Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by
) is a member of the laminin family, which is mainly expressed in the basement ...membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of
, a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPβ pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPβ pathway.
Emerging evidence suggests that epithelial‐mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is ...crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor‐related miRNAs were significantly decreased. Among these miRNAs, miR‐125b expression was most strongly suppressed. We also found down‐regulation of miR‐125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR‐125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR‐125b promoted the EMT phenotype in vitro and in vivo. Moreover, we found that miR‐125b attenuated EMT‐associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR‐125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR‐125b suppressed EMT and EMT‐associated traits of HCC cells by targeting small mothers against decapentaplegic (SMAD)2 and 4. Most important, the therapeutic delivery of synthetic miR‐125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR‐125b for liver cancer. Conclusion: miR‐125b exerts inhibitory effects on EMT and EMT‐associated traits in HCC by SMAD2 and 4. Ectopic expression of miR‐125b provides a promising strategy to treat HCC. (Hepatology 2015;62:801–815)
Morphine‐induced scratching (MIS) is a common adverse effect associated with the use of morphine as analgesia after surgery. However, the treatment of MIS is less than satisfactory due to its unclear ...mechanism, which needs to be enunciated. We found that intrathecal (i.t.) injections of morphine significantly enhanced scratching behavior in C57BL/6J male mice as well as increased the expressions of protein kinase C β (PKCβ), phosphorylated p38 mitogen‐activated protein kinases (MAPK), and ionized calcium‐binding adapter molecule 1 (Iba1) within spinal cord dorsal horn. Conversely, using the kappa opioid receptor antagonist nalbuphine significantly attenuated scratching behavior, reduced PKCβ expression and p38 phosphorylation, and decreased spinal dorsal horn microglial activation, while PKCδ and KOR expression elevated. Spinal PKCβ silencing mitigated MIS and microglial activation. Still, knockdown of PKCδ reversed the inhibitory effect of nalbuphine on MIS and microglial activation, indicating that PKCδ is indispensable for the antipruritic effects of nalbuphine. In contrast, PKCβ is crucial for inducing microglial activation in MIS in male mice. Our findings show a distinct itch cascade of morphine, PKCβ/p38MAPK, and microglial activation, but an anti‐MIS pathway of nalbuphine, PKCδ/KOR, and neuron activation.
PKCβ was activated, evoking microglia activation and p38 MAPK phosphorylation, resulting in morphine‐induced scratching. Whereas nalbuphine interrupts PKCβ activation and inhibits microglia/p‐p38 MAPK pathway, is via activate KOR‐PKCδ pathway. PKCβ and PKCδ compensate each other in MIS when one is absent.
A comparative study based on MgH
2
ball-milled with altered Ni particle sizes under different conditions was conducted to reveal the effect of close contact between hydrides and metal catalysts on ...their hydrogen sorption properties. It is found that the Mg + nano-Ni (5 at%) composites not only exhibit a substantial decreased onset desorption temperature by approximately 180 °C but also dramatically enhance the absorption kinetics by sixteen times in comparison with those of pure MgH
2
. This remarkable kinetics enhancement can be explained by the superior catalytic effect of Ni present in composites that highly depends on its particle size and its close contact with MgH
2
.
Decidualization is a process in which endometrial stromal fibroblasts differentiate into specialized secretory decidual cells and essential for the successful establishment of pregnancy. The ...underlying mechanism during decidualization still remains poorly defined. Because decidualization and fibroblast activation share similar characteristics, this study was to examine whether fibroblast activation is involved in decidualization. In our study, fibroblast activation-related markers are obviously detected in pregnant decidua and under in vitro decidualization. ACTIVIN A secreted under fibroblast activation promotes in vitro decidualization. We showed that arachidonic acid released from uterine luminal epithelium can induce fibroblast activation and decidualization through PGI
and its nuclear receptor PPARδ. Based on the significant difference of fibroblast activation-related markers between pregnant and pseudopregnant mice, we found that embryo-derived TNF promotes CPLA
phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI
-PPARδ-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA
phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization.
Decidualization is essential to the successful pregnancy in mice. The molecular mechanisms and effects of Aurora kinase A (Aurora A) remain poorly understood during pregnancy. This study is the first ...to investigate the expression and role of Aurora A during mouse decidualization.
Quantitative real time polymerase chain reaction, western blotting and in situ hybridization were used to determine the expression of Aurora A in mouse uteri. Aurora A activity was inhibited by Aurora A inhibitor to explore the role of Aurora A on decidualization via regulating the Aurora A/Stat3/Plk1/Cdk1 signaling pathway.
Aurora A was strongly expressed at implantation sites compared with inter-implantation sites. Furthermore, Aurora A was also significantly increased in oil-induced deciduoma compared with control. Both Aurora A mRNA and protein were significantly increased under in vitro decidualization. Under in vitro decidualization, Prl8a2, a marker of mouse decidualization, was significantly decreased by TC-S 7010, an Aurora A inhibitor. Additionally, Prl8a2 was reduced by Stat3 inhibitor, Plk1 inhibitor and Cdk1 inhibitor, respectively. Moreover, the protein levels of p-Stat3, p-Plk1 and p-Cdk1 were suppressed by TC-S 7010. The protein levels of p-Stat3, p-Plk1 and p-Cdk1 were also suppressed by S3I-201, a Stat3 inhibitor). SBE 13 HCl (Plk1 inhibitor) could reduce the protein levels of p-Plk1 and p-Cdk1. Collectively, Aurora A could regulate Stat3/Plk1/Cdk1 signaling pathway.
