Association between clustering of cardiovascular risk factors and resting heart rate in Chinese population: a cross-sectional study.

BACKGROUND: Epidemiologic studies have explored the association between a single cardiovascular risk factor (CVRF) and resting heart rate (RHR), but the research on the relation of multiple risk factors with RHR remains scarce. This study aimed to explore the associations between CVRFs clustering and the risk of elevated RHR. METHODS: In this cross-sectional study, adults aged 35-75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August 2020. We focused on seven risk factors: hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, alcohol use, and low physical activity. Multivariate logistic regression was used to calculate odds ratios (OR) for elevated RHR (> 80 beats/min). RESULTS: Among 1,045,405 participants, the mean age was 55.67 ± 9.86 years, and 60.4% of participants were women. The OR (95% CI) for elevated RHR for the groups with 1, 2, 3, 4 and ≥ 5 risk factor were 1.11 (1.08-1.13), 1.36 (1.33-1.39), 1.68 (1.64-1.72), 2.01 (1.96-2.07) and 2.58 (2.50-2.67), respectively (P trend < 0.001). The association between the CVRFs clustering number and elevated RHR was much more pronounced in young males than in other age-sex subgroups. Clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk factors. CONCLUSIONS: There was a significant positive association between the CVRFs clustering number and the risk of elevated RHR, particularly in young males. Compared clusters comprising more behavioral risk factors, clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR. RHR may serve as an indicator of the cumulative effect of multiple risk factors.

Production of indole and hydrogen sulfide by the oxygen-tolerant mutant strain Clostridium sp. Aeroto-AUH-JLC108 contributes to form a hypoxic microenvironment.

In this study, the oxygen-tolerant mutant strain Clostridium sp. Aeroto-AUH-JLC108 was found to produce indole when grown aerobically. The tnaA gene coding for tryptophanase responsible for the production of indole was cloned. The tnaA gene from Aeroto-AUH-JLC108 is 1677 bp and has one point mutation (C36G) compared to the original anaerobic strain AUH-JLC108. Phylogenetic analyses based on the amino acid sequence showed significant homology to that of TnaA from Flavonifractor. Furthermore, we found that the tnaA gene also exhibited cysteine desulfhydrase activity. The production of hydrogen sulfide (H2S) was accompanied by decrease in the amount of the dissolved oxygen in the culture medium. Similarly, the amount of indole produced by strain Aeroto-AUH-JLC108 obviously decreased the oxidation-reduction potential (ORP) in BHI liquid medium. The results demonstrated that production of indole and H2S helped to form a hypoxic microenvironment for strain Aeroto-AUH-JLC108 when grown aerobically.

Fermentation of soymilk by Lactobacillus acidipiscis isolated from Chinese stinky tofu capable of efficiently biotransforming isoflavone glucosides to dihydrodaidzein and dihydrogenistein.

BACKGROUND: The soy isoflavone microbial metabolites dihydrodaidzein (DHD), dihydrogenistein (DHG), equol and 5-hydroxy-equol are generally more biologically active than their precursors daidzein and genistein. Bacteria responsible for isoflavone metabolism have been isolated and identified. Fermented soymilk is a potential functional food; however, there are few lactic acid bacteria capable of metabolizing soy isoflavones. RESULTS: A newly isolated Gram-positive facultative anaerobic bacterium, which was named Lactobacillus acidipiscis HAU-FR7, was isolated from the traditional Chinese fermented soy product 'stinky tofu'. Bacterium strain HAU-FR7 can grow under aerobic conditions and can also convert most of the daidzin and genistin in soymilk into DHD and DHG, respectively. The concentrations of DHD and DHG produced were 183 and 134 µmol L-1 , respectively, after fermentation for 24 h. Strain HAU-FR7 does not produce the biogenic amines cadaverine, putrescine, histamine or tyramine, and an antibiotic susceptibility test showed that HAU-FR7 is sensitive to nine of the ten tested antibiotics, except for vancomycin. Moreover, the 1,1-diphenyl-2- picrylhydrazyl free radical scavenging capacity of soymilk fermented with HAU-FR7 was significantly higher than that of unfermented soymilk. CONCLUSION: A facultative anaerobic lactic acid bacterium, designated Lactobacillus acidipiscis HAU-FR7, is capable of reducing the soy isoflavone glucosides daidzin and genistin in soymilk to DHD and DHG efficiently, even in the presence of atmospheric oxygen. The biotransformation activity of HAU-FR7 grown in soymilk is higher than that in de Man-Rogosa-Sharpe liquid culture medium. © 2022 Society of Chemical Industry.

