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Introduction: Oral cancer, one of the most common cancers worldwide constitutes a major public health problem and is one of the leading cancer sites among men and women in India. Increased uptake of glucose in cancer cells are mediated by glucose transporters. Among 14 isoforms of glucose transporters, Glucose transporter 1 (GLUT-1) isoform expression predominate Oral squamous cell carcinoma (OSCC). Aim: To emphasize the expression of GLUT-1 in OSCC and to assess its role in tumor progression and prognosis. Materials and Methods: Hand searching and electronic databases such as PubMed/Medline, Google scholar and Science- Direct were done for mesh terms such as OSCC, GLUT-1, prognosis, tumor markers, prognostic marker and risk predictor. Studies were pooled and relevant articles were evaluated. Results: Final analysis identified thirteen articles after considering the inclusion and exclusion criteria. These studies evalu- ated 926 OSCC cases and 70 healthy controls for GLUT-1 immunoexpression. The data was extracted and evaluated manu- ally. GLUT-1 expression was found to be elevated in OPMDs and OSCC than in healthy controls. The pattern of expression of GLUT-1, its correlation with clinico-pathological features, role in tumour progression and prognosis, expression in tumor invasive front, correlation with other markers and role in therapeutics are also discussed in detail
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ABSTRACT Objective: MCM3AP-AS1 has been characterized as an oncogenic long non-coding RNA (lncRNA) in several cancers including papillary thyroid cancer (PTC), but its role in PTC has not been fully elucidated. Considering the critical role of lncRNAs in cancer biology, further functional analysis of MCM3AP-AS1 in PTC may provide novel insights into PTC management. Subjects and methods: Paired tumor and non-tumor tissues were collected from 63 papillary thyroid carcinoma (PTC) patients. Expression levels of MCM3AP-AS1 , miR-218 and GLUT1 in tissue samples were analyzed by qRT-PCR. Cell transfection was performed to explore the interactions among MCM3AP-AS1 , miR-218 and GLUT1 . Cell proliferation assay was performed to evaluate the effects of MCM3AP-AS1 and miR-218 on cell proliferation. Results: MCM3AP-AS1 accumulated to high levels in PTC tissues and was affected by clinical stage. MCM3AP-AS1 showed a positive correlation with GLUT1 across PTC tissues. RNA interaction prediction showed that MCM3AP-AS1 could bind to miR-218 , which can directly target GLUT1 . MCM3AP-AS1 and miR-218 showed no regulatory role regulating the expression of each other, but overexpression of MCM3AP-AS1 upregulated GLUT1 and enhanced cell proliferation. In contrast, overexpression of miR-218 downregulated GLUT1 and attenuated cell proliferation. In addition, miR-218 suppressed the role of MCM3AP-AS1 in regulating the expression of GLUT1 and cell proliferation. Conclusions: MCM3AP-AS1 may serve as a competing endogenous RNA of miR-218 to upregulate GLUT1 in PTC, thereby promoting cell proliferation. The MCM3AP-AS1/miR-218/GLUT1 pathway characterized in the present study might serve as a potential target to treat PTC.
