Sterol transport proteins in yeast: a review / 生物工程学报

Sterols are a class of cyclopentano-perhydrophenanthrene derivatives widely present in living organisms. Sterols are important components of cell membranes. In addition, they also have important physiological and pharmacological activities. With the development of synthetic biology and metabolic engineering technology, yeast cells are increasingly used for the heterologous synthesis of sterols in recent years. Nevertheless, since sterols are hydrophobic macromolecules, they tend to accumulate in the membrane fraction of yeast cells and consequently trigger cytotoxicity, which hampers the further improvement of sterols yield. Therefore, revealing the mechanism of sterol transport in yeast, especially understanding the working principle of sterol transporters, is vital for designing strategies to relieve the toxicity of sterol accumulation and increasing sterol yield in yeast cell factories. In yeast, sterols are mainly transported through protein-mediated non-vesicular transport mechanisms. This review summarizes five types of sterol transport-related proteins that have been reported in yeast, namely OSBP/ORPs family proteins, LAM family proteins, ABC transport family proteins, CAP superfamily proteins, and NPC-like sterol transport proteins. These transporters play important roles in intracellular sterol gradient distribution and homeostasis maintenance. In addition, we also review the current status of practical applications of sterol transport proteins in yeast cell factories.

Automatic radiolabeling of the norepinephrine transporter targeted tracer 18F-mFBG and evaluation of 18F-mFBG PET/CT imaging in pheochromocytoma / 中华核医学与分子影像杂志

Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.

Characterization of the nigroestriatal system in a sample of patients with amyotrophic lateral sclerosis / Caracterização do sistema nigroestriatal em uma amostra de pacientes com esclerose lateral amiotrófica

Abstract Background The coexistence of amyotrophic lateral sclerosis (ALS) with clinical forms of Parkinson disease (PD), although uncommon, is found to a greater degree than one would expect by chance. The pathological mechanisms of ALS and PD are still not fully understood, and the coexistence of these two diseases suggests that they could share mechanisms in common. Objective Here we present a sample of patients with clinically definitive or probable ALS who were evaluated with single-photon emission computed tomography SPECT/TRODAT and compared with non-ALS controls. Methods Patients with clinically definite or probable ALS were assessed with the amyotrophic lateral sclerosis functional rating scale (ALSFRS) to define severity and had their demographic data collected. The TRODAT results of patients with ALS were compared with those of patients with a diagnosis of PD with less than 10 years of duration, and with patients with a diagnosis of others movement disorders not associated with neurodegenerative diseases. Results A total of 75% of patients with ALS had TRODAT results below the levels considered normal; that was also true for 25% of the patients in the control group without neurodegenerative disease, and for 100% of the patients in the PD group. A statistically significant difference was found between patients with ALS and the control group without neurodegenerative disease in the TRODAT values < 0.05. Conclusions Our study fits with the neuropathological and functional evidence that demonstrates the existence of nigrostriatal dysfunction in patients with ALS. Further research to better understand the role of these changes in the pathophysiological process of ALS needs to be performed.

Resumo Antecedentes A coexistência da esclerose lateral amiotrófica (ELA) com formas clínicas da doença de Parkinson (DP), embora incomum, é encontrada em um grau maior do que seria esperado ao acaso. Os mecanismos patológicos da ELA e da DP ainda não são totalmente compreendidos e a coexistência dessas duas doenças sugere que elas podem compartilhar mecanismos em comum. Objetivo Apresentamos uma amostra de pacientes com ELA clinicamente definida ou provável que foram avaliados com tomografia computadorizada por emissão de fóton único (SPECT)/TRODAT e comparados com controles sem ELA. Métodos Pacientes com ELA clinicamente definida ou provável foram avaliados com a escala funcional de esclerose lateral amiotrófica (ALSFRS) para definir a gravidade e foram coletados os seus dados demográficos. Os resultados do TRODAT de pacientes com ELA foram comparados com aqueles de pacientes com diagnóstico de DP com menos de 10 anos de duração e com pacientes com diagnóstico de outros distúrbios do movimento não associados a doenças neurodegenerativas. Resultados Um total de 75% dos pacientes com ELA apresentou resultados de TRODAT abaixo dos níveis considerados normais; 25% no grupo controle sem doença neurodegenerativa e 100% no grupo DP. Uma diferença estatisticamente significativa foi encontrada entre os pacientes com ELA e o grupo controle sem doença neurodegenerativa nos valores de TRODAT p< 0,05. Conclusões Nosso estudo está de acordo com as evidências neuropatológicas e funcionais que demonstram a existência de disfunção nigroestriatal em pacientes com ELA. Mais pesquisas para entender melhor o papel dessas mudanças no processo fisiopatológico da ELA precisam ser realizadas.

