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1.
Cancer Control ; 30: 10732748231210733, 2023.
Article in English | MEDLINE | ID: mdl-37969067

ABSTRACT

BACKGROUND: The aim of this retrospective study was to construct and clinically apply a nomogram for cancer-specific survival (CSS) in patients diagnosed with base-of-tongue squamous cell carcinoma (BOTSCC) to predict their survival prognosis. METHODS: We collected 8448 patients diagnosed with BOTSCC during 2004-2015 from the Surveillance, Epidemiology, and End Results (SEER) database and divided 30% and 70% of them into validation and training cohorts, respectively. We utilized backward stepwise regression in the Cox model to select variables. Predictive variables were subsequently identified from the variables selected above by using multivariate Cox regression. The new survival model was compared with the American Joint Committee on Cancer (AJCC) prognosis model using the following variables: calibration curve, time-dependent area under the receiver operating characteristic curve (AUC), concordance index (C-index), integrated discrimination improvement (IDI), decision-curve analysis (DCA), and net reclassification improvement (NRI). RESULTS: A nomogram was established for predicting the CSS probability in patients with BOTSCC. Factors including sex, race, age at diagnosis, marital status, radiotherapy status, chemotherapy status, TNM AJCC stage, surgery status, tumor size, and months from diagnosis to treatment were selected through multivariate Cox regression as independent predictors of CSS. Calibration plots indicated that the model we established had satisfactory calibration ability. The AUC, C-index, IDI, DCA, and NRI results illustrated that the nomogram performed explicit prognoses more accurately than did the AJCC system alone. CONCLUSION: We identified the relevant factors affecting the survival of BOTSCC patients and analyzed the data on patients suffering from BOTSCC in the SEER database. These factors were used to construct a new nomogram to give clinical staff a more-visual prediction model for the 3-, 5-, and 8-year probabilities of CSS for patients newly diagnosed with BOTSCC, thereby aiding clinical decision making.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Laryngeal Neoplasms , Tongue Neoplasms , Humans , Prognosis , Nomograms , Carcinoma, Squamous Cell/therapy , Retrospective Studies , Tongue Neoplasms/therapy , Squamous Cell Carcinoma of Head and Neck , Tongue , SEER Program
2.
J Clin Monit Comput ; 37(6): 1521-1531, 2023 12.
Article in English | MEDLINE | ID: mdl-37436598

ABSTRACT

We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology.  The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.


Subject(s)
End Stage Liver Disease , Liver Transplantation , Humans , Arterial Pressure , End Stage Liver Disease/surgery , Bilirubin , Severity of Illness Index , Blood Pressure , Retrospective Studies
3.
J Chin Med Assoc ; 86(8): 748-755, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37220416

ABSTRACT

BACKGROUND: Liver transplantation (LT) is being increasingly performed for alcohol-related liver disease (ALD). It is unclear whether the increasing frequency of LTs in ALD patients has a negative impact on deceased-donor (DDLT) allocation and whether the current policy of 6 months of abstinence before transplantation effectively prevents recidivism after transplantation or improves long-term outcomes. METHODS: A total of 506 adult LT recipients, including 97 ALD patients, were enrolled. The outcomes of ALD patients were compared with those of non-ALD patients. The 97 ALD patients were further divided into group A (6-month abstinence) and group N (nonabstinence) based on the pretransplant alcohol withdrawal period. The incidence of relapsed drinking and the long-term outcomes were compared between the two groups. RESULTS: The prevalence of LT for ALD significantly increased after 2016 (27.0% vs 14.0%; p < 0.01), but the frequency of DDLT for ALD remained unchanged (22.6% vs 34.1%, p = 0.210). After a median follow-up of 56.9 months, patient survival was comparable between the ALD and non-ALD patients (1, 3, and 5 years posttransplant: 87.6%, 84.3%, and 79.5% vs 82.8%, 76.6%, and 72.2%, respectively; p = 0.396). The results were consistent irrespective of the transplant type and disease severity. In ALD patients, 22 of the 70 (31.4%) patients reported relapsed drinking after transplantation, and the prevalence in group A had a higher tendency than that in group N (38.3% vs 17.4%, p = 0.077). Six months of abstinence or nonabstinence did not result in a survival difference, and de novo malignancies were the leading cause of late patient death in ALD patients. CONCLUSION: LT achieves favorable outcomes for ALD patients. Six months of abstinence pretransplant did not predict the risk of recidivism after transplantation. The high incidence of de novo malignancies in these patients warrants a more comprehensive physical evaluation and better lifestyle modifications to improve long-term outcomes.


