The prognosis of pancreatic cancer is poor with the overall 5-year survival rate of less than 5%changing minimally over the past decades and future projections predicting it developing into the second leading cause of...The prognosis of pancreatic cancer is poor with the overall 5-year survival rate of less than 5%changing minimally over the past decades and future projections predicting it developing into the second leading cause of cancer related mortality within the next decade.Investigations into the mechanisms of pancreatic cancer development,progression and acquired chemoresistance have been constant for the past few decades,thus resulting in the identification of human nucleoside transporters and factors affecting cytotoxic uptake via said transporters.This review summaries the aberrant expression and role of human nucleoside transports in pancreatic cancer,more specifically human equilibrative nucleoside transporter 1/2(hENT1,hENT2),and human concentrative nucleoside transporter 1/3(hCNT1,hCNT3),while briefly discussing the connection and importance between these nucleoside transporters and mucins that have also been identified as being aberrantly expressed in pancreatic cancer.The review also discusses the incidence,current diagnostic techniques as well as the current therapeutic treatments for pancreatic cancer.Furthermore,we address the importance of chemoresistance in nucleoside analogue drugs,in particular,gemcitabine and we discuss prospective therapeutic treatments and strategies for overcoming acquired chemoresistance in pancreatic cancer by the enhancement of human nucleoside transporters as well as the potential targeting of mucins using a combination of mucolytic compounds with cytotoxic agents.展开更多
Facile direct esterification reactions between 2′,3′-O-isopropylidene-nucleosides and Fmoc- or trityl-protected amino acids %via% N,N-dicyclohexyl-carbodiimide(DCC) mediated condensation are described. These reactio...Facile direct esterification reactions between 2′,3′-O-isopropylidene-nucleosides and Fmoc- or trityl-protected amino acids %via% N,N-dicyclohexyl-carbodiimide(DCC) mediated condensation are described. These reactions offer a mild and convenient method to synthesize aminoacylated nucleoside derivatives.展开更多
AIM:To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues(NAs)themselves in patients with chronic hepatitis B(CHB)receiving NA therapy.METHODS:Fifty-two...AIM:To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues(NAs)themselves in patients with chronic hepatitis B(CHB)receiving NA therapy.METHODS:Fifty-two hepatitis B envelope antigen(HBeAg)positive CHB patients were enrolled and divided equally into two groups.One group received telbivudine(LDT,600 mg/d),and the other group received lamivudine(LAM,100 mg/d).Clinical,virological and immunological parameters were assessed at the baseline and at 4,12,24,36 and 48 wk.RESULTS:Both groups achieved significant hepatitis B virus(HBV)replication inhibition and alanine aminotransferase normalization at 48 wk.At the baseline,compared to healthy controls,CHB patients had a lower circulating CD8 T cell frequency(29.44%±11.55%vs 37.17%±7.30%,p=0.03)and higher frequencies of programmed death 1 positive CD8 T cells(pD-1+CD8 T)(16.48%±10.82%vs 7.02%±3.62%,p=0.0001)and CD4+CD25+Foxp3+T regulatory cells(Tregs)(23.64%±9.38%vs 13.60%±6.06%,p=0.001).On therapy,at the beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid(HBV DNA)and HBeAg declining,the frequencies of pD-1+CD8 T cells and Treg cells gradually and significantly declined at 12 and 24 wk in both therapy groups.At treatment week 4,patients treated with LDT had a lower frequency of pD-1+CD8 T cells compared to patients treated with LAM(10.08%±6.83%vs 20.51%±20.96%,p=0.02).The frequency of pD-1+CD8 T cells in all of the CHB patients was significantly correlated with both the HBV DNA level(r=0.45,p=0.01)and HBeAg level(r=0.47,p=0.01)at treatment week 24,but the frequency of Treg cells was only significantly correlated with the HBeAg level(r=0.44,p=0.02).Furthermore,the ability of CD8 T cells to secrete pro-inflammatory cytokines was partially restored after 24 wk of therapy.CONCLUSION:NA-mediated HBV suppression could down-regulate the production of negative regulators of host immunity during the first 24 wk of therapy and could partially restore the ability of CD8 T cells to secrete pro-inflammatory cytokines.This immune modulating response may be correlated with the levels of both HBV DNA and HBeAg.展开更多
BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants signif...BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.展开更多
Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donor...Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.展开更多
Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bi...Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.展开更多
