BACKGROUND Juxtaglomerular cell tumor(JGCT)of the kidney,also known as reninoma,is a rare renal tumor that typically clinically manifests as hypertension,hypokalemia,high renin,and high aldosterone.It is a cause of se...BACKGROUND Juxtaglomerular cell tumor(JGCT)of the kidney,also known as reninoma,is a rare renal tumor that typically clinically manifests as hypertension,hypokalemia,high renin,and high aldosterone.It is a cause of secondary hypertension.Pregnancy with JGCT is rarer and easily misdiagnosed as pregnancy-induced hypertension,thus affecting treatment.CASE SUMMARY A 28-year-old woman presented in early pregnancy with hypertension(blood pressure of 229/159 mmHg),nausea,and occasional dizziness and headache.The patient was diagnosed with pregnancy-induced hypertension,and no relief was found after symptomatic treatment;hence,the pregnancy was terminated by artificial abortion.Her blood pressure remained high following termination of pregnancy.Blood tests suggested hypokalemia(2.997 mmol/L),blood aldo-sterone measured 613 ng/L,and computed tomography urography showed a tumor in the right kidney.Therefore,laparoscopic partial nephrectomy was performed.After surgery,the patient’s blood pressure returned to normal,and blood potassium,aldosterone,and renin normalized.Postoperative pathological examination revealed JGCT.After long-term follow-up,the patient became pregnant again 6 mo after surgery.No hypertension occurred during pregnancy,and the patient delivered a healthy female neonate.CONCLUSION Patients with pregnancy complicated by JGCT are difficult to diagnose.Herein,we advise surgeons on proper handling of such situations.展开更多
Curcumin exerts a neuroprotective effect on Alzheimer’s disease;however,it is not known whether microRNAs are involved in this protective effect.This study was conducted using swAPP695-HEK293 cells as an Alzheimer’s...Curcumin exerts a neuroprotective effect on Alzheimer’s disease;however,it is not known whether microRNAs are involved in this protective effect.This study was conducted using swAPP695-HEK293 cells as an Alzheimer’s disease cell model.swAPP695-HEK293 cells were treated with 0,0.5,1,2,5,and 10μM curcumin for 24 hours.The changes in miR-15b-5p,miR-19a-3p,miR-195-5p,miR-101-3p,miR-216b-5p,miR-16-5p and miR-185-5p expression were assessed by real-time quantitative polymerase chain reaction.The mRNA and protein levels of amyloid precursor protein,amyloid-β40 and amyloid-β42 were evaluated by quantitative real-time polymerase chain reaction,western blot assays and enzyme-linked immunosorbent assays.swAPP695-HEK293 cells were transfected with miR-15b-5p mimic,or treated with 1μM curcumin 24 hours before miR-15b-5p inhibitor transfection.The effects of curcumin on amyloid precursor protein,amyloid-β40 and amyloid-β42 levels were evaluated by western blot assays and enzyme-linked immunosorbent assay.Luciferase assays were used to analyze the interaction between miR-15b-5p and the 3′-untranslated region of amyloid precursor protein.The results show that amyloid precursor protein and amyloid-βexpression were enhanced in swAPP695-HEK293 cells compared with HEK293 parental cells.Curcumin suppressed the expression of amyloid precursor protein and amyloid-βand up-regulated the expression of miR-15b-5p in swAPP695-HEK293 cells.In addition,we found a negative association of miR-15b-5p expression with amyloid precursor protein and amyloid-βlevels in the curcumin-treated cells.Luciferase assays revealed that miR-15b-5p impaired the luciferase activity of the plasmid harboring the 3′-untranslated region of amyloid precursor protein.These findings indicate that curcumin down-regulates the expression of amyloid precursor protein and amyloid-βin swAPP695-HEK293 cells,which was partially mediated by miR-15b-5p via targeting of the 3′-untranslated region of amyloid precursor protein.展开更多
