The Role of Galectin-3 in the Kidneys Chen, Szu-Chia; Kuo, Po-Lin
International Journal of Molecular Sciences,
04/2016, Letnik:
17, Številka:
4
Journal Article, Book Review
Recenzirano
Odprti dostop
Galectin-3 is a 32- to 35-kDa member of the galectin family of b-galactoside-binding lectins, which is characterized by a carbohydrate recognition domain. Through its carbohydrate-binding function, ...it regulates cell growth, differentiation, and inflammation. It also plays a complex, context-dependent role in the kidneys. During development, it promotes nephrogenesis and is strongly expressed in the ureteric bud and its derivatives. An increase in the concentration of galectin-3 has been reported to be associated with fibrosis of the kidneys. Elevated levels of plasma galectin-3 are also associated with increased risks of rapid renal function decline, incident chronic kidney disease, and progressive renal impairment, and also with cardiovascular end points, infection, and all-cause mortality in patients with renal function impairment. This review discusses a general survey on galectin-3 expressions in nephrogenesis, kidney injury animal models, clinical renal diseases, renal transplantation and the potential role of galectin-3 for treatment in kidney disease.
Coronary artery disease (CAD) covers a wide spectrum from persons who are asymptomatic to those presenting with acute coronary syndromes (ACS) and sudden cardiac death. Coronary atherosclerotic ...disease is a chronic, progressive process that leads to atherosclerotic plaque development and progression within the epicardial coronary arteries. Being a dynamic process, CAD generally presents with a prolonged stable phase, which may then suddenly become unstable and lead to an acute coronary event. Thus, the concept of ＂stable CAD＂ may be misleading, as the risk for acute events continues to exist, despite the use of pharmacological therapies and revascularization. Many advances in coronary care have been made, and guidelines from other international societies have been updated. The 2023 guidelines of the Taiwan Society of Cardiology for CAD introduce a new concept that categorizes the disease entity according to its clinical presentation into acute or chronic coronary syndromes (ACS and CCS, respectively). Previously defined as stable CAD, CCS include a heterogeneous population with or without chest pain, with or without prior ACS, and with or without previous coronary revascularization procedures. As cardiologists, we now face the complexity of CAD, which involves not only the epicardial but also the microcirculatory domains of the coronary circulation and the myocardium. New findings about the development and progression of coronary atherosclerosis have changed the clinical landscape. After a nearly 50-year ischemia-centric paradigm of coronary stenosis, growing evidence indicates that coronary atherosclerosis and its features are both diagnostic and therapeutic targets beyond obstructive CAD. Taken together, these factors have shifted the clinicians' focus from the functional evaluation of coronary ischemia to the anatomic burden of disease. Research over the past decades has strengthened the case for prevention and optimal medical therapy as central interventions in patients with CCS. Even though functional capacity has clear prognostic implications, it does not include the evaluation of non-obstructive lesions, plaque burden or additional risk-modifying factors beyond epicardial coronary stenosis-driven ischemia. The recommended first-line diagnostic tests for CCS now include coronary computed tomographic angiography, an increasingly used anatomic imaging modality capable of detecting not only obstructive but also non-obstructive coronary plaques that may be missed with stress testing. This non-invasive anatomical modality improves risk assessment and potentially allows for the appropriate allocation of preventive therapies. Initial invasive strategies cannot improve mortality or the risk of myocardial infarction. Emphasis should be placed on optimizing the control of risk factors through preventive measures, and invasive strategies should be reserved for highly selected patients with refractory symptoms, high ischemic burden, high-risk anatomies, and hemodynamically significant lesions. These guidelines provide current evidence-based diagnosis and treatment recommendations. However, the guidelines are not mandatory, and members of the Task Force fully realize that the treatment of CCS should be individualized to address each patient's circumstances. Ultimately, the decision of healthcare professionals is most important in clinical practice.
Triple negative breast cancer (TNBC) lacks specific drug targets and remains challenging. Palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor is approved for metastatic estrogen ...receptor (ER)-positive and human epithermal growth factor 2 (HER2)-negative breast cancer. The nature of cell cycle inhibition by palbociclib suggests its potential in TNBC cells. Retinoblastoma (RB, a known substrate of CDK4/6) pathway deregulation is a frequent occurrence in TNBC and studies have revealed that pharmacological CDK4/6 inhibition induces a cooperative cytostatic effect with doxorubicin in RB-proficient TNBC models. In addition, recent studies reported that anti-androgen therapy shows preclinical efficacy in androgen-receptor (AR)-positive TNBC cells. Here we examined the effect of palbociclib in combination with an anti-androgen enzalutamide in TNBC cells.
