit neuropathic pain in vivo and downreguation of XIST decreased ZEB1, which can be reversed by miR-150 inhibitors. Taken these together, we indicated that XIST can induce neuropathic pain development in CCI rats via upregulating ZEB1 by acting as a sponge of miR-150. It was revealed that XIST/miR-150/ZEB1 axis can be provided as a therapeutic target in neuropathic pain.

Inhibition of miR-200b/miR-429 contributes to neuropathic pain development through targeting zinc finger E box binding protein-1.

Many studies have reported that microRNAs participate in neuropathic pain development. Previously, miR-200b and miR-429 are reported to be involved in various diseases. In our current study, we focused on their roles in neuropathic pain and we found that miR-200b and miR-429 were significantly decreased in chronic constriction injury (CCI) rat spinal cords and isolated microglials. miR-200b and miR-429 overexpression were able to relieve neuropathic pain through modulating PWT and PWL in CCI rats. Meanwhile, we observed that both miR-200b and miR-429 upregulation could repress neuroinflammation via inhibiting inflammatory cytokines such as IL-6, IL-1ß, and TNF-α in CCI rats. By carry out bioinformatics technology, Zinc finger E box binding protein-1 (ZEB1) was predicted as target of miR-200b, and miR-429 and dual-luciferase reporter assays confirmed the correlation between them. ZEB1 has been reported to regulate a lot of diseases. Here, we found that ZEB1 was greatly increased in CCI rats and miR-200b and miR-429 overexpression markedly suppressed ZEB1 mRNA expression in rat microglial cells. In addition, knockdown of ZEB1 can reduce neuropathic pain development and co-transfection of LV-anti-miR-200b/miR-429 reversed this phenomenon in vivo. Taken these together, our results suggested that miR-200b/miR-429 can serve as an important regulator of neuropathic pain development by targeting ZEB1.

Transduced PEP-1-heme oxygenase-1 fusion protein reduces remote organ injury induced by intestinal ischemia/reperfusion.

BACKGROUND: A fusion protein composed of heme oxygenase-1 (HO-1) and cell-penetrating peptide PEP-1 has been shown to reduce local intestinal injury after intestinal ischemia/reperfusion (I/R). In this study, we investigated the effects of PEP-1-HO-1 fusion protein on remote organ injury induced by intestinal I/R in rats. MATERIAL AND METHODS: We randomly assigned 24 male Sprague-Dawley rats to 3 groups: Sham, I/R, and I/R plus PEP-1-HO-1 treatment (HO). The model of intestinal I/R was established by occluding the superior mesenteric artery for 45 min followed by 120-min reperfusion. In HO group, PEP-1-HO-1 was administered intravenously 30 min before ischemia, while animals in the Sham and I/R groups received the equal volume of physiological saline. At the end of the experiment, lung, liver, and blood samples were collected and analyzed. RESULTS: Malondialdehyde levels and histological injury scores were increased, and superoxide dismutase activities were decreased in the lung and liver tissues in the I/R group compared with the Sham group (P<0.05). Serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin-6, and lung tissue wet weight to dry weight ratio were increased in the I/R group compared with the Sham group (P<0.05). NF-κB expression in intestinal tissues was significantly higher in the I/R group than in the Sham group. These changes were significantly reversed by treatment with PEP-1-HO-1. CONCLUSIONS: This study demonstrates that administration of PEP-1-HO-1 has a protective role against lung and liver injury after intestinal I/R, attributable to the reduction of released proinflammatory cytokines regulated by NF-κB.

Transduced PEP-1-heme oxygenase-1 fusion protein protects against intestinal ischemia/reperfusion injury.

