Effect of L-T4 gel combined with metformin on the content of Ach and MCT8 in hippocampus of rats with hypothyroidism / 中华内分泌外科杂志

Objective:To study the effects of L-T4 gel combined with metformin on Ach and MCT8 content in hippocampus of hypothyroidism model rats.Methods:40 rats were randomly divided into 5 groups, normal control group (CON group) , hypothyroidism group (Hypo group) , L-T4 replacement group (L-T4 group) , metformin treatment group (MET group) and combined treatment group (L-T4+MET group) by random number table. Rats in CON group were given normal drinking water, and rats in the other four groups were given drinking water containing 0.05% propylthiouracil for 6-week hypothyroidosis modeling. At the 5th week of modeling, rats in MET group were given 1ml/100g metformin solution by intragastric administration, and rats in L-T4 group were applied with L-T4 gel agent at a dose of 0.1g/100g. L-t4+MET group were treated with L-T4 gel and metformin solution. At the end of 6-week modeling, the blood of abdominal aorta was collected, and the hippocampal tissue of the brain was quickly separated on an ice platform. Meanwhile, the trachea and thyroid were cut out and photographed to record their size. They were stored in a -80℃ refrigerator or soaked in 4% paraformaldehyde for fixation and used for immunohistochemical staining. T-test was used to confirm the difference between the data of each group, one-way analysis of variance was used to compare the means between multiple groups, and chi-square test was used when the count data were expressed as percentage ( χ2) . P<0.05 was used to indicate statistical significance between the data, and the difference was statistically significant. Results:Nishner staining showed that the optical density of the Hypo group was lower than that of the CON group ( t=8.944, P<0.001) , the optical density of the MET group was higher than that of the Hypo group ( t=4.472, P<0.001) , and the optical density of the L-T4 group was higher than that of the Hypo group ( t=4.472, P<0.001) . The optical density of rats in the combined treatment group was higher than that in the Hypo group ( t=8.944, P<0.001) , and recovered to the level of the CON group ( P=1.000) . After 2 weeks of treatment, the total thyroxine level (TT4) of the Hypo group was lower than that of the CON group ( t=14.536, P<0.001) , and the TT4 level of the MET group was higher than that of the Hypo group ( t=6.924, P<0.001) . TT4 level of L-T4 group was higher than that of Hypo group ( t=4.892, P<0.001) , TT4 level of combined treatment group was higher than that of Hypo group ( t=12.890, P<0.05) , and recovered to the level of CON group ( t=0.494, P=0.709) . After the study, the thyroid tissue of each group was collected. The thyroid tissue weight of the Hypo group was higher than that of the CON group ( t=7.906, P<0.001) , the thyroid tissue weight of the MET group and L-T4 group was lower than that of the Hypo group (MET: t=2.000, P<0.001; L-T4: t=3.000, P<0.001) , but higher than that of the CON group (MET: t=3.000, P<0.001; L-T4: t=2.000, P<0.001) . The thyroid weight of L-T4+MET group was similar to that of CON group ( P=1.000) . HE staining showed that the size of thyroid follicles was different in the combined treatment group, and the number of glial and absorbed vacuoles basically recovered similar to that of CON. After treatment, the Ach level in the Hypo group was lower than that in the CON group ( t=3.618, P<0.001) , the Ach level in the MET group was higher than that in the Hypo group ( t=3.121, P=0.016) , the Ach level in the L-T4 group was higher than that in the Hypo group ( t=3.321, P=0.027) , and the Ach level in the combined treatment group was higher than that in the Hypo group ( t=3.202, P=0.001) . And recovered to the level of CON group ( t=3.362, P=0.605) . After treatment, the MCT8 level in the Hypo group was higher than that in the CON group ( t=11.254, P<0.001) , the MCT8 level in the MET group was lower than that in the Hypo group ( t=5.679, P<0.001) , and the MCT8 level in the L-T4 group was lower than that in the Hypo group ( t=5.813, P<0.001) . The MCT8 level of the combined treatment group was lower than that of the Hypo group ( t=8.624, P<0.001) , and recovered to the level of the CON group ( t=0.587, P=0.477) . Conclusion:L-T4 gel combined with metformin has a good therapeutic effect on hypothyroidism, which can increase the level of Ach and decrease the level of MCT8 in hippocampus.

