The high-density lipoprotein cholesterol (HDL-C)-concentration-dependent association between anti-inflammatory capacity and sepsis: A single-center cross-sectional study.

INTRODUCTION: Known to have pleiotropic functions, high-density lipoprotein (HDL) helps to regulate systemic inflammation during sepsis. As preserving HDL-C level is a promising therapeutic strategy for sepsis, the interaction between HDL and sepsis worth further investigation. This study aimed to determine the impact of sepsis on HDL's anti-inflammatory capacity and explore its correlations with disease severity and laboratory parameters. METHODS AND MATERIALS: We enrolled 80 septic subjects admitted to the intensive care unit and 50 controls admitted for scheduled coronary angiography in this cross-sectional study. We used apolipoprotein-B depleted (apoB-depleted) plasma to measure the anti-inflammatory capacity of HDL-C. ApoB-depleted plasma's anti-inflammatory capacity is defined as its ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical-vein endothelial cells. A subgroup analysis was conducted to investigate in septic subjects according to disease severity. RESULTS: ApoB-depleted plasma's anti-inflammatory capacity was reduced in septic subjects relative to controls (VCAM-1 mRNA fold change: 50.1% vs. 35.5%; p < 0.0001). The impairment was more pronounced in septic subjects with than in those without septic shock (55.8% vs. 45.3%, p = 0.0022). Both associations were rendered non-significant with the adjustment for the HDL-C level. In sepsis patients, VCAM-1 mRNA fold change correlated with the SOFA score (Spearman's r = 0.231, p = 0.039), lactate level (r = 0.297, p = 0.0074), HDL-C level (r = -0.370, p = 0.0007), and inflammatory markers (C-reactive protein level: r = 0.441, p <0.0001; white blood cell: r = 0.353, p = 0.0013). CONCLUSION: ApoB-depleted plasma's anti-inflammatory capacity is reduced in sepsis patients and this association depends of HDL-C concentration. In sepsis patients, this capacity correlates with disease severity and inflammatory markers. These findings explain the prognostic role of the HDL-C level in sepsis and indirectly support the rationale for targeting HDL-C as sepsis treatment.

Impacts of the SYNTAX score I, II and SYNTAX score II 2020 on left main revascularization.

Patients with left main coronary artery disease (LMCAD) with a high SYNTAX score (SS) were excluded from randomized studies that comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to compare PCI and CABG in the real-world practice and investigate the impact of SS I, SS II, and SS II 2020 on clinical outcomes. In total, 292 Patients with LMCAD (173 PCI, 119 CABG) treated between 2017 and 2021 were enrolled. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, stroke, or myocardial infarction (MI). The mean SS I was high in both groups (PCI vs. CABG: 31.64 ± 11.45 vs. 32.62 ± 11.75, p = 0.660). The primary outcome occurred in 28 patients (16.2%) in the PCI group and in 19 patients (16.0%) in the CABG group without significant difference [adjusted hazard ratio, 95% CI = 0.98 (0.51-1.90), p = 0.97] over the follow-up period (26.9 ± 17.7 months). No significant difference was observed in all-cause mortality (11.6% vs. 11.8%, p = 0.93) or stroke rates (3.5% vs. 5.0%, p = 0.51) between groups. However, PCI was associated with higher MI (4.6% vs. 0.8%, p < 0.05) and revascularization rates (26% vs. 5.9%, p < 0.001). Prognostic value of the SS I, SS II and SS II 2020 on the primary outcome was not relevant in the PCI group. Among patients with LMCAD, PCI and CABG did not significantly differ in the composite endpoint of all-cause death, stroke, and MI. These results support the potential expansion of PCI indications in LMCAD management for whom are ineligible for CABG with complex coronary artery disease.

Dysfunction of circulating endothelial progenitor cells in major depressive disorder.

