Tratamiento con TRIAC en pacientes pediátricos con deficiencia de MCT8 / Treatment with TRIAC in pediatric patients with MCT8

Los transportadores de monocarboxilatos (MCT) permiten el ingreso celular de hormonas tiroideas, especialmente en el sistema nervioso central (SNC), donde son indispensables para el neurodesarrollo. La deficiencia de MCT8 produce la combinación de hipotiroidismo en SNC e hipertiroidismo periférico, caracterizada por T3 elevada. El único tratamiento actualmente disponible es el ácido 3,3',5-triyodotiroacético (TRIAC), un análogo de hormonas tiroideas que tiene como objetivo mejorar la tirotoxicosis periférica y prevenir la progresión del deterioro neurológico. En el presente artículo, se evalúan las características clínicas, imagenológicas, bioquímicas y genéticas de 4 pacientes con deficiencia de MCT8 tratados con TRIAC hasta la fecha, las dosis utilizadas y la respuesta al tratamiento.

Monocarboxylate transporters (MCTs) allow the cellular entry of thyroid hormones, especially into the central nervous system (CNS), where they are crucial for neurodevelopment. MCT8 deficiency results in the combination of hypothyroidism in the CNS and peripheral hyperthyroidism, characterized by elevated T3 levels. The only treatment currently available is 3,3',5-triiodothyroacetic acid (TRIAC), a thyroid hormone analogue aimed at improving peripheral thyrotoxicosis and preventing the progression of neurological impairment. Here we assess the clinical, imaging, biochemical, and genetic characteristics of 4 patients with MCT8 deficiency who have received TRIAC to date, the doses used, and the response to treatment.

Association between the organic cation transporter 3 methylation and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and has a high death rate in the world. This research while examining the expression of OCT3 at the mRNA level has also studied gene methylation profile in patients with HCC in comparison with people without HCC. The volunteers were: patients with HCC (n=81) and a healthy control group (n=90). The expression of OCT3was studied using the qRT-PCR method. The methylation profile was evaluated by genomic DNA using methylation specific PCR (MSP) method. The expression level of OCT3 marker mRNA in patients has decreased significantly compared to healthy individuals (0.58 ± 0.311 vs 1.20 ± 0.355, P <0.001). No significant statistical relationship was found between demographic data and OCT3 expression in participants (P >0.05). The amount of methylation (UM + MM) in cancer patients has raised vs controls (P <0.001) and has increased the risk of cancer (OR=0.379, 95% CI=1.171-2.839, P <0.001, and OR=2.727, 95% CI=1.251-5.945, P <0.001, respectively).Changes in OCT3 levels appear to be associated with HCC. Also, changing the methylation pattern of this gene can reveal HCC pathology.

Application of sodium-glucose cotransporter 2 inhibitors in acute myocardial infarction / 中国临床药理学与治疗学

SGLT2 inhibitors currently have clear benefits in the treatment of heart failure whether combined with diabetes or not. Ventricular remodeling after myocardial infarction leads to the occurrence and development of heart failure, and eventually leads to death. There are relatively few studies on SGLT2 inhibitors in patients with myocardial infarction. The purpose of this article is to review the research progress of SGLT2 inhibitors application before and after myocardial infarction.

Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin

Body is equipped with organic cation transporters (OCTs). These OCTs mediate drug transport and are also involved in some disease process. We aimed to investigate whether liver failure alters intestinal, hepatic and renal Oct expressions using bile duct ligation (BDL) rats. Pharmacokinetic analysis demonstrates that BDL decreases plasma metformin exposure, associated with decreased intestinal absorption and increased urinary excretion. Western blot shows that BDL significantly downregulates intestinal Oct2 and hepatic Oct1 but upregulates renal and hepatic Oct2. In vitro cell experiments show that chenodeoxycholic acid (CDCA), bilirubin and farnesoid X receptor (FXR) agonist GW4064 increase OCT2/Oct2 but decrease OCT1/Oct1, which are remarkably attenuated by glycine-β-muricholic acid and silencing FXR. Significantly lowered intestinal CDCA and increased plasma bilirubin levels contribute to different Octs regulation by BDL, which are confirmed using CDCA-treated and bilirubin-treated rats. A disease-based physiologically based pharmacokinetic model characterizing intestinal, hepatic and renal Octs was successfully developed to predict metformin pharmacokinetics in rats. In conclusion, BDL remarkably downregulates expressions of intestinal Oct2 and hepatic Oct1 protein while upregulates expressions of renal and hepatic Oct2 protein in rats, finally, decreasing plasma exposure and impairing hypoglycemic effects of metformin. BDL differently regulates Oct expressions via Fxr activation by CDCA and bilirubin.

Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

Effects of hypoxia on the expression and function of P-gp in Caco-2 cells / 中南大学学报(医学版)

OBJECTIVES@#Hypoxia can alter the oral bioavailability of drugs, including various substrates (drugs) of P-glycoprotein (P-gp), suggesting that hypoxia may affect the function of P-gp in intestinal epithelial cells. Currently, Caco-2 monolayer model is the classic model for studying the function of intestinal epithelial P-gp. This study combines the Caco-2 monolayer model with hypoxia to investigate the effects of hypoxia on the expression and function of P-gp in Caco-2 cells, which helps to elucidate the mechanism of changes in drug transport on intestinal epithelial cells in high-altitude hypoxia environment.@*METHODS@#Normally cultured Caco-2 cells were cultured in 1% oxygen concentration for 24, 48, and 72 h, respectively. After the extraction of the membrane proteins, the levels of P-gp were measured by Western blotting. The hypoxia time, with the most significant change of P-gp expression, was selected as the subsequent study condition. After culturing Caco-2 cells in transwell cells for 21 days and establishing a Caco-2 monolayer model, they were divided into a normoxic control group and a hypoxic group. The normoxic control group was continuously cultured in normal condition for 72 h, while the hypoxic group was incubated for 72 h in 1% oxygen concentration. The integrity and polarability of Caco-2 cells monolayer were evaluated by transepithelial electrical resistance (TEER), apparent permeability (Papp) of lucifer yellow, the activity of alkaline phosphatase (AKP), and microvilli morphology and tight junction structure under transmission electron microscope. Then, the Papp of rhodamine 123 (Rh123), a kind of P-gp specific substrate, was detected and the efflux rate was calculated. The Caco-2 cell monolayer, culturing at plastic flasks, was incubated for 72 h in 1% oxygen concentration, the expression level of P-gp was detected.@*RESULTS@#P-gp was decreased in Caco-2 cells with 1% oxygen concentration, especially the duration of 72 h (P<0.01). In hypoxic group, the TEER of monolayer was more than 400 Ω·cm2, the Papp of lucifer yellow was less than 5×10-7 cm/s, and the ratio of AKP activity between apical side and basal side was greater than 3. The establishment of Caco-2 monolayer model was successful, and hypoxia treatment did not affect the integrity and polarization state of the model. Compared with the normoxic control group, the efflux rate of Rh123 was significantly reduced in Caco-2 cell monolayer of the hypoxic group (P<0.01). Hypoxia reduced the expression of P-gp in Caco-2 cell monolayer (P<0.01).@*CONCLUSIONS@#Hypoxia inhibits P-gp function in Caco-2 cells, which may be related to the decreased P-gp level.

Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study

Abstract Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. Objectives This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. Methodology OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. Results CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. Conclusion OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.

Prenatal diagnosis of a fetus with harlequin ichthyosis caused by novel splice-site mutation in ABCA12 gene / 中华围产医学杂志

This article reported a rare case of harlequin ichthyosis which was indicated with multiple structural abnormalities by prenatal ultrasound and diagnosed by trio-based whole-exome sequencing (Trio-WES). Prenatal diagnosis was performed because the ultrasound at 24 +4 gestational weeks revealed the fetus presenting with eclabium, flattened nose, short mandible, small auricle and abnormal posture of the toes. Copy number variation sequencing (CNV-seq) showed no chromosome aneuploidy or pathogenic copy number variants over 100 kb in the fetal or parental samples. Trio-WES showed that the fetus carried two heterozygous mutations, c.2593-1G>A and c.7444C>T in ABCA12. Sanger sequencing confirmed that c.2593-1G>A, a previously unreported variant, was paternally inherited and c.7444C>T was maternally inherited. Both parents had normal phenotype. The fetus was finally diagnosed with harlequin ichthyosis. After prenatal counseling, the parents made an informed choice to terminate the pregnancy at 28 +4 gestational weeks. The stillborn fetus showed multiple malformations The variants in this case expand the spectrum of variants in ABCA12 gene.

Correlation and protective effect of diabetes mellitus in aortic aneurysm disease / 国际外科学杂志

Diabetes mellitus is a metabolic disease characterized by hyperglycemia. It is found that the incidence and mortality of abdominal aortic aneurysm (AAA) in diabetes mellitus patients are lower than that in non-diabetes mellitus patients. This review will present the protective role of diabetes mellitus and its treatment on the aortic disease process, aiming to provide more support for the clinical treatment of AAA.

