Cyclosporin A-mediated translocation of HuR improves MTX-induced cognitive impairment in a mouse model via NCOA4-mediated ferritinophagy.

Chemotherapy-induced cognitive impairment (CICI) is a subject that requires critical solutions in neuroscience and oncology. However, its potential mechanism of action remains ambiguous. The aim of this study was to investigate the vital role of HuR in the neuroprotection of cyclosporin A (CsA) during methotrexate (MTX)-induced cognitive impairment. A series of Hu-antigen R (HuR) gain and loss experiments were used to examine cyclosporin A (CsA)-mediated translocation of HuR's ability to improve MTX-induced cognitive impairment through NCOA4-mediated ferritinophagy in vitro and in vivo. Obtained results show that the administration of CsA alleviated MTX-induced cognitive impairment in mice. The presence of MTX promoted the shuttling of HuR from the cytoplasm to the nucleus, whereas treatment with CsA increased cytoplasmic HuR expression levels and the levels of ferritinophagy-related proteins, such as NCOA4 and LC3II, compared to the MTX group. However, applying KH-3, an inhibitor of HuR, reversed CsA's impact on the expression of ferritinophagy-related proteins in the hippocampus and in vitro. Also, treatment with CsA attenuated microglial activation by altering Iba-1 expression and decreased TNF-α and IL-1ß levels in mice hippocampi. Moreover, KH-3 neutralized CsA's effects on the expression of both Iba-1 and HuR in vivo and in vitro. In summary, CsA was confirmed to have a neuroprotective role in CICI. Its possible underlying mechanisms may be involved in the translocation of HuR. Mediating the translocation of HuR during CICI could mitigate neruoinflammation and neuronal apoptosis via NCOA4-mediated ferritinophagy and, thus, alleviate cognitive impairment in mice with CICI.

Bibliometric Analysis of Research Relating to Perineal Pain Reported over the Period 1981 to 2021.

BACKGROUND: Perineal pain is a painful neuropathic condition, which does not have a standard diagnostic or treatment approach. As such, we sought to evaluate the global scientific output of research into perineal pain and explore trends from 1981 to 2021 using bibliometric methods. METHODS: Articles on perineal pain were retrieved from the Web of Science (WoS) database. We analyzed the content and quality of publications from within the specified timeframe. We also utilized VOSviewer to mine and cluster data from retrieved articles. RESULTS: A total of 1917 articles were collected. The number of related papers published increased year by year. Articles were most frequently published by authors in the United States and France. Although the US remains at the center of this field, publications from China have become more frequent in recent years. We also found that French academic institutions dominate the field of perineal pain, and Jean-Jacques Labat from Nantes Universite is the most published author in the field. "Episiotomy", "pain", "management", "prostatectomy", "pelvic pain", and "complication" were frequently cited as keywords. CONCLUSION: The increasing number of publications each year indicates that perineal pain has gained more attention as an important research topic.

Association of the Timeless Gene with Prognosis and Clinical Characteristics of Human Lung Cancer.

(1) Background: As the most common malignant tumor type worldwide, it is necessary to identify novel potential prognostic biomarkers to improve the poor prognosis of lung cancer. The Timeless gene, a circadian rhythm-related gene, is associated with several types of cancer. However, studies analyzing the clinical significance of the Timeless gene in patients with lung cancer are currently limited. (2) Methods: In the present study, the expression levels and prognostic potential of the Timeless gene and its co-expressed genes in different subtypes of lung cancer were explored using multiple bioinformatics approaches. The correlations between the Timeless gene and its co-expressed genes were validated using A549 and NCI-H226 cells by transfecting them with expression vectors and analyses using Western blot and reverse transcription-quantitative PCR. (3) Results: The Oncomine and GEPIA database analyses indicated that the expression of the Timeless gene was significantly higher in lung cancer as compared to that in the normal tissue. Using the UALCAN database, significant differences in Timeless gene expression were determined among different stages of lung cancer and between genders. A Kaplan-Meier plotter analysis indicated that high expression of the Timeless gene was associated with poor overall survival (OS) and progression-free survival (PFS) of patients with lung cancer. In the cBioPortal and GEPIA database analyses, extra spindle pole bodies like 1 (ESPL1) was the top correlated gene of Timeless in patients with lung cancer. Similar to the Timeless gene, high expression of the ESPL1 gene was also associated with poor OS and PFS. Of note, overexpression of the Timeless gene increased the expression level of ESPL1 at both the mRNA and protein levels. (4) Conclusion: The present study explored the clinical significance of the Timeless gene and its correlated gene ESPL1 in patients with lung cancer, thereby providing a potential therapeutic target for lung cancer.