BACKGROUND: Heme oxygenase-1 (HO-1) has been shown to have antioxidant and anti-apoptotic properties. The present study transduced HO-1 protein into intestinal tissues using PEP-1, a cell-penetrating peptide, and investigated its potentiality in prevention against intestinal ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: PEP-1-HO-1 fusion protein was administered intravenously to explore the time and dose characteristics through measuring serum HO-1 levels. Twenty-four male Sprague-Dawley rats were randomly divided into three groups: sham, intestinal I/R (II/R), II/R + PEP-1-HO-1 fusion protein (HO). The model was established by occluding the superior mesenteric artery for 45 min followed by 120 min reperfusion. In HO group, PEP-1-HO-1 was administered intravenously 30 min before ischemia, whereas animals in sham and II/R groups received the equal volume of physiological saline. After the experiment, the intestines were harvested for determination of histologic injury, wet/dry ratio, enzyme activity, apoptosis, and His-probe protein (one part of PEP-1-HO-1). RESULTS: Levels of serum HO-1 were dose- and time-dependent manner after intravenous injection of PEP-1-HO-1. I/R caused deterioration of histologic characteristics and increases in histologic injury scoring, wet/dry ratio, myeloperoxidase activity, malondialdehyde, and intestinal apoptosis. These changes were also accompanied by a decrease in superoxide dismutase activity (P < 0.05). PEP-1-HO-1 treatment significantly reversed these changes (P < 0.05). Furthermore, His-probe protein expression was only detected in PEP-1-HO-1-treated animals. CONCLUSION: Treatment of PEP-1-HO-1 attenuates intestinal I/R injury, which might be attributable to its antioxidant and anti-apoptotic roles of HO-1.

Efficient chiral hydrogel template based on supramolecular self-assembly driven by chiral carbon dots for circularly polarized luminescence.

Since the chiral emission of excited states is observed on carbon dots (CDs), exploration towards the design and synthesis of chiral CDs nanomaterials with circularly polarized luminescence (CPL) properties has been at a brisk pace. In this regard, the "host and guest" co-assembly strategy based on the combination of CDs and chiral templates has been of unique interest recently for its convenient operation, multicolor tunable CPL, and wide application of prepared CDs-composited materials in optoelectronic devices and information encryption. However, the existing chiral templates that match perfectly with chiral CDs exhibiting optical activity both in ground and excited states are rather scarce. In this work, we synthesize the chiral CDs that could induce the spontaneous supramolecular self-assembly of N-(9-fluorenylmethox-ycarbonyl) (Fmoc)-protected glutamic acid to form chiral hydrogels with helical nanostructure. The co-assembled hydrogels show powerful chiral template function, which not only enable chiral CDs with a luminescence dissymmetry factor (glum) up to 10-2, but also have universal chiral transfer to inserted dye molecules, realizing full-color CPL and Förster resonance energy transfer (FRET) CPL as well as the distinction between left and right circularly polarized light. This CPL-active template based on chiral CDs enriches the design scenario of chiral functionalized nanomaterials.

Emodin alleviates intestinal ischemia/reperfusion-induced lung injury by upregulating HO-1 expression via PI3K/AkT pathway.

BACKGROUND: Emodin, a natural anthraquinone derivative found in various Chinese medicinal herbs, has been proved to be an effective therapeutic agent in the treatment of many diseases. However, its effect on lung injury after intestinal ischemia/reperfusion injury remains unknown. This research was designed to investigate whether emodin protects against intestinal ischemia/reperfusion-induced lung injury and to elucidate the underlying molecular mechanisms in vivo and in vitro. METHODS: Intestinal ischemia/reperfusion injury was induced by occluding the superior mesenteric artery in mice, and mouse lung epithelial-12 cells were subjected to oxygen-glucose deprivation and reoxygenation to establish an in vitro model. RESULTS: Our data indicated that emodin treatment reduced intestinal ischemia/reperfusion-induced oxidative stress, inflammation and apoptosis in lung tissues and alleviated lung injury. However, the protective effects of emodin on intestinal ischemia/reperfusion-induced lung injury were reversed by the protein kinase B inhibitor triciribine or the heme oxygenase-1 inhibitor tin protoporphyrin IX. The protein kinase inhibitor triciribine also downregulated the expression of heme oxygenase-1. CONCLUSION: In conclusion, our data suggest that emodin treatment protects against intestinal ischemia/reperfusion-induced lung injury by enhancing heme oxygenase-1 expression via activation of the PI3K/protein kinase pathway. Emodin may act as a potential therapeutic agent for the prevention and treatment of lung injury induced by intestinal ischemia/reperfusion.