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Abstract This study aimed to investigate the activities of novel 20(R)-3,20-dihydroxy-19-norpregn-1,3,5(10)-trienes (kuz7 and kuz8b) of natural 13ß- and epimeric 13α-series against triple-negative MDA-MB-231 breast cancer cells. High antiproliferative activity of synthesized compounds kuz8b and kuz7 against MDA-MB-231 triple-negative cancer cells was revealed. The steroid kuz7 of natural 13ß-configuration was more active against MDA-MB-231 cells than the 13α-steroid kuz8b. Cell cycle analysis revealed common patterns for the action of both tested compounds. The number of cells in the subG1 phase increased in a dose-dependent manner, indicating induction of apoptosis, which was also verified by PARP cleavage. In contrast, the number of cells in the G0/G1 phase decreases with increasing compound concentration. Steroid kuz7 at micromolar concentrations reduced the expression of GLUT1, a glucose transporter. High efficacy of the combination of kuz7 with biguanide metformin was shown, and synergistic effects on MDA-MB-231 cell growth and expression of the anti-apoptotic protein Bcl-2 were revealed. According to the obtained results, including the high activity of kuz7 against triple-negative cancer cells, the detected induction of apoptosis, and the decrease in GLUT1 expression, 13ß-steroid kuz7 is of interest for further preclinical studies both alone and in combination with the metabolic drug metformin
Subject(s)
Steroids/agonists , Breast Neoplasms/pathology , Glucose Transporter Type 1/adverse effects , Pharmaceutical Preparations/administration & dosage , Apoptosis , Metformin/administration & dosageABSTRACT
In recent years, with the deepening of tumor biology research, people have a newer and more comprehensive understanding of complex tumor metabolism reprogramming. The glucose transport protein-1(GLUT-1) is a glucose transporter widely expressed in the cell membranes of various tissues and represents unusual overexpression in the plasma membrane of virous cancer cell. GLUT-1 can transport man-nose, galactose, glucosamine and ascorbic acid (AA). GLUT-1 is overexpressed in different degrees on the plasma membrane of different tumor cells. Overexpressed GLUT-1 will make tumor cells take in more glucose to reprogram the metabolic mode of cells, and at the same time, it influences the change of tumor microenvironment. And the regulation of GLUT-1 in tumors has been the focus of attention in recent years, and the upstream regulators that have been reported mainly include phosphatase and tension homolog deleted on chromosome ten (PTEN) and hypoxia inducible factor (HIF). GLUT-1 also plays an important role in tumorigenesis and development by influencing the p53 and cellular tumorigenic gene (c-Myc) pathways. The review introduces structure and function of GLUT-1, the effects of transporting different substrates in tumor metabolic reprogramming, the regulation of GLUT-1, and the current treatment of GLUT-1. Meanwhile, the review discusses mechanisms and development of the role of GLUT-1 in cancer metabolism reprogramming, and points out the existing problems to provide reference for the research of metabolism reprogramming and targeted therapy of malignant tumors.
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Glucose transporters (GLUTs) encoded by the solute carrier family 2 (SLC2) gene belong to the major facilitator superfamily (MFS) and are responsible for the transmembrane transport of glucose in the body. As the earliest discovered member of the GLUTs, glucose transporter 1 (GLUT1) is mainly found in the blood-brain barrier and erythrocyte membrane, and plays an important role in maintaining stable blood glucose concentration and energy supply to the brain. The transmembrane transport capacity of GLUT1 is not only related to the gene expression of SLC2 A1 on the cellular membrane, but also to the transport kinetic regulation of GLUT1. Generally, SLC2 A1 expression is regulated at the transcriptional, post-transcriptional, translational and post-translational levels, and the transport kinetics regulation includes a series of GLUT1 inhibitors, such as intramembrane glycan-binding site inhibitor, extramembrane glycan-binding site inhibitor, adenosine-binding effect inhibitors and the highly selective inhibitor BAY-876. SLC2 A1 gene deletions and mutations can cause embryonic mortality and GLUT1 deficiency syndrome. In contrast, abnormally high SLC2 A1 expression is associated with various diabetic complications (e. g. diabetic retinopathy and diabetic nephropathy), neurocognitive impairment and tumorigenesis. In this paper, the structure, function, expression and activity regulation of GLUT1 and its relationship with diseases were reviewed to provide a reference for the GLUT1-related clinical research and drug development.
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Resumen Cuando los alimentos cubren los requerimientos energéticos, el organismo almacena el exceso de calorías como glucógeno en el hígado y el músculo, y los triacilgliceroles en el tejido adiposo. Morfológica y funcionalmente se clasifica en blanco y pardo. El pardo tiene gran cantidad de mitocondrias, almacena los triacilgliceroles en vacuolas y disipa la energía en forma de calor; el blanco almacena energía en gotas lipídicas que ocupan la mayor parte de su volumen. Después de la ingesta de alimentos se libera insulina, lo que hace que externen GLUT4 para absorber glucosa. Los quilomicrones o las lipoproteínas de muy baja densidad (VLDL) transportan los triacilgliceroles a los depósitos de tejido adiposo. Durante el ayuno, por acción del glucagón, se liberan enzimas que degradarán a los tri, di y monogliceroles para liberar a los ácidos grasos. El tejido adiposo libera citocinas pro y antiinflamatorias, así como leptina, adiponectina que regulan el apetito y la saciedad. La proteína cinasa activada por AMP se activa como respuesta a una baja en la cantidad de energía de la célula y le ayuda a mantener un balance energético. En el adipocito promueve la degradación de los triacilgliceroles para liberar a los ácidos grasos que se emplearán como fuente energética. Se requiere de mayor cantidad de estudios para conocer más sobre la función del tejido adiposo como regulador del metabolismo y no solo como almacén de energía.