Subject(s)
Alcoholism , Liver Diseases, Alcoholic , Liver Transplantation , Substance Withdrawal Syndrome , Adult , Humans , Liver Diseases, Alcoholic/surgery , Liver Diseases, Alcoholic/epidemiology , Recurrence
4.
Int J Mol Sci ; 24(6)2023 Mar 16.
Article in English | MEDLINE | ID: mdl-36982743

ABSTRACT

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.


Subject(s)
Atherosclerosis , Obesity, Morbid , Mice , Male , Animals , Weight Loss/physiology , Diet, High-Fat/adverse effects , Hyperplasia , Vascular Endothelial Growth Factor A , Mice, Inbred C57BL , Obesity, Morbid/surgery , Gastrectomy/methods , Atherosclerosis/etiology
5.
Antioxid Redox Signal ; 38(1-3): 215-233, 2023 01.
Article in English | MEDLINE | ID: mdl-35713239

ABSTRACT

Aims: Trimethylamine-N-oxide (TMAO) is a metabolite generated from dietary choline, betaine, and l-carnitine, after their oxidization in the liver. TMAO has been identified as a novel independent risk factor for atherosclerosis through the induction of vascular inflammation. However, the effect of TMAO on neointimal formation in response to vascular injury remains unclear. Results: This study was conducted using a murine model of acutely disturbed flow-induced atherosclerosis induced by partial carotid artery ligation. 3,3-Dimethyl-1-butanol (DMB) was used to reduce TMAO concentrations. Wild-type mice were divided into four groups [regular diet, high-TMAO diet, high-choline diet, and high-choline diet+DMB] to investigate the effects of TMAO elevation and its inhibition by DMB. Mice fed high-TMAO and high-choline diets had significantly enhanced neointimal hyperplasia and advanced plaques, elevated arterial elastin fragmentation, increased macrophage infiltration and inflammatory cytokine secretion, and enhanced activation of nuclear factor (NF)-κB, the NLRP3 inflammasome, and endoplasmic reticulum (ER) stress relative to the control group. Mice fed high-choline diets with DMB treatment exhibited attenuated flow-induced atherosclerosis, inflammasome expression, ER stress, and reactive oxygen species expression. Human aortic smooth muscle cells (HASMCs) were used to investigate the mechanism of TMAO-induced injury. The HASMCs were treated with TMAO with or without an ER stress inhibitor to determine whether inhibition of ER stress modulates the TMAO-induced inflammatory response. Innovation: This study demonstrates that TMAO regulates vascular remodeling via ER stress. Conclusion: Our findings demonstrate that TMAO elevation promotes disturbed flow-induced atherosclerosis and that DMB administration mitigates vascular remodeling, suggesting a rationale for a TMAO-targeted strategy for the treatment of atherosclerosis. Antioxid. Redox Signal. 38, 215-233.


