Sepsis is a systemic inflammatory response that can lead to organ dysfunction and/or circulatory disorders in severe cases. The dysregulated inflammatory response plays a pivotal role in ...sepsis-induced liver injury. A variety of microRNAs and lncRNAs have been shown to be involved in the inflammatory response. However, their role in regulating sepsis-induced liver injury remains to be revealed.
Human hepatic tissue and healthy tissue were used for in vivo level detection. And Raw264.7 cells and Kupffer cells were used for in vitro modelling. The relative mRNA expression and the protein levels of TNF-α, IL-6 and IL-1β were detected by q-PCR or by enzyme-linked immunosorbent assay (ELISA), respectively. The binding of lncRNA NEAT1/Let-7a and Let-7a/TLR4 was detected by dual-luciferase reporter assay. RNA Immunoprecipitation (RIP) was used to detect the targeting relationship between lncRNA NEAT1 and Let-7a. Western blotting (WB) was used to detect TLR4 expression in different cell models.
The overexpression of lncRNA NEAT1 accompanied by Let-7a inhibition and TLR4 activation was found in sepsis-induced liver injury patients. Similarly, LPS stimulation upregulated lncRNA NEAT1 expression, and lncRNA NEAT1 inhibition decreased the levels of inflammatory cytokines in vitro. Let-7a inhibitor treatment as well as TLR4 overexpression rescued the expression of inflammatory cytokines in lncRNA NEAT1-knockdown cells. Moreover, Let-7a interacted with both lncRNA NEAT1 and TLR4.
We demonstrate that lncRNA NEAT1 interacts with Let-7a, targeting TLR4 to contribute to the LPS-induced inflammatory response. Our assay can provide a potential therapeutic target for sepsis-induced liver injury.
•LncRNA NEAT1was significantly upregulated in sepsis-induced liver injury patients.•Suppression of lncRNA NEAT1 attenuated LPS-induced inflammatory response in vitro.•The lncRNA NEAT1/Let-7a/TLR4 axis was identified.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Ethylene is a gaseous hormone which plays important roles in both plant growth and development and stress responses. Based on studies in the dicot model plant species Arabidopsis, a linear ethylene ...signaling pathway has been established, according to which ethylene is perceived by ethylene receptors and transduced through CONSTITUTIVE TRIPLE RESPONSE 1 (CTR1) and ETHYLENE‐INSENSITIVE 2 (EIN2) to activate transcriptional reprogramming. In addition to this canonical signaling pathway, an alternative ethylene receptor‐mediated phosphor‐relay pathway has also been proposed to participate in ethylene signaling. In contrast to Arabidopsis, rice, a monocot, grows in semiaquatic environments and has a distinct plant structure. Several novel regulators and/or mechanisms of the rice ethylene signaling pathway have recently been identified, indicating that the ethylene signaling pathway in rice has its own unique features. In this review, we summarize the latest progress and compare the conserved and divergent aspects of the ethylene signaling pathway between Arabidopsis and rice. The crosstalk between ethylene and other plant hormones is also reviewed. Finally, we discuss how ethylene regulates plant growth, stress responses and agronomic traits. These analyses should help expand our knowledge of the ethylene signaling mechanism and could further be applied for agricultural purposes.
Ethylene plays vital roles in plant growth and development and stress responses. In this review, we summarize the latest progress and compare the conserved and divergent aspects of the ethylene signaling pathway between Arabidopsis and rice. The agricultural significance of ethylene signaling in crops is also discussed.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Reliable and noninvasive biomarkers for the early diagnosis of non‐small‐cell lung cancer (NSCLC) are an unmet need. This study aimed to screen and validate potential urinary biomarkers for the early ...diagnosis of NSCLC. Using protein mass spectrometry, urinary MDH2 was found to be abundant both in patients with lung cancer and lung cancer model mice compared with controls. Urine samples obtained as retrospective and prospective cohorts including 1091 NSCLC patients and 736 healthy controls were measured using ELISA. Patients with stage I NSCLC had higher urinary MDH2 compared with healthy controls. The area under the receiver‐operating characteristic curve (AUC) for the urinary MDH2 was 0.7679 and 0.7234 in retrospective and prospective cohorts to distinguish stage I cases from controls. Urinary MDH2 levels correlated with gender and smoking history. MDH2 expression levels were elevated in lung cancer tissues. MDH2 knockdown using shRNA inhibited the proliferation of lung cancer cells. Our study demonstrated that urinary MDH2 concentration was higher in early‐stage NSCLC patients compared with that in controls and that MDH2 could serve as a potential biomarker for early detection of NSCLC.
