Matrix metalloproteinase-9 induces cardiac fibroblast migration, collagen and cytokine secretion: inhibition by salvianolic acid B from Salvia miltiorrhiza

Cardiac fibroblasts play the key role in cardiac function and matrix metalloproteinases-9 (MMP-9) is a well known contributor to the development of myocardial remodeling. However, the direct regulation of MMP-9 on the function of cardiac fibroblasts and the underlying mechanism are far from elucidation. In the present research, recombinant protein encoding catalytic domain of MMP-9 (MMP-9 CD) was constructed and the function of neonatal cardiac fibroblasts was investigated by cell proliferation assay, migration assay, picrosirius red assay, multiplex cytokine assay and fibroblast phenotype detection. 200 nM MMP-9 CD stimulated cardiac fibroblasts migration (169.4±22.5% versus 100±0%, p<0.01), increased collagen synthesis (1.5±0.2 fold, p<0.05), up-regulated the secretion of ICAM (574.0±40.1 versus 268.5±8.6pg/ml, p<0.01), TNF-α (192.6±11.0 versus 14.4±1.8pg/ml, p<0.001), IL-6 (1500.9±70.2 versus 323.4±40.6pg/ml, p<0.001) and sVCAM-1 (30.3±4.3 versus 7.0±0.1 pg/ml, p<0.05) and down-regulated VEGF (436.5±148.9 versus 1034.3±28.1 pg/ml, p<0.05) significantly with modest effects on proliferation. Accompanying with these regulations, transition of fibroblasts to myofibroblast was confirmed by immunofluorescent stain of α-smooth muscle actin (α-SMA) with MMP-9 CD treatment. Furthermore, salvianolic acid B (SalB) inhibited the effects of MMP-9 CD significantly. In conclusion, our results provide evidence for a direct influence of MMP-9 on cardiac fibroblast migration, collagen and cytokine secretion, which can be attenuated by SalB.     

中国新归化种广布苋的分布及其与腋花苋的关系

本文报道了中国苋科苋属的一新记录归化植物——广布苋(Amaranthus graecizans L．)。该种植株常匍匐,叶片狭长椭圆形至线状披针形,有时线形或菱形卵形,长至少为宽的2.5倍,花被片3枚,近等长,与中国有分布的本属其他物种有所区别。该种原产于欧洲地中海地区、非洲北部至亚洲西部,归化于欧洲其他地区、东亚、澳大利亚、北美洲以及我国的河南、河北和山东等地区。该种易与苋属其他种类相混淆,因此其在我国的分布区可能被低估。此外,本文还对该种的种下等级以及该种的相似种进行了区分,并对该种下亚种Amaranthus graecizans subsp. thellungianus (Nevski) Gusev与国内文献记载的腋花苋(Amaranthus roxburghianus Kung)之间的关系作了说明与澄清。     

Cytological and morphology characteristics of natural microsporogenesis within Camellia oleifera

Camellia oleifera is believed to exhibit a complex intraspecific polyploidy phenomenon. Abnormal microsporogenesis can promote the formation of unreduced gametes in plants and lead to sexual polyploidy, so it is hypothesized that improper meiosis probably results in the formation of natural polyploidy in Camellia oleifera. In this study, based on the cytological observation of meiosis in pollen mother cells (PMCs), we found natural 2n pollen for the first time in Camellia oleifera, which may lead to the formation of natural polyploids by sexual polyploidization. Additionally, abnormal cytological behaviour during meiosis, including univalent chromosomes, extraequatorial chromosomes, early segregation, laggard chromosomes, chromosome stickiness, asynchronous meiosis and deviant cytokinesis (monad, dyads, triads), was observed, which could be the cause of 2n pollen formation. Moreover, we confirmed a relationship among the length–width ratio of flower buds, stylet length and microsporogenesis. This result suggested that we can immediately determine the microsporogenesis stages by phenotypic characteristics, which may be applicable to breeding advanced germplasm in Camellia oleifera.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12298-021-01002-5.     

Ferrous Iron Induces Nrf2 Expression in Mouse Brain Astrocytes to Prevent Neurotoxicity

Free radical damage caused by ferrous iron is involved in the pathogenesis of secondary brain injury after intracerebral hemorrhage (ICH). NF‐E2‐related factor 2 (Nrf2), a major phase II gene regulator that binds to antioxidant response element, represents an important cellular cytoprotective mechanism against oxidative damage. We hypothesized that Nrf2 might protect astrocytes from damage by Fe²⁺. Therefore, we examined cytotoxicity in primary astrocytes induced by iron overload and evaluated the effects of Fe²⁺ on Nrf2 expression. The results demonstrated that 24‐h Fe²⁺ exposure exerted time‐ and concentration‐dependent cytotoxicity in astrocytes. Furthermore, Fe²⁺ exposure in astrocytes resulted in time‐ and concentration‐dependent increases in Nrf2 expression, which preceded Fe²⁺ toxicity. Nrf2‐specific siRNA further knocked down Nrf2 levels, resulting in greater Fe²⁺‐induced astrocyte cytotoxicity. These data indicate that induction of Nrf2 expression could serve as an adaptive self‐defense mechanism, although it is insufficient to completely protect primary astrocytes from Fe²⁺‐induced neurotoxicity.     

A model study of interactions between TcAChE peripheral site segment Tyr70Val71 and loop 1 of Fasciculin 2

The continuous chain of residues (Thr7 to Ala12) of Loop1 of Fas2 (F1) and its interaction with the peripheral binding sites (Tyr70-Val71) of AChE (P1) has been studied. Our results suggest that the flexibility of Loop1 might be caused by either the partially protonated guanidine group of Arg11 under experimental conditions or by the interaction with the negatively charged center of substrates. The binding energy of F1-P1 is predicted to be -16.6 kcal/mol at the B3LYP/6-311G(d,p) level, which is assumed to originate from one isolated O7...HN10 H-bond, one possible O10...HC71 unconventional O...HC type H-bonding, and the improved pi-bonding cooperativity around the peptide group of the AChE segment Tyr70-Val71. The classical Kitaura-Morokuma energy decomposition analysis, the NPA charge analysis, and the AIM analysis consistently reveal that the peptide group in segment P1 is more polarizable, which might play the key role in the interactions between F1 and P1. The PCM solvent effect corrected results reveal decrease of the interaction energy of the considered model. The importance of Thr8 of Fas2 in the P-site binding of AChE is also concluded. Site-directed mutations on either the Fas2 residue of Thr8 or the AChE residue of Tyr70 are expected to alter the binding behavior of the Loop1 of Fas2 with AChE.     

Characterization of phytoplankton assemblages in a tropical coastal environment using Kohonen self‐organizing map

This study was aimed at understanding the main abiotic environmental factors controlling the distribution patterns of abundance and composition of phytoplankton (size less than 10 μm) assemblages in the coastal waters of south‐eastern Côte d'Ivoire. Data were collected during two cruises, in January (low‐water period) and October (high‐water period) of 2014. A total of 67 species were identified and assigned to Bacillariophyceae (49%), Cyanophyceae (21%), Chlorophyceae (13%), Euglenophyceae (10%), Dinophyceae (4%) and Chrysophyceae (3%). Three biotic zones (I, IIA and IIB) were distinguishable on a Kohonen self‐organizing map after an unsupervised learning process. The diatom genera Eunotia sp., Navicula sp. and Actinoptychus senarius are significantly associated with I, IIA and IIB biotic zones, respectively. A clear seasonal cum salinity trend was apparent in phytoplankton distribution patterns. Turbidity and nitrate levels were the main abiotic factors controlling phytoplankton distribution in I, the upland tidal regions of the lagoon. In regions along the lagoon–sea continuum, phosphate and turbidity exert the most control during the low‐water season (IIA), while total dissolved solids control phytoplankton distribution during the high‐water season (IIB). These are climate‐sensitive parameters whose concentrations depend on prevailing hydroclimatic processes. Therefore, seasonality can have important consequences on phytoplankton community and inadvertently the productivity of these systems.     

Association of Common Variants in LOX with Keratoconus: A Meta-Analysis

Background

Several case-control studies have been performed to examine the association of genetic variants in lysyl oxidase (LOX) with keratoconus. However, the results remained inconclusive and great heterogeneity might exist across populations.

Method

A comprehensive literature search for studies that published up to June 25, 2015 was performed. Summary odds ratios (OR) and 95% confidence intervals (CI) of each single nucleotide polymorphism (SNP) were estimated with fixed effects model when I ²<50% in the test for heterogeneity or random effects model when I ²>50%. Publication bias was evaluated using funnel plots and Egger’s test.

Results

A total of four studies including 1,467 keratoconus cases and 4,490 controls were involved in this meta-analysis. SNPs rs2956540 and rs10519694 showed significant association with keratoconus, with ORs of 0.71 (95% CI: 0.63–0.80, P = 1.43E-08) and 0.77 (95% CI: 0.61–0.97, P = 0.026), respectively. In contrast, our study lacked sufficient evidences to support the association of rs1800449/rs2288393 with keratoconus across populations.

Conclusion

This meta-analysis suggested that two LOX variants, rs2956540 and rs10519694, may affect individual susceptibility to keratoconus, while distinct heterogeneity existed within this locus. Larger-scale and multi-ethnic genetic studies on keratoconus are required to further validate the results.