Hypoxia-Inducible Ubiquitin Specific Peptidase 13 Contributes to Tumor Growth and Metastasis via Enhancing the Toll–LikeReceptor4/Myeloid Differentiation Primary Response Gene 88/Nuclear Factor-κB Pathway in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the main causes of cancer death around the world. The activation of the differentiation of the 4 / myeloid receiver type main response gene 88 / nuclear factor-κB (TLR4 / MyD88 / NF-κB) contributes to the development and progression of HCC. The ubiquitine-proteasome system regulates the TLR4 expression. However, if the PEPTIDASE 13 (USP13) specific to Ubiquitin (USP13) stabilizes TLR4 and facilitates the progression of HCC remains uncertain.
Here, a quantitative analysis of real-time PCR (QRT-PCR) and immunohistochemistry revealed that the USP13 expression in HCC tissues was greater than that of non-tumor focoise tissues. In addition, the high expression of USP13 was detected in HCC cells (SK-HEP-1, HEPG2, HUH7 and HEP3B) relative to LO2 cells. Interestingly, the positive staining of USP13 was closely correlated at the tumor size ≥ 5 cm and at the stage of the advanced tumor and conferred on a significantly lower survival of patients with SCH. Then, USP13 Hashingdown has significantly reduced proliferation, epithelial-messenchymatory transition (EMT), migration and invasion of HEP3B and HUH7 cells, while USP13 overexpression improved these biological behaviors of HEPG2 and LO2 cells.
The silence of USP13 has significantly limited the growth and pulmonary metastasis of HCC cells in vivo. Mechanically, USP13 depletion significantly marked the TLR4 / MYD88 / NF-κB channel in HCC cells. USP13 interacted with TLR4 and inhibited the degradation of the Ubiquitine-mediated TLR4. Significantly, the TLR4 re-expression remarkably reversed the effects of USP13 isolation on HCC cells. The USP13 expression was clearly regulated in HCC cells under hypoxia conditions. NOTABLY, USP13 BULLDOWN has repressed the activation induced by hypoxia of the TLR4 / MYD88 / NF-κB channel in HCC cells. In conclusion, our study discovered that the USP13 induced by hypoxia facilitated HCC progression through the improvement of TLR4 desubility and the subsequent activation of the TLR4 / MYD88 / NF-KB channel.
Preparation of anti-em> toll </ em> – <em> like </ em> <em> </ em> – <em> 4 </ em> nano-antibodies and its effect on the negative sepsy of Gram negative
The essence of sepsis is the excessive immune response caused by infectious factors, resulting in the release of a large number of inflammatory factors and the injury of tissues and organs. Once the reaction is triggered, it will develop according to its own rules and will not depend on infection factors. The occurrence and severity of sepsis depend entirely on the body’s reaction. When pathogens invade the body, they rely on pattern recognition receivers to play a defensive role, TLR4 is the main switch of innate immunity. Current research shows that the LPS can induce the subsequent regulation of TLR4 gene expression in monocytes, neutrophils and other immune cells. The regulated TLR4, as a new receiver, mediate more cell activation and the release of inflammatory mediators.
Under this positive return, the inflammatory response is constantly amplified, which finally leads to the development of sepsis. In this study, the TLR4 extracellular domain antigen was obtained by the expression and purification of proteins, as well as the anti-TLR4 C-terminal and intermediate domain nano-antibody were obtained by the technology for preparing the Anti-phage antibody library. The in vitro and in vivo experiments confirmed that anti-TLR4 antibody can effectively reduce the release of inflammatory factors and improve the survival rate of animals, while the C-terminal and intermediate terminal are closed at the same time, The effect is more obvious. . The clinical treatment of sepsis provides new ideas and strategies.
Hypoxia-Inducible Ubiquitin Specific Peptidase 13 Contributes to Tumor Growth and Metastasis via Enhancing the Toll–LikeReceptor4/Myeloid Differentiation Primary Response Gene 88/Nuclear Factor-κB Pathway in Hepatocellular Carcinoma
Activation of <em> toll </ em> <em> as </ em> <em> </ em> <em> 4 </ em> (TLR <em> 4 </ em>) promotes apoptosis cardiomyocyte through Sirt2 dependent p53 deacetylation
Cardiomyocyte inflammation followed by apoptosis and fibrosis is an important mediator for the development and progression of heart failure. Activating the type 4 receptor (TLR4), an important inflammation regulator, causes progression of cardiac hypertrophy and injury. However, the precise mechanism of the adverse cardiac results of the TLR4 is still elusive. This study was designed to find the role of TLR4 in cardiac fibrosis and apoptosis and its molecular mechanism.
The rats were treated with a TLR4 agonist (LPS 12.5 μg / kg / day) by the osmotic pump for 14 days. To simulate the in vitro condition, H9C2 cells were treated with LPS (1 μg / ml). Similarly, H9C2 cells were transfected with the TLR4 and Sirt2 C-DNA clone for overexpression. The oxidative stress of myocardial, inflammation, fibrosis and mitochondrial parameters have been evaluated both in vitro and in vivo. Cardiac inflammation after the treatment of LPS has been confirmed by an increased expression of TNF-α and IL-6 in the rat’s heart. There was a marked increase in oxidative stress as observed by the increase of the Tbars and a decrease in endogenous antioxidants (GSH and Catalase), as well as mitochondrial dysfunction, as measured by a mitochondrial complex activity in the hearts of rats treated by The LPS. Histopathological examination showed the presence of cardiac fibrosis after the treatment of LPS. The expression of proteins of the nuclear P53 and CASPASE-7-7 / CASPASE-9 has been considerably increased in the LP-treated heart.
Description: A sandwich quantitative ELISA assay kit for detection of Human Arginine Vasopressin Receptor 1B (AVPR1B) in samples from tissue homogenates or other biological fluids.
Human Arginine Vasopressin Receptor 1B (AVPR1B) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Human Arginine Vasopressin Receptor 1B (AVPR1B) in samples from tissue homogenates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Arginine Vasopressin Receptor 1B (AVPR1B) in samples from tissue homogenates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Mouse Arginine Vasopressin Receptor 1B (AVPR1B) in samples from tissue homogenates or other biological fluids.
Rat Arginine Vasopressin Receptor 1B (AVPR1B) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Rat Arginine Vasopressin Receptor 1B (AVPR1B) in samples from tissue homogenates or other biological fluids.
Rat Arginine Vasopressin Receptor 1B (AVPR1B) ELISA Kit
Description: A sandwich quantitative ELISA assay kit for detection of Rat Arginine Vasopressin Receptor 1B (AVPR1B) in samples from tissue homogenates or other biological fluids.
Human Arginine Vasopressin Receptor 1B (AVPR1B) ELISA Kit
Description: A polyclonal antibody for detection of AVP Receptor V2 from Human, Mouse. This AVP Receptor V2 antibody is for WB, ELISA. It is affinity-purified from rabbit serum by affinity-chromatography using the specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from part region of human AVP Receptor V2 protein at amino acid sequence of 1-50
Description: A polyclonal antibody for detection of AVP Receptor V2 from Human, Mouse. This AVP Receptor V2 antibody is for WB, ELISA. It is affinity-purified from rabbit serum by affinity-chromatography using the specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from part region of human AVP Receptor V2 protein at amino acid sequence of 1-50
Description: A polyclonal antibody for detection of AVP Receptor V2 from Human, Mouse. This AVP Receptor V2 antibody is for WB, ELISA. It is affinity-purified from rabbit serum by affinity-chromatography using the specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from part region of human AVP Receptor V2 protein at amino acid sequence of 1-50
Description: A polyclonal antibody for detection of AVP Receptor V2 from Human. This AVP Receptor V2 antibody is for WB, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human AVP Receptor V2 at AA range: 40-120
Description: A polyclonal antibody for detection of AVP Receptor V2 from Human. This AVP Receptor V2 antibody is for WB, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human AVP Receptor V2 at AA range: 40-120
Description: A polyclonal antibody for detection of AVP Receptor V2 from Human. This AVP Receptor V2 antibody is for WB, IF, ELISA. It is affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific immunogenand is unconjugated. The antibody is produced in rabbit by using as an immunogen synthesized peptide derived from the Internal region of human AVP Receptor V2 at AA range: 40-120
Description: A polyclonal antibody against Avpr1b. Recognizes Avpr1b from Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB; Recommended dilution: WB:1:1000-1:5000
Description: A polyclonal antibody against AVPR1B. Recognizes AVPR1B from Human. This antibody is Unconjugated. Tested in the following application: WB, IF, ELISA;WB:1/500-1/2000.IF:1/200-1/1000.ELISA:1/20000
Description: A polyclonal antibody against AVPR1B. Recognizes AVPR1B from Human, Mouse, Rat. This antibody is Unconjugated. Tested in the following application: IHC, ELISA;IHC-p:1:50-300, ELISA:1:10000-20000
Description: A polyclonal antibody against AVP. Recognizes AVP from Human, Rat. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC; Recommended dilution: WB:1:200-1:1000, IHC:1:20-1:200
Description: Copeptin is a 39-amino acid glycopeptide, cleaved from the C-terminus of pre- provasopressin (pre-proAVP). It has been suggested as a biomarker in diagnosis and prognosis of several diseases, such as acute myocardial infarction, heart failure, hyponatremia, and sepsis.
Description: Copeptin is a 39-amino acid glycopeptide, cleaved from the C-terminus of pre- provasopressin (pre-proAVP). It has been suggested as a biomarker in diagnosis and prognosis of several diseases, such as acute myocardial infarction, heart failure, hyponatremia, and sepsis.
Description: Copeptin is a 39-amino acid glycopeptide, cleaved from the C-terminus of pre- provasopressin (pre-proAVP). It has been suggested as a biomarker in diagnosis and prognosis of several diseases, such as acute myocardial infarction, heart failure, hyponatremia, and sepsis.
Description: Copeptin is a 39-amino acid glycopeptide, cleaved from the C-terminus of pre- provasopressin (pre-proAVP). It has been suggested as a biomarker in diagnosis and prognosis of several diseases, such as acute myocardial infarction, heart failure, hyponatremia, and sepsis.
Description: This gene encodes a member of the vasopressin/oxytocin family and preproprotein that is proteolytically processed to generate multiple protein products. These products include the neuropeptide hormone arginine vasopressin, and two other peptides, neurophysin 2 and copeptin. Arginine vasopressin is a posterior pituitary hormone that is synthesized in the supraoptic nucleus and paraventricular nucleus of the hypothalamus. Along with its carrier protein, neurophysin 2, it is packaged into neurosecretory vesicles and transported axonally to the nerve endings in the neurohypophysis where it is either stored or secreted into the bloodstream. The precursor is thought to be activated while it is being transported along the axon to the posterior pituitary. Arginine vasopressin acts as a growth factor by enhancing pH regulation through acid-base transport systems. It has a direct antidiuretic action on the kidney, and also causes vasoconstriction of the peripheral vessels. This hormone can contract smooth muscle during parturition and lactation. It is also involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of water excretion and cardiovascular functions. Mutations in this gene cause autosomal dominant neurohypophyseal diabetes insipidus (ADNDI). This gene is present in a gene cluster with the related gene oxytocin on chromosome 20.
Description: A polyclonal antibody against Avpr1b. Recognizes Avpr1b from Rat. This antibody is HRP conjugated. Tested in the following application: ELISA
Description: A polyclonal antibody against Avpr1b. Recognizes Avpr1b from Rat. This antibody is FITC conjugated. Tested in the following application: ELISA
Description: A polyclonal antibody against Avpr1b. Recognizes Avpr1b from Rat. This antibody is Biotin conjugated. Tested in the following application: ELISA
Description: A polyclonal antibody against AVP. Recognizes AVP from Human. This antibody is FITC conjugated. Tested in the following application: ELISA
Description: A polyclonal antibody against AVP. Recognizes AVP from Human. This antibody is Biotin conjugated. Tested in the following application: ELISA
Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human AVP (Center). This antibody is tested and proven to work in the following applications:
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Mouse Arginine Vasopressin Receptor 1B (AVPR1B) in Tissue homogenates and other biological fluids.
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Mouse Arginine Vasopressin Receptor 1B (AVPR1B) in Tissue homogenates and other biological fluids.
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Mouse Arginine Vasopressin Receptor 1B (AVPR1B) in Tissue homogenates and other biological fluids.
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Mouse Arginine Vasopressin Receptor 1B (AVPR1B) in Tissue homogenates and other biological fluids.
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Similar to in vivo study, the nuclear translocation of P53, mitochondrial and cell apoptosis dysfunction were observed in the H9C2 cells treated with LPS. Our data also indicates that SIRT2 reduced expression was associated with an increase in acetylation of P53 after the treatment of the LPS. In conclusion, TLR4 activation in rats promotes cardiac inflammation, mitochondrial dysfunction, apoptosis and fibrosis. P53 and CASPASE 7 / CASPASE 9 were found to play an important role in the apoptosis mediated by TLR4. Our data suggest that TLR4-mediated fibrosis reduction and apoptosis could be a new approach in the treatment of heart failure, taking into account the major role played by TLR4 in cardiac inflammation.
Parker