Adenosine A2A Receptor Antagonist Improves Cognitive Impairment by Inhibiting Neuroinflammation and Excitatory Neurotoxicity in Chronic Periodontitis Mice.

The adenosine A2A receptor antagonist SCH58261 has been reported to have anti-inflammatory effects. However, its role in chronic periodontitis (CP)-induced cognitive impairment, which is associated with Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS), remains unclear. This study investigated the role of SCH58261 in mice with CP-induced cognitive impairment. C57BL/6J mice were used to develop CP model by injecting 0.5 mg/kg P. gingivalis LPS into the palatal gingival sulcus of maxillary first molars twice a week for four weeks. The mice were divided into control, P. gingivalis LPS (P-LPS), P-LPS + SCH58261, and SCH58261 groups. The passive avoidance test (PAT) and Morris water maze (MWM) were used to assess cognition in mice. Furthermore, CD73/adenosine, neuroinflammation, glutamate transporters, and glutamate were assessed. Compared with the P-LPS group, 0.1 and 0.5 mg/kg SCH58261 increased latency and decreased error times in PAT, but increased platform crossing number in MWM. SCH58261 inhibited microglial activation, and decreased pro-inflammatory cytokines and glutamate levels, but increased GLT-1 and PSD95 expression in the hippocampus. This was the first report of SCH58261 treatment for CP-induced cognitive impairment, which may be related to its anti-inflammatory activities and anti-glutamate excitatory neurotoxicity. This suggests that SCH58261 can be used as a novel agent to treat cognitive impairment.

Publication Trends on Mitophagy in the World and China: A 16-Year Bibliometric Analysis.

In the past 16 years, research on mitophagy has increasingly expanded to a wider range of subjects. Therefore, comprehensively analyzing the relevant progress and development trends on mitophagy research requires specific methods. To assess the hotspots, directions, and quality of results in this field worldwide, we used multiple tools to examine research progress and growing trends in research on the matter during the last 16 years (from 2005 to 2020). We also compared the quantity and quality of the literature records on mitophagy published by research institutions in China and other developed countries, reviewed China's contribution, and examined the gap between China and these developed countries. According to the results of our bibliometric analysis, the United States and its research institutes published the most papers. We identified cell biology as the most commonly researched subject on mitophagy and AUTOPHAGY as the most popular journal for research on mitophagy. We also listed the most cited documents from around the world and China. With gradually increased funding, China is progressively becoming prominent in the field of mitophagy; nevertheless, the gap between her and major countries in the world must be closed.

Dexmedetomidine reverses MTX-induced neurotoxicity and inflammation in hippocampal HT22 cell lines via NCOA4-mediated ferritinophagy.

