Objective To review the application advancements of ATP-binding cassette (ABC) transporter in medical research.Methods Relevant literatures about the applications of ABC families in medical research were reviewed. Results ABC families mainly took roles in transporting substances across cell membrane. Some of them were useful for the prediction of drug resistance and the prognosis of malignant tumors. Others were target s for molecular researches. Their expressions or mutations might be related with the occurrence of diseases. Conclusion ABC families are very important in the diagnosis and therapy for diseases. Thus they are very promising tools for future medical research.
Pulmonary arterial hypertension (PAH) is a severe, progressive disease leading to right ventricular failure and finally death. Lung transplantation is recommended for PAH patients who do not respond to targeted drug combination therapy or World Health Organization functional class (WHO FC) Ⅲ or Ⅳ. However, only 3% of PAH patients can recieve the lung transplantation. A novel implantable interatrial shunt device (ISD) can create a relatively fixed right-to-left shunt established by balloon atrial septostomy (BAS). The device may decompress the right sided chambers, facilitate left heart filling, improve organ perfusion and reduce the likelihood of syncope, acute pulmonary hypertensive crisis and death. The systemic oxygen transport improves despite hypoxemia. Implantation is simple, feasible and safe, and the X-ray time and operation time are short. There is no severe complication or thrombosis during the mid-term follow-up of the clinical studies and the device remained patent. The syncope symptoms, six-minute walk distance, cardiac index and systemic oxygen transport improve significantly in the patients. ISD may be currently the last alternative treatment to improve symptoms and prolong survival in currently drug-resistant patients with severe PAH.
Objective To investigate the disease-causing gene of Stargardt disease. Method Fifteen patients with Stargardt disease were analyzed with 11 primers of the 11 exons of ABCR gene by using PCR-SSCP and DNA direct sequencing techniques. Results Three newly detected disease-causing mutations were found. Among those mutations, one is a frameshift mutation and others are single base transition. Conclusion This research confirmed that ABCR gene is associated with Stargardt disease, and 3 new mutations of ABCR gene were found. (Chin J Ocul Fundus Dis,2000,16:240-243)
Objective To systematically review the efficacy and safety of different SGLT2 inhibitors in the treatment of heart failure. Methods The Cochrane Library, Web of Science, PubMed and EMbase databases were searched for randomized controlled trials on the efficacy and safety of SGLT2 inhibitors in patients with heart failure from inception to July 2, 2021. Two researchers independently screened literature, extracted data and evaluated the risk of bias of the included studies. Network meta-analysis was then performed using Stata 16.0 software. Results A total of 16 randomized controlled trials, including 15 312 patients, involving 5 interventions, namely dapagliflozin, empagliflozin, canagliflozin, sotagliflozin and ertugliflozin were included. Results of network meta-analysis showed that there was no significant difference in the compound outcome of hospitalization for heart failure or cardiovascular death, hospitalization for heart failure, all-cause mortality, risk of cardiovascular mortality and serious adverse reactions among patients with heart failure among 5 different SGLT2 inhibitors (P>0.05). Compared with placebo, both selective and non-selective SGLT2 inhibitors improved the risk of hospitalization for heart failure, hospitalization for heart failure, or compound cardiovascular mortality (P<0.05), while only selective SGLT2 inhibitors improved the risk of cardiovascular mortality, all-cause mortality, and serious adverse events (P<0.05). However, there was no significant difference between them (P>0.05). The area under the cumulative ordering probability curve of selective and non-selective SGLT2 inhibitors ranked first and second, except for the combined outcome of heart failure or cardiovascular death. Conclusion The current evidence indicates that there is no significant difference in the efficacy and safety of the 5 different SGLT2 inhibitors in the treatment of heart failure, and there is no significant difference between selective SGLT2 inhibitors and non-selective SGLT2 inhibitors. Due to the limited quantity and quality of included studies, more high-quality studies are needed to verify the above conclusion.
ObjectiveTo study the effects of Ghrelin for glucose metabolism and insulin sensitivity of L6 rat myoblasts in palmitic acid induced, and to explore its possible mechanisms. MethodsThe L6 rat myoblasts were cultured until differentiation, then using palmitic acid(0.3 mmol/L) for 16 hours. The experimental group was treated with different doses of Ghrelin(1, 10, and 100 nmol/L) for 8 hours, then the glucose uptake was detected by using glucose oxidase peroxidase method(GOD-POD), the cell membrane glucose transporter 4(GLUT-4) protein staining was observated under confocal microscopy, and the expressions of total protein kinase B(Akt), phosphorylated protein kinase B(pAkt), total glycogen synthase kinase-3β(GSK-3β), and phosphorylated glycogen synthase kinase-3β(pGSK-3β) were detected by using immunoblotting(Western blot). ResultsGhrelin enhanced the glucose uptake of L6 rat myoblasts with insulin resistance, the cell membrane Glut-4 stain was deepen, the expressions of pAkt and pGSK-3βprotein increased, and this effect could be PI3K blocker(LY294002) eliminated. ConclusionGhrelin promotes the glucose uptake of L6 rat myoblasts through PI3K/Akt/GSK-3βsignaling pathway, so as to improve the sensitivity of insulin in L6 rats muscle cells.
Sodium-glucose cotransporter (SGLT) -2 inhibitors is a new type of oral sugar-lowering drug. Instead of relying on insulin, it lowers blood sugar by inhibiting the reabsorption of near-curvy tube glucose, which is drained from the urine. SGLT-2 inhibitors not only have a sugar-lowering effect, but also benefit significantly in cardiovascular disease, and this drug has the advantages of permeable diuretic, reducing capacity load, and improving ventricular remodeling. SGLT-2 inhibitors can improve the diastolic function of patients with heart failure with preserved ejection fraction (HFpEF) and reduce the risk of adverse cardiovascular events. SGLT-2 inhibitors can benefit patients with HFpEF. Therefore, this article will discuss the progress of SGLT-2 inhibitors in HFpEF.
Objective To observe the different effect such as high concentration of glucose and high concentration of insulin on GLUT1 of Rabbit Retinal Muuml;ller Cell in vitro. Methods Rabbit retinal Muuml;ller cells were cultured in vitro with suspended constitution，which were divided as the following groups: common control group，high glucose group，insulin group，high glucose combined insulin group. Laser confocal microscope combined with immunocytochemical and fluorescence staining method to quantitatively analyze the expression condition of GLUT1. Results The expression of GLUT1 has been enhanced obviously by high glucose and high insulin，which locates mainly in the cytoplasm that near to the nucleus. Conclusion Rabbit retinal Muuml;ller cells can express GLUT1，and the expression of GLUT1 can be reinforced by high glucose and high insulin. （Chin J Ocul Fundus Dis，2008，24：265-267）
ObjectiveTo investigate the effect of expressions of nucleoside transporters subtype (hENT1 and hENT2) on 5-fluorouracil(5-FU) cytotoxicity in breast cancer cell lines(MDA-MB-231, MDA-MB-468, SK-BR-3, MCF-7). MethodsFour breast cancer cell lines were chosen to detect the mRNA expressions of hENT1 and hENT2 by RT-PCR. Cells were incubated in the medium with a serial concentrations of 5-FU from 1.28×104 ng/L to 2.00×108 ng/L for 48 h. Then the cell proliferation in each cell line was measured by MTT assay and the IC50 was evaluated. Results①The mRNA expressions of hENT1 and hENT2 in the MDA-MB-231, MDA-MB-468, or SK-BR-3 cells were significantly higher than thoes in the MCF-7 cells(P < 0.05). The mRNA expression of hENT2 was detected in the MDA-MB-231, MDA-MB-468, or SK-BR-3 cells, not detected in the MCF-7 cells. 2MTT showed that IC50 of 5-FU in the MDAMB-231, MDA-MB-468, or SK-BR-3 cells was significantly lower than that in the MCF-7 cells(P < 0.05). There was no statistical difference of IC50 among the three lines(MDA-MB-231, MDA-MB-468, and SK-BR-3)(P > 0.05).③The three lines(MDA-MB-231, MDA-MB-468, and SK-BR-3) with lower IC50 of 5-FU highly expressed hENTs, and MCF-7 cell with the higher IC50 of 5-FU expressed less hENTs. ConclusionsThe expressions of hENTs in breast cancer cell lines can significantly influence 5-FU cytotoxic effect. It is implicated that the hENTs expressions might be the clue to the choice of nucleoside anticancer drugs in clinic.