Subject(s)
Atherosclerosis , Inflammasomes , Animals , Humans , Mice , Atherosclerosis/drug therapy , Atherosclerosis/etiology , Carotid Arteries/metabolism , Choline/metabolism , Disease Models, Animal , Inflammasomes/metabolism , NF-kappa B/metabolism , Oxidative Stress , Vascular Remodeling
6.
Am J Respir Crit Care Med ; 207(3): 323-335, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36191258

ABSTRACT

Rationale: Obstructive sleep apnea (OSA)-induced endothelial cell (EC) dysfunction contributes to OSA-related cardiovascular sequelae. The mechanistic basis of endothelial impairment by OSA is unclear. Objectives: The goals of this study were to identify the mechanism of OSA-induced EC dysfunction and explore the potential therapies for OSA-accelerated cardiovascular disease. Methods: The experimental methods include data mining, bioinformatics, EC functional analyses, OSA mouse models, and assessment of OSA human subjects. Measurements and Main Results: Using mined microRNA sequencing data, we found that microRNA 210 (miR-210) conferred the greatest induction by intermittent hypoxia in ECs. Consistently, the serum concentration of miR-210 was higher in individuals with OSA from two independent cohorts. Importantly, miR-210 concentration was positively correlated with the apnea-hypopnea index. RNA sequencing data collected from ECs transfected with miR-210 or treated with OSA serum showed a set of genes commonly altered by miR-210 and OSA serum, which are largely involved in mitochondrion-related pathways. ECs transfected with miR-210 or treated with OSA serum showed reduced [Formula: see text]o2 rate, mitochondrial membrane potential, and DNA abundance. Mechanistically, intermittent hypoxia-induced SREBP2 (sterol regulatory element-binding protein 2) bound to the promoter region of miR-210, which in turn inhibited the iron-sulfur cluster assembly enzyme and led to mitochondrial dysfunction. Moreover, the SREBP2 inhibitor betulin alleviated intermittent hypoxia-increased systolic blood pressure in the OSA mouse model. Conclusions: These results identify an axis involving SREBP2, miR-210, and mitochondrial dysfunction, representing a new mechanistic link between OSA and EC dysfunction that may have important implications for treating and preventing OSA-related cardiovascular sequelae.


Subject(s)
Cardiovascular Diseases , MicroRNAs , Sleep Apnea, Obstructive , Vascular Diseases , Animals , Mice , Humans , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/genetics , Hypoxia/genetics , MicroRNAs/genetics
7.
Sci Data ; 9(1): 639, 2022 10 21.
Article in English | MEDLINE | ID: mdl-36271001

ABSTRACT

Long-term data of fish assemblages collected in the rocky intertidal zone provides a valuable resource for elucidating the temporal variations in species diversity and intertidal ecosystems. In this study, we describe a long-term time-series dataset of fish collected by counting the number of anesthetized fish at sampling stations in the rocky tidepools on the southern coast of Taiwan. The species assemblages were monitored seasonally at the two stations for 16 y (2000-2008 and 2012-2018). In total, 86 samples containing 5137 individuals belonging to 82 species were recorded. Our data can be used for elucidating the temporal variations in fish assemblages and intertidal ecosystems and as background information for the resilience of the fish community conservation in coastal areas. The current study presents valuable data for researchers to understand the temporal and spatial variations in species abundance, richness, diversity, and composition in relation to climate change, environmental factors, and human activities.


Subject(s)
Ecosystem , Fishes , Animals , Humans , Biodiversity , Climate Change , Taiwan , Time Factors
8.
Int J Mol Sci ; 23(6)2022 Mar 12.
Article in English | MEDLINE | ID: mdl-35328486

ABSTRACT

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.