Genetic variants in the SLC16A11 gene are associated with increased BMI and insulin levels in nondiabetic Chilean population

ABSTRACT Objective: To study the association of SLC16A11 gene variants with obesity and metabolic markers in nondiabetic Chilean adults. Materials and methods: This cross-sectional study included 263 non-diabetic adults. The genotype of the rs75493593 polymorphism of SLC16A11 gene was performed by real-time PCR. It's association with adiposity markers (body weight, BMI, waist circumference and fat mass percentage), metabolic markers (glucose, insulin, HOMAIR, leptin, total cholesterol, LDLc, HDLc, triglycerides, ALT, GGT and hsCRP) and blood pressure was analyzed by linear regression. Results: The minor allele (T) of the SLC16A11 gene (rs75493593) has a frequency of 29.7% among Chileans. Risk genotypes (GT and TT) were associated with a significant 1.49 mU/l increase in plasmatic insulin for each copy of the minor allele (95% CI: 0.12, 2.87, p < 0.05). This association remained significant after adjusting for socio-demographic variables, physical activity and smoking (1.36 mU/l, 95% CI: 0.16, 2.58 p < 0.05), but was lost when BMI was included as a confounding factor. Higher BMI was also significantly associated with polymorphic genotypes in SLC16A11, independent of socio-demographic variables. Conclusion: The minor allele of the SLC16A11 gene (T) is highly prevalent among Chileans and is associated with increased insulin and BMI in nondiabetic individuals. These findings suggest that the genetic variant in SLC16A11 is not only associated with type 2 diabetes as previously shown in Mexicans, but is also related to early metabolic alterations in healthy subjects that may lead to type 2 diabetes.

Loss of monocarboxylate transporter 1 aggravates white matter injury after experimental subarachnoid hemorrhage in rats / 医学前沿

Monocarboxylic acid transporter 1 (MCT1) maintains axonal function by transferring lactic acid from oligodendrocytes to axons. Subarachnoid hemorrhage (SAH) induces white matter injury, but the involvement of MCT1 is unclear. In this study, the SAH model of adult male Sprague-Dawley rats was used to explore the role of MCT1 in white matter injury after SAH. At 48 h after SAH, oligodendrocyte MCT1 was significantly reduced, and the exogenous overexpression of MCT1 significantly improved white matter integrity and long-term cognitive function. Motor training after SAH significantly increased the number of ITPR2

Effect of silencing monocarboxylate transporter 4 on the malignant biological behaviors of prostate cancer PC3 cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effects of silencing monocarboxylate transporter 4 (MCT4) on the proliferation, migration and invasion of prostate cancer PC3 cells and its possible molecular mechanism. Methods: RNA interference technology was used to transfect siRNA-MCT4 (si-MCT4) and negative control plasmid (si-NC) into PC3 cells, respectively. The content of lactic acid in the cell culture medium of transfected PC3 cells was detected by lactic acid assay after culturing for 96 h. The proliferation, migration and invasion ability of PC3 cells were detected by CCK-8 and Transwell assay, respectively. Western blotting was used to detect the silencing effect and the expressions of integrin β 4-FAK-SRC-MEK-ERK signaling pathway associated proteins (integrin β4, p-FAK, p-SRC, p-ERK1/2, p-MEK1/2) and EMT associated proteins (E-cadherin and N-cadherin). Results: PC3 cell line with silenced MCT4 was successfully constructed. Compared with the control group, the content of extracellular lactic acid in the PC3 cell culture medium of the si-MCT4 group was significantly decreased (P<0.01), and the proliferation, migration and invasion of cells were significantly decreased (P<0.05 or P<0.01). Compared with the control group, the protein expressions of integrin β4, p-FAK, p-SRC, p-MEK1/2, p-ERK1/2 and N-cadherin were significantly decreased (all P<0.01), while the protein expression of E-cadherin was significantly increased (P<0.01). Conclusion: Silencing MCT4 can significantly inhibit the proliferation, migration and invasion of PC3 cells, the mechanism of which may be related to the inhibition of lactic acid level in cell culture medium and suppression of integrin β4-FAK-SRC-MEKERK signaling pathway associated proteins as well as EMT associated proteins.