An Arabidopsis Retention and Splicing complex regulates root and embryo development through pre-mRNA splicing.

Pre-mRNA splicing is an important step in the posttranscriptional processing of transcripts and a key regulator of development. The heterotrimeric retention and splicing (RES) complex plays vital roles in the growth and development of yeast, zebrafish, and humans by mediating pre-mRNA splicing of multiple genes. However, whether the RES complex is conserved in plants and what specific functions it has remain unknown. In this study, we identified Arabidopsis (Arabidopsis thaliana) BUD13 (AtBUD13), GROWTH, DEVELOPMENT AND SPLICING 1 (GDS1), and DAWDLE (DDL) as the counterparts of the yeast RES complex subunits Bud site selection protein 13 (Bud13), U2 snRNP component Snu17 (Snu17), and Pre-mRNA leakage protein 1, respectively. Moreover, we showed that RES is an ancient complex evolutionarily conserved in eukaryotes. GDS1 directly interacts with both AtBUD13 and DDL in nuclear speckles. The BUD13 domain of AtBUD13 and the RNA recognition motif domain of GDS1 are necessary and sufficient for AtBUD13-GDS1 interaction. Mutants of AtBUD13, GDS1, and DDL failed to properly splice multiple genes involved in cell proliferation and showed defects in early embryogenesis and root development. In addition, we found that GDS1 and DDL interact, respectively, with the U2 small nuclear ribonucleoproteins auxiliary factor AtU2AF65B and the NineTeen Complex-related splicing factor SKIP, which are essential for early steps of spliceosome assembly and recognition of splice sites. Altogether, our work reveals that the Arabidopsis RES complex is important for root and early embryo development by modulating pre-mRNA splicing.

Meta-analysis of arterial anastomosis techniques in head and neck free tissue transfer.

The present meta-analysis aimed to investigate the differences in the incidence of thrombosis and vascular compromise in arterial anastomosis between microvascular anastomotic devices and hand-sewn techniques during free tissue transfer in the head and neck. We searched for articles in PubMed/Medline, CNKI, WANFANG DATA, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science, from January 1, 1962 till April 1, 2020 that reported data of microvascular anastomosis during free tissue transfer in the head and neck. The incidence of arterial thrombosis or vascular compromise, or both was the primary outcome. The secondary outcome was anastomotic time. We also assessed the sensitivity and the risk of bias. This meta-analysis included 583 arterial anastomoses from six studies. The group using microvascular anastomotic devices tended to have an increased incidence of arterial thrombosis and vascular compromise (risk ratio (RR), 3.42; P = 0.38; 95% confidence interval (CI), 0.91-12.77). The hand-sewn technique took significantly longer to perform the anastomosis compared with that of the microvascular anastomotic devices (weighted mean difference, 15.26 min; P<0.01; 95% CI, 14.65-15.87). Microvascular anastomotic devices might increase the risk of arterial thrombosis and vascular compromise compared with the hand-sewn technique; however, further randomized controlled trials are needed to provide a more accurate estimate. The application of microvascular anastomotic devices will help to reduce anastomotic surgery time and achieve acceptable vessel opening, benefiting from the developments of arterial couplers and microsurgical techniques.

Plant-Specific AtS40.4 Acts as a Negative Regulator in Abscisic Acid Signaling During Seed Germination and Seedling Growth in Arabidopsis.

