Construction of pain prediction model for patients undergoing hepatic arterial chemoembolization.

OBJECTIVE: To construct a predictive model for pain in patients undergoing hepatic arterial chemoembolization (TACE) in interventional operating room. METHODS: Through literature review and expert interviews, a questionnaire was prepared for the assessment of pain factors in patients with hepatic arterial chemoembolization. A prospective cohort study was used to select 228 patients with hepatic arterial chemoembolization in a tertiary and first-class hospital. The data of the patients in the pain group and the non-pain group were compared, and a rapid screening prediction model was constructed by univariate analysis and logistic regression analysis, and its prediction effect was tested. RESULTS: Tumor size, liver cancer stage, and chemoembolization with drug-loaded microspheres and pirarubicin hydrochloride (THP) mixed with lipiodol were independent predictors of pain in patients after hepatic arterial chemoembolization. Finally, the pain prediction model after TACE was obtained. The results of Hosmer-Lemeshow test showed that the model fit was good (χ2 = 13.540, p = 0.095). The area under the receiver operating characteristic curve was 0.798, p < 0.001. CONCLUSION: The rapid screening and prediction model of pain in patients undergoing hepatic arterial chemoembolization has certain efficacy, which is helpful for clinical screening of patients with high risk of pain, and can provide reference for predictive pain management decision-making.

A CD8+ T Cell-Related Genes Expression Signature Predicts Prognosis and the Efficacy of Immunotherapy in Breast Cancer.

Immunotherapy has been applied to patients with breast cancer. However, only part of patients benefits from the current immunotherapy. Accurate prediction of individual response to immunotherapy can be beneficial for breast cancer management. CD8+ T cells are the main force of anti-tumor immunity. This study aimed to establish a CD8+ T cell-related gene expression signature for prediction of breast cancer prognostic and immunotherapy efficacy. RNA-seq transcriptomic data was the basics of this research. Weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis established the prognostic signature. We identified 290 CD8+ T cell-related genes in the training set and established a risk-score model based on 8-genes panel (SOCS1, IL10, CAMK4, CXCL13, KIR2DS4, TESPA1, CD70 and ICAM4). Subsequently, univariate Cox regression analysis suggested that high risk-score was a risk factor for breast cancer (HR = 3.1, 95%CI 2.0-4.8, P < 0.001). In tumor microenvironment, high-risk tumors present decreased tumor infiltrating CD8+ T cells and increased M2 macrophages. The low-risk patients may benefit more from immune checkpoint blockade immunotherapy than the high-risk patients. Moreover, breast tumors which sensitive to immune checkpoint inhibitor (ICI) showed higher IL10 expression.

Structural dynamics of Ru clusters during nitrogen dissociation in ammonia synthesis.

The dynamic evolution of catalyst structures greatly influences the reactivity, especially sub-nanometer clusters, exhibiting complex configurational fluctuation. In the present work, we study the structural dynamics of a Ru19 cluster during the dissociation of N2 and calculate the reaction free energies using ab initio molecular dynamics (AIMD). Our AIMD calculation predicts a peak-shaped reaction entropy curve due to the adsorption-induced phase transition of the Ru19 cluster. The low melting points of sub-nanometer clusters make it possible to activate N2 at low temperatures. This work demonstrates that the dynamic changes of cluster structures have a non-negligible effect on reaction free energy and offer an opportunity for achieving ammonia synthesis under mild conditions.

Size-dependent phase transitions boost catalytic activity of sub-nanometer gold clusters.

The characterization and identification of the dynamics of cluster catalysis are crucial to unraveling the origin of catalytic activity. However, the dynamical catalytic effects during the reaction process remain unclear. Herein, we investigate the dynamic coupling effect of elementary reactions with the structural fluctuations of sub-nanometer Au clusters with different sizes using ab initio molecular dynamics and the free energy calculation method. It was found that the adsorption-induced solid-to-liquid phase transitions of the cluster catalysts give rise to abnormal entropy increase, facilitating the proceeding of reaction, and this phase transition catalysis exists in a range of clusters with different sizes. Moreover, clusters with different sizes show different transition temperatures, resulting in a non-trivial size effect. These results unveil the dynamic effect of catalysts and help understand cluster catalysis to design better catalysts rationally.

