Traditionally, coconut dregs will be used as animal feed after the extraction of coconut oil and coconut milk from the copra. This study was carried out to discover the commercial value of coconut dregs as a solid sub...Traditionally, coconut dregs will be used as animal feed after the extraction of coconut oil and coconut milk from the copra. This study was carried out to discover the commercial value of coconut dregs as a solid substrate in the production of amylase through solid state fermentation （SSF） since this agro-waste is fairly rich in nutrients, providing the necessary nutrients supplementation for better microbial activity to produce enzymes. In this study, amylase is to be produced from coconut dregs by Aspergillus niger through solid state fermentation （SSF）. Three parameters were covered, which are incubation time, initial moisture content of substrate and inoculum sizes. SSF was carried out by using incubator at 37 ~C to test for enzyme activity at these following parameters： incubation time： 24, 48, 72, 96 and 120 hours; substrate moisture content： 64, 66, 68, 70 and 72% （w/w）; inoculum sizes： 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 mL spore suspension （5.5 × 10^6 spores/mL）. Enzyme activities were measured through the estimation of liberated reducing sugars after the assay of amylase enzyme by using DNS （3, 5 dinitrosalicylic acid） method. Highest enzyme activities were obtained at these following parameters： incubation time： 72 hours （31.76 U/gds）; initial moisture content ofsubstrate： 66% （26.66 U / gds） and inoculum sizes： 2.0 mL （30.56 U/gds）.展开更多
The transport of fattening pigs is characterized by a strong human-animal interaction. Consequent handling is important because of animal welfare, meat quality and matching economic consequences. During road transport...The transport of fattening pigs is characterized by a strong human-animal interaction. Consequent handling is important because of animal welfare, meat quality and matching economic consequences. During road transport, human impact can be divided in different steps: 1) driving pigs from the pens via an alley to the trailer, 2) loading, 3) actual transport, 4) unloading to the lairage, and 5) the final phase driving pigs to the stunning. An inadequate design and a poor condition of the facilities will negatively affect the ease of handling pigs. Because of the consequences, acute stress during transport and slaughter should be minimized by acting on the education of people, on equipment and on preparation of animals for the journey. Education programs have to be repeated regularly so that knowledge can be refreshed.展开更多
During liver injury,intrahepatic macrophage compartment is augmented by circulating monocytes that infiltrate the liver driven by C-C motif chemokine ligand/C-C motif chemokine receptor(CCL/CCR)axis including CCL1‒CCR...During liver injury,intrahepatic macrophage compartment is augmented by circulating monocytes that infiltrate the liver driven by C-C motif chemokine ligand/C-C motif chemokine receptor(CCL/CCR)axis including CCL1‒CCR8 axis,thereby contributing to liver inflammation.Numerous small molecular receptor antagonists,including R243,have been developed for targeting CCR8;however,these agents face challenges in clinical translation,potentially attributed to their poor pharmacokinetic profiles,lack of target specificity,and potential adverse effects.In this study,we designed four CCR8 antagonizing peptides(AP8i-AP8iv)and performed molecular characterization in silico and therapeutic investigation in vitro and in vivo.Based on in silico docking,molecular dynamic simulation using homology build model and in-vitro(competitive)binding studies,AP8ii(YEWRFYHG)evidenced highly favorable and selective interactions at the CCR8-active site.AP8ii inhibited CCL1-driven chemotaxis and LPS/IFNg-induced pro-inflammatory activation of monocytes-macrophages in vitro.In a CCl4-induced acute liver injury mouse model,AP8ii treatment decreased intrahepatic infiltration of circulating monocytes.Moreover,AP8ii reduced liver inflammation,as indicated by decreased F4/80,IL6 and iNOS expression,diminished ALT levels,and attenuated fibrosis,as indicated by reduced collagen-I expression.In conclusion,we report a novel CCR8-antagonizing peptide that inhibited CCL1-driven intrahepatic monocytes infiltration and differentiation into pro-inflammatory phenotype,consequently ameliorating liver inflammation and fibrogenesis in an acute liver injury mouse model.展开更多
Endothelin-1/endothelin A receptor(ET-1/ETAR)pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells(HSCs)-a key cell type involved in the pathogenesis of liver fibros...Endothelin-1/endothelin A receptor(ET-1/ETAR)pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells(HSCs)-a key cell type involved in the pathogenesis of liver fibrosis.Inactivating HSCs by blocking the ET-1/ETAR pathway using a selective ETAR antagonist(ERA)represents a promising therapeutic approach for liver fibrosis.Unfortunately,small-molecule ERAs possess limited clinical potential due to poor bioavailability,short half-life,and rapid renal clearance.To improve the clinical applicability,we conjugated ERA to superparamagnetic iron-oxide nanoparticles(SPIONs)and investigated the therapeutic efficacy of ERA and ERA-SPIONs in vitro and in vivo and analyzed liver uptake by in vivo and ex vivo magnetic resonance imaging(MRI),HSCs-specific localization,and ET-1/ETAR-pathway antagonism in vivo.In murine and human liver fibrosis/cirrhosis,we observed overexpression of ET-1 and ETAR that correlated with HSC activation,and HSC-specific localization of ETAR.ERA and successfully synthesized ERA-SPIONs demonstrated significant attenuation in TGFβ-induced HSC activation,ECM production,migration,and contractility.In an acute CCl4-induced liver fibrosis mouse model,ERA-SPIONs exhibited higher liver uptake,HSC-specific localization,and ET-1/ETAR pathway antagonism.This resulted in significantly reduced liver-to-body weight ratio,plasma ALT levels,andα-SMA and collagen-I expression,indicating attenuation of liver fibrosis.In conclusion,our study demonstrates that the delivery of ERA using SPIONs enhances the therapeutic efficacy of ERA in vivo.This approach holds promise as a theranostic strategy for the MRI-based diagnosis and treatment of liver fibrosis.展开更多
文摘Traditionally, coconut dregs will be used as animal feed after the extraction of coconut oil and coconut milk from the copra. This study was carried out to discover the commercial value of coconut dregs as a solid substrate in the production of amylase through solid state fermentation （SSF） since this agro-waste is fairly rich in nutrients, providing the necessary nutrients supplementation for better microbial activity to produce enzymes. In this study, amylase is to be produced from coconut dregs by Aspergillus niger through solid state fermentation （SSF）. Three parameters were covered, which are incubation time, initial moisture content of substrate and inoculum sizes. SSF was carried out by using incubator at 37 ~C to test for enzyme activity at these following parameters： incubation time： 24, 48, 72, 96 and 120 hours; substrate moisture content： 64, 66, 68, 70 and 72% （w/w）; inoculum sizes： 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 mL spore suspension （5.5 × 10^6 spores/mL）. Enzyme activities were measured through the estimation of liberated reducing sugars after the assay of amylase enzyme by using DNS （3, 5 dinitrosalicylic acid） method. Highest enzyme activities were obtained at these following parameters： incubation time： 72 hours （31.76 U/gds）; initial moisture content ofsubstrate： 66% （26.66 U / gds） and inoculum sizes： 2.0 mL （30.56 U/gds）.
