Diastasis Recti Abdominis: A Practical and Effective Width-Length Classification Based on Ultrasound Measurements and its Clinical Validation.

OBJECTIVES: This study aimed to establish a simple and practical classification to guide the clinical treatment of diastasis recti abdominis (DRA) based on ultrasound characteristics with different severities of DRA, and to verify its clinical utility. METHODS: We retrospectively enrolled 301 DRA patients as pilot cohort and divided into Conservative Treatment Group and Surgical Group according to clinical outcomes. A new Width-Length classification was summarized based on ultrasound measurements of the width and length of midline separation. Then, 100 DRA patients were enrolled prospectively as validation cohort, and diagnostic performance was evaluated by clinical treatment. RESULTS: The Width-Length classification in pilot cohort was as follows: Type 1 (n = 108), open only at M3; Type 2 (n = 63), open at M3 and either M2 or M4 (inter-rectus distance at M3 <47 mm); Type 3 (n = 44), open at M3 and either M2 or M4 (inter-rectus distance at M3 ≥47 mm); Type 4 (n = 74), open at M3, along with other two sites of M1, M2, M4, or M5; Type 5 (n = 12), open at M2, M3, and M4, along with M1 or M5, or both. DRA patients in Type 1-2 were recommended for conservative treatment, and in Type 3-5 were recommended for surgical treatment (all P < .05). In the validation cohort, the accuracy of Width-Length classification in determining treatment strategy was 86.0%. CONCLUSIONS: This study proposes a Width-Length classification based on the width and length of midline separation on ultrasound, which was validated to be simple, practical and effective in guiding DRA treatment.

Chiral-induced synthesis of chiral covalent organic frameworks core-shell microspheres for HPLC enantioseparation.

Two chiral covalent organic frameworks (CCOFs) core-shell microspheres based on achiral organic precursors by chiral-induced synthesis strategy for HPLC enantioseparation are reported for the first time. Using n-hexane/isopropanol as mobile phase, various kinds of racemates were selected as analytes and separated on the CCOF-TpPa-1@SiO2 and CCOF-TpBD@SiO2-packed columns with a low column backpressure (3 ~ 9 bar). The fabricated two CCOFs@SiO2 chiral columns exhibited good separation performance towards various racemates with high column efficiency (e.g., 19,500 plates m-1 for (4-fluorophenyl)ethanol and 18,900 plates m-1 for 1-(4-chlorophenyl)ethanol) and good reproducibility. Some effects have been investigated such as the analyte mass and column temperature on the HPLC enantioseparation. Moreover, the chiral separation results of the CCOF-TpPa-1@SiO2 chiral column and the commercialized Chiralpak AD-H column show a good complementarity. This study demonstrates that the usage of chiral-induced synthesis strategy for preparing CCOFs core-shell microspheres as a novel stationary phase has a good application potential in HPLC.

Asymmetric catalytic synthesis of chiral covalent organic framework composite (S)-DTP-COF@SiO2 for HPLC enantioseparations by normal-phase and reversed-phase chromatographic modes.

A novel CCOF core-shell composite material (S)-DTP-COF@SiO2 was prepared via asymmetric catalytic and in situ growth strategy. The prepared (S)-DTP-COF@SiO2 was utilized as separation medium for HPLC enantioseparation using normal-phase and reversed-phase chromatographic modes, which displays excellent chiral separation performance for alcohols, esters, ketones, and epoxides, etc. Compared with chiral commercial chromatographic columns (Chiralpak AD-H and Chiralcel OD-H columns) and some previously reported chiral CCOF@SiO2 (CC-MP CCTF@SiO2 and MDI-ß-CD-modified COF@SiO2)-packed columns, there are 4, 3, 13, and 15 tested racemic compounds that could not be resolved on the Chiralpak AD-H column, Chiralcel OD-H column, CC-MP CCTF@SiO2 column, and MDI-ß-CD-modified COF@SiO2 column, respectively, which indicates that the resolution effect of (S)-DTP-COF@SiO2-packed column can be complementary to the other ones. The effects of the analyte mass, column temperature, and mobile phase composition on the enantiomeric separation were investigated. The chiral column exhibits good reproducibility after multiple consecutive injections. The RSDs (n = 5) of the peak area and retention time were less than 1.5% for repetitive separation of 2-methoxy-2-phenylethanol and 1-phenyl-1-pentanol. The chiral core-shell composite (S)-DTP-COF@SiO2 exhibited good enantiomeric separation performance, which not only demonstrates its potential as a novel CSP material in HPLC but also expands the range of applications for chiral COFs.

