The anorectic action of the pancreatic hormone amylin is mainly mediated through the area postrema (AP). Amylin activates AP neurons using a heterodimeric receptor (AMY) composed of the calcitonin receptor (CTR) and the receptor activity modifying protein (RAMP 1, 2 or 3). The aim of the following experiments is to test the effects of the long acting amylin analogue (LAAMA) in RAMP1/3 knock-out (KO) male **** and in neuronal CTR KO Nestin-CreCTR male ****. In vitro, LAAMA exerted an equipotent effect on CTR and AMYs that was maintained across species. Following one week of 45% high fat diet, WT, RAMP1/3 KO and Nestin-CreCTR **** were injected daily for one week with vehicle or LAAMA. LAAMA decreased body weight gain in WT and in RAMP1/3 KO **** suggesting that RAMP1/3 are not necessary for LAAMA-induced effects. However, LAAMA was not able to produce any body lowering and anorectic effects in Nestin-CreCTR ****. This was accompanied by the absence of any c-Fos signal in the AP opposite to WT control ****. Together, these results suggest that LAAMA's effects are mainly mediated through CTR rather than specific AMY. https://www.selleckchem.com/products/yap-tead-inhibitor-1-peptide-17.html The study of LAAMA or any amylin receptor agonist in different receptor KO mouse models helps disentangle the underlying mechanisms used by these molecules.The purpose of this study was to investigate the role of glycyrrhizic acid (GA) in regulating myocardial ischemia-reperfusion injury (MIRI) in rats as well as the underlying mechanism. H9c2 cells were subjected to hypoxia/re-oxygenation (H/R) to mimic the MIRI in vitro, while a rat model of ischemia-reperfusion (I/R) was constructed by occlusion of the left anterior descending coronary artery for 0.5 h followed by 2 h of reperfusion. While flow cytometry and TUNEL assay were performed to analyze apoptosis in cells and myocardial tissue, echocardiography, hematoxylin and eosin staining, and Masson's trichrome staining were conducted to evaluate cardiac function and pathological changes, respectively. The levels of serum CK, CK-MB, LDH, AST, TNF-α, and IL-6 as well as the contents of MDA and *** in tissues were measured by ELISA, while Western blot analysis was performed to detect the expression of endoplasmic reticulum stress (ERS)-related proteins. GA treatment significantly reduced apoptosis in H9c2 cells, while it alleviated left ventricular dysfunction, fibrosis and myocardial apoptosis, down-regulated the levels of CK, CK-MB, LDH, AST, TNF-α, IL-6, and MDA, and up-regulated *** levels in I/R rats. Moreover, GA treatment led to a decrease in the expression of CHOP, GRP78, and p-PERK in both H/R cells and I/R rats. This study demonstrates that cardioprotective role of GA in MIRI may involve the attenuation of ERS-induced apoptosis and inflammation, potentially providing an alternative strategy for intervention of MIRI.Monocytes are differentiated into macrophages. In this study, mitochondrial DNA copy number (mtDNAcn) levels and downstream events such as the expression of respiratory chain mRNAs were investigated during the phorbol 12-myristate 13-acetate (PMA)-induced differentiation of monocytes. Although PMA treatment increased mtDNAcn, the expression levels of mRNAs encoded in mtDNA were decreased. The levels of mitochondrial transcription factor A mRNA and protein were also decreased. The levels of coenzyme Q10 remained unchanged. These results imply that, although mtDNAcn is considered as a health marker, the levels of mtDNAcn may not always be consistent with the parameters of mitochondrial functions.The introduction of enzyme nanoreactors in medicine is relatively new. However, this technology has already been experimentally successful in cancer treatments, struggle against toxicity of reactive oxygen species in inflammatory processes, detoxification of drugs and xenobiotics, and correction of metabolic and genetic defects by using encapsulated enzymes, acting in single or cascade reactions. Biomolecules, e.g. enzymes, antibodies, reactive proteins capable of inactivating toxicants in the body are called bioscavengers. In this review, we focus on enzyme-containing nanoreactors for in vivo detoxification of