Multiple sclerosis (MS) is an inflammatory demyelination disease characterized by autoimmune damage to the central nervous system. In this disease, failure of remyelination could cause persistent ...disability. Cordycepin, also known as 3′-deoxyadenosine, exerts anti-inflammatory, anti-oxidic, anti-apoptotic and neuroprotective effects. The cuprizone (CPZ) model has been widely used to study MS as it mimics some characteristics of demyelination disease. To determine whether cordycepin promotes remyelination and functional recovery after CPZ-induced demyelination, we administered cordycepin to the CPZ-induced demyelination mice. Cordycepin reversed CPZ-induced loss of body weight and rescued motor dysfunction in the model mice. Cordycepin effectively promoted remyelination and enhanced MBP expression in the corpus callosum. Cordycepin also inhibited the CPZ-induced increase in the number of Iba1-positive microglia, GFAP-positive astrocytes and Olig2-positive oligodendroglial precursor cells in the corpus callosum and cerebral cortex. Pro-inflammatory cytokine expression (IL-1β and IL-6) was inhibited while anti-inflammatory cytokine IL-4 and neurotrophic factor BDNF release was elevated in the corpus callosum and hippocampus after cordycepin treatment. In addition, we also found that cordycepin ameliorated CPZ-induced body weight loss, motor dysfunction, demyelination, glial cells activation and pro-inflammatory cytokine expression in the corpus callosum and hippocampus. Our results suggest that cordycepin may represent a useful therapeutic agent in demyelination-related diseases via suppression of neuroinflammation.
•Cordycepin promoted remyelination and rescued motor dysfunction after cuprizone-induced demyelination.•Cordycepin inhibited the cuprizone-induced increase in the positive number of microglia, astrocytes and OPCs.•Cordycepin inhibited cuprizone-induced pro-inflammatory cytokine expression (IL-1β and IL-6).•Cordycepin promoted anti-inflammatory cytokine IL-4 and neurotrophic factor BDNF release.
Rice (Oryza sativa L.) inflorescence (panicle) architecture is an important agronomic trait for rice breeding. A number of high-yielding japonica rice strains, characterized by an erect panicle (EP) ...of their architecture, have been released as commercial varieties in China. But no EP-type indica varieties are released so far. Here, we identified two allelic erect-panicle mutants in indica rice, erect panicle2-1 (ep2-1) and erect panicle2-2 (ep2-2), exhibiting the characteristic erect panicle phenotype. Both mutants were derived from spontaneous mutation. We cloned the EP2 gene by way of a map-based cloning strategy, and a transgenic complementation test rescued the phenotype of ep2-1. Anatomical investigations revealed that the ep2 mutants have more vascular bundles and a thicker stem than that of wild-type plants, explaining the panicle erectness phenotype in ep2 mutants. It was shown that EP2 was specifically expressed in the vascular bundles of internodes by GUS staining and RT-PCR. EP2 encodes a novel plant-specific protein, which localizes to the endoplasmic reticulum with unknown biochemical function. In addition, EP2 also regulates other panicle characteristics, such as panicle length and grain size, but grain number per panicle shows little change, indicating that the mutation of the ep2 gene could be applied in EP-type indica rice breeding.
•Lentinan treatment led to a robust antidepressant-like effect in the tail suspension test and forced swim test after 60min of treatment in mice.•Dectin-1, the receptor of lentinan, mediated the ...antidepressant-like effects of lentinan.•The prefrontal Dectin-1/AMPA receptor signaling pathway was essential for the robust antidepressant-like effects evoked by lentinan.
Lentinan (LNT) is an immune regulator and its potential and mechanism for the treatment of mood disorder is of our interest. Dectin-1 is a β-glucan (including LNT) receptor that regulates immune functions in many immune cell types. Cumulative evidence has suggested that the glutamatergic system seems to play an important role in the treatment of depression. Here, we studied the antidepressant-like effects of LNT and its therapeutical target in regulating the functions of AMPA receptors. We found that 60min treatment with LNT leads to a significant antidepressant-like effect in the tail suspension test (TST) and the forced swim test (FST) in mice. The antidepressant-like effects of LNT in TST and FST remained after 1day or 5days of injections. Additionally, LNT did not show a hyperactive effect in the open field test. Dectin-1 receptor levels were increased after LNT treatment for 5days and the specific Dectin-1 inhibitor laminarin was able to block the antidepressant-like effects of LNT. After 5days of treatment, LNT enhanced p-GluR1 (S845) in the prefrontal cortex (PFC); however, the total GluR1, GluR2, and GluR3 expression levels remained unchanged. We also found that the AMPA-specific blocker GYKI 52466 was able to block the antidepressant-like effects of LNT. This study identified LNT as a novel antidepressant with clinical potential and a new antidepressant mechanism for regulating prefrontal Dectin-1/AMPA receptor signaling.