Subject(s)
Dipeptidyl-Peptidase IV Inhibitors , Sepsis , Thrombosis , Animals , Dipeptidyl Peptidase 4 , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases , Disease Models, Animal , Human Umbilical Vein Endothelial Cells , Humans , Hypoglycemic Agents/pharmacology , Inflammation/drug therapy , Linagliptin/pharmacology , Linagliptin/therapeutic use , Lipopolysaccharides/pharmacology , Mice , Microcirculation , Sepsis/complications , Sepsis/drug therapy , Thrombosis/drug therapy , Thrombosis/etiology , Tumor Necrosis Factor-alpha/pharmacology
9.
Zootaxa ; 5189(1): 45-56, 2022 Sep 23.
Article in English | MEDLINE | ID: mdl-37045203

ABSTRACT

A new freshwater goby of Rhinogobius Gill, 1859, were collected from the Minjiang river basin, Fujian Province, PR China. The new goby, Rhinogobius lianchengensis n. sp. can be well distinguished from other congeneric species by the following combination of features: second dorsal fin I/8; anal fin I/6-7; pectoral fin modally 16-17; longitudinal scale rows 33-34; predorsal scales 0-3; vertebral count 27; and specific coloration pattern: scale pocket of lateral body with distal brown to blackish brown mark; cheek deep brown on dorsal half with 7-8 somewhat parallel oblique deep brown bars after the vertical stripe on snout in male; opercle brown to yellowish brown with net-like deep brown marks in both sexes; branchiostegal membrane bright yellow background with 16-19 deep red or brownish red spots in male; first dorsal fin with a black mark in male; pectoral fin base with a median patch of blackish spots surrounding with some irregularly large brown marks; and caudal fin yellow with 3-4 vertical rows of deep brown spots. A diagnostic key to all nominal Rhinogobius species from Fujian Province, PR China is provided.


Subject(s)
Perciformes , Rivers , Female , Male , Animals , Fishes , Gills , China
10.
Zootaxa ; 5189(1): 29-44, 2022 Sep 23.
Article in English | MEDLINE | ID: mdl-37045204

ABSTRACT

A new freshwater rhinogoby has been collected and surveyed from northern Taiwan. The new species, Rhinogobius yangminshanensis n. sp. with fluvial life history can be well distinguished from other congeners by the following combination of features: (1) fin rays: second dorsal fin rays I/9; anal fin rays I/8; pectoral fin rays modally 16; (2) squamation: longitudinal scale series 28-30 (modally 29); perdorsal scales 9-10 (modally 9); (4) vertebral count 27; (5) rear edge of mouth: merely extending to vertical of anterior margin of pupil in male and (6) specific colouration: lateral side with 6-7 longitudinal rows of bright orange to orange red spots in male which general size about 1/2 of pupil diameter. Cheek and opercle with 24-35 orange spots in male. Branchiostegal membrane with many minute orange spots in male. Caudal fin with distally orange zone in male with about 3 vertical rows of orange or orange red spots. First dorsal fin with broad orange band on distally 1/3 area. A middle black spot in abterior first dorsal fin. Pectoral fin with two rows red orange spots in male. The phylogenetic comparisons have revealed that the great mitogenetic differences of R. yangminshanensis with all other congeneric species and sister species would be R. rubromaculatus in Taiwan. A diagnostic key to all valid species of Rhinogobius from Taiwan is also provided.


Subject(s)
Gills , Perciformes , Male , Animals , Phylogeny , Taiwan , Fishes , Fresh Water
11.
Zootaxa ; 5189(1): 18-28, 2022 Sep 23.
Article in English | MEDLINE | ID: mdl-37045205

ABSTRACT

A new species of freshwater gobiid fish of genus Rhinogobius Gill, 1859, were collected from the upper tributary of Dongshi river basin of Janchou City in southern region of Fujian Province, China. Rhinogobius lingtongyanensis n. sp. can be well distinguished from other congeners by the following features: (1) fins: second dorsal fin rays I/8; anal fin rays I/7; pectoral fin rays modally 16; (2) squamation: longitudinal scale series 25-27 (modally 26); predorsal scales 3-6 (modally 5-6); (3) vertebral count 26; and (4) specific colouration in male: lateral body with 6-7 major patches of irregularly grayish to brownish black marks; cheek blackish brown with four oblique grayish black stripes; branchiostegal membrane grayish blue without any light spots; first dorsal fin broad grayish brown band in middle, outer margin pinkish orange; pectoral fin base with longitudinal deep brown bar in upper region; and caudal fin gray with four vertical rows of brown spots, its base with a short brownish black bar. It belongs to the non-diadromous, fluvial hill-stream species. A diagnostic key to all valid species from Fujian Province, China is also provided in this paper.


