A practical synthesis of （S）-N-（2-ethyl-6-methylphenyl）alanine, a key intermediate for （S）-metolachlor, was completed by means of lipase-catalyzed hydrolytic kinetic resolution and chemical racemization of the r...A practical synthesis of （S）-N-（2-ethyl-6-methylphenyl）alanine, a key intermediate for （S）-metolachlor, was completed by means of lipase-catalyzed hydrolytic kinetic resolution and chemical racemization of the remaining ester. The effects of operating temperature and enzyme concentration on the activity and enantioselectivity of enzyme were initially studied, and it was found that the enantioselectivity of CAL-B towards the resolution was not high enough to obtain enantiomerically pure compound（E=12.1）. When diethyl ether（15%, volume fraction） was added in the reaction medium, the lipase gave an excellent enantioselectivity（E=117.8）, which is about 9.7-fold that in pure buffered aqueous solution. For overcoming the limitation of a maximum theoretical yield of 50%, the acid product was separated from the remaining ester by a simple extraction procedure and the remaining ester was racemized with aldehyde and acetic acid under microwave irradiation or conventional heating condition, The results show the microwave irradiation was more effective than the conventional heating method and gave the desired （R,S）-N-（2- ethyl-6-methylphenyl）alanine methyl ester a high yield（92%） with R/S=50/50 in 1 h.展开更多
AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divid...AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls(HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral Ld T daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array(CBA) method. RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97(123.26-492.79) pg/m L vs 184.50(135.56-292.16) pg/m L, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with Ld T [175.51(103.90-331.91) pg/m L vs 184.50(135.56-292.16) pg/m L, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB(r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to Ld T treatment at 24 wk(48.15% vs 15.79%, P = 0.023) and 52 wk(66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary nonresponse at week 12 after treatment initiation were lower than those in patients with primary response [64.44(49.85-172.08) pg/m L vs 190.54(121.35-355.28) pg/m L, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with Ld T. CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to Ld T treatment.展开更多
Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resi...Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148 M, GPR120 R270 H and TM6SF2 E167 K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148 M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2 E167 K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270 H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury.展开更多
patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury ma...patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury may occur because of the treatment as well.Ischemia,cytokine storm,and hypoxia were identified as the three major factors contributing to liver damage during COVID-19.Indeed,raised liver enzymes during hospitalizations may be attributed to medications used,as well as sepsis and shock.As a result,the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14%to 53%.Aminotransferases and bilirubin are found most often elevated.Usually,increased gamma-glutamyltransferase,alkaline phosphatase,and decreased serum albumin levels are demonstrated.Additionally,although there is no specific treatment for COVID-19,many of the drugs used to treat the infection are hepatotoxic.In this mini-review,we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm.Furthermore,data show that liver injury can be an independent predictor of severe COVID-19,the need for hospitalization,and death.展开更多
基金Supported by the National Natural Science Foundation of China(No.20802025)the Hi-Tech Research and Development Program of China(No.2007AA021306)Jilin Provincial Science & Technology Sustentation Program,China(No.20070553)
文摘A practical synthesis of （S）-N-（2-ethyl-6-methylphenyl）alanine, a key intermediate for （S）-metolachlor, was completed by means of lipase-catalyzed hydrolytic kinetic resolution and chemical racemization of the remaining ester. The effects of operating temperature and enzyme concentration on the activity and enantioselectivity of enzyme were initially studied, and it was found that the enantioselectivity of CAL-B towards the resolution was not high enough to obtain enantiomerically pure compound（E=12.1）. When diethyl ether（15%, volume fraction） was added in the reaction medium, the lipase gave an excellent enantioselectivity（E=117.8）, which is about 9.7-fold that in pure buffered aqueous solution. For overcoming the limitation of a maximum theoretical yield of 50%, the acid product was separated from the remaining ester by a simple extraction procedure and the remaining ester was racemized with aldehyde and acetic acid under microwave irradiation or conventional heating condition, The results show the microwave irradiation was more effective than the conventional heating method and gave the desired （R,S）-N-（2- ethyl-6-methylphenyl）alanine methyl ester a high yield（92%） with R/S=50/50 in 1 h.
文摘AIM: To investigate serum interleukin(IL)-38 level and its clinical role in predicting virological response(VR) to telbivudine(Ld T) in patients with chronic hepatitis B(CHB).METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls(HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral Ld T daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array(CBA) method. RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97(123.26-492.79) pg/m L vs 184.50(135.56-292.16) pg/m L, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with Ld T [175.51(103.90-331.91) pg/m L vs 184.50(135.56-292.16) pg/m L, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB(r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to Ld T treatment at 24 wk(48.15% vs 15.79%, P = 0.023) and 52 wk(66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary nonresponse at week 12 after treatment initiation were lower than those in patients with primary response [64.44(49.85-172.08) pg/m L vs 190.54(121.35-355.28) pg/m L, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with Ld T. CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to Ld T treatment.
文摘Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148 M, GPR120 R270 H and TM6SF2 E167 K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148 M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2 E167 K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270 H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury.
文摘patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury may occur because of the treatment as well.Ischemia,cytokine storm,and hypoxia were identified as the three major factors contributing to liver damage during COVID-19.Indeed,raised liver enzymes during hospitalizations may be attributed to medications used,as well as sepsis and shock.As a result,the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14%to 53%.Aminotransferases and bilirubin are found most often elevated.Usually,increased gamma-glutamyltransferase,alkaline phosphatase,and decreased serum albumin levels are demonstrated.Additionally,although there is no specific treatment for COVID-19,many of the drugs used to treat the infection are hepatotoxic.In this mini-review,we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm.Furthermore,data show that liver injury can be an independent predictor of severe COVID-19,the need for hospitalization,and death.