Research progress on the antihypertensive effect of sodium-glucose synergistic transporter 2 inhibitors / 中华全科医师杂志

Diabetes mellitus is a chronic metabolic disease, in which the abnormality of glucose and lipid metabolism may cause multisystem damage. Sodium-glucose synergistic transporter 2 (SGLT2) inhibitors are a novel type of hypoglycemic drug that can lower blood sugar level by inhibiting the absorption of glucose through renal tubules. Studies have shown that SGLT2 inhibitors also have a lowering effect on blood pressure, but the mechanism is not fully elucidated. In this article the hypotensive effects of SGLT2 inhibitors and possible mechanisms are reviewed.

Ivermectina: ¿Un antiparasitario frente a SARS-CoV-2? / Ivermectin: an antiparasitic drug to fight SARS-CoV-2?

RESUMEN La capacidad de propagación y letalidad del SARS-CoV-2 en todo el mundo motiva la urgente necesidad de desarrollar una estrategia terapéutica apropiada para controlar los casos de COVID-19. El desarrollo de nuevos fármacos frente a este nuevo virus es apremiante debido a su rápida diseminación. Se han propuesto alternativas paralelas empleando fármacos ya disponibles para fines similares. Esta revisión describe el potencial antiviral de la ivermectina, así como sus mecanismos de acción frente a algunos virus, y discute su probable aplicación contra el SARS-CoV-2.

ABSTRACT The global spread and lethality of SARS-CoV-2 prompt the urgent need to develop an appropriate therapeutic strategy to control COVID-19 cases. The development of new drugs to fight this novel virus is urgent due to its rapid spread. Parallel alternatives have been proposed by using drugs already available for similar purposes. This review article describes the antiviral potential of ivermectin as well as its mechanisms of action against some viruses, and discusses its probable use to fight SARS-CoV-2.

Analysis on drug transporters-mediated interaction between drugs and metformin / 中国基层医药

Objective:To investigate the potential drug interactions of outpatient prescriptions containing metformin combined with other drugs from the perspective of drug transporters.Methods:The prescriptions containing metformin that were used in the Outpatient Department of Hainan General Hospital, China between July and December 2019 were collected. The potential interaction between drugs and metformin used in the prescriptions was analyzed according to drug instructions, Drugbank, PubMed databases.Results:A total of 15 568 outpatient prescriptions containing metformin were collected, including 9 146 prescriptions for male patients and 6 422 prescriptions for female patients. A total of 14 902 prescriptions contained combined medication. The drugs used in combination included other hypoglycemic drugs, antiplatelet drugs, antihypertensive drugs, lipid-lowering drugs, and neuroprotective drugs. The drug transporters including aspirin, atorvastatin calcium, repaglinide, bisoprolol, metoprolol and clopidogrel had a potential interaction with metformin. There were 11 614 prescriptions containing drug transporters and metformin, including 5 938 prescriptions inhibiting organic cation transporter 1 and 5676 prescriptions inhibiting organic cation transporter 2.Conclusion:There is no incompatibility between the outpatient prescriptions containing metformin and the commonly used drugs for chronic diseases, but the outpatient doctors do not have enough knowledge about dose adjustment caused by potential interaction.

Research progress of magnesium ion and its transporters in tumors / 肿瘤

In recent years, researchers have found that magnesium ion homeostasis imbalance is common in tumor cells, and the deficiency and supplement of magnesium ion can affect the occurrence and development of tumor. As an abundant divalent cation in cells, magnesium ion plays an important role in maintaining genetic stability, metabolism, cell growth and proliferation, signal transduction and other physiological processes. Magnesium ion homeostasis is regulated by a variety of transporters, and the research reports on the changes of magnesium ion transporters expression leading to the imbalance of magnesium ion homeostasis which affects the occurrence, development and treatment prognosis of tumors are increasing year by year. In this article, magnesium ion and its related transport proteins include magnesium ion transient receptor potential melastatin (TRPM) protein, magnesium transporter (MagT) protein, cyclin and cystathionine beta-synthase (CBS) domain divalent metal cation transport mediator (CNNM) protein and solute carrier (SLC) protein and other related reports in tumors are summarized, with the purpose of providing ideas for exploring whether magnesium ion and its transporters can become new targets for tumor diagnosis, treatment and prognosis.

