Unleashing the potential of tungsten disulfide: Current trends in biosensing and nanomedicine applications.

The discovery of graphene ignites a great deal of interest in the research and advancement of two-dimensional (2D) layered materials. Within it, semiconducting transition metal dichalcogenides (TMDCs) are highly regarded due to their exceptional electrical and optoelectronic properties. Tungsten disulfide (WS2) is a TMDC with intriguing properties, such as biocompatibility, tunable bandgap, and outstanding photoelectric characteristics. These features make it a potential candidate for chemical sensing, biosensing, and tumor therapy. Despite the numerous reviews on the synthesis and application of TMDCs in the biomedical field, no comprehensive study still summarizes and unifies the research trends of WS2 from synthesis to biomedical applications. Therefore, this review aims to present a complete and thorough analysis of the current research trends in WS2 across several biomedical domains, including biosensing and nanomedicine, covering antibacterial applications, tissue engineering, drug delivery, and anticancer treatments. Finally, this review also discusses the potential opportunities and obstacles associated with WS2 to deliver a new outlook for advancing its progress in biomedical research.

What Affects Vocational Teachers' Acceptance and Use of ICT in Teaching? A Large-Scale Survey of Higher Vocational College Teachers in China.

This study aimed to explore what factors affect teachers' acceptance and instructional use of ICT in Chinese higher vocational colleges. Grounded in the modified UTAUT model, the current study investigated the direct and indirect effects of teachers' performance expectancy, effort expectancy, external conditions, and behavioral intentions on using ICT in teaching. A total of 6087 teachers from 219 vocational colleges in 28 provinces in China participated in a large-scale survey. Structural equation modeling revealed that the teachers' psychological perceptions (including performance expectancy, effort expectancy, and intention to use ICT technology) and the external support conditions (including professional development support, infrastructures, the climate of organizational reform and innovation, and teacher performance assessment mechanisms) significantly directly affect the use of ICT in Chinese higher vocational college teachers' teaching practice. Moreover, this study confirmed the mediating role of teachers' intention to use ICT in teaching in the relationship between teachers' psychological perceptions and ICT instructional usage behavior. However, there were differences in the significance of these variables in the chain effect of teachers' intention to use ICT. These findings expand our understanding of the factors influencing ICT use in teaching among VET teachers in China, thus providing practical implications for higher vocational college managers to promote teachers' ICT teaching behaviors.

Reversible domain closure modulates GlnBP ligand binding affinity.

Glutamine binding protein (GlnBP) is an Escherichia Coli periplasmic binding protein, which binds and carries glutamine to the inner membrane ATP-binding cassette (ABC) transporter. GlnBP binds the ligand with affinity around 0.1µM measured by isothermal titration calorimetry (ITC) and ligand binding stabilizes protein structure shown by its increase in thermodynamic stability. However, the molecular determinant of GlnBP ligand binding is not known. Electrostatic and hydrophobic interaction between GlnBP and glutamine are critical factors. We propose that the freedome of closure movement is also vital for ligand binding. In order to approve this hypothesis, we generate a series of mutants with different linker length that has different magnitude of domain closure. Mutants show different ligand binding affinity, which indicates that the propensity of domain closure determines the ligand binding affinity. Ligand binding triggers gradual ensemble conformational change. Structural changes upon ligand binding are monitored by combination of small angle x-ray scattering (SAXS) and NMR spectroscopy. Detailed structure characterization of GlnBP contributes to a better understanding of ligand binding and provides the structural basis for biosensor design.

Coronary Anomalies in 11,267 Southwest Chinese Patients Determined by Angiography.