Abstract When food meets energy requirements, the body stores in the liver and in the muscle the excess of calories as glycogen and triacylglycerols in the adipose tissue. Morphologically and functionally, it is classified into white and brown tissues. Brown tissue has many large mitochondria and stores triacylglycerols in vacuoles and dissipates energy as heat; white tissue stores energy as lipid droplets that occupy most of the adipocyte's volume. After food intake insulin is released, which causes GLUT4 externalization into the cellular membrane to absorb glucose. Chylomicrons or VLDL transport triacylglycerols to adipose tissue depots. During fasting, by the action of glucagon, enzymes are released that will degrade tri-, di- and mono-glycerols to release fatty acids. Adipose tissue releases pro and anti-inflammatory cytokines, as well as leptin and adiponectin that regulate appetite and satiety. AMPK is activated in response to a decrease in the cell's energy and helps it to maintain its energetic balance. In the adipocyte, it promotes the degradation of triacylglycerols releasing fatty acids to be used as an energy source. More studies are needed to learn more about the function of adipose tissue as a regulator of the metabolism and not only as an energy storage.
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Type 2 diabetes mellitus( T2 DM) is a common chronic metabolic disease characterized by persistent hyperglycemia and insulin resistance. In pancreatic β-cells,glucose-stimulated insulin secretion( GSIS) plays a pivotal role in maintaining the balance of blood glucose level. Previous studies have shown that geniposide,one of the active components of Gardenia jasminoides,could quickly regulate the absorption and metabolism of glucose,and affect glucose-stimulated insulin secretion in pancreatic β cells,but the specific mechanism needs to be further explored. Emerging evidence indicated that glycosylation of glucose transporter( GLUT) has played a key role in sensing cell microenvironmental changes and regulating glucose homeostasis in eucaryotic cells. In this study,we studied the effects of geniposide on the key molecules of GLUT2 glycosylation in pancreatic β cells. The results showed that geniposide could significantly up-regulate the mRNA and protein levels of Glc NAc T-Ⅳa glycosyltransferase( Gn T-Ⅳa) and galectin-9 but had no signi-ficant effect on the expression of clathrin,and geniposide could distinctively regulate the protein level of Gn T-Ⅳa in a short time( 1 h) under the conditions of low and medium glucose concentrations,but had no significant effect on the protein level of galectin-9. In addition,geniposide could also remarkably affect the protein level of glycosylated GLUT2 in a short-time treatment. The above results suggested that geniposide could quickly regulate the protein level of Gn T-Ⅳa,a key molecule of protein glycosylation in INS-1 rat pancreatic βcells and affect the glycosylation of GLUT2. These findings suggested that the regulation of geniposide on glucose absorption,metabolism and glucose-stimulated insulin secretion might be associated with its efficacy in regulating GLUT2 glycosylation and affecting its distribution on the cell membrane and cytoplasm in pancreatic β cells.
Subject(s)
Animals , Rats , Diabetes Mellitus, Type 2/metabolism , Glucose/metabolism , Glycosylation , Insulin/metabolism , Insulin-Secreting Cells/metabolism , IridoidsABSTRACT
Objective: To investigate the modulatory effects of bitter gourd extract on the insulin signaling pathway in the liver and skeletal muscle tissues of diabetic rats. Methods: The ethanolic extract of bitter gourd was prepared and its contents of total polyphenols and flavonoids were assayed. A neonatal streptozotocin-induced diabetic rat model was established and the diabetic rats were assigned into different groups and were treated with different doses of bitter gourd extract (100, 200, 400, or 600 mg/kg) or with glibenclamide (0.1 mg/kg) for 30 d. Fasting blood glucose, insulin, and lipid profile were evaluated and the insulin signaling pathway in the liver and skeletal muscle of rats was investigated. The correlations between homeostasis model assessment (HOMA) and the components of insulin signaling pathway were also evaluated. Results: Different doses of bitter gourd extract significantly ameliorated fasting blood glucose level and HOMA index for insulin resistance. Moreover, bitter gourd extract increased serum insulin and improved disrupted serum lipid profile. The levels of insulin receptor substrate-1 (IRS-1), p-insulin receptor β (p-IR-β), protein kinase C (PKC), GLUT2, and GLUT4 were improved by treatment with bitter gourd extract. The best results were obtained with 400 mg/kg dose of the extract, the effect of which was equivalent to that of glibenclamide. HOMA in the bitter gourd treated rats was negatively correlated with p-IR-β, IRS-1 and PKC in hepatic and skeletal muscle. HOMA was also negatively correlated with skeletal muscle GLUT4. Conclusions: Bitter gourd extract improves glucose homeostasis and lipid profile in diabetic rats via enhancement of insulin secretion and sensitivity. Therefore, bitter gourd can be used as a potential pharmacological agent for the treatment of type 2 diabetes mellitus.