Beta-adrenergic pathway activation in head and neck cancer: a comprehensive analysis of the clinical and genomic features using integrated bioinformatics / Ativação da via beta-adrenérgica no câncer de cabeça e pescoço: uma análise abrangente das características clínicas e gênomicas utilizando a bioinformática

O estresse crônico leva à ativação da via de sinalização beta-adrenérgica. Sua ativação tem sido implicada na progressão de diferentes tipos de câncer, mas seu papel nos carcinomas espinocelulares de cabeça e pescoço (CECPs) permanece indefinido. O objetivo deste estudo foi investigar o papel da ativação da via betaadrenérgica na progressão dos CECPs, avaliar seu impacto na sobrevida dos pacientes e buscar possíveis terapias para pacientes que encontravam-se com a via beta-adrenérgica ativa. Quinhentos e vinte pacientes do The Cancer Genome Atlas com CECPs primários foram divididos em dois grupos: ADRB2baixa / SLC6A2baixa e ADRB2alta / SLC6A2alta. A associação de características clinicopatológicas e genômicas entre os grupos foram analisadas utilizando bioinformática. Os genes diferencialmente expressos (DEGs) foram identificados através da análise da expressão diferencial. A análise de sobrevida também foi realizada com base nas expressões ADRB2 e SLC6A2. Foram identificados medicamentos em potencial para tratamento de CECPs com base nos DEGs. Houve associação entre as expressões ADRB2 e SLC6A2 com idade, raça, localização do tumor, grau histológico, invasão perineural e status do HPV p16. Foram identificados 898 DEGs entre os grupos. Foi demonstrado que a expressão ADRB2alta / SLC6A2alta influenciou a proliferação, adesão e invasão de células CECPs além da angiogênese. Pacientes com carcinomas espinocelular de laringe e faringe apresentando expressão ADRB2alta / SLC6A2alta tiveram menor sobrevida. Por fim, 56 drogas antineoplásicas e imunoterápicas aprovadas pelo Food Drugs Administration foram identificadas como potenciais alvos para o tratamento personalizado. Significância: Estes achados sugerem fortemente um papel proeminente da sinalização beta-adrenérgica no CECPs ao estimular um fenótipo tumoral mais agressivo. Estas alterações tiveram um impacto negativo no prognóstico dos pacientes com CECP em região de faringe e laringe(AU)

Chronic stress leads to the activation of the beta-adrenergic pathway. Its activation has been implicated in the progression of different types of cancer but its role on head and neck squamous cell carcinomas (HNSCCs) remains undefined. The aim of this study was to investigate the influence of the beta-adrenergic pathway activation in the progression of HNSCCs, assess its impact in the survival of the patients, and explore the potential targets. Five hundred and twenty The Cancer Genome Altas patients with primary HNSCCs were divided in two groups: ADRB2low / SLC6A2low and ADRB2high / SLC6A2high. The association of clinicopathological and genomic features between the groups was analyzed using a bioinformatic approach. Differentially expressed genes (DEGs) were identified through differential expression analysis. Survival analysis was also performed based on ADRB2 and SLC6A2 expressions. Potential drugs for treatment of HNSCC were identified based on the DEGs. There was association between ADRB2 and SLC6A2 expressions with age, race, tumor site, histologic grade, perineural invasion, and HPV p16 status. It was identified 898 DEGs between the groups. It was demonstrated that ADRB2high / SLC6A2high expression influenced HNSCC cells proliferation, adhesion, invasion, and angiogenesis. Patients with larynx and pharynx squamous cell carcinomas presenting ADRB2high / SLC6A2high expression showed had lower survival rates. Finally, 56 Food Drugs Administration-approved antineoplastic and immunotherapeutic drugs were identified as potential targets for the personalized treatment. Significance: These findings strongly suggest a prominent role of beta-adrenergic pathway in HNSCC by stimulating a more aggressive tumoral phenotype. These alterations were shown to negatively impact the prognosis of patients with larynx and pharynx squamous cell carcinomas(AU)