The incidence of chemotherapy-induced cognitive impairment (CICI) has attracted massive attention. Some studies have demonstrated the neuroprotective effects of dexmedetomidine (DEX). Here, alterations in nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy were investigated as the possible causes of DEX's neuroprotection of HT22 cells against methotrexate (MTX)-induced neurotoxicity. We used various concentrations of DEX and NCOA4-siRNA to treat MTX-induced neurotoxicity and inflammation in HT22 cells. The biomarkers of HT22 cells viability, apoptosis and inflammatory were tested. The expression of ferritinophagy markers were detected in the HT22 cells by using western blot and Immunofluorescence. We found that 10 and 50 ng/mL of DEX alleviated MTX-induced hippocampal neuronal inflammatory injuries. Meanwhile, DEX also reversed MTX-induced iron and ROS overproduction. Increasing DEX concentrations caused significant falls in the expression of ferritin heavy chain 1 (FTH1). DEX also increased vital ferritinophagy markers, NCOA4 and LC3II. NCOA4-siRNA transfection annulled the neuroprotective effects of DEX on MTX-induced inflammation in HT22 cells. Additionally, because NCOA4-siRNA disrupted ferritinophagy, DEX's inhibitory impact on MTX-induced iron and ROS overproduction in HT22 cells was also annihilated. DEX weakened MTX-provoked neurontoxicity in HT22 cells, possibly by improving NCOA4-mediated ferritinophagy. Our discoveries present further mechanisms for understanding the protective effects of DEX against MTX-induced cognitive impairment.

Changes in the Clinical Characteristics of 62 Patients Who Died from Coronavirus Disease 2019.

BACKGROUND: Since the first reports of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in December 2019 in Wuhan, China, the virus has spread to other parts of China and across the world. Although a few studies have assessed the clinical course of coronavirus disease 2019 (COVID-19), the changes in clinical characteristics during disease progression remain unclear. METHODS: We retrospectively analyzed the clinical characteristics of 62 patients who died from COVID-19 at the Central Hospital of Wuhan between January 26 and February 17, 2020. We compared the clinical features on admission and at the last follow-up before death. RESULTS: Of the 62 patients with COVID-19, 41 (66%) patients were male, and 21 (34%) were female. The median age was 72 years (interquartile range (IQR), 54-88), and 45 (72.5%) patients had preexisting conditions. The median time from symptom onset to the first visit at the clinic was three days, while the median time from symptom onset to death was 18.5 days. During disease progression, the amounts of arterial gases worsened, and liver, renal, and heart dysfunction was observed. Due to the cytokine storm, infection-related biomarkers, including lactic acid, C-reactive protein, and interleukine-6, gradually worsened during hospitalization. CONCLUSION: Our findings suggest that during hospitalization, many COVID-19 patients experienced multiple organ dysfunction and cytokine storm. The time from symptom onset to death was only 18.5 days, highlighting the disease's rapid progression. The better understanding of the clinical changes during disease progression might provide further insight into the COVID-19 pathophysiology.

Surgery/Anesthesia disturbs mitochondrial fission/fusion dynamics in the brain of aged mice with postoperative delirium.

Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate the effects of laparotomy under 1.4% isoflurane anesthesia for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice. Mice in Surgery/Anesthesia group showed unbalanced fission/fusion dynamics, with decreased DISC1 expression and increased expression of Drp1 and Mfn2 in the mitochondrial fraction, leading to excessive mitochondrial fission and disturbed mitochondrial morphogenesis in the hippocampus and prefrontal cortex. In addition, surgical mice presented mitochondrial dysfunction, demonstrated by abnormally activated oxidative stress (increased ROS level, decreased SOD level) and energy deficits (decreased levels of ATP and MMP). Surgery/Anesthesia also decreased the expression of neuronal/synaptic plasticity-related proteins such as PSD-95 and BDNF. Furthermore, Surgery/Anesthesia induced delirium-like behavior in aged mice. In conclusion, Surgery/Anesthesia disturbed mitochondrial fission/fusion dynamics and then impaired mitochondrial function in the brain of aged mice; these effects may be involved in the underlying mechanism of POD.

Long non-coding RNA RBM5-AS1 promotes the aggressive behaviors of oral squamous cell carcinoma by regulation of miR-1285-3p/YAP1 axis.