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Objective: To explore the effect of hirudin on hyperuricemia rats and its mechanism. Methods: Male Wistar rats were randomly divided into control group, model group, allopurinol (30 mg/kg) group, hirudin low-, middle- and high-dose (0.2, 0.4, 0.8 g/kg) group. Rats were ig potassium oxonate (0.75 g/kg) to induce hyperglycemia model, once a day for five weeks. And all administration groups were respectively ig corresponding doses of drugs. The level of uric acid in serum and urine of rats were measured by biochemical method; The level of organic anion transporter 1 (OAT1) in kidney was measured by immunohistochemistry; The protein expressions of glucose transporter 9 (GLUT9), OAT1 and urate transporter 1 (URAT1) in kidney were measured by western blotting; The expression levels of GLUT9, OAT1 and URAT1 mRNA in kidney were detected by qRT-PCR. Results: Compared with control group, the level of uric acid in serum and urine of rats in model group was significantly increased (P < 0.01), the expressions of GLUT9, URAT1 mRNA and protein were significantly increased (P < 0.01), the expressions of OAT1 mRNA and protein were significantly decreased (P < 0.01). Compared with model group, the level of uric acid in serum and urine of rats in hirudin group were significantly decreased (P < 0.01), the expressions of GLUT9, URAT1 mRNA and protein were significantly reduced (P < 0.01), the expressions of OAT1 mRNA and protein were significantly increased (P < 0.01). Conclusion Hirudin can reduce the uric acid by regulating the expressions of renal urate transporters OAT1, URAT1 and GLUT9 in hyperuricemia rats.
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Objective: To study the chemical constituents of ethyl acetate extract from the whole herb of Pholidota articulata. Methods: Silica gel and Sephadex LH-20 gel column chromatographic techniques were used to separate and purify the chemical constituents. Their structures were elucidated based on NMR spectroscopic and reported data. Results: A total of 17 compounds were isolated from 78% ethyl acetate extracts of P. articulata and identified as flavidin (1), flaccidin (2), imbricatin (3), coelonin (4), lusianthridin (5), hircinol (6), gigantol (7), batatasin III (8), 5,3'-dihydroxy-3-methoxybibenzyl (9), cirrhopetalidin (10), β-sitosterol (11), stigmasterol (12), glut-5-en-3-ol (13), laurostearic acid (14), 4, 4'-dihydroxydiphenylmethane (15), 3-methoxy-benzaldehyde (16), and trans-cinnamic acid (17). Conclusion: Compounds 3-17 are isolated from this plant for the first time. In addition, compounds 9, 10, 13, and 16 are found in the genus Pholidota for the first time.
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@#The aim of this study was to investigate the effect of Compound Yihe Tea on improving insulin resistance in obesity mice. Thirty-two male C57BL/6J mice were randomly divided into 4 groups: the normal fat diet group(NFD group), high fat diet group(HFD group), Compound Yihe Tea low dosage group［20 mg/(kg ·d), YH-L group］ and high dosage group［40 mg/(kg ·d), YH-H group］. NFD group was given standard feed, and the remaining mice were administered with high fat diet. After 6 weeks, YH-H and YH-L groups were given Compound Yihe Tea for 6 weeks. Blood glucose was measured at week 11 and serum levels of total cholesterol(TC), serum triglyceride(TG), low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were measured at week 12. Liver tissues were prepared for oil red O and HE staining. Immunohistochemical analysis was used to test the protein expression of GLUT4 in liver. Protein expressions of PI3K, Akt and GLUT4 in epididymis white adipose tissue(WAT)were tested by Western blot. The results showed that Compound Yihe Tea could effectively reduce body weights and the serum levels of TC, TG and LDL-C. Furthermore Compound Yihe Tea could improve the histopathological changes of liver, up-regulate the protein expression of PI3K, Akt and GLUT4 in epididymis WAT and the protein expression of GLUT4 in liver. Compound Yihe Tea can reduce the fat accumulation in liver tissue, improve the indexes of blood glucose and lipid levels, and improve insulin resistance via PI3K-AKT-GLUT4 pathway.
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@#[Abstract] Objective: To explore whether gambogic acid can enhance the sensitivity of glioma U251 cells to temozolomide and further explore its mechanism. Methods: U251 cells were cultured in vitro and divided into blank control group, gambogic acid treatment group, temozolomide alone treatment group and combined treatment group. The cells survival rates of cells in each group was detected by CCK-8 assay. Flow cytometry was used to detect cell apoptosis and changes in ROS level. Western blotting was used to detect the changes in protein expressions. Results: CCK-8 results showed that the cells survival rates of the four groups after treatment for 24 h were (98.65±3.68)%, (93.58±2.47)%, (66.81±2.39)% and (38.65±4.13)%, respectively. It can be seen that the combined treatment could significantly increase the inhibitory effect of temozolomide on U251 cells. The proportion of apoptotic U251 cells in the combined treatment group was (61.43±2.58)%, which was significantly higher than that of (26.68±1.82)% in the temozolomide-treated group. Combined treatment of gambogic acid and temozolomide could up-regulate ROS level in U251 cells, reduce the expressions of GLUT-3 and p-AKT, and inhibit the GLUT-3/AKT signaling pathway. Conclusion: Gambogic acid combined with temozolomide can enhance the sensitivity of U251 cells to temozolomide by up-regulating ROS level and inhibiting GLUT-3/AKT signaling pathway in U251 cells, and provides a theoretical basis for the application of gambogic acid in the treatment of glioma.
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OBJECTIVE：To study the effects of Purple frute scens leaves polysaccharides （PPLPs）on oxidative stress and PI3K/AKT/GLUT4 signaling pathway of pancreatic tissues in diabetes mellitus （DM）model mice. METHODS ：Totally 60 mice were given intraperitoneal injection of STZ （60 mg/kg）to induce DM model. The 40 successful modeling mice were randomly divided into model group ，metformin group （positive control ，200 mg/kg），PPLPs high-dose and low-dose groups （400，200 mg/kg），with 10 mice in each group. Another 10 healthy mice were selected as the normal group （normal saline ）. They were given relevant medicine intragastrically ，once a day ，for consecutive 28 days. During the experiment ，general information and body weight of mice were observed ；oral glucose tolerance （OGTT）test（determining FBG at 0，30，60，120 min after giving 40％ glucose solution ）was conducted. After last medication ，the changes of related blood glucose indexes （FBG，FINS，ISI，IRI）， blood lipid indexes （HDL-C，LDL-C，TC，TG）and oxidant stress indexes （MDA content and the activities of SOD ，CAT， GSH-Px）as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were determined. RESULTS ：During the experiment ，compared with normal group ，the mice were slow in action ，the feed consumption and water consumption increased，and body weight significantly increased in model group （P＜0.05）. 0，30，60，120 min after giving glucose ，the FBG content of mice were all increased significantly （P＜0.05）. After last medication ，the contents of FINS and HDL-C in serum as well as ISI ，the activities of SOD ，CAT and GSH-Px as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were all decreased significantly （P＜0.05）；the contents of FBG and LDL-C ，TC and TG in serum as well as IRI ， 疗。E-mail：sunguangping83@163.com MDA content in pancreatic tissue were all increased significantly（P＜0.05）. Compared with model group ，the general condition and OGTT of mice in each administration group was improved；the contents of FINS and HDL-C in serum as well as ISI ，the activities of SOD ，CAT and GSH-Px as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were all increased significantly （P＜0.05）；the contents of FBG，LDL-C，TC and TG in serum as well as IRI ，MDA content of pancreatic tissue were decreased significantly （P＜0.05）. CONCLUSIONS：PPLPs has anti-diabetic effects ，which are related to reducting oxidative stress level and promoting the activation of PI 3K/AKT/GLUT4 signaling pathway.
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With the improvement of people's living standard and the change of dietary structure, the prevalence of gout has increased gradually with the increased intake of protein, sugar and fat. There has been a positive correlation between gout and age, and the age of onset decreased gradually. The inflammation induced by sodium urate crystal is the pathological basis of gout, which activates innate immunity, releases many kinds of inflammatory mediators, such as interleukin(IL)-1β, IL-6 and tumor necrosis factor(TNF)-α, and then causes inflammatory cascade reaction and acute attacks, such as joint redness, swelling and heat pain. There is a spontaneous remission mechanism in gout. For one thing, macrophages reduce the stimulation of monosodium urate(MSU) through phagocytosis of MSU crystals as foreign bodies, for another, differentiated and mature macrophages secrete anti-inflammatory factor transforming growth factor(TGF)-β1, inhibit the expression of inflammatory factors and promote spontaneous relief of acute gout attack. In addition to the activation mechanism of intracellular signaling molecules associated with inflammatory response, the inflammatory mechanism of gout also involves complement activation, cell activation and other pathways. The complications caused by gout, such as cardiovascular system damage and joint destruction, are seriously harmful to human health. At present, western drugs, such as allopurinol and febuxostat, exert an effect in inhibiting xanthine oxidase. Benzimarone has effect in reducing renal absorption of uric acid and promoting uric acid excretion by inhibiting uric acid transporter 1(URAT1) and glucose transporter 9(GLUT9). Even Lesinurad and other medicines in current studies are based on the inhibition of uric acid re-absorption, but with adverse reactions that limit the clinical application. The treatment of gout with traditional Chinese medicine(TCM) has multi-target characteristics, with advantages in reducing uric acid, resisting inflammation and improving joint function and a high safety. It has been gradually popularized and applied in clinical treatment of gout. Therefore, it is a promising research direction to treat gout with TCM and western medicine based on the pathomechanism of gout.
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Glucose transporter type 1 deficiency syndrome is a rare neurometabolic disorder caused by mutations of the solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) gene,characterized by complex manifestations including early onset epilepsy,motor and mental retardation,and movement disorders and so on.Ketogenic-diet is most suitable therapy and should be commenced as early as possible because timing the initiation of the diet may prevent seizure,movement disorder,and cognitive impairment.This review aims to improve the clinicians' understanding of glucose transporter type 1 deficiency syndrome to ensure the diagnosis as early as possible.
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Glucose transporter type 1 deficiency syndrome is a rare neurometabolic disorder caused by mutations of the solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) gene, characterized by complex manifestations including early onset epilepsy, motor and mental retardation, and movement disorders and so on. Ketogenic-diet is most suitable therapy and should be commenced as early as possible because timing the initiation of the diet may prevent seizure, movement disorder, and cognitive impairment. This review aims to improve the clinicians′ understanding of glucose transporter type 1 deficiency syndrome to ensure the diagnosis as early as possible.