Efficacy of agomelatine with cognitive behavioral therapy for delayed sleep-wake phase disorder in young adults: A randomized controlled study.

BACKGROUND: Delayed sleep-wake phase disorder (DSWPD) is common and easily misdiagnosed in young people, and to date, there is no evidence-based treatment. PURPOSE: A nonblinded randomized controlled study evaluated the effect of agomelatine therapy (AT) and cognitive behavior therapy (CBT) on DSWPD in young adults. METHODS: Sixty adolescents and young adults (range = 19-24 years, mean = 22 years, 52% female) diagnosed with DSWPD were randomized to receive 4 weeks of agomelatine therapy with or without cognitive behavior therapy. Sleep diaries, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and World Health Organization wellbeing questionnaire (WHO-5) were measured pre-treatment and post-treatment. RESULTS: Agomelatine therapy for 4 weeks shifted the sleep-wake rhythm (p < .001) forward in both groups at the week 4 assessment. There were no significant differences in sleep onset (p = .099) and sleep offset (p = .959) between the CBT group and the no treatment (NT) group at the follow-up visits. However, significant differences were found in sleep duration (p = .002), sleep quality (p=0.005), sleep difficulties (p < .001), daytime sleepiness (p = .001), and wellbeing (p = .007) between groups. CONCLUSIONS: The improvements were received largely through the sleep-promoting effects of agomelatine therapy, and combining with cognitive behavior therapy on maintenance of altered sleep rhythms might be feasible.

In situ growth preparation of a new chiral covalent triazine framework core-shell microspheres used for HPLC enantioseparation.

The manufacturing of chiral covalent triazine framework core-shell microspheres CC-MP CCTF@SiO2 composite is reported as stationary phase for HPLC enantioseparation. The CC-MP CCTF@SiO2 core-shell microspheres were prepared by immobilizing chiral COF CC-MP CCTF constructed using cyanuric chloride and (S)-2-methylpiperazine on the surface of activated SiO2 through an in-situ growth approach. Various racemates as analytes were separated on the CC-MP CCTF@SiO2-packed column. The experimental results indicate that 19 pairs of enantiomers were well separated on the CC-MP CCTF@SiO2-packed column, including alcohols, phenols, amines, ketones, and organic acids. Among them, there are 17 pairs of enantiomers that can achieve baseline separation with good peak shapes. Their resolution values on this chiral column are between 0.4 and 5.61. The influences of analyte mass, column temperature, and composition of the mobile phase on the resolution of enantiomers were studied. In addition, the chiral resolution ability of CC-MP CCTF@SiO2-packed column was compared with the commercial chiral chromatographic columns (Chiralpak AD-H and Chiralcel OD-H columns) and some CCOF@SiO2 chiral columns (ß-CD-COF@SiO2, CTpBD@SiO2, and MDI-ß-CD-modified COF@SiO2). The CC-MP CCTF@SiO2-packed column exhibited some unique advantages and can complement these chiral columns in chiral separations. The research results show that the CC-MP CCTF@SiO2 chiral column offered high column efficiency (e.g., 17680 plates m-1 for ethyl mandelate), low column backpressure (5-9 bar), high enantioselectivity, and excellent chiral resolution ability for HPLC enantioseparation with good stability and reproducibility. The relative standard deviations (RSD) (n = 5) of the retention time, and peak areas by repeated separation of ethyl mandelate are 0.23% and 0.67%, respectively. It demonstrates that the CC-MP CCTF@SiO2 core-shell microsphere composite has great potential in enantiomeric separation by HPLC.

Phylogenetic Analysis and Serological Investigation of Porcine Circovirus Indicates Frequent Infection with Various Subtypes.