Subject(s)
Perciformes , Rivers , Male , Animals , Fishes , Fresh Water , China
12.
J Intensive Care ; 9(1): 65, 2021 Oct 21.
Article in English | MEDLINE | ID: mdl-34674768

ABSTRACT

BACKGROUND: Trimethylamine N-oxide (TMAO) is a microbiota-derived metabolite, which is linked to vascular inflammation and atherosclerosis in cardiovascular (CV) diseases. But its effect in infectious diseases remains unclear. We conducted a single-center prospective study to investigate association of TMAO with in-hospital mortality in septic patients admitted to an intensive care unit (ICU). METHODS: Totally 95 septic, mechanically ventilated patients were enrolled. Blood samples were obtained within 24 h after ICU admission, and plasma TMAO concentrations were determined. Septic patients were grouped into tertiles according to TMAO concentration. The primary outcome was in-hospital death, which further classified as CV and non-CV death. Besides, we also compared the TMAO concentrations of septic patients with 129 non-septic patients who were admitted for elective coronary angiography (CAG). RESULTS: Septic patients had significantly lower plasma TMAO levels than did subjects admitted for CAG (1.0 vs. 3.0 µmol/L, p < 0.001). Septic patients in the lowest TMAO tertile (< 0.4 µmol/L) had poorer nutrition status and were given longer antibiotic courses before ICU admission. Circulating TMAO levels correlated positively with daily energy intake, the albumin and prealbumin concentration. Compared with those in the highest TMAO tertile, septic patients in the lowest TMAO tertile were at greater risk of non-CV death (hazard ratio 2.51, 95% confidence interval 1.21-5.24, p = 0.014). However, TMAO concentration was no longer an independent predictor for non-CV death after adjustment for disease severity and nutritional status. CONCLUSION: Plasma TMAO concentration was inversely associated with non-CV death among extremely ill septic patients, which could be characterized as TMAO paradox. For septic patients, the impact of malnutrition reflected by circulating TMAO levels was greater than its pro-inflammatory nature.

13.
Sci Rep ; 10(1): 20683, 2020 11 26.
Article in English | MEDLINE | ID: mdl-33244142

ABSTRACT

Galectin-1, a ß-galactoside-binding lectin mediating inflammation and neovascularization, is reported to attenuate ventricular remodeling after myocardial infarction. But its role in stable coronary artery disease (CAD) has not been fully elucidated. This study aimed to identify the relationship between the circulating galectin-1 level and the severity of CAD in patients with suspected CAD. Pre-procedure galectin-1 and high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in 834 subjects who underwent scheduled coronary angiography. Subjects were grouped into tertiles of the galectin-1 levels. SYNTAX scores were calculated to evaluate the severity of CAD. All patients were followed until January 2019 or the occurrence of major adverse cardiovascular events (MACE). Patients with higher galectin-1 concentrations were older; had greater prevalence of hypertension, diabetes, chronic kidney disease, and heart failure; and were more likely to present with higher hs-CRP levels and SYNTAX scores. During the follow-up period of 1.3 ± 1.1 years, patients in the highest tertile of galectin-1 were associated with a greater risk of MACE after adjustment for age, sex, comorbidities, co-medications, serum levels of hemoglobin, creatinine, hs-CRP, ejection fraction, SYNTAX scores, and revascularization modalities (adjusted hazard ratio 10.95, 95% confidence interval 2.29-52.47, p = 0.003). Galectin-1 showed better discriminatory performance than hs-CRP, and non-inferior performance to SYNTAX scores, in predicting the incidence of MACE.