C4'-H bond dissociation enthalpies of nucleosides were predicted using theoretical methods to a precision of 1-2 Kcal/mol. It was found that the stability of the C4' nucleoside radical is slightly dependent on...C4'-H bond dissociation enthalpies of nucleosides were predicted using theoretical methods to a precision of 1-2 Kcal/mol. It was found that the stability of the C4' nucleoside radical is slightly dependent on the base. The orders of stability are dA < dG < dT < dC for deoxynucleosides and U < G < A = C for nucleosides.展开更多
A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity an...A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively.展开更多
An environmentally benign and highly efficient one-pot preparation of α-aminophosphonates under solvent-free conditions was developed. By employing this method, 5-aminophosphonate substituted pyrimidine nucleosides w...An environmentally benign and highly efficient one-pot preparation of α-aminophosphonates under solvent-free conditions was developed. By employing this method, 5-aminophosphonate substituted pyrimidine nucleosides were synthesized in good to excellent yields starting from 5-forrnyl-2'-deoxyuridine, aniline and dimethylphosphite.展开更多
Ganoderma(lingzhi)is a famous herbal medicine and edible supplement in oriental countries for a long history.In this study,a simple micellar electrokinetic chromatography(MEKC)method was established for the analysis o...Ganoderma(lingzhi)is a famous herbal medicine and edible supplement in oriental countries for a long history.In this study,a simple micellar electrokinetic chromatography(MEKC)method was established for the analysis of nucleosides and bases,the major bioactive components in Ganoderma for the first time.By optimizing the borate concentration,the sodium dodecyl sulfate(SDS)concentration and the pH value of running buffer,10 nucleosides and bases achieved an ideal separation.In real sample analysis,the developed method was successfully used to determine the 10 target analytes in 23 batches of Ganoderma samples from different regions.Results indicated that contents of 10 investigated analytes in each sample showed obvious variation.The principal components analysis(PCA)and hierarchical cluster analysis(HCA)analysis classified the samples into three groups,and the HCA tree visualized the relationships which was mainly contributed by geographical partition.The results indicated geographical origin to be an important factor that affect the accumulation of nucleosides and bases in Ganoderma.In summary,this study provides a simple and practical strategy for quality assessment and cultivation reference of Ganoderma.展开更多
A pair of new anticancer nucleosides based on 1,2,4-triazole nucleosides and 1-((2-hydroxyethoxy) methyl)-5-(phenylthio)-1H-1,2,4-triazole-3-carboxamide have been synthesized, and have given the corresponding products...A pair of new anticancer nucleosides based on 1,2,4-triazole nucleosides and 1-((2-hydroxyethoxy) methyl)-5-(phenylthio)-1H-1,2,4-triazole-3-carboxamide have been synthesized, and have given the corresponding products in excellent yields. Its structures and conformations were confirmed by single crystal X-ray diffraction.展开更多
A new purine nucleoside coupled with an amino acid derivative, N^2-(l-methoxycarbonylethyl)guanosine 1, along with β- carboline and russulaceramide was isolated from the fruiting bodies of Amanita exitialis, a newl...A new purine nucleoside coupled with an amino acid derivative, N^2-(l-methoxycarbonylethyl)guanosine 1, along with β- carboline and russulaceramide was isolated from the fruiting bodies of Amanita exitialis, a newly described poisonous mushroom. Its structure was elucidated by spectroscopic methods. This is the first report of naturally occurring nucleosides in which an a-amino acid derivative is bonded through its a-amino nitrogen to a nucleobase aglycone by a C-N bond. The new compound was found to be toxic in brine shrimp lethality test (BST). C 2009 Published by Elsevier B.V. on behalf of Chinese Chemical Society.展开更多
Novel pyrimidine nucleoside-3,5-dicyanopyridine hybrids (4) or pyridine attached acylureas (5) were selectively and efficiently prepared from the reaction of 2′-deoxyuddin-5-yl-methylene malononitrile (1), malo...Novel pyrimidine nucleoside-3,5-dicyanopyridine hybrids (4) or pyridine attached acylureas (5) were selectively and efficiently prepared from the reaction of 2′-deoxyuddin-5-yl-methylene malononitrile (1), malononitrile (2) and thiophenol (3) or from an unexpected uracil ring-opening and pyddine ring-forming sequence via the reaction of 1 and 3. It is the first time such a sequence has ever been reported.展开更多
Some novel lipids bearing nucleosides were designed and synthesized as gene vectors, and the structures of these compounds were characterized by UV, IR, 1HNMR, 13CNMR and elemental analysis.