Acupuncture up-regulates MCT2 expression of peri-ischemic cortex in middle cerebral artery occlusion rats / 针刺研究

OBJECTIVE: To observe the effect of manual acupuncture (MA)＋ electroacupuncture (EA) on changes of neurological function and expression of monocarboxylate transporter 2(MCT2)in cerebral ischemia (CI) rats, so as to explore its mechanism underlying improvement of ischemic cerebrovascular disease. METHODS: Eighty male Wistar rats were equally randomized into four groups: normal control (normal), sham operation (sham), model and acupuncture. The CI model was induced by middle cerebral artery occlusion (MCAO) with a thread embolus. Manual acupuncture stimulation (mild twisting reinforcing-reducing method) was applied to "Baihui"(GV20)and "Fengfu"(GV16) for 10 min. EA (1 mA, 2 Hz /15 Hz) was respectively applied to bilateral "Quchi" (LI11) and "Zusanli"(ST36) for 20 min, once per day for 7 days. The neurological deficit severity was evaluated according to Zea Longa's methods. The activity of lactate dehydrogenase (LDH), fructose-6-phosphate kinase (PFK) and pyruvate kinase (PK) in the peri-ischemic cortex tissue was detected by enzymatic chemistry, and the expression of MCT2 detected by immunofluorescence histochemistry, Western blot and quantitative real-time PCR, separately. RESULTS: After CI and in comparison with the normal and sham groups, the Zea Longa's score, the fluorescence intensity and the expression level of MCT2 protein were significantly increased (P0.05). Following the intervention and in comparison with the model group, the Zea Longa's score was considerably decreased in the acupuncture group (P<0.01), the activity of LDH, PFK and PK，and the expression levels of MCT2 protein and mRNA were considerably or further up-regulated in the acupuncture group (P<0.01, P<0.05). CONCLUSION: Acupuncture intervention can improve neurological function in CI rats, which is possibly related with its effects in up-regulating the expression of MCT2 and promoting the utilization of lactate in peri-ischemic cortex.

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.

Study of acupuncture combined with rat nerve growth factor on neurobehavioral ability of cerebral palsy infant rats and its brain tissue growth and metabolism associated proteins / 中国针灸

<p><b>OBJECTIVE</b>To study the effects of acupuncture combined with rat nerve growth factor (NGF) on the cerebral palsy infant rats and the proteins which associated with growth, apoptosis and metabolism.</p><p><b>METHODS</b>Seventy infant rats were selected, Fifty infant rats of which were made the cerebral palsy infant model by the ligation of unilateral carotid artery for cerebral ischemia and oxygen-deficient environment, then the 30 model rats were randomly divided into a model group, a NGF group and a combined group, 10 rats in each group. Twenty infant rats were used in the sham-operated group and the blank control group, 10 rats in each group. The treatment was not given in the blank control group. The rats in the sham-operated group were cut the neck skin and separated the left carotid artery, and then sutured and disinfected the wound. The intraperitoneal injection of NGF (2000 U•kg•d) was used in the NGF group. Based on the injection in the NGF group, acupuncture was used in the combined group, once a day, and the acupoints were "Baihui" (GV 20), left "nieⅠ" (extra), "Dazhui" (GV 14), "Jizhong" (extra), "Quchi" (LI 11), "Yongquan" (KI 1), "Hegu" (LI 4), "Zhoujie" (extra) and "Xiqianxue" (extra). The same volume of saline was intraperitoneally injected in the model group for continuous 14 days. Neurobehavioral ability score was evaluated after treatment. TUNEL were conducted to detect the brain cell apoptosis rate and the expressions of apoptosis associated gene Bax, Bcl-2 and Casp3 were detected by PCR. The level of nerve growth associated protein (GAP-43) and energy metabolism-related protein monocarboxylate transporter protien 1(MCT 1) were detected by Western blot.</p><p><b>RESULTS</b>After intervention, the neurobehavioral ability of baby rats in the blank control and sham-operated group was normal, but there was various degrees of abnormity in the model group, NGF group and combined group. The scores of neurobehavioral ability of the combined group and NGF group were better than those of the model control (all <0.05), and the scores in the combined group was better than those in the NGF group (all <0.05). The left brain cell apoptosis rate, expressions of Bax and Casp3 in the combined group and NGF group were lower and the expressions of Bcl-2 were higher than those of the model group (all <0.05), with more obvious results of Bax and Gasp3 in the combined group than those in the NGF group (all <0.05). The protein levels of GAP-43 and MCT 1 in the combined group and NGF group were higher than those in the model group (all <0.05), with higher expressions in the combined group compared with those in the NGF group (both <0.05).</p><p><b>CONCLUSION</b>Acupuncture combined with NGF could improve the neurobehavioral ability of cerebral palsy infant rats, inhibit the nerve cell apoptosis and improve the brain tissue injure and energy metabolism by up-regulating the expressions of GAP-43 and MCT 1.</p>

A Novel c.826G>A Mutation in a Boy with Allan-Herndon-Dudley Syndrome: Clinical Significance of Thyroid Function Tests in Developmental Delay of Unknown Origin