Subject(s)
Cardiovascular System/metabolism , Cardiovascular System/pathology , Coronary Artery Disease/metabolism , Coronary Artery Disease/pathology , Galectin 1/metabolism , Aged , Aged, 80 and over , C-Reactive Protein/metabolism , Coronary Angiography/methods , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Female , Heart Failure/metabolism , Heart Failure/pathology , Humans , Hypertension/metabolism , Hypertension/pathology , Male , Middle Aged , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Severity of Illness Index
14.
JCI Insight ; 5(23)2020 12 03.
Article in English | MEDLINE | ID: mdl-33119548

ABSTRACT

Proprotein convertase subtilisin/kexin type 9 (PCSK9) affects cholesterol homeostasis by targeting hepatic LDL receptor (LDLR) for lysosomal degradation. Clinically, PCSK9 inhibitors effectively reduce LDL-cholesterol (LDL-C) levels and the incidence of cardiovascular events. Because microRNAs (miRs) are integral regulators of cholesterol homeostasis, we investigated the involvement of miR-483 in regulating LDL-C metabolism. Using in silico analysis, we predicted that miR-483-5p targets the 3'-UTR of PCSK9 mRNA. In HepG2 cells, miR-483-5p targeted the PCSK9 3'-UTR, leading to decreased PCSK9 protein and mRNA expression, increased LDLR expression, and enhanced LDL-C uptake. In hyperlipidemic mice and humans, serum levels of total cholesterol and LDL-C were inversely correlated with miR-483-5p levels. In mice, hepatic miR-483 overexpression increased LDLR levels by targeting Pcsk9, with a significant reduction in plasma total cholesterol and LDL-C levels. Mechanistically, the cholesterol-lowering effect of miR-483-5p was significant in mice receiving AAV8 PCSK9-3'-UTR but not Ldlr-knockout mice or mice receiving AAV8 PCSK9-3'-UTR (ΔBS) with the miR-483-5p targeting site deleted. Thus, exogenously administered miR-483 or similarly optimized compounds have potential to ameliorate hypercholesterolemia.


Subject(s)
Hypercholesterolemia/genetics , MicroRNAs/genetics , Proprotein Convertase 9/genetics , Animals , Atherosclerosis/metabolism , Cholesterol/genetics , Cholesterol/metabolism , Cholesterol, LDL/genetics , Cholesterol, LDL/metabolism , Female , Hep G2 Cells , Humans , Hypercholesterolemia/metabolism , Hyperlipidemias/metabolism , Lipid Metabolism , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs/metabolism , Proprotein Convertase 9/metabolism , Proprotein Convertases/genetics , Receptors, LDL/metabolism
15.
Anesth Analg ; 130(5): 1244-1254, 2020 05.
Article in English | MEDLINE | ID: mdl-32287131

