Baicalin Induces Ferroptosis in Gastric Cancer Cells via p53-mediated SLC7A11 Down-regulation / 中国实验方剂学杂志

ObjectiveTo explore the inhibitory effect of different concentration of baicalin （0， 100， 200， 400 μmol·L-1） on the proliferation of human gastric cancer SGC-7901 cells and the underlying mechanism. MethodSGC-7901 cells were treated with baicalin. Then methyl thiazolyl tetrazolium （MTT） assay was employed to examine the inhibitory effect of baicalin on the cells. At the same time， ferrostatin-1 （Fer-1） was added to observe the viability of cells after baicalin treatment. The expression of ferroptosis-related genes was detected by Real-time polymerase chain reaction （Real-time PCR） and Western blot. The content of malondialdehyde （MDA） and the level of glutathione （GSH） were detected respectively by MTT assay and enzyme-linked immunosorbent assay. The role of tumor protein 53 （p53）/solute carrier family 7 member 11 （SLC7A11） pathway in the regulation of ferroptosis was investigated respectively via overexpression and small interfering RNA （siRNA） methods. ResultCompared with the blank group， baicalin decreased the viability of SGC-7901 （P<0.05， P<0.01） in a dose- and time-dependent manner. The intervention of Fer-1 significantly alleviated the decrease of SGC-7901 cell viability caused by baicalin （P<0.01）. In addition， compared with the baicalin group， Fer-1+baicalin group showed decrease in MDA content and the mRNA and protein levels of prostaglandin-endoperoxide synthase 2 （PTGS2） in the cells （P<0.01）， and increase in GSH activity and mRNA and protein levels of glutathione peroxidase 4 （GPX4） （P<0.01）. The protein level of SLC7A11 in the baicalin group was decreased compared with that in the blank group （P<0.05， P<0.01） in a dose-dependent manner. Compared with the baicalin group， the reactive oxygen species （ROS） level and MDA content in SLC7A11-overexpressing cells were significantly decreased after baicalin treatment （P<0.01）， and the GSH activity was significantly increased （P<0.01）. The fluorescence intensity of p53 in the cells of the baicalin group was increased compared with that of the blank group （P<0.01）. Compared with the baicalin group， the expression level of p53 protein in the cells transfected with p53 siRNA was significantly decreased after baicalin treatment （P<0.01）， and the expression level of SLC7A11 was significantly increased （P<0.01）. ConclusionBaicalin can effectively inhibit the proliferation of SGC-7901 cells by regulating p53/SLC7A11-mediated ferroptosis.

Research progress of solute carriers related genes in malignant tumors / 国际肿瘤学杂志

As a transport channel for amino acids, solute carrier (SLC) exists in all kinds of cells, and its function is to transport various amino acids and provide necessary nutrients for the growth and development of cells. In recent years, SLC7A5 and SLC7A11 genes of SLC7 family members have been found to be highly expressed in various malignant tumors, which can promote the occurrence and development of tumors by providing necessary amino acids for tumors. Studies have shown that these genes are associated with a variety of malignant tumors, and their expression is closely related to the growth, metastasis, treatment and prognosis of tumor cells. Moreover, the results of multiple studies suggest that SLC7A5 and SLC7A11 genes can be used as therapeutic targets for malignant tumors. Clarifying the expression and clinical significance of the above genes in malignant tumors, the molecular biological mechanism and the progress of molecular targeted therapy are helpful to provide a new way for the diagnosis and treatment of malignant tumors.

Gitelman syndrome, a rare cause of refractory hypokalemia. A case report / Símdrome de Gitelman, causa rara de hipopotasemia refractaria. Reporte de caso

Abstract Introduction: Gitelman syndrome is a rare hereditary primary renal tubular disorder, with a prevalence of approximately 1 to 10 cases per 40 000 people. It does not have specific symptoms, so its diagnosis depends on high clinical suspicion by the treating physical and a sequential approach to hypokalemia, especially in young patients. Thus, a diagnostic algorithm is proposed at the end of this report. Case presentation: A 23-year-old woman with a history of hospitalization due to hypokalemia presented to the emergency service with intermittent cramping in her lower limbs, which was exacerbated by gastrointestinal symptoms. Laboratory tests reported the following findings: metabolic alkalosis, elevated levels of potassium, magnesium, chloride and sodium in urine, and reduced levels of calcium in urine. Thus, potassium supplementation and eplerenone administration were started, obtaining the complete resolution of symptoms. At her last follow-up appointment, the patient was asymptomatic, and her serum electrolyte levels were normal. In addition, during her hospital stay and due to the high suspicion of Gitelman syndrome, a genetic study was performed, which reported a mutation of the SCL12A3 gene, confirming the diagnosis. Conclusion: The sequential approach to a patient with recurrent hypokalemia is very important to reach an accurate diagnosis among a wide range of differential diagnoses.