Allan-Herndon-Dudley syndrome (AHDS) is an X-linked intellectual disability caused by monocarboxylate transporter 8 (MCT8) deficiency. AHDS manifests in global developmental delay, axial hypotonia, quadriplegia, movement disorders in male patients, and most of them show the delayed or hypomyelination on brain magnetic resonance images. Typically, Triiodothyronine (T3) levels are markedly elevated, thyroid stimulating hormone (TSH) levels are normal or elevated, and free thyroxine (T4) levels are normal or decreased. In AHDS patients, early neurological manifestations are easily mistaken as cerebral palsy with unknown origin. Here, we present a novel c.826G>A mutation in a boy with severe axial hypotonia, limb dystonia and developmental delay. Thyroid function test including TSH, T3, and free T4 levels was the important clue for the diagnosis of AHDS of the patient.

Effect of celastrol on anti-proliferation and energy metabolism in SGC-7901 cells and ECV304 cells / 中草药

Objective: To investigate the activity of celastrol on the proliferation and the mechanism of energy metabolism to human gastric cancer cells (SGC-7901) and human umbilical vein endothelial cells (ECV304). Methods: SGC-7901 and ECV304 were determined to analyze the proliferation inhibitory rate of celastrol to two kinds of cells by MTT method and growth curve; HE staining method was used to observe the morphological changes; Using spectrophotometric method, the activities of the enzymes in glycolytic pathway (hexokinase, pyruvate kinase, and lactate dehydrogenase) were determined, the enzyme in the tricarboxylic acid cycle (succinate dehydrogenase), and the level of ATP which was the end-products in energy metabolism were determined; The Western blotting method was used to determine the expression levels of hypoxia inducible factor (HIF-1α) and single carboxyl transporter (MCF-4). Results: The proliferation inhibition of celastrol to SGC-7901 and ECV304 cells showed in a time-and dose-dependent manner, led to morphologic changes of cells, reduced the activity of HK, LDH, and SDH, lowered the level of ATP; There was no effect to PK. The protein expression levels of HIF-1α and MCF-4 were significantly reduced. The inhibition of celastrol to SGC-7901 was stronger than that of ECV304 cells. Conclusion: Celastrol influence energy metabolism of the two cells by reducing the expression levels of HIF-1α and MCF-4 is significant, and then proliferation can be inhibited. It shows a double inhibition on human gastric cancer cells and angiogenesis of tumor.

Interaction between basigin and monocarboxylate transporter 2 in the mouse testes and spermatozoa / 亚洲男科学杂志(英文版)

Basigin is a member of the immunoglobulin superfamily and plays various important roles in biological events including spermatogenesis. To examine the basigin molecular variants during spermatogenesis and sperm maturation in the mouse, immunoprecipitated basigin samples from testis and epididymal spermatozoa were analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The results demonstrated that basigin molecules from the testis and spermatozoa were separable into two major bands and that the differences in the molecular sizes were possibly because of an endoproteolytic cleavage. Since basigin is known to be a chaperone for the monocarboxylate transporter 1 (MCT1), the localization of basigin, MCT1 and MCT2 was examined during postnatal testicular development. Immunohistochemical studies showed different expression patterns of MCT1 and MCT2. MCT1 was localized on the surface of spermatogonia, spermatocytes, and spermatids. In contrast, MCT2 appeared on the principal piece of spermatozoa in the testis, where basigin was also observed. In mature epididymal spermatozoa, MCT2 was located on the midpiece, where basigin co-localized with MCT2 but not with MCT1. Furthermore, MCT2 was immunoprecipitated with basigin in mouse testes and sperm. These results suggest that basigin has a functional role as a binding partner with MCT2 in testicular and epididymal spermatozoa.

The expression and role of monocarboxylate transporter 1 in tumor / 国际肿瘤学杂志

The monocarboxylate transporters (MCTs) family, especially MCT1, plays an important role in tumor metabolism.MCT1 mediates a variety of monocarboxylic acids across the plasma membrane, and determines to take in or export lactic acid according to the metaboliuc state, thus maintaining the special tumor cells metabolism model.Considering the emerging evidence for the role of MCT1 in the tumor genesis, metabolism, invasion and metastasis, MCT1 is expected to be a new target for cancer therapy.