The Novel microRNA Rno-miR-686-3p Is Associated with the Ischaemic Penumbra.

INTRODUCTION: We explored microRNA (miRNA) profiles correlated with the penumbra in three different phases of ischaemic stroke, using a permanent middle cerebral artery occlusion (p-MCAO) rat model. MATERIALS AND METHODS: A 2-mm coronal section was cut from the optic chiasma in the caudal direction, and the penumbra was located in the area between a longitudinal line approximately 2 mm from the midline and a transverse diagonal line at the "2-o'clock" position. Total RNA was extracted from tissue specimens and peripheral blood samples, followed by deep sequencing analysis. RESULTS: We identified nine novel miRNA candidates in tissues and evaluated their expression levels using real-time quantitative polymerase chain reaction. In situ hybridization was conducted to assess miRNA localization in the brain. Of these nine candidates, we identified and characterized a novel miRNA, rno-miR-686-3p, which was localized in cell nuclei of the cortex, and associated with the penumbra. rno-miR-686-3p was downregulated at 1 (p = 0.042), 3 (p = 0.032), and 4 h (p = 0.007) post-p-MCAO in the penumbra. A total of 297 potential target genes were predicted. Moreover, functional annotation clustering and pathway enrichment analysis predicted that rno-miR-686-3p participates in transcriptional regulation and the Wnt and cyclic adenosine monophosphate (cAMP) signalling pathways. CONCLUSION: rno-miR-686-3p is a novel miRNA associated with the ischaemic penumbra that is implicated in transcriptional regulation and modulation of the Wnt and cAMP signalling pathways. Furthermore, it may serve as a possible new biomarker with potential value for detecting the existence of the penumbra.

In Situ Raman Monitoring and Manipulating of Interfacial Hydrogen Spillover by Precise Fabrication of Au/TiO2 /Pt Sandwich Structures.

The spillover of hydrogen species and its role in tuning the activity and selectivity in catalytic hydrogenation have been investigated in situ using surface-enhanced Raman spectroscopy (SERS) with 10 nm spatial resolution through the precise fabrication of Au/TiO2 /Pt sandwich nanostructures. In situ SERS study reveals that hydrogen species can efficiently spillover at Pt-TiO2 -Au interfaces, and the ultimate spillover distance on TiO2 is about 50 nm. Combining kinetic isotope experiments and density functional theory calculations, it is found that the hydrogen spillover proceeds via the water-assisted cleavage and formation of surface hydrogen-oxygen bond. More importantly, the selectivity in the hydrogenation of the nitro or isocyanide group is manipulated by controlling the hydrogen spillover. This work provides molecular insights to deepen the understanding of hydrogen activation and boosts the design of active and selective catalysts for hydrogenation.

Activation and function of receptor tyrosine kinases in human clear cell renal cell carcinomas.