Porcine circoviruses (PCVs) are notorious for triggering severe diseases in pigs and causing serious economic losses to the swine industry. In the present study, we undertook a comprehensive approach for the investigation of PCV prevalence, including the phylogenetic analysis of obtained PCV sequences, the determination of major circulating genotypes and serological screening based on different recombinant Cap proteins with specific immunoreactivity. Epidemiological surveillance data indicate that PCV2d and PCV3a are widely distributed in Southwest China, while PCV4 has only sporadic circulation. Meanwhile, serological investigations showed high PCV2 antibody positivity in collected serum samples (>50%), followed by PCV4 (nearly 50%) and PCV3 (30-35%). The analysis supports different circulation patterns of PCV2, PCV3 and PCV4 and illustrates the PCV2/PCV3 genetic evolution characteristics on a nationwide basis. Taken together, our findings add up to the current understanding of PCV epidemiology and provide new tools and insight for PCV antiviral intervention.

Chiral Covalent-Organic Framework MDI-ß-CD-Modified COF@SiO2 Core-Shell Composite for HPLC Enantioseparation.

The chiral covalent-organic framework (CCOF) is a new kind of chiral porous material, which has been broadly applied in many fields owing to its high porosity, regular pores, and structural adjustability. However, conventional CCOF particles have the characteristics of irregular morphology and inhomogeneous particle size distribution, which lead to difficulties in fabricating chromatographic columns and high column backpressure when the pure CCOFs particles are directly used as the HPLC stationary phases. Herein, we used an in situ growth strategy to prepare core-shell composite by immobilizing MDI-ß-CD-modified COF on the surface of SiO2-NH2. The synthesized MDI-ß-CD-modified COF@SiO2 was utilized as a novel chiral stationary phase (CSP) to explore its enantiomeric-separation performance in HPLC. The separation of racemates and positional isomers on MDI-ß-CD-modified COF@SiO2-packed column (column A) utilizing n-hexane/isopropanol as the mobile phase was investigated. The results demonstrated that column A displayed remarkable separation ability for racemic compounds and positional isomers with good reproducibility and stability. By comparing the MDI-ß-CD-modified COF@SiO2-packed column (column A) with commercial Chiralpak AD-H column and the previously reported ß-CD-COF@SiO2-packed column (column B), the chiral recognition ability of column A can be complementary to that of Chiralpak AD-H column and column B. The relative standard deviations (RSDs) of the retention time and peak area for the separation of 1,2-bis(4-fluorophenyl)-2-hydroxyethanone were 0.28% and 0.79%, respectively. Hence, the synthesis of CCOFs@SiO2 core-shell composites as the CSPs for chromatographic separation has significant research potential and application prospects.

Extracellular vesicles from bone marrow stromal cells reduce the impact of stroke on glial cell activation and blood brain-barrier permeability via a putative miR-124/PRX1 signalling pathway.

Ischaemic stroke (IS) is a cerebrovascular disease caused by cerebral infarction and cerebral artery occlusion. In this study, we proposed that EVs from bone marrow stromal cells (BMSCs) could reduce the impact of stroke by reducing the resultant glial cell activation and blood-brain barrier (BBB) leak. We furthermore investigated some of the signalling mechanisms. The transient middle cerebral artery occlusion (t-MCAO) mouse model was established. The behavioural deficits and neuronal damage were verified using Bederson's scale and the 28-point neurological score. The area of cerebral infarction was detected. The expressions of astrocytes/microglia markers and BBB permeability were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. The internalization of EVs by astrocytes/microglia in the peripheral area was detected by fluorescence labelling. The expressions of astrocyte/microglia markers were measured by RT-qPCR. Levels of TNF-α and IL-1ß in microglia were detected by ELISA. BBB permeability was evaluated. The downstream target genes and pathway of miR-124 were analysed. Microglia/astrocytes were treated by oxygen-glucose deprivation reoxygenation (OGD/R). OGD/R microglia/astrocyte conditioned medium was used to culture bEnd.3 cells. The transendothelial electric resistance (TEER) of bEnd.3 cells was measured, and BBB permeability was characterized. Our results suggested that EVs from BMSCs can indeed reduce the extent of stroke-mediated damage and evidenced that these effects are mediated via expression of the non-coding RNA, miR-124 that may act via the peroxiredoxin 1 (PRX1). Our results provided further motivation to pursue the use of modified EVs as a treatment option for neurological diseases.

The methyltransferase METTL3 promotes tumorigenesis via mediating HHLA2 mRNA m6A modification in human renal cell carcinoma.

