This study intends to promote bone marrow mesenchymal stem cells (BMSCs) differentiation into neural stem cells by down-regulating p38 MAPK/NF-κB to heal neurodegeneration. 26 patients with neurodegenerative diseases were enrolled from the Department of Neurology along
with recruitment of 26 other healthy controls followed by analysis of p38 MAPK/NF-κB signaling pathway expression by ELISA. BMSCs were cultured and characterized by flow cytometry. Western blot and qRTPCR measured the p38 MAPK/NF-κB expression in the absence or presence
of p38 MAPK/NF-κB inhibitors. p38 MAPK/NF-κB expression in 26 neurodegenerative patients was significantly higher than that of 26 healthy controls. The qRT-PCR and western blot results showed that the neural stem cell-specific proteins expression was increased as
days went; after addition of p38 MAPK/NF-κB inhibitor, the expression of related specific genes were significantly decreased. In conclusion, inhibition of the expression of p38 MAPK/NF-κB signaling pathway can heal neurodegeneration by promoting the differentiation
of BMSCs into neural stem cells.
The BMSCs-exosome plays a role in regulating tumor micro-environment so as to affect tumor cell biological behaviors. However, whether it affects the biological characteristics of epithelial ovarian cancer (EOC) cells remains unclear. Our study aimed to discuss whether BMSCs-exosome
affects EOC cell proliferative ability. BMSCs cells were cultivated to isolate exosome which was used to treat EOC cells at different concentrations (25, 50, and 100 μmol/L) followed by measuring cell proliferation by CCK-8, cell invasion and migration by Transwell, MKP-1and MAPK/ERK
protein level by Western Blot. BMSCs-exosome showed positive expression of CD9, CD63 and CD81 and negative CD116 and CD19. It could significantly inhibit EOC cell proliferation, invasion and migration in a dose-dependent manner along with reduced expression of MAPK/ERK. In conclusion, BMSCs-exosome
inhibits EOC cell biological behaviors possibly through regulation of MKP-1 and MAPK/ERK signal pathway, indicating that it might be used as a novel approach for treating EOC.
To elucidate the communication between exosomes (exo) derived from BMSCs and injured lung cells. BMSC-exo was isolated and characterized. Lung epithelial cells A549 were incubated with BMSC-exo, and treated by LPS to induce cell damage. CCK-8 assay was carried out to test cell proliferation,
flow cytometry was adopted to analyze cell apoptosis, and RT-qPCR as well as Western blot analysis were selected to assess expression of apoptosis- and anti-apoptosis related proteins. Functional experiment was performed to identify the role of microRNA (miRNA)-328 in lung injury. LPS treatment
significantly inhibited the viability of A549 cells, induced apoptosis of A549 cells by increasing Bax and casepase-3 levels and reducing Bcl-2 expression, whilst declined expression of miR-328 and suppressed the phosphorylation activation of the MAPK/ERK pathway. Meanwhile, the amount of
IL-6, IL-1β and TNF-α were elevated in injured cells, but, the presence of BMSC-exo eliminated the elevation of the contents. Importantly, treatment with BMSC-exo increased miR-328 expression, activated MAPK MAPK/ERK pathway, inhibited apoptosis, and enhanced cell
proliferation. However, the effect of BMSC-exo was attenuated when the cells were silenced for miR-328 expression. Collectively, BMSC-exo enriched miR-328 could relieve acute lung injury through MAPK/ERK pathway.
Drought stress severely restricts edible fungus production. The genus Auricularia has a rare drought tolerance, a rehydration capability, and is nutrient rich.
The key genes and metabolic pathways involved in drought-stress and rehydration were investigated using a transcriptome analysis to clarify the relevant molecular mechanisms. In total, 173.93 Mb clean reads, 26.09 Gb of data bulk, and 52,954 unigenes were obtained. Under drought-stress and rehydration conditions, 14,235 and 8539 differentially expressed genes, respectively, were detected. ‘Tyrosine metabolic’, ‘caffeine metabolism’, ‘ribosome’, ‘phagosome’, and ‘proline and arginine metabolism’, as well as ‘peroxisome’ and ‘mitogen-activated protein kinase signaling’ pathways, had major roles in A. fibrillifera responses to drought stress. ‘Tyrosine’ and ‘caffeine metabolism’ might reveal unknown mechanisms for the antioxidation of A. fibrillifera under drought-stress conditions. During the rehydration process, ‘diterpenoid biosynthesis’, ‘butanoate metabolism’, ‘C5-branched dibasic acid’, and ‘aflatoxin biosynthesis’ pathways were significantly enriched. Gibberellins and γ-aminobutyric acid were important in the recovery of A. fibrillifera growth after rehydration. Many genes related to antibiotics, vitamins, and other health-related ingredients were found in A. fibrillifera.
These findings suggested that the candidate genes and metabolites involved in crucial biological pathways might regulate the drought tolerance or rehydration of Auricularia, shedding light on the corresponding mechanisms and providing new potential targets for the breeding and cultivation of drought-tolerant fungi.