BACKGROUND: The prevalence of coronary artery anomalies (CAAs) is rare and varies among different countries or areas. More importantly, the symptoms exhibited by some CAAs make the diagnosis of coronary artery disease (CAD) difficult and hamper the physician from making the right intervention for CAD patients. OBJECTIVE: To investigate the prevalence of CAAs in 11,267 patients from three hospitals in Southwest China. METHODS: 11,267 patients who have undergone coronary angiography from three Southwest China hospitals were investigated retrospectively. Dominance patterns, prevalence, and the location of each CAA were recorded and analyzed. RESULTS: The presence of a dominant right coronary artery (RCA) was found in 60.58% of patients. CAAs were found in 11.12% (1258) patients, and 87.66% anomalies were located in the left anterior descending (LAD) artery and its branches. Most of CAAs were found to be myocardial bridges (MBs, 1060 cases, 9.41%). Other CAAs included anomalous coronary origin (43 cases, 0.38%), coronary artery fistulas (CAFs, 36 cases, 0.32%), and coronary artery aneurysm or ectasia (119 cases, 1.06%). It also noted that most anomalies were found with RCA originating from the left coronary sinus (79.07%), most CAFs were located in the LAD and its branches (58.33%), and most coronary artery ectasias were located in the RCA (43.25%). CONCLUSIONS: CAAs in patients from Southwest China were unique compared to other studies. Recognition of these CAAs is important for accurate diagnosis and treatment choice of patients with chest pain.

Current and Perspective Diagnostic Techniques for COVID-19.

Since late December 2019, the coronavirus pandemic (COVID-19; previously known as 2019-nCoV) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been surging rapidly around the world. With more than 1,700,000 confirmed cases, the world faces an unprecedented economic, social, and health impact. The early, rapid, sensitive, and accurate diagnosis of viral infection provides rapid responses for public health surveillance, prevention, and control of contagious diffusion. More than 30% of the confirmed cases are asymptomatic, and the high false-negative rate (FNR) of a single assay requires the development of novel diagnostic techniques, combinative approaches, sampling from different locations, and consecutive detection. The recurrence of discharged patients indicates the need for long-term monitoring and tracking. Diagnostic and therapeutic methods are evolving with a deeper understanding of virus pathology and the potential for relapse. In this Review, a comprehensive summary and comparison of different SARS-CoV-2 diagnostic methods are provided for researchers and clinicians to develop appropriate strategies for the timely and effective detection of SARS-CoV-2. The survey of current biosensors and diagnostic devices for viral nucleic acids, proteins, and particles and chest tomography will provide insight into the development of novel perspective techniques for the diagnosis of COVID-19.

The characteristics of coronary stenosis in 11,267 patients from Southwest China: a retrospective study.

The characteristics of coronary stenosis vary among the different countries or areas. 11,267 patients who have undergone coronary angiography (CAG) from three Southwest China hospitals were investigated. Patient characteristics, coronary stenosis and stent-implant information were recorded and analyzed according to two criteria: "visible stenosis" and "≥ 50% stenosis". The patients who have undergone CAG increased year by year, with patients from 60 to 69 years-old taking the highest ratio (34.69%). Based on the "≥ 50% stenosis" criteria, the stenotic frequency was 40.54% for Southwest China patients getting CAG. Only 8.14% patients suffered ≥ 3 stenotic vessels, while 11.58 and 20.82% patients had 2 or 1 stenotic vessel, respectively. However, when using the "visible stenosis" criteria, the stenotic frequency increased to 64.68%. The prevalence of stenosis increased with age based on the "visible stenosis" criteria. There were more male patients with stenosis than female except patients over 80 years old. The stenosis affected almost all main coronary arteries and their branches, with the most affected artery being the left anterior descending artery. There were 3246 cases (28.8%) implanted with 5423 stents with a concurrent age-dependent increasing tendency for stent-implant frequency and average implanted stent number. The numbers of patients who have undergone CAG and suffered from CVD increased rapidly. In these patients, positive rate of CAG was 64.67%, which increased to 72.2% in patients over 60-years old. The incidence of ≥ 75% stenosis and multiple stenosis increased with age, however it should be noticed there were 18.93% for ≥ 75% stenosis and 19.52% for multiple stenosis in patients under 40 years old.