BACKGROUND: As an important N6-methyladenosine (m6A) regulator, abnormal expression of methyltransferase-like protein 3 (METTL3) has been reported in certain human cancers. Although some data have shown that METTL3 plays an essential role in the progression of clear-cell renal cell carcinoma RCC (ccRCC), the detailed mechanism still remains largely undetermined. METHODS: Immunohistochemistry (IHC) assay was used to examine the expression of METTL3 and its clinical implications in human ccRCC by using tissue-microarray (TMA). The cellular models based on ccRCC cell lines such as 786-O and ACHN, were established by operating METTL3 and HHLA2 via knockdown or overexpression, followed by in vitro cellular function studies and in vivo subcutaneous transplantation tumor model. RESULTS: We found that METTL3 expression in ccRCC tissues was significantly higher compared with adjacent normal tissues. We also found the overall survival (OS) of the patients with low METTL3 expression was significantly better compared with the patients with high METTL3 expression. Furthermore, HHLA2highMETTL3high could serve as a better prognostic predictor for ccRCC patients. Depletion of METTL3 could significantly inhibit the cell viability, migration, and invasion abilities in ccRCC cell lines. Cellular studies further revealed that METTL3 could regulate HHLA2 expression via m6A modification of HHLA2 mRNA. In vitro studies revealed that HHLA2 overexpression could reverse the inhibition of cellular functions mediated by METTL3 depletion. The subcutaneous transplantation tumor model confirmed that HHLA2 overexpression could reverse the inhibition of tumor growth mediated by METTL3 depletion. CONCLUSION: Our study indicated that METTL3 served as an important prognostic predictor for ccRCC patients, and we demonstrated a novel regulatory mechanism of HHLA2 by mRNA epigenetic modification via METTL3. Moreover, we found that the METTL3/HHLA2 axis could promote tumorigenesis of ccRCC. Collectively, our current findings provided new insights into the therapeutic strategy against this malignancy targeting METTL3.

Increased expression of METTL3 in pancreatic cancer tissues associates with poor survival of the patients.

BACKGROUND: Methyltransferase-like 3 (METTL3) expression could be found in various normal and cancerous tissues. As of now, the clinical significance of METTL3 expression in human pancreatic cancer (PC) tissues still remains to be understood. Our present study aims to investigate the prognostic value and clinical implications of METTL3 expression in PC tissues. METHODS: The TCGA, GTEx, and GEO public databases were used to study the mRNA expression level of the m6A family members and its relationship among PC tissues and normal pancreatic tissue. The immunohistochemistry was used to analyze the difference of METTL3 expression between cancer tissues and adjacent normal tissues. The prognostic value was evaluated by using the Log-rank survival analysis and Cox model analysis. PAAD samples from TCGA and GEO databases were used to perform the immune infiltration analysis and gene set enrichment analysis based on the genes that were highly correlated with METTL3. RESULTS: Based on the analysis of TCGA, GTEx, and GEO public database, we found that the m6A family members showed a higher correlation in PC tissues compared to normal pancreatic tissues, and the mRNA expression level of the m6A family members showed a significant difference between PC tissues and adjacent normal tissues. Moreover, scRNA-seq data indicated that METTL3 showed a higher expression level in malignant epithelial cells. Our immunohistochemistry results also confirmed that the intensity of METTL3 immunostaining in PC tissues was significantly higher than that in adjacent normal tissues (P = 0.015). The overall survival (OS) of PC patients with high expression of METTL3 protein were significantly poorer than those with low expression of METTL3 protein (HR = 1.788, 95% CI 1.071-2.984, P = 0.026). Further analysis of PC data from the database showed that METTL3 expression was associated with a variety of tumor-infiltrating immune cells and was involved in m6A modification and metabolism in PC tissues. CONCLUSION: Increased METTL3 expression at the protein level could be found in PC tissues, suggesting that the METTL3 expression was involved in the progression of PC and could serve as an important marker for prognostic prediction of this malignancy.

LncRNA Snhg8 attenuates microglial inflammation response and blood-brain barrier damage in ischemic stroke through regulating miR-425-5p mediated SIRT1/NF-κB signaling.