Intrathecal injection of monocarboxylate transporter inhibitor α-cyano-4-hydroxy-cinnamate attenuates neuropathic pain in rats / 中华行为医学与脑科学杂志

Objective To investigate the effects of intrathecal injection of α-cyano-4-hydroxy-cinnamate (4-CIN) in rats with neuropathic pain induced by chronic constriction injury of sciatic nerve (CCI).Methods Eighteen male SD rats were divided randomly into 3 groups(n=6):sham group (group S),CCI model group (group C0) and 4-CIN group (group C1).Group C0 and C1 were operated with the model of neuropathic pain induced by chronic constriction injury of sciatic nerve ; and group S were treated as sham operated rats.Two days after operation,group C1 received intrathecal injection of 100 μmol 4-CIN dissolved in 10％ DMSO 10 μl,while group C0 received intrathecal injection of 10％ DMSO 10 μl only.The paw withdrawal thermal latency(PWTL) and paw withdrawal mechanical threshold(PWMT) were tested 1 d before operation and 1 d,3 d,7 d,10 d,14 d after operation(T0-5).Results The basic values of PWMT and PWTL before operation showed no statistically significant differences among the three groups.On T1-5,the PWMT((11.71 ±2.81) g,(9.76± 1.00) g,(8.22± 1.33) g,(6.50± 1.48) g,(4.67± 1.03) g) and PWTL((11.36±2.18) s,(11.60±2.54) s,(8.54± 1.42) s,(7.59± 1.00) s,(6.88± 0.42) s) in group C0 were significantly lower than those in group S (P＜0.05).However,there were no significant differences between group S and C1 on T2-5(P＞0.05).Conclusion Intrathecal administration of 4-CIN can attenuate neuropathic pain in rats induced by CCI.

The Expression of Glut-1, CAIX, and MCT4 in Mucinous Carcinoma / 한국유방암학회지

PURPOSE: The aim of this study was to assess the expression of metabolism-related proteins including glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX) and monocarboxylate transporter 4 (MCT4) in breast mucinous carcinoma and to evaluate the implications of the results. METHODS: Immunohistochemical staining for Glut-1, CAIX, and MCT4 was performed on tissue sections from 59 cases of mucinous carcinoma to evaluate the association between the expression of metabolism-related proteins and clinicopathologic factors. Mucinous carcinoma was subclassified into type A and type B according to histopathological characteristics. RESULTS: Of the 59 patients, 35 patients (59.3%) were type A mucinous carcinoma and 24 patients (40.7%) were type B mucinous carcinoma. Stromal expression of MCT4 was significantly associated with a high histologic grade (p=0.022) and type B mucinous carcinoma (p=0.016). There were significant positive correlations between the expression of Glut-1, CAIX and tumoral expression of MCT4 (p<0.05). CONCLUSION: We assessed the expression of metabolism-related proteins including Glut-1, CAIX, and MCT4 in breast mucinous carcinoma and found that the stromal expression of MCT4 was higher in type B mucinous carcinoma than in type A, which reflected a difference in the tumor microenvironment.

Advances in thyroid hormone transporters / 中华内分泌代谢杂志

Thyroid hormones play important roles in growth, development, and metabolism of various cells and tissues. It has been assumed for a long time that thyroid hormones are lipophilic and enter cells by passive diffusion, but it has become increasingly clear that cellular uptake and efflux of thyroid hormones are mediated by transporters. The discovery of these thyroid hormone transporters will lead to a better understanding of the tissuespecific regulation of thyroid hormones.

Expressions of MCT1 and CD147 in human gliomas and their correlations with prognosis / 第三军医大学学报

Objective To investigate the expressions and correlation of monocarboxylate transporter-1 (MCT1) and CD147 in human gliomas,and analyzee the relationship between their expressions and prognosis.Methods Immunohistochemistry SP methods were applied to detect the expressions of MCT1 and CD147 in 28 cases of low grade gliomas and 32 cases high grade gliomas.Their expression level and correlation were analyzed statistically.Prospective cohorts were set to acquire follow-up data.Kaplan-Meier curve and Cox multi-factor model were used to analyze patients’ prognosis.Results Both CD147 and MCT1 had strong expressions in human gliomas.The positive expression rate of MCT1 and CD147 (93.8% and 90.6%) and the strong positive expression rate (73.3% and 72.4%) in high grade gliomas were significantly enhanced compared with that of low grade gliomas (positive expression rate:46.4% and 50%,strong positive expression rate:30.8% and 35.7%,P

Advances in the Study of the MCT Gene Family / 生物化学与生物物理进展

monocarboxylate transporter (MCT) are vital transmembran e transporters involved in multiple cellular functions including the regulation of intracellul ar pH and lactate transport. At least eight isoforms of MCT have been cloned and characterized to date, they constitute a new gene family of mammal transporters . These isoforms have the differences in substrate and inhibitor specificities a nd tissue distribution. Thus it may provide a new way of diagonosis and treating for dieases such as cancer by investigating on the structure and function and r egulational mechanism of MCT.