BACKGROUND: The receptor tyrosine kinases (RTKs) play critical roles in the development of cancers. Clear cell renal cell carcinoma (ccRCC) accounts for 75% of the RCC. The previous studies on the RTKs in ccRCCs mainly focused on their gene expressions. The activation and function of the RTKs in ccRCC have not been fully investigated. METHODS: In the present study, we analyzed the phosphorylation patterns of RTKs in human ccRCC patient samples, human ccRCC and papillary RCC cell lines, and other kidney tumor samples using human phospho-RTK arrays. We further established ccRCC patient-derived xenograft models in nude mice and assessed the effects of RTKIs (RTK Inhibitors) on the growth of these cancer cells. Immunofluorescence staining was used to detect the localization of keratin, vimentin and PDGFRß in ccRCCs. RESULTS: We found that the RTK phosphorylation patterns of the ccRCC samples were all very similar, but different from that of the cell lines, other kidney tumor samples, as well as the adjacent normal tissues. 9 RTKs, EGFR1-3, Insulin R, PDGFRß, VEGFR1, VEGFR2, HGFR and M-CSFR were found to be phosphorylated in the ccRCC samples. The adjacent normal tissues, on the other hand, had predominantly only two of the 4 EGFR family members, EGFR and ErbB4, phosphorylated. What's more, the RTK phosphorylation pattern of the xenograft, however, was different from that of the primary tissue samples. Treatment of the xenograft nude mice with corresponding RTK inhibitors effectively inhibited the Erk1/2 signaling pathway as well as the growth of the tumors. In addition, histological staining of the cancer samples revealed that most of the PDGFRß expressing cells were localized in the vimentin-positive periepithelial stroma. CONCLUSIONS: Overall, we have identified a set of RTKs that are characteristically phosphorylated in ccRCCs. The phosphorylation of RTKs in ccRCCs were determined by the growing environments. These phosphorylated/activated RTKs will guide targeting drugs development of more effective therapies in ccRCCs. The synergistical inhibition of RTKIs combination on the ccRCC suggest a novel strategy to use a combination of RTKIs to treat ccRCCs.

Diagnosis of Hyperacute and Acute Ischaemic Stroke: The Potential Utility of Exosomal MicroRNA-21-5p and MicroRNA-30a-5p.

BACKGROUND: Early and accurate diagnosis of ischaemic stroke (IS) requires the use of an optimized biomarker. Exosomal microRNAs have the potential to serve as biomarkers owing to their stability and specificity. We investigated the expression levels of plasma-derived exosomal microRNA-21-5p and microRNA-30a-5p in the different phases of IS. METHODS: One hundred forty-three patients with IS and 24 non-stroke controls were enrolled. The patients were divided into the following 5 groups: 1 group for the hyperacute phase IS (HIS, within 6 h); two for the acute phase IS (AIS, including days 1-3 and days 4-7); one for the subacute phase IS (SIS, days 8-14); and one for the recovery phase IS (RIS, days >14). Plasma exosomes were isolated using a QIAGEN exoRNeasy kit and examined by transmission electron -microscopy, nanoparticle tracking, and flow cytometry. The expression levels of miRNA-21-5p and miRNA-30a-5p were detected by quantitative real-time polymerase chain reaction. RESULTS: The plasma exosomal miR-21-5p levels in SIS and RIS were significantly higher than that in controls (p < 0.05 and p < 0.01 respectively). The levels of miR-30a-5p in HIS were significantly higher (p < 0.05) and in AIS (days 1-3) were lower than that in controls (p < 0.05). In AIS (days 1-3), both miRNAs were decreased compared with the HIS group (p = 0.053 and 0.001, respectively). The area under the curve (AUC) of the miR-21-5p was 0.714 for SIS (95% CI 0.570-0.859, p = 0.007), 0.734 for RIS (95% CI 0.596-0.871, p = 0.003); the AUC of the miR-30a-5p was 0.826 for HIS (95% CI 0.665-0.988, p = 0.001), 0.438 for AIS (days 1-3; 95% CI 0.240-0.635, p = 0.516). CONCLUSIONS: The plasma-derived exosomal miR-21-5p and miRNA-30a-5p in combination are promising biomarkers for diagnosing IS and distinguishing among HIS, SIS, and RIS, especially miRNA-30a-5p for the diagnosis of the HIS phase. Our results provide a new reference for clinicians to apply in early-stage diagnosis and identifies the possible value of biomarkers for IS thrombolysis therapy.

Fastigial nucleus stimulation regulates neuroprotection via induction of a novel microRNA, rno-miR-676-1, in middle cerebral artery occlusion rats.