Abscisic acid (ABA) is an important phytohormone regulating plant growth, development and stress responses. A multitude of key factors implicated in ABA signaling have been identified; however, the regulation network of these factors needs for further information. AtS40.4, a plant-specific DUF584 domain-containing protein, was identified previously as a senescence regulator in Arabidopsis. In this study, our finding showed that AtS40.4 was negatively involved in ABA signaling during seed germination and early seedling growth. AtS40.4 was highly expressed in seeds and seedlings, and the expression level was promoted by ABA. AtS40.4 was localized both in the nucleus and the cytoplasm. Moreover, the subcellular localization pattern of AtS40.4 was affected by ABA. The knockdown mutants of AtS40.4 exhibited an increased sensitivity to ABA, whereas the overexpression of AtS40.4 decreased the ABA response during seed germination and seedling growth of Arabidopsis. Furthermore, AtS40.4 was involved in ABRE-dependent ABA signaling and influenced the expression levels of ABA INSENTIVE (ABI)1-5 and SnRK2.6. Further genetic evidence demonstrated that AtS40.4 functioned upstream of ABI4. These findings support the notion that AtS40.4 is a novel negative regulator of the ABA response network during seed germination and early seedling growth.

Lychee seed polyphenol protects the blood-brain barrier through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy in bEnd.3 cells and APP/PS1 mice.

Blood-brain barrier (BBB) dysfunction has been implicated in Alzheimer's disease (AD) and is closely linked to the release of proinflammatory cytokines in brain capillary endothelial cells. We have previously reported that lychee seed polyphenols (LSP) exerted anti-neuroinflammatory effect. In this study, we aimed to explore the protective effect of LSP on BBB integrity. The monolayer permeability of bEnd.3 cells, and the mRNA level and protein expression of tight junction proteins (TJs), including Claudin 5, Occludin, and ZO-1, were examined. In addition, the inhibition of Aß(25-35)-induced NLRP3 inflammasome activation, and the autophagy induced by LSP were investigated by detecting the expression of NLRP3, caspase-1, ASC, LC3, AMPK, mTOR, and ULK1. Furthermore, the cognitive function and the expression of TJs, NLRP3, caspase-1, IL-1ß, and p62 were determined in APP/PS1 mice. The results showed that LSP significantly decreased the monolayer permeability and inhibited the NLRP3 inflammasome in Aß(25-35)-induced bEnd3 cells. In addition, LSP induced autophagy via the AMPK/mTOR/ULK1 pathway in bEnd.3 cells, and improved the spatial learning and memory function, increased the TJs expression, and inhibited the expression of NLRP3, caspase-1, IL-1ß, and p62 in APP/PS1 mice. Therefore, LSP protects BBB integrity in AD through inhibiting Aß(25-35)-induced NLRP3 inflammasome activation via the AMPK/mTOR/ULK1-mediated autophagy.

Polyphenols isolated from lychee seed inhibit Alzheimer's disease-associated Tau through improving insulin resistance via the IRS-1/PI3K/Akt/GSK-3ß pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Lychee seed, the seed of Litchi chinensis Sonn. is one of the commonly used in traditional Chinese medicine (TCM). It possesses many pharmacological effects such as blood glucose and lipid-lowering effects, liver protection, and antioxidation. Our preliminary studies have proven that an active fraction derived from lychee seed (LSF) can significantly decrease the blood glucose level, inhibit amyloid-ß (Aß) fibril formation and Tau hyperphosphorylation, and improve the cognitive function and behavior of Alzheimer's disease (AD) model rats. AIM OF THE STUDY: The aim of this study was to identify the main active components in LSF that can inhibit the hyperphosphorylation of Tau through improving insulin resistance (IR) in dexamethasone (DXM)-induced HepG2 and HT22 cells. MATERIALS AND METHODS: The isolation was guided by the bioactivity evaluation of the improvement effect of IR in HepG2 and HT22 cells. The mRNA and protein expressions of IRS-1, PI3K, Akt, GSK-3ß, and Tau were measured by RT-PCR, Western blotting, and immunofluorescence methods, respectively. RESULTS: After extraction, isolation, and elucidation using chromatography and spectrum technologies, three polyphenols including catechin, procyanidin A1 and procyanidin A2 were identified from fractions 3, 5, and 9 derived from LSF. These polyphenols inhibit hyperphosphorylated Tau via the up-regulation of IRS-1/PI3K/Akt and down-regulation of GSK-3ß. Molecular docking result further demonstrate that these polyphenols exhibit good binding property with insulin receptor. CONCLUSIONS: catechin, procyanidin A1, and procyanidin A2 are the main components in LSF that inhibit Tau hyperphosphorylation through improving IR via the IRS-1/PI3K/Akt/GSK-3ß pathway. Therefore, the findings in the current study provide novel insight into the anti-AD mechanism of the components in LSF derived from lychee seed, which is valuable for the further development of a novel drug or nutrient supplement for the prevention and treatment of AD.