Resumen Introducción. El síndrome de Gitelman es un trastorno tubular renal primario hereditario poco frecuente, con una prevalencia aproximada de 1 a 10 casos por cada 40 000 personas; su sintomatologia es inespecífica, por lo que su diagnóstico depende de la alta sospecha clínica por parte del médico tratante y de un abordaje secuencial de la hipopotasemia, sobre todo en pacientes jóvenes, para lo cual se propone un algoritmo diagnóstico al final de este reporte. Presentación de caso. Mujer de 23 años con antecedente de hospitalización por hipopotasemia, quien consultó por calambres musculares intermitentes en miembros inferiores, los cuales se agudizaron debido a síntomas gastrointestinales. En los exámenes de laboratorio se reportaron los siguientes hallazgos: alcalosis metabólica, niveles elevados de potasio, magnesio, cloro y sodio en orina, y niveles reducidos de calcio en orina, por lo que se inició suplementación de potasio y manejo con eplerenona, obteniéndose resolución completa de los síntomas. En su último control, la paciente se encontraba asintomática y sus niveles séricos de electrolitos eran normales. Además, durante la hospitalización, y debido a la alta sospecha de síndrome de Gitelman, se solicitó estudio genético que reportó mutación del gen SCL12A3, confirmándose el diagnóstico. Conclusión. El abordaje secuencial de un paciente con hipopotasemia recurrente es de gran importancia para realizar un diagnóstico certero ante una amplia gama de diagnósticos diferenciales.

Analysis of solute carrier organic anion transporter family member 1b1 and apolipoprotein E genes in a population from southern Yunnan / 中国基层医药

Objective:To analyze the distribution of solute carrier organic anion transporter family member 1b1 ( SLCO1B1) and apolipoprotein E ( ApoE) genes in a population from southern Yunnan. Methods:The data of 104 patients who received treatment in Southern Central Hospital of Yunnan Province (The First People's Hospital of Honghe State) between May 2019 and June 2020 were collected. The distribution of SLCO1B1 and ApoE genes and their relationship with nationality, sex, and age were analyzed and compared between different regions. Results:The percentage of patients carrying *1a/*1a, *1a/*1b, *1b/*1b, *1a/*15, *1b/*15, five phenotypes of SLCO1B1 gene, in the population from southern Yunnan was 4.81%, 32.69%, 42.31%, 12.50% and 7.69% respectively. Phenotypes *1a/*5, *5/*5, *5/*15 and *15/*15 were not detected. Normal metabolic phenotype of SLCO1B1 accounted for 79.81%, and intermediate metabolic phenotype of SLCO1B1 accounted for 20.19%. Weak metabolic phenotype was not detected. The percentage of patients carrying E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, five phenotypes of ApoE gene in the population from southern Yunnan was 0.96%, 16.35%, 70.19%, 11.54% and 0.96% respectively. E2/E4 phenotype was not detected. The percentage of patients with ApoE protective phenotype, ApoE normal phenotype, and ApoE risk phenotype was 17.31%, 70.19% and 12.50% respectively. The observed polymorphism mutation frequency of SLCO1B1 and ApoE genes was consistent with the Hardy-Weinberg equilibrium ( P > 0.05), suggesting constancy and a population representation. The Fisher test showed that SLCO1B1 gene distribution differed significantly between ethnic minorities and Han nationality in southern Yunnan ( P = 0.013). There was no significant difference in SLCO1B1 gene distribution between different sexes and between different ages (all P > 0.05). There was no significant difference in ApoE gene distribution between ethnic minorities and Han nationality, between different sexes, and between different ages in the population from southern Yunnan (all P > 0.05). Conclusion:SLCO1B1 gene distribution is related to nationality in the population from southern Yunnan, but it is unrelated to sex and age. ApoE gene distribution is unrelated to nationality, sex and age.