OBJECTIVES: Despite mounting evidence demonstrates circulating endothelial progenitor cells (cEPCs) quantitative changes in depression, no study has investigated cEPC functions in major depressive disorder (MDD). We investigated the role of cEPC adhesive and apoptotic functions in MDD. METHODS: We recruited 68 patients with MDD and 56 healthy controls (HCs). The depression symptoms, anxiety, psychosomatic symptoms, subjective cognitive dysfunction, quality of life, and functional disability were evaluated using the Hamilton Depression Rating Scale and Montgomery-Åsberg Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression and Somatic Symptoms Scale (DSSS), Perceived Deficits Questionnaire-Depression, 12-Item Short Form Health Survey (SF-12), and Sheehan Disability Scale (SDS), respectively. Working memory and executive function were assessed using a 2-back task and Wisconsin Card Sorting Test (WCST). Inflammatory marker (soluble interleukin-6 receptor, C-reactive protein, and tumor necrosis factor-α receptor-1), cEPC adhesive, and apoptotic levels were measured using in vitro assays. RESULTS: The MDD patients showed significantly lower cEPC adhesive levels than the HCs, and this difference in adhesive function remained statistically significant even after adjusting for inflammatory marker levels. The cEPC adhesion levels were in inverse correlations with commission and omission errors in 2-back task, the percent perseverative response and percent perseverative errors in WCST, and the DSSS and SDS scores, but in positive correlations with SF-12 physical and mental component scores. cEPC apoptotic levels did not differ significantly between the groups. CONCLUSION: The findings indicate that cEPC adhesive function is diminished in MDD and impacts various aspects of cognitive and psychosocial functions associated with the disorder.

Tumor Necrosis Factor Superfamily 14 (LIGHT) Restricts Neovascularization by Decreasing Circulating Endothelial Progenitor Cells and Function.

Tumor necrosis factor superfamily 14 (TNFSF14) is also known as the LT-related inducible ligand (LIGHT). It can bind to the herpesvirus invasion mediator and lymphotoxin-ß receptor to perform its biological activity. LIGHT has multiple physiological functions, including strengthening the synthesis of nitric oxide, reactive oxygen species, and cytokines. LIGHT also stimulates angiogenesis in tumors and induces the synthesis of high endothelial venules; degrades the extracellular matrix in thoracic aortic dissection, and induces the expression of interleukin-8, cyclooxygenase-2, and cell adhesion molecules in endothelial cells. While LIGHT induces tissue inflammation, its effects on angiogenesis after tissue ischemia are unclear. Thus, we analyzed these effects in the current study. In this study, the animal model of hind limb ischemia surgery in C57BL/6 mice was performed. Doppler ultrasound, immunohistochemical staining, and Western blotting were employed to analyze the situation of angiogenesis. In addition, human endothelial progenitor cells (EPCs) were used for in vitro studies to analyze the possible mechanisms. The results in the animal study showed that LIGHT injection inhibited angiogenesis in ischemic limbs. For the in vitro studies, LIGHT inhibited the expression of integrins and E-selectin; decreased migration and tube formation capabilities, mitochondrial respiration, and succinate dehydrogenase activity; and promoted senescence in EPCs. Western blotting revealed that the impairment of EPC function by LIGHT may be due to its effects on the proper functioning of the intracellular Akt signaling pathway, endothelial nitrite oxide synthase (eNOS), and mitochondrial respiration. In conclusion, LIGHT inhibits angiogenesis after tissue ischemia. This may be related to the clamped EPC function.

Vertical Sleeve Gastrectomy Offers Protection against Disturbed Flow-Induced Atherosclerosis in High-Fat Diet-Fed Mice.