Colletotrichum fructicola, the causal agent of pear anthracnose, causes significant annual economic losses. Mitogen-activated protein kinase (MAPK) cascades are highly conserved signal transduction pathways that play a crucial role in mediating cellular responses to environmental and host signals in plant pathogenic fungi. In this study, we identified an ortholog of the FUS3/KSS1-related MAPK gene, CfMK1, and characterized its function in C. fructicola. The Cfmk1 deletion mutants exhibited poorly developed aerial hyphae, autolysis, no conidial mass or perithecia on solid plates. However, the conidiation of the Cfmk1 mutant in PDB liquid medium was normal compared with that of the wild type (WT). Conidia of the Cfmk1 mutant exhibited a reduced germination rate on glass slides or plant surfaces. The Cfmk1 deletion mutants were unable to form appressoria and lost the capacity to penetrate plant epidermal cells. The ability of the Cfmk1 mutants to infect pear leaves and fruit was severely reduced. Moreover, RNA sequencing (RNA-seq) analysis of the WT and Cfmk1 mutant was performed, and the results revealed 1886 upregulated and 1554 downregulated differentially expressed genes (DEGs) in the mutant. The DEGs were significantly enriched in cell wall and pathogenesis terms, which was consistent with the defects of the Cfmk1 mutant in cell wall integrity and plant infection. Overall, our data demonstrate that CfMK1 plays critical roles in the regulation of aerial hyphal growth, asexual and sexual reproduction, autolysis, appressorium formation, and pathogenicity.
Mitogen-activated protein kinase 4 (MPK4) was first identified as a negative regulator of systemic acquired resistance. It is also an important kinase involved in many other biological processes in plants, including cytokinesis, reproduction, and photosynthesis. Arabidopsis thaliana mpk4 mutant is dwarf and sterile. Previous omics studies including genomics, transcriptomics, and proteomics have revealed new functions of MPK4 in different biological processes. However, due to challenges in metabolomics, no study has touched upon the metabolomic profiles of the mpk4 mutant. What metabolites and metabolic pathways are potentially regulated by MPK4 are not known. Metabolites are crucial components of plants, and they play important roles in plant growth and development, signaling, and defense. Here we used targeted and untargeted metabolomics to profile metabolites in the wild type and the mpk4 mutant. We found that in addition to the jasmonic acid and salicylic acid pathways, MPK4 is involved in polyamine synthesis and photosynthesis. In addition, we also conducted label-free proteomics of the two genotypes. The integration of metabolomics and proteomics data allows for an insight into the metabolomic networks that are potentially regulated by MPK4.
Immune-mediated hepatic injury plays a key role in the initiation and pathogenesis of diverse liver diseases. However, treatment choice for immune-mediated hepatic injury remains limited. Corilagin, a natural ellagitannin extracted from various traditional Chinese medicines, has been demonstrated to exhibit multiple pharmacological activities, such as anti-inflammatory, anti-tumor, and hepatoprotective properties. The present study aimed to investigate the effects of corilagin on immune-mediated hepatic injury using a murine model of concanavalin A (Con A)-induced hepatitis, which is well-characterized to study acute immune-mediated hepatitis. Herein, mice were administered corilagin (25 mg/kg) intraperitoneally twice at 12 h intervals, and 1 h later, the mice were challenged with Con A (20 mg/kg body weight); serum and liver samples were collected after 12 h. The results showed that corilagin significantly increased the survival of mice and reduced serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels. In addition, corilagin markedly improved histopathological damage, hepatocyte apoptosis, and oxidative stress in the liver. The activation of M1 macrophages in the hepatic mononuclear cells was also significantly reduced compared with that in the control group. The expression of M1 macrophage-associated proinflammatory cytokines and genes, including interleukin (IL)-6, IL-12, and inducible nitric oxide synthase (iNOS), was also decreased after corilagin treatment. Finally, the results demonstrated that corilagin regulated macrophage polarization by modulating the mitogen-activated protein kinases (MAPK), nuclear factor (NF)-κB, and interferon regulatory factor (IRF) signaling pathways. Thus, the findings indicate that corilagin protects mice from Con A-induced immune-mediated hepatic injury by limiting M1 macrophage activation via the MAPK, NF-κB, and IRF signaling pathways, suggesting corilagin as a possible treatment choice for immune-mediated hepatic injury.
So far, a number of acupuncture studies have shown anti-inflammatory effects of acupuncture treatment, mostly known at specific point ST36. However, there is no literature that oversaw the inflammation-regulatory effects of acupuncture in each tissue. Therefore, we investigated how acupuncture at specific acupoint ST36 regulates inflammation and its underlying mechanisms. We searched literatures on PubMed until July 2021 using the keywords “animal, acupuncture, ST36, inflammation, immune,” and 292 literatures were searched. We ultimately selected 69 studies to determine the anti-inflammatory actions of acupuncture at ST36 and classified the changes of inflammatory mediators according to target regions. Forty-three studies were included in body fluids, 27 studies in the digestive system, 17 studies in the nervous system, and 30 studies in other tissues or organs. In this review, we found that acupuncture at ST36 has clinical benefits in relieving inflammation through several mechanisms such as vagus nerve activation, toll-like receptor 4 (TLR4)/NF-κB signaling, macrophage polarization, mitogen-activated protein kinase (MAPK) signaling pathway, and cholinergic anti-inflammatory pathway. We expect that these data will inform further studies related to ST36 acupuncture on inflammation.
AbstractBactrocera dorsalis is an invasive polyphagous pest causing considerable ecological and economic damage worldwide. We report a high-quality chromosome-level genome assembly and combine various transcriptome data to explore the molecular mechanisms of its rapid adaptation to new environments. The expansions of the DDE transposase superfamily and key gene families related to environmental adaptation and enrichment of the expanded and unique gene families in metabolism and defence response pathways explain its environmental adaptability. The relatively high but not significantly different expression of heat-shock proteins, regardless of the environmental conditions, suggests an intrinsic mechanism underlying its adaptation to high temperatures. The mitogen-activated protein kinase pathway plays a key role in adaptation to new environments. The prevalence of duplicated genes in its genome explains the diversity in the B. dorsalis complex. These findings provide insights into the genetic basis of the invasiveness and diversity of B. dorsalis, explaining its rapid adaptation and expansion.