Increasing studies have indicated that abnormal expressed long noncoding RNAs (lncRNAs) play a vital role in ischemic stroke. Small nucleolar RNA host gene 8 (Snhg8), a member of lncRNAs, has been found to induce neuronal apoptosis in chronic cerebral ischemia models. Here, we aim to explore the function and molecular mechanism of Snhg8 in modulating microglial inflammation as well as brain microvascular endothelial cell (BMEC) damage following ischemic injury. Our data suggested that Snhg8 was low-expressed in the brain tissues of mice that underwent middle cerebral artery occlusion (MCAO) surgery and oxygen-glucose deprivation (OGD)-treated primary microglia and BMECs. Gain- or loss-of function approaches found that Snhg8 upregulation not only attenuated ischemic induced inflammatory response in microglia but also relieved BMECs injury both in vitro and in vivo. Furthermore, we conducted a bioinformatics analysis to explore the underlying mechanism of Snhg8. The results indicated that Snhg8 served as a competitive endogenous RNA by sponging miR-425-5p, which was proved to promote microglial inflammation and BMECs injury by targeting sirtuin1 (SIRT1)-mediated nuclear factor-κB (NF-κB) pathway. Overall, these results revealed that the Snhg8/miR-425-5p/SIRT1/NF-κB axis plays a critical role in the regulation of cerebral ischemia-induced microglial inflammation and brain-blood barrier damage.

Anxiety and depression and its correlates in patients with coronavirus disease 2019 in Wuhan.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) first broke-out in Wuhan China in December 2019, and spread throughout the entire country within a short time. This cross-sectional study investigated the prevalence of depression and anxiety and associated risk factors were analysed in patients with COVID-19. METHODS: This single-center cross-sectional study focussed on measuring depression and anxiety using self-report scales. Linear regression was used to determine independent predictors for depression and anxiety. RESULTS: A total of 78 patients who were confirmed to have COVID-19 were enrolled in the study. Prevalence of depression and anxiety symptoms were diagnosed in 35.9% and 38.5% of the patients, respectively. Multivariate linear regression analysis found female gender was an independent predictor for higher depression severity index. Having family members who were diagnosed with COVID-19 and family members who died from COVID-19 were independently associated with higher depression severity index and anxiety score. CONCLUSIONS: Patients with COVID-19 especially those who had family members diagnosed with COVID-19 or died from COVID-19 were more susceptible to depression and anxiety than were other patients. Effective strategies should be pursued to improve the mental health of this patient population.Key pointsPatients with COVID-19 showed a significantly high prevalence of depression and anxiety.Female patients were associated with higher risk of depression.Patients with family members diagnosed as COVID-19 or died from this disease were associated with higher risk of depression and anxiety.

N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine attenuates oxygen-glucose deprivation and reoxygenation-induced cerebral ischemia-reperfusion injury via regulation of microRNAs.

Cerebral ischemia-reperfusion injury is a common complication that occurs during stroke treatment. Increasingly, microRNAs have been found to participate in the modulation of neuron function; however, the role of microRNAs in cerebral ischemia-reperfusion injury remains unclear. We developed a mechanism of cerebral ischemia-reperfusion injury using a cellular model of oxygen-glucose deprivation and reoxygenation-induced injury in human neuroblastoma SH-SY5Y cells. We found that treatment of oxygen-glucose deprivation and reoxygenation promoted the apoptosis of SH-SY5Y cells. Analysis of microRNAs sequencing revealed that the expression of microRNA-27a-5p was induced, and microRNA-29b-3p expression was inhibited in neuroblastoma cells exposed to oxygen-glucose deprivation and reoxygenation. Either inhibition of microRNA-27a-5p or overexpression of microRNA-29b-3p mitigated oxygen-glucose deprivation and reoxygenation-induced cellular apoptosis. Bach1 was authenticated as a target gene of microRNA-27a-5p. Also, microRNA-27a-5p mediated the expression of Bach 1 along with its downstream signaling. N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protected against oxygen-glucose deprivation and reoxygenation-induced apoptosis while decreasing miR-27a-5p expression and increasing microRNA-29b-3p expression. These results suggested that microRNA-27a-5p and microRNA-29b-3p may contribute to oxygen-glucose deprivation and reoxygenation-induced cellular injury. At the same time, N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine protects SH-SY5Y cells against oxygen-glucose deprivation and reoxygenation-induced injury partly through the inhibition of microRNA-27-a-5p and promotion of the Bach1/HO-1 signaling pathway.

Long non-coding RNA MALAT1 regulates angiogenesis following oxygen-glucose deprivation/reoxygenation.