Bariatric surgery reduces body weight, enhances metabolic and diabetic control, and improves outcomes on obesity-related comorbidities. However, the mechanisms mediating this protection against cardiovascular diseases remain unclear. We investigated the effect of sleeve gastrectomy (SG) on vascular protection in response to shear stress-induced atherosclerosis using an overweighted and carotid artery ligation mouse model. Eight-week-old male wild-type mice (C57BL/6J) were fed a high-fat diet (HFD) for two weeks to induce weight gain and dysmetabolism. SG was performed in HFD-fed mice. Two weeks after the SG procedure, partial carotid-artery ligation was performed to promote disturbed flow-induced atherosclerosis. Compared with the control mice, HFD-fed wild-type mice exhibited increased body weight, total cholesterol level, hemoglobin A1c, and enhanced insulin resistance; SG significantly reversed these adverse effects. As expected, HFD-fed mice exhibited greater neointimal hyperplasia and atherosclerotic plaques than the control group, and the SG procedure attenuated HFD-promoted ligation-induced neointimal hyperplasia and arterial elastin fragmentation. Besides, HFD promoted ligation-induced macrophage infiltration, matrix metalloproteinase-9 expression, upregulation of inflammatory cytokines, and increased vascular endothelial growth factor secretion. SG significantly reduced the above-mentioned effects. Moreover, HFD restriction partially reversed the intimal hyperplasia caused by carotid artery ligation; however, this protective effect was significantly lower than that observed in SG-operated mice. Our study demonstrated that HFD deteriorates shear stress-induced atherosclerosis and SG mitigates vascular remodeling, and this protective effect was not comparable in HFD restriction group. These findings provide a rationale for using bariatric surgery to counter atherosclerosis in morbid obesity.

Recent Advancements in Electroporation Technologies: From Bench to Clinic.

Over the past decade, the increased adoption of electroporation-based technologies has led to an expansion of clinical research initiatives. Electroporation has been utilized in molecular biology for mammalian and bacterial transfection; for food sanitation; and in therapeutic settings to increase drug uptake, for gene therapy, and to eliminate cancerous tissues. We begin this article by discussing the biophysics required for understanding the concepts behind the cell permeation phenomenon that is electroporation. We then review nano- and microscale single-cell electroporation technologies before scaling up to emerging in vivo applications.

Efficacy and Safety of Combined Ethanol-Lipiodol Mixture and Drug-Eluting Bead TACE for Large HCC.

Purpose: To evaluate treatment response, survival and safety of a novel TACE using combination of ethanol-Lipiodol mixture and drug-eluting beads in patients with large unresectable HCC, single tumor >8 cm or multiple tumors with the largest tumor diameter >5 cm and total tumor diameter >10 cm. Patients and Methods: Between June 2016 and February 2020, a total of 27 patients were enrolled in this retrospective cohort study. Treatment response was assessed at first month after the treatment; progression-free survival (PFS) and overall survival (OS) were evaluated. The prognostic factors associated with patient survival were statistically analyzed by the Cox regression model. Adverse events were recorded. Results: The maximum diameter of the tumors ranged from 5 cm to 17 cm (mean 10.48 cm). The objective response and disease control rates were 56% and 78%, respectively, at 1-month follow-up. The median survival time was 15.9 months (95% CI, 9.03-34.76 months). The OS rates were 76.9% at six months, 65.2% at one year and 44.8% at two years. AFP >400 ng/mL (p = 0.0306), maximum tumor size >10cm (p = 0.0240) were potential risk factors for OS. Regarding safety, major complications occurred in one patient (1/27, 3.7%), presenting with transient hepatic encephalopathy. Conclusion: Combined DEB-TACE appeared to have favorable objective tumor response. It can be an effective treatment option for large unresectable HCC.

Yttrium-90 Radioembolization as the Major Treatment of Hepatocellular Carcinoma.

Background: The purpose of this study was to assess the safety and efficacy of Yttrium-90 radioembolization using in unresectable hepatocellular carcinoma. Methods: From 2017 to 2021, 32 patients with unresectable hepatocellular carcinoma, with mean tumor diameter about 7cm (21 males, 11 females; median age, 57.5 years of age), treated with Yttrium-90 radioembolization using resin microspheres were reviewed at pre-Yttrium-90 and post-Yttrium-90 follow-up. Tumor response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Outcomes including overall survival and progression-free survival were reported. Results: Median follow-up was 18 months. At follow-up examinations at 3-, 6-, and 12-months follow-up, the overall survival rates were 94%, 87% and 59%, and the progression-free survival rates were 78%, 64% and 60%, respectively. Complete response, partial response, stable disease, and progressive disease were noted in 7 (21.9%), 14 (43.7%), 4 (12.5%), and 7 (21.9%) patients, respectively. The disease control rate was 78.1%, the objective response rate was 65.6%, and the successful downstage rate was 34.4% (11 of 32). Nine of thirty-two patients underwent resection or transplantation after Yttrium-90 radioembolization with 2-year overall survival being 100%. No serious adverse events occurred after Yttrium-90 treatment. Worse overall survival was related to the larger tumor, higher stage, Eastern Cooperative Oncology Group performance status, and Child-Pugh score. And worse progression-free survival was related to the higher tumor burden, and pre-Yttrium-90 serum α-fetoprotein level >100. Conclusion: Yttrium-90 Radioembolization can control hepatocellular carcinoma well even in advanced diseases. Patients successfully downstaging/bridging to resection or transplantation have excellent overall survival.