Previous studies have shown that fastigial nucleus stimulation (FNS) reduces tissue damage resulting from focal cerebral ischemia. Although the mechanisms of neuroprotection induced by FNS are not entirely understood, important data have been presented in the past two decades. MicroRNAs (miRNAs) are a newly discovered group of non-coding small RNA molecules that negatively regulate target gene expression and are involved in the regulation of cell proliferation and cell apoptosis. To date, no studies have demonstrated whether miRNAs can serve as mediators of the brain's response to FNS, which leads to endogenous neuroprotection. Therefore, this study investigated the profiles of FNS-mediated miRNAs. Using a combination of deep sequencing and microarray with computational analysis, we identified a novel miRNA in the rat ischemic cortex after 1 h of FNS. This novel miRNA (PC-3p-3469_406), herein referred to as rno-miR-676-1, was upregulated in rats with cerebral ischemia after FNS. In vivo observations indicate that this novel miRNA may have antiapoptotic effects and contribute to neuroprotection induced by FNS. Our study provides a better understanding of neuroprotection induced by FNS. MicroRNA (miRNA) is defined as a small non-coding RNA that fulfills both the expression and biogenesis criteria. Here, we describe a novel miRNA in the rat ischemic cortex expressed after 1 h of fastigial nucleus stimulation (FNS). The miRNA was functionally characterized by secondary structure, quantitative expression, the conservation analysis, target gene analysis, and biological functions. We consider rno-miR-676-1 to be a true microRNA and present evidence for its neuroprotective effects exerted after induction by FNS.

The effective combination therapies with irinotecan for colorectal cancer.

Colorectal cancer is the third most common type of cancer worldwide and has become one of the major human disease burdens. In clinical practice, the treatment of colorectal cancer has been closely related to the use of irinotecan. Irinotecan combines with many other anticancer drugs and has a broader range of drug combinations. Combination therapy is one of the most important means of improving anti-tumor efficacy and overcoming drug resistance. Reasonable combination therapy can lead to better patient treatment options, and inappropriate combination therapy will increase patient risk. For the colorectal therapeutic field, the significance of combination therapy is to improve the efficacy, reduce the adverse effects, and improve the ease of treatment. Therefore, we explored the clinical advantages of its combination therapy based on mechanism or metabolism and reviewed the rationale basis and its limitations in conducting exploratory clinical trials on irinotecan combination therapy, including the results of clinical trials on the combination potentiation of cytotoxic drugs, targeted agents, and herbal medicine. We hope that these can evoke more efforts to conduct irinotecan in the laboratory for further studies and evaluations, as well as the possibility of more in-depth development in future clinical trials.

[Effects of cerebellar fastigial nucleus electrical stimulation on telomerase reverse transcriptase expression and mitochondrial apoptotic pathway in rats with focal cerebral ischemia and reperfusion].

OBJECTIVE: To study the effects of cerebellar fastigial nucleus (FN) electrical stimulation on telomerase reverse transcriptase expression and mitochondrial apoptotic pathway in rats with focal cerebral ischemia and reperfusion. METHODS: A total of 100 adult male Wistar rats were randomly divided into 3 groups: sham operation group, modeling group (2-hour cerebral ischemia, followed by 24, 48 & 72-hour reperfusion) and FN-stimulating group (electrical stimulation of FN for 1-hour one day before 2-hour cerebral ischemia, followed by 24, 48 & 72-hour reperfusion). HE (hematoxylin and eosin) and TTC (triphenyl tetrazolium chloride) staining were used to observe the morphological changes in rat brain and measure the ischemic lesion volumes. The expressions of TERT (telomerase reverse transcriptase) and Bax were detected by immunohistochemical methods and apoptotic cells by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling). The co-expression of TERT and Bax was detected by immunofluorescence double-labeling plus laser confocal microscopy. RESULTS: The morphological changes in rat brain were less greater in the FN-stimulating group than those in the modeling group. And the size of the cerebral infarct was significantly smaller in the FN-stimulating group (78.1 ± 2.9, 83.1 ± 4.5, 83.7 ± 4.8) than that in the modeling group (120.9 ± 8.2, 137.0 ± 4.2, 141.1 ± 3.3) (P < 0.05) at all reperfusion time points. As compared with the modeling group (16.1 ± 2.7, 16.9 ± 2.4, 11.6 ± 3.5), the FN-stimulating group (31.1 ± 3.5, 30.0 ± 3.4, 18.9 ± 3.3) had a significantly larger number of TERT-positive cells (P < 0.05) and a significantly reduced number of TUNEL-positive cells (49.6 ± 2.8, 67.0 ± 3.7, 46.8 ± 3.2 vs 40.2 ± 3.1, 54.8 ± 2.8, 37.3 ± 2.4) (P < 0.05). The number of Bax-positive cells at different reperfusion time points in the FN-stimulating group was not significantly different from those in the modeling group (P > 0.05). TERT partially co-localized with Bax in the cytoplasm. The number of double-labeled cells was significantly higher in the FN-stimulating group than that in the modeling group (14.1 ± 1.3, 12.9 ± 2.4, 9.0 ± 2.0 vs 8.2 ± 1.1, 6.3 ± 2.4, 6.0 ± 2.9) (P < 0.05). CONCLUSION: The expression of TERT significantly increases after a stimulation of FN. TERT may bind to Bax and inhibit Bax-mediated apoptosis by suppressing the mitochondrial relocalization of Bax from cytosol.