Effects of solute carrier family 39A14 on proliferation, migration and invasion of diffuse large B-cell lymphoma OCI-LY3 cells / 肿瘤研究与临床

Objective:To investigate the effects of solute carrier family 39 (SLC39) A14 on proliferation, migration and invasion of diffuse large B-cell lymphoma (DLBCL) OCI-LY3 cells.Methods:The human DLBCL cell line OCI-LY3 was divided into Vector group (transfected with empty control plasmid) and SLC39A14 group (transfected with SLC39A14 plasmid). The proliferation of OCI-LY3 cells in the two groups was detected by CCK-8 method, the migration and invasion of cells were detected by Transwell method, and the expression level of SLC39A14 protein and the expressions of PI3K-AKT-mTOR signaling pathway-related proteins in OCI-LY3 cells were detected by Western blotting.Results:Compared with the Vector group, the cell proliferation ability in the SLC39A14 group was increased from day 3 to day 5 (all P < 0.05).The results of Transwell cell migration assay showed that the number of migrating cells after 36 h in the Vector group was (64±4) cells, and that in the SLC39A14 group was (236±25) cells. The cell migration ability in the SLC39A14 group was increased, and the difference was statistically significant ( t = 15.02, P < 0.05). The results of Transwell cell invasion assay showed that the number of invasive cells in the Vector group was (32±2) cells, and that in the SLC39A14 group was (127±17) cells. The cell invasion ability in the SLC39A14 group was increased, and the difference was statistically significant ( t = 8.33, P < 0.05).The results of Western blotting showed that the expression levels of pmTOR, pAKT and pPI3K proteins in the SLC39A14 group were all increased. Conclusions:SLC39A14 may be involved in the occurrence and development of DLBCL through PI3K-AKT-mTOR signaling pathway.

Expression of peptide/histidine transporter solute carrier family 15 member 4 in peripheral blood mononuclear cells and its clinical significance in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To investigate the expression and clinical significance of peptide/histidine transporter solute carrier family 15 member 4 (SLC15A4) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).Methods:Fifty-five patients with SLE were divided into active SLE group and stable SLE group according to SLE disease activity index (SLEDAI) score, and 13 healthy volunteers were used as controls. The expression of SLC15A4 in PBMCs were detected by Western blot method. Moreover, the correlation between the expression of SLC15A4 and clinical and laboratory parameters of SLE patients were analyzed. The expression of SLC15a4 in the three groups was compared based on one-way analysis of variance (ANOVA), and the correlation between SLC15A4 expression level and clinical indicators was analyzed by Pearson correlation.Results:The expression levels of SLC15A4 in active SLE group, stable SLE group and healthy control group were (0.96±0.19), (0.88±0.14), (0.78±0.24), respectively. The expression level of SLC15A4 in SLE with active disease was higher than that in healthy controls ( F=4.47, P=0.015). In addition, the expression of SLC15A4 in PBMCs of SLE patients was positively correlated with the quantity of anti-double stranded DNA (anti-dsDNA) antibody, erythrocyte sedimentation rate (ESR) and systemic lupus erythematosus disease activity index (SLEDAI) ( r=0.29, P=0.031; r=0.36, P=0.007; r=0.32, P=0.017, respectively). However, the expression of SLC15A4 in PBMCs had no significant correlation with 24-h urinary protein ( r=0.45, P=0.127) and C3 ( r=0.20, P=0.133). Conclusion:SLC15A4 is involved in the pathogenesis of SLE and its expression in PBMCs of SLE patients can be used as an index to evaluate disease activity.