Luminal pressure gradient and risk of arteriovenous fistula nonmaturation.

While arteriovenous fistula (AVF) nonmaturation is a major issue of hemodialysis care, an effective treatment to improve AVF maturation remains lacking. AVF introduces pulsatile arterial blood flow into its venous limb and produces high luminal pressure gradient, which may have adverse effect on vascular remodeling. As such, the aim of the present study is to investigate effect of luminal pressure gradient on AVF nonmaturation. This single-center, prospective observational study includes patients receiving autologous AVF creation. Participants received early postoperative ultrasound 5-7 days after surgery to collect parameters including diameters, flow rates, and volume at inflow and outflow sites. Luminal pressure gradient was estimated by using modified Bernoulli equation. The outcome was spontaneous AVF maturation within 8 weeks after surgery without intervention. Thirty patients were included, of which the mean age was 66.9 years and 70% were male. At the end of study, 13 (43.3%) patients had spontaneous AVF maturation. All demographic and laboratory characteristics were similar between patients with mature and nonmature AVF. Regarding ultrasonographic parameters, nonmature AVF showed significantly higher inflow/outflow diameter ratio, inflow velocity, and luminal pressure gradient. While these 3 parameters were significantly correlated, multivariate logistic regression showed their significant association with AVF nonmaturation. Receiver operating characteristic curve exhibited their high predictive value for AVF nonmaturation. Our findings showed that higher inflow/outflow ratio, inflow velocity, and AVF luminal pressure gradient in early postoperative ultrasound predicted risk of AVF nonmaturation. Reducing inflow/outflow diameter ratio or inflow rate may be an approach to improve AVF maturation. The predictive value of this early assessment might have impact on the clinical practice of AVF care.

Sacubitril/Valsartan in Patients With Heart Failure and Concomitant End-Stage Kidney Disease.

Background Heart failure with reduced ejection fraction (HFrEF) is a chronic disease with substantial mortality. Management of HFrEF has seen significant breakthrough after the launch of neprilysin inhibitor. The PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impacton Global Mortality and Morbidity in Heart Failure) trial showed that sacubitril/valsartan significantly reduces HFrEF mortality and the heart failure hospitalization rate. However, in patients with advanced kidney disease, who have the highest prevalence of heart failure, the efficacy and safety of sacubitril/valsartan remains uncertain. We aim to study the efficiency of sacubitril/valsartan in patients with end-stage kidney disease. Methods and Results Heart function was screened by echocardiogram among all patients with end-stage kidney disease in 2 hospitals. Patients with HFrEF received either sacubitril/valsartan or conventional treatment. Fifteen echocardiographic parameters were compared before and after treatment. After 1-year sacubitril/valsartan treatment, parameters of systolic (left ventricular ejection fraction 31.3% to 45.1%, P<0.0001; left ventricular end-systolic volume 95.7 to 70.1 mL, P=0.006; left ventricular internal diameter at end-systole phase 47.2 to 40.1 mm, P=0.005), and diastolic (E/A ratio 1.3 to 0.8, P=0.009; E/Med e' ratio 25.3 to 18.8, P=0.010) function improved in patients with HFrEF and end-stage kidney disease. These parameters were unchanged in the conventional treatment group. Serum potassium did not increase in the sacubitril/valsartan group. Conclusions Sacubitril/valsartan improves left ventricular systolic and diastolic function in patients with HFrEF and end-stage kidney disease.

Melatonin Improves Ischemia-Induced Circulation Recovery Impairment in Mice with Streptozotocin-Induced Diabetes by Improving the Endothelial Progenitor Cells Functioning.

Patients with diabetes mellitus tend to develop ischemia-related complications and have compromised endothelial progenitor cell (EPC) function. Melatonin protects against ischemic injury, possibly via EPC modulation. We investigated whether melatonin pretreatment could restore EPC function impairment and improve circulation recovery in a diabetic critical limb ischemia mouse model. Under 25 mM high-glucose medium in vitro, EPC proliferation, nitric oxide production, tube formation, and endothelial nitric oxide synthase (eNOS) phosphorylation were significantly suppressed. Hyperglycemia promoted EPC senescence and apoptosis as well as increased reactive oxygen species (ROS) production. Melatonin treatment reversed the harmful effects of hyperglycemia on EPC through adenosine monophosphate-activated protein kinase-related mechanisms to increase eNOS phosphorylation and heme oxygenase-1 expression. In an in-vivo study, after a 4-week surgical induction of hindlimb ischemia, mice with streptozotocin (STZ)-induced diabetes showed significant reductions in new vessel formation, tissue reperfusion, and EPC mobilization in ischemic hindlimbs compared to non-diabetic mice. Mice with STZ-induced diabetes that received melatonin treatment (10 mg/kg/day, intraperitoneal) had significantly improved blood perfusion ratios of ischemic to non-ischemic limb, EPC mobilization, and densities of capillaries. In addition, a murine bone marrow transplantation model to support these findings demonstrated that melatonin stimulated bone marrow-originated EPCs to differentiate into vascular endothelial cells in femoral ligation-induced ischemic muscles. In summary, this study suggests that melatonin treatment augments EPC function along with neovascularization in response to ischemia in diabetic mice. We illustrated the protective effects of melatonin on EPC H2O2 production, senescence, and migration through melatonin receptors and modulating eNOS, AMPK, and HO-1 activities at the cellular level. Thus, melatonin might be used to treat the impairment of EPC mobilization and circulation recuperation in response to ischemic injury caused by chronic hyperglycemia. Additional studies are needed to elucidate the applicability of the results in humans.

Cardiac Dopamine-Secreting Paraganglioma with Involved Skull Base and Retroperitoneum After a History of Pheochromocytoma Post Adrenalectomy.

Cardiac paragangliomas are exceedingly rare. Herein, we describe a patient with a large dopaminesecreting cardiac paraganglioma who had a history of pheochromocytoma after right adrenalectomy. The cardiac surgery was uneventful and without blood pressure fluctuations.The measurement of plasma-free metanephrines or urinary fractionated metanephrines is used as an initial screening test for pheochromocytoma or paraganglioma detection. However, these results must be combined with those of a plasma 3-methoxytyramine test to accurately establish the rare dopaminergic phenotype of pheochromocytomas or paragangliomas, if suspected. F-FDOPA (6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine)-based positron emission tomography (PET) and PET-computed tomography are relatively sensitive and specific; therefore, these techniques are recommended for patients with pheochromocytomas or paragangliomas before operation or during postoperative follow-up.

A Scoring System for Predicting Microvascular Invasion in Hepatocellular Carcinoma Based on Quantitative Functional MRI.

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is a histopathological marker and risk factor for HCC recurrence. We integrated diffusion-weighted imaging (DWI) and magnetic resonance (MR) image findings of tumors into a scoring system for predicting MVI. In total, 228 HCC patients with pathologically confirmed MVI who underwent surgical resection or liver transplant between November 2012 and March 2021 were enrolled retrospectively. Patients were divided into a right liver lobe group (n = 173, 75.9%) as the model dataset and a left liver lobe group (n = 55, 24.1%) as the model validation dataset. Multivariate logistic regression identified two-segment involved tumor (Score: 1; OR: 3.14; 95% CI: 1.22 to 8.06; p = 0.017); ADCmin ≤ 0.95 × 10-3 mm2/s (Score: 2; OR: 10.88; 95% CI: 4.61 to 25.68; p = 0.000); and largest single tumor diameter ≥ 3 cm (Score: 1; OR: 5.05; 95% CI: 2.25 to 11.30; p = 0.000), as predictive factors for the scoring model. Among all patients, sensitivity was 89.66%, specificity 58.04%, positive predictive value 68.87%, and negative predictive value 84.41%. For validation of left lobe group, sensitivity was 80.64%, specificity 70.83%, positive predictive value 78.12%, and negative predictive value 73.91%. The scoring model using ADCmin, largest tumor diameter, and two-segment involved tumor provides high sensitivity and negative predictive value in MVI prediction for use in routine functional MR.