Long non-coding RNAs (lncRNAs) have been identified as playing critical roles in multiple diseases. However, little is known regarding their roles and mechanisms in post-stroke angiogenesis. Our studies focused on deciphering the functional roles and the underlying mechanisms of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the process of angiogenesis following oxygen-glucose deprivation/reoxygenation (OGD/R). We characterized the up-regulation of MALAT1 expression in the process of angiogenesis after hypoxic injury in vivo and in vitro. We further showed that compared with the empty vector, MALAT1 knockdown had significantly reduced the capacity for angiogenesis, which was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT), scratching, cell cycle and immunofluorescent staining. Thus, our findings suggest that MALAT1 may mediate proangiogenic function in OGD/R. To further explore the potential mechanisms, we used lentiviruses expressing shMALAT1 and empty vector; the results revealed that shMALAT1 reduced the expression of 15-lipoxygenase 1 (15-LOX1), vascular endothelial growth factor (VEGF) and the phosphorylation of signal transducers and activators of transcription 3 (pSTAT3). Taken together, our results are the first to propose that MALAT1 may regulate angiogenesis through the 15-LOX1/STAT3 signalling pathway, and they may provide a critical target for the treatment of hypoxic injury and an avenue for therapeutic angiogenesis.

The Proangiogenic Roles of Long NonCoding RNAs Revealed by RNA-Sequencing Following Oxygen-Glucose Deprivation/Re-Oxygenation.

BACKGROUND/AIMS: With advances in RNA-sequencing (RNA-seq), exploring the expression and transcripts of different classes of genes are now possible. Our purpose was to analyse to the long non-coding RNAs (lncRNAs) in mouse brain microvascular endothelial cells (bEnd.3) after oxygen-glucose deprivation/re-oxygenation (OGD/R). METHODS: RNA-seq was employed to explore the expression of lncRNAs, and quantitative real-time PCR (qRT-PCR) was used to identify the results of RNA-seq. Furthermore, the biological functions of the lncRNAs were identified by cell viability, wound healing, transwell, tube formation and immunofluorescent staining assays. Finally, the molecular mechanisms involving the differentially expressed lncRNAs were further explored by bioinformatics and Western blotting (WB). RESULTS: In total, 2710 lncRNAs were found, 33 of which were significantly differentially expressed, with 18 upregulated lncRNAs and 15 downregulated lncRNAs in brain microvascular endothelial cells following OGD/R. Among the dysregulated genes, G protein-coupled receptor 137b-pseudogene (Gpr137b-ps), predicted gene 32856 (Gm32856), small nucleolar RNA host gene 17 (snhg17), chaperonin containing Tcp1 and subunit 6a (Cct6a) were significantly upregulated lncRNAs; this finding was further validated using qRT-PCR. Moreover, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes (KEGG) pathway analyses were employed to decipher the potential target genes and signaling pathways of the differentially expressed lncRNAs. Finally, we selected pseudogene-expressed lncRNA Gpr137b-ps as a candidate gene, and report for the first time that pseudogenes can mediate angiogenesis and their potential target genes, namely, 15-lipoxygenase1 (15-LOX1), Signal Transducer and Activator of Transcription 3 (S TAT3) and vascular endothelial growth factor (VEGF). CONCLUSION: Therefore, our study revealed that Gpr137b-ps plays critical roles in the process of angiogenesis, suggesting avenues for the development of future therapeutic strategies that contribute to promoting angiogenesis following I/R.

D Rhamnose ß-hederin inhibits migration and invasion of human breast cancer cell line MDA-MB-231.

Many natural products have been shown to have inhibitory effects on the metastatic process of various cancers including breast cancer. An active triterpenoid saponin D Rhamnose ß-hederin (DRß-H) from Clematis ganpiniana, has been known induce the apoptosis of breast cancer cells, but the effect of DRß-H on the metastasis of breast cancer cells is largely unknown. In this study, we demonstrated that a non-cytotoxic concentration of DRß-H markedly suppressed wound healing migration, migration through the chamber and invasion through the matrigel. In addition, DRß-H regulated expression of RNPC1, E-cadherin proteins of MDA-MB-231 cells. Furthermore, RNPC1 knockdown decreased the DRß-H-induced up-regulation of RNPC1 and E-Cadherin in MDA-MB-231 cells. RNPC1 knockdown reduced the anti-metastasis activities of DRß-H, meaning that the up-rugulation of RNPC1 by DRß-H is essential for its anti-metastatis activities. These results suggest that DRß-H might be a potential therapeutic candidate for the treatment of breast cancer metastasis.

Discovery of Metabolite Biomarkers for Acute Ischemic Stroke Progression.

Stroke remains a major public health problem worldwide; it causes severe disability and is associated with high mortality rates. However, early diagnosis of stroke is difficult, and no reliable biomarkers are currently established. In this study, mass-spectrometry-based metabolomics was utilized to characterize the metabolic features of the serum of patients with acute ischemic stroke (AIS) to identify novel sensitive biomarkers for diagnosis and progression. First, global metabolic profiling was performed on a training set of 80 human serum samples (40 cases and 40 controls). The metabolic profiling identified significant alterations in a series of 26 metabolites with related metabolic pathways involving amino acid, fatty acid, phospholipid, and choline metabolism. Subsequently, multiple algorithms were run on a test set consisting of 49 serum samples (26 cases and 23 controls) to develop different classifiers for verifying and evaluating potential biomarkers. Finally, a panel of five differential metabolites, including serine, isoleucine, betaine, PC(5:0/5:0), and LysoPE(18:2), exhibited potential to differentiate AIS samples from healthy control samples, with area under the receiver operating characteristic curve values of 0.988 and 0.971 in the training and test sets, respectively. These findings provided insights for the development of new diagnostic tests and therapeutic approaches for AIS.

Effect of a comprehensive health education program on pre-hospital delay intentions in high-risk stroke population and caregivers.

OBJECTIVE: Many factors influence pre-hospital delays in the event of stroke. This study aimed to develop and evaluate a comprehensive educational program for decreasing pre-hospital delays in high-risk stroke population. METHODS: We enrolled 220 high-risk stroke population and caregivers from six urban communities in Harbin from May 2013 to May 2015, and randomly divided them into intervention and control groups. We implemented a comprehensive educational program (intervention group), comprising public lectures, instructional brochures, case videos, simulations, and role-playing from May 2013 to May 2015. We delivered conventional oral education in the control group. We compared stroke pre-hospital delay behavioral intention (SPDBI), pre-hospital stroke symptom coping test (PSSCT), and stroke pre-symptoms alert test (SPSAT) results between the groups before and 6, 12, and 18 months after health intervention. RESULTS: There were significant differences between before and after intervention (P < 0.01). SPDBI, PSSCT, and SPSAT scores were significantly different between the groups (P < 0.01). The interaction between time and intervention method was significant (P < 0.01). According to multivariate repeated measures analysis of variance, SPDBI, PSSCT, and SPSAT scores were significantly different at each time after intervention (P < 0.05). CONCLUSION: The comprehensive educational program was significantly effective in decreasing SPDBI, improving knowledge, enhancing stroke pre-symptoms alert, and reducing the possibility of pre-hospital delays.

Wnt/ß-catenin signalling pathway mediated aberrant hippocampal neurogenesis in kainic acid-induced epilepsy.

Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis with massive neuronal loss and severe gliosis. Aberrant neurogenesis has been shown in the epileptogenesis process of temporal lobe epilepsy. However, the molecular mechanisms underlying aberrant neurogenesis remain unclear. The roles of Wnt signalling cascade have been well established in neurogenesis during multiple aspects. Here, we used kainic acid-induced rat epilepsy model to investigate whether Wnt/ß-catenin signalling pathway is involved in the aberrant neurogenesis in temporal lobe epilepsy. Immunostaining and western blotting results showed that the expression levels of ß-catenin, Wnt3a, and cyclin D1, the key regulators in Wnt signalling pathway, were up-regulated during acute epilepsy induced by the injection of kainic acids, indicating that Wnt signalling pathway was activated in kainic acid-induced temporal lobe epilepsy. Moreover, BrdU labelling results showed that blockade of the Wnt signalling by knocking down ß-catenin attenuated aberrant neurogenesis induced by kainic acids injection. Altogether, Wnt/ß-catenin signalling pathway mediated hippocampal neurogenesis during epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy. Temporal lobe epilepsy is a chronic disorder of nerve system, mainly characterized by hippocampal sclerosis. Aberrant neurogenesis has been shown to involve in the epileptogenesis process of temporal lobe epilepsy. In the present study, we discovered that Wnt3a/ß-catenin signalling pathway serves as a link between aberrant neurogenesis and underlying remodelling in the hippocampus, leading to temporal lobe epilepsy, which might provide new strategies for clinical treatment of temporal lobe epilepsy.