Malate dehydrogenase 2 was significantly elevated both in urine and in cancer tissues of NSCLC patients. The level of MDH2 in urine could serve as an assistant biomarker for the early diagnosis of NSCLC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Circular RNAs are non-coding RNAs, and are enriched in the CNS. Dorsal horn neurons of the spinal cord contribute to pain-like hypersensitivity after nerve injury in rodents. Here we show that spinal ...nerve ligation is associated with an increase in expression of circAnks1a in dorsal horn neurons, in both the cytoplasm and the nucleus. Downregulation of circAnks1a by siRNA attenuates pain-like behaviour induced by nerve injury. In the cytoplasm, we show that circAnks1a promotes the interaction between transcription factor YBX1 and transportin-1, thus facilitating the nucleus translocation of YBX1. In the nucleus, circAnks1a binds directly to the Vegfb promoter, increases YBX1 recruitment to the Vegfb promoter, thereby facilitating transcription. Furthermore, cytoplasmic circAnks1a acts as a miRNA sponge in miR-324-3p-mediated posttranscriptional regulation of VEGFB expression. The upregulation of VEGFB contributes to increased excitability of dorsal horn neurons and pain behaviour induced by nerve injury. We propose that circAnks1a and VEGFB are regulators of neuropathic pain.
Ethylene plays essential roles during adaptive responses to water-saturating environments in rice, but knowledge of its signaling mechanism remains limited. Here, through an analysis of a rice ...ethylene-response mutant mhz1, we show that MHZ1 positively modulates root ethylene responses. MHZ1 encodes the rice histidine kinase OsHK1. MHZ1/OsHK1 is autophosphorylated at a conserved histidine residue and can transfer the phosphoryl signal to the response regulator OsRR21 via the phosphotransfer proteins OsAHP1/2. This phosphorelay pathway is required for root ethylene responses. Ethylene receptor OsERS2, via its GAF domain, physically interacts with MHZ1/OsHK1 and inhibits its kinase activity. Genetic analyses suggest that MHZ1/OsHK1 acts at the level of ethylene perception and works together with the OsEIN2-mediated pathway to regulate root growth. Our results suggest that MHZ1/OsHK1 mediates the ethylene response partially independently of OsEIN2, and is directly inhibited by ethylene receptors, thus revealing mechanistic details of ethylene signaling for root growth regulation.
ABSTRACT
Abiotic stress is one of the most important factors reducing soybean yield. It is essential to identify regulatory factors contributing to stress responses. A previous study found that the ...tandem CCCH zinc‐finger protein GmZF351 is an oil level regulator. In this study, we discovered that the GmZF351 gene is induced by stress and that the overexpression of GmZF351 confers stress tolerance to transgenic soybean. GmZF351 directly regulates the expression of GmCIPK9 and GmSnRK, leading to stomata closing, by binding to their promoter regions, which carry two CT(G/C)(T/A)AA elements. Stress induction of GmZF351 is mediated through reduction in the H3K27me3 level at the GmZF351 locus. Two JMJ30‐demethylase‐like genes, GmJMJ30‐1 and GmJMJ30‐2, are involved in this demethylation process. Overexpression of GmJMJ30‐1/2 in transgenic hairy roots enhances GmZF351 expression mediated by histone demethylation and confers stress tolerance to soybean. Yield‐related agronomic traits were evaluated in stable GmZF351‐transgenic plants under mild drought stress conditions. Our study reveals a new mode of GmJMJ30‐GmZF351 action in stress tolerance, in addition to that of GmZF351 in oil accumulation. Manipulation of the components in this pathway is expected to improve soybean traits and adaptation under unfavorable environments.
The soybean zinc finger protein GmZF351 regulates oil levels and mainly works in seeds. However, the histone demethylase GmJMJ30‐1/2 activates GmZF351 in leaves and roots to improve stress tolerance by mechanisms that differ from the mechanisms acting in seeds.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
Soybean (Glycine max) is one of the most important oilseed crops. However, the regulatory mechanism that governs the process of oil accumulation in soybean remains poorly understood.
In this ...study, GmZF392, a tandem CCCH zinc finger (TZF) protein which was identified in our previous RNA‐seq analysis of seed‐preferred transcription factors, was found to function as a positive regulator of lipid production.
GmZF392 promotes seed oil accumulation in both transgenic Arabidopsis and stable transgenic soybean plants by binding to a bipartite cis‐element, containing TG‐ and TA‐rich sequences, in promoter regions, activating the expression of genes in the lipid biosynthesis pathway. GmZF392 physically interacts with GmZF351, our previously identified transcriptional regulator of lipid biosynthesis, to synergistically promote downstream gene expression. Both GmZF392 and GmZF351 are further upregulated by GmNFYA, another transcription factor involved in lipid biosynthesis, directly (in the former case) and indirectly (in the latter case). Promoter sequence diversity analysis showed that the GmZF392 promoter may have been selected at the origin of the Glycine genus and further mildly selected during domestication from wild soybeans to cultivated soybeans.
