Generally, the lysozyme degradation on chitosan (CTS) is slower than that of chitin (CT). The CTS can be fabricated in scaffold form but it is difficult to fabricate CT scaffold under mild conditions. The method for t...Generally, the lysozyme degradation on chitosan (CTS) is slower than that of chitin (CT). The CTS can be fabricated in scaffold form but it is difficult to fabricate CT scaffold under mild conditions. The method for the preparation of scaffold from N-acetylated CTS (N-CTS) was investigated in this research. By using this method, the scaffolds could be fabricated chitosan to chitin with the degree of acetylation (DA) 18% - 70%. Among these scaffolds, the highest degradation of scaffold by lysozyme was observed on the N-CTS scaffold with DA 60%, which determined by examination of the reducing end contents in the degradation media and by measuring the weight loss of scaffolds. Moreover, the best condition for the degradation of N-CTS scaffold with DA70% by lysozyme was also investigated. The maximum degradation rate of the scaffold was observed on the treatment with lysozyme 500 mg/l of acetate buffer at pH 4.5, 37°C, 100 rpm and for 7 days.展开更多
Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to...Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.展开更多
Diabetic retinopathy(DR)is a form of microangiopathy.Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina.New approaches are needed,which reduce...Diabetic retinopathy(DR)is a form of microangiopathy.Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina.New approaches are needed,which reduce the risk and improve the outcomes of DR while complementing current therapeutic approaches.Homocysteine(Hcy)elevation and oxidative stress are potential therapeutic targets in DR.Common genetic polymorphisms such as those of methylenetetrahydrofolate reductase(MTHFR),increase Hcy and DR risk and severity.Patients with DR have high incidences of deficiencies of crucial vitamins,minerals,and related compounds,which also lead to elevation of Hcy and oxidative stress.Addressing the effects of the MTHFR polymorphism and addressing comorbid deficiencies and insufficiencies reduce the impact and severity of the disease.This approach provides safe and simple strategies that support conventional care and improve outcomes.Suboptimal vitamin co-factor availability also impairs the release of neurotrophic and neuroprotective growth factors.Collectively,this accounts for variability in presentation and response of DR to conventional therapy.Fortunately,there are straightforward recommendations for addressing these issues and supporting traditional treatment plans.We have reviewed the literature for nutritional interventions that support conventional therapies to reduce disease risk and severity.Optimal combinations of vitamins B1,B2,B6,L-methylfolate,methylcobalamin(B12),C,D,natural vitamin E complex,lutein,zeaxanthin,alpha-lipoic acid,and n-acetylcysteine are identified for protecting the retina and choroid.Certain medical foods have been successfully used as therapy for retinopathy.Recommendations based on this review and our clinical experience are developed for clinicians to use to support conventional therapy for DR.DR from both type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM)have similar retinal findings and responses to nutritional therapies.展开更多
AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.
The growth inhibitory effects of D-glucosamine hydrochloride （GlcNH2-HCl）, D-glucosamine （GlcNH2） and N-acetyl glucosamine （NAG） on human hepatoma SMMC-7721 cells in vitro were investigated. The results showed t...The growth inhibitory effects of D-glucosamine hydrochloride （GlcNH2-HCl）, D-glucosamine （GlcNH2） and N-acetyl glucosamine （NAG） on human hepatoma SMMC-7721 cells in vitro were investigated. The results showed that GlcNH2.HCl and GlcNH2 resulted in a concentration-dependent reduction in hepatoma cell growth as measured by MTT （3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide） assay. This effect was accompanied by a marked increase in the proportion of S cells as analyzed by flow cytometry. In addition, human hepatoma SMMC-7721 cells treated with GlcNH2-HCl resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis. NAG could not inhibit the proliferation of SMMC-7721 cells. GlcNH2-HCl exhibited antitumor activity against Sarcoma 180 in Kunming mice at dosage of 125-500 mg/kg, dose of 250 mg/kg being the best. GlcNH2-HCl at dose of 250 mg/kg could enhance significantly the thymus index, and spleen index and could promote T lymphocyte proliferation induced by ConA. The antitumor effect of GlcNH2-HCl is probably host-mediated and cytocidal.展开更多
