Ischemic brain injury is associated with neuroinflammatory response, which essentially involves glial activation and neutrophil infiltration. Transcription factors nuclear factor-κB (NF-κB) and ...signal transducer and activator of transcription 3 (STAT3) contribute to ischemic neuroinflammatory processes and secondary brain injury by releasing proinflammatory mediators. Kaempferol-3-O-rutinoside (KRS) and kaempferol-3-O- glucoside (KGS) are primary flavonoids found in Carthamus tinctorius L. Recent studies demonstrated that KRS protected against ischemic brain injury. However, little is known about the underlying mechanisms. Flavonoids have been reported to have antiinflammatory properties. Herein, we explored the effects of KRS and KGS in a transient focal stroke model.
Rats were subjected to middle cerebral artery occlusion for 2 hours followed by 22 h reperfusion. An equimolar dose of KRS or KGS was administered i.v. at the beginning of reperfusion. The results showed that KRS or KGS significantly attenuated the neurological deficits, brain infarct volume, and neuron and axon injury, reflected by the upregulation of neuronal nuclear antigen-positive neurons and downregulation of amyloid precursor protein immunoreactivity in the ipsilateral ischemic hemisphere. Moreover, KRS and KGS inhibited the expression of OX-42, glial fibrillary acidic protein, phosphorylated STAT3 and NF-κB p65, and the nuclear content of NF-κB p65. Subsequently, these flavonoids inhibited the expression of tumor necrosis factor α, interleukin 1β, intercellular adhesion molecule 1, matrix metallopeptidase 9, inducible nitric oxide synthase, and myeloperoxidase.
Our findings suggest that postischemic treatment with KRS or KGS prevents ischemic brain injury and neuroinflammation by inhibition of STAT3 and NF-κB activation and has the therapeutic potential for the neuroinflammation-related diseases, such as ischemic stroke.
Blocking TLR4/peroxiredoxin (Prx6) signaling is proposed to be a novel therapeutic strategy for ischemic stroke because extracellular Prx6 released from ischemic cells may act as an endogenous ligand ...for TLR4 and initiate destructive immune responses in ischemic brain. Our previous studies showed that ligustilide (LIG) exerted antineuroinflammatory and neuroprotective effects against ischemic insult, but the underlying mechanisms remain unclear. This study investigated whether the TLR4/Prx6 pathway is involved in the protective effect of LIG against postischemic neuroinflammation and brain injury induced by transient middle cerebral artery occlusion (MCAO) in rats. Intraperitoneal LIG administration (20 and 40mg/kg/day) at reperfusion onset after MCAO resulted in a reduction of brain infarct size and improved neurological outcome over 72h. LIG-induced neuroprotection was accompanied by improvement of neuropathological alterations, including neuron loss, astrocyte and microglia/macrophage activation, neutrophil and T-lymphocyte invasion, and regulation of inflammatory mediators expression. Moreover, LIG significantly inhibited the expression and extracellular release of Prx6 and activation of TLR4 signaling, reflected by decreased TLR4 expression, extracellular signal-regulated kinase 1/2 phosphorylation, and transcriptional activity of NF-κB and signal transducer and activator of transcription 3 in the ischemic brain. Our results demonstrate that LIG may provide an early and direct neuroprotection by inhibiting TLR4/Prx6 signaling and subsequent immunity and neuroinflammation after cerebral ischemia. These findings support the translational potential of blocking TLR4/Prx6 signaling for the treatment of ischemic stroke.
•Brain ischemia induced release of peroxiredoxin 6 into cerebrospinal fluid.•Toll-like receptor 4 and peroxiredoxin 6 levels were increased in ischemic brain.•Ligustilide attenuated postischemic neuroinflammation and brain injury.•Ligustilide reduced Toll-like receptor 4/peroxiredoxin 6 in ischemic brain.•Toll-like receptor 4 signaling was inhibited by ligustilide.
Isoprothiolane (IPT) resistance has emerged in Magnaporthe oryzae, due to the long-term usage of IPT to control rice blast in China, yet the mechanisms of the resistance remain largely unknown. ...Through IPT adaptation on PDA medium, we obtained a variety of IPT-resistant mutants. Based on their EC50 values to IPT, the resistant mutants were mainly divided into three distinct categories, i.e., low resistance (LR, 6.5 ≤ EC50 < 13.0 μg/mL), moderate resistance 1 (MR-1, 13.0 ≤ EC50 < 25.0 μg/mL), and moderate resistance 2 (MR-2, 25.0 ≤ EC50 < 35.0 μg/mL). Molecular analysis of MoIRR (Magnaporthe oryzae isoprothiolane resistance related) gene demonstrated that it was associated only with the moderate resistance in MR-2 mutants, indicating that other mechanisms were associated with resistance in LR and MR-1 mutants. In this study, we mainly focused on the characterization of low resistance to IPT in M. oryzae. Mycelial growth and conidial germination were significantly reduced, indicating fitness penalties in LR mutants. Based on the differences of whole genome sequences between parental isolate and LR mutants, we identified a conserved MoVelB gene, encoding the velvet family transcription factor, and genetic transformation of wild type isolate verified that MoVelB gene was associated with the low resistance. Based on molecular analysis, we further demonstrated that the velvet family proteins VelB and VeA were indispensable for IPT toxicity and the deformation of the VelB-VeA-LaeA complex played a vital role for the low IPT-resistance in M. oryzae, most likely through the down-regulation of the secondary metabolism-related genes or CYP450 genes to reduce the toxicity of IPT.
Zeolite imidazole skeleton (ZIF-8) is a promising option for self-cleaning of building exterior walls due to its large specific surface area, high antibacterial activity and low biotoxicity. However, ...it suffers from low antibacterial efficiency and yield under visible light irradiation. To address the issues, we developed the photocatalytic materials T-ZIF-8-TDI (thermally treated-ZIF-8-toluene 2,4-diisocyanate) by modifying ZIF-8 with thermal oxygen sensitization and chemical bonding. The results show that the yield of T-ZIF-8-TDI photocatalytic antibacterial agent is increased to 11.5 times of that of T-ZIF-8, while maintaining the crystal structure of T-ZIF-8 and thermal stability up to 60 °C. Furthermore, T-ZIF-8-TDI exhibits extended optical response range to the near-infrared region, significantly narrowed band gap, improved photogenerated electron–hole separation efficiency, reduced recombination rate, and excellent photocatalytic performance. When the concentration of antibacterial agent is 600 mg·L
−1
, the antibacterial rate of
Escherichia coli
(
E. coli
) reaches 99.99% irradiated by visible light for 30 min, and when the concentration of antibacterial agent is 200 mg·L
−1
, the antibacterial rate of
Staphylococcus aureus
(
S. aureus
) reaches 99.99% irradiated by visible light for 25 min. We also analyzed the reasons in detail from the aspects of bacterial species and antibacterial mechanism, and proposed the antibacterial mechanism of ·O
2
−
and h
+
as the main active species. These findings suggest that T-ZIF-8-TDI photocatalytic antibacterial agent has potential for use in self-cleaning of building exterior walls.
Graphical abstract
Isoprothiolane (IPT), a systemic fungicide, has been applied to control rice blast since the 1970s. Although resistance to IPT has been observed, the mechanism of resistance still has not been fully ...elucidated. In this study, nucleotide polymorphisms were detected between two IPT-resistant mutants generated in the lab, and their parental wild type isolates using a whole-genome sequencing approach. In the genomes of the two resistant mutants, single point mutations were identified in a gene encoding a Zn
2
Cys
6
transcription factor-like protein. Notably, either knocking out the gene or replacing the wild type allele with the mutant allele (R343W) in a wild type isolate resulted in resistance to IPT, indicating that the gene is associated with IPT resistance, and thus was designated as
MoIRR
(
Magnaporthe oryzae
isoprothiolane resistance related). Along with point mutations R343W in mutant 1a_mut, and R345C in 1c_mut, a 16 bp insertion in 6c_mut was also located in the Fungal_TF_MHR domain of MoIRR, revealing that this domain may be the core element for IPT resistance. In addition, IPT-resistant mutants and transformants showed cross-resistance with iprobenfos (IBP), which was consistent with previous observations. These results indicated that MoIRR is strongly connected to resistance to choline biosynthesis inhibitor (CBI), and further work should focus on investigating downstream effects of MoIRR.