Our study reveals a regulatory module containing three transcription factors in the lipid biosynthesis pathway, and manipulation of the module may improve oil production in soybean and other oilseed crops.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Seed weight is usually associated with seed size and is one of the important agronomic traits that determine yield. Understanding of seed weight control is limited, especially in soybean plants. Here ...we show that Glycine max JASMONATE‐ZIM DOMAIN 3 (GmJAZ3), a gene identified through gene co‐expression network analysis, regulates seed‐related traits in soybean. Overexpression of GmJAZ3 promotes seed size/weight and other organ sizes in stable transgenic soybean plants likely by increasing cell proliferation. GmJAZ3 interacted with both G. max RESPONSE REGULATOR 18a (GmRR18a) and GmMYC2a to inhibit their transcriptional activation of cytokinin oxidase gene G. max CYTOKININ OXIDASE 3‐4 (GmCKX3‐4), which usually affects seed traits. Meanwhile, the GmRR18a binds to the promoter of GmMYC2a and activates GmMYC2a gene expression. In GmJAZ3‐overexpressing soybean seeds, the protein contents were increased while the fatty acid contents were reduced compared to those in the control seeds, indicating that the GmJAZ3 affects seed size/weight and compositions. Natural variation in JAZ3 promoter region was further analyzed and Hap3 promoter correlates with higher promoter activity, higher gene expression and higher seed weight. The Hap3 promoter may be selected and fixed during soybean domestication. JAZ3 orthologs from other plants/crops may also control seed size and weight. Taken together, our study reveals a novel molecular module GmJAZ3‐GmRR18a/GmMYC2a‐GmCKXs for seed size and weight control, providing promising targets during soybean molecular breeding for better seed traits.
The soybean jasmonate ZIM doman (JAZ) protein GmJAZ3 regulates seed traits by orchestrating jasmonate and cytokinin signaling. JAZ3 was domesticated in soybean and this gene family shares conserved functions throughout monocots and dicots.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Soybean is an important crop worldwide, but its production is severely affected by salt stress. Understanding the regulatory mechanism of salt response is crucial for improving the salt tolerance of ...soybean. Here, we reveal a role for nuclear factor Y subunit GmNFYA in salt tolerance of soybean likely through the regulation of histone acetylation. GmNFYA is induced by salt stress. Overexpression of GmNFYA significantly enhances salt tolerance in stable transgenic soybean plants by inducing salt‐responsive genes. Analysis in soybean plants with transgenic hairy roots also supports the conclusion. GmNFYA interacts with GmFVE, which functions with putative histone deacetylase GmHDA13 in a complex for transcriptional repression possibly by reducing H3K9 acetylation at target loci. Under salt stress, GmNFYA likely accumulates and competes with GmHDA13 for interaction with GmFVE, leading to the derepression and maintenance of histone acetylation for activation of salt‐responsive genes and finally conferring salt tolerance in soybean plants. In addition, a haplotype I GmNFYA promoter is identified with the highest self‐activated promoter activity and may be selected during future breeding for salt‐tolerant cultivars. Our study uncovers the epigenetic regulatory mechanism of GmNFYA in salt‐stress response, and all the factors/elements identified may be potential targets for genetic manipulation of salt tolerance in soybean and other crops.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer‐caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the ...metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel could be an effective strategy for inhibiting breast cancer metastasis. However, their inherent defects, in terms of short blood circulation half‐life and lack of tumor targeting, not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by a nanodelivery system, and explore its mechanism. Herein, a paclitaxel‐conjugated and mifepristone‐loaded hydrogel (PM‐nano) was prepared by self‐assembly. Its characterizations were studied. The antimetastatic effect was evaluated in vitro and in vivo and its mechanism was also explored by western blot assay. The resultant PM‐nano was developed with favorable water solubility and good biocompatibility. Moreover, PM‐nano displayed increased cell uptake properties and stimulated drug release in the tumor micro‐acidic environment. The PM‐nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. The PM‐nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase‐like orphan receptor 1 and MMPs. Taken together, PM‐nano showed superior antimetastatic effects against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for limiting metastasis.
A novel supramolecular hydrogel coloaded with paclitaxel and mifepristone has good water solubility, fine cell uptake, and biosafety. It can significantly limit the metastasis of breast cancer in vitro and in vivo. It might act by mifepristone/glucocorticoid receptor/ROR1 and MMPs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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