ABSTRACT

BACKGROUND: Cardiovascular waveforms contain information for clinical diagnosis. By learning and organizing the subtle change of waveform morphology from large amounts of raw waveform data, unsupervised manifold learning helps delineate a high-dimensional structure and display it as a novel 3-dimensional (3D) image. We hypothesize that the shape of this structure conveys clinically relevant inner dynamics information. METHODS: To validate this hypothesis, we investigate the electrocardiography (ECG) waveform for ischemic heart disease and arterial blood pressure (ABP) waveform in dynamic vasoactive episodes. We model each beat or pulse to be a point lying on a manifold-like a surface-and use the diffusion map (DMap) to establish the relationship among those pulses. The output of the DMap is converted to a 3D image for visualization. For ECG datasets, first we analyzed the non-ST-elevation ECG waveform distribution from unstable angina to healthy control in the 3D image, and we investigated intraoperative ST-elevation ECG waveforms to show the dynamic ECG waveform changes. For ABP datasets, we analyzed waveforms collected under endotracheal intubation and administration of vasodilator. To quantify the dynamic separation, we applied the support vector machine (SVM) analysis and reported the total accuracy and macro-F1 score. We further performed the trajectory analysis and derived the moving direction of successive beats (or pulses) as vectors in the high-dimensional space. RESULTS: For the non-ST-elevation ECG, a hierarchical tree structure comprising consecutive ECG waveforms spanning from unstable angina to healthy control is presented in the 3D image (accuracy = 97.6%, macro-F1 = 96.1%). The DMap helps quantify and visualize the evolving direction of intraoperative ST-elevation myocardial episode in a 1-hour period (accuracy = 97.58%, macro-F1 = 96.06%). The ABP waveform analysis of Nicardipine administration shows interindividual difference (accuracy = 95.01%, macro-F1 = 96.9%) and their common directions from intraindividual moving trajectories. The dynamic change of the ABP waveform during endotracheal intubation shows a loop-like trajectory structure, which can be further divided using the manifold learning knowledge obtained from Nicardipine. CONCLUSIONS: The DMap and the generated 3D image of ECG or ABP waveforms provides clinically relevant inner dynamics information. It provides clues of acute coronary syndrome diagnosis, shows clinical course in myocardial ischemic episode, and reveals underneath physiological mechanism under stress or vasodilators.


Subject(s)
Databases, Factual , Electrocardiography/methods , Heart Rate/physiology , Imaging, Three-Dimensional/methods , Unsupervised Machine Learning , Wavelet Analysis , Humans , Signal Processing, Computer-Assisted
16.
Toxins (Basel) ; 12(4)2020 04 08.
Article in English | MEDLINE | ID: mdl-32276394

ABSTRACT

Chronic kidney disease (CKD) accelerates the development of neointima formation at the anastomosis site of arteriovenous (AV) fistulas. Accumulation of certain uremic toxins has a deleterious effect on the cardiovascular system. The oral charcoal adsorbent, AST-120, reduces circulating and tissue uremic toxins, but its effect on neointima formation at an AV fistula is unknown. To understand the effect of CKD and AST-120 on neointima formation, we created AV fistulas (common carotid artery to the external jugular vein in an end-to-side anastomosis) in mice with and without CKD. AST-120 was administered in chow before and after AV fistula creation. Administration of AST-120 significantly decreased serum indoxyl sulfate levels in CKD mice. CKD mice had a larger neointima area than non-CKD mice, and administration of AST-120 in CKD mice attenuated neointima formation. Both smooth muscle cell and fibrin components were increased in CKD mice, and AST-120 decreased both. RNA expression of MMP-2, MMP-9, TNFα, and TGFß was increased in neointima tissue of CKD mice, and AST-120 administration neutralized the expression. Our results provided in vivo evidence to support the role of uremic toxin-binding therapy on the prevention of neointima formation. Peri-operative AST-120 administration deserves further investigation as a potential therapy to improve AV fistula patency.


Subject(s)
Arteriovenous Shunt, Surgical/adverse effects , Carbon/administration & dosage , Graft Occlusion, Vascular/prevention & control , Indican/blood , Muscle, Smooth, Vascular/pathology , Neointima , Oxides/administration & dosage , Renal Insufficiency, Chronic/complications , Toxins, Biological/blood , Uremia/complications , Administration, Oral , Adsorption , Animals , Collagen/metabolism , Disease Models, Animal , Graft Occlusion, Vascular/blood , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/pathology , Male , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice, Inbred C57BL , Muscle, Smooth, Vascular/metabolism , Renal Insufficiency, Chronic/blood , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Uremia/blood , Vascular Patency
17.
Sci Data ; 7(1): 84, 2020 03 09.
Article in English | MEDLINE | ID: mdl-32152315