organophosphorous compounds (OP) to be used for prophylaxis and post-exposure treatment of OP poisoning. A particular attention is devoted to bioscavenger-containing injectable nanoreactors operating in the bloodstream. The nanoreactor concept implements single or multiple enzymes and cofactors co-encapsulated in polymeric semi-permeable nanocontainers. Thus, the detoxification processes take place in a confined space containing highly concentrated bioscavengers. The article deals with historical and theoretical backgrounds about enzymatic detoxification of OPs in nanoreactors, nanoreactor polymeric enveloppes, realizations and advantages over other approaches using bioscavengers.Lanthanide ions (Ln3+) doped hydroxyapatite (HAP) particles are well established in biomedical areas. Although Ln elements are closely located in the periodic table and have plenty of similar characteristics, the minor differences in the effective ionic radii could cause alterations in the physicochemical and biological properties of HAP substitutes. The present study synthesized lanthanum-(La-) and gadolinium-(Gd-) doped HAP particles (La-HAP and Gd-HAP). And the effects of two types of particles on bone marrow stem cells (BMSCs) viability were also measured and compared in vitro. The results indicated that the Gd-HAP adsorbed more serum proteins from culture media and inhibited the new layer of apatite formation on its surface when comparing to La-HAP with a similar crystalline structure, particle size, and Zeta potential. These surface modifications can significantly reduce the cell adhesion of Gd-HAP, simultaneously decreasing the Gd-HAP particle uptake efficiency. Moreover, the cell viability of Gd-HAP remained higher than that of La-HAP in culture periods. We concluded that a slight variation in the effective ionic radii between Gd3+ and La3+ could alter the adsorption of serum proteins on the particles' surface, modulating subsequent cellular responses. The present work provides an interesting view that Gd-HAP is endowed with better cellular biocompatibility than La-HAP.
The anorectic action of the pancreatic hormone amylin is mainly mediated through the area postrema (AP). Amylin activates AP neurons using a heterodimeric receptor (AMY) composed of the calcitonin receptor (CTR) and the receptor activity modifying protein (RAMP 1, 2 or 3). The aim of the following experiments is to test the effects of the long acting amylin analogue (LAAMA) in RAMP1/3 knock-out (KO) male mice and in neuronal CTR KO Nestin-CreCTR male mice. In vitro, LAAMA exerted an equipotent effect on CTR and AMYs that was maintained across species. Following one week of 45% high fat diet, WT, RAMP1/3 KO and Nestin-CreCTR mice were injected daily for one week with vehicle or LAAMA. LAAMA decreased body weight gain in WT and in RAMP1/3 KO mice suggesting that RAMP1/3 are not necessary for LAAMA-induced effects. However, LAAMA was not able to produce any body lowering and anorectic effects in Nestin-CreCTR mice. This was accompanied by the absence of any c-Fos signal in the AP opposite to WT control mice. Together, these results suggest that LAAMA's effects are mainly mediated through CTR rather than specific AMY. https://www.selleckchem.com/products/yap-tead-inhibitor-1-peptide-17.html The study of LAAMA or any amylin receptor agonist in different receptor KO mouse models helps disentangle the underlying mechanisms used by these molecules.The purpose of this study was to investigate the role of glycyrrhizic acid (GA) in regulating myocardial ischemia-reperfusion injury (MIRI) in rats as well as the underlying mechanism. H9c2 cells were subjected to hypoxia/re-oxygenation (H/R) to mimic the MIRI in vitro, while a rat model of ischemia-reperfusion (I/R) was constructed by occlusion of the left anterior descending coronary artery for 0.5 h followed by 2 h of reperfusion. While flow cytometry and TUNEL assay were performed to analyze apoptosis in cells and myocardial tissue, echocardiography, hematoxylin and eosin staining, and Masson's trichrome staining were conducted to evaluate cardiac function and pathological changes, respectively. The levels of serum CK, CK-MB, LDH, AST, TNF-α, and IL-6 as well as the contents of MDA and SOD in tissues were measured by ELISA, while Western blot analysis was performed to detect the expression of endoplasmic reticulum stress (ERS)-related proteins. GA treatment significantly reduced apoptosis in H9c2 cells, while it alleviated left ventricular dysfunction, fibrosis and myocardial apoptosis, down-regulated the levels of CK, CK-MB, LDH, AST, TNF-α, IL-6, and MDA, and up-regulated SOD levels in I/R rats. Moreover, GA treatment led to a decrease in the expression of CHOP, GRP78, and p-PERK in both H/R cells and I/R rats. This study demonstrates that cardioprotective role of GA in MIRI may involve the attenuation of ERS-induced apoptosis and inflammation, potentially providing an alternative strategy for intervention of MIRI.Monocytes are differentiated into macrophages. In this study, mitochondrial DNA copy number (mtDNAcn) levels and downstream events such as the expression of respiratory chain mRNAs were investigated during the phorbol 12-myristate 13-acetate (PMA)-induced differentiation of monocytes. Although PMA treatment increased mtDNAcn, the expression levels of mRNAs encoded in mtDNA were decreased. The levels of mitochondrial transcription factor A mRNA and protein were also decreased. The levels of coenzyme Q10 remained unchanged. These results imply that, although mtDNAcn is considered as a health marker, the levels of mtDNAcn may not always be consistent with the parameters of mitochondrial functions.The introduction of enzyme nanoreactors in medicine is relatively new. However, this technology has already been experimentally successful in cancer treatments, struggle against toxicity of reactive oxygen species in inflammatory processes, detoxification of drugs and xenobiotics, and correction of metabolic and genetic defects by using encapsulated enzymes, acting in single or cascade reactions. Biomolecules, e.g. enzymes, antibodies, reactive proteins capable of inactivating toxicants in the body are called bioscavengers. In this review, we focus on enzyme-containing nanoreactors for in vivo detoxification of organophosphorous compounds (OP) to be used for prophylaxis and post-exposure treatment of OP poisoning. A particular attention is devoted to bioscavenger-containing injectable nanoreactors operating in the bloodstream. The nanoreactor concept implements single or multiple enzymes and cofactors co-encapsulated in polymeric semi-permeable nanocontainers. Thus, the detoxification processes take place in a confined space containing highly concentrated bioscavengers. The article deals with historical and theoretical backgrounds about enzymatic detoxification of OPs in nanoreactors, nanoreactor polymeric enveloppes, realizations and advantages over other approaches using bioscavengers.Lanthanide ions (Ln3+) doped hydroxyapatite (HAP) particles are well established in biomedical areas. Although Ln elements are closely located in the periodic table and have plenty of similar characteristics, the minor differences in the effective ionic radii could cause alterations in the physicochemical and biological properties of HAP substitutes. The present study synthesized lanthanum-(La-) and gadolinium-(Gd-) doped HAP particles (La-HAP and Gd-HAP). And the effects of two types of particles on bone marrow stem cells (BMSCs) viability were also measured and compared in vitro. The results indicated that the Gd-HAP adsorbed more serum proteins from culture media and inhibited the new layer of apatite formation on its surface when comparing to La-HAP with a similar crystalline structure, particle size, and Zeta potential. These surface modifications can significantly reduce the cell adhesion of Gd-HAP, simultaneously decreasing the Gd-HAP particle uptake efficiency. Moreover, the cell viability of Gd-HAP remained higher than that of La-HAP in culture periods. We concluded that a slight variation in the effective ionic radii between Gd3+ and La3+ could alter the adsorption of serum proteins on the particles' surface, modulating subsequent cellular responses. The present work provides an interesting view that Gd-HAP is endowed with better cellular biocompatibility than La-HAP.
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