The NLRP3 inflammasome (NOD-like receptor family, pyrin domain containing 3) is an intracellular protein complex that plays an important role in innate immune sensing. Its activation leads to the ...maturation of caspase-1 and regulates the cleavage of interleukin (IL)-1β and IL-18. Various studies have shown that activation of the immune system plays a pivotal role in the development of fatigue. However, the mechanisms underlying the association between immune activation and fatigue remained elusive, and few reports have described the involvement of NLRP3 inflammasome activation in fatigue.
We established a mouse fatigue model with lipopolysaccharide (LPS, 3 mg/kg) challenge combined with swim stress. Both behavioural and biochemical parameters were measured to illustrate the characteristics of this model. We also assessed NLRP3 inflammasome activation in the mouse diencephalon, which is the brain region that has been suggested to be responsible for fatigue sensation. To further identify the role of NLRP3 inflammasome activation in the pathogenesis of chronic fatigue syndrome (CFS), NLRP3 KO mice were also subjected to LPS treatment and swim stress, and the same parameters were evaluated.
Mice challenged with LPS and subjected to the swim stress test showed decreased locomotor activity, decreased fall-off time in a rota-rod test and increased serum levels of IL-1β and IL-6 compared with untreated mice. Serum levels of lactic acid and malondialdehyde (MDA) were not significantly altered in the treated mice. We demonstrated increased NLRP3 expression, IL-1β production and caspase-1 activation in the diencephalons of the treated mice. In NLRP3 KO mice, we found remarkably increased locomotor activity with longer fall-off times and decreased serum IL-1β levels compared with those of wild-type (WT) mice after LPS challenge and the swim stress test. IL-1β levels in the diencephalon were also significantly decreased in the NLRP3 KO mice. By contrast, IL-6 levels were not significantly altered.
These findings suggest that LPS-induced fatigue is an IL-1β-dependent process and that the NLRP3/caspase-1 pathway is involved in the mechanisms of LPS-induced fatigue behaviours. NLRP3/caspase-1 inhibition may be a promising therapy for fatigue treatment.
The
(
) stem leaf is rich in flavonoids. However, because of a lack of research on the flavonoid extraction process and functional development of
stem leaf, these parts are discarded as agricultural ...wastes. Therefore, in this study, we intend to optimize the extraction process and develop the skin-whitening functions of
stem leaf extracts. The extraction process of the stem and leaf of
flavonoid (SLPF) is optimized based on the Box⁻Behnken design (BBD) and the response surface methodology (RSM). The optimum extraction conditions of the SLPF are as follows: the extraction time, the ethanol concentration, the sodium dodecyl sulfate (SDS) content and the liquid material ratio (
/
, which are 52 min, 48.7%, 1.9%, and 20:1, respectively. Under the optimal extraction conditions, the average total SLPF content is 2.10%. The antioxidant activity and anti-deposition of melanin of mouse B16 cells of
stem leaf extracts are studied. The results indicate that the EC
values of reducing activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activities, the superoxide anion removal ability, and the 2,2-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) free radical removal ability are 7.212, 2.893, 2.949, and 0.855 mg/mL, respectively. The extracts IC
values of the tyrosinase and melanin synthesis are 0.045 and 0.046 mg/mL, respectively. Therefore, the optimal processing technology for the SLPF obtained in this study not only increases its utilization rate, but also decreases material costs. The extracts from the
stem leaf may be developed as food or beauty products.
Photocathode based on p-type PbS quantum dots (QDs) combing a novel signal amplification strategy utilizing catalase (CAT) mimetics was designed and utilized for sensitive photoelectrochemical (PEC) ...detection of DNA. The bio-bar-coded Pt nanoparticles (NPs)/G-quadruplex/hemin exhibited high CAT-like activity following the Michaelis–Menten model for decomposing H2O2 to water and oxygen, whose activity even slightly exceeded that of natural CAT. The bio-bar-code as a catalytic label was conjugated onto the surface of PbS QDs modified electrodes through the formed sandwich-type structure due to DNA hybridization. Oxygen in situ generated by the CAT mimetics of the bio-bar-code of Pt NPs/G-quadruplex/hemin acted as an efficient electron acceptor of illuminated PbS QDs, promoting charge separation and enhancing cathodic photocurrent. Under optimal conditions, the developed PEC biosensor for target DNA exhibited a dynamic range of 0.2pmol/L to 1.0nmol/L with a low detection limit of 0.08pmol/L. The high sensitivity of the method was resulted from the sensitive response of PbS QDs to oxygen and the highly efficient CAT-like catalytic activity of the bio-bar-coded Pt NPs/G-quadruplex/hemin.