The human genome encodes far more long non-coding RNA (lncRNA) genes than protein coding genes. However, the function of majority of the lncRNAs is poorly understood. Numerous lncRNAs were aberrantly expressed in various cancers and found to be associated with development and progression of cancer. Little is known about the role of lncRNAs in oral squamous cell carcinoma (OSCC). In this study, we identified lncRNA RBM5-AS1 to be highly expressed in OSCC tumor tissues and cancer cell lines. RBM5-AS1 promotes the proliferation, migration, and invasion of OSCC cells in vitro. We also found that RBM5-AS1 regulates the level of miR-1285-3p as a competitive endogenous RNA (ceRNA), therefore regulate the expression level of an oncogene-YAP1, a target of miR-1285-3p. The information obtained in this study is valuable for understanding the regulatory mechanism of lncRNA in the development of OSCC and for developing new strategies for the diagnosis and treatment of OSCC.

A Bibliometric Analysis of Publications on Oxycodone from 1998 to 2017.

BACKGROUND: Oxycodone is a widely used opioid analgesic, which is involved in cancer pain and non-cancer pain. This study is intended to understand the publication characteristics of oxycodone research field and assess the quality of pertinent articles from 1998 to 2017. METHODS: Oxycodone-related publications from 1998 to 2017 were retrieved from the Web of Science (WOS) and PubMed database. These papers were coded across several categories, such as total number, journals, countries, institutions, authors and citations reports. And the analysis of co-occurrence keywords was handled by VOSviewer software. RESULTS: According to search strategies, a total of 2659 articles on oxycodone were published in world from 1998 to 2017 in WOS. Among the top 10 most productive organizations, six of them were American institutes, two of them were pharmaceutical enterprises and the other three were Finnish, Australian and Canadian institutes, which is similar with the distribution by country/region. Drewes AM from Denmark published most articles and PAIN MEDICINE is the most productive journal in oxycodone area. Meanwhile, clinical studies occupy a dominant position during the past 20 years. The 10 most cited papers were listed. Among these articles, 8 of them are reviews and 2 of those are meta-analysis. And the last decade (2008-2017) displayed that the newest keywords focus on "double-blind", "randomized controlled trial" and "neuropathic pain". CONCLUSIONS: The findings provided a comprehensive overview of oxycodone research. In view of the adverse effects of oxycodone, high-quality oxycodone studies both in basic studies and clinical trials need to be completed.

Publication Trends for Alzheimer's Disease Worldwide and in China: A 30-Year Bibliometric Analysis.

Background: Alzheimer's disease, the most common form of dementia, has tremendous social and economic impact worldwide. This study aimed to analyze global trends in Alzheimer's disease research and to investigate China's contribution to this research. Methods: The quantity and influence of publications related to Alzheimer's disease in China and elsewhere were compared. The Web of Science (WOS) and PubMed databases were searched from 1988 to 2017 using the terms "Alzheimer's disease" or "Alzheimers disease." Global Alzheimer's disease publications were classified and analyzed. Keywords, countries, and institutions publishing articles on Alzheimer's disease were analyzed, and citations of these articles were examined. Results: A total of 181,116 articles regarding Alzheimer's disease research were identified and analyzed. Neuroscience and neurology were the main research categories both globally and in China. Basic research dominated Alzheimer's publications, accounting for 30.93% of global publications and 95.31% of publications in China. A total of 8,935 journals published articles related to Alzheimer's disease. The journal Neurobiology of Aging published the most Alzheimer's disease-related articles, numbering 5,206 over the time period examined. The National Institutes of Health, the National Institute on Aging, and the Department of Health and Human Services jointly sponsored 11,809 articles, ranking first in the world. The National Natural Science Foundation of China funded the largest number of studies on Alzheimer's disease in China and recognized the importance of traditional Chinese medicine in Alzheimer's disease research. Conclusions: The present study provides data for global researchers to understand research perspectives and develop future research directions. In recent years, Chinese researchers have contributed significantly to global Alzheimer's research. Still, strengthening international cooperation could improve the quality and number of publications regarding Alzheimer's disease.