The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants,some of which are resistant to vaccines and drugs targeting viral elements.Targeting host dependency factors,e.g.cellular proteins requi...The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants,some of which are resistant to vaccines and drugs targeting viral elements.Targeting host dependency factors,e.g.cellular proteins required for viral replication,would help prevent the development of resistance.However,it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host factors.To this end,we compared three variants of concern and found that the host transcriptional response was conserved,differing only in kinetics and magnitude.Clustered regularly interspaced short palindromic repeats screening identified host genes required for each variant during infection.Most of the genes were shared by multiple variants.We validated our hits with small molecules and repurposed the US Food and Drug Administration-approved drugs.All the drugs were highly active against all the tested variants,including new variants that emerged during the study(Delta and Omicron).Mechanistically,we identified reactive oxygen species production as a key step in early viral replication.Antioxidants such as N-acetyl cysteine(NAC)were effective against all the variants in both human lung cells and a humanized mouse model.Our study supports the use of available antioxidant drugs,such as NAC,as a general and effective anti-COVID-19 approach.展开更多
1H magnetic resonance spectroscopy and diffusion weighted imaging features of the cerebellar vermis in 17 medulloblastoma patients were retrospectively analyzed, and 17 healthy volunteers were selected as controls. 1H...1H magnetic resonance spectroscopy and diffusion weighted imaging features of the cerebellar vermis in 17 medulloblastoma patients were retrospectively analyzed, and 17 healthy volunteers were selected as controls. 1H magnetic resonance spectroscopy showed that in all 17 medulloblastoma patients, N-acetyl aspartate and creatine peaks were significantly decreased, the choline peak was significantly increased, and there was evidence of a myo-inositol peak. Further, 11 patients showed a low taurine peak at 3.4 ppm, five patients showed a lipid peak at 0.9-1.3 ppm, and three patients showed a negative lactic acid peak at 1.33 ppm. Compared with the control group, the ratios of N-acetyl aspartate/choline and N-acetyl aspartate/creatine were significantly decreased, and the ratio of choline/creatine was increased, in medulloblastoma patients. Diffusion weighted imaging displayed hyperintensity and decreased apparent diffusion coefficient in medulloblastoma patients. These findings indicate that 1H magnetic resonance spectroscopy and diffusion weighted imaging are useful for qualitative diagnosis of medulloblastoma.展开更多
文摘Generally, the lysozyme degradation on chitosan (CTS) is slower than that of chitin (CT). The CTS can be fabricated in scaffold form but it is difficult to fabricate CT scaffold under mild conditions. The method for the preparation of scaffold from N-acetylated CTS (N-CTS) was investigated in this research. By using this method, the scaffolds could be fabricated chitosan to chitin with the degree of acetylation (DA) 18% - 70%. Among these scaffolds, the highest degradation of scaffold by lysozyme was observed on the N-CTS scaffold with DA 60%, which determined by examination of the reducing end contents in the degradation media and by measuring the weight loss of scaffolds. Moreover, the best condition for the degradation of N-CTS scaffold with DA70% by lysozyme was also investigated. The maximum degradation rate of the scaffold was observed on the treatment with lysozyme 500 mg/l of acetate buffer at pH 4.5, 37°C, 100 rpm and for 7 days.
文摘Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.
基金Grant/financial support:The work was supported by the NIH Center Grant P30,EY014801,NINDS 1R01NS111115-01(Wang)a grant from Research to Prevent Blindness(RPB).
文摘Diabetic retinopathy(DR)is a form of microangiopathy.Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina.New approaches are needed,which reduce the risk and improve the outcomes of DR while complementing current therapeutic approaches.Homocysteine(Hcy)elevation and oxidative stress are potential therapeutic targets in DR.Common genetic polymorphisms such as those of methylenetetrahydrofolate reductase(MTHFR),increase Hcy and DR risk and severity.Patients with DR have high incidences of deficiencies of crucial vitamins,minerals,and related compounds,which also lead to elevation of Hcy and oxidative stress.Addressing the effects of the MTHFR polymorphism and addressing comorbid deficiencies and insufficiencies reduce the impact and severity of the disease.This approach provides safe and simple strategies that support conventional care and improve outcomes.Suboptimal vitamin co-factor availability also impairs the release of neurotrophic and neuroprotective growth factors.Collectively,this accounts for variability in presentation and response of DR to conventional therapy.Fortunately,there are straightforward recommendations for addressing these issues and supporting traditional treatment plans.We have reviewed the literature for nutritional interventions that support conventional therapies to reduce disease risk and severity.Optimal combinations of vitamins B1,B2,B6,L-methylfolate,methylcobalamin(B12),C,D,natural vitamin E complex,lutein,zeaxanthin,alpha-lipoic acid,and n-acetylcysteine are identified for protecting the retina and choroid.Certain medical foods have been successfully used as therapy for retinopathy.Recommendations based on this review and our clinical experience are developed for clinicians to use to support conventional therapy for DR.DR from both type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM)have similar retinal findings and responses to nutritional therapies.
文摘AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity.