Regulatory role of Slc1a2 on the maturation and function of dendritic cells / 国际生物医学工程杂志

Objective:To investigate the regulatory effects of nuclear factor-κB (NF-κB) on dendritic cell (DC) maturation and function through solute carrier family 1 member 2 (Slc1a2).Methods:Mouse bone marrow-derived DCs were transfected with Slc1a2-specific siRNA and an overexpression Slc1a2 eukaryotic expression vector. The real-time fluorescence quantitation (RT-PCR) and Western Blot methods were used to detect knockdown and overexpression efficiency. The expression of surface molecules (CD40, CD80) and major histocompatibility complex Ⅱ (MHCⅡ) of DCs was detected by flow cytometry. ELISA was used to detect the secretion of the cytokines interleukin (IL)-12, IL-6, and transforming growth factor-β (TGF-β). The effects of knockdown of Slc1a2 on DC maturation and function and the effects of overexpression of Slc1a2 on DC maturation and function were reflected by the above assay results. A mixed lymphocyte culture assay was used to investigate the effect of Slc1a2 on T cell proliferation, and an ELISA was used to detect the lavel of IL-17A. Changes in the relative fluorescence intensity of FITC in DCs were analyzed by flow cytometry to investigate the ability of Slc1a2 overexpression on antigen phagocytosis. Finally, DCs were pretreated with an NF-κB inhibitor, toluoylphenylalanine chloromethyl ketone (TPCK), and the effect of TPCK on the expression of Slc1a2 in DCs and DC maturation was examined.Results:Slc1a2 expression was found to be high in DC treated with lipopolysaccharides (LPS) ( P<0.001). The knockdown of Slc1a2 decreased DC maturation and ability to stimulate the proliferation of CD4 + T cells ( P<0.001) and inhibited IL-17 secretion ( P<0.01). Overexpression of Slc1a2 promoted DC maturation and ability to stimulate the proliferation of CD4 + T cells(all P<0.01) Pretreatment of DC with the NF-κB inhibitor TPCK inhibited the expression of Slc1a2 at mRNA and protein levels induced by LPS. Conclusions:NF-κB regulates Slc1a2 expression, which affects the maturation and function of DC.

Comparative proteomic profiling of hippocampi in mice treated with Jingui Shenqi Pills and Liuwei Dihuang Pills / 中国中药杂志

The effects of Jingui Shenqi Pills(Jingui) and Liuwei Dihuang Pills(Liuwei) which respectively tonify kidney Yang and kidney Yin on brain function have attracted great attention, while the differences of protein expression regulated by Jingui and Liuwei remain to be studied. This study explored the difference of protein expression profiles in the hippocampi of mice orally administrated with the two drugs for 7 days. The protein expression was quantified using LC-MS/MS. The results showed that among the 5 860 proteins tested, 151, 282 and 75 proteins responded to Jingui alone, Liuwei alone, and both drugs, respectively. The ratio of up-regulated proteins to down-regulated proteins was 1.627 in Jingui group while only 0.56 in Liuwei group. The proteins up-regulated by Jingui were mainly involved in membrane transport, synaptic vesicle cycle, serotonergic synapse, dopaminergic synapse and so on, suggesting that Jingui may play a role in promoting the transport of neurotransmitter in the nervous system. The proteins down-regulated by Liuwei were mainly involved in membrane transport, synapse, ion transport(potassium and sodium transport), neurotransmitter transport, innate and acquired immune responses, complement activation, inflammatory response, etc. In particular, Liuwei showed obvious down-regulation effect on the members of solute carrier(SLC) superfamily, which suggested that Liuwei had potential inhibitory effect on membrane excitation and transport. Finally, consistent results were obtained in the normal mouse and the mouse model with corticosterone-induced depressive-like behavior. This study provides an experimental basis for understanding the effect of Jingui and Liuwei on brain function from protein network.

Optimal indicator for changing the filter during the continuous renal replacement therapy in intensive care unit patients with acute kidney injury: A crossover randomized trial / 世界急诊医学杂志（英文）