ABSTRACT

The assemblage of fish species in the rocky intertidal zone is highly affected by the destructive impact of human activities and has an extended impact on land-sea interactions. There are a few long-term research projects that have focused on rocky intertidal ecosystems, especially on the resident fish community. Here, we describe a long-term time series dataset of fish collected by counting the number of anesthetized fishes at sampling stations in rocky tidepools in the intertidal zones on the northern coast of Taiwan. The species assemblages were monitored seasonally at three stations from 1999 to 2018. In total, 144 samples containing 1,577 individuals belonging to 106 species were recorded in the surveys. The resulting data can be used as background information for conservation and resilience studies of the fish community in coastal areas and to establish reasonable conservation strategies. This study presents valuable data to ecologists and fisheries biologists interested in understanding the temporal patterns of species abundance, richness, and composition in relation to environmental factors, climate change, and anthropogenic pressures.


Subject(s)
Conservation of Natural Resources , Ecosystem , Fishes/classification , Animals , Climate Change , Environment , Taiwan
18.
Proc Natl Acad Sci U S A ; 116(26): 12974-12979, 2019 06 25.
Article in English | MEDLINE | ID: mdl-31182601

ABSTRACT

Pulsatile shear (PS) and oscillatory shear (OS) elicit distinct mechanotransduction signals that maintain endothelial homeostasis or induce endothelial dysfunction, respectively. A subset of microRNAs (miRs) in vascular endothelial cells (ECs) are differentially regulated by PS and OS, but the regulation of the miR processing and its implications in EC biology by shear stress are poorly understood. From a systematic in silico analysis for RNA binding proteins that regulate miR processing, we found that nucleolin (NCL) is a major regulator of miR processing in response to OS and essential for the maturation of miR-93 and miR-484 that target mRNAs encoding Krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS). Additionally, anti-miR-93 and anti-miR-484 restore KLF2 and eNOS expression and NO bioavailability in ECs under OS. Analysis of posttranslational modifications of NCL identified that serine 328 (S328) phosphorylation by AMP-activated protein kinase (AMPK) was a major PS-activated event. AMPK phosphorylation of NCL sequesters it in the nucleus, thereby inhibiting miR-93 and miR-484 processing and their subsequent targeting of KLF2 and eNOS mRNA. Elevated levels of miR-93 and miR-484 were found in sera collected from individuals afflicted with coronary artery disease in two cohorts. These findings provide translational relevance of the AMPK-NCL-miR-93/miR-484 axis in miRNA processing in EC health and coronary artery disease.


Subject(s)
Coronary Artery Disease/genetics , Mechanotransduction, Cellular/genetics , MicroRNAs/metabolism , Phosphoproteins/metabolism , RNA-Binding Proteins/metabolism , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Adult , Aged , Animals , Case-Control Studies , Cells, Cultured , Computational Biology , Coronary Artery Disease/blood , Coronary Artery Disease/pathology , Endothelial Cells/pathology , Endothelium, Vascular/cytology , Endothelium, Vascular/pathology , Female , Gene Knockdown Techniques , Humans , Kruppel-Like Transcription Factors/genetics , Male , Mice , MicroRNAs/antagonists & inhibitors , MicroRNAs/blood , Middle Aged , Nitric Oxide Synthase Type III/genetics , Phosphorylation , Protein Processing, Post-Translational , RNA Processing, Post-Transcriptional , Serine/metabolism , Stress, Mechanical , Nucleolin
19.
Sci Rep ; 9(1): 3806, 2019 03 07.
Article in English | MEDLINE | ID: mdl-30846741

ABSTRACT

Response surface models (RSMs) were used to predict effects of multiple drugs interactions. Our study was aimed to validate accuracy of the previous published volunteer models during transoesophageal echocardiography (TEE). This is a cross-sectional study with 20 patients scheduled for transesophageal echocardiography in Taipei Veterans General Hospital, Taiwan. Effect-site concentration pairs of alfentanil and propofol were recorded and converted to equivalent remifentanil and propofol effect-site concentrations. Observer's Assessment of Alertness/Sedation (OAA/S) scores were assessed every 2 minutes. Using these data, previous published models of loss of response (LