Interleukin-1ß-Induced Senescence Promotes Osteoblastic Transition of Vascular Smooth Muscle Cells.

INTRODUCTION: Interleukin (IL)-1ß, as a key biomarker and mediator of vascular calcification in patients with end-stage renal disease (ESRD), may be involved in the process of premature senescence of vascular smooth muscle cells (VSMCs). This work sought to investigate whether IL-1ß-induced premature senescence contributes to the process of osteoblastic transition and vascular calcification in VSMCs. METHODS: Eighty-eight patients with ESRD (aged 25-81 years), 11 healthy individuals, and 15 cases of lesion-free distal radial arteries from dialysis ESRD patients with angiostomy were collected in this study. Immunohistochemical analysis was performed to detect expression of IL-1ß, p21, and bone morphogenetic protein-2 (BMP2) in the distal radial arteries. Primary human VSMCs from healthy neonatal umbilical cords were incubated with test agents for 1-3 days. Intracellular levels of reactive oxygen species (ROS) and senescence-associated-ß-galactosidase (SA-ß-gal) staining were used to detect senescent cells. Alizarin red staining and the calcium content of the cell layer were used to detect mineral deposition in VSMCs. RESULTS: Coincident with positive staining of IL-1ß, p21, and BMP2 in the lesion-free distal radial arteries, 66.67% patients showed mineral deposition. Serum IL-1ß was 0.24 ± 0.57, 1.20 ± 2.95, and 9.41 ± 40.52 pg/mL in 11 healthy individuals, 20 patients without calcification, and 53 patients with calcification, respectively. Analysis of the cross-table chi-square test showed cardiovascular calcification is not correlated with levels of serum IL-1ß in patients with ESRD (p = 0.533). In response to IL-1ß, VSMCs showed a senescence-like phenotype, such as flat and enlarged morphology, increased expression of p21, an increased activity of SA-ß-gal, and increased levels of ROS. IL-1ß-induced senescence of VSMCs was required for the activation of IL-1ß/NF-κB/p53/p21 signaling pathway. IL-1ß-induced senescent VSMCs underwent calcification due to osteoblastic transition mainly depending upon the upregulation of BMP2. Resveratrol, an activator of sirtuin-1, postponed the IL-1ß-induced senescence through blocking the NF-κB/p53/p21 pathway and attenuated the osteoblastic transition and calcification in VSMCs. CONCLUSIONS: High levels of IL-1ß in medial smooth muscles of arteries may play roles in inducing senescence-associated calcification. IL-1ß-induced senescence depending on the activation of the NF-κB/p53/p21 signaling pathway and contributing to osteoblastic transition of VSMCs.

Morphogenic Regulators Baby boom and Wuschel Improve Monocot Transformation.

While transformation of the major monocot crops is currently possible, the process typically remains confined to one or two genotypes per species, often with poor agronomics, and efficiencies that place these methods beyond the reach of most academic laboratories. Here, we report a transformation approach involving overexpression of the maize (Zea mays) Baby boom (Bbm) and maize Wuschel2 (Wus2) genes, which produced high transformation frequencies in numerous previously nontransformable maize inbred lines. For example, the Pioneer inbred PHH5G is recalcitrant to biolistic and Agrobacterium tumefaciens transformation. However, when Bbm and Wus2 were expressed, transgenic calli were recovered from over 40% of the starting explants, with most producing healthy, fertile plants. Another limitation for many monocots is the intensive labor and greenhouse space required to supply immature embryos for transformation. This problem could be alleviated using alternative target tissues that could be supplied consistently with automated preparation. As a major step toward this objective, we transformed Bbm and Wus2 directly into either embryo slices from mature seed or leaf segments from seedlings in a variety of Pioneer inbred lines, routinely recovering healthy, fertile T0 plants. Finally, we demonstrated that the maize Bbm and Wus2 genes stimulate transformation in sorghum (Sorghum bicolor) immature embryos, sugarcane (Saccharum officinarum) callus, and indica rice (Oryza sativa ssp indica) callus.

Amino-Modified Graphene Oxide from Kish Graphite for Enhancing Corrosion Resistance of Waterborne Epoxy Coatings.

Waterborne epoxy (WEP) coatings with enhanced corrosion resistance were prepared using graphene oxide (GO) that was obtained from kish graphite, and amino-functionalized graphene oxide (AGO) was modified by 2-aminomalonamide. The structural characteristics of the GO and AGO were analyzed using X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). And the anti-corrosive performance of waterborne epoxy-cased composite coatings with different addition amounts of AGO was investigated using electrochemical measurements, pull-off adhesion tests, and salt spray tests. The results indicate that AGO15/WEP with 0.15 wt.% of AGO has the best anti-corrosive performance, and the lowest frequency impedance modulus increased from 1.03 × 108 to 1.63 × 1010 ohm·cm-2 compared to that of WEP. Furthermore, AGO15/WEP also demonstrates the minimal corrosion products or bubbles in the salt spray test for 200 h, affirming its exceptional long-term corrosion protection capability.

Structural characterization and anti-inflammatory activity of a novel neutral polysaccharide isolated from Smilax glabra Roxb.

Crude polysaccharides isolated from Smilax glabra were screened for anti-inflammatory activity using mice ear swelling animal experiments, during which the neutral polysaccharide S1 was identified. The structural characteristics and anti-inflammatory effects of the anti-inflammatory S1 polysaccharide were then investigated. The results showed that S1 was mainly composed of rhamnose, arabinose, galactose, glucose, xylose, and mannose. The structure of the main chain consisted of →6)-α-Galp-(1 â†’ 6)-ß-Galp-(1 â†’ 4)-α-Xylp-(1 â†’ 6)-ß-Galp-(1→, with branched chains comprising α-Araf-(1 â†’ 4)-α â†’ Manp-(1 â†’ and ß-Rhap-(1 â†’ 4)-α-Glcp-(1 â†’ units. Furthermore, S1 did not have a triple helix conformation. S1 could inhibit NO secretion, reduce the levels of pro-inflammatory factors (IL-6 and TNF-α), and significantly reduce LPS-stimulated inflammatory damage in RAW 264.7 cells by inhibiting activation of the NF-κB (p65) pathway. These results shed light on the possibility of S1 to be developed as a novel anti-inflammatory drug for therapeutic purposes.

Sleep Promotion by 3-Hydroxy-4-Iminobutyric Acid in Walnut Diaphragma juglandis Fructus.

Insufficient sleep can produce a multitude of deleterious repercussions on various domains of human well-being. Concomitantly, the walnut (Juglans mandshurica) confers numerous salutary biological activities pertaining to sleep. Nevertheless, the sedative and hypnotic capacities of walnut's functional constituents remain obscure. In this investigation, we analyzed the sedative and hypnotic components of the walnut Diaphragma juglandis fructus and innovatively discovered a compound, defined as 3-hydroxy-4-iminobutyric acid (HIBA), which disrupts motor activity and enhances sleep duration by regulating the neurotransmitters (GABA, DA, etc.) within the brain and serum of mice. Subsequently, a metabolomics approach of the serum, basal ganglia, hypothalamus, and hippocampus as well as the gut microbiota was undertaken to unravel the underlying molecular mechanisms of sleep promotion. Our data reveal that HIBA can regulate the metabolism of basal ganglia (sphingolipids, acylcarnitines, etc.), possibly in relation to HIBA's influence on the gut microbiome (Muribaculum, Bacteroides, Lactobacillus, etc.). Therefore, we introduce a novel natural product, HIBA, and explicate the modulation of sleep promotion in mice based on the microbiota-gut-brain axis. This study contributes fresh insights toward natural product-based sleep research.

Isolation and identification of anti-inflammatory and analgesic polysaccharides from Coix seed (Coix lacryma-jobi L.var. Ma-yuen (Roman.) Stapf).

Coix seed is a nutrient-rich food and traditional Chinese medicine with anti-inflammatory and analgesic properties. Polysaccharides from Coix seed have been rarely investigated for structure and activities. In this study, the analgesic and anti-inflammatory effects were investigated in vivo and in vitro. The results showed that Coix seed had a significant influence on reducing the number of writhing, increasing the pain threshold and alleviating the swelling degree caused by acute inflammation. Column chromatography was used to obtain two active compounds of Coix seed. Compound 1 was (1→6)-α-glucan with a molecular weight of 6.81 × 105 Da. The chemical connection of compound 2 was as follows: α-Frup (2→ [1)-α-Glcp (6]5→1)-α-Glcp (4→1)-α-Glcp, which was isolated in Coix seed for the first time. LPS-induced inflammation in RAW264.7 cells was well inhibited by compounds. These findings offered a preliminary investigation into the analgesic and anti-inflammatory properties of Coix seed, which may be helpful for application.

Advances on Cyclocarya paliurus polyphenols: Extraction, structures, bioactivities and future perspectives.

Cyclocaryapaliurus (C. paliurus) is an edible and medicinal plant, distributed in southern China. As a kind of new food raw material, the leaves of C. paliurus are processed as tea products in daily life. C. paliurus is recognized as a good source to polyphenols, showing excellent bioactivities, which has attracted more and more attention. Polyphenols are important functional bioactive components in C. paliurus. C. paliurus polyphenols perform nutritional functions in anti-diabetes, anti-hyperlipidemic, anti-obesity, anti-oxidant, and other activities. In this review, we summarize the research progress of extraction technologies, structural characteristics, and bioactivities of C. paliurus polyphenols. Other potential functions of C. paliurus polyphenols are prospected. This review provides a reference for further research and applications of C. paliurus polyphenols in a field of functional food and medicines.

Facile and Controllable Synthesis of CuS@Ni-Co Layered Double Hydroxide Nanocages for Hybrid Supercapacitors.

The synthesis of battery-type electrode materials with hollow nanostructures for high-performance hybrid supercapacitors (HSCs) remains challenging. In this study, hollow CuS@Ni-Co layered double hydroxide (CuS-LDH) composites with distinguished compositions and structures are successfully synthesized by co-precipitation and the subsequent etching/ion-exchange reaction. CuS-LDH-10 with uniformly dispersed CuS prepared with the addition of 10 mg of CuS shows a unique hollow polyhedral structure constituted by loose nanosphere units, and these nanospheres are composed of interlaced fine nanosheets. The composite prepared with 30 mg of CuS addition (CuS-LDH-30) is composed of a hollow cubic morphology with vertically aligned nanosheets on the CuS shell. The CuS-LDH-10 and CuS-LDH-30 electrodes exhibit high specific capacity (765.1 and 659.6 C g-1 at 1 A g-1, respectively) and superior cycling performance. Additionally, the fabricated HSC delivers a prominent energy density of 52.7 Wh kg-1 at 804.5 W kg-1 and superior cycling performance of 87.9% capacity retention after 5000 cycles. Such work offers a practical and effortless route for synthesizing unique metal sulfide/hydroxide composite electrode materials with hollow structures for high-performance HSCs.

Both high glucose and phosphate overload promote senescence-associated calcification of vascular muscle cells.

PURPOSE: The NAD+-dependent deacetylase, sirtuin 1 (SIRT1), plays an important role in vascular calcification induced by high glucose and/or high phosphate levels. However, the mechanism by which SIRT1 regulates this process is still not fully understood. Thus, this study aimed to determine the role of high glucose and phosphate in vascular calcification and the molecular mechanisms underlying SIRT1 regulation. METHODS: Vascular smooth muscle cells (VSMCs) were cultured under normal, high phosphate, and/or high-glucose conditions for 9 days. Alizarin red staining and calcification content analyses were used to determine calcium deposition. VSMC senescence was detected by ß-galactosidase (SA-ß-Gal) staining and p21 expression. RESULTS: Mouse VSMCs exposed to high phosphate and high glucose in vitro showed increased calcification, which was correlated with the induction of cell senescence, as confirmed by the increased SA-ß-galactosidase activity and p21 expression. SRT1720, an activator of SIRT1, inhibits p65 acetylation, the nuclear factor-κ-gene binding (NF-κB) pathway, and VSMC transdifferentiation, prevents senescence and reactive oxygen species (ROS) production, and reduces vascular calcification. In contrast, sirtinol, an inhibitor of SIRT1, increases p65 acetylation, activates the NF-κB pathway, induces vascular smooth muscle cell transdifferentiation and senescence, and promotes vascular calcification. CONCLUSIONS: High glucose and high phosphate levels induce senescence and vascular calcification in VSMCs, and the combined effect of high glucose and phosphate can inhibit SIRT1 expression. SIRT1 inhibits vascular smooth muscle cell senescence and osteogenic differentiation by inhibiting NF-κB activity, thereby inhibiting vascular calcification.

A negative feedback loop involving NF-κB/TIR8 regulates IL-1ß-induced epithelial- myofibroblast transdifferentiation in human tubular cells.

Renal tubular epithelial-myofibroblast transdifferentiation (EMT) plays a central role in the development of renal interstitial fibrosis (RIF). The profibrotic cytokine interleukin (IL)-1 and the IL-1 receptor (IL-1R) also participate in RIF development, and Toll/IL-1R 8 (TIR8), a member of the Toll-like receptor superfamily, has been identified as a negative regulator of IL-1R signaling. However, the functions of TIR8 in IL-1-induced RIF remain unknown. Here, human embryonic kidney epithelial cells (HKC) and unilateral ureteric obstruction (UUO)-induced RIF models on SD rats were used to investigate the functions of TIR8 involving IL-1ß-induced EMT. We showed that IL-1ß primarily triggers TIR8 expression by activating nuclear factor-κB (NF-κB) in HKC cells. Conversely, high levels of TIR8 in HKC cells repress IL-1ß-induced NF-κB activation and inhibit IL-1ß-induced EMT. Moreover, in vitro and in vivo findings revealed that TIR8 downregulation facilitated IL-1ß-induced NF-κB activation and contributed to TGF-ß1-mediated EMT in renal tubular epithelial cells. These results suggested that TIR8 exerts a protective role in IL-1ß-mediated EMT and potentially represents a new target for RIF treatment.

Maize DELLA proteins dwarf plant8 and dwarf plant9 as modulators of plant development.

DELLA proteins are nuclear-localized negative regulators of gibberellin signaling found ubiquitously throughout higher plants. Dominant dwarfing mutations of DELLA proteins have been primarily responsible for the dramatic increases in harvest index of the 'green revolution'. Maize contains two genetic loci encoding DELLA proteins, dwarf plant8 (d8) and dwarf plant 9 (d9). The d8 gene and three of its dominant dwarfing alleles have been previously characterized at the molecular level. Almost 20 years after the initial description of the mutant, this investigation represents the first molecular characterization of d9 and its gibberellin-insensitive mutant, D9-1. We have molecularly, subcellularly and phenotypically characterized the gene products of five maize DELLA alleles in transgenic Arabidopsis. In dissecting the molecular differences in D9-1, a critical residue for normal DELLA function has been uncovered, corresponding to E600 of the D9 protein. The gibberellin-insensitive D9-1 was found to produce dwarfing and, notably, earlier flowering in Arabidopsis. Conversely, overexpression of the D9-1 allele delayed flowering in transgenic maize, while overexpression of the d9 allele led to earlier flowering. These results corroborate findings that DELLA proteins are at the crux of many plant developmental pathways and suggest differing mechanisms of flowering time control by DELLAs in maize and Arabidopsis.

Triterpenoid saponins from the rhizome of Polygonatum sibiricum.

Three new triterpenoid saponins, polygonoides C (1), D (2), and E (3), were obtained from the ethanolic extract of the rhizome of Polygonatum sibiricum Redoute. On the basis of NMR and ESI-MS spectra, and chemical evidence, the structures of the three new compounds were elucidated as 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranosyl-3ß,7ß,22ß-trihydroxy-oleanolic acid (1), 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranosyl-3ß,7ß,22ß-trihydroxy-oleanolic acid methyl ester (2), and 3-O-ß-D-glucopyranosyl-(1→3)-ß-D-glucopyranosyl-(1→4)-[α-L-rhamno-pyranosyl-(1→2)]-ß-D-glucopyranosyl-3ß,21ß-dihydroxy-oleanolic acid 28-O-ß-D-glucopyranosyl-(1→3)-ß-D-glucopyranosyl-(1→3)-ß-D-glucopyranoside (3).

Two new steroidal saponins from the rhizome of Polygonatum sibiricum.

Two new furostanol saponins, polygonoides A (1) and B (2), along with three known compounds, were obtained from the ethanolic extract of the rhizome of Polygonatum sibiricum Redoute. On the basis of acid hydrolysis and comprehensive spectroscopic analyses, the structures of polygonoides A and B were elucidated as (25R)-26-O-beta-D-glucopyranosyl-furost-5,22(23)-dien-3beta,26-diol-3-O-alpha-L-rhamnopyranosyl-(1 --> 3)-beta-D-glucopyranosyl-(1 --> 4)-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (1) and 22 alpha-(propionyloxy)-furost-5-en-3beta,20 alpha-diol-3-O-beta-D-glucopyranosyl-(1 --> 4)-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (2).

[Isolation and structure determination of steroidal saponin from Dioscorea zingiberensis].

To study the chemical constituents of Dioscorea zingiberensis Wright, the EtOH extract of fresh rhizomes of D. zingiberensis was concentrated and partitioned further to produce petroleum ether-, ethylacetate-, n-butanol- and water-soluble fractions. The water-soluble fraction was subjected to column chromatography on macro resin AB-8, and the final products were obtained by repeated reversed-phase ODS and MCI gel CHP 20P column chromatography. Structures of compounds were elucidated by 1H NMR, 13C NMR, 135DEPT, HMQC, HMBC and TOCSY spectroscopic analyses. A new steroidal saponin was isolated, which was identified as (25R)-26-O-(beta-D-glucopyranosyl)-furost-5-en-3 beta, 16, 20, 26-tetraol-22-seco-3-O-beta-D-glucopyranosyl-(1--> 3)-beta-D-glucopyranosyl-(1--> 4)-[alpha-L-rhamnopyranosyl-(1-->2)]-beta-D-glucopyranoside. The compound is a novel skeletally steroidal saponin, named as zingiberenin F (1). It was reported for the first time from D. zingiberensis Wright.

The synergistic action of phosphate and interleukin-6 enhances senescence-associated calcification in vascular smooth muscle cells depending on p53.

Cardiovascular calcification is associated with cardiovascular morbidity and mortality of patients with end-stage renal diseases (ESRD). Hyperphosphatemia and many of the inflammatory markers and mediators, including interleukin-6 (IL-6), are considered as the major risk factors of cardiovascular calcification. Although cellular senescence may be involved in cardiovascular calcification caused by phosphate overload and (or) IL-6 in patients with ESRD, less is known about the underlying mechanisms for phosphate- and IL-6-induced senescence-associated calcification of vascular smooth muscle cells (VSMCs). In the present study, we investigated the correlation between cellular senescence and vascular calcification induced by loading phosphate and (or) IL-6 in VSMCs. Our findings show that p53 plays a major role in senescence-associated vascular calcification induced by phosphate overload. IL-6 induces senescence-associated calcification in VSMCs depending upon activation of the IL-6/soluble IL-6 receptor (sIL-6R)/signal transducer and activator of transcription 3 (STAT3)/p53/p21 pathway. We demonstrate that the synergistic action of phosphate overload and IL-6 enhances senescence-associated calcification in a p53-dependent manner and is inhibited by an anti-aging agent (resveratrol) in a dose-dependent manner.

[Isolation and structure determination of steroidal saponin from Dioscorea zingiberensis].

To study the chemical constituents of Dioscorea zingiberensis Wright, the EtOH extract of fresh rhizomes of D. zingiberensis was concentrated and partitioned further to produce petroleum ether-, ethylacetate-, n-butanol- and water-soluble fractions. The water-soluble fraction was subjected to column chromatography on macro resin AB-8, and the final products were obtained by repeated reversed-phase ODS and MCI gel CHP 20P column chromatography. Structures of compounds were elucidated by means of 1H NMR, 13C NMR, 135DEPT, HMQC, HMBC and TOCSY spectroscopic analyses. Five steroidal saponins were isolated, in which one new steroidal saponin was identified as (25R)-26-O-(beta-D-glucopyranosyl) -furost-5-en-3beta, 22xi, 26-triol-4beta-acetoxyl-3-O-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopy ranosyl-(1-->4)-[alpha-L-rhamnopyranosyl-(1-->2)]-beta-D-glucopyranoside (V). The compound V is a new compound, named as zingiberenin G. The compounds I, II and III were reported for the first time from D. zingiberensis Wright.

[Study on the chemical constituents of flavones from corn silk].

The three flavones were isolated from water extracts of corn silk by chromatography on macroporous resin, polyamide, ODS and Sephadex LH-20. Three compounds were identified as formononetin (7-hydroxy-4'-methoxyisoflavone) ( I ) ,2"-O-alpha-L-rham-nosyl-6-C-( 3-deoxyglucosyl) -3 '-methoxyluteolin( II ) ,2"-O-alpha-L-rhamnosyl-6-C-( 6-deoxy-ax-5-methyl-xylo-hexos-4-ulosyl) -3'-methoxyluteolin( II ). Compounds ( I ) and ( II ) were isolated from the corn silk for the first time.

[Study on the chemical structure from the roots of Actinidia deliciosa].

Active compounds from Actinidia deliciosa were separated and identified. Column chromatography was used for isolation. Physicochemical and spectroscopic analysis were employed for structural identification. 5 compounds were isolated and identified as 2alpha, 3beta, 19, 23-tetrahydroxylolean-12-en-28-oic acid( I ), 2alpha, 3alpha, 23-trihydroxy-urs-12-en-28-oic acid( II ) , 2alpha, 3beta, 19,23-tetra-hydroxyl-urs-12-en-oic acid( I ) , undecanoic acid( IV) ,beta-sitoserol( V ). I , IV and V were isolated from roots of Actinidia deliciosa for the first time.