MDA-MB-453, BT-549, MDA-MB-231 and MDA-MB-468 TNBC cell lines were used for in vitro studies. Protein expressions were assessed by Western blot analysis. Cytostatic effect was examined by MTT assay. Cell cycle and apoptosis were examined by flow cytometry.
Palbociclib showed inhibitory effect in RB-proficient TNBC cells, and enzalutamide inhibited cell viability in AR-positive TNBC cells. Enzalutamide treatment could enhance the palbociclib-induced cytostatic effect in AR-positive/RB-proficient TNBC cells. In addition, palbociclib-mediated G1 arrest in AR-positive/RB-proficient TNBC cells was attenuated by RB knockdown.
Our study provided a preclinical rationale in selecting patients who might have therapeutic benefit from combining CDK4/6 inhibitors with AR antagonists.
This study with the area-efficient design for improving electrostatic discharge (ESD) and Latch-up (LU) abilities in the ultra-high voltage (UHV) n-channel Lateral-Diffused MOSFET (nLDMOS) is ...investigated via a TSMC 0.5-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> UHV Bipolar CMOS DMOS (BCD) process. There are two architectures of these nLDMOS devices with embedded Schottky diodes in the electrode area. Firstly, the drain side is divided into three concentric circles and embedded with Schottky diodes. The influence of these samples with different layout arrangements on ESD is evaluated. For the second item, UHV nLDMOS devices with the source side embedded Schottky diodes by two alternative layout types are developed. Experimental results showed that an UHV nLDMOS with embedded Schottky diodes at the drain side can significantly improve ESD ability, especially for the fully embedded Schottky diodes at the drain side (being with the highest figure of merit (FOM) value in the ESD, LU, and cell-area considerations). On the other hand, with embedded Schottky diodes at the source side can increase the holding voltage which can effectively improve the LU immunity.
This study evaluated short-term (1-month) and long-term (1-year) mortality risks associated with the glomerular filtration rate (eGFR) on admission for patients with intracerebral hemorrhage.
From ...the Taiwan Stroke Registry data from April 2006 to December 2016, we identified and stratified patients with intracerebral hemorrhage into five subgroups by the eGFR level on admission: ≥90, 60-89, 30-59, 15-29, and <15 mL/min/1.73 m2 or on dialysis. Risks for 1-month and 1-year mortality after intracerebral hemorrhage were compared by the eGFR levels.
Both the 1-month and 1-year mortality rates progressively increased with the decrease in eGFR levels. The 1-month mortality rate in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was approximately 5.5-fold greater than that in patients with eGFR ≥ 90 mL/min/1.73 m2 (8.31 versus 1.50 per 1000 person-days), with an adjusted hazard ratio (HR) of 4.59 95% confidence interval (CI) = 2.71-7.78. Similarly, the 1-year mortality in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was 7.5 times that in patients with eGFR ≥ 90 mL/min/1.73 m2 (2.34 versus 0.31 per 1000 person-days), with an adjusted HR of 4.54 (95% CI 2.95-6.98).
Impairment of renal function is an independent risk factor for mortality in patients with intracerebral hemorrhage in a gradual way. The eGFR level is a prognostic indicator for patients with intracerebral hemorrhage.
Sodium-glucose cotransporter type 2 (SGLT2) inhibitors have demonstrated to reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) in large trials independent of glycemic ...control. The mechanisms of this cardioprotective property remain uncertain. Evidence suggests positive hemodynamic changes and favorable cardiac remodeling contributing to the clinical outcomes but results were conflicting. We aim to investigate the potential impact on hemodynamic parameters, cardiac structure and functions. This prospective observational study included T2DM patients receiving canagliflozin 100 mg per day in addition to their antidiabetic treatment. We analyzed hemodynamic parameters assessed by echocardiographic measurements and impedance cardiography (ICG) to evaluate systolic and diastolic functions from baseline to 24 weeks after treatment. A total of 47 patients (25 males and 22 females) averaging 64.6 ± 10.9 years had a significant reduction in HbA1c, body weight, and systolic blood pressure. Hematocrit increased significantly, while NT-proBNP remained unchanged. E/e', left atrium (LA) volume, and LA stiffness were reduced, while left ventricle (LV) global longitudinal strain (GLS) and LA strain rates increased at 24 weeks by conventional and speckle tracking echocardiography. LV mass and ejection fraction showed no differences. ICG suggested significant improvement in hemodynamic parameters with increased stroke volume index and cardiac output index and decreased systemic vascular resistance index at 12 and 24 weeks. Canagliflozin improved hemodynamic parameters and had a favorable impact on LA and LV reverse remodeling. These changes may explain the beneficial effect on cardiovascular outcomes in large clinical trials.