[Relationship between Q192R polymorphisms in paraoxonase 1 gene and young ischemic stroke].

OBJECTIVE: To investigate the relationship between polymorphisms in paraoxonase1 (PON1) gene Gln192Arg (Q192R) and arterial ischemic stroke in young adults. METHODS: The Q192R genotype was analyzed by polymerase chain reaction in 131 young adults with ischemic stroke and 135 age- and gender-matched controls. The plasma lipids were also determined in patients and controls respectively. Furthermore, carotid artery intima-media thickness (IMT) in patients were measured by carotid ultrasonography. RESULTS: The distributions of Q192R genotype frequency were significantly different between patients with ischemic stroke and control individuals. And the patients had more RR genotypes than control individuals (P < 0.05). Odds ratio (OR) for stroke were 1.743 (95% confidence interval [CI], 1.032-2.943) in subjects with RR genotype. We also studied the relationship between the polymorphisms and the lipid concentration in patients and control individuals. However, no significant association was detected between Q/R192 genotype and any of lipid measurements. Further, the prevalence of cigarette smoking, hypertension and diabetes showed no significant difference between RR and non-RR genotypes in patients. Body mass index (BMI) in two groups did not differ significantly. But IMT of patients with RR genotype obviously increased in comparison to those without RR genotype (P < 0.05). CONCLUSION: The PON1 gene Q192R polymorphism may be associated with the susceptibility of ischemic stroke in young adults. RR genotype is a genetic risk for young adults with ischemic stroke through an increased carotid artery intima-media thickness and an accelerated atherosclerotic process.

Identification of Serum Biomarkers for Ischemic Penumbra by iTRAQ-Based Quantitative Proteomics Analysis.

PURPOSE: Ischemic penumbra is the main therapeutic target for acute ischemic stroke. The aim in this study is to investigate the potential serum biomarkers of penumbra that could fulfill a complementary role in the acute stroke clinical decision-making process. EXPERIMENTAL DESIGN: An established focal cerebral ischemia model is applied in rats. Using isobaric tags for relative and absolute quantitation combined with liquid chromatography-tandem mass spectrometry, the global expression profiles of proteins in ischemic penumbra tissue and serum from rats subjected to different ischemic times are identified and quantified. Candidate biomarkers are screened out with bioinformatics analysis and further validated by western blotting. RESULTS: Herein, a total of 4568 proteins in the penumbra and 1915 proteins in the serum are identified. Two proteins related to the penumbra, RHOA, and CDC42, are screened out through an integrative analysis. The expression levels of RHOA and CDC42 in the penumbra and serum gradually increase synchronously with the prolonged ischemia time. CONCLUSIONS AND CLINICAL RELEVANCE: The study provides the results of a proteomic analysis to identify serum biomarkers of the penumbra. Upregulation of RHOA and CDC42 may be useful for the early assessment of ischemic penumbra and could serve as potential serum biomarkers.