Honokiol-Mediated Mitophagy Ameliorates Postoperative Cognitive Impairment Induced by Surgery/Sevoflurane via Inhibiting the Activation of NLRP3 Inflammasome in the Hippocampus.

BACKGROUND: The potential mechanism of postoperative cognitive impairment is still largely unclear. The activation of NLRP3 inflammasome had been reported to be involved in neurodegenerative diseases, including postoperative cognitive change, and is closely related to mitochondrial ROS and mitophagy. Honokiol (HNK) owns multiple organic protective effects. This study is aimed at observing the neuroprotective effect of HNK in postoperative cognitive change and examining the role of HNK in the regulation of mitophagy and the relationship between these effects and NLRP3 inflammasome activation in mice induced by surgery/anesthesia. METHODS: In this study, mice were divided into several groups: control group, surgery group, surgery+HNK group, and surgery+HNK+3-methyladenine (3-MA) group. Hippocampal tissue samples were harvested and used for proinflammatory cytokines, mitochondrial ROS, and malondialdehyde (MDA) assay. The process of mitophagy and the activation of NLRP3 inflammasome were observed by Western blot, immunohistochemistry, and transmission electron microscopy. RESULTS: The results showed that HNK treatment obviously recovered the postoperative decline and enhanced the expressions of LC3-II, Beclin-1, Parkin, and PINK1 at protein levels after surgery/sevoflurane treatment, which are both an autophagy marker and a mitophagy marker. In addition, HNK attenuated mitochondrial structure damage and reduced mtROS and MDA generation, which are closely associated with NLRP3 inflammasome activation. Honokiol-mediated mitophagy inhibited the activation of NLRP3 inflammasome and neuroinflammation in the hippocampus. Using 3-MA, an autophagy inhibitor, the neuroprotective effects of HNK on mitophagy and NLRP3 inflammasome activation were eliminated. CONCLUSION: These results indicated that HNK-mediated mitophagy ameliorates postoperative cognitive impairment induced by surgery/sevoflurane. This neuroprotective effect may be involved in inhibiting the activation of NLRP3 inflammasome and suppressing inflammatory responses in the hippocampus.

Investigation of Key Genes and Pathways in Inhibition of Oxycodone on Vincristine-Induced Microglia Activation by Using Bioinformatics Analysis.

INTRODUCTION: The neurobiological mechanisms underlying the chemotherapy-induced neuropathic pain are only partially understood. Among them, microglia activation was identified as the key component of neuropathic pain. The aim of this study was to identify differentially expressed genes (DEGs) and pathways associated with vincristine-induced neuropathic pain by using bioinformatics analysis and observe the effects of oxycodone on these DEG expressions in a vincristine-induced microglia activation model. METHODS: Based on microarray profile GSE53897, we identified DEGs between vincristine-induced neuropathic pain rats and the control group. Using the ToppGene database, the prioritization DEGs were screened and performed by gene ontology (GO) and signaling pathway enrichment. A protein-protein interaction (PPI) network was used to explore the relationship among DEGs. Then, we built the vincristine-induced microglia activation model and detected several DEG expressions by real-time polymerase chain reaction (PCR) and western blotting. Meanwhile, the effects of different concentrations of oxycodone on inflammatory response in primary microglia induced by vincristine were observed. RESULTS: A total of 38 genes were differentially expressed between normal and vincristine-treated rats. GO and pathway enrichment analysis showed that prioritization DEGs are involved in cAMP metabolic process, inflammatory response, regulation of cell proliferation, and chemokine pathway. The in vitro studies showed that vincristine had dose-dependent cytotoxic effects in microglia. Compared to the control group, vincristine (0.001 µg/ml) could lead to inflammation in primary microglia induced by vincristine and upregulated the CXCL10, CXCL9, SFRP2, and PF4 mRNA and made an obvious reduction in IRF7 mRNA. At protein levels, oxycodone (50, 100 ng/ml) decreased the expression of CXCL10 and CXCL9 in activated microglia. CONCLUSION: Our study obtained several DEG expressions and signaling pathways in the vincristine-induced neuropathic pain rat model by bioinformatics analysis. Oxycodone could alleviate the vincristine-induced inflammatory signaling in primary microglia and downregulate some DEGs. Further molecular mechanisms need to be explored in the future.