Magnolol reduces myocardial injury induced by renal ischemia and reperfusion.

BACKGROUND: Magnolol is a component of the bark of Magnolia officinalis, which is a traditional herbal remedy used in China. In this study, we investigated whether magnolol can reduce myocardial injury induced by renal ischemia and reperfusion (I/R). METHODS: Renal I/R was elicited by a 60-minute occlusion of the bilateral renal arteries and a 24-hour reperfusion in Sprague-Dawley rats. Magnolol was administered intravenously 10 minutes before renal I/R to evaluate its effects on myocardial injury induced by renal I/R. RESULTS: Renal I/R significantly increased the serum levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and cardiac troponin I and caused myocardial damage. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei and caspase-3 activation was significantly increased in the myocardium, indicating increase of apoptosis. Echocardiography revealed left ventricular dysfunction, as evidenced by reduction of left ventricular ejection fraction and left ventricular fractional shortening. Furthermore, serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 were significantly elevated, while the IL-10 level was suppressed. However, intravenously, pretreatment with magnolol at doses of 0.003 and 0.006 mg/kg 10 minutes before renal I/R significantly prevented the increases of CPK, LDH, and cardiac troponin I levels, as well as the histological damage and the apoptosis in the myocardium. Echocardiography showed significant improvement of left ventricular function. Furthermore, the increases in TNF-α, IL-1ß, and IL-6 and the decrease in IL-10 were significantly limited, while Bcl-2 was increased and Bax was decreased in the myocardium. Phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was increased, while phosphorylation of p38 and c-Jun N-terminal kinase was reduced. CONCLUSION: Magnolol reduces myocardial injury induced by renal I/R. The underlying mechanisms for this effect might be related to modulation of the production of pro- and anti-inflammatory cytokines and the limiting of apoptosis.

The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Ameliorates Endothelial Inflammation and Microvascular Thrombosis in a Sepsis Mouse Model.

The pathophysiology of sepsis involves inflammation and hypercoagulability, which lead to microvascular thrombosis and compromised organ perfusion. Dipeptidyl peptidase (DPP)-4 inhibitors, e.g., linagliptin, are commonly used anti-diabetic drugs known to exert anti-inflammatory effects. However, whether these drugs confer an anti-thrombotic effect that preserves organ perfusion in sepsis remains to be investigated. In the present study, human umbilical vein endothelial cells (HUVECs) were treated with linagliptin to examine its anti-inflammatory and anti-thrombotic effects under tumor necrosis factor (TNF)-α treatment. To validate findings from in vitro experiments and provide in vivo evidence for the identified mechanism, a mouse model of lipopolysaccharide (LPS)-induced systemic inflammatory response syndrome was used, and pulmonary microcirculatory thrombosis was measured. In TNF-α-treated HUVECs and LPS-injected mice, linagliptin suppressed expressions of interleukin-1ß (IL-1ß) and intercellular adhesion molecule 1 (ICAM-1) via a nuclear factor-κB (NF-κB)-dependent pathway. Linagliptin attenuated tissue factor expression via the Akt/endothelial nitric oxide synthase pathway. In LPS-injected mice, linagliptin pretreatment significantly reduced thrombosis in the pulmonary microcirculation. These anti-inflammatory and anti-thrombotic effects were independent of blood glucose level. Together the present results suggest that linagliptin exerts protective effects against endothelial inflammation and microvascular thrombosis in a mouse model of sepsis.

Harmonic acoustics for dynamic and selective particle manipulation.

Precise and selective manipulation of colloids and biological cells has long been motivated by applications in materials science, physics and the life sciences. Here we introduce our harmonic acoustics for a non-contact, dynamic, selective (HANDS) particle manipulation platform, which enables the reversible assembly of colloidal crystals or cells via the modulation of acoustic trapping positions with subwavelength resolution. We compose Fourier-synthesized harmonic waves to create soft acoustic lattices and colloidal crystals without using surface treatment or modifying their material properties. We have achieved active control of the lattice constant to dynamically modulate the interparticle distance in a high-throughput (>100 pairs), precise, selective and reversible manner. Furthermore, we apply this HANDS platform to quantify the intercellular adhesion forces among various cancer cell lines. Our biocompatible HANDS platform provides a highly versatile particle manipulation method that can handle soft matter and measure the interaction forces between living cells with high sensitivity.

Elevated serum galectin-1 concentrations are associated with increased risks of mortality and acute kidney injury in critically ill patients.

BACKGROUND: Galectin-1 (Gal-1), a member of the ß-galactoside binding protein family, is associated with inflammation and chronic kidney disease. However, the effect of Gal-1 on mortality and acute kidney injury (AKI) in critically-ill patients remain unclear. METHODS: From May 2018 to March 2020, 350 patients admitted to the medical intensive care unit (ICU) of Taipei Veterans General Hospital, a tertiary medical center, were enrolled in this study. Forty-one patients receiving long-term renal replacement therapy were excluded. Serum Gal-1 levels were determined within 24 h of ICU admission. The patients were divided into tertiles according to their serum Gal-1 levels (low, serum Gal-1 < 39 ng/ml; median, 39-70 ng/ml; high, ≥71 ng/ml). All patients were followed for 90 days or until death. RESULTS: Mortality in the ICU and at 90 days was greater among patients with elevated serum Gal-1 levels. In analyses adjusted for the body mass index, malignancy, sepsis, Sequential Organ Failure Assessment (SOFA) score, and serum lactate level, the serum Gal-1 level remained an independent predictor of 90-day mortality [median vs. low: adjusted hazard ratio (aHR) 2.11, 95% confidence interval (CI) 1.24-3.60, p = 0.006; high vs. low: aHR 3.21, 95% CI 1.90-5.42, p < 0.001]. Higher serum Gal-1 levels were also associated with a higher incidence of AKI within 48 h after ICU admission, independent of the SOFA score and renal function (median vs. low: aHR 2.77, 95% CI 1.21-6.34, p = 0.016; high vs. low: aHR 2.88, 95% CI 1.20-6.88, p = 0.017). The results were consistent among different subgroups with high and low Gal-1 levels. CONCLUSION: Serum Gal-1 elevation at the time of ICU admission were associated with an increased risk of mortality at 90 days, and an increased incidence of AKI within 48 h after ICU admission.

Electrochemical micro-aptasensors for exosome detection based on hybridization chain reaction amplification.

Exosomes are cell-derived nanovesicles that have recently gained popularity as potential biomarkers in liquid biopsies due to the large amounts of molecular cargo they carry, such as nucleic acids and proteins. However, most existing exosome-based analytical sensing methods struggle to achieve high sensitivity and high selectivity simultaneously. In this work, we present an electrochemical micro-aptasensor for the highly sensitive detection of exosomes by integrating a micropatterned electrochemical aptasensor and a hybridization chain reaction (HCR) signal amplification method. Specifically, exosomes are enriched on CD63 aptamer-functionalized electrodes and then recognized by HCR products with avidin-horseradish peroxidase (HRP) attached using EpCAM aptamers as bridges. Subsequently, the current signal that is generated through the enzyme reaction between the HRP enzyme and 3,3',5,5'-tetramethylbenzidine (TMB)/H2O2 directly correlates to the amount of bound HRP on the HCR products and thus to the number of target exosomes. By introducing anti-EpCAM aptamers, micro-aptasensors can detect cancerous exosomes with high specificity. Due to the micropatterned electrodes and HCR dual-amplification strategy, the micro-aptasensors achieve a linear detection response for a wide range of exosome concentrations from 2.5×103 to 1×107 exosomes/mL, with a detection limit of 5×102 exosomes/mL. Moreover, our method successfully detects lung cancer exosomes in serum samples of early-stage and late-stage lung cancer patients, showcasing the great potential for early cancer diagnosis.

