Effect of task-oriented training assisted by force feedback hand rehabilitation robot on finger grasping function in stroke patients with hemiplegia: a randomised controlled trial.

BACKGROUND: Over 80% of patients with stroke experience finger grasping dysfunction, affecting independence in activities of daily living and quality of life. In routine training, task-oriented training is usually used for functional hand training, which may improve finger grasping performance after stroke, while augmented therapy may lead to a better treatment outcome. As a new technology-supported training, the hand rehabilitation robot provides opportunities to improve the therapeutic effect by increasing the training intensity. However, most hand rehabilitation robots commonly applied in clinics are based on a passive training mode and lack the sensory feedback function of fingers, which is not conducive to patients completing more accurate grasping movements. A force feedback hand rehabilitation robot can compensate for these defects. However, its clinical efficacy in patients with stroke remains unknown. This study aimed to investigate the effectiveness and added value of a force feedback hand rehabilitation robot combined with task-oriented training in stroke patients with hemiplegia. METHODS: In this single-blinded randomised controlled trial, 44 stroke patients with hemiplegia were randomly divided into experimental (n = 22) and control (n = 22) groups. Both groups received 40 min/day of conventional upper limb rehabilitation training. The experimental group received 20 min/day of task-oriented training assisted by a force feedback rehabilitation robot, and the control group received 20 min/day of task-oriented training assisted by therapists. Training was provided for 4 weeks, 5 times/week. The Fugl-Meyer motor function assessment of the hand part (FMA-Hand), Action Research Arm Test (ARAT), grip strength, Modified Ashworth scale (MAS), range of motion (ROM), Brunnstrom recovery stages of the hand (BRS-H), and Barthel index (BI) were used to evaluate the effect of two groups before and after treatment. RESULTS: Intra-group comparison: In both groups, the FMA-Hand, ARAT, grip strength, AROM, BRS-H, and BI scores after 4 weeks of treatment were significantly higher than those before treatment (p < 0.05), whereas there was no significant difference in finger flexor MAS scores before and after treatment (p > 0.05). Inter-group comparison: After 4 weeks of treatment, the experimental group's FMA-Hand total score, ARAT, grip strength, and AROM were significantly better than those of the control group (p < 0.05). However, there were no statistically significant differences in the scores of each sub-item of the FMA-Hand after Bonferroni correction (p > 0.007). In addition, there were no statistically significant differences in MAS, BRS-H, and BI scores (p > 0.05). CONCLUSION: Hand performance improved in patients with stroke after 4 weeks of task-oriented training. The use of a force feedback hand rehabilitation robot to support task-oriented training showed additional value over conventional task-oriented training in stroke patients with hand dysfunction. CLINICAL TRIAL REGISTRATION INFORMATION: NCT05841108.

FAT10 Silencing Prevents Liver Fibrosis through Regulating SIRT1 Expression in Hepatic Stellate Cells.

Background and objectives: Hepatic stellate cell (HSC) activation is the cardinal factor due to the accumulation of extracellular matrix proteins during the development of liver fibrosis. The aim of the present study was to find new targets for developing drugs to treat liver fibrosis, by screening the key genes involved in the activation of hepatic stellate cells. Methods: Differentially expressed genes were identified through TCGA database. RT-PCR, immunohistochemistry (IHC) assay, western blot, and ELISA were performed to evaluate the expression levels of FAT10 and fibrotic molecules. In vitro experiments were conducted to investigate the signaling pathways and biological functions of FAT10 in LX-2 cell lines. Results: In the present study, expression profiles obtained from the Gene Expression Omnibus (GEO) were used to explore the different genes expression between HSCs treated with or without carbon tetrachloride (CCl4). Human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10) was selected for further investigations. In animal model of carbon tetrachloride-induced liver fibrosis, the expression of FAT10 on activated HSCs is upregulated. In vitro, silencing FAT10 reduced TGF-ß1-induced ECM activation and accumulation in LX-2 cells, and also suppressed the inflammatory response of LX-2 cells. Further Transwell results suggested that knockdown of FAT10 could inhibit TGF-ß1-induced LX-2 cell migration and invasion. Mechanistically, FAT10 promotes its fibrotic activity through regulating sirtuin 1 (SIRT1), with a concomitant activation of ECM. Conclusions: These findings indicated an unexpected role of FAT10 in liver fibrosis development, suggesting that silencing FAT10 might represent a new strategy for the treatment of fibrotic liver diseases.

Electrophysiological Properties of Tetraploid Cardiomyocytes Derived from Murine Pluripotent Stem Cells Generated by Fusion of Adult Somatic Cells with Embryonic Stem Cells.

Most cardiomyocytes (CMs) in the adult mammalian heart are either binucleated or contain a single polyploid nucleus. Recent studies have shown that polyploidy in CMs plays an important role as an adaptive response to physiological demands and environmental stress and correlates with poor cardiac regenerative ability after injury. However, knowledge about the functional properties of polyploid CMs is limited. In this study, we generated tetraploid pluripotent stem cells (PSCs) by fusion of murine embryonic stem cells (ESCs) and somatic cells isolated from bone marrow or spleen and performed a comparative analysis of the electrophysiological properties of tetraploid fusion-derived PSCs and diploid ESC-derived CMs. Fusion-derived PSCs exhibited characteristics of genuine ESCs and contained a near-tetraploid genome. Ploidy features and marker expression were also retained during the differentiation of fusion-derived cells. Fusion-derived PSCs gave rise to CMs, which were similar to their diploid ESC counterparts in terms of their expression of typical cardiospecific markers, sarcomeric organization, action potential parameters, response to pharmacologic stimulation with various drugs, and expression of functional ion channels. These results suggest that the state of ploidy does not significantly affect the structural and electrophysiological properties of murine PSC-derived CMs. These results extend our knowledge of the functional properties of polyploid CMs and contribute to a better understanding of their biological role in the adult heart.

Aromatic Heterocycles as Productive Dienophiles in the Inverse Electron-Demand Diels-Alder Reactions of 1,3,5-Triazines.

Heterocycles are often found as the structural nucleus in natural products and biological active compounds. Consequently, research toward the discovery and development of novel and efficient synthetic methodologies is of constant interest to organic chemists. Diels-Alder reactions are powerful at forming multiple bonds simultaneously, often with stereoselectivity, and thus are one of the most widely used synthetic methodologies in organic syntheses. Inverse electron-demand Diels-Alder (IEDDA) reactions, a subclass of Diels-Alder reactions, have been developed for the efficient synthesis of various heterocycles, with 1,3,5-triazines used as azadienes. The initial 1,3,5-triazine IEDDA reactions mostly included nonaromatic, electron-rich species such as vinyl ethers, enamines, ynamines, and amidines as dienophiles, producing in high yields pyrimidine derivatives with excellent regioselectivity. We hypothesized that some electron-rich aromatic heterocycles could be studied as potential dienophiles for 1,3,5-triazine IEDDA reactions; 5-aminopyrazoles proved to be productive dienophiles leading to high yields of pyrazolopyrimidines. Subsequently, many studies were reported to investigate the mechanism and scope of this new type of IEDDA reaction. Mechanistically, this new type of IEDDA reaction is quite interesting since it entails two aromatic compounds proceeding through a perceived high energy nonaromatic transition state, leading to a new aromatic compound, a counterintuitive process. Both theoretical and experimental studies provide key insights to this reaction mechanism, with learnings from these studies possibly stimulating unconventional thinking in other areas. Theoretical calculations of these cascade reactions of amino-substituted heterocycles with 1,3,5-triazines indicate that the reactions occur in a stepwise fashion via a highly polar zwitterionic intermediate; elimination of ammonia from IEDDA adducts and subsequent retro Diels-Alder reaction drive the reaction toward the fully aromatized IEDDA products. This amino substituent is critical in determining the regioselectivity and driving the cascade reactions to completion. With regard to reaction scope, many amino-heterocycles such as pyrroles, imidazoles, furans, thiophenes, and indoles all proved to be productive dienophiles for this new IEDDA reaction, leading to various fused-pyrimidines in a single step with moderate to high yields and high regioselectivity. Application of this new IEDDA reaction with 1,3,5-triazines was reported to lead to interesting heterocyclic compounds such as nucleoside natural product nebularine and analogues, as well as fluorine-containing fused pyrimidines with potential for biological activities.Herein, the scope of various aromatic heterocycles as dienophiles in the 1,3,5-triazine IEDDA reaction is reviewed. Moreover, both experimental and theoretical studies of the mechanisms for this interesting cascade IEDDA reaction are discussed. Finally, applications of this new type (aromatic heterocycles as dienophiles with 1,3,5-triazines as azadienes) of IEDDA reaction are also covered.

Astragalin flavonoid inhibits proliferation in human lung carcinoma cells mediated via induction of caspase-dependent intrinsic pathway, ROS production, cell migration and invasion inhibition and targeting JAK/STAT signalling pathway.

The aim of the current study was to investigate the anti-lung cancer effects of astragalin. Studies were also undertaken to evaluate its effects on apoptosis induction, ROS production, cellular migration and invasion and JAK/STAT3 signalling pathway. MTT assay was used to evaluate cell viability in NSCLC A549 cells after exposure to astragalin molecule. Apoptosis was investigated using AO/EB staining, comet assay and western blotting assay. Fluorescence microscopy was implemented to estimate ROS production. Cell migration and invasion were measured using transwell chambers assay. Effects of astragalin on JAK/STAT pathway were investigated using western blotting assay. Results showed astragalin molecule induced inhibition of proliferation in A549 cells in a dose-dependent fashion. Further, the antiproliferative effects were found to mediate via apoptosis as suggested by AO/EB staining and western blotting assay. Astragalin modulated the expressions of caspase-3, caspase-9, Bax, Bak, Cyt-c Bcl-2, XIAP and Bcl-xL. Astragalin induced DNA damage in A549 cells which too indicated apoptotic cell death. Astragalin molecule enhanced the production of ROS by A549 cells. It inhibited both cell migration and invasion of A549 cells in a concentration-dependent manner. Finally, astragalin drug was observed with remarkable potential of targeting JAK/STAT pathway in A549 NSCLC cells. These results indicated that astragalin drug could prove helpful in lung cancer treatment and research provided more in-vivo studies are performed.

Effect of gastric cancer stem cell on gastric cancer invasion, migration and angiogenesis.

Purpose: Using the gastric cancer cell line SGC7901 and gastric cancer stem cell (CSC-G), we conducted this study to investigate the role of cancer stem cells in invasion, metastasis and tumor angiogenesis. Methods: Stem cell markers (OCT4, SOX2, C-Myc and Klf4) expression was detected by RT-PCR and Western blotting. The proliferation, migration, invasion abilities, L-OHP and 5-FU resistance, angiogenesis were assessed using in vitro spherical clone formation assays, plate cloning experiments, transwell migration, transwell invasion, drug resistance, scratch-wound migration, ring formation assay, and their tumorigenic and ability were assessed using a tumor formation experiment in mice. Results: Compared with the SGC7901, the expression of Oct4, Sox2, Klf4 and CD44 mRNA was significantly higher in CSC-G, the mRNA relative expression of E-cadherin in CSC-G was lower than SGC7901, while the expression of c-Myc did not significantly change. The proliferation, drug resistance, migration, and invasion abilities were significantly higher in CSC-G, and the tumorigenic ability in mice was also significantly higher. Conclusion: The proliferation, drug resistance, migration, invasion, and tumorigenic abilities of CSC-G significantly were higher than SGC7901. CSC-G plays important roles in proliferation, migration, invasion, and tumorigenicity.

Amantadine hydrochloride monitoring by dried plasma spot technique: High-performance liquid chromatography-tandem mass spectrometry based clinical assay.

Amantadine plasma concentrations correlate well with desired therapeutic effects and adverse outcomes; information on amantadine exposure could be useful when multiple amantadine clearance pathways are impaired or non-compliance is suspected. Micro-sampling strategies, like dried plasma spot, would be particularly useful because ambulatory patients that do not attend a clinic can easily sample a few drops of blood by themselves at the required time of the dosing interval. We developed and validated a dried-plasma-spot-based high performance liquid chromatography-tandem mass spectrometry assay to quantify amantadine. This assay met relevant validation requirements within a hematocrit range of 20-50% and was linear from 100 to 2000 ng/mL. Amantadine was stable in dried plasma spots for up to 21 days at room temperature, regardless of whether the dried plasma spot was protected from light or not. The correlation between paired dried and wet plasma concentrations was assessed in 52 patients. Deming regression coefficients between wet plasma and simultaneously pipetted dried plasma spots were used to predict plasma concentrations. Bland-Altman plots revealed a strong agreement between dried and wet plasma concentrations, supporting the clinical usefulness of dried plasma spots for amantadine monitoring with a self-sampling strategy at a convenient time and place for the patient.

Therapeutic effect against retinal neovascularization in a mouse model of oxygen-induced retinopathy: bone marrow-derived mesenchymal stem cells versus Conbercept.

BACKGROUND: To study the therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSC) against retinal neovascularization and to compare with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Neonatal C57BL/6 mice were exposed in hyperoxygen and returned to room air to develop oxygen-induced retinopathy (OIR). Red fluorescent protein-labeled BMSC and Conbercept were intravitreally injected into OIR mice, respectively. Inhibition of neovascularization and apoptosis in OIR mice were assessed through retinal angiography, histopathology and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: BMSC were able to migrate and integrate into the host retina, significantly inhibit retinal neovascular tufts and remodel the capillary network after injecton. Treatment with BMSC increased the retinal vascular density, decreased the number of acellular capillaries and inhibited retinal cell death. This effect was not inferior to current anti-VEGF therapy by using Conbercept. CONCLUSIONS: Intravitreal injection of BMSC exerts a protective effect against retinal neovascularization and offers a therapeutic strategy for oxygen-induced retinopathy.

miR-487a performs oncogenic functions in osteosarcoma by targeting BTG2 mRNA.

Aberrant microRNA (miRNA) expression plays a critical role in osteosarcoma (OS) pathogenesis. In this study, we elucidated the involvement of miR-487a in OS and the underlying molecular mechanisms. We found that miR-487a was upregulated in OS clinical samples and cell lines. Knockdown of miR-487a suppressed OS cell growth and invasion and induced apoptosis; however, overexpression of miR-487a promoted OS cell growth and invasion. Accordingly, downregulation of miR-487a significantly suppressed tumor growth of OS xenografts in vivo. Furthermore, B-cell translocation gene 2 (BTG2) mRNA was found to be a novel target of miR-487a. Knockdown of BTG2 using small interfering RNA (siRNA) recapitulated the oncogenic effects of miR-487a, whereas BTG2 overexpression partially reversed these effects. Finally, miR-487a levels were found to be negatively correlated with BTG2 expression in OS clinical samples. Collectively, our data suggest that miR-487a is an oncogenic miRNA in OS and it lowers BTG2 expression.

Leukemia inhibitory factor inhibits the proliferation of gastric cancer by inducing G1-phase arrest.

Leukemia inhibitory factor (LIF), a member of the interleukin-6 cytokine family, plays a complex role in cancer. LIF inhibits the proliferation and survival of several myeloid leukemia cells but promotes tumor progression and metastasis in many solid tumors. However, the relationship between LIF and gastric cancer has not been well understood. LIF was downregulated in gastric cancer as detected by western blot analysis and immunohistochemistry (IHC). Notably, LIF was downregulated in approximately 70% (56/80) of primary gastric cancers, in which it was significantly associated with advanced clinical stage, lymph node metastasis, and poor overall survival (median 5-year survival = 26 vs. 43 months for patients with high LIF expression and low LIF expression gastric cancer, respectively). To study the potential function of LIF in the downregulation of gastric cancer, we monitored the behavior using proliferation, cell cycle, and flow cytometry analysis. Overexpression of LIF inhibited the gastric cancer cell cycle in the G1 phase. In our experiment, overexpression of LIF by lentivirus upregulated P21 and downregulated cyclin D1. Recombinant human LIF also downregulated P21 and cyclin D1 at various times. A further in vivo tumor formation study in nude mice indicated that overexpression of LIF in gastric cancer significantly delayed the progress of tumor formation. These findings indicate that LIF may serve as a negative regulator of gastric cancer.

Prognostic value of ZEB-1 in solid tumors: a meta-analysis.

BACKGROUND: Zinc-finger E-box binding homeobox 1 (ZEB-1) plays crucial roles in epithelial-to-mesenchymal transition during tumor carcinogenesis. Published studies have examined the potential value of ZEB-1 as a biomarker for the prognosis of cancer. Nevertheless, the prognostic significance of ZEB-1 in human solid tumor remains inconclusive. Therefore, we performed the present meta-analysis to evaluate the prognostic value of ZEB-1 in patients with solid tumors. METHODS: The 13 included studies (1616 patients) were exact electronic searched from Web of Science, PubMed and EBSCO until September 2018. Pooled hazard ratios (HR) and the corresponding 95% confidence intervals (CI) for overall survival (OS) were analyzed through random or fixed effects models. Univariate and multivariate analyses were independently performed. Subgroup analyses, heterogeneity and publication bias were investigated to further enhance reliability. RESULTS: This research indicated that elevated expression of ZEB-1 significantly predicted worse OS in patients with solid tumors. In the univariate analysis, the pooled HR for OS was 1.66 (95% CI: 1.45-1.90; P < 0.01). Meanwhile, in multivariate analysis, the pooled HR for OS was 2.28 (95% CI: 1.58-3.30; P < 0.01). Begg's funnel plot and Begg's test did not show evidence of significant publication bias, both in univariate analysis and multivariate analysis. CONCLUSIONS: High expression of ZEB-1 was associated with poorer OS, suggesting that ZEB-1 may be a potential biomarker for the prediction of prognosis, and a novel therapeutic target in human solid tumors.

Therapeutic effect of gradual attention training on language function in patients with post-stroke aphasia: a pilot study.

OBJECTIVE: To investigate the effect of gradual attention training on language function with aphasia. DESIGN: Randomized controlled trial. PARTICIPANTS: A total of 40 patients (mean age: 53.47 years) with post-stroke aphasia came from the stroke rehabilitation unit of rehabilitation department in the First Hospital of Jilin University, of which 13 (32.5%) had intracerebral hemorrhage, 28 inpatients and 12 outpatients, 11 women and 29 men, 34 within three-month stroke and 6 within three months to one year. INTERVENTIONS: All participants were divided into control and experimental groups. Both groups received language treatment 20 minutes a day, six days/week, for five weeks, and the experimental group received gradual attention training 20 minutes a day, six days/week, for five weeks. MAIN MEASURES: Language function was assessed pre- and post-treatment by components of the Western Aphasia Battery (WAB) which included spontaneous speech, auditory comprehension, repetition, and naming and then calculated the aphasia quotient (AQ). RESULTS: The mean (SD) AQ of the experimental group and control group, respectively, was 25.71 (12.63) and 26.2 (12.31) at baseline. After treatment, the AQ mean (SD) was 43.08 (15.14) in the experimental group, which showed a significant improvement compared to 33.48 (14.04) in the control group (P = 0.02).All items of WAB were higher in experimental group than those in control group, especially in auditory comprehension and naming (P = 0.02, 0.01). CONCLUSION: Gradual attention training seemed to improve language function in post-stroke aphasia, specifically function of listening comprehension and naming.

Autophagy: A Role in the Apoptosis, Survival, Inflammation, and Development of the Retina.

Autophagy is a lysosomal degradation process that maintains cellular homeostasis by removing dysfunctional organelles and unfolded proteins. Increasing evidence has shown that autophagy proteins are involved in retinal physiology and pathology and that defective autophagy contributes to retinal degeneration. In retinal diseases, autophagy plays a dual role: promoting retinal cell survival and death. Autophagy at a normal level helps retinal cells defend themselves against harmful stress; however, excessive autophagy results in retinal deterioration. Both synergistic and antagonistic roles of autophagy and apoptosis in the retina have been reported in the literature. In this review, we summarize the roles of autophagy in the development of the retina and retinal diseases. This review highlights the importance of autophagy in retinal diseases, and targeting autophagy may provide a new therapeutic approach for retinal diseases.

Aptamer-Functionalized Magnetic Conjugated Organic Framework for Selective Extraction of Traces of Hydroxylated Polychlorinated Biphenyls in Human Serum.

A solid-phase extraction adsorbent based on an aptamer-functionalized magnetic conjugated organic framework (COF) was developed for selective extraction of traces of hydroxylated polychlorinated biphenyls. This material has advantages such as superparamagnetism of the magnetic core, high surface area and porous structure of the COF, and high specific affinity of the aptamer. In combination with HPLC-MS, the aptamer-functionalized magnetic COF was used for the capture of hydroxy-2',3',4',5,5'-pentachlorobiphenyl in human serum. The method provided a linear range of 0.01-40 ng mL-1 with a good correlation coefficient (R2 =0.9973). The limit of detection was as low as 2.1 pg mL-1 . Furthermore, the material showed good reusability and could be applied in at least ten extraction cycles with recoveries greater than 90 %.

Safety and efficacy of transpupillary silicone oil removal in combination with micro-incision phacoemulsification cataract surgery: comparison with 23-gauge approach.

BACKGROUND: To evaluate safety and efficacy of transpupillary silicone oil removal combined with micro-incision phacoemulsification cataract surgery, and to compare results of transpupillary with 23-gauge three-port vitrectomy approach. METHODS: Consecutive cases that underwent silicone oil removal using either transpupillary or three-port approach in combination with micro-incision phacoemulsification cataract surgery were retrospectively reviewed. The main outcome measures were postoperative detachment rate, silicone oil residuals, best corrected visual acuity (BCVA) and intraocular pressure (IOP). RESULTS: A total of 64 cases were included, 19 in transpupillary and 45 in three-port. Postoperative detachment rate within 3 months in transpupillary versus three-port was 15.8% versus 4.4% (p = 0.14), Silicone oil residuals was 7.4 ± 3.2% versus 7.1 ± 2.8% (transpupillary vs. three-port, p = 0.71). Preoperative versus postoperative BCVA (logMAR) was 1.49 ± 0.61 versus 1.42 ± 0.61 in transpupillary approach (p = 0.28) and 1.53 ± 0.48 versus 1.45 ± 0.57 in three-port approach (p = 0.11). Transpupillary approach resulted in lower IOP at postoperative day 2 (12.2 ± 2.3 mmHg vs. 13.5 ± 2.2 mmHg, p < 0.05), while postoperative follow-up at 1 month revealed no significant difference (p = 0.21). CONCLUSIONS: Transpupillary silicone oil removal combined with micro-incision phacoemulsification cataract surgery is less invasive and can be an alternative in some circumstances.

Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells.

BACKGROUND/AIMS: This study investigated the effect of mechanical stress on tendon-bone healing in a rabbit anterior cruciate ligament (ACL) reconstruction model as well as cell proliferation and matrix formation in co-culture of bone-marrow mesenchymal stem cells (BMSCs) and tendon cells (TCs). METHODS: The effect of continuous passive motion (CPM) therapy on tendon-bone healing in a rabbit ACL reconstruction model was evaluated by histological analysis, biomechanical testing and gene expressions at the tendon-bone interface. Furthermore, the effect of mechanical stretch on cell proliferation and matrix synthesis in BMSC/TC co-culture was also examined. RESULTS: Postoperative CPM therapy significantly enhanced tendon-bone healing, as evidenced by increased amount of fibrocartilage, elevated ultimate load to failure levels, and up-regulated gene expressions of Collagen I, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin at the tendon-bone junction. In addition, BMSC/TC co-culture treated with mechanical stretch showed a higher rate of cell proliferation and enhanced expressions of Collagen I, Collagen III, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin than that of controls. CONCLUSION: These results demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of BMSCs and TCs in tendon-bone healing.

Design of a ruthenium(III) immobilized affinity material based on a ß-cyclodextrin-functionalized poly(glycidyl methacrylate-ethylene dimethacrylate) monolith for the enrichment of hippuric acid.

Immobilized metal affinity chromatography has drawn great attention as a widespread separation and purification approach. In this work, ruthenium was firstly introduced into the preparation of immobilized metal affinity chromatography considering its affinity to N,O-donor ligands. A ß-cyclodextrin-functionalized poly(glycidyl methacrylate-ethylene dimethacrylate) monolith was designed and employed as the supporting material in immobilized metal affinity chromatography. Thiosemicarbazide was introduced into the synthesis process, which not only acted as a bridge between ß-cyclodextrin and glycidyl methacrylate, but also chelated with ruthenium because of its mixed hard-soft donor characteristics. The developed monolithic ruthenium(III)-immobilized metal affinity chromatography column was utilized for the adsorption and separation of hippuric acid, a biological indicator of toluene exposure. To achieve high extraction capacity, the parameters affecting the extraction efficiency were investigated with an orthogonal experiment design, L9 (34 ). Under the optimized conditions, the enrichment factor of hippuric acid was 16.7-fold. The method reproducibility was investigated in terms of intra- and interday precisions with relative standard deviations lower than 8.7 and 9.5%, respectively. In addition, ruthenium(III)-immobilized metal affinity chromatography material could be used for up to 80 extractions without an apparent change in extraction recovery.

Ligand-Controlled Regiodivergent and Enantioselective Copper-Catalyzed Hydroallylation of Alkynes.

A ligand-controlled regiodivergent and enantioselective copper-catalyzed intermolecular hydroallylation of alkynes with allylic phosphates and hydrosilanes has been achieved for the first time. The chiral bidentate sulfonate-containing N-heterocyclic carbene ligated CuCl complex leads to enantioenriched SN 2'-type products, whereas the use of the IMesCuCl catalyst affords SN 2-type products. Thus a range of chiral branched and achiral linear 1,4-dienes could be facilely synthesized from readily available alkynes in a regiodivergent manner.

miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2.

miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non-neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy.

MiRNAs associated polymorphisms in the 3'UTR of MET promote the risk of non-small cell lung cancer.

BACKGROUND/AIMS: MET can act as an oncogene and its signaling server has essential roles in regulating tumorigenesis. Polymorphisms in MET have been reported to be associated with poor prognosis in human cancer, but an association with the risk of human non-small-cell lung cancer (NSCLC) has not been found so far. In this study rs41281081 and rs76322625, located in the 3'UTR of MET, were selected to evaluate their relationship with the risk of NSCLC among the Chinese population. METHODS: A questionnaire, SNaPshot genotype assay, real time PCR assay, cell transfection and the dual luciferase reporter assay were used. Single-nucleotide polymorphisms (SNPs) of rs41281081 and rs76322625 in the 3' untranslated region (UTR) of MET was involved as a risk factor in the occurrence of NSCLC. RESULTS: SNP rs41281081 could be regulated by miR-335 and rs76322625 could be regulated by miR-1026 to cause an up-regulation of MET in patients with NSCLC. Furthermore, the carriers of the GA and AA genotypes in rs41281081, and the CU and UU genotypes in rs76322625 presented with poor cell differentiation and large tumor size, as well as a high probability of metastasis. CONCLUSION: Our findings have shown that the SNPs rs41281081 and rs76322625 in MET 3'UTR, through disruption of the regulatory role of miR-335 and miR-1026 in MET expression, may act as promoting factors in the pathogenesis of NSCLC.