Microbial production of monoterpenoid indole alkaloids(MIAs)provides a sustainable and eco-friendly means to obtain compounds with high pharmaceutical values.However,efficient biosynthesis of MIAs in heterologous micr...Microbial production of monoterpenoid indole alkaloids(MIAs)provides a sustainable and eco-friendly means to obtain compounds with high pharmaceutical values.However,efficient biosynthesis of MIAs in heterologous microorganisms is hindered due to low supply of key precursors such as geraniol and its derivative 8-hydroxygeraniol catalyzed by geraniol 8-hydroxylase(G8H).In this study,we developed a facile evolution platform to screen strains with improved yield of geraniol by using the SCRaMbLE system embedded in the Sc2.0 synthetic yeast and confirmed the causal role of relevant genomic targets.Through genome mining,we identified several G8H enzymes that perform much better than the commonly used CrG8H for 8-hydroxygeraniol production in vivo.We further showed that the N-terminus of these G8H enzymes plays an important role in cellular activity by swapping experiments.Finally,the combination of the engineered chassis,optimized biosynthesis pathway,and utilization of G8H led to the final strain with more than 30-fold improvement in producing 8-hydroxygeraniol compared with the starting strain.Overall,this study will provide insights into the construction and optimization of yeast cells for efficient biosynthesis of 8-hydroxygeraniol and its derivatives.展开更多
The site-specific incorporation of the noncanonical amino acid(ncAA)into proteins via genetic code expansion(GCE)has enabled the development of new and powerful ways to learn,regulate,and evolve biological functions i...The site-specific incorporation of the noncanonical amino acid(ncAA)into proteins via genetic code expansion(GCE)has enabled the development of new and powerful ways to learn,regulate,and evolve biological functions in vivo.However,cellular biosynthesis of ncAA-containing proteins with high efficiency and fidelity is a formidable challenge.In this review,we summarize up-to-date progress towards improving the efficiency and orthogonality of GCE and enhancing intracellular compatibility of introduced translation machinery in the living cells by creation and optimization of orthogonal translation components,constructing genomically recoded organism(GRO),utilization of unnatural base pairs(UBP)and quadruplet codons(four-base codons),and spatial separation of orthogonal translation.展开更多
基金Supported by Medical and Health Technology Project of Hangzhou,No.A20220540.
文摘BACKGROUND Juxtaglomerular cell tumor(JGCT)of the kidney,also known as reninoma,is a rare renal tumor that typically clinically manifests as hypertension,hypokalemia,high renin,and high aldosterone.It is a cause of secondary hypertension.Pregnancy with JGCT is rarer and easily misdiagnosed as pregnancy-induced hypertension,thus affecting treatment.CASE SUMMARY A 28-year-old woman presented in early pregnancy with hypertension(blood pressure of 229/159 mmHg),nausea,and occasional dizziness and headache.The patient was diagnosed with pregnancy-induced hypertension,and no relief was found after symptomatic treatment;hence,the pregnancy was terminated by artificial abortion.Her blood pressure remained high following termination of pregnancy.Blood tests suggested hypokalemia(2.997 mmol/L),blood aldo-sterone measured 613 ng/L,and computed tomography urography showed a tumor in the right kidney.Therefore,laparoscopic partial nephrectomy was performed.After surgery,the patient’s blood pressure returned to normal,and blood potassium,aldosterone,and renin normalized.Postoperative pathological examination revealed JGCT.After long-term follow-up,the patient became pregnant again 6 mo after surgery.No hypertension occurred during pregnancy,and the patient delivered a healthy female neonate.CONCLUSION Patients with pregnancy complicated by JGCT are difficult to diagnose.Herein,we advise surgeons on proper handling of such situations.