Nucleosides were phosphorylated with different N- (O, O-diisopropyl) phosphoryl amino acids to give nucleoside mono phosphates in aqueous solution. 2', 3', and 5'-isomers had been confirmed by comparison w...Nucleosides were phosphorylated with different N- (O, O-diisopropyl) phosphoryl amino acids to give nucleoside mono phosphates in aqueous solution. 2', 3', and 5'-isomers had been confirmed by comparison with authentic samples on the basis of HPLC analysis. The conversion percentage of nucleoside indicated that N- (O, O-diisopropyl) phosphoryl aspartic acid reacted with adenosine and guanosine at a much higher rate than other kinds of N- phosphoryl amino acids. while phosphorylation of cytidine and uridine was relatively easy by using N- (O, O-diisopropyl) phosphoryl threonine. The result could give some clue to the prebiotic code origin of nucleic acid and protein.展开更多
Two new nucleoside derivatives containing benzophenoxazinone moiety were synthesized. Their luminescence spectra show that they have strong near infrared fluorescence. Our study provides a new method for direct intr...Two new nucleoside derivatives containing benzophenoxazinone moiety were synthesized. Their luminescence spectra show that they have strong near infrared fluorescence. Our study provides a new method for direct introduction of near infrared fluorescent probe to bioactive molecules.展开更多
Aspergillus flavus causes serious disease on important agriculture crops, and its secondary metabolic products-aflatoxins are most potent toxin and carcinogen for animal and human, Structural and functional studies of...Aspergillus flavus causes serious disease on important agriculture crops, and its secondary metabolic products-aflatoxins are most potent toxin and carcinogen for animal and human, Structural and functional studies ofA. flavus proteins may provide insights into the identification of potential therapeutic targets and prevention of damage caused by A. flavus. Here, we report the expression, purification, crystallization and preliminary crystallographic analysis of NDK protein from A. flavus. The NDK protein was expressed in E. coli and purified by using a series of chromatographic methods to 〉98% purity. The recombinant protein was crystallized and the crystals diffracted to 2.4 A^° resolution. The crystal of NDK is in space group of C121 with a = 190.84, b = 169.47, c = 146.94 A^°. Preliminary data analysis indicated that the NDK molecule assembles into a multimer in the asymmetric unit.展开更多
A series of 4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide nucleosides was designed, synthesized and evaluated against vesicular stomatitis virus (VSV) in Wish cell. The antiviral activities of all compound...A series of 4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide nucleosides was designed, synthesized and evaluated against vesicular stomatitis virus (VSV) in Wish cell. The antiviral activities of all compounds were stronger than those of acyclovir, while their toxicities were similar to those of acyclovir.展开更多
In the presence of tetrazole,2'-substituted nucleosidesreacted ster■os■ifi■ally with n-BuOPIN■_2H_5■_2I_2 to nucleoside 3',5'-■lopnosphites with avial n-Buo group.The stereochemistry of oxidation of...In the presence of tetrazole,2'-substituted nucleosidesreacted ster■os■ifi■ally with n-BuOPIN■_2H_5■_2I_2 to nucleoside 3',5'-■lopnosphites with avial n-Buo group.The stereochemistry of oxidation of■y■lophosphite was investigated.展开更多