Immunohistochemical expressionof sodium-dependent glucose transporter - 2 (SGLT-2) in clear cell renal carcinoma: possible prognostic implications

ABSTRACT Purpose: Glucose is a major energy resource for tumor cell survival and growth, and its influx into cells is mainly carried out by facilitative glucose transporters (GLUTs). Sodium - dependent glucose transporters (SGLTs) have been highlighted as playing important roles in diabetic treatment. However, their potential roles in cancer remain unclear. We examined expression patterns of SGLTs in tumor tissues together with conventional pathological variables to determine prognostic significance in patients with renal cell carcinoma (RCC). Materials and Methods: Nephrectomy specimens were obtained from 68 patients. GLUT - 1, - 2 and SGLT - 1, - 2 expression in tumor and adjacent normal tissues were analyzed by immunohistochemical staining, and intensity was quantified using an image analyzer. Results: The four glucose transporters evaluated were broadly distributed in tumor tissues as well as throughout the normal parenchyma. There was no significant correlation between transporter expression and conventional pathological variables. However, increased SGLT - 2 expression was significantly associated with shorter overall survival (p < 0.01), regardless of metastatic status. Conclusions: We propose possible prognostic significance of SGLT - 2 expression in human RCC. Given that glucose is a major energy resource for tumor cells and that glucose transport is largely mediated by SGLT, SGLT - 2 may serve as a possible therapeutic target in RCC.

Carnitine-acylcarnitine translocase deficiency with homozygous mutation of c.199-10T＞G: a case report and literature review / 中华围产医学杂志

Objective To investigate the clinical features of carnitine-acylcarnitine translocase deficiency (CACTD) with c.199-10T＞G homozygous mutation and the characteristics of SLC25A20 gene mutation.Methods This study retrospectively analyzed the clinical data,biochemical and genetic features,treatment and outcome of a boy with CACTD with c.199-10T＞G homozygous mutation,who admitted to Guangzhou Women and Children's Medical Center in September 2017.Pertinent articles were retrieved from China National Knowledge Infrastructure (CNKI),Wanfang Database,National Center for Biotechnology Information and PubMed from the establishment of these databases to April 2018 using key words including CACT,SLC25A20 and carnitine-acylcarnitine translocase.Clinical information of all affected cases in the retrieved publications was analyzed.Results (1) The full-term boy born vaginally at a local hospital was transferred to neonatal intensive care unit (NICU) of Guangzhou Women and Children's Medical Center at 2 days and 5 hours due to groaning,cyanosis and severe hypoglycemia (0.8 mmol/L) at 15 h after birth.His elder brother with similar symptoms died of unknown reason at 50 days of age.In this case,ammonemia,liver enzyme and creatine kinase were significantly elevated,amino acid analysis suggested liver damage,and high amounts of dicarboxylic aciduria,low free carnitine,markedly increased long-chain acylcarnitine and hypoketotic hypoglycemia were also observed.His electrocardiogram showed atrioventricular block and ventricular tachycardia.After a series of treatments,including repeated electrical cardioversion,lidocaine and amiodarone for arrhythmia,arginine for blood ammonia level reduction,formula supplement containing L-carnitine and medium-chain fatty acid,the patient whose conditions had significantly improved and was discharged at the request of his parents at 29 days old.Two weeks later,he was re-admitted due to diarrhea,and discharged two days later when he was 45 days old.He was lost to follow up since then.(2) A homozygous mutation of c.199-10T＞G was detected in this boy in SLC25A20 gene,which was also carried by his parents.(3) Thirtytwo publications in English were retrieved,involving 50 cases of CACTD and 100 sequenced alleles.A total of 40 mutations in SLC25A20 gene were found so far,and c.199-10T＞G was the most common mutation with a frequency of 22/100.It was identified in 13 patients,including nine homozygous mutations and four compound heterozygous mutations.Symptoms presented within 72 h after birth (25 min-52 h) in all the 13 infants,such as hypoketotic hypoglycemia,hyperammonemia,elevated liver enzyme and creatine kinase,significantly decreased free carnitine level,markedly increased level of long-chain acylcarnitine,dicarboxylic aciduria,arrhythmia and cardiomyopathy.The mortality rate of CACTD was 11/12 (the outcome of one case was not reported).Conclusions c.199-10T＞G is the most common SLC25A20 gene mutation reported in Asia population with severe phenotypes and poor outcomes.Early diagnosis and timely treatment of CACTD are crucial.Inborn metabolic diseases such as CACTD should be considered if unexplainable exacerbation of clinical signs in neonatal period,or sudden infant death occurs.