SIRT3 activator honokiol ameliorates surgery/anesthesia-induced cognitive decline in mice through anti-oxidative stress and anti-inflammatory in hippocampus.

AIMS: Increasing evidence indicates that neuroinflammatory and oxidative stress play two pivotal roles in cognitive impairment after surgery. Honokiol (HNK), as an activator of Sirtuin3 (SIRT3), has potential multiple biological functions. The aim of these experiments is to evaluate the effects of HNK on surgery/anesthesia-induced cognitive decline in mice. METHODS: Adult C57BL/6 mice received a laparotomy under sevoflurane anesthesia and HNK or SIRT3 inhibitor (3-TYP) treatment. Cognitive function and locomotor activity of mice were evaluated using fear conditioning test and open field test on postoperative 1 and 3 days. Neuronal apoptosis in CA1 and CA3 area of hippocampus was examined using TUNEL assay. And Western blot was applied to measure the expression of pro-inflammatory cytokines and SIRT3/SOD2 signaling-associated proteins in hippocampus. Meanwhile, SIRT3 positive cells were calculated by immunohistochemistry. The mitochondrial membrane potential, malondialdehyde (MDA), and mitochondrial radical oxygen species (mtROS) were detected using standard methods. RESULTS: Honokiol attenuated surgery-induced memory loss and neuronal apoptosis, decreased neuroinflammatory response, and ameliorated oxidative damage in hippocampus. Notably, surgery/anesthesia induced an obviously decrease in hippocampal SIRT3 expression, whereas the HNK increased SIRT3 expression and thus decreased the acetylation of superoxide dismutase 2 (SOD2). However, 3-TYP treatment inhibited the HNK's rescuing effects. CONCLUSIONS: These results suggested that activation of SIRT3 by honokiol may attenuate surgery/anesthesia-induced cognitive impairment in mice through regulation of oxidative stress and neuroinflammatory in hippocampus.

The publication trend of neuropathic pain in the world and China: a 20-years bibliometric analysis.

BACKGROUND: There has been tremendous change on neuropathic pain research in the past 20 years in China and around the world. We analyzed the global trend of neuropathic pain research and compared China's quantity and quality of neuropathic pain-related publications with other developed countries. METHODS: Using terms "neuropathic pain", we retrieved related publications from the Web of Science (WOS) database and PubMed database. From different aspects, such as the number of papers, total citations, average citations per item, H-index, research types, orientation, institutions, journals and funding, global neuropathic pain publications were classified and analyzed. RESULTS: From 1998 to 2017, 21,733 articles regarding neuropathic pain research were published worldwide. Of these, 9.394% were contributed by authors from Chinese institutions, which followed USA and ranked second. However, the quality indicators of publications, including total citations, average citations per item and H-index, were relatively low in China. High contribution journals and the 10 most-cited articles on neuropathic pain in world and China were also listed, which also can reflect the quality of neuropathic pain. Based on National Natural Science Foundation of China (NSFC), basic research was the main articles type, accounting for 32.91% of China's neuropathic pain research. CONCLUSION: Global neuropathic pain research increased rapidly during the 1998 to 2017 period. The USA was still the leader of neuropathic research. Although China had made great achievements, there was a significant gap in the high-quality studies between China and other leading countries.

Oxycodone ameliorates the inflammatory response induced by lipopolysaccharide in primary microglia.