Regulation of flowering transition by alternative splicing: the role of the U2 auxiliary factor.

Flowering transition is regulated by complex genetic networks in response to endogenous and environmental signals. Pre-mRNA splicing is an essential step for the post-transcriptional regulation of gene expression. Alternative splicing of key flowering genes has been investigated in detail over the past decade. However, few splicing factors have been identified as being involved in flowering transition. Human heterodimeric splicing factor U2 snRNP auxiliary factor (U2AF) consists of two subunits, U2AF35 and U2AF65, and functions in 3' splice site recognition in mRNA splicing. Recent studies reveal that Arabidopsis U2AF65a/b and U2AF35a/b play important roles in the splicing of key flowering genes. We summarize recent advances in research on splicing-regulated flowering transition by focusing on the role of Arabidopsis U2AF in the splicing of key flowering-related genes at ambient temperature and in the abscisic acid signaling pathways.

Architecture of Wheat Inflorescence: Insights from Rice.

The inflorescence architecture of grass crops affects the number of kernels and final grain yield. Great progress has been made in genetic analysis of rice inflorescence development in the past decades. However, the advances in wheat largely lag behind those in rice due to the repetitive and polyploid genomes of wheat. In view of the similar branching patterns and developmental characteristics between rice and wheat, the studies on inflorescence architecture in rice will facilitate related studies in wheat in the future. Here, we review the developmental regulation of inflorescences in rice and wheat and highlight several pathways that potentially regulate the inflorescence architecture of wheat.

AtBUD13 affects pre-mRNA splicing and is essential for embryo development in Arabidopsis.

Pre-mRNA splicing is an important step for gene expression regulation. Yeast Bud13p (bud-site selection protein 13) regulates the budding pattern and pre-mRNA splicing in yeast cells; however, no Bud13p homologs have been identified in plants. Here, we isolated two mutants that carry T-DNA insertions at the At1g31870 locus and shows early embryo lethality and seed abortion. At1g31870 encodes an Arabidopsis homolog of yeast Bud13p, AtBUD13. Although AtBUD13 homologs are widely distributed in eukaryotic organisms, phylogenetic analysis revealed that their protein domain organization is more complex in multicellular species. AtBUD13 is expressed throughout plant development including embryogenesis and AtBUD13 proteins is localized in the nucleus in Arabidopsis. RNA-seq analysis revealed that AtBUD13 mutation predominantly results in the intron retention, especially for shorter introns (≤100 bases). Within this group of genes, we identified 52 genes involved in embryogenesis, out of which 22 are involved in nucleic acid metabolism. Our results demonstrate that AtBUD13 plays critical roles in early embryo development by effecting pre-mRNA splicing.

AtU2AF65b functions in abscisic acid mediated flowering via regulating the precursor messenger RNA splicing of ABI5 and FLC in Arabidopsis.