Efficacy and indications of transradial and transfemoral approaches for peripheral artery stent implantation.

The transradial approach (TRA) has become an attractive alternative to the transfemoral approach (TFA) in percutaneous coronary intervention. To date, however, these two approaches have not been systematically compared in various percutaneous peripheral artery interventions (PPAIs). In the present study 258 patients with peripheral artery disease that underwent PPAI via the TRA (n=75) or the TFA (n=183) were analyzed. Clinical factors and outcomes in these two groups were compared. The puncture time was significantly longer (P<0.05) and the prevalence of artery vasospasm significantly higher (P<0.05) in patients who underwent PPAI via the TRA rather than via the TFA. However, the complication rate was significantly lower (P<0.05) and the artery compression time (P<0.05) and time bedridden (P<0.05) were significantly shorter via the TRA than via the TFA. These results suggest that PPAI via the TRA was associated with a lower complication rate, and shorter artery compression time and bedridden time than PPAI via the TFA. The TRA may be preferable for bilateral vertebral artery stenosis, whereas the TFA may be preferable for interventional treatment of carotid and subclavian artery stenosis. Therefore, the catheter length, artery support and push force should be comprehensively considered before choosing the TRA or TFA in the interventional treatment of renal artery stenosis.

Noninvasive measurement of cardiac output during 6-minute walk test by inert gas rebreathing to evaluate heart failure.

OBJECTIVE: The objective of this study was to assess the clinical value of cardiac output (CO) measurements using the inert gas rebreathing (IGR) method during the 6-minute walk test (6MWT) in evaluation of chronic heart failure (CHF). METHODS AND RESULTS: A total of 56 CHF patients in our hospital who conformed to the Framingham CHF diagnostic criteria were recruited to this study from October 2007 to February 2009. Subjects were asked to complete a 6MWT and a bicycle exercise test. The CO was measured during both tests using IGR. B-type natriuretic peptide (BNP) levels and the left ventricular ejection fraction (LVEF) were measured at rest. The 6MWT did not correlate with BNP, LVEF, peak cardiac output (PCO), or CO during the 6MWT (CO6MWT). A negative correlation between CO6MWT and BNP as well as a strong correlation between CO6MWT and PCO was observed. When atrial fibrillation and valvular heart disease patients were excluded, CO6MWT and LVEF became significantly correlated. After grouping patients into tertiles according to their PCO values, the PCO remained correlated with CO6MWT within each group. The mean difference between CO6MWT and PCO decreased with decreases in the mean PCO in each group. No significant differences were found in the third tertile (PCO < 10.1 L/min). CONCLUSIONS: The IGR method during 6MWT is safe and reliable to evaluate cardiac function in patients with CHF.

Induced pluripotent stem cells alleviate lung injury from mesenteric ischemia-reperfusion.

BACKGROUND: Mesenteric ischemia-reperfusion (I/R) injury is a serious pathophysiologic process that can trigger the development of multiorgan dysfunction. Acute lung injury is a major cause of death among mesenteric I/R patients, as current treatments remain inadequate. Stem cell-based therapies are considered novel strategies for treating several devastating and incurable diseases. This study examined whether induced pluripotent stem cells (iPSCs) lacking c-myc (i.e., induced using only the three genes oct4, sox2, and klf4) can protect against acute lung injury in a mesenteric I/R mouse model. METHODS: C57BL/6 mice were randomly divided into the following groups: sham/no treatment, vehicle treatment with phosphate-buffered saline, treatment with iPSCs, and treatment with iPSC-conditioned medium. The mice were subjected to mesenteric ischemia for 45 minutes followed by reperfusion for 24 hours. After I/R, the lungs and the ileum of the mice were harvested. Lung injury was evaluated by histology, immunohistochemistry, and analyses of the levels of inflammatory cytokines, cleaved caspase 3, and 4-hydroxynonenal. RESULTS: The intravenously delivered iPSCs engrafted to the lungs and the ileum in response to mesenteric I/R injury. Compared with the phosphate-buffered saline-treated group, the iPSC-treated group displayed a decreased intensity of acute lung injury 24 hours after mesenteric I/R. iPSC transplantation significantly reduced the expression of proinflammatory cytokines, oxidative stress markers, and apoptotic factors in injured lung tissue and remarkably enhanced endogenous alveolar cell proliferation. iPSC-conditioned medium treatment exerted a partial effect compared with iPSC treatment. CONCLUSION: When considering the anti-inflammatory, antioxidant, and antiapoptotic properties of iPSCs, the transplantation of iPSCs may represent an effective treatment option for mesenteric I/R-induced acute lung injury.

Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells.

Genistein is one of the most studied isoflavonoids with potential antitumor efficacy, but its poor water solubility limits its clinical application. Nanoparticles (NPs), especially biodegradable NPs, entrapping hydrophobic drugs have promising applications to improve the water solubility of hydrophobic drugs. In this work, TPGS-b-PCL copolymer was synthesized from ε-caprolactone initiated by d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) through ring-opening polymerization and characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, and thermogravimetric analysis. The genistein-loaded NPs were prepared by a modified nanoprecipitation method and characterized in the aspects of particle size, surface charge, morphology, drug loading and encapsulation efficiency, in vitro drug release, and physical state of the entrapped drug. The TPGS-b-PCL NPs were found to have higher cellular uptake efficiency than PCL NPs. MTT and colony formation experiments indicated that genistein-loaded TPGS-b-PCL NPs achieved the highest level of cytotoxicity and tumor cell growth inhibition compared with pristine genistein and genistein-loaded PCL NPs. Furthermore, compared with pristine genistein and genistein-loaded PCL NPs, the genistein-loaded TPGS-b-PCL NPs at the same dose were more effective in inhibiting tumor growth in the subcutaneous HeLa xenograft tumor model in BALB/c nude mice. In conclusion, the results suggested that genistein-loaded biodegradable TPGS-b-PCL nanoparticles could enhance the anticancer effect of genistein both in vitro and in vivo, and may serve as a potential candidate in treating cervical cancer.

Renal denervation using catheter-based radiofrequency ablation with temperature control: renovascular safety profile and underlying mechanisms in a hypertensive canine model.

OBJECTIVE: Renal denervation is a novel method for hypertension treatment. In this study, we aimed to investigate the safety and efficacy of radiofrequency ablation (RFA) at ablation temperatures of 45 °C or 50 °C and its possible mechanisms. METHODS: A hypertensive canine model was established by abdominal aortic constriction in 20 healthy hybrid dogs. These dogs were then randomly assigned to the treatment and the control groups, with dogs in the treatment group further randomly assigned to receive RFA at ablation temperatures of 45 °C or 50 °C. In the treatment group, RFA was performed at 1 month after modeling; renal angiography was performed at 2 months after ablation. The arterial vessels of the dogs were examined histologically with hematoxylin and eosin staining. Changes in blood pressure in the foreleg and whole-body norepinephrine spillover rate were also assessed. RESULTS: No arterial stenosis, dissection, thrombosis or other abnormalities were detected in the treated vessels by renal angiography, yet histology results showed minimal to mild renal arterial injury. Renal denervation resulted in a marked decrease in the whole-body norepinephrine spillover rate (p < 0.05) in addition to significantly reducing blood pressure (p < 0.05), with no significant differences detected between the 45 °C and 50 °C subgroups for both (p > 0.05). CONCLUSION: Renal denervation can be performed without acute major adverse events, using catheter-based RFA with temperature control. The procedure was feasible in reducing blood pressure by at least partially inhibiting sympathetic drive and systemic sympathetic outflow.