基金supported by the Science and Technology Planning Project of Guangdong Province of China,No.2016A020226022(to HYL)the Medical and Health Technology Project of Guangzhou of China,No.20161A011068(to HYL)the Guangzhou Science Technology and Innovation Commission of China,No.201704020043(to QCG)
文摘Curcumin exerts a neuroprotective effect on Alzheimer’s disease;however,it is not known whether microRNAs are involved in this protective effect.This study was conducted using swAPP695-HEK293 cells as an Alzheimer’s disease cell model.swAPP695-HEK293 cells were treated with 0,0.5,1,2,5,and 10μM curcumin for 24 hours.The changes in miR-15b-5p,miR-19a-3p,miR-195-5p,miR-101-3p,miR-216b-5p,miR-16-5p and miR-185-5p expression were assessed by real-time quantitative polymerase chain reaction.The mRNA and protein levels of amyloid precursor protein,amyloid-β40 and amyloid-β42 were evaluated by quantitative real-time polymerase chain reaction,western blot assays and enzyme-linked immunosorbent assays.swAPP695-HEK293 cells were transfected with miR-15b-5p mimic,or treated with 1μM curcumin 24 hours before miR-15b-5p inhibitor transfection.The effects of curcumin on amyloid precursor protein,amyloid-β40 and amyloid-β42 levels were evaluated by western blot assays and enzyme-linked immunosorbent assay.Luciferase assays were used to analyze the interaction between miR-15b-5p and the 3′-untranslated region of amyloid precursor protein.The results show that amyloid precursor protein and amyloid-βexpression were enhanced in swAPP695-HEK293 cells compared with HEK293 parental cells.Curcumin suppressed the expression of amyloid precursor protein and amyloid-βand up-regulated the expression of miR-15b-5p in swAPP695-HEK293 cells.In addition,we found a negative association of miR-15b-5p expression with amyloid precursor protein and amyloid-βlevels in the curcumin-treated cells.Luciferase assays revealed that miR-15b-5p impaired the luciferase activity of the plasmid harboring the 3′-untranslated region of amyloid precursor protein.These findings indicate that curcumin down-regulates the expression of amyloid precursor protein and amyloid-βin swAPP695-HEK293 cells,which was partially mediated by miR-15b-5p via targeting of the 3′-untranslated region of amyloid precursor protein.
基金supported by grants from the National Key Research and Development Program of China (No.2021YFC2100800 to Y.Z.)the Science,Technology and Innovation Commission of Shenzhen Municipality under grant (No.JCYJ20180507183534578)the Tip-top Scientific and Technical Innovative Youth Talents of Guangdong Special Support Program (2019TQ05Y876 to Y.S.)。
文摘Microbial production of monoterpenoid indole alkaloids(MIAs)provides a sustainable and eco-friendly means to obtain compounds with high pharmaceutical values.However,efficient biosynthesis of MIAs in heterologous microorganisms is hindered due to low supply of key precursors such as geraniol and its derivative 8-hydroxygeraniol catalyzed by geraniol 8-hydroxylase(G8H).In this study,we developed a facile evolution platform to screen strains with improved yield of geraniol by using the SCRaMbLE system embedded in the Sc2.0 synthetic yeast and confirmed the causal role of relevant genomic targets.Through genome mining,we identified several G8H enzymes that perform much better than the commonly used CrG8H for 8-hydroxygeraniol production in vivo.We further showed that the N-terminus of these G8H enzymes plays an important role in cellular activity by swapping experiments.Finally,the combination of the engineered chassis,optimized biosynthesis pathway,and utilization of G8H led to the final strain with more than 30-fold improvement in producing 8-hydroxygeraniol compared with the starting strain.Overall,this study will provide insights into the construction and optimization of yeast cells for efficient biosynthesis of 8-hydroxygeraniol and its derivatives.
基金the National Key Research and Development Program of China(No.2018YFA0900100)National Natural Science Foundation of China(No.31901029 to X.F.and No.31800078 to Y.S.)+1 种基金Natural Science Foundation of Guangdong Province,China(No.2021A1515010995 to X.F.)Guangdong Provincial Key Laboratory of Genome Read and Write(No.2017B030301011).
文摘The site-specific incorporation of the noncanonical amino acid(ncAA)into proteins via genetic code expansion(GCE)has enabled the development of new and powerful ways to learn,regulate,and evolve biological functions in vivo.However,cellular biosynthesis of ncAA-containing proteins with high efficiency and fidelity is a formidable challenge.In this review,we summarize up-to-date progress towards improving the efficiency and orthogonality of GCE and enhancing intracellular compatibility of introduced translation machinery in the living cells by creation and optimization of orthogonal translation components,constructing genomically recoded organism(GRO),utilization of unnatural base pairs(UBP)and quadruplet codons(four-base codons),and spatial separation of orthogonal translation.