In mammalians and yeast, the splicing factor U2AF65/Mud2p functions in precursor messenger RNA (pre-mRNA) processing. Arabidopsis AtU2AF65b encodes a putative U2AF65 but its specific functions in plants are unknown. This paper examines the function of AtU2AF65b as a negative regulator of flowering time in Arabidopsis. We investigated the expression and function of AtU2AF65b in abscisic acid (ABA)-regulated flowering as well as the transcript abundance and pre-mRNA splicing of flowering-related genes in the knock-out mutants of AtU2AF65b. The atu2af65b mutants show early-flowering phenotype under both long-day and short-day conditions. The transcript accumulation of the flowering repressor gene FLOWERING LOCUS C (FLC) is reduced in the shoot apex of atu2af65b, due to both increased intron retention and reduced transcription activation. Reduced transcription of FLC results, at least partially, from the abnormal splicing and reduced transcript abundance of ABSCISIC ACID-INSENSITIVE 5 (ABI5), which encodes an activator of FLC in ABA-regulated flowering signaling. Additionally, the expression of AtU2AF65b is promoted by ABA. Transition to flowering and splicing of FLC and ABI5 in the atu2af65b mutants are compromised during ABA-induced flowering. ABA-responsive AtU2AF65b functions in the pre-mRNA splicing of FLC and ABI5 in shoot apex, whereby AtU2AF65b is involved in ABA-mediated flowering transition in Arabidopsis.

RNA Splicing of FLC Modulates the Transition to Flowering.

Flowering is a critical stage of plant development and is closely correlated with seed production and crop yield. Flowering transition is regulated by complex genetic networks in response to endogenous and environmental signals. FLOWERING LOCUS C (FLC) is a central repressor in the flowering transition of Arabidopsis thaliana. The regulation of FLC expression is well studied at transcriptional and post-transcriptional levels. A subset of antisense transcripts from FLC locus, collectively termed cold-induced long antisense intragenic RNAs (COOLAIR), repress FLC expression under cold exposure. Recent studies have provided important insights into the alternative splicing of COOLAIR and FLC sense transcripts in response to developmental and environmental cues. Herein, at the 20th anniversary of FLC functional identification, we summarise new research advances in the alternative splicing of FLC sense and antisense transcripts that regulates flowering.

Polyphenols Derived from Lychee Seed Suppress Aß (1-42)-Induced Neuroinflammation.

Amyloid-ß (Aß) is commonly recognized as the most important factor that results in neuronal cell death and accelerates the progression of Alzheimer's disease (AD). Increasing evidence suggests that microglia activated by Aß release an amount of neurotoxic inflammatory cytokines that contribute to neuron death and aggravate AD pathology. In our previous studies, we found that lychee seed fraction (LSF), an active fraction derived from the lychee seed, could significantly improve the cognitive function of AD rats and inhibit Aß-induced neuroinflammation in vitro, and decrease neuronal injuries in vivo and in vitro. In the current study, we aimed to isolate and identify the specific components in LSF that were responsible for the anti-neuroinflammation effect using preparative high performance liquid chromatography (pre-HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) methods. To this end, we confirmed two polyphenols including catechin and procyanidin A2 that could improve the morphological status of BV-2 cells and suppress the release, mRNA levels, and protein expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) through downregulating the nuclear factor-κB (NF-κB) signaling pathway using ELISA, RT-PCR, and Western blotting methods. Furthermore, catechin and procyanidin A2 could inhibit Aß-induced apoptosis in BV-2 cells by upregulating Bcl-2 and downregulating Bax protein expression. Therefore, the current study illustrated the active substances in lychee seed, and first reported that catechin and procyanidin A2 could suppress neuroinflammation in Aß-induced BV-2 cells, which provides detailed insights into the molecular mechanism of catechin and procyanidin A2 in the neuroprotective effect, and their further validations of anti-neuroinflammation in vivo is also essential in future research.

1H Nuclear Magnetic Resonance Based Metabolomics Approach Reveals the Metabolic Mechanism of (-)-5-Hydroxy-equol against Hepatocellular Carcinoma Cells in Vitro.