Transduction of PEP-1-heme oxygenase-1 fusion protein reduces myocardial ischemia/reperfusion injury in rats.

Recent studies have uncovered that overexpression of heme oxygenase-1 (HO-1) by induction or gene transfer provides myocardial protection. In the present study, we investigated whether HO-1 protein mediated by cell-penetrating peptide PEP-1 could confer cardioprotection in a rat model of myocardial ischemia/reperfusion (I/R) injury. Male Sprague-Dawley rats were subjected to 30 minutes of ischemia by occluding the left anterior descending coronary artery and to 120 minutes of reperfusion to prepare the model of I/R. Animals were randomized to receive PEP-1-HO-1 fusion protein or saline 30 minutes before a 30-minute occlusion. I/R increased myocardial infarct size and levels of malondialdehyde, serum tumor necrosis factor alpha, and interleukin 6 and reduced myocardial superoxide dismutase activity. Administration of PEP-1-HO-1 reduced myocardial infarct size and levels of malondialdehyde, serum tumor necrosis factor alpha, and interleukin 6 and increased myocardial superoxide dismutase and HO-1 activities. His-probe protein was only detected in PEP-1-HO-1-transduced hearts. In addition, transduction of PEP-1-HO-1 markedly reduced elevated myocardial tissue nuclear factor-κB induced by I/R. The results suggested that transduction of PEP-1-HO-1 fusion protein decreased myocardial reperfusion injury, probably by attenuating the production of oxidants and proinflammatory cytokines regulated by nuclear factor-κB.

Chiral Carbon Dots: Synthesis and Applications in Circularly Polarized Luminescence, Biosensing and Biology.

Chiral carbon dots (CDs) are a novel luminescent zero-dimensional carbon-based nanomaterial with chirality. They not only have the advantages of good biocompatibility, multi-color-emission, easy functionalization, but also exhibits highly symmetrical chiral optical characteristics, which broadens their applicability to enantioselectivity of some chiral amino acids like cysteine and lysine, asymmetric catalysis as well as biomedicine in gene expression and antibiosis. In addition, the exploration of the excited state chirality of CDs has developed its excellent circularly polarized luminescence (CPL) properties, opening up a new application scenario like recognition of chiral light sources and anti-counterfeit printing with information encryption. This review mainly focuses on the mature synthesis approaches of chiral CDs, including chiral ligand method and supramolecular self-assembly method, then we consider emerging applications of chiral CDs in CPL, biosensing and biological effect. Finally, we concluded with a perspective on the potential challenges and future opportunities of such fascinating chiral CDs.

Inhibition of lncRNA NEAT1 protects endothelial cells against hypoxia/reoxygenation­induced NLRP3 inflammasome activation by targeting the miR­204/BRCC3 axis.

Cardiovascular ischemia/reperfusion (I/R) injury is primarily caused by oxygen recovery after prolonged hypoxia. Previous studies found that the long non coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) was involved in cardiovascular pathology, and that NOD­like receptor protein 3 (NLRP3) inflammasome activation­dependent pyroptosis played a key role in cardiovascular I/R injury. The present study aimed to explore the molecular mechanism of I/R pathogenesis in order to provide novel insights for potential future therapies. Cell viability and lactate dehydrogenase enzyme activity assays were used to detect cell injury after human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia/reoxygenation (H/R). The expression of the NEAT1/microRNA (miR)­204/BRCA1/BRCA2­containing complex subunit 3 (BRCC3) axis was examined by reverse transcription­quantitative PCR, and the associations among genes were confirmed by luciferase reporter assays. Western blotting and ELISA were used to measure the level of NLRP3 inflammasome activation­dependent pyroptosis. The results demonstrated that NEAT1, BRCC3 expression and NLRP3 inflammasome activation­dependent pyroptosis were significantly increased in H/R­injured HUVECs, whereas silencing BRCC3 or NEAT1 attenuated H/R­induced injury and pyroptosis. NEAT1 positively regulated BRCC3 expression via competitively binding with miR­204. Moreover, NEAT1 overexpression counteracted miR­204 mimic­induced injury, BRCC3 expression and NLRP3 inflammasome activation­dependent pyroptosis. Taken together, these findings demonstrated that inhibition of lncRNA NEAT1 protects HUVECs against H/R­induced NLRP3 inflammasome activation by targeting the miR­204/BRCC3 axis.

Six-Degree-of-Freedom Posture Measurement Technologies Using Position Sensitive Detectors (PSDs): State of the Art.

Six degree-of-freedom (6-DOF) posture measurement is an important academic research topic which has been broadly applied in many fields. As a high-speed photoelectronic sensor with ultra-high resolution and precision, position sensitive detector (PSD) has shown to be one of the most competitive candidates in 6-DOF measurement. This review presents the research progress of PSD-based 6-DOF posture measurement systems in the field of large-scale equipment assembly, ultra-precision manufacturing and other emerging areas. A total of six methods for implementing 6-DOF measurement are summarized and their advantages and limitations are discussed. Meanwhile, the paper illustrates challenges, potential solutions and future development trends.

Circ_0005075 targeting miR-151a-3p promotes neuropathic pain in CCI rats via inducing NOTCH2 expression.

Neuropathic pain is a most challenging diseases worldwide, caused by the injury of nerve system. CircularRNAs (circRNAs) are revealed to be involved in various diseases, includingneuropathic pain. However, the waycircRNAsparticipate in the progress ofneuropathic painstill needs further study. Identifyingthe possible circRNAexpression patterns of neuropathic painis of great significance to understand its underlying mechanism. Previously, circ_0005075 has been regarded as an important oncogene in multiple cancers and it has been characterized as an inflammation­associated circRNA in various processes. Nevertheless, the functional role of circ_0005075 in neuropathic pain development is still poorly known. In our present study, we observed circ_0005075 was obviously increased in CCI rat models. Knockdown of circ_0005075 repressed thebehaviors of neuropathic pain including mechanical and thermal hyperalgesia. Moreover, loss of circ_0005075 could repress the neuroinflammation via targeting COX-2, IL-6 and TNF-α whereas inducing IL-10 in vivo. Additionally, we predicted miR-151a-3p as the potential target of circ_0005075 using bioinformatics analysis. We displayed that miR-151a-3p was greatly reduced in CCI rats and circ_0005075 reversed the repressive effect of miR-151a-3p on neuropathic pain. For another, NOTCH2 has been shown to induce a variety of intracellular responses correlated withneuropathic pain. Here, we found NOTCH2 expression was strongly induced in CCI rats and miR-151a-3p. In addition, circ_0005075 significantly rescued NOTCH2 expression, which could be repressed by miR-151a-3p. To sum up, we indicated that loss ofcirc_0005075relieved neuropathic pain progression by inducement of miR-151a-3p and inactivation of NOTCH2 signaling.

Piplartine attenuates the proliferation of hepatocellular carcinoma cells via regulating hsa_circ_100338 expression.

Researches have pointed that piplartine inhibits the proliferation of hepatocellular carcinoma (HCC) cells, however, the underlying mechanisms has not been well defined. Currently, more and more studies have pointed out that circRNAs can regulate tumor cell proliferation, involve in the tumorigenesis mechanism of various tumors. In this study, we explored whether piplartine may participate in the development of HCC through the regulation of ability of HCC cell proliferation by circRNA. Based on the chip analysis, we selected candidate circRNAs that are highly correlated with HCC. CircRNA expression in OSCC cells treated with piplartine was detected by qRT-PCR. We found that only the expression of hsa_circ_100338 (circ-100338) was observably reduced. The expression characteristics of circ-100338 in HCC cell lines were also verified by qRT-PCR. Subsequently, whether or notcirc-100338 can regulate ZEB1 via competitively binding to miR-141-3p was determined by the RIP assay and dual luciferase reporter gene assay. The effect of the circ-100338/miR-141-3p/ZEB1 axis on the proliferation of HCC cell was tested by EdU and CCK-8 assay. Results showed that circ-100338 expression was observably increased in HCC cell lines. Simultaneously, circ-100338 can regulate the expression of ZEB1by competitively binding to miR-141-3p. Moreover high expression of circ-100338 can stimulate the proliferation of HCC cells. Our current study revealed that circ-100338 played as a ceRNA in promoting the progression of HCC by sponging miR-141-3p, while piplartine can participate in the development of HCC by inhibiting the expression of circ-100338.