•PbS QDs with p-type conductivity was prepared for PEC biosensing.•The bio-bar-coded Pt NPs/G-quadruplex/hemin exhibited high catalase-like activity.•The Pt NPs/G-quadruplex/hemin in situ generated oxygen for signal amplification.•This PEC methodology could detect DNA with high sensitivity.
Mitochondria are important organelles in virtually all eukaryotic cells, and are involved in a wide range of physiological and pathophysiological processes. Besides the generation of cellular energy ...in the form of adenosine triphosphate, mitochondria are also involved in calcium homeostasis, reactive oxygen species production and the activation of the intrinsic cell death pathway, thus determining cell survival and death. Mitochondrial abnormalities have been implicated in a wide range of disorders, including neurodegenerative disease such as Parkinson's disease (PD), and considered as a primary cause and central event responsible for the progressive loss of dopaminergic neurons in PD. Thus, reversion or attenuation of mitochondrial dysfunction should alleviate the severity or progression of the disease. The present review systematically summarizes the possible mechanisms associated with mitochondria-mediated dopaminergic neuron damage in PD, in an attempt to elucidate the requirement for further studies for the development of effective PD treatments.
Mycothiol (MSH) plays important roles in maintaining cytosolic redox homeostasis and in adapting to reactive oxygen species in the high-(G + C)-content Gram-positive
Actinobacteria
. However, its ...physiological roles are ill defined compared to glutathione, the functional analog of MSH in Gram-negative bacteria and most eukaryotes. In this research, we explored the impact of intracellular MSH on cellular physiology by using MSH-deficient mutants in the model organism
Corynebacterium glutamicum
. We found that intracellular MSH contributes significantly to resistance to alkylating agents, glyphosate, ethanol, antibiotics, heavy metals and aromatic compounds. In addition, intracellular MSH is beneficial for withstanding oxidative stress induced by various oxidants in
C. glutamicum
. This study greatly expanded our current knowledge on the physiological functions of mycothiol in
C. glutamicum
and could be applied to improve the robustness of this scientifically and commercially important species in the future.
The molecular markers(cpSSR, cpSNP and cpIndel) were developed based on the whole genome sequence of Panax notoginseng chloroplast genome, which provide a powerful tool for the evaluation and ...analysis of the future P. notoginseng germplasm resources. The 89 P. notoginseng samples from 9 groups were used for the experiment, and the data for the study were derived from NCBI and the GenBank numbers were: KJ566590, KP036468, KR021381 and KT001509. Through sequence alignment, 30 polymorphic sites(SNP and Indel) were identified, including 16 cpSNP and 14 cpIndel; cpSNP and cpIndel accounted for far more than the gene region in the intergenic region. The developed cpSSR reached 87-89, the repeat unit was mainly composed of trinucleotide, accounting for 70%-71%, and the dinucleotide was the least, accounting for 7%. Eighteen cpDNA molecular markers were developed, including 7 cpSSR primers, 6 cpIndel primers, and 5 cpSNP primers. The MatK gene and ycf1 primers were chosen as control. According to the results of DNA g
Most of the current techniques for the photoelectrochemical detection based on the hole oxidation of the reductive substances (acting as electron donor) present in the electrolytes. In this paper, we ...report a new concept to construct photoelectrochemical sensors based on the interaction between photo-excited electrons of quantum dots (QDs) and electron acceptors. It was found that benzoquinone (BQ) could act as an efficient electron acceptor of the photo-excited CdS QDs, thus blocking the electron transfer of CdS to the indium tin oxide (ITO) electrode, leading to decreased photocurrent. Based on this phenomenon, a novel photoelectrochemical sensor for dopamine (DA) was developed. DA can be oxidized under weakly alkaline (pH9.0) solution or by electro-deposition in neutral (pH7.0) solution to form poly-dopamine. Poly-dopamine has abundant benzoquinone (BQ) groups, which acted as electron acceptors of the conduction band electrons of the photo-excited CdS QDs, leading to decreased photocurrent of CdS QDs. The method could detect DA with highly selectivity and sensitivity. This photoelectrochemical strategy based on photo-induced electron transfer between the electron acceptor and QDs opened a new avenue for the design of novel photoelectrochemical sensors.