Background:To compare the efficacy and safety of Chinese herbal medicine combined with nucleoside antiviral drugs and nucleoside antiviral drugs alone in treating recurrent genital herpes.Methods:PubMed,Embase,Web of ...Background:To compare the efficacy and safety of Chinese herbal medicine combined with nucleoside antiviral drugs and nucleoside antiviral drugs alone in treating recurrent genital herpes.Methods:PubMed,Embase,Web of Science,Cochrane Library,Chinese Biomedical Literature Database,China National Knowledge Internet,VIP Database,and Wanfang Data were searched from inception to April 2021.Randomized controlled trials on the efficacy and safety of oral Chinese herbal medicine combined with nucleoside antiviral drugs for recurrent genital herpes were collected.All included trials were independently assessed by two reviewers with the Cochrane risk-of-bias tool,and a meta-analysis was conducted using Review Manager 5.4.Results:Compared with the use of nucleoside antiviral drugs alone,combination therapy with oral Chinese herbal medicine plus nucleoside antiviral drugs effectively reduced the herpes recurrence rate after the end of treatment(3 months:P=0.0002;6 months:P<0.00001;1 year:P<0.00001)and the number of recurrences each year(P<0.00001),improved the recurrent Genital Herpes Quality of Life Questionnaire score(P<0.00001),and regulated the levels of interferon-γ,interleukin-2,tumor necrosis factor-α,and T lymphocyte subsets in the peripheral blood,and the difference was statistically significant.Different subgroups reported mixed results with respect to the efficacy in the short term.The incidence of adverse reactions and the time of symptom disappearance between the two groups were not significantly different.Conclusion:Chinese herbal medicine combined with nucleoside antiviral drugs can effectively reduce the recurrence rate of recurrent genital herpes,improve the patient’s quality of life and enhance the body’s immunity.Considering the possible risk of publication bias,more high-quality randomized controlled trials are still needed to verify the conclusions of this article.展开更多
文摘The prognosis of pancreatic cancer is poor with the overall 5-year survival rate of less than 5%changing minimally over the past decades and future projections predicting it developing into the second leading cause of cancer related mortality within the next decade.Investigations into the mechanisms of pancreatic cancer development,progression and acquired chemoresistance have been constant for the past few decades,thus resulting in the identification of human nucleoside transporters and factors affecting cytotoxic uptake via said transporters.This review summaries the aberrant expression and role of human nucleoside transports in pancreatic cancer,more specifically human equilibrative nucleoside transporter 1/2(hENT1,hENT2),and human concentrative nucleoside transporter 1/3(hCNT1,hCNT3),while briefly discussing the connection and importance between these nucleoside transporters and mucins that have also been identified as being aberrantly expressed in pancreatic cancer.The review also discusses the incidence,current diagnostic techniques as well as the current therapeutic treatments for pancreatic cancer.Furthermore,we address the importance of chemoresistance in nucleoside analogue drugs,in particular,gemcitabine and we discuss prospective therapeutic treatments and strategies for overcoming acquired chemoresistance in pancreatic cancer by the enhancement of human nucleoside transporters as well as the potential targeting of mucins using a combination of mucolytic compounds with cytotoxic agents.
文摘Facile direct esterification reactions between 2′,3′-O-isopropylidene-nucleosides and Fmoc- or trityl-protected amino acids %via% N,N-dicyclohexyl-carbodiimide(DCC) mediated condensation are described. These reactions offer a mild and convenient method to synthesize aminoacylated nucleoside derivatives.