Effects of quercetin on hyper-proliferation of gastric mucosal cells in rats treated with chronic oral ethanol through the reactive oxygen species-nitric oxide pathway.

AIM: To investigate the effect of quercetin (3,3',4',5,7-pentahydroxy flavone), a major flavonoid in human diet, on hyper-proliferation of gastric mucosal cells in rats treated with chronic oral ethanol. METHODS: Forty male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into control group (tap water ad libitum), ethanol treatment group (6 mL/L ethanol), quercetin treatment group (intragastric gavage with 100 mg/kg of quercetin per day), and ethanol plus quercetin treatment group (quercetin and 6 mL/L ethanol). Expression levels of proliferating cell nuclear antigen (PCNA) and Cyclin D1 were detected by Western blot to assay gastric mucosal cell proliferation in rats. To demonstrate the influence of quercetin on the production of extra-cellular reactive oxygen species/nitrogen species (ROS/RNS) in rats, changes in levels of thiobarbituric acid reactive substance (TBARS), protein carbonyl, nitrite and nitrate (NOx) and nitrotyrosine (NT) were determined. The activity of inducible nitric oxide synthase (NOS) including iNOS and nNOS was also detected by Western blot. RESULTS: Compared to control animals, cell proliferation in the gastric mucosa of animals subjected to ethanol treatment for 7 days was significant increased (increased to 290% for PCNA density P < 0.05, increased to 150 for Cyclin D1 density P < 0.05 and 21.6 +/- 0.8 vs 42.3 +/- 0.7 for PCNA positive cells per view field), accompanied by an increase in ROS generation (1.298 +/- 0.135 micromol vs 1.772 +/- 0.078 micromol for TBARS P < 0.05; 4.36 +/- 0.39 mmol vs 7.48 +/- 0.40 mmol for carbonyl contents P < 0.05) and decrease in NO generation (11.334 +/- 0.467 micromol vs 7.978 +/- 0.334 micromol P < 0.01 for NOx; 8.986 +/- 1.351 micromol vs 6.854 +/- 0.460 micromol for nitrotyrosine P < 0.01) and nNOS activity (decreased to 43% P<0.05). This function was abolished by the co-administration of quercetin. CONCLUSION: The antioxidant action of quercetin relies, in part, on its ability to stimulate nNOS and enhance production of NO that would interact with endogenously produced reactive oxygen to inhibit hyper-proliferation of gastric mucosal cells in rats treated with chronic oral ethanol.

miR-146a induces apoptosis in neuroblastoma cells by targeting BCL11A.

Aberrant expression of miR-146a has been reported to be involved in the progression and metastasis of various types of human cancers; however, its potential role in human neuroblastoma is still poorly understood. The purpose of our study was to investigate the molecular mechanism and possible role of miR-146a in human neuroblastoma. In this study, targeted genes were predicted by bioinformatic analysis and confirmed by dual-Luciferase reporter assay. The expression level of miR-146a in the human neuroblastoma SK-N-SH cell line was detected by quantitative RT-PCR. We used flow cytometric analysis to determine apoptosis and necrosis of SK-N-SH cells after transfection with miR-146a inhibitor, miR-146a mimic, and negative controls. The expression level of target genes was detected by RT-PCR and Western blotting. We identified BCL11A as a target of miR-146a. Thus, miR-146a targets the 3'UTR of BCL11A and inhibits its mRNA and protein expression. Overexpression of miR-146a can inhibit the growth and promote the apoptosis of human neuroblastoma SK-N-SH cells through inhibiting the expression of BCL11A. Furthermore, we found that upregulation of BCL11A by miR-146a inhibitor can promote SK-N-SH cells growth and protect SK-N-SH cells against apoptosis. Our results showed that miR-146a is a potential tumor suppressor gene in human neuroblastoma via directly targeting BCL11A. These findings suggest that miR-146a might be a new candidate target for treatment of human neuroblastoma.