Age, estimated glomerular filtration rate and ejection fraction score predicts contrast-induced acute kidney injury in patients with diabetes and chronic kidney disease: insight from the TRACK-D study.

BACKGROUND: The occurrence of contrast induced acute kidney injury (CIAKI) has a pronounced impact on morbidity and mortality. The aim of the present study was to appraise the diagnostic efficacy of age, estimated glomerular filtration rate (eGFR) and ejection fraction (AGEF) score (age/EF(%)+1 (if eGFR was <60 ml × min(-1)× 1.73 m(-2))) as an predictor of CIAKI in patients with diabetes mellitus (DM) and concomitant chronic kidney disease (CKD). METHODS: The AGEF score was calculated for 2 998 patients with type 2 DM and concomitant CKD who had undergone coronary/peripheral arterial angiography. CIAKI was defined as an increase in sCr concentration of 0.5 mg/dl (44.2 mmol/L) or 25% above baseline at 72 hours after exposure to the contrast medium. Post hoc analysis was performed by stratifying the rate of CIAKI according to AGEF score tertiles. The diagnostic efficacy of the AGEF score for predicting CIAKI was evaluated with receiver operating characteristic (ROC) analysis. RESULTS: The AGEF score ranged from 0.49 to 3.09. The AGEF score tertiles were defined as follows: AGEFlow ≤ 0.92 (n = 1 006); 0.92 1.16 (n = 992). The incidence of CIAKI was significantly different in patients with low, middle and high AGEF scores (AGEFlow = 1.1%, AGEFmid = 2.3% and AGEFhigh = 5.8%, P < 0.001). By multivariate analysis, AGEF score was an independent predictor of CIAKI (odds ratio = 4.96, 95% CI: 2.32-10.58, P < 0.01). ROC analysis showed that the area under the curve was 0.70 (95% CI: 0.648-0.753, P < 0.001). CONCLUSION: The AGEF score is effective for stratifying risk of CIAKI in patients with DM and CKD undergoing coronary/peripheral arterial angiography. (Clinical Trial identifier: NCT00786136).

Successful transcatheter patent ductus arteriosus occluder embolization of a congenital left coronary artery aneurysm and fistulas draining into the right atrium.

Coronary artery aneurysms and fistulas are very rare congenital anomalies. They occur in 0.2%-0.4% of all congenital heart diseases. In this article, we report a case of a 39-year-old girl with a left coronary artery aneurysm and fistula draining into the right atrium. An intervention is successfully achieved by transcatheter occluder embolization using a patent ductus arteriosus (PDA) occluder.

Fixed-combination of amlodipine and diuretic chronotherapy in the treatment of essential hypertension: improved blood pressure control with bedtime dosing-a multicenter, open-label randomized study.

Previous studies have demonstrated that individual anti-hypertension medications have different effects when administered in the morning vs. the evening. However, the impact of administration timing on fixed combinations of anti-hypertensive medications on blood pressure control is still unknown. In the present study, we examined the administration time-dependent effects of a fixed combination of amlodipine and diuretics (amlodipine complex) on blood pressure in hypertensive subjects. Eighty patients from Chongqing City were enrolled in this study. Subjects were randomly assigned to receive a single pill (amlodipine complex, each tablet containing amlodipine 5 mg and hydrochlorothiazide 25 mg), either in the morning (0800 hours, n=40) or at bedtime (2200 hours, n=40). Blood pressure was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 24 consecutive hours before and after the 12 weeks of treatment. Following treatment, the 24-h mean systolic and diastolic blood pressures were reduced significantly in both the morning and bedtime groups. However, the morning blood pressure surge was reduced to a greater degree in the bedtime group. In addition, the nocturnal blood pressure and the 24 h mean blood pressure were lower in the bedtime group. More patients converted from having a non-dipper to dipper blood pressure in the bedtime group. These findings confirm that amlodipine complexes have different efficiencies depending on treatment time. Administration of amlodipine complexes at bedtime could optimize the anti-hypertensive effect by augmenting blood pressure-lowering effects, increasing the diurnal/nocturnal ratio of blood pressure, normalizing the blood pressure pattern and minimizing the morning blood pressure surge.

Feasibility and application of single 5F multipurpose catheter in coronary and peripheral angiography via a transradial approach.

OBJECTIVE: Atherosclerosis is a systemic disease, in which coronary and peripheral angiographies are required to be done at the same time in a large number of patients. To shorten the procedure time, and reduce complications, we tested the feasibility and the safety of using a single 5F multipurpose catheter, via transradial approach, for coronary, cerebral and renal angiographies. METHODS: One thousand and ninety-two patients were enrolled in the study. The procedure time, local vessel complications, duration of hospitalization, and costs were evaluated. RESULTS: Among 1092 patients, the radial artery puncture was successful in 1081 patients, a successful coronary angiography via the radial artery was done in 1074 patients, and the remaining 18 patients had to be accessed via the femoral artery. Thus, successful angiography rate was 97.7% for the right coronary artery, 95.8% for the left coronary artery, 100% for the right cerebral artery, 95.2% for the left subclavian artery, 96.1% for the left carotid artery and 83.1% for the renal artery. The failures were caused by abnormal curvature of the aortic arch and abnormal origins of the above-mentioned arteries. There were 1460 artery stenosis lesions found in 661 patients and 624 lesions (93.3%) needed stents via the transradial approach. The mean procedure time was 20.9 ± 9.3 min including puncture, angiography and hemostasis time. There were 4.35% complications. No local hematoma, hand ischemia, or cerebral infraction was found in this study. CONCLUSION: Angiography using a single 5F multipurpose catheter, via transradial approach, is associated with a short procedure time and a low rate of complications without affecting the angiography success rate.

[Effects of lipid-modulation and antiplatelet treatment on the endothelial lipase expression].

OBJECTIVE: To investigate the effects of lipid-modulation and antiplatelet treatment on the expression of endothelial lipase (EL) of patients with coronary artery disease (CAD), and investigate the role of EL in the development of CAD. METHODS: One hundred and fifty-seven cases were divided into three groups according to clinical manifestations and the results of coronary artery angiography: control group (n=41) with more than one risk factors of CAD and the vessel lesions was <30%; stable angina pectoris (SAP) group (n=55); acute coronary syndrome (ACS) group (n=61). The EL positive cell rate was measured 2 weeks after cessation of lipid-modulation and aspirin treatment, and 6 months after treatment with simvastatin and/or aspirin. The drug was ceased for the complications or not tolerance for the treatment. RESULTS: Except the patients in control group with aspirin treatment, the EL positive cell rate was significantly decreased among other groups [control group with simvastatin: (3.93±0.87)% vs. (5.28±1.05)%, SAP group: (8.16±2.11)% vs. (15.12±2.53)%, ACS group: (13.93±3.22)% vs. (38.44±4.36)%; SAP group with aspirin: (10.57±4.07)% vs. (14.66±2.29)%, ACS group: (18.28±5.14)% vs. (40.27±3.96)%; control group with aspirin and simvastatin: (3.13±0.87)% vs. (5.33±1.25)%, SAP group: (5.68±2.20)% vs. (14.89±2.15)%, ACS group: (7.81±3.96)% vs. (39.27±5.17)%, P<0.05 or P<0.01]. CONCLUSION: The treatment with lipid-modulation and/or antiplatelet drug may significantly decrease the expression of EL, implying that EL participates in the progression of CAD.

Inhibitory effect of ETB receptor on Na(+)-K(+) ATPase activity by extracellular Ca(2+) entry and Ca(2+) release from the endoplasmic reticulum in renal proximal tubule cells.

The kidney is important in the long-term regulation of blood pressure and sodium homeostasis. Stimulation of ETB receptors in the kidney increases sodium excretion, in part, by decreasing sodium transport in the medullary thick ascending limb of Henle and in collecting duct. However, the role of ETB receptor on Na(+)-K(+) ATPase activity in renal proximal tubule (RPT) cells is not well defined. The purpose of this study is to test the hypothesis that ETB receptor inhibits Na(+)-K(+) ATPase activity in rat RPT cells, and investigate the mechanism(s) by which such an action is produced. In RPT cells from Wistar-Kyoto rats, stimulation of ETB receptors by the ETB receptor agonist, BQ3020, decreased Na(+)-K(+) ATPase activity, determined by ATP hydrolysis (control=0.38+/-0.02, BQ3020=0.26+/-0.03, BQ788=0.40+/-0.06, BQ3020+BQ788=0.37+/-0.04, n=5, P<0.01). The ETB receptor-mediated inhibition of Na(+)-K(+) ATPase activity was dependent on an increase in intracellular calcium, because this effect was abrogated by a chelator of intracellular-free calcium (BAPTA-AM; 5 x 10(-3) M 15 min(-1)), Ca(2+) channel blocker (10(-6) M 15 min(-1) nicardipine) and PI3 kinase inhibitor (10(-7) M per wortmannin). An inositol 1,4,5-trisphosphate (IP3) receptor blocker (2-aminoethyl diphenyl borate; 10(-4) M 15 min(-1)) also blocked the inhibitory effect of the ETB receptor on Na(+)-K(+)ATPase activity (control=0.39+/-0.06, BQ3020=0.25+/-0.01, 2-APB=0.35+/-0.05, BQ3020+ 2-APB=0.35+/-0.06, n=4, P<0.01). The calcium channel agonist (BAY-K8644; 10(-6) M 15 min(-1)) inhibited Na(+)-K(+) ATPase activity, an effect that was blocked by a phosphatidylinositol-3 kinase inhibitor (10(-7) M 15 min(-1) wortmannin). In rat RPT cells, activation of the ETB receptor inhibits Na(+)-K(+) ATPase activity by facilitating extracellular Ca(2+) entry and Ca(2+) release from endoplasmic reticulum.

D3 dopamine receptor regulation of ETB receptors in renal proximal tubule cells from WKY and SHRs.

BACKGROUND: The dopaminergic and endothelin systems, by regulating sodium transport in the renal proximal tubule (RPT), participate in the control of blood pressure. The D(3) and ETB receptors are expressed in RPTs, and D(3) receptor function in RPTs is impaired in spontaneously hypertensive rats (SHRs). Therefore, we tested the hypothesis that D(3) receptors can regulate ETB receptors, and that D(3) receptor regulation of ETB receptors in RPTs is impaired in SHRs. METHODS: ETB receptor expression in RPT cells was measured by immunoblotting and reverse transcriptase-PCR and ETB receptor function by measuring Na(+)-K(+) ATPase activity. D(3)/ETB receptor interaction was studied by co-immunoprecipitation. RESULTS: In Wistar-Kyoto (WKY) RPT cells, the D(3) receptor agonist, PD128907, increased ETB receptor protein expression, effects that were blocked by removal of calcium in the culture medium. The stimulatory effect of D(3) on ETB receptor mRNA and protein expression was also blocked by nicardipine. In contrast, in SHR RPT cells, PD128907 decreased ETB receptor expression. Basal D(3)/ETB receptor co-immunoprecipitation was three times greater in WKY than in SHRs. The absolute amount of D(3)/ETB receptor co-immunoprecipitation induced by a D(3) receptor agonist was also greater in WKY than in SHRs. Stimulation of ETB receptors decreased Na(+)-K(+) ATPase activity in WKY but not in SHR cells. Pretreatment with PD128907 augmented the inhibitory effect of BQ3020 on Na(+)-K(+) ATPase activity in WKY but not in SHR cells. CONCLUSIONS: D(3) receptors regulate ETB receptors by physical receptor interaction and govern receptor expression and function. D(3) receptor regulation of ETB receptors is aberrant in RPT cells from SHRs.