The point mutation R343W in MoIRR, a putative Zn
Cys
transcription factor, introduces isoprothiolane (IPT) resistance in
. However, the function of MoIRR has not been characterized. In this study, ...the function of MoIRR was investigated by subcellular localization observation, transcriptional autoactivation test, and transcriptomic analysis. As expected, GFP-tagged MoIRR was translocated in the nucleus, and its C-terminal could autonomously activate the expression of reporter genes
and
in absence of any prey proteins in Y2HGold, suggesting that MoIRR was a typical transcription factor. Transcriptomic analysis was then performed for resistant mutant 1a_mut (R343W), knockout transformant ΔMoIRR-1, and their parental wild-type isolate H08-1a. Upregulated genes in both 1a_mut and ΔMoIRR-1 were involved in fungicide resistance-related KEGG pathways, including the glycerophospholipid metabolism and Hog1 MAPK pathways. All MoIRR deficiency-related IPT-resistant strains exhibited increased susceptibility to fludioxonil (FLU) that was due to the upregulation of Hog1 MAPK pathway genes. The results indicated a correlation between FLU susceptibility and MoIRR deficiency-related IPT resistance in
. Thus, using a mixture of IPT and FLU could be a strategy to manage the IPT-resistant populations of
in rice fields.
Abstract Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a neuroprotective factor by modulating insulin-like growth factor 1 signaling and oxidative stress. In the ...present study, we investigated the potential role of Klotho in the therapeutic effect of ligustilide against Alzheimer’s disease (AD)-like neuropathologies and memory impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. Ligustilide treatment (10 and 40 mg/kg for 8 weeks, intragastrically) in 10-month-old SAMP8 mice reduced memory deficits, amyloid-β1–42 accumulation, tau phosphorylation, and neuron loss, increased mitochondrial manganese-superoxide dismutase and catalase expression and activity, and decreased malondialdehyde, protein carbonyl, and 8-hydroxydesoxyguanosine levels in the brain. Ligustilide upregulated Klotho expression in the cerebral choroid plexus and serum, decreased Akt and Forkhead box class O1 phosphorylation. Moreover, ligustilide inhibited the insulin-like growth factor 1 pathway and induced Forkhead box class O1 activation in 293T cells along with Klotho upregulation. An inverse correlation was found between Klotho expression and the AD phenotype, suggesting that Klotho might be a novel therapeutic target for age-related AD, and Klotho upregulation might contribute to the neuroprotective effect of ligustilide against AD.
Monilinia fructicola has been widely reported as the causal agent of brown rot disease on many Rosaceae family fruits worldwide. It has been reported on stone fruits, e.g., peach, plum, cherry, ...apricot and mume; as well as pome fruits, e.g., apple, pear and hawthorn. Loquat is a member of the Eriobotrya genus in subfamily Maloideae along with apple, pear and hawthorn. So far, loquat has not been reported as the host of any Monilia species. In June 2019, brown rot symptoms were observed on loquat fruits in an orchard in Wuhan, Hubei Province, China. Thirty single spore isolates were obtained and identified as M. fructicola based on morphological characteristics and molecular analysis. This is the first report of loquat brown rot disease caused by Monilia species in the world. Furthermore, upon artificial inoculation, all three Monilia species from peach in China, i.e., M. fructicola, M. mumecola and M. yunnanensis, could cause typical brown rot disease on loquat fruits. At the same time, M. fructicola isolates from loquat showed virulence similar to those isolates from peach when the pathogenicity test was conducted on peach fruits. These results suggested that loquat could be infected by other Monilia species and that isolates from loquat also have potential to damage other Rosaceae family fruits in practice.
, the causal agent of scab disease of peach, mume, and apricot, is widely distributed around the world. Scab of stone fruits is an important disease in China. However, little is known about the ...population biology and genetic diversity of the
. To better understand the genetic diversity and population structure of
, 186 single-spore isolates from different hosts and geographic regions were obtained and analyzed by using 31 simple sequence repeat (SSR) markers. This included 156 isolates from peach spanning 14 provinces, 15 isolates from mume and 15 isolates from apricot in Huazhong Agricultural University (HZAU). Diversity analysis with SSR markers showed a low incidence of polymorphisms within mume isolates (32.59% of markers), but a higher incidence of polymorphisms within peach isolates (42.96%) and apricot isolates (57.04%). Within peach isolates, Nei's average gene diversity ranged from 0.07 for Hebei population to 0.18 for Hubei population. AMOVA analysis revealed that 13% of the observed genetic diversity was partitioned among the geographic populations, while 40% of the observed genetic diversity was partitioned among the host populations. Other analyses (PCoA, STRUCTURE, DAPC, MSN, and UPGMA) indicated that the Chinese
populations could be clustered into three distinct genetic groups, which correspond to the host boundaries of peach, mume and apricot. The genetic identity of
isolates throughout the range is dependent on hosts, but not geographic regions.
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