@#BACKGROUND: The study aims to investigate an optimal indicator for changing the filter during the continuous renal replacement therapy (CRRT) in intensive care unit (ICU) patients with acute kidney injury (AKI). METHODS: Patients with AKI requiring CRRT in an ICU were randomly divided into two groups for crossover trial, i.e., groups A and B. Patients in the group A were firstly treated with continuous veno-venous hemofiltration (CVVH), followed by continuous veno-venous hemodiafiltration (CVVHDF). Patients in the group B were firstly treated with CVVHDF followed by CVVH. Delivered doses of solutes with different molecular weights at the indicated time points between groups were compared. A correlation analysis between the delivered dose and pre-filter pressure (PPRE) and transmembrane pressure (PTM) was performed. Receiver operating characteristic (ROC) curves were constructed to evaluate the accuracy of PTM as an indicator for filter replacement. RESULTS: A total of 50 cases were analyzed, 27 in the group A and 23 in the group B. Delivered doses of different molecular-weight solutes significantly decreased before changing the filter in both modalities, compared with those at the initiation of treatment (all P<0.05). In the late stage of CRRT, the possible rebound of serum medium-molecular-weight solute concentration was observed. PTM was negatively correlated with the delivered dose of medium-molecular-weight solute in both modalities. The threshold for predicting the rebound of serum concentration of medium-molecular-weight solute by PTM was 146.5 mmHg (1 mmHg=0.133 kPa). CONCLUSIONS: The filter can be used as long as possible within the manufacturer's safe use time limits to remove small-molecular-weight solutes. PTM of 146.5 mmHg may be an optimal indicator for changing the filter in CRRT therapies to remove medium-molecular-weight solutes.

Research progress of solute carriers in mediating nanomedicine across the blood-brain barrier / 中国药科大学学报

@#As a structural barrier between the brain and the systemic circulation, the blood-brain barrier prevents macromolecules and most small-molecule drugs from entering the brain, which make it difficuct to treat central diseases.Various solute carriers such as glucose transporters and amino acid transporters which can transport various nutrients into the brain, are highly expressed on the blood-brain barrier.The ligand corresponding to the transporter is modified on the nano-drug carrier, and the drug is carried across the blood-brain barrier through transporter-mediated transport, which can achieve high-efficiency delivery of drugs to the brain and improve the diagnostic sensitivity and therapeutic effect of central diseases.In this paper, we review different types of solute carriers to mediate nanoformulations such as liposomes, metal nanoparticles, polymer micelles and dendrimers across the blood-brain barrier for the treatment of brain diseases and discuss the opportunities and challenges of this strategy in future applications.

Recent advances in drug development targeting bile acids transporters and related disease / 药学学报

Bile acids (BAs) are a major component of bile salt, which plays a vital role in the metabolism of lipids in humans. Ninety-five percent of bile acids are recycled by the enterohepatic circulation (EHC), and therefore EHC is essential for bile acid homeostasis. There are four transporters that mediate the transmembrane transport of bile acids, each of which plays an important role in the enterohepatic circulation. Gene defects in bile acid transporters can lead to disorders of the enterohepatic circulation, ultimately leading to clinical phenotypes such as metabolic diseases and even death. Bile transporter expression is altered in patients with various metabolic disease states, suggesting that disruption of bile acid transporters may be a pivotal pathological mechanism for the development of metabolism diseases. Thus, many drugs targeting bile acid transporters are being developed. We provide a concise overview of the progress of bile acid transporters research, discuss the relationship between different bile acid transporters and disease development, and summarize the current progress in drug development targeting bile acid transporters.

Influência do substrato de pó de coco na lixiviação de água residuária / Influence of coconut powder substrate on leaching of wastewater

RESUMO Nas últimas décadas, têm-se observado o crescimento da demanda de água e o agravamento dos cenários de escassez hídrica, bem como a ampliação de alternativas de reuso de água de efluentes de qualidade inferior, em particular de esgotos domésticos tratados. Objetivou-se, com este trabalho, avaliar a influência do substrato de pó de coco no controle de transporte de solutos em solos irrigados com esgoto tratado doméstico. A água residuária doméstica tratada provém da Unidade Experimental de Tratamento e Reúso Hidroagrícola, no distrito de Mutuca-PE. O delineamento experimental foi em esquema fatorial (2 × 3), cujos fatores avaliados compreenderam dois tipos de solos típicos da região (Neossolo Litólico e Argissolo Amarelo) e três tratamentos (sem pó de coco, 1 cm de pó de coco e 2 cm de pó de coco), com cinco repetições. Os parâmetros de transporte dos íons sódio e potássio foram obtidos por ajuste numérico, utilizando-se o modelo STANMOD. Constatou-se a existência de interação com soluto, sódio e potássio, em solo arenoso. O modelo STANMOD apresentou ótimo desempenho na simulação do transporte de solutos no solo. A cobertura de pó de coco mostrou-se eficiente na diminuição da lixiviação de íons em ambos os solos estudados.

ABSTRACT In the last decades, there has been an increase in the demand for water and the aggravation of water scarcity scenarios, as well as the expansion of water reuse alternatives for lower quality effluents, in particular treated domestic sewage. The objective of this study was to evaluate the influence of coconut powder substrate on the control of solute transport in irrigated soils with treated sewage reuse. The treated domestic wastewater comes from the Experimental Unit for Treatment and Agricultural Reuse in the district of Mutuca, Pernambuco. The experimental design was in a factorial scheme (2 × 3), whose evaluated factors comprised two types of soils typical of the region (Leptosols and Yellow Argisol) and three treatments (no coconut powder, 1 cm coconut powder, and 2 cm coconut powder) with five replicates. The transport parameters of the sodium and potassium ions were obtained by numerical adjustment using the STANMOD model. It was found the existence of interaction with solute, sodium, and potassium in sandy soil. The STANMOD model presented excellent performance in the simulation of solute transport in the soil. Soil coverage with coconut powder was shown to be efficient in reducing leaching of ions in both studied soils.

Research progress on the gene polymorphism of tacrolimus transporter in organ transplantation / 器官移植

Tacrolimus (Tac) is a commonly used immunosuppressant after organ transplantation, which has high immunosuppressive efficacy. However, the pharmacokinetics of Tac significantly differ among individuals, and gene polymorphism is the main influencing factor. In recent years, the gene polymorphism of drug transporter has become a novel research hotspot. Nevertheless, the effect of the gene polymorphism of transporter on Tac pharmacokinetics remains controversial. Consequently, the correlation between the gene polymorphism of transporter and Tac blood concentration plays a significant role in guiding Tac-based individualized immunosuppressive therapy. In this article, the research progresses on the gene polymorphism of adenosine triphosphate-binding cassette (ABC) transporter and solute carrier (SLC) transporter in organ transplantation was reviewed. The correlation between the gene polymorphism of transporter and Tac blood concentration was summarized, aiming to provide reference for Tac-based individualized therapy.

The association between SLC11A1 gene polymorphism and treatment failure of pulmonary tuberculosis / 预防医学

Objective@#To analyze the association between recombinant solute carrier family 11, member 1 ( SLC11A1 ) rs17235409 polymorphism and treatment failure of pulmonary tuberculosis, so as to provide the basis for the prevention and treatment of pulmonary tuberculosis.@*Methods@#The patients with pulmonary tuberculosis registered for treatment at the Urumqi Center for Disease Control and Prevention in 2019 was recruited and collected demographic, clinical and treatment information from National Infectious Diseases Reporting System. The polymorphism of SLC11A1 rs17235409 was detected by multiple ligase chain reaction and Hardy-Weinberg balance test was performed. The multivariate logistic regression analysis was conducted for the association between rs17235409 and the treatment outcome of tuberculosis.@*Results@#A total of 731 cases of pulmonary tuberculosis patients were enrolled, and 37 cases failed, with a failure rate of 5.06%. The failure rate of the patients with G/A was 8.55%, with G/G was 4.23%. The results of multivariate logistic regression analysis showed that the patients with G/A were more likely to fail in the treatment than those with G/G ( OR=2.213, 95%CI: 1.041-4.702 ). The males with G/A were more likely to fail in the treatment than those with G/G ( OR=2.547, 95%CI: 1.021-6.356 ). @*Conclusion@#The rs17235409 polymorphism of SLC11A1 is associated with the failure of tuberculosis treatment, and the patients with G/A are more likely to fail.

Betaine supplementation improved L-threonine fermentation of Escherichia coli THRD by upregulating zwf (glucose-6-phosphate dehydrogenase) expression

BACKGROUND: The supplementation of betaine, an osmoprotective compatible solute, in the cultivation media has been widely used to protect bacterial cells. To explore the effects of betaine addition on industrial fermentation, Escherichia coli THRD, an L-threonine producer, was used to examine the production of L-threonine with betaine supplementation and the underlying mechanism through which betaine functions was investigated. RESULTS: Betaine supplementation in the medium of E. coli THRD significantly improved L-threonine fermentation parameters. The transcription of zwf and corresponding enzyme activity of glucose-6-phosphate dehydrogenase were significantly promoted by betaine addition, which contributed to an enhanced expression of zwf that provided more nicotinamide adenine dinucleotide phosphate (NADPH) for L-threonine synthesis. In addition, as a result of the betaine addition, the betaine-stimulated expression of enhanced green fluorescent protein (eGFP) under the zwf promoter within a plasmid-based cassette proved to be a transcription-level response of zwf. Finally, the promoter of the phosphoenolpyruvate carboxylase gene ppc in THRD was replaced with that of zwf, while L-threonine fermentation of the new strain was promoted by betaine addition. Conclusions: We reveal a novel mode of betaine that facilitates the microbial production of useful compounds. Betaine supplementation upregulates the expression of zwf and increases the NADPH synthesis, which may be beneficial for the cell growth and thereby promote the production of L-threonine. This finding might be useful for the production of NADPH-dependent amino acids and derivatives in E. coli THRD or other E. coli strains.

A case-control study of the association between the polymorphisms of APOE and SLCO1B1 and the severity of coronary artery disease / 中华检验医学杂志

Objective The single nucleotide polymorphisms (SNPs) of APOE and SLCO1B1 were examined to explore their association with the risk and severity of coronary heart disease(CAD). Methods A total of 1267 cases of consecutive coronary heart disease (CAD)-suspected inpatients visiting department of Cardiology in Peking University Peoples' Hospital from March 2017 to november were recruited into this case-control study, and then 391 CAD cases and 223 non-CAD controls were enrolled for final analysis after screening by coronary angiography and exclusion criteria. The severity of the CAD cases were evaluated according to Gensini scores. The SNPs of APOE(388T>C, 526C>T) and SLCO1B1(388A>G, 521T>C) were detected using Real-time PCR and further verified using Sanger sequencing. Environmental risk factors were collected, and the correlations between SNPs of APOE and SLCO1B1 and the risk and severity of CAD were performed by SPSS version 16.0. Results The SNPs of all the subjects included in CAD group and non-CAD group were successfully detected, with an accordance of 100％ to Sanger sequencing. The distribution of APOE and SLCO1B1 gene were subjected to Hardy-Weinberg. The distributions of APOE gene ε3/ε3 genotypes and ε3 allele were most commonly found in both CAD group and non-CAD group (ε3/ε3: 70.8％,73.1％;ε3: 83.5％,85.2％;respectively). APOE genotypes and alleles were comparable between the CAD cases and non-CAD controls (P>0.05). The frequencies of APOE gene ε4+genotype were more likely to be found in the subgroup of CAD with Gensini score≥72 (P<0.05). The distributions of SLCO1B1 gene *1b/*1b genotypes and *1b allele were most commonly found in both CAD group and non-CAD group (*1b/*1b: 37.3％, 36.8％; *1b: 60.1％, 61.7％; respectively). There was no significant difference in genotype and allele frequencies of SLCO1B1 between the two groups and among subgroups with different severity of CAD (P>0.05). Conclusion This study observed no association between SNPs of APOE, SLCO1B1 and the risk of CAD in this population. However, APOE gene ε4 +genotype may increase the severity of CAD.

Regulation of mitochondrial carrier SLC25A13 on breast cancer cell cycle in vitro / 上海交通大学学报（医学版）

Objective·To investigate the role of mitochondrial solute carrier family 25 member 13 (SLC25A13) on breast cancer development.Methods·SLC25A13 mRNA and protein expressions in invasive breast cancer tissues and normal breast tissues were from The Cancer Genome Atlas (TCGA) breast cancer dataset. Survival analysis was conducted online by Kaplan-Meier software. MCF-7 cell line was used for in vitro cell assay.Knockdown of SLC25A13 and sirtuin 2 (SIRT2) were conducted by siRNA transfection. Cell viability was measured with trypan blue exclusion. Cell cycle arrest was determined by flow cytometry. The mRNA expression of SLC25A13 and P27 were detected by quantitative PCR. The protein level of SLC25A13, P27 and SIRT2 were detected by Western blotting. Protein half-life of P27 was assessed by Western blotting after ycloheximide treatment. Results·SLC25A13 was up-regulated in invasive breast cancer tissues. High expression of SLC25A13 correlated with poor overall survival and breast cancer recurrence. SLC25A13 knockdown inhibited MCF-7 cell cycle progression. P27 and SIRT2 both accumulated after SLC25A13 knockdown. P27 accumulation resulted from prolonged protein half-life. Knockdown of SIRT2 restored cell cycle arrest as well as P27 accumulation caused by SLC25A13 silencing. Conclusion·High expression of SLC25A13 may promote cell cycle progression via SIRT2 in breast cancer development.

Comparison of three PET methods to assess peritoneal membrane transport

The peritoneal equilibration test (PET) is the most widespread method for assessing water and solute transport across the peritoneal membrane. This study compared three methods: traditional PET (t-PET), mini-PET, and modified PET (mod-PET). Non-diabetic adults (n=21) who had been on peritoneal dialysis (PD) for at least three months underwent t-PET (glucose 2.5%-4 h), mini-PET (glucose 3.86%-1 h), and mod-PET (glucose 3.86%-4 h) to determine dialysate-to-plasma concentration ratio (D/P) for creatinine and dialysate-to-baseline dialysate concentration ratio (D/D0) for glucose. Agreement between methods regarding D/P creatinine and D/D0 glucose was assessed using analysis of variance (ANOVA), Pearson's correlation coefficient, and Bland-Altman analysis. D/P creatinine differed between t-PET and mini-PET (P<0.001) and between mod-PET and mini-PET (P<0.01) but not between t-PET and mod-PET (P=0.746). The correlation of D/P creatinine with t-PET vs mod-PET was significant (r=0.387, P=0.009) but not that of t-PET vs mini-PET (r=0.088, P=0.241). Estimated bias was −0.029 (P=0.201) between t-PET and mod-PET, and 0.206 (P<0.001) between t-PET and mini-PET. D/D0 glucose differed between t-PET and mod-PET (P=0.003) and between mod-PET and mini-PET (P=0.002) but not between t-PET and mini-PET (P=0.885). The correlations of D/D0 glucose in t-PET vs mod-PET (r=−0.017, P=0.421) or t-PET vs mini-PET (r=0.152, P=0.609) were not significant. Estimated bias was 0.122 (P=0.026) between t-PET and mod-PET, and 0.122 (P=0.026) between t-PET and mini-PET. The significant correlation of D/P creatinine between t-PET and mod-PET suggested that the latter is a good alternative to t-PET. There was no such correlation between t-PET and mini-PET.

Regulation of mitochondrial carrier slc25a13 on breast cancer cell cycle in vitro / 上海交通大学学报（医学版）

Objective:To investigate the role of mitochondrial solute carrier family 25 member 13 (SLC25A13) on breast cancer development. Methods:SLC25A13 mRNA and protein expressions in invasive breast cancer tissues and normal breast tissues were from The Cancer Genome Atlas (TCGA) breast cancer dataset. Survival analysis was conducted online by Kaplan-Meier software. MCF-7 cell line was used for in vitro cell assay. Knockdown of SLC25A13 and sirtuin 2 (SIRT2) were conducted by siRNA transfection. Cell viability was measured with trypan blue exclusion. Cell cycle arrest was determined by flow cytometry. The mRNA expression of SLC25A13 and P27 were detected by quantitative PCR. The protein level of SLC25A13, P27 and SIRT2 were detected by Western blotting. Protein half-life of P27 was assessed by Western blotting after cycloheximide treatment. Results:SLC25A13 was up-regulated in invasive breast cancer tissues. High expression of SLC25A13 correlated with poor overall survival and breast cancer recurrence. SLC25A13 knockdown inhibited MCF-7 cell cycle progression. P27 and SIRT2 both accumulated after SLC25A13 knockdown. P27 accumulation resulted from prolonged protein half-life. Knockdown of SIRT2 restored cell cycle arrest as well as P27 accumulation caused by SLC25A13 silencing. Conclusion:High expression of SLC25A13 may promote cell cycle progression via SIRT2 in breast cancer development.

Essential characteristics and functions of SLC25 family in tumor / 国际肿瘤学杂志

The solute carrier protein 25 family (SLC25)is one of superfamily in solute carrier protein family. The members of SLC25 family function by transporting various solutes across the mitochondrial mem-brane. Their substrates vary in property,molecular size and mode of transport,and they closely involve in nu-merous physiological functions. More and more researches indicate that some members of SLC25 family are ab-normally expressed in tumors,and some of them play important roles in the occurrence and development of tumors. For example,some members participate in tumorigenesis by regulating cell metabolism,death and pro-liferation.