1H nuclear magnetic resonance (NMR)-based metabolomics can rapidly detect metabolic shift under various stimulus; thus, it facilitated the dissection of the therapeutic mechanisms of compounds. (-)-5-Hydroxy-equol is an isoflavone metabolite that be obtained by microbial biotransformation. In the current work, the effect of (-)-5-hydroxy-equol on hepatocellular carcinoma (HCC) cells and its mechanism have been explored based on 1H NMR-based metabolomics approach. Our results revealed that (-)-5-hydroxy-equol can significantly inhibit the proliferation, migration, and invasion of SMMC-7721 cells and inhibit the proliferation of HepG2 cells. Metabolomics revealed that 17 differential metabolites involving in amino acid metabolism and energy metabolism were significantly changed inside and outside of the cells after treatment of (-)-5-hydroxy-equol. Specifically, (-)-5-hydroxy-equol at a concentration of 30 µM significantly decreased the concentrations of pyruvate, glutamate, and glucose. Because glycometabolism is a crucial feature of cancer-specific metabolism, we further verified enzymes and proteins that are closely relevant to glycometabolism. Our results indicated that (-)-5-hydroxy-equol-modulated glycolysis in HCC through the inhibition of activities of hexokinase, phosphofructokinase, and pyruvate kinase, and the expression of pyruvate kinase M2. This study revealed that metabolomic analysis integrating with further verifications at the biochemical level can facilitate understanding the anti-HCC mechanisms of (-)-5-hydroxy-equol.

Actin filaments regulate the adhesion between the plasma membrane and the cell wall of tobacco guard cells.

During the opening and closing of stomata, guard cells undergo rapid and reversible changes in their volume and shape, which affects the adhesion of the plasma membrane (PM) to the cell wall (CW). The dynamics of actin filaments in guard cells are involved in stomatal movement by regulating structural changes and intracellular signaling. However, it is unclear whether actin dynamics regulate the adhesion of the PM to the CW. In this study, we investigated the relationship between actin dynamics and PM-CW adhesion by the hyperosmotic-induced plasmolysis of tobacco guard cells. We found that actin filaments in guard cells were depolymerized during mannitol-induced plasmolysis. The inhibition of actin dynamics by treatment with latrunculin B or jasplakinolide and the disruption of the adhesion between the PM and the CW by treatment with RGDS peptide (Arg-Gly-Asp-Ser) enhanced guard cell plasmolysis. However, treatment with latrunculin B alleviated the RGDS peptide-induced plasmolysis and endocytosis. Our results reveal that the actin depolymerization is involved in the regulation of the PW-CW adhesion during hyperosmotic-induced plasmolysis in tobacco guard cells.

Isolation and Characterization of a Human Intestinal Bacterium Eggerthella sp. AUH-JLD49s for the Conversion of (-)-3'-Desmethylarctigenin.

Arctiin is the most abundant bioactive compound contained in the Arctium lappa plant. In our previous study, we isolated one single bacterium capable of bioconverting arctigenin, an aglycone of arctiin, to 3'-desmethylarctigenin (3'-DMAG) solely. However, to date, a specific bacterium capable of producing other arctiin metabolites has not been reported. In this study, we isolated one single bacterium, which we named Eggerthella sp. AUH-JLD49s, capable of bioconverting 3'-DMAG under anaerobic conditions. The metabolite of 3'-DMAG by strain AUH-JLD49s was identified as 3'-desmethyl-4'-dehydroxyarctigenin (DMDH-AG) based on electrospray ionization mass spectrometry (ESI-MS) and 1H and 13C nuclear magnetic resonance spectroscopy. The bioconversion kinetics and bioconversion capacity of strain AUH-JLD49s were investigated. In addition, the metabolite DMDH-AG showed an inhibitory effect on cell growth of human colon cancer cell line HCT116 and human breast cancer cell line MDA-MB-231.

[Expressions of glutathione S-transferase P1 and 4- hydroxynonenal and the progression of prostate cancer].

OBJECTIVE: To investigate the expressions of glutathione S-transferase (GSTP1) and tetra-hydroxynonenal (4-HNE) in prostate cancer (PCa) and their clinical significance. METHODS: We determined the expressions of GSTP1 and 4-HNE in 40 patients with PCa and another 42 with benign prostatic hyperplasia (BPH) by immunohistochemistry and analyzed their relationship with Gleason grades. RESULTS: The expression rate of GSTP1 was 92.9% in the BPH tissue, and those in the highly, moderately, and lowly differentiated PCa tissues were 58.3%, 20.0%, and 16.7%, respectively, significantly higher in the BPH than in the PCa group (P <0.01). However, the positive rate of 4-HNE was only 5.0% in the BPH tissue, markedly lower than 91.6%, 100.0%, and 100.0% in the highly, moderately, and lowly differentiated PCa tissues (P <0.01). There was a negative correlation between the expression of GSTP1 and that of 4-HNE in the PCa tissue (r = －2.73, P <0.01). CONCLUSIONS: Expression deletion of GSTP1 and high expression of 4-HNE may play an important role in the progression of prostate cancer.