ObjectiveTo summarize the effectiveness and experience of Wanger grade 3-5 diabetic foot treated with vacuum sealing drainage (VSD) combined with transverse tibial bone transport.MethodsBetween March 2015 and January 2018, 21 patients with refractory diabetic foot who failed conservative treatment were treated with VSD combined with transverse tibial bone transport. There were 15 males and 6 females, aged 55-88 years (mean, 65 years). The diabetes history was 8-15 years (mean, 12.2 years). The duration of diabetic foot ranged from 7 to 84 days (mean, 35.3 days). The size of diabetic foot ulcer before operation ranged from 2 cm×2 cm to 8 cm×5 cm. According to Wanger classification, 8 cases were rated as grade 3, 11 cases as grade 4, and 2 cases as grade 5. Among the 21 cases, angiography of lower extremity before operation was performed in 5 cases, CT angiography of lower extremity in 16 cases, all of which indicated that the arteries below the knee were narrowed to varying degrees and not completely blocked. Preoperative foot skin temperature was (29.28±0.77)℃, C-reactive protein was (38.03±31.23) mg/L, leukocyte count was (9.44±2.21)×109/L, and the visual analogue scale (VAS) score was 6.8±1.5, and ability of daily living (Barthel index) was 54.3±10.3.ResultsAfter operation, 2 patients with Wanger grade 4 and smoking history failed treatment and had an major amputation (amputation above ankle joint) at 30 days and 45 days after operation, respectively. One patient with Wanger grade 5 and chronic heart failure died of cardiac arrest at 60 days after operation. The remaining 18 patients were followed up 6-24 months (mean, 9.2 months). The external fixator was removed at 40-62 days after operation, with an average of 46 days. All the wounds healed, with a healing time of 50-120 days (mean, 62.5 days). The pain of 18 patients’ feet was relieved obviously, and there was no recurrence of ulcer in situ or other parts. There was no complication such as tibial fracture and ischemic necrosis of lower leg skin after operation. After ulcer healing, the foot skin temperature was (30.86±0.80)℃, C-reactive protein was (22.90±18.42) mg/L, VAS score was 2.4±1.2, and Barthel index was 77.3±4.6, all showing significant differences when compared with preoperative ones (P<0.05); the leukocyte count was (8.91±1.72)×109/L, showing no significant difference (t=1.090, P=0.291).ConclusionVSD combined with transverse tibial bone transport can effectively promote the healing of Wanger grade 3-5 diabetic foot wounds, but smokers, unstable blood glucose control, and chronic heart failure patients have the risk of failure.
Objective To investigate the clinical significance of the three iodide transporters in thyroid diseases. Methods Literatures about the Na+/I- symporter (NIS), pendrin and human apical iodide transporter (hAIT) in recent years were reviewed and their expressions in different thyroid diseases were also analyzed. Results NIS proteins express at the basolateral membrane of thyrocytes in normal thyroid tissue, while pendrin and hAIT proteins are limited to the apical membrane of thyrocytes lining in the follicular lumen. In the tissues of thyroid carcinomas, it was found that the NIS proteins expressed in the cytoplasm and their expressions decreased; The mutation of NIS gene may be one of the main causes of congenital hypothyroidism. The expression of prendrin protein may be related to the function of follicles: its expression level increased significantly both in Graves diseases and toxic adenomas, but significantly decreased in differentiated thyroid carcinoma. However, the correlation between the decrease and the degrees of differentiation of carcinoma cell line are still disputable. The expression of hAIT protein does not significantly altered in hyperfunctioning tissues. It only slightly decreased occasionally in hypofunctioning adenomas, but it decreased significantly in thyroid carcinomas. Conclusion The abnormal expressions of the three iodide transporters may be related closely with the type of thyroid diseases. However, their pathogenic mechanisms and the causes of their abnormal expression are still unknown, which need to be studied further.