Dexmedetomidine Ameliorates Lung Injury Induced by Intestinal Ischemia/Reperfusion by Upregulating Cannabinoid Receptor 2, Followed by the Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway.

Intestinal ischemia/reperfusion (I/R) is a clinical emergency, which often causes lung injury with high morbidity and mortality. Although dexmedetomidine has been identified to have a protective effect on lung injury caused by intestinal I/R, its specific mechanism is still elucidated. In recent years, the cannabinoid (CB2) receptor pathway has been found to be involved in I/R injury of some organs. In the current study, we investigated whether the CB2 receptor pathway contributes to the protective effect of dexmedetomidine on the intestinal I/R-induced lung injury in rats. Dexmedetomidine treatment upregulated the expression of CB2 receptor and suppressed the I/R-induced increases in lung injury scores, inflammatory cell infiltration, lung wet/dry ratio, MPO activity, MDA level, inflammatory cytokines, and caspase-3 expression while augmenting SOD activity and Bcl-2 expression, indicating attenuation of lung injury. Dexmedetomidine treatment also increased the expression of Akt. The protective effects of dexmedetomidine treatment were reversed by the CB2 receptor antagonist AM630 or the PI3K inhibitor wortmannin. And the CB2 receptor antagonist AM630 also downregulated the expression of Akt. Thus, our findings suggest that treatment with dexmedetomidine provides a protective role against lung injury caused by intestinal I/R in rats, possibly due to the upregulation of the CB2 receptor, followed by the activation of the PI3K/Akt pathway.

Direct Peritoneal Resuscitation with Pyruvate Protects the Spinal Cord and Induces Autophagy via Regulating PHD2 in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury.

Direct peritoneal resuscitation with pyruvate (Pyr-PDS) has emerged as an interesting candidate to alleviate injury in diverse organs, while the potential mechanism has yet to be fully elucidated. To explore the effect of autophagy in the spinal cord ischemia-reperfusion (SCIR) injury and the underlying mechanism, we established a model of SCIR in vivo and in vitro. In vivo, male SD rats underwent aortic occlusion for 60 min and then followed by intraperitoneally infused with 20 mL of pyruvate or normal saline for 30 min, and the spinal cords were removed for analysis after 48 h of reperfusion. The functional and morphological results showed that Pyr-PDS alleviated SCIR injury; meanwhile, the expression of autophagy-related genes and transmission electron microscopy displayed autophagy was activated by SCIR injury, and Pyr-PDS treatment could further upregulate the degree of autophagy which plays a protective part in the SCIR injury, while there is no significant difference after treatment with saline. In addition, SCIR injury inhibited expression of PHD2, which results to activate its downstream HIF-1α/BNIP3 pathway to promote autophagy. In the Pyr-PDS, the results revealed PHD2 was further inhibited compared to the SCIR group, which could further activate the HIF-1α/BNIP3 signaling pathway. Additionally, oxygen-glucose deprivation and reoxygenation were applied to SH-SY5Y cells to mimic anoxic conditions in vitro, and the expression of autophagy-related genes, PHD2, and its downstream HIF-1α/BNIP3 pathway showed the same trend as the results in vivo. Besides, IOX2, a specific inhibitor of PHD2 was also treated to SH-SY5Y cells during reoxygenation, in which the result is as same as the pyruvate group. Then, we observed the expression of autophagy-related genes and the HIF-1α signal pathway in the process of reoxygenation; the results showed that as the reoxygenation goes, the expression of the HIF-1α signal pathway and degree of autophagy came to decrease gradually, while treated with pyruvate could maintain autophagy high and stable through keeping PHD2 at a lower level during reoxygenation, and the latter was observed downregulated during reoxygenation process from 0 to 24 hours in a time-effect way. The above results indicated that direct peritoneal resuscitation with pyruvate showed effective protection to ischemia-reperfusion of the spinal cord through activating autophagy via acting on PHD2 and its downstream HIF-1α/BNIP3 pathway.