Preparation and imaging of 18 F-VUIIS1008 targeting TSPO in rheumatoid arthritis model / 中华核医学与分子影像杂志

Objective To synthesize a novel 18 F labeled probe targeting translocator protein ( TSPO) ligand 2-( 5, 7-diethyl-2-( 4-( 2-fluoroethoxy ) phenyl ) pyrazolo [ 1, 5-a ] pyrimidin-3-yl )-N, N-diethylacet-amide (VUIIS1008), and evaluate its biodistribution and imaging in rheumatoid arthritis (RA) model. Methods The tosylate substrate was labeled with 18 F using a tosyloxy for fluorine nucleophilic aliphatic substitution to obtain 18 F-VUIIS1008. The labeling efficiency, radiochemical purity, and stability in vitro were determined. In vitro cellular uptake and competitive binding assay were performed on RAW264.7 mac-rophage cells. Biodistribution and microPET/CT imaging were investigated on RA mice established by Com-plete Freund's Adjuvant. Two-sample t test was used to analyze the data. Results 18 F-VUIIS1008 was syn-thesized with the labeling yield up to (41.00±5.00)％, the radiochemical purity>98.00％, and the specific radioactivity >1. 52 × 108 MBq/mmol. 18 F-VUIIS1008 was highly stable with the radiochemical purity >98. 00％ at 4 h after incubation in mouse serum. In vitro, it also exhibited high specific TSPO binding in RAW264.7 macrophage cells. The uptake ratio was (14.00±0.30)％ at 1 h after incubation, and decreased significantly ((4.00±0.70)％;t=12.894, P<0.05) after adding excessive unlabeled VUIIS1008. The half maximal inhibitory concentration (IC50) of 18F-VUIIS1008 binding to TSPO was 0.05 nmol/L in RAW264.7 macrophage cells. In vivo distribution results showed that the uptake of 18 F-VUIIS1008 in the left arthritic ankles reached the peak value of (1.33±0.02) percentage activity of injection dose per gram of tissue (％ID/g) at 1 h after injection. The radioactivity ratio of left ankle arthritic tissue to blood ( A/B) and to normal muscle ( A/M) was 4.40±0.22 and 1.65±0.07 respectively. MicroPET/CT imaging demonstrated that 18F-VUIIS1008 could specifically target and retained in the inflammation site. Conclusion 18 F-VUIIS1008 can be easily synthe-sized with high radiochemical purity and can clearly visualized in RA imaging with low background, suggesting its potential as a novel promising molecular probe targeting TSPO for RA PET imaging.

Correlations between striatal dopamine transporter distribution, glucose metabolism and clinical symptoms in Parkinson's disease / 中华核医学与分子影像杂志

Objective To investigate the correlations among striatal dopamine transporter (DAT) distribution,glucose metabolism and Parkinson's disease (PD) clinical symptoms.Methods Twenty-five clinically confirmed idiopathic PD patients (17 males,8 females,age:(59.8± 9.2) years) who underwent 11 C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl) tropane (CFT) and 18 F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed.The detailed clinical scores were systematically collected from all patients.Correlations between DAT distribution,glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis.Results There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores,non-motor symptoms scale (NMSS) scores,activity of daily living scale (ADL) scores (r values:0.580,0.522,0.557,all P＜0.05).The CFT uptake of ipsilateral caudate nucleus,anterior putamen,and posterior putamen were negatively correlated with UPDRS motor scores (r values:-0.496,-0.492,-0.457,all P＜0.05),while those had no significant correlations with NMSS scores (r values:-0.420,-0.402,-0.355,all P＞0.05).The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values:-0.502,-0.522,both P＜0.05).There were no significant correlations between CFT uptake in contralateral striatal,anterior putamen,posterior putamen and PDRP values,UPDRS motor scores,NMSS scores and ADL scores(r values:from-0.466 to-0.129,all P＞0.05).The presence of the significant correlations between UPDRS motor scores,ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values:from-0.90 to-0.47,all P＜0.05).The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms.The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values:0.47-0.90,both P＜0.01),precentral gyrus and insula (r values:-0.90 to-0.47,all P＜0.01).Conclusion The correlations between DAT distribution,glucose metabolism and PD clinical symptoms are complicated,which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms.