A new concept based on electron transfer between QDs and electron acceptors. Benzoquinone block the electron transfer of CdS to ITO, leading to low photocurrent. Based on this result, a novel photoelectrochemical sensor for dopamine was developed. Display omitted
•A novel concept for the construction of photoelectrochemical sensor.•The method has good sensitivity and selectivity for the detection of dopamine.•The detection was based on photo-induced electron transfer.
Diacylglycerol kinase (DGK) is an enzyme that plays a pivotal role in abiotic and biotic stress responses in plants by transforming the diacylglycerol into phosphatidic acid. However, there is no ...report on the characterization of soybean
genes in spite of the availability of the soybean genome sequence. In this study, we performed genome-wide analysis and expression profiling of the
gene family in the soybean genome. We identified 12
genes (namely
) which all contained conserved catalytic domains with protein lengths and molecular weights ranging from 436 to 727 amino acids (aa) and 48.62 to 80.93 kDa, respectively. Phylogenetic analyses grouped
genes into three clusters-cluster I, cluster II, and cluster III-which had three, four, and five genes, respectively. The qRT-PCR analysis revealed significant
gene expression levels in both leaves and roots coping with polyethylene glycol (PEG), salt, alkali, and salt/alkali treatments. This work provides the first characterization of the
gene family in soybean and suggests their importance in soybean response to abiotic stress. These results can serve as a guide for future studies on the understanding and functional characterization of this gene family.
Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype and how to manipulate them for therapeutic ...purposes remain to be explored. Here, we show that in the TME, RARγ is downregulated in macrophages, and its expression correlates with poor prognosis in patients with colorectal cancer (CRC). In macrophages, RARγ interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), which prevents TRAF6 oligomerization and autoubiquitination, leading to inhibition of nuclear factor κB signaling. However, tumor-derived lactate fuels H3K18 lactylation to prohibit RARγ gene transcription in macrophages, consequently enhancing interleukin-6 (IL-6) levels in the TME and endowing macrophages with tumor-promoting functions via activation of signal transducer and activator of transcription 3 (STAT3) signaling in CRC cells. We identified that nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding to RARγ to inhibit TRAF6-IL-6-STAT3 signaling. This study unravels lactate-driven macrophage function remodeling by inhibition of RARγ expression and highlights NDGA as a candidate compound for treating CRC.
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•TAMs with low expression of RARγ exhibit oncogenic functions in CRC•Tumor-derived lactate inhibits macrophage RARγ expression via histone lactylation•RARγ regulates TRAF6-IL-6-STAT3 signaling to connect inflammation and tumorigenesis•Nordihydroguaiaretic acid effectively exhibits antitumor action by targeting RARγ
Li et al. show that tumor-associated macrophages exhibiting low expression of RARγ are linked to an unfavorable prognosis in patients with colorectal cancer (CRC). Lactylation-induced RARγ downregulation in macrophages contributes to CRC tumorigenesis by boosting TRAF6-IL-6-STAT3 signaling. Nordihydroguaiaretic acid targets RARγ to impede tumor growth within the tumor microenvironment.
High temperature is one of the major abiotic stresses that limit edible mushroom growth and development. The understanding of physiological alterations in response to heat stress and the ...corresponding mechanisms involved is vital for the breeding of heat-resistant edible mushroom strains. Although trehalose functions as a protectant against abiotic stresses in fungi, the putative role of trehalose in thermotolerance remains to be elucidated. In this study, we found heat stress inhibited the growth of two Pleurotus pulmonarius strains, heat-sensitive and less-sensitive, and the inhibition was more significant for the sensitive strain. Heat stress leads to the increase of lipid peroxidation and intracellular trehalose accumulation, with a higher level in the heat-sensitive strain, and this effect is independent of exogenous trehalose application. In addition, a lower concentration of exogenous trehalose application in sensitive strain than in less-sensitive strain was found to alleviate the inhibition of mycelium growth and further increase the intracellular trehalose concentration by heat stress. Thus, the protective effects of trehalose were more remarkable in the sensitive strain. The activities of intracellular trehalose metabolic enzymes, i.e., trehalose-6-phosphate synthase, trehalose phosphorylase and neutral trehalase, were determined, and our data indicated that the changes of these enzymes activities in the sensitive strain were more beneficial to accumulate trehalose than that in the less-sensitive strain.
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