AIM: To investigate the associations of hepatitis B virus (HBV) genotype with HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA detection in different groups of HBV-infected patients in sout...AIM: To investigate the associations of hepatitis B virus (HBV) genotype with HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA detection in different groups of HBV-infected patients in southwest Iran. METHODS: A total of 89 HBsAg-positive serum samples were collected from the same number of patients. All sera were then investigated to determine HBV DNA and serological markers. For all the polymerase chain reaction (PCR)-positive samples, biochemical, histopathological assays and genotyping were also performed. RESULTS: Genotype D was the only type of HBV foundin different clinical forms of acute and chronic infections. There was a high prevalence of HBeAg-negative HBV- infected patients with chronic hepatitis (52.7%). Out of 55 patients with chronic hepatitis, seven (12.7%) were diagnosed with cirrhosis. A significant association between the presence of anti-HBe antibody and an increase in ALT level, among either HBeAg-negative (P = 0.01) or HBeAg-positive (P = 0.026) patients, was demonstrated. No significant differences were observed between the clinical outcomes of HBeAg-positive and -negative individuals (P = 0.24). CONCLUSION: Genotype D has been recognized as the only type of HBV found in different clinical forms of HBV infections, including cirrhosis, among the residents of southwest Iran. Anti-HBe possibly plays a role in disease progression in some patients with chronic hepatitis, at least for a period of disease.展开更多
The development of natural biomaterials applied for hard tissue repair and regeneration is of great importance,especially in societies with a large elderly population.Self-assembled peptide hydrogels are a new generat...The development of natural biomaterials applied for hard tissue repair and regeneration is of great importance,especially in societies with a large elderly population.Self-assembled peptide hydrogels are a new generation of biomaterials that provide excellent biocompatibility,tunable mechanical stability,injectability,trigger capability,lack of immunogenic reactions,and the ability to load cells and active pharmaceutical agents for tissue regeneration.Peptide-based hydrogels are ideal templates for the deposition of hydroxyapatite crystals,which can mimic the extracellular matrix.Thus,peptide-based hydrogels enhance hard tissue repair and regeneration compared to conventional methods.This review presents three major self-assembled peptide hydrogels with potential application for bone and dental tissue regeneration,including ionic self-complementary peptides,amphiphilic(surfactant-like)peptides,and triple-helix(collagen-like)peptides.Special attention is given to the main bioactive peptides,the role and importance of self-assembled peptide hydrogels,and a brief overview on molecular simulation of self-assembled peptide hydrogels applied for bone and dental tissue engineering and regeneration.展开更多
AIM: To investigate the differentiation of human Wharton's jelly derived mesenchymal stromal cells(WJMSCs) to insulin producing clusters(IPC) this study was conducted. METHODS: The umbilical cords samples were col...AIM: To investigate the differentiation of human Wharton's jelly derived mesenchymal stromal cells(WJMSCs) to insulin producing clusters(IPC) this study was conducted. METHODS: The umbilical cords samples were collected from full term caesarian section mothers and the WJ-MSCS were cultured from tissue explants in High glucose-Dulbecco's Modified Eagle Medium(H-DMEM); H-DMEM supplemented with 10% fetal bovine serum(FBS) and antibiotics. The expression of CD90, CD44, CD105, CD34 and CD133 as well as osteogenic and adipogenic differentiation of cells in appropriate medium were also evaluated. The cells were differentiated toward IPC with changing the culture medium and adding the small molecules such as nicotinic acid, epidermal growth factor, and exendin-4 during 3 wk period. The gene expression of PDX1, NGN3, Glut2, insulin was monitored by reveres transcription polymerase chain reaction method. The differentiated clusters were stained with Dithizone(DTZ) which confirms the presence of insulin granules. The insulin challenge test(low and high glucose concentration in Krebs-Ringer HEPES buffer) was also used to evaluate the functional properties of differentiated clusters.RESULTS: WJ-MSCS were positive for mesenchymal surface markers(CD90, CD44, CD105), and negative for CD34 and CD133. The accumulation of lipid vacuoles and deposition of calcium mineral in cells were considered as adipogenic and osteogenic potential of WJ-MSCS. The cells also expressed the transcriptional factors such as Nanog and OCT4. During this three step differentiation, the WJ-MSCS morphology was gradually changed from spindle shaped cells in to epithelioid cells and eventually to three dimensional clusters. The clusters expressed PDX1, NGN3, Glut2, and insulin. The cells became bright red color when stained with DTZ and the insulin secretion was also confirmed. In glucose challenge test a significant increase in insulin secretion from 0.91 ± 0.04 μIu/mL(2.8 mmol/L glucose) to to 8.34 ± 0.45 μIu/mL(16.7 mmol/L glucose) was recorded(P < 0.05). The insulin secretion of undifferentiated WJ-MSCS was not changed in this challenge test.CONCLUSION: WJ-MSCs have the ability to differentiate in to islet-like cells in vitro. However, this process needs further optimization in order to generate efficient and functional IPCs.展开更多
The authors regret that an error has been identified in Fig.5 of this original article.Specifically,the representative image of BDL group was incorrectly selected during figure assembly.The corrected version of Fig.5 ...The authors regret that an error has been identified in Fig.5 of this original article.Specifically,the representative image of BDL group was incorrectly selected during figure assembly.The corrected version of Fig.5 is shown below.This correction does not affect the overall results,interpretations,and conclusions of the study.展开更多
Background and aim:Cholestasis-associated renal injury or cholemic nephropathy(CN)is a serious clinical problem.Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN.There is ...Background and aim:Cholestasis-associated renal injury or cholemic nephropathy(CN)is a serious clinical problem.Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN.There is no specific pharmacological intervention for CN.Metformin is an anti-diabetic drug administered for decades.On the other hand,novel pharmacological properties have emerged for this drug.The effect of metformin on oxidative stress parameters has been well-recognized in different experimental models.It has also been found that metformin positively affected mitochondrial function.The current study aimed to evaluate the effects of metformin in an animal model of CN.Methods:Rats underwent bile duct ligation(BDL)and were treated with metformin(250 and 500 mg/kg)for 14 consecutive days.Two weeks after the BDL operations,urine,serum,and kidney samples were collected and analyzed.Results:Markers of oxidative stress,including reactive oxygen species(ROS)formation,lipid peroxida-tion,protein carbonylation,depleted antioxidant capacity,and decreased glutathione(GSH)levels were detected in BDL animals.Moreover,mitochondrial indices,including adenosine triphosphate(ATP)level,dehydrogenase activity,mitochondrial membrane potential,and mitochondrial permeability,were impaired in the kidney of cholestatic rats.Renal histopathological alterations in cholestatic animals included tubular degeneration and interstitial inflammation,cast formation,and fibrosis.It was found that metformin significantly alleviated oxidative stress and improved mitochondrial indices in the kidney of cholestatic rats.Tissue histopathological alterations were also mitigated in metformin-treated groups.Conclusions:Metformin could be a candidate for managing CN.The nephroprotective role of metformin is primarily associated with its effects on oxidative stress parameters and mitochondrial function.展开更多
Background and aim:The liver is the primary organ affected by cholestasis,and complications such as renal injury,renal failure,and the need for renal transplantation are associated with cholestatic liver disease.There...Background and aim:The liver is the primary organ affected by cholestasis,and complications such as renal injury,renal failure,and the need for renal transplantation are associated with cholestatic liver disease.There is substantial evidence indicating that reactive oxygen species(ROS)and mitochondrial impairment are fundamental mechanisms underlying cholestasis-induced hepatic and renal injury.Edaravone(EDV)is a potent radical scavenger and antioxidant that may prevent oxidative stress and improve impaired mitochondrial function in various diseases.This study was performed to evaluate the effects and mechanisms of action of EDV on hepatic and renal injury in an animal model of cholestasis.Methods:Rats subjected to bile duct ligation(BDL)were treated with EDV 1 or 10 mg/kg/day intraper-itoneally for 14 consecutive days.Biomarkers of oxidative stress and mitochondrial impairment in the liver and kidney were assessed in EDV-treated and untreated rats with cholestasis.Results:Significant increases in tissue ROS level,lipid peroxidation,protein carbonylation,and oxidized glutathione level were detected in rats subjected to BDL.Additionally,significant decreases in tissue glutathione level and antioxidant capacity were observed in the hepatic and renal tissues of rats with cholestasis.Markers of mitochondrial impairment,including mitochondrial depolarization,lipid perox-idation,mitochondrial permeabilization,depleted adenosine triphosphate content,and decreased de-hydrogenase activity,were also detected in rats subjected to BDL.Furthermore,portal inflammation,necrosis,and tissue fibrosis were detected in the liver and significant tubular atrophy and interstitial inflammation,as well as fibrotic lesions,were detected in the kidneys of rats with cholestasis.EDV treatment significantly mitigated cholestasis-associated hepatic and renal injury.Conclusions:The antioxidative properties of EDV and its positive effects on the indices of mitochondrial function may be critical factors contributing to protection against cholestasis-associated hepatic and renal injury.展开更多
Bacteria can be programmed to deliver natural materials with defined biological and mechanical properties for controlling cell growth and differentiation.Here,we present an elastic,resilient and bioactive polysacchari...Bacteria can be programmed to deliver natural materials with defined biological and mechanical properties for controlling cell growth and differentiation.Here,we present an elastic,resilient and bioactive polysaccharide derived from the extracellular matrix of Pantoea sp.BCCS 001.Specifically,it was methacrylated to generate a new photo crosslinkable hydrogel that we coined Pantoan Methacrylate or put simply PAMA.We have used it for the first time as a tissue engineering hydrogel to treat VML injuries in rats.The crosslinked PAMA hydrogel was super elastic with a recovery nearing 100%,while mimicking the mechanical stiffness of native muscle.After inclusion of thiolated gelatin via a Michaelis reaction with acrylate groups on PAMA we could also guide muscle progenitor cells into fused and aligned tubes-something reminiscent of mature muscle cells.These results were complemented by sarcomeric alpha-actinin immunostaining studies.Importantly,the implanted hydrogels exhibited almost 2-fold more muscle formation and 50%less fibrous tissue formation compared to untreated rat groups.In vivo inflammation and toxicity assays likewise gave rise to positive results confirming the biocompatibility of this new biomaterial system.Overall,our results demonstrate that programmable polysaccharides derived from bacteria can be used to further advance the field of tissue engineering.In greater detail,they could in the foreseeable future be used in practical therapies against VML.展开更多
文摘AIM: To investigate the associations of hepatitis B virus (HBV) genotype with HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA detection in different groups of HBV-infected patients in southwest Iran. METHODS: A total of 89 HBsAg-positive serum samples were collected from the same number of patients. All sera were then investigated to determine HBV DNA and serological markers. For all the polymerase chain reaction (PCR)-positive samples, biochemical, histopathological assays and genotyping were also performed. RESULTS: Genotype D was the only type of HBV foundin different clinical forms of acute and chronic infections. There was a high prevalence of HBeAg-negative HBV- infected patients with chronic hepatitis (52.7%). Out of 55 patients with chronic hepatitis, seven (12.7%) were diagnosed with cirrhosis. A significant association between the presence of anti-HBe antibody and an increase in ALT level, among either HBeAg-negative (P = 0.01) or HBeAg-positive (P = 0.026) patients, was demonstrated. No significant differences were observed between the clinical outcomes of HBeAg-positive and -negative individuals (P = 0.24). CONCLUSION: Genotype D has been recognized as the only type of HBV found in different clinical forms of HBV infections, including cirrhosis, among the residents of southwest Iran. Anti-HBe possibly plays a role in disease progression in some patients with chronic hepatitis, at least for a period of disease.
文摘The development of natural biomaterials applied for hard tissue repair and regeneration is of great importance,especially in societies with a large elderly population.Self-assembled peptide hydrogels are a new generation of biomaterials that provide excellent biocompatibility,tunable mechanical stability,injectability,trigger capability,lack of immunogenic reactions,and the ability to load cells and active pharmaceutical agents for tissue regeneration.Peptide-based hydrogels are ideal templates for the deposition of hydroxyapatite crystals,which can mimic the extracellular matrix.Thus,peptide-based hydrogels enhance hard tissue repair and regeneration compared to conventional methods.This review presents three major self-assembled peptide hydrogels with potential application for bone and dental tissue regeneration,including ionic self-complementary peptides,amphiphilic(surfactant-like)peptides,and triple-helix(collagen-like)peptides.Special attention is given to the main bioactive peptides,the role and importance of self-assembled peptide hydrogels,and a brief overview on molecular simulation of self-assembled peptide hydrogels applied for bone and dental tissue engineering and regeneration.
基金Supported by A grant from Iran National Science Foundation(INSF)
文摘AIM: To investigate the differentiation of human Wharton's jelly derived mesenchymal stromal cells(WJMSCs) to insulin producing clusters(IPC) this study was conducted. METHODS: The umbilical cords samples were collected from full term caesarian section mothers and the WJ-MSCS were cultured from tissue explants in High glucose-Dulbecco's Modified Eagle Medium(H-DMEM); H-DMEM supplemented with 10% fetal bovine serum(FBS) and antibiotics. The expression of CD90, CD44, CD105, CD34 and CD133 as well as osteogenic and adipogenic differentiation of cells in appropriate medium were also evaluated. The cells were differentiated toward IPC with changing the culture medium and adding the small molecules such as nicotinic acid, epidermal growth factor, and exendin-4 during 3 wk period. The gene expression of PDX1, NGN3, Glut2, insulin was monitored by reveres transcription polymerase chain reaction method. The differentiated clusters were stained with Dithizone(DTZ) which confirms the presence of insulin granules. The insulin challenge test(low and high glucose concentration in Krebs-Ringer HEPES buffer) was also used to evaluate the functional properties of differentiated clusters.RESULTS: WJ-MSCS were positive for mesenchymal surface markers(CD90, CD44, CD105), and negative for CD34 and CD133. The accumulation of lipid vacuoles and deposition of calcium mineral in cells were considered as adipogenic and osteogenic potential of WJ-MSCS. The cells also expressed the transcriptional factors such as Nanog and OCT4. During this three step differentiation, the WJ-MSCS morphology was gradually changed from spindle shaped cells in to epithelioid cells and eventually to three dimensional clusters. The clusters expressed PDX1, NGN3, Glut2, and insulin. The cells became bright red color when stained with DTZ and the insulin secretion was also confirmed. In glucose challenge test a significant increase in insulin secretion from 0.91 ± 0.04 μIu/mL(2.8 mmol/L glucose) to to 8.34 ± 0.45 μIu/mL(16.7 mmol/L glucose) was recorded(P < 0.05). The insulin secretion of undifferentiated WJ-MSCS was not changed in this challenge test.CONCLUSION: WJ-MSCs have the ability to differentiate in to islet-like cells in vitro. However, this process needs further optimization in order to generate efficient and functional IPCs.
文摘The authors regret that an error has been identified in Fig.5 of this original article.Specifically,the representative image of BDL group was incorrectly selected during figure assembly.The corrected version of Fig.5 is shown below.This correction does not affect the overall results,interpretations,and conclusions of the study.
基金This work was financially supported by the Vice-Chancellor of Research Affairs of Shiraz University of Medical Sciences,Shiraz,Iran(Grant No.19444).
文摘Background and aim:Cholestasis-associated renal injury or cholemic nephropathy(CN)is a serious clinical problem.Previous studies mentioned that oxidative stress and mitochondrial impairment play a role in CN.There is no specific pharmacological intervention for CN.Metformin is an anti-diabetic drug administered for decades.On the other hand,novel pharmacological properties have emerged for this drug.The effect of metformin on oxidative stress parameters has been well-recognized in different experimental models.It has also been found that metformin positively affected mitochondrial function.The current study aimed to evaluate the effects of metformin in an animal model of CN.Methods:Rats underwent bile duct ligation(BDL)and were treated with metformin(250 and 500 mg/kg)for 14 consecutive days.Two weeks after the BDL operations,urine,serum,and kidney samples were collected and analyzed.Results:Markers of oxidative stress,including reactive oxygen species(ROS)formation,lipid peroxida-tion,protein carbonylation,depleted antioxidant capacity,and decreased glutathione(GSH)levels were detected in BDL animals.Moreover,mitochondrial indices,including adenosine triphosphate(ATP)level,dehydrogenase activity,mitochondrial membrane potential,and mitochondrial permeability,were impaired in the kidney of cholestatic rats.Renal histopathological alterations in cholestatic animals included tubular degeneration and interstitial inflammation,cast formation,and fibrosis.It was found that metformin significantly alleviated oxidative stress and improved mitochondrial indices in the kidney of cholestatic rats.Tissue histopathological alterations were also mitigated in metformin-treated groups.Conclusions:Metformin could be a candidate for managing CN.The nephroprotective role of metformin is primarily associated with its effects on oxidative stress parameters and mitochondrial function.