Our study shows that Aurora A is expressed in decidual cells and should be important for mouse decidualization. Aurora A/Stat3/Plk1/Cdk1 signaling pathway may be involved in mouse decidualization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Heat stress commonly leads to inhibition of photosynthesis in higher plants. The transcriptional induction of heat stress-responsive genes represents the first line of inducible defense against ...imbalances in cellular homeostasis. Although heat stress transcription factor HsfA2 and its downstream target genes are well studied, the regulatory mechanisms by which HsfA2 is activated in response to heat stress remain elusive. Here, we show that chloroplast ribosomal protein S1 (RPS1) is a heat-responsive protein and functions in protein biosynthesis in chloroplast. Knockdown of RPS1 expression in the rps1 mutant nearly eliminates the heat stress-activated expression of HsfA2 and its target genes, leading to a considerable loss of heat tolerance. We further confirm the relationship existed between the downregulation of RPS1 expression and the loss of heat tolerance by generating RNA interference-transgenic lines of RPS1. Consistent with the notion that the inhibited activation of HsfA2 in response to heat stress in the rps1 mutant causes heat-susceptibility, we further demonstrate that overexpression of HsfA2 with a viral promoter leads to constitutive expressions of its target genes in the rps1 mutant, which is sufficient to reestablish lost heat tolerance and recovers heat-susceptible thylakoid stability to wild-type levels. Our findings reveal a heat-responsive retrograde pathway in which chloroplast translation capacity is a critical factor in heat-responsive activation of HsfA2 and its target genes required for cellular homeostasis under heat stress. Thus, RPS1 is an essential yet previously unknown determinant involved in retrograde activation of heat stress responses in higher plants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Endometrial decidualization plays a pivotal role during early pregnancy. Compromised decidualization has been tightly associated with recurrent implantation failure (RIF). Primary cilium is an ...antenna-like sensory organelle and acts as a signaling nexus to mediate Hh, Wnt, TGFβ, BMP, FGF, and Notch signaling. However, whether primary cilium is involved in human decidualization is still unknown. In this study, we found that primary cilia are present in human endometrial stromal cells. The ciliogenesis and cilia length are increased by progesterone during in vitro and in vivo decidualization. Primary cilia are abnormal in the endometrium of RIF patients. Based on data from both assembly and disassembly of primary cilia, it has been determined that primary cilium is essential to human decidualization. Trichoplein (TCHP)-Aurora A signaling mediates cilia disassembly during human in vitro decidualization. Mechanistically, primary cilium modulates human decidualization through PTEN-PI3K-AKT-FOXO1 signaling. Our study highlights primary cilium as a novel decidualization-related signaling pathway.
Liquid metals have attracted a lot of attention as self‐healing materials in many fields. However, their applications in secondary batteries are challenged by electrode failure and side reactions due ...to the drastic volume changes during the “liquid‐solid‐liquid” transition. Herein, a simple encapsulated, mass‐producible method is developed to prepare room‐temperature liquid metal‐infilled microcapsules (LMMs) with highly conductive carbon shells as anodes for lithium‐ion batteries. Due to the reasonably designed voids in the microcapsule, the liquid metal particles (LMPs) can expand freely without damaging the electrode structure. The LMMs‐based anodes exhibit superior capacity of rete‐performance and ultra‐long cycling stability remaining 413 mAh g−1 after 5000 cycles at 5.0 A g−1. Ex situ X‐ray powder diffraction (XRD) patterns and electrochemical impedance spectroscopy (EIS) reveal that the LMMs anode displays a stable alloying/de‐alloying mechanism. DFT calculations validate the electronic structure and stability of the room‐temperature LMMs system. These findings will bring some new opportunities to develop high‐performance battery systems.
A simple encapsulated, mass‐producible method is developed to prepare room‐temperature liquid metal‐infilled microcapsules (LMMs) with highly conductive carbon shells as anodes for lithium‐ion batteries. The LMMs‐based anodes exhibit superior capacity of rete‐performance and ultra‐long cycling stability. These findings will bring some new opportunities to develop high‐performance battery systems.
Ubiquitin specific protease 5 (USP5) is a vital deubiquitinating enzyme that regulates various physiological functions by removing ubiquitin chains from target proteins. This review provides an ...overview of the structural and functional characteristics of USP5. Additionally, we discuss the role of USP5 in regulating diverse cellular processes, including cell proliferation, apoptosis, DNA double-strand damage, methylation, heat stress, and protein quality control, by targeting different substrates. Furthermore, we describe the involvement of USP5 in several pathological conditions such as tumors, pathological pain, developmental abnormalities, inflammatory diseases, and virus infection. Finally, we introduce newly developed inhibitors of USP5. In conclusion, investigating the novel functions and substrates of USP5, elucidating the underlying mechanisms of USP5-substrate interactions, intensifying the development of inhibitors, and exploring the upstream regulatory mechanisms of USP5 in detail can provide a new theoretical basis for the treatment of various diseases, including cancer, which is a promising research direction with considerable potential. Overall, USP5 plays a critical role in regulating various physiological and pathological processes, and investigating its novel functions and regulatory mechanisms may have significant implications for the development of therapeutic strategies for cancer and other diseases.
Display omitted
•USPS regulates various cellular biology processes.•USPS links to diseases: tumors, pain, abnormalities, inflammation, and viral infections.•12 new USPS inhibitors for potential cancer, pain, and inflammation therapy.
PDF