The Potential Cardioprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors / 임상당뇨병

The potential mechanism by which sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent cardiovascular disease (CVD) is being widely investigated. Improved insulin resistance, along with decreased body fat mass associated with SGLT2 inhibitor treatment is consistent with previously well-established factors contributing to the prevention of CVD. These factors are responsible for reduction of oxidative stress as well as improvement of systemic inflammation. Because heart failure was one of the most dramatically improved cardiovascular events in various clinical trials and because SGLT2 inhibitors promote osmotic diuresis and natriuresis, hemodynamic changes are considered as a critical mechanism responsible for the cardioprotective effect of SGLT2 inhibitors. Restored tubuloglomerular feedback by SGLT2 inhibitors might play a role in renoprotection, which in turn, leads to fewer CVDs. Finally, blood ketone body increments in response to SGLT2 inhibition might act as a “super-fuel” for salvaging the failing diabetic heart.

Correlations between striatal dopamine transporter distribution, glucose metabolism and clinical symptoms in Parkinson′s disease / 中华核医学与分子影像杂志

Objective@#To investigate the correlations among striatal dopamine transporter (DAT) distribution, glucose metabolism and Parkinson′s disease (PD) clinical symptoms.@*Methods@#Twenty-five clinically confirmed idiopathic PD patients (17 males, 8 females, age: (59.8±9.2) years) who underwent 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane (CFT) and 18F-fluorodeoxyglucose (FDG) PET imaging from January 2015 to December 2016 were reviewed. The detailed clinical scores were systematically collected from all patients. Correlations between DAT distribution, glucose metabolism and clinical symptoms were evaluated at global and voxel levels using Pearson correlation analysis.@*Results@#There were significantly positive correlations between the PD-related pattern (PDRP) value and unified PD rating scale (UPDRS) motor scores, non-motor symptoms scale (NMSS) scores, activity of daily living scale (ADL) scores (r values: 0.580, 0.522, 0.557, all P<0.05). The CFT uptake of ipsilateral caudate nucleus, anterior putamen, and posterior putamen were negatively correlated with UPDRS motor scores (r values: -0.496, -0.492, -0.457, all P<0.05), while those had no significant correlations with NMSS scores (r values: -0.420, -0.402, -0.355, all P>0.05). The CFT uptake of ipsilateral caudate nucleus and anterior putamen were negatively correlated with ADL scores (r values: -0.502, -0.522, both P<0.05). There were no significant correlations between CFT uptake in contralateral striatal, anterior putamen, posterior putamen and PDRP values, UPDRS motor scores, NMSS scores and ADL scores(r values: from -0.466 to -0.129, all P>0.05). The presence of the significant correlations between UPDRS motor scores, ADL scores and the CFT radioactive count were confirmed in left caudate nucleus and left putamen (r values: from -0.90 to -0.47, all P<0.05). The metabolic PET imaging disclosed a set of brain regions correlating with the clinical symptoms. The presence of significant correlations between the metabolic PET imaging and CFT uptake were confirmed in bilateral caudate nucleus (r values: 0.47-0.90, both P<0.01), precentral gyrus and insula (r values: -0.90 to -0.47, all P<0.01).@*Conclusion@#The correlations between DAT distribution, glucose metabolism and PD clinical symptoms are complicated, which promote the understanding in the proper application of dopaminergic and metabolic PET imaging in PD and offer more evidences in PD pathophysiological mechanisms.