基金Supported by The Shanghai Natural Science Fund,No.09ZR1400500the National Natural Science Foundation of China,No.30972600+1 种基金the GuangHui Fund of Hepatitis Prevention Fund Committee China,No.GHZ20100204the Shanghai Health Bureau Fund,No.2012092
文摘AIM:To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues(NAs)themselves in patients with chronic hepatitis B(CHB)receiving NA therapy.METHODS:Fifty-two hepatitis B envelope antigen(HBeAg)positive CHB patients were enrolled and divided equally into two groups.One group received telbivudine(LDT,600 mg/d),and the other group received lamivudine(LAM,100 mg/d).Clinical,virological and immunological parameters were assessed at the baseline and at 4,12,24,36 and 48 wk.RESULTS:Both groups achieved significant hepatitis B virus(HBV)replication inhibition and alanine aminotransferase normalization at 48 wk.At the baseline,compared to healthy controls,CHB patients had a lower circulating CD8 T cell frequency(29.44%±11.55%vs 37.17%±7.30%,p=0.03)and higher frequencies of programmed death 1 positive CD8 T cells(pD-1+CD8 T)(16.48%±10.82%vs 7.02%±3.62%,p=0.0001)and CD4+CD25+Foxp3+T regulatory cells(Tregs)(23.64%±9.38%vs 13.60%±6.06%,p=0.001).On therapy,at the beginning 24 wk with the levels of hepatitis B virus deoxyribonucleic acid(HBV DNA)and HBeAg declining,the frequencies of pD-1+CD8 T cells and Treg cells gradually and significantly declined at 12 and 24 wk in both therapy groups.At treatment week 4,patients treated with LDT had a lower frequency of pD-1+CD8 T cells compared to patients treated with LAM(10.08%±6.83%vs 20.51%±20.96%,p=0.02).The frequency of pD-1+CD8 T cells in all of the CHB patients was significantly correlated with both the HBV DNA level(r=0.45,p=0.01)and HBeAg level(r=0.47,p=0.01)at treatment week 24,but the frequency of Treg cells was only significantly correlated with the HBeAg level(r=0.44,p=0.02).Furthermore,the ability of CD8 T cells to secrete pro-inflammatory cytokines was partially restored after 24 wk of therapy.CONCLUSION:NA-mediated HBV suppression could down-regulate the production of negative regulators of host immunity during the first 24 wk of therapy and could partially restore the ability of CD8 T cells to secrete pro-inflammatory cytokines.This immune modulating response may be correlated with the levels of both HBV DNA and HBeAg.
基金Supported by the National Natural Science Foundation of China,No.81573507,No.81473283,No.81173131,and No.81320108027Guangdong Provincial Key Laboratory Construction Foundation,No.2017B030314030+1 种基金The National Key Research and Development Program,No.2016YFC0905003the 111 Project,No.B16047
文摘BACKGROUND Thiopurine-induced leukopenia(TIL)is a life-threatening toxicity and occurs with a high frequency in the Asian population.Although nucleoside diphosphate-linked moiety X-type motif 15(NUDT15)variants significantly improve the predictive sensitivity of TIL,more than 50%of cases of this toxicity cannot be predicted by this mutation.The potential use of the 6-thioguanine nucleotide(6TGN)level to predict TIL has been explored,but no decisive conclusion has been reached.Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes?AIM To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes.METHODS Patients’clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017.NUDT15 R139C,thiopurine S methyltransferase,and 6TGN concentrations were measured.RESULTS A total of 411 Crohn’s disease patients were included.TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8×10^8 red blood cells(RBC),which was not different from that of patients without TIL(P=0.071).Then,we compared the 6TGN levels based on NUDT15 R139C.For CC(n=342)and CT(n=65)genotypes,the median 6TGN level in patients with TIL was significantly higher than that in patients without(474.8 vs 306.0 pmol/8×10^8 RBC,P=9.4×10-^5;291.7 vs 217.6 pmol/8×10^8 RBC,P=0.039,respectively).The four TT carriers developed TIL,with a median 6TGN concentration of 135.8 pmol/8×10^8 RBC.The 6TGN cut-off levels were 411.5 and 319.2 pmol/8×108 RBC for the CC and CT groups,respectively.CONCLUSION The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes.Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.
基金Supported by National High Technology Research and Development Program(863 Program)of China,Grant No.2012AA021001
文摘Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.
基金the Project for Sci-ence and Technology Plan of Liaoning Province(No.2011225020).
文摘Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.
基金NNSFC(No.20272057)the State Ministry of Education for the financial support.
文摘C4'-H bond dissociation enthalpies of nucleosides were predicted using theoretical methods to a precision of 1-2 Kcal/mol. It was found that the stability of the C4' nucleoside radical is slightly dependent on the base. The orders of stability are dA < dG < dT < dC for deoxynucleosides and U < G < A = C for nucleosides.
文摘A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively.