基金This study was financially supported by the Vice-Chancellor of Research Affairs of Shiraz University of Medical Sciences(Grant number:97-01-36-18730)Shanxi Agricultural University(Grant numbers:2018YJ33 and K271999031 for National Natural Science Foundation of China and Outstanding Doctors Volunteering to Work in Shanxi Province,respectively).
文摘Background and aim:The liver is the primary organ affected by cholestasis,and complications such as renal injury,renal failure,and the need for renal transplantation are associated with cholestatic liver disease.There is substantial evidence indicating that reactive oxygen species(ROS)and mitochondrial impairment are fundamental mechanisms underlying cholestasis-induced hepatic and renal injury.Edaravone(EDV)is a potent radical scavenger and antioxidant that may prevent oxidative stress and improve impaired mitochondrial function in various diseases.This study was performed to evaluate the effects and mechanisms of action of EDV on hepatic and renal injury in an animal model of cholestasis.Methods:Rats subjected to bile duct ligation(BDL)were treated with EDV 1 or 10 mg/kg/day intraper-itoneally for 14 consecutive days.Biomarkers of oxidative stress and mitochondrial impairment in the liver and kidney were assessed in EDV-treated and untreated rats with cholestasis.Results:Significant increases in tissue ROS level,lipid peroxidation,protein carbonylation,and oxidized glutathione level were detected in rats subjected to BDL.Additionally,significant decreases in tissue glutathione level and antioxidant capacity were observed in the hepatic and renal tissues of rats with cholestasis.Markers of mitochondrial impairment,including mitochondrial depolarization,lipid perox-idation,mitochondrial permeabilization,depleted adenosine triphosphate content,and decreased de-hydrogenase activity,were also detected in rats subjected to BDL.Furthermore,portal inflammation,necrosis,and tissue fibrosis were detected in the liver and significant tubular atrophy and interstitial inflammation,as well as fibrotic lesions,were detected in the kidneys of rats with cholestasis.EDV treatment significantly mitigated cholestasis-associated hepatic and renal injury.Conclusions:The antioxidative properties of EDV and its positive effects on the indices of mitochondrial function may be critical factors contributing to protection against cholestasis-associated hepatic and renal injury.
基金the Danish Council for Independent Research(Technology and Production Sciences,8105-00003B)Denmark,the Novo Nordisk Foundation(NNF22OC0079994 in the call"Project Grants in the Natural and Technical Sciences 2022)+2 种基金Denmark,and the VIDI research programme with project number R0004387which is(partly)financed by The Netherlands Organization for Scientific Research(NWO),The Netherlands.This work has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no.951747Masoud Hasany and Mehdi Mehrali would like to acknowledge the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 899987.
文摘Bacteria can be programmed to deliver natural materials with defined biological and mechanical properties for controlling cell growth and differentiation.Here,we present an elastic,resilient and bioactive polysaccharide derived from the extracellular matrix of Pantoea sp.BCCS 001.Specifically,it was methacrylated to generate a new photo crosslinkable hydrogel that we coined Pantoan Methacrylate or put simply PAMA.We have used it for the first time as a tissue engineering hydrogel to treat VML injuries in rats.The crosslinked PAMA hydrogel was super elastic with a recovery nearing 100%,while mimicking the mechanical stiffness of native muscle.After inclusion of thiolated gelatin via a Michaelis reaction with acrylate groups on PAMA we could also guide muscle progenitor cells into fused and aligned tubes-something reminiscent of mature muscle cells.These results were complemented by sarcomeric alpha-actinin immunostaining studies.Importantly,the implanted hydrogels exhibited almost 2-fold more muscle formation and 50%less fibrous tissue formation compared to untreated rat groups.In vivo inflammation and toxicity assays likewise gave rise to positive results confirming the biocompatibility of this new biomaterial system.Overall,our results demonstrate that programmable polysaccharides derived from bacteria can be used to further advance the field of tissue engineering.In greater detail,they could in the foreseeable future be used in practical therapies against VML.