Epidural Labor Analgesia Is Associated with a Decreased Risk of the Edinburgh Postnatal Depression Scale in Trial of Labor after Cesarean: A Multicenter, Prospective Cohort Study.

Postpartum depression is a disabling mental disorder commonly seen in parturients under trial of labor after cesarean, which causes serious harm to the parturients. The etiology is unclear. We hypothesized that epidural labor analgesia can reduce the incidence rate of postpartum depression. Enrolled multiparas were divided into the epidural labor analgesia group (n = 263) or nonanalgesia group (n = 160) according to their own request. Edinburgh Postnatal Depression Scale was used to assess their mental status at 48 hours and 42 days after delivery. Relative perinatal variables were collected and further analyzed using univariate analysis and multivariate logistic regression analysis to assess the relation of epidural analgesia with the occurrence of postpartum depression under trial of labor after cesarean. The Edinburgh Postnatal Depression Scale score 48 hours ≥ 10 in the no epidural analgesia group was 26.42% while the epidural analgesia group was 8.49% (OR, 0.209; 95% CI, 0.096-0.429; P < 0.001). The Edinburgh Postnatal Depression Scale score 42 day ≥ 10 in the no epidural analgesia group was 25.16% while the epidural analgesia group was 6.59% (OR, 0.235; 95% CI, 0.113-0.469; P < 0.001). The incidence of postpartum depression was significantly lower in the epidural labor analgesia group at 48 hours and 42 days. There was also a significant relation between the Edinburgh Postnatal Depression Scale scores at 48 hours and 42 days after delivery. Epidural analgesia, discomfort within 42 days, and self-rating anxiety scale are independent predictors of postpartum depression for trial of labor after cesarean in 42 days. Epidural labor analgesia is associated with a decreased risk of postpartum depression. Further study with a large sample size and more centers is needed to evaluate the impact of epidural analgesia on the occurrence of postpartum depression. Chinese Clinical Trial Register, ChiCTR-ONC-17010654.

Clinicopathological evaluation of immunohistochemical Ki-67 and endothelial nitric oxide synthase expression in intracranial ependymoma.

PURPOSE: To analyze the association between Ki-67 and eNOS expression with the pathological grades of patients with intracranial ependymomas, and to determine its value in distinguishing the progression of the disease. METHODS: A clinicopathological study was undertaken in 82 patients with intracranial ependymomas. Tissue samples, obtained by tumour resection, were divided into three groups: low-grade, mid-grade and high-grade ependymomas. Tissue samples obtained from 15 patients with brain contusion were used as control. Immuno-histochemical staining was performed to analyze the association between Ki-67 and eNOS expression with various tumour grades. The cell proliferating marker Ki-67 was assessed by positive cell count. The levels of eNOS positive expression were evaluated as slight, moderate and intense. RESULTS: 48 of 82 cases (58.54%) expressed Ki-67 protein. Expression of Ki-67 and eNOS was negative in all control samples. Positive cell rates were 2.65+/-0.83 % in the low-grade, 9.63+/-0.08 % in the mid-grade, and 28.41+/-0.71 % in the high-grade ependymoma groups. In low-grade ependymomas there were 8 and 12 cases that expressed eNOS slightly or moderately. In the mid-grade ependymoma group eNOS was expressed moderately in 10 cases and intensely in 15. In the high-grade group 20 cases showed intense positive expression of eNOS. The Ki-67 positive cell counts for slight, moderate and intense eNOS expression were 2.20, 6.07 and 22.25, respectively. CONCLUSION: Ki-67 and eNOS expression in intracranial ependymoma tissue was associated with the histopathological grade and malignant degree.