基金National Natural Science Foundation of China(Nos.20772025 and 20972042)the Program for Science & Technology Innovation Talents in Universities of Henan Province(No.2008HASTIT006)+1 种基金Innovation Scientists and Technicians Troop Construction Projects of Henan Province(No.104100510019)the Natural Science Foundation of Henan Province(Nos.092300410192 and 094300510054)
文摘An environmentally benign and highly efficient one-pot preparation of α-aminophosphonates under solvent-free conditions was developed. By employing this method, 5-aminophosphonate substituted pyrimidine nucleosides were synthesized in good to excellent yields starting from 5-forrnyl-2'-deoxyuridine, aniline and dimethylphosphite.
基金financially supported by the Research Committee of the University of Macao(MYRG2018-00239-ICMS and MYRG2014-00089-ICMS-QRCM)the Macao Science and Technology Development Fund(162/2017/A3)Guangzhou International Science and Technology Cooperation Project(File no.201807010044)。
文摘Ganoderma(lingzhi)is a famous herbal medicine and edible supplement in oriental countries for a long history.In this study,a simple micellar electrokinetic chromatography(MEKC)method was established for the analysis of nucleosides and bases,the major bioactive components in Ganoderma for the first time.By optimizing the borate concentration,the sodium dodecyl sulfate(SDS)concentration and the pH value of running buffer,10 nucleosides and bases achieved an ideal separation.In real sample analysis,the developed method was successfully used to determine the 10 target analytes in 23 batches of Ganoderma samples from different regions.Results indicated that contents of 10 investigated analytes in each sample showed obvious variation.The principal components analysis(PCA)and hierarchical cluster analysis(HCA)analysis classified the samples into three groups,and the HCA tree visualized the relationships which was mainly contributed by geographical partition.The results indicated geographical origin to be an important factor that affect the accumulation of nucleosides and bases in Ganoderma.In summary,this study provides a simple and practical strategy for quality assessment and cultivation reference of Ganoderma.
文摘A pair of new anticancer nucleosides based on 1,2,4-triazole nucleosides and 1-((2-hydroxyethoxy) methyl)-5-(phenylthio)-1H-1,2,4-triazole-3-carboxamide have been synthesized, and have given the corresponding products in excellent yields. Its structures and conformations were confirmed by single crystal X-ray diffraction.
基金supported by the Knowledge Innovation Program of the Chinese Academy of Sciences(No.KSCX2-YW-N-036).
文摘A new purine nucleoside coupled with an amino acid derivative, N^2-(l-methoxycarbonylethyl)guanosine 1, along with β- carboline and russulaceramide was isolated from the fruiting bodies of Amanita exitialis, a newly described poisonous mushroom. Its structure was elucidated by spectroscopic methods. This is the first report of naturally occurring nucleosides in which an a-amino acid derivative is bonded through its a-amino nitrogen to a nucleobase aglycone by a C-N bond. The new compound was found to be toxic in brine shrimp lethality test (BST). C 2009 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
基金the National Natural Science Foundation of China(No.20772025)the Program for Science & Technology Innovation Talents in Universities of Henan Province(No.2008HASTIT006)the Natural Science Foundation of Department of Education of Henan Province(No.2008A150013)
文摘Novel pyrimidine nucleoside-3,5-dicyanopyridine hybrids (4) or pyridine attached acylureas (5) were selectively and efficiently prepared from the reaction of 2′-deoxyuddin-5-yl-methylene malononitrile (1), malononitrile (2) and thiophenol (3) or from an unexpected uracil ring-opening and pyddine ring-forming sequence via the reaction of 1 and 3. It is the first time such a sequence has ever been reported.
基金This research was supported by the National Natural Science Foundation of China.
文摘Some novel lipids bearing nucleosides were designed and synthesized as gene vectors, and the structures of these compounds were characterized by UV, IR, 1HNMR, 13CNMR and elemental analysis.