Expression and clinical significance of glucose transporters 1, monocarboxylate transporter 1 and monocarboxylate transporter 4 in colon cancer / 中国基层医药

Objective To investigate the correlation between the expression of glucose transporters 1 (GLUT1),monocarboxylate transporter 1 (MCT1),monocarboxylate transporter 4(MCT4) and clinical characteristics in colon cancer. Methods From January 2008 to January 2016,the carcinoma tissues of 84 cases with colon cancer after gastrointestinal surgery, and 40 samples of corresponding adjacent normal colon tissues in the First People＇s Hospital of Hangzhou were collected. The clinical data were collected. Immunohistochemistry was performed to detect the expression of GLUT1, MCT1 and MCT4, the results were analyzed. Results The positive expression rates of MCT1,GLUT1 and MCT4 in colon cancer were 54. 8% (46/84),47. 6% (40/84),58. 3% (49/84),respectively, which were significantly higher than those of the control group[12. 5% (5/40),7. 5% (3/40),15. 0% (6/40)],the differences were statistically significant (χ2=19. 987,19. 253,20. 615,all P＜0. 01). The expressions of GLUT1, MCT1,and MCT4 were not related to gender,age and tumor size,but related to lesion location,differentiation,lymph node metastasis,distant metastasis and clinical stage( GLUT1:χ2=6. 227,11. 629,10. 029,14. 817,4. 709;MCT1:χ2=6. 891,8. 615,9. 185,5. 337,16. 131;MCT4:χ2=8. 641,7. 077,12. 131,6. 917,7. 077;all P ＜0. 05). Conclusion High expression of GLUT1,MCT1 and MCT4 were observed in colon cancer. GLUT1,MCT1 and MCT4 may affect the development of colon cancer through energy metabolism pathway in colon cancer tissues.

Formation mechanism of tumor acidic microenvironment and its effects on tumor progression / 肿瘤

Tumor microenvironment plays an important role in the formation and development of tumors, and the acidity is one of the remarkable features of tumor microenvironment. Due to excessive proliferation of tumor cells and abnormal structure of tumor blood vessels, the tumor tissues are usually in a hypoxia state, leading to changes in the metabolic processes of tumor cells. Compared with the normal tissues which mainly rely on aerobic oxidation to obtain energy, the metabolism of tumor cells dominatingly depends on the anaerobic glycolysis. Therefore, the lactate acid produced by glycolysis and the carbon dioxide produced by respiration together result in the acidification of tumor microenvironment (TME), and affects many aspects of tumorigenesis and development. This review focuses on the formation mechanism of tumor acidic microenvironment and its impacts on tumor progression, including tumor immunity, invasion, autophagy and resistance to anti-cancer treatment.

Effect of rs3910105 in the Synuclein Gene on Dopamine Transporter Availability in Healthy Subjects

PURPOSE: The present study investigated associations between dopamine transporter (DAT) availability and α-synuclein levels in cerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA on DAT availability in healthy subjects. MATERIALS AND METHODS: The study population comprised healthy controls who underwent 123I-FP-CIT single-photon emission computed tomography screening. Five SNCA probes were used to target the boundaries of exon 3 and exon 4 (SNCA-E3E4), transcripts with a long 3′UTR region (SNCA-3UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare short transcript isoforms that comprise exons 1–4 (SNCA-007). RESULTS: In total, 123 healthy subjects (male 75, female 48) were included in this study. DAT availability in the caudate nucleus (p=0.0661) and putamen (p=0.0739) tended to differ according to rs3910105 genotype. In post-hoc analysis, DAT availability in the putamen was lower in subjects of TT genotype than those of CC/CT (p=0.0317). DAT availability in the caudate nucleus also showed a trend similar to that in the putamen (p=0.0597). Subjects of CT genotype with rs3910105 showed negative correlations with DAT availability in the putamen with SNCA-E3E4 (p=0.037, rho=−0.277), and SNCA-E4E6 (p=0.042, rho=−0.270), but not those of CC/TT genotypes. CONCLUSION: This is the first study to investigate the association of rs3910105 in SNCA with DAT availability. rs3910105 had an effect on DAT availability, and the correlation between DAT availability and SNCA transcripts were significant in CT genotypes of rs3910105.

Relationship between expression of glucose transporter 1 and clinicopathological features and prognosis of patients with gastric cancer: a Meta-analysis / 肿瘤研究与临床

Objective To investigate the expression of glucose transporters 1 (GLUT-1) in gastric cancer and its relation with clinicopathological characteristics and prognosis. Methods PubMed, Web of Science,EMbase,Cochrane Library,WanFang Databases and China National Knowledge Internet(CNKI)were used to search literatures about GLUT-1 and gastric cancer. From the day of establishment to May 15, 2017, according to the inclusion and exclusion criteria, 2 researchers independently screened studies, extracted data and assessed quality of the included studies. Effect value and 95 % CI was calculated respectively. Then Meta-analysis was conducted by using RevMan5.3 software. Results A total of 11 articles were enrolled, including 1 714 cases in the gastric cancer group and 431 cases in the normal gastric mucosa group. The results of Meta-analysis showed that GLUT-1 expression was higher in the gastric cancer group than that in the normal group, and there was a significant difference (OR= 24.23, 95 % CI 11.86-49.51, P< 0.000 01). The expression of GLUT-1 was not related with age, gender, tumor size and invasion depth (all P> 0.05), but related with differentiated degree (OR= 0.41, 95 % CI 0.25-0.67, P= 0.000 4), lymphatic metastasis (OR=5.11, 95 % CI 2.73-9.56, P<0.000 1), and TNM staging (OR= 0.32, 95 % CI 0.20-0.51, P< 0.000 01). Moreover, GLUT-1 had a correlation with the overall survival rate of gastric cancer (HR= 1.61, 95 % CI 1.30-1.99, P < 0.000 1). Conclusions GLUT-1 protein expression is higher in gastric cancer tissues than that in normal gastric mucosa, and it is related to tumor differentiation degree, lymph node metastasis, TNM staging.Besides,GLUT-1 may be correlated with poor prognosis of patients with gastric cancer.

Advances in placental glucose transport in hyperglycemic pregnant women / 中华围产医学杂志

As a common pregnancy complication,hyperglycemia in pregnancy has an important impact on pregnancy outcomes and the short-and long-term health of both mothers and babies.Placenta is important for maternal-fetal transport of nutrients and its capability of glucose transportation,which is influenced by the expression and regulation of glucose transporters,is crucial for hyperglycemia in pregnancy women.In this review,we summarized research results on the distribution and expression of several common placental glucose transporters in women with different types of hyperglycemia in pregnancy and their association with offspring development,as well as the main regulatory mechanisms affecting the expression of glucose transporters in order to provide evidences for understanding the mechanism of the effect of hyperglycemia in pregnancy on maternal and fetal health.

Effects of aldosterone on the protein expressions and the urea transport activity of UT-A1 and UT-A3 / 中华肾脏病杂志

Objective To investigate the effects of protein expressions and the urea transport activity of aldosterone on urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) in HEK293 cells and Xenopus laevis oocytes.Methods (1) Western Blot was used to investigate the protein expressions of UT-A1 and UT-A3.(2) Cell surface biotinylation was used to investigate the protein expressions of UT-A1 and UT-A3 on the cell surface of Xenopus laevis oocytes.(3) 14C-urea transport experiment was conducted to investigate the transport activity of UT-A1 and UT-A3 in Xenopus laevis oocytes.Results (1) Compared with UT-A1 or UT-A3 high expression groups,the total protein levels of UT-A 1 and UT-A3 were all significantly reduced in aldosterone treatment groups (all P ＜ 0.01).(2) Compared with UT-A1 or UT-A3 high expression groups,the levels of protein expression on cell surface were all significantly reduced in aldosterone groups (all P ＜ 0.01).(3) Compared with UT-A1 or UT-A3 high expression groups,14C-urea transport experiment results showed that aldosterone treatment groups had significantly reduced the urea transporter activity of UT-A1 (1 min:94.32±9.044vs 40.68±4.274,P＜0.01,n=6;3 min:165.0±4.7 vs 80.3±0.6,P＜0.01,n=6),and UT-A3 (1 min:204.6± 3.1 vs 176.7± 9.1,P＜0.05,n=6;3 min:371.4 ± 14.9 vs 318.8 ± 12.0,P＜0.05,n=6).Conclusion Aldosterone can directly down-regulate the protein expressions of UT-A1 and UT-A3 in both total protein and cell surface level,which reduces their urea transport activity.