BACKGROUND: Activation of microglia participates in a wide range of pathophysiological processes in the central nervous system. Some studies reported that oxycodone (6-deoxy-7,8-dehydro-14-hydroxy-3-O-methyl-6oxomorphine) could inhibit the overactivation of glial cells in rats' spinal cords. In the present study, we observed the effect of oxycodone on inflammatory molecules and pathway in lipopolysaccharide (LPS)-stimulated primary microglia in rats. MATERIALS AND METHODS: Neonatal rats' primary microglia were exposed to various concentrations (25, 50, 100 ng/mL) of oxycodone for 1 h after LPS stimulation for 24 h. The levels of pro-inflammatory mediators, IL-1ß, TNF-α, and TGF-ß1/smad2/3 signaling pathway were measured. The activation situation of microglia and the expression of TßR1 were observed by immunofluorescence. RESULTS: Oxycodone at 25 ng/mL did not change the levels of proinflammatory molecules and TGF-ß1/smad2/3 signaling pathway in primary microglia, which was increased by LPS. Oxycodone at 50 and 100 ng/mL could significantly suppress LPS-induced production of TNF-α and IL-1ß and the expression of TNF-αmRNA, IL-1ßmRNA, and TGF-ß1/smad2/3 signaling pathway. CONCLUSION: These findings indicate that oxycodone, at relatively high clinically relevant concentration, can inhibit inflammatory response in LPS-induced primary microglia. The detailed mechanism needs to be investigated in future.

Altered hippocampal microRNA expression profiles in neonatal rats caused by sevoflurane anesthesia: MicroRNA profiling and bioinformatics target analysis.

Although accumulating evidence has suggested that microRNAs (miRNAs) have a serious impact on cognitive function and are associated with the etiology of several neuropsychiatric disorders, their expression in sevoflurane-induced neurotoxicity in the developing brain has not been characterized. In the present study, the miRNAs expression pattern in neonatal hippocampus samples (24 h after sevoflurane exposure) was investigated and 9 miRNAs were selected, which were associated with brain development and cognition in order to perform a bioinformatic analysis. Previous microfluidic chip assay had detected 29 upregulated and 24 downregulated miRNAs in the neonatal rat hippocampus, of which 7 selected deregulated miRNAs were identified by the quantitative polymerase chain reaction. A total of 85 targets of selected deregulated miRNAs were analyzed using bioinformatics and the main enriched metabolic pathways, mitogen-activated protein kinase and Wnt pathways may have been involved in molecular mechanisms with regard to neuronal cell body, dendrite and synapse. The observations of the present study provided a novel understanding regarding the regulatory mechanism of miRNAs underlying sevoflurane-induced neurotoxicity, therefore benefitting the improvement of the prevention and treatment strategies of volatile anesthetics related neurotoxicity.

Posttreatment with propofol attenuates lipopolysaccharide-induced up-regulation of inflammatory molecules in primary microglia.

BACKGROUND: Activation of microglia is involved in a broad range of neuroinflammatory diseases. Suppression of microglial activation may, therefore, contribute to alleviate the progression of neuroinflammatory diseases. It has been reported that propofol has a potent anti-inflammatory property. In the present study, we investigated the effects of posttreatment with propofol on the production of inflammatory molecules in lipopolysaccharide (LPS)-stimulated microglia. MATERIALS AND METHODS: Microglia were exposed to various concentrations (25, 50, 100, 250 µM) of propofol for 1 h after LPS stimulation for 24 h. The levels of proinflammatory mediators inducible nitric oxide synthase (iNOS)/nitric oxide (NO), cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were measured. RESULTS: Propofol at a concentration of 25 µM did not affect the production of proinflammatory mediators, which was enhanced by LPS. At the concentrations of 50, 100, and 250 µM, propofol significantly inhibited LPS-mediated production of NO, PGE2, TNF-α, and IL-1ß and the expression of iNOSmRNA, COX-2mRNA, TNF-α mRNA, and IL-1ß mRNA. CONCLUSIONS: These results suggest that propofol, at clinically relevant concentrations, can reduce inflammatory responses in LPS-induced inflammation in activated microglia and might be an intravenous anesthetic of choice when patients with neuroinflammatory diseases require sedation and/or general anesthesia.