基金This prqiect was supported by the National Natural Science Foundation of China, National Science Technology Committee of Chi
文摘Nucleosides were phosphorylated with different N- (O, O-diisopropyl) phosphoryl amino acids to give nucleoside mono phosphates in aqueous solution. 2', 3', and 5'-isomers had been confirmed by comparison with authentic samples on the basis of HPLC analysis. The conversion percentage of nucleoside indicated that N- (O, O-diisopropyl) phosphoryl aspartic acid reacted with adenosine and guanosine at a much higher rate than other kinds of N- phosphoryl amino acids. while phosphorylation of cytidine and uridine was relatively easy by using N- (O, O-diisopropyl) phosphoryl threonine. The result could give some clue to the prebiotic code origin of nucleic acid and protein.
文摘Two new nucleoside derivatives containing benzophenoxazinone moiety were synthesized. Their luminescence spectra show that they have strong near infrared fluorescence. Our study provides a new method for direct introduction of near infrared fluorescent probe to bioactive molecules.
基金supported by National 973 Program(No.2013CB127802)of Ministry of Science and Technology of Chinathe National Natural Science Foundation of China(Nos.31172297 and 31400100)
文摘Aspergillus flavus causes serious disease on important agriculture crops, and its secondary metabolic products-aflatoxins are most potent toxin and carcinogen for animal and human, Structural and functional studies ofA. flavus proteins may provide insights into the identification of potential therapeutic targets and prevention of damage caused by A. flavus. Here, we report the expression, purification, crystallization and preliminary crystallographic analysis of NDK protein from A. flavus. The NDK protein was expressed in E. coli and purified by using a series of chromatographic methods to 〉98% purity. The recombinant protein was crystallized and the crystals diffracted to 2.4 A^° resolution. The crystal of NDK is in space group of C121 with a = 190.84, b = 169.47, c = 146.94 A^°. Preliminary data analysis indicated that the NDK molecule assembles into a multimer in the asymmetric unit.
基金the National Natural Science Foundation of China(No.30572240).
文摘A series of 4H-[1,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide nucleosides was designed, synthesized and evaluated against vesicular stomatitis virus (VSV) in Wish cell. The antiviral activities of all compounds were stronger than those of acyclovir, while their toxicities were similar to those of acyclovir.
文摘In the presence of tetrazole,2'-substituted nucleosidesreacted ster■os■ifi■ally with n-BuOPIN■_2H_5■_2I_2 to nucleoside 3',5'-■lopnosphites with avial n-Buo group.The stereochemistry of oxidation of■y■lophosphite was investigated.
基金supported by the National Natural Science Foundation of China(No.81874483,No.81273787).
文摘Background:To compare the efficacy and safety of Chinese herbal medicine combined with nucleoside antiviral drugs and nucleoside antiviral drugs alone in treating recurrent genital herpes.Methods:PubMed,Embase,Web of Science,Cochrane Library,Chinese Biomedical Literature Database,China National Knowledge Internet,VIP Database,and Wanfang Data were searched from inception to April 2021.Randomized controlled trials on the efficacy and safety of oral Chinese herbal medicine combined with nucleoside antiviral drugs for recurrent genital herpes were collected.All included trials were independently assessed by two reviewers with the Cochrane risk-of-bias tool,and a meta-analysis was conducted using Review Manager 5.4.Results:Compared with the use of nucleoside antiviral drugs alone,combination therapy with oral Chinese herbal medicine plus nucleoside antiviral drugs effectively reduced the herpes recurrence rate after the end of treatment(3 months:P=0.0002;6 months:P<0.00001;1 year:P<0.00001)and the number of recurrences each year(P<0.00001),improved the recurrent Genital Herpes Quality of Life Questionnaire score(P<0.00001),and regulated the levels of interferon-γ,interleukin-2,tumor necrosis factor-α,and T lymphocyte subsets in the peripheral blood,and the difference was statistically significant.Different subgroups reported mixed results with respect to the efficacy in the short term.The incidence of adverse reactions and the time of symptom disappearance between the two groups were not significantly different.Conclusion:Chinese herbal medicine combined with nucleoside antiviral drugs can effectively reduce the recurrence rate of recurrent genital herpes,improve the patient’s quality of life and enhance the body’s immunity.Considering the possible risk of publication bias,more high-quality randomized controlled trials are still needed to verify the conclusions of this article.