Insulin increases D5 dopamine receptor expression and function in renal proximal tubule cells from Wistar-Kyoto rats.

BACKGROUND: Ion transport in the renal proximal tubule (RPT) is regulated by numerous hormones and humoral factors, including insulin and dopamine. Previous studies show an interaction between insulin and the D(1) receptor. Because both D(1) and D(5) receptors belong to the D(1)-like receptor subfamily, it is possible that an interaction between insulin and the D(5) dopamine receptor exists in RPT cells from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). METHODS: D(5) receptor expression in immortalized RPT cells from WKY and SHRs was quantified by immunoblotting and D(5) receptor function by measuring Na(+)-K(+) ATPase activity. RESULTS: Insulin increased the expression of the D(5) receptor. Stimulation with insulin (10(-7) mol/l) for 24 h increased D(5) receptor expression in RPT cells from WKY rats. This effect of insulin on D(5) receptor expression was aberrant in RPT cells from SHRs. The stimulatory effect of insulin on D(5) receptor expression in RPT cells from WKY rats was inhibited by a protein kinase C (PKC) inhibitor (PKC inhibitor peptide 19-31, 10(-6) mol/l) or a phosphatidylinositol 3 (PI3) kinase inhibitor (wortmannin, 10(-6) mol/l), indicating that both PKC and PI3 kinase were involved in the signaling pathway. Stimulation of the D(5) receptor heterologously expressed in HEK293 cells with fenoldopam (10(-7) mol/l/15 min) inhibited Na(+)-K(+) ATPase activity, whereas pretreatment with insulin (10(-7) mol/l/24 h) increased the D(5) receptor-mediated inhibition. CONCLUSIONS: Insulin and D(5) receptors interact to regulate renal sodium transport; an aberrant interaction between insulin and D(5) receptor may participate in the pathogenesis of hypertension.

D1-like receptors inhibit insulin-induced vascular smooth muscle cell proliferation via down-regulation of insulin receptor expression.

OBJECTIVE: Vascular smooth muscle cell (VSMC) proliferation is central to the development of vascular diseases, including hypertension, which is regulated by numerous hormones and humoral factors. Our previous study showed that the stimulatory effect of norepinephrine on VSMC proliferation is inhibited by D1-like receptors and the D3 dopamine receptor, a member of the D2-like receptor family. Insulin is a proliferative hormone but it is not known if there is any interaction between insulin and D1-like receptors. We hypothesized that Dl-like receptors may have an inhibitory effect on the insulin-induced VSMC proliferation; aberrant insulin and Dl-like receptor functions could be involved in the pathogenesis of essential hypertension. METHODS: VSMC proliferation was determined by [H]-thymidine incorporation; insulin receptor mRNA and protein expressions were determined by RT-PCR, immunoblotting, and immunohistochemistry. RESULTS: Insulin increased VSMC proliferation in immortalized aortic A10 cells, determined by [H]-thymidine incorporation. Although the D1-like receptor, by itself, had no effect on VSMC proliferation, stimulation with fenoldopam, a D1-like receptor agonist, inhibited the stimulatory effect of insulin. The inhibitory effect of fenoldopam on insulin-mediated VSMC proliferation was receptor specific, because its effect could be blocked by SCH23390, a D1-like receptor antagonist. Fenoldopam also inhibited insulin receptor mRNA and protein expression, which was time dependent and concentration dependent. A PKC or MAP kinase inhibitor blocked the inhibitory effect of fenoldopam on insulin receptor expression, indicating that PKC and MAP kinase were involved in the signaling pathway. CONCLUSION: The inhibitory effect of D1-like receptors on insulin-mediated VSMC proliferation may play an important role in the regulation of blood pressure.