Lychee seed saponins improve cognitive function and ameliorate hippocampal neuronal injury in Alzheimer disease rat model induced by Aβ25-35 through AKT/GSK3β pathway / 中国药理学与毒理学杂志

OBJECTIVE Lychee seed, a famous traditional Chinese medicine, recently were reported to improve the learning and memory abilities in mice. However, it is still unclear whether lychee seed saponins (LSS) can improve the cognitive function and associated mechanisms. METHODS In present studies, we established the Alzheimer disease (AD) model by injecting Aβ25-35 into the lateral ventricle of rats. Then the spatial learning and memory abilities of LSS- treated rats were evaluated with the Morris water maze, meanwhile the protein expressions of AKT, GSK3β and Tau in the hippo?campal neuron were analyzed by immunohistochemistry and Western blotting. RESULTS The results showed LSS can improve the cognitive functions of AD rats through shortening the escape latency, increasing the number across the platform, platform quadrant dwell time and the percentage of the total distance run platform quadrant. The protein expression of AKT was significantly up-regulated and that of GSK3β and Tau were decreased remarkably in the hippocampal CA1 area. CONCLUSION Our study is the first to show that LSS significantly improve the cognitive function and prevent hippocampal neuronal injury of the rats with AD by activation of the PI3K/AKT/GSK3β signaling pathway, suggesting LSS may be developed into the nutrient supplement for the treatment of AD.

The effects of knockdown of rho-associated kinase 1 and zipper-interacting protein kinase on gene expression and function in cultured human arterial smooth muscle cells.

Rho-associated kinase (ROCK) and zipper-interacting protein kinase (ZIPK) have been implicated in diverse physiological functions. ROCK1 phosphorylates and activates ZIPK suggesting that at least some of these physiological functions may require both enzymes. To test the hypothesis that sequential activation of ROCK1 and ZIPK is commonly involved in regulatory pathways, we utilized siRNA to knock down ROCK1 and ZIPK in cultured human arterial smooth muscle cells (SMC). Microarray analysis using a whole-transcript expression chip identified changes in gene expression induced by ROCK1 and ZIPK knockdown. ROCK1 knockdown affected the expression of 553 genes, while ZIPK knockdown affected the expression of 390 genes. A high incidence of regulation of transcription regulator genes was observed in both knockdowns. Other affected groups included transporters, kinases, peptidases, transmembrane and G protein-coupled receptors, growth factors, phosphatases and ion channels. Only 76 differentially expressed genes were common to ROCK1 and ZIPK knockdown. Ingenuity Pathway Analysis identified five pathways shared between the two knockdowns. We focused on cytokine signaling pathways since ROCK1 knockdown up-regulated 5 and down-regulated 4 cytokine genes, in contrast to ZIPK knockdown, which affected the expression of only two cytokine genes (both down-regulated). IL-6 gene expression and secretion of IL-6 protein were up-regulated by ROCK1 knockdown, whereas ZIPK knockdown reduced IL-6 mRNA expression and IL-6 protein secretion and increased ROCK1 protein expression, suggesting that ROCK1 may inhibit IL-6 secretion. IL-1ß mRNA and protein levels were increased in response to ROCK1 knockdown. Differences in the effects of ROCK1 and ZIPK knockdown on cell cycle regulatory genes suggested that ROCK1 and ZIPK regulate the cell cycle by different mechanisms. ROCK1, but not ZIPK knockdown reduced the viability and inhibited proliferation of vascular SMC. We conclude that ROCK1 and ZIPK have diverse, but predominantly distinct regulatory functions in vascular SMC and that ROCK1-mediated activation of ZIPK is not involved in most of these functions.