Sitagliptin attenuates arterial calcification by downregulating oxidative stress-induced receptor for advanced glycation end products in LDLR knockout mice.

Diabetes is a complex disease characterized by hyperglycemia, dyslipidemia, and insulin resistance. Plasma advanced glycation end products (AGEs) activated the receptor for advanced glycation end products (RAGE) and the activation of RAGE is implicated to be the pathogenesis of type 2 diabetic mellitus (T2DM) patient vascular complications. Sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, is a new oral hypoglycemic agent for the treatment of T2DM. However, the beneficial effects on vascular calcification remain unclear. In this study, we used a high-fat diet (HFD)-fed low-density lipoprotein receptor deficiency (LDLR-/-) mice model to investigate the potential effects of sitagliptin on HFD-induced arterial calcification. Mice were randomly divided into 3 groups: (1) normal diet group, (2) HFD group and (3) HFD + sitagliptin group. After 24 weeks treatment, we collected the blood for chemistry parameters and DPP4 activity measurement, and harvested the aorta to evaluate calcification using immunohistochemistry and calcium content. To determine the effects of sitagliptin, tumor necrosis factor (TNF)-α combined with S100A12 was used to induce oxidative stress, activation of nicotinamide adenine dinucleotide phosphate (NADPH), up-regulation of bone markers and RAGE expression, and cell calcium deposition on human aortic smooth muscle cells (HASMCs). We found that sitagliptin effectively blunted the HFD-induced artery calcification and significantly lowered the levels of fasting serum glucose, triglyceride (TG), nitrotyrosine and TNF-α, decreased the calcium deposits, and reduced arterial calcification. In an in-vitro study, both S100A12 and TNF-α stimulated RAGE expression and cellular calcium deposits in HASMCs. The potency of S100A12 on HASMCs was amplified by the presence of TNF-α. Sitagliptin and Apocynin (APO), an NADPH oxidase inhibitor, inhibited the TNF-α + S100A12-induced NADPH oxidase and nuclear factor (NF)-κB activation, cellular oxidative stress, RAGE expression, osteo transcription factors expression and calcium deposition. In addition, treatment with sitagliptin, knockdown of RAGE or TNF-α receptor blunted the TNF-α + S100A12-induced RAGE expression. Our findings suggest that sitagliptin may suppress the initiation and progression of arterial calcification by inhibiting the activation of NADPH oxidase and NF-κB, followed by decreasing the expression of RAGE.

Optimal blood pressure for patients with end-stage renal disease following coronary interventions.

Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end-stage renal disease (ESRD) (eGFR < 15 ml/min/1.73m2 ) still unclear. The authors aimed to investigate the ideal achieved BP in ESRD patients with CAD after coronary intervention. Five hundred and seventy-five ESRD patients who had undergone percutaneous coronary interventions (PCIs) were enrolled and their clinical outcomes were analyzed according to the category of systolic BP (SBP) and diastolic BP (DBP) achieved. The clinical outcomes included major cardiovascular events (MACE) and MACE plus hospitalization for congestive heart failure (total cardiovascular (CV) event).The mean systolic BP was 135.0 ± 24.7 mm Hg and the mean diastolic BP was 70.7 ± 13.1 mm Hg. Systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg had the lowest MACE (11.0%; 13.2%) and total CV event (23.3%; 21.1%). Patients with systolic BP < 120 mm Hg had a higher risk of MACE (HR: 2.01; 95% CI: 1.17-3.46, p = .008) than those with systolic BP 140-149 mm Hg. Patients with systolic BP ≥ 160 mm Hg (HR: 1.84; 95% CI, 3.27-1.04, p = .04) and diastolic blood BP ≥ 90 mm Hg (HR: 2.19; 95% CI: 1.15-4.16, p = .02) had a higher risk of total CV event rate when compared to those with systolic BP 140-149 mm Hg and diastolic BP 80-89 mm Hg. A J-shaped association between systolic (140-149 mm Hg) and diastolic (80-89 mm Hg) BP and decreased cardiovascular events for CAD was found in patients with ESRD after undergoing PCI in non-Western population.