Flowering time in crops is an important agronomic character and is closely related to yield. However, the molecular mechanisms of flowering regulation in rapeseed remain elusive. In the current ...study, we report a rapeseed mutant with an early flowering (
eaf
) phenotype. The results of field observation showed that the flowering time of the mutant was about 18 days earlier than that of the wild type (WT, Zhongshuang 11), but there were no significant differences in other agronomic characters. Proteomic and transcriptomic analyses revealed that flowering and hormone-related proteins and genes were significantly differentially expressed between WT and
eaf
, indicating that the differential expression of flowering and hormone-related genes may be the main reason for early flowering in the mutant. Besides, the up-regulation of stress-related genes in the
eaf
mutant may be another possible reason of the mutant’s early flowering. Taken together, our findings provide a clue for dissecting the molecular mechanisms of early flowering in the mutant, and also potential materials for rapeseed molecular biology research.
Unusual Pd deactivation and inhibition pathways were observed in a C–N coupling system. Irreversible catalyst deactivation involved C–H insertion of Pd into BippyPhos leading to an off-cycle ...palladaphosphacyclobutene. Product inhibition led to deactivated Pd but released ligand in the process, allowing it to react with additional Pd precursor to re-enter the catalytic cycle. In situ recycling of the ligand allowed for an input L/Pd ratio of ≪1 with no impact on reaction kinetics.
Status epilepticus (SE) is a neurological disorder associated with high morbidity and mortality rates, and is often difficult to treat. Moreover, the underlying mechanism of SE remains unknown. The ...lithium-pilocarpine model is a validated animal model that can reproduce the main clinical and neuropathological features of SE. In the present study, this SE model was utilized and SE was successfully established in rats, as determined by the corresponding epileptic electroencephalogram. Histology, immunohistochemistry, western blot analysis and co-immunoprecipitation were used to detect the phosphorylation (p-) of AKT substrate of 40 kDa (PRAS40), the combination of p-PRAS40 and 14-3-3 protein and the activation of the PI3K/mTOR signaling pathway in SE. In addition, the present study analyzed the dynamics of the expression of autophagy-associated factors in the hippocampus after SE induction, and the influence of suppressing the p- of PRAS40 on the autophagy process was detected in the pathogenesis of SE. The results indicated that increased p-PRAS40 expression could activate the mTOR pathway to decrease the level of autophagy. However, inhibition of the mTOR signaling pathway promoted autophagy flux. These results may provide further understanding of p-PRAS40 functions in SE.
The development of an improved short and efficient commercial synthesis of the JAK2 inhibitor, a complex pyrrolopyridine, BMS-911543, is described. During the discovery and development of this ...synthesis, a Pd-catalyzed C–H functionalization was invented which enabled the rapid union of the key pyrrole and imidazole fragments. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only six steps (longest linear sequence) from readily available materials.
Acute lung injury (ALI) is characterized by increased pulmonary vascular permeability in response to the accumulation of inflammatory cells, release of inflammatory cytokines, and activated oxidative ...stress. The present study was performed to investigate the effect of sodium houttuyfonate
(SH), an extract of Houttuynia cordata, on inflammatory response and oxidative stress in ALI induced by lipopolysaccharides (LPS). Male C57BL/6 mice were randomly allocated to control, LPS, dimethyl sulfoxide (DMSO), and SH groups. The ALI model was established by intratracheal LPS injection.
Lung tissue was collected 6 h after LPS injection for histopathological analysis, measurement of wet-to-dry ratio, myeloperoxidase (MPO) and oxidative stress levels, and the p38, jun N-terminal kinase (JNK), extracellular regulated kinase (ERK), and p65 phosphorylation levels. Bronchoalveolar
fluid (BALF) was collected for the detection of protein concentration, MPO and cytokine levels. The histopathological test showed that SH significantly alleviates damage to pulmonary tissue. Improved vascular permeability was indicated by reduced BALF protein level and lung wet-to-dry ratio
in the SH group. MPO levels were decreased in lung tissue and BALF. Oxidative stress and inflammatory responses were inhibited by SH, as indicated by MDA, SOD and cytokine levels. The MAPK and NF-KB pathways were inhibited as shown by the attenuated phosphorylation of p38, JNK,
ERK and p65. Sodium houttuyfonate exhibited a protective role against LPS-induced lung injury through anti-oxidative and anti-inflammatory effects. The MAPK and NF-K B pathways may be inhibited by sodium houttuyfonate. Sodium Houttuynin has a good effect on a variety of acute infectious
diseases, but its solubility and stability are insufficient, which limits its efficacy. Nano delivery system can enhance the effective ingredients of traditional Chinese medicine, reduce the toxic and side effects of drugs, and improve their medicinal properties. Therefore, this paper adopts
nano delivery system to assist drug use and improve research efficiency.
The analysis of elemental impurities in pharmaceuticals has traditionally been performed using plasma-based instrumental techniques, such as inductively coupled plasma-optical emission spectroscopy ...or inductively coupled plasma-mass spectrometry, due to their inherent sensitivity, selectivity, and precision; however, during development activities, there are a variety of sample types that do not require the sensitivity that these expensive and time-consuming techniques provide. Pharmaceutical process chemists often need a rapid and relative determination of the elemental content to direct them in optimizing the effectiveness or efficiency of their synthetic process. This article will provide the application of a field-portable X-ray fluorescence instrument as a hands-on screening tool for chemists to determine the effectiveness of metal catalyst scavenger studies. Three case studies will be provided to illustrate the usefulness of the technique.
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