Plasma Exosomal miRNA-122-5p and miR-300-3p as Potential Markers for Transient Ischaemic Attack in Rats.

Background: Differentiation of transient ischaemic attack (TIA) from ischaemic stroke within the thrombolysis time window is difficult. Although TIA may be diagnosed within this window, the latest imaging technologies are complex and costly. Serum markers, which are non-invasive, rapid and economic, are used for diagnosis and prognosis of various diseases. Exosome-derived miRNA markers for TIA are unknown. Methods: We examined focal brain ischaemia produced by occlusion of the middle cerebral artery (MCAo) for 5 min, 10 min, and 2 h in rats. Exosomal miRNAs with consistent trends in cerebrospinal fluid (CSF) and plasma were identified by deep sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). The areas under the curve (AUC) of the receiver operating characteristic (ROC) curve were used to evaluate the diagnostic accuracy of these miRNAs for TIA in rats. Results: Rno-miR-122-5p and rno-miR-300-3p were selected. Plasma exosomal rno-miR-122-5p was significantly downregulated in 10 min ischaemic rats compared with control and 5 min plasma. Plasma exosomal rno-miR-300-3p was significantly upregulated in 5 min ischaemic rats compared with control, 10 min and 2 h rats. Plasma and CSF levels of these miRNAs were correlated. ROC analysis showed high AUC values for rno-miR-122-5p (0.960) and rno-miR-300-3p (0.970) in the 10 and 5 min rats, respectively, compared with controls. Conclusions: Plasma exosomal rno-miR-122-5p and rno-miR-300-3p may be blood-based TIA biomarkers.

[Clinical observation on effect of modified Daotan Decoction combined with small dose risperidone in treating chronic schizophrenia].

OBJECTIVE: To evaluate the clinical efficacy of modified Daotan Decoction (DD) combining low dosage of risperidone in treating chronic schizophrenia patients of phlegm-dampness blockage type, and compare with patients treated with risperidone alone. METHODS: Sixty-five inpatients were randomly assigned to two groups, the treatment group (34 cases) treated with DD (with conventional dosage) one dose per day and risperidone 3.16 +/- 0.73 mg/d, and the control group (31 cases) treated with risperidone 5.11 +/- 1.27 mg/d alone, the course for both groups was 8 weeks. The effect was evaluated with positive and negative syndrome scale (PANSS), and the adverse reaction was assessed with treatment emergent symptom scale (TESS). RESULTS: There was no significant difference in the overall efficacy between the two groups, but the improvement of the negative symptoms, illness provocation and general psychopathologic condition was significantly better in the treatment group than that in the control group respectively (P < 0.05). Moreover, the adverse reaction was milder and less in the former than that in the latter. CONCLUSION: The treatment of DD combined with low dosage of risperidone is effective on chronic schizophrenia and shows less adverse reaction.

Decreased miR-146a expression in acute ischemic stroke directly targets the Fbxl10 mRNA and is involved in modulating apoptosis.

BACKGROUND: miR-146a, a strong pro-apoptotic factor in some pathophysiological processes, is reported to be involved in ischemic stroke (IS), though its role remains unclear. Fbxl10 is an active anti-apoptotic factor and a predicted target of miR-146a. We hypothesized that dysregulation of miR-146a contributes to ischemic injury by targeting Fbxl10. METHODS: Circulating miRNAs were detected by miRNA microarray and qRT-PCR. miR-146a targets were predicted using bioinformatics and confirmed with a dual luciferase reporter assay. We used an in vitro ischemic model of oxygen-glucose deprivation and reperfusion (OGD/R) to mimic cerebral ischemia/reperfusion (I/R) conditions. Expression of miR-146a, Fbxl10 and Bcl2l2 mRNAs, and Fbxl10 and Bcl2l2 proteins was verified by qRT-PCR and Western blotting. The effects of miR-146a on neuronal cell apoptosis were evaluated by flow cytometry. RESULTS: A significant reduction in miR-146a expression was observed in acute ischemic stroke (AIS). A dual-luciferase reporter assay showed that Fbxl10, but not Bcl2l2, is a target of miR-146a. Transfection with miR-146a mimics promoted apoptosis in SK-N-SH cells and significantly reduced expression of Fbxl10. Conversely, miR-146a inhibition attenuated OGD/R-induced neuronal cell death and significantly up-regulated Fbxl10 expression. CONCLUSIONS: miR-146a expression was significantly down-regulated in AIS, and Fbxl10 was identified as a target of miR-146a. Moreover, up-regulation of Fbxl10, a miR-146a target, likely protects neurons from ischemic death.

Plasma Exosomal miR-422a and miR-125b-2-3p Serve as Biomarkers for Ischemic Stroke.

BACKGROUND: MircroRNA (MiRNA) levels are associated with disease pathophysiology and are high in plasma exosomes. Plasma exosomal miRNAs serve as potential therapeutic targets and diagnosis biomarkers in some diseases but few studies have examined them in Ischemic Stroke (IS). Therefore, we explored the potential predictive value of plasma exosomal miR-422a and miR-125b-2-3p in different IS phases (acute and subacute phases). METHODS: Fifty-five IS patients and 25 age and sex matched healthy controls were recruited. Patients were classified into two groups: 27 patients in acute phase (days 1-3) and 28 patients in subacute phase (days 4-14). The plasma exosomal levels of miR-422a and miR-125b-2-3p were examined via quantitative real-time polymerase chain reaction (qRT-PCR). The Areas Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve were constructed to evaluate the diagnostic accuracy of these miRNAs in IS. RESULTS: The expression levels of plasma exosomal miR-422a and miR-125b-2-3p were significantly decreased in the subacute phase group (P<0.001, P<0.001, respectively), and the miR-422a levels were increased in the acute phase group (P<0.005) as compared to the controls. Additionally, the expression levels of plasma exosomal miR-422a and miR-125b-2-3p were significantly decreased in the subacute phase group than in the acute phase group (P<0.001, P<0.005, respectively). ROC analysis showed high AUC values for miR-422a and miR-125b-2-3p in the subacute phase group as compared to those in healthy controls: 0.971 and 0.889, respectively, and miR-422a in the acute phase group as compared to healthy controls were 0.769. CONCLUSION: Plasma exosomal miR-422a and miR-125b-2-3p may serve as blood-based biomarkers for monitoring and diagnosing in IS patients, with plasma exosomal miR-422a showing the best diagnostic value. The use of these two plasma exosomal miRNAs in combination may be powerful for determining IS stage.

Aqueous extract from Aconitum carmichaelii Debeaux reduces liver injury in rats via regulation of HMGB1/TLR4/NF-ΚB/caspase-3 and PCNA signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii Debeaux is a well-known Chinese herb that has been used to treat liver diseases for many years in China. We investigated the effects of aqueous extract from Aconitum carmichaelii Debeaux (AEACD) on acute liver failure and identified the possible mechanisms of these effects. MATERIAL AND METHODS: Specific pathogen-free (SPF) male Wistar rats were used to establish acute liver failure model by intraperitoneal injection of D-galactosamine (D-GalN) and treated with Stronger Neo-Minophagen C (SNMC) and AEACD by gavage. Then, the serum biochemical parameters, the pathological scores in the liver tissue, the mRNA expressions of toll- like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), high mobility group box 1 (HMGB1) and caspase-3, the proliferating cell nuclear antigen (PCNA) positive rates were analyzed. RESULTS: The liver function was improved, the pathological scores were decreased, the expressions the TLR4, NF-κB, HMGB1, and caspase-3 were inhibited, and the PCNA positive rates were increased by both SNMC and AEACD, but AEACD induced greater effects. CONCLUSIONS: AEACD protected liver function by inhibiting inflammatory reaction, apoptosis and promoting liver tissue regeneration in the acute liver failure rats induced by D-galactosamine.