基金Project (No. 2001AA625050) supported by the Hi-Tech Researchand Development Program (863) of China
文摘The growth inhibitory effects of D-glucosamine hydrochloride （GlcNH2-HCl）, D-glucosamine （GlcNH2） and N-acetyl glucosamine （NAG） on human hepatoma SMMC-7721 cells in vitro were investigated. The results showed that GlcNH2.HCl and GlcNH2 resulted in a concentration-dependent reduction in hepatoma cell growth as measured by MTT （3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide） assay. This effect was accompanied by a marked increase in the proportion of S cells as analyzed by flow cytometry. In addition, human hepatoma SMMC-7721 cells treated with GlcNH2-HCl resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis. NAG could not inhibit the proliferation of SMMC-7721 cells. GlcNH2-HCl exhibited antitumor activity against Sarcoma 180 in Kunming mice at dosage of 125-500 mg/kg, dose of 250 mg/kg being the best. GlcNH2-HCl at dose of 250 mg/kg could enhance significantly the thymus index, and spleen index and could promote T lymphocyte proliferation induced by ConA. The antitumor effect of GlcNH2-HCl is probably host-mediated and cytocidal.
基金supported by the CaRiPaRo Foundation(NewTarCoV2)the Ministry of Education,University and Research(PRIN-2020KSY3KL)+13 种基金supported by the Telethon Foundation Core Grant,European Research Council(ERC)(CellKarma)Regione Campania(PO-FESR 2014-2020,PO-FESR 2014-2020)Italian Ministry of Health(Piano Operativo Salute Traiettoria 3,‘Genomed’).supported by the Giovanni Armenise-Harvard Foundation,the Telethon Foundation(TCP13013)ERC(ERC Starting Grant,‘MetEpiStem’)supported by ERC(ERC Consolidator 615879)the Bill and Melinda Gates Foundation(OPP1035881 and OPP1097238)the Italian Foundation for Cancer Research(AIRC 21850)the Collaborative Center for XDP at Massachusetts General Hospital(239295)supported by the Italian Foundation for Cancer Research(AIRC-MFAG 25745)University of Padua(STARS Consolidator Grant,‘EMERALD’)supported by the Italian Foundation for Cancer Research(AIRC 2135)Italian Ministry of Health(RCR-201923669115,NET-201602361632)supported by the EVA-GLOBAL project that has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement number 871029EVA-GLOBAL provided access to SARS-CoV-2 Alpha and Delta isolates(human nCoV19 isolate/England/MIG457/2020 and hCoV-19/Netherlands/NH-RIVM-27142/2021_P2).
文摘The high mutation rate of SARS-CoV-2 leads to the emergence of multiple variants,some of which are resistant to vaccines and drugs targeting viral elements.Targeting host dependency factors,e.g.cellular proteins required for viral replication,would help prevent the development of resistance.However,it remains unclear whether different SARS-CoV-2 variants induce conserved cellular responses and exploit the same core host factors.To this end,we compared three variants of concern and found that the host transcriptional response was conserved,differing only in kinetics and magnitude.Clustered regularly interspaced short palindromic repeats screening identified host genes required for each variant during infection.Most of the genes were shared by multiple variants.We validated our hits with small molecules and repurposed the US Food and Drug Administration-approved drugs.All the drugs were highly active against all the tested variants,including new variants that emerged during the study(Delta and Omicron).Mechanistically,we identified reactive oxygen species production as a key step in early viral replication.Antioxidants such as N-acetyl cysteine(NAC)were effective against all the variants in both human lung cells and a humanized mouse model.Our study supports the use of available antioxidant drugs,such as NAC,as a general and effective anti-COVID-19 approach.
基金supported by the National Natural Science Foundation of China, No. 81171315the Fundamental Research Funds of the Central Universities, No. 303275894the Natural Science Foundation of Hubei Province, No.2009CDA071
文摘1H magnetic resonance spectroscopy and diffusion weighted imaging features of the cerebellar vermis in 17 medulloblastoma patients were retrospectively analyzed, and 17 healthy volunteers were selected as controls. 1H magnetic resonance spectroscopy showed that in all 17 medulloblastoma patients, N-acetyl aspartate and creatine peaks were significantly decreased, the choline peak was significantly increased, and there was evidence of a myo-inositol peak. Further, 11 patients showed a low taurine peak at 3.4 ppm, five patients showed a lipid peak at 0.9-1.3 ppm, and three patients showed a negative lactic acid peak at 1.33 ppm. Compared with the control group, the ratios of N-acetyl aspartate/choline and N-acetyl aspartate/creatine were significantly decreased, and the ratio of choline/creatine was increased, in medulloblastoma patients. Diffusion weighted imaging displayed hyperintensity and decreased apparent diffusion coefficient in medulloblastoma patients. These findings indicate that 1H magnetic resonance spectroscopy and diffusion weighted imaging are useful for qualitative diagnosis of medulloblastoma.