文摘The transport of fattening pigs is characterized by a strong human-animal interaction. Consequent handling is important because of animal welfare, meat quality and matching economic consequences. During road transport, human impact can be divided in different steps: 1) driving pigs from the pens via an alley to the trailer, 2) loading, 3) actual transport, 4) unloading to the lairage, and 5) the final phase driving pigs to the stunning. An inadequate design and a poor condition of the facilities will negatively affect the ease of handling pigs. Because of the consequences, acute stress during transport and slaughter should be minimized by acting on the education of people, on equipment and on preparation of animals for the journey. Education programs have to be repeated regularly so that knowledge can be refreshed.
文摘During liver injury,intrahepatic macrophage compartment is augmented by circulating monocytes that infiltrate the liver driven by C-C motif chemokine ligand/C-C motif chemokine receptor(CCL/CCR)axis including CCL1‒CCR8 axis,thereby contributing to liver inflammation.Numerous small molecular receptor antagonists,including R243,have been developed for targeting CCR8;however,these agents face challenges in clinical translation,potentially attributed to their poor pharmacokinetic profiles,lack of target specificity,and potential adverse effects.In this study,we designed four CCR8 antagonizing peptides(AP8i-AP8iv)and performed molecular characterization in silico and therapeutic investigation in vitro and in vivo.Based on in silico docking,molecular dynamic simulation using homology build model and in-vitro(competitive)binding studies,AP8ii(YEWRFYHG)evidenced highly favorable and selective interactions at the CCR8-active site.AP8ii inhibited CCL1-driven chemotaxis and LPS/IFNg-induced pro-inflammatory activation of monocytes-macrophages in vitro.In a CCl4-induced acute liver injury mouse model,AP8ii treatment decreased intrahepatic infiltration of circulating monocytes.Moreover,AP8ii reduced liver inflammation,as indicated by decreased F4/80,IL6 and iNOS expression,diminished ALT levels,and attenuated fibrosis,as indicated by reduced collagen-I expression.In conclusion,we report a novel CCR8-antagonizing peptide that inhibited CCL1-driven intrahepatic monocytes infiltration and differentiation into pro-inflammatory phenotype,consequently ameliorating liver inflammation and fibrogenesis in an acute liver injury mouse model.
文摘Endothelin-1/endothelin A receptor(ET-1/ETAR)pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells(HSCs)-a key cell type involved in the pathogenesis of liver fibrosis.Inactivating HSCs by blocking the ET-1/ETAR pathway using a selective ETAR antagonist(ERA)represents a promising therapeutic approach for liver fibrosis.Unfortunately,small-molecule ERAs possess limited clinical potential due to poor bioavailability,short half-life,and rapid renal clearance.To improve the clinical applicability,we conjugated ERA to superparamagnetic iron-oxide nanoparticles(SPIONs)and investigated the therapeutic efficacy of ERA and ERA-SPIONs in vitro and in vivo and analyzed liver uptake by in vivo and ex vivo magnetic resonance imaging(MRI),HSCs-specific localization,and ET-1/ETAR-pathway antagonism in vivo.In murine and human liver fibrosis/cirrhosis,we observed overexpression of ET-1 and ETAR that correlated with HSC activation,and HSC-specific localization of ETAR.ERA and successfully synthesized ERA-SPIONs demonstrated significant attenuation in TGFβ-induced HSC activation,ECM production,migration,and contractility.In an acute CCl4-induced liver fibrosis mouse model,ERA-SPIONs exhibited higher liver uptake,HSC-specific localization,and ET-1/ETAR pathway antagonism.This resulted in significantly reduced liver-to-body weight ratio,plasma ALT levels,andα-SMA and collagen-I expression,indicating attenuation of liver fibrosis.In conclusion,our study demonstrates that the delivery of ERA using SPIONs enhances the therapeutic efficacy of ERA in vivo.This approach holds promise as a theranostic strategy for the MRI-based diagnosis and treatment of liver fibrosis.