Purpose
No standard strategy exists for managing cervical spondylotic myelopathy (CSM). The efficacy of spinous process-splitting laminoplasty, its impact on cervical alignment change and the ...incidence of postoperative neck pain remain unclear. We analyzed the parameters of cervical alignment and cord morphology in CSM.
Methods
The radiographic parameters investigated were pre- and postoperative C2–C7 lordosis (CL), C2–C7 sagittal vertical axis (CSVA), T1 slope (TS), TS minus CL (TS − CL) and cervical spinal cord morphology. Myelopathy severity was measured using two different functional scores. Statistical analysis was performed to determine significant differences between preoperative and follow-up radiological findings and change in functional scores.
Results
This retrospective study comprised 85 CSM patients from a single institute, with a minimum follow-up of 24 months. Overall, 63.5% (
n
= 54) of patients had improvement in their postoperative cervical lordotic alignment; 36.5% (
n
= 31) developed progressive aggravation of the cervical kyphotic alignment. Pearson correlation analysis showed that CSVA, TS and T1–CL were independent predictors of CL curve change. Based on the receiver operating characteristic curve, the cutoff value for CSVA was 2.89 cm with a postoperative visual analog scale (VAS) > 4. The cutoff value of the TS − CL was 20 degrees with a postoperative VAS > 4. CSVA, TS and TS − CL had a significant association with variation in CL. CSVA and TS − CL had a significant association with postoperative neck pain.
Conclusions
CSVA, T1 slope and T1–CL are good predictors of postoperative degenerative kyphotic change and neck pain. Careful consideration of their preoperative cutoff values can improve postoperative outcomes.
Level of evidence
IV.
Graphic abstract
These slides can be retrieved under Electronic Supplementary Material.
Background
Being woman is associated with higher survival rates after transcatheter aortic valve replacement (TAVR) despite the increase in periprocedural complications. The left ventricle (LV) ...remodelling process that follows TAVR is considered to play an important role. We aim to investigate whether gender difference affects the process of LV remodelling after TAVR.
Materials and Methods
A total of 100 patients (50 men and 50 women) after TAVR were enrolled. Echocardiography was performed at baseline before the TAVR procedure and repeated upon discharge, and at three, nine and 12 months post‐TAVR.
Results
Women exhibited an early regression of LV mass and the LV mass index (LVMi) decreased 12.0% from 148.3 ± 48.0 to 130.5 ± 43.7 g/m2 at just a median of 17 days after the procedure (P < .001). Almost one‐half of the LVMi regression occurred by 17 days post‐TAVR and the LVMi regressed 22.0% by 12 months post‐TAVR. In contrast, the regression of LVMi in men seemed to be more gradual and the significant regression of LVMi from baseline began to be observed since three months later after TAVR. The LVMi reduction at nine months was 11.5% and achieved 15.4% over one year. Multivariable logistic regression analysis showed only the female sex, better LVEF and greater baseline LVMi were independently associated with greater LVMi regression after TAVR, indicating female gender is an independent predictor for favourable LV remodelling after TAVR.
Conclusion
In conclusion, female patients with AS had favourable reverse remodelling with greater and earlier LV mass regression post‐TAVR compared with the male patients.
The adverse effect of COVID-19 pandemic among individuals has been very disturbing especially among healthcare workers. This study aims to examine the prevalence of post-traumatic stress disorder ...(PTSD) symptoms, sleep problems, and psychological distress among COVID-19 frontline healthcare workers in Taiwan. Hence, a total of 500 frontline healthcare workers were recruited to participate in this cross-sectional study. They responded to measures on fear of COVID-19, depression, anxiety, stress, insomnia, PTSD, perceived stigma, and self-stigma. The results indicated a prevalence rate of 15.4% for PTSD symptoms, 44.6% for insomnia, 25.6% for depressive symptoms, 30.6% for anxiety symptoms, and 23.4% for stress among the participants. There were significantly positive interrelationships between all these variables. Anxiety symptoms and fear of COVID-19 predicted PTSD whereas symptoms of anxiety, fear of COVID-19, and stress predicted insomnia. The prevalence rates of the psychological problems reveal a worrying view of mental health challenges among Taiwanese frontline healthcare workers. Anxiety symptoms and fear of COVID-19 are the common predictive factors of PTSD and sleep problems suggesting that mental healthcare services for them may help prevent future occurrence of psychological problems by allaying fears of healthcare workers. Therefore, there should be mental healthcare services for healthcare workers during the COVID-19 pandemic.
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