Clinical characteristics and genetic analysis of a pedigree with Stargardt disease caused by a novel mutation in ABCA4 gene / 中华检验医学杂志

Objective:To explore the clinical characteristics and genetics of a pedigree with Stargardt disease, and investigate the pathogenicity of ABCA4 (ATP binding cassette subfamily A member 4) gene mutations in Stargardt disease.Methods:The proband was admitted to the Second People′s Hospital of Jinan in May 2021 due to diminution of vision. The proband was diagnosed with Stargardt disease according to the clinical diagnostic criteria of Stargardt disease. Detailed ophthalmological examinations was also performed on family members of the proband. Genomic DNA were extracted from the proband and the family members, and the whole exon sequencing was performed to find pathogenic gene mutations. The hazard of mutations was analyzed by polyphen-2, SIFT and MutationTaster websites. Sanger sequencing was used to verify the mutations. Conserved analysis of homologous species and 3-dimensional (3D) molecular model of the protein were used to analyze the pathogenicity.Results:Ophthalmological examinations showed reduced binocular vision, macular atrophy and "bull′s eye sign" in the proband and there was no abnormal signs and symptoms among the family members. Through whole exon sequencing analysis and Sanger sequencing verification, the compound heterozygous mutations (c.215G>A and c.6563T>C) of ABCA4 gene were co-segregated with this disease in this family. SIFT, Polyphen-2 and MutationTaster predicted that these two mutations were pathogenic. Conservative analysis and 3D molecular model of protein showed that mutations could cause changes in protein structure and affect protein function.Conclusion:The compound heterozygous mutations (C.215G>A and C.6563T>C) of ABCA4 gene are the pathogenic mutations of Stargardt disease in this pedigree.

Effect of Bixie deacidification fang on hyperuricemia mouse model and its effect on the expression of renal urate transporter / 药学实践杂志

Objective To investigate the anti-hyperuricemia effects of Bixie deacidification fang on hyperuricemia mice and its mechanism of renal protein transport. Methods The effects of Bixie deacidification fang were investigated on hyperuricemia mice induced by potassium oxonate. Bixie deacidification fang was administered to hyperuricemia mice daily at doses of 220, 440 and 880 mg/kg for 10 days, and allopurinol (5mg/kg) was given as positive control. Serum and urine levels of uric acid and creatinine were determined by colorimetric method. Simultaneously, protein levels of urate transporter 1 (URAT1) and organic anion transporter 1 (OAT1) in the kidney were analyzed by Western blot. Results Compared with the model group, high-dose of Bixie deacidification fang inhibited xanthine oxidase (XOD) activities in serum (18.12±1.33 u/L) and that in liver (70.15±5.20 u/g protein) (P<0.05), decrease levels of serum uric acid (2.04 ± 0.64mg/L) (P<0.05) and serum creatinine (0.35±0.18µmol/L) and blood urea nitrogen (BUN)(8.83±0.71mmol/L) (P<0.05), ncreased levels of urine uric acid (38.34±8.23mg/L), urine creatinine (34.38±1.98mmol/L), down-regulated of URAT1 and up-regulated of OAT1 protein expressions (P<0.05) in the renal tissue of hyperuricemia mice. Conclusion Bixie deacidification fang recipe may promote the excretion of uric acid in the kidney by up-regulating the expression of OAT1 protein to promote the excretion of uric acid, and down-regulating the expression of URAT1 protein to inhibit the reabsorption of uric acid.

A review: drug-drug interactions of epithelial growth factor receptor-tyrosine kinase inhibitors / 中华肿瘤杂志

Mutations in the epithelial growth factor receptor (EGFR) is a driving factor that causes non-small cell lung carcinoma (NSCLC). The epithelial growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is a crucial discovery in the treatment of lung cancer, particularly the efficacy of EGFR-TKIs is superior to that of the standard chemotherapy for patients with EGFR mutation-positive advanced NSCLC. Patients with NSCLC use EGFR-TKIs and other medications simultaneously is commonly seen, especially among those with comorbidities, which increases the risk of drug-drug interactions (DDIs) of EGFR-TKIs. The most common mechanisms underlying the DDIs of EGFR-TKIs are modulations of cytochrome P450 (CYP) and drug transporters [including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)], as well as gastrointestinal acid-inhibitory drugs [proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RA)]. Inhibitors or inducers of CYP enzymes and drug transporters can inhibit or accelerate the metabolism of EGFR-TKIs, which increase or reduce the exposure of EGFR-TKIs, thereby affect the efficacy and safety of EGFR-TKIs. In addition, PPIs or H(2)RA can decrease the solubility, bioavailability and efficacy of EGFR-TKIs. This review summarizes the mechanisms of DDIs of gefitinib, erlotinib, icotinib, afatinib, dacomitinib and osimertinib; the management recommendations for DDIs of those EGFR-TKIs from the Chinese and global guideline, as well as from the recent pre-clinical and clinical studies, which provide the reference and evidence for managing the combination therapies of EGFR-TKIs and other medications in clinics.

Progress in Research on Glutamine Metabolism in Energy Metabolism of Gastric Cancer / 胃肠病学

Gastric cancer is one of the most common malignant tumors of digestive system. Due to lack of early diagnosis methods, the mortality rate of gastric cancer is relatively high. For meeting their own needs, the tumor cells can reprogram their metabolism, and glutamine metabolism plays an important role in tumor cell growth and proliferation. Therefore, it needs to elucidate the new potential molecular mechanisms of gastric cancer and to discover the potential biomarkers related to glutamine metabolism, so as to provide new targets and schemes for the diagnosis and treatment of gastric cancer. This article reviewed the progress in research on glutamine metabolism in energy metabolism of gastric cancer.

Correlation between organic cation transporter gene polymorphisms and the toxicities and clinical response of oxaliplatin / 中国临床药理学与治疗学

AIM: To investigate the relationship between genotypes of rs628031, rs650284, rs683369 of SLC22A1 gene and the toxicities and clinical response of oxaliplatin in patients with colorectal cancer. METHODS: A total of 72 patients diagnosed as colorectal cancer during January 2018 to June 2018 were selected and all patients received oxaliplatin treatment. Their peripheral venous blood was collected and genotyping was conducted by using SNaPshot. The toxicities including gastrointestinal toxicity, hematological toxicity and peripheral neurotoxicity were evaluated according to the Common Terminology Criteria Adverse Events (CTCAE) Version 5.0. Clinical response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1). RESULTS: The results of Chi-test showed that different genotypes of SLC22A1 SNP sites rs628031 and rs683369 may be related to the toxicities and clinical response of oxaliplatin significantly. Specifically, when compared with the patients with GG type of rs628031, the patients with the GA or AA type had a lower incidence of grade 3 nausea and vomiting (P=0.017) and may also be less responsive to efficacy (P=0.008). When compared with the patients with CC type of rs683369, the patients with the GC or GG type had a lower incidence of grade 3 nausea and vomiting (P=0.002) and may also be less responsive to efficacy (P=0.014).CONCLUSION: The polymorphisms of SLC22A1 gene are closely related to the toxicities and clinical response of oxaliplatin in patients with colorectal cancer, which may be helpful for improving clinical treatment.

Alteración en la expresión de proteínas transportadoras de colesterol y moléculas inmunomoduladoras en pacientes con VIH-1 / Altered expression of cholesterol transport proteins and immunomodulators molecules in HIV-1 infected patients

Debido a que la terapia antirretroviral no logra controlar la activación inmune asociada a la infección por VIH-1, el estudio de moléculas inmunomoduladoras puede proporcionar alternativas para su control. En este sentido, el propósito de este estudio fue evaluar la expresión transcripcional de moléculas asociadas con el metabolismo del colesterol-HDL (C-HDL) y con la respuesta inflamatoria mediada por el inflamasoma NLRP3 en pacientes infectados con VIH-1. En este estudio transversal, se incluyeron 23 pacientes VIH-1 sin tratamiento antirretroviral, con diferentes estadios de progresión, 7 de los cuales son controladores (Carga viral <2000 copias/mL) y 16 progresores (Carga viral >2000 copias/mL), además de 7 controles sanos. En células mononucleares de sangre periférica, se cuantificaron los niveles de la expresión transcripcional de ABCA-1, ABCA-3, Caspasa-5 y TXNIP mediante RT-PCR. Se evaluó la asociación de estos parámetros con variables demográficas y de laboratorio, y se encontró que los individuos VIH-1 progresores mostraron niveles significativamente menores de TXNIP y ABCA-3, sugiriendo que durante la infección por VIH-1 se produce una alteración en la expresión de estas moléculas. Dada la complejidad de las interacciones inmuno-metabólicas durante la infección por VIH-1, se necesitan estudios adicionales para establecer los mecanismos precisos involucrados en estas alteraciones

Because antiretroviral therapy fails to control the immune activation that occurs during HIV-1 infection, the study of immunomodulatory molecules may provide alternative strategies for their control. In this sense, the aim of the research was to evaluate the transcriptional expression of molecules associated with the metabolism of high-density lipoproteins and with the inflammatory response mediated by the NLRP3 inflammasome in patients infected with HIV-1. This is a cross-sectional study, which included 23 HIV-1 patients without antiretroviral treatment, with different stages of progression, 7 of which are controllers (Viral load <2000 copies/mL) and 16 progressors (Viral load >2000 copies/mL), in addition to 7 healthy controls. In peripheral blood mononuclear cells, the levels of transcriptional expression of ABCA-1, ABCA-3, Caspase-5 and TXNIP were quantified by RT-PCR. The association of these parameters with laboratory and demographic variables was evaluated and it was found that HIV-1 progressing individuals showed significantly lower levels of TXNIP and ABCA-3, suggesting that during HIV-1 infection there is an alteration in the expression of these molecules. Given the complexity of the immuno-metabolic interactions during HIV-1 infection, additional studies are needed to establish the precise mechanisms involved in these alterations

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.

Regulation of cysteine metabolism and new strategies for cancer treatment / 中国药科大学学报

@#In order to sustain prodigious anabolic needs, tumor cells need metabolic reprogramming that differs from untransformed somatic cells.Besides glucose metabolism in tumor, amino acid metabolism also plays an important role in tumor cell proliferation, migration, and invasion.It is an emerging trend in tumor energy metabolism research.The metabolic pathway of cysteine, a glucose-producing amino acid, involves a variety of enzymes and products, regulating physiological and pathological processes such as oxidative stress, energy metabolism, and autophagy.This article focuses on the exogenous transport and endogenous conversion pathways of cysteine in tumor cells, the various regulatory mechanisms of cysteine metabolism pathways on the occurrence and development of tumors, and the potential therapeutic targets based on cysteine metabolism pathways, which can provide a theoretical basis for clinical use of drugs against tumors.

Research progress of correlation between multidrug resistance and transporters and traditional Chinese medicine intervention / 中国中药杂志

With the emergence of drug resistance in Western medicine, the repeated administration of clinical first-line drugs becomes more severe. There are many factors leading to multidrug resistance(MDR), so it is very difficult to solve the problem. Since traditional Chinese medicine(TCM) has been used in the field of MDR in recent years, the research on the transporter-associated drug resistance and intervention of TCM has gradually become a hot spot. Therefore, in order to further explore the relationships among drug resistance, transporters, and TCM intervention, we review the relevant research progress in recent years and comb the achievements and limitations of this research at present. In the end, we put forward the research direction of changing body's ADME through the host's transporters and gastrointestinal flora, which provides new ideas for future research.

Progress of studies on ATP-binding cassette transporters and transportation of secondary metabolites in medicinal plants / 中国中药杂志

ATP-binding cassette(ABC) transporters are one of the largest protein families in organisms, with important effects in regulating plant growth and development, root morphology, transportation of secondary metabolites and resistance of stress. Environmental stress promotes the biosynthesis and accumulation of secondary metabolites, which determines the quality of medicinal plants. Therefore, how to improve the accumulation of secondary metabolites has been a hotspot in studying medicinal plants. Many studies have showed that ABC transporters are extremely related to the transportation and accumulation of secondary metabolites in plants. Recently, with the great development of genomics and transcriptomic sequencing technology, the regulatory mechanisms of ABC transporters on secondary metabolites have attached great attentions in medicinal plants. This paper reviewed the mechanisms of different groups of ABC transporters in transporting secondary metabolites through cell membranes. This paper provided key theoretical basis and technical supports in studying the mechanisms of ABC transporters in medicinal plant, and promoting the accumulation of secondary metabolites, in order to improve the quality of medicinal plants.

Advances in plant heavy metal transporter P1B-ATPases / 生物工程学报

P1B-ATPases are a group of proteins that can transport heavy metal ions across membranes by hydrolyzing ATP and they are a subclass of the P-type ATPase family. It was found that P1B-ATPases are mainly responsible for the active transport of heavy metal ions in plants and play an important role in the regulation of heavy metal homeostasis in plants. In this paper, we dissusses the mechanism of P1B-ATPases from the structure and classification of P1B-ATPases, and review the current research progress in the function of P1B-ATPases, in order to provide reference for future research and application of P1B-ATPases in improving crop quality and ecological environment management.