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Aim:The study evaluated the effects of the combined extracts of Vernonia amygdalina(VA) and Gongronema latifolium(GL) on pancreatic GLUT 2 expression and caspase 3 activity in streptozotocin (STZ, 45 mg/Kg)-induced diabetic rats.Study Design:Fifteen Albino rats were used for the study and were placed in 3 groups of 5 rats each: A -normal control, B –Diabetic control and C–experimental group.Place and Duration of Study:The study was carried out in the department of Anatomy, University of Calabar.Duration:6 months.Methodology:Half of the diabetic rats were treated with VA+GL (400mg/kg, ratio 1:1, DE group) for 28 days, while the other half was untreated and served as diabetic control (DC). Normal control (NC) rats were untreated. After 28 days, the rats were sacrificed and their blood glucose, serum GLUT 2 and caspase 3 activity were measured. Histochemical evaluation of the pancreas was also carried out.Results:Blood glucose concentrations for the 3 groups were 60.31±7.28, 257.00±4.43, and 116.60±10.11 mg/dl for NC, DC and DE respectively. This represented a 4-fold increase in the DC compared with NC and a significant amelioration in the extract-treated DE group compared with DC group. Serum GLUT 2 concentrations were 70 ng/ml in NC, dropped to 8 ng/ml (p<0.05) in the DC and recovered to 20ng/ml in DE (p<0.05). Serum caspase was 3.2 ng/ml for NC, increased to 8.5 ng/ml in DC (p<0.05) and reduced to 1.8ng/ml in DE (p<0.05). The histology of the pancreas showed distorted, degenerated and shrunken β-cells mass in DC compared with NC and DE groups. The DE group showed clear signs of regeneration of the islet cells which was corroborated by positive Feulgen’s reactioncompared with the DC group. Conclusion:The data suggests that the combined VA+GL extract has the potential to effectively reverse pancreatic damage in diabetes
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Trichomonas vaginalis (T. vaginalis), the etiologic agent of human trichomoniasis, is a flagellated protozoan parasite, has been associated sith advese pregnancy outcomes, HIV transmission, and infertilityh. A total of one hundred and fifty-seven (157) women at childbearing age (14-49 years), were included in the presnt study, eighty six (86) symptomatic fertile while the other seventy-one (71) were infertile with or without sumptoms attending the Gynecology outpatient Department in Al-Emamayn Al-Kadhimayn Medical City, the High Institute of Infertility Diagnosis and Assisted Reproductive Technoligies at Al-Nahrain University in Baghdad, the maternity Teaching hospital, and Dr. Khawer center for infertility and IVF in Erbil province in Iraq. Two vaginal swab specimens were obtained from each of them:; one swab was immediately examined by wet mount microscopy, the other swab for molecular study (DNA extraction and p3 nested PCR). One hundred (100) samples positive in one or more test were identified: 20 (12.7%) infecions were detected by wet mount microscopy, while nested PCR was positive in 100 (63.7%) samples. These positive samples were seguenced and phylogenetic tree were done and, there was no association between the variations in glut (p3) gene of T. vaginalis isolated from infected women (fertile and infertile)
Subject(s)
Humans , Female , Pregnancy , Adolescent , Adult , Pregnancy Complications/etiology , Specimen Handling/classification , Trichomonas Infections/etiology , Trichomonas vaginalis/genetics , Alleles , Fertility , Glutaminase/genetics , Infertility, FemaleABSTRACT
Objective: The study was designed to investigate the antitumor effect of Pulsatilla chinensis saponins components and the synergistic effect of its effect components on tumor glycolysis. Methods: NCI-H460 cell lines were cultured in vitro, MTT assay was used to detect the inhibitory rate of various components of Pulsatilla chinensis saponins. The compatibility and synergistic antitumor effect of different effect components were studied by Calcusyn 3.0 software. Biochemical assay and Elisa assay were used to detect the glycolysis related metabolites (pyruvate, lactic acid, and glucose) and enzymes (GLUT1, HK, PKM2, and LDHA). Energy metabolism related gene members from KEGG pathway database and key protein (ERK1/2, Ras, GLUT1, MCT4) were detected by qRT-PCR and Western blotting. Results: The antitumor results in vitro showed that PSD, R13 and PSA in Pulsatilla chinensis saponins had the strongest antitumor activity for human lung cancer NCI-H460 cells and the IC50 were 5.2, 4.6, and 7.9 μg/mL, respectively. Using Calcusyn 3.0 software to confirm the distribution ratio of three effective monomers in Pulsatilla chinensis saponins and determine the synergistic antitumor effect after compatibility. The results of biochemical and Elisa assay showed that the content of pyruvate, lacate, glucose, HK, PKM2 and LDHA were significantly decreased and the GLUT1 content was significantly increased compared with the blank group (P < 0.05),; Compared with each monomer group, the content of pyruvic acid, lactic acid, glucose, HK, PKM2 and LDHA in the combined group were significantly decreased and the content of GLUT1 was significantly increased (P < 0.05). Real-time PCR results show that the combinations group has the most nodes in the network diagram, and its target was more than each monomer group. Western blotting results showed that compared with the blank group, the combinations group significantly decreased the expression of ERK1/2, Ras, GLUT1, and MCT4 protein (P < 0.05). Conclusion: The combination of effect components of Pulsatilla chinensis saponins has synergistic antitumor effect on NCI-H460 cells and the antitumor mechanism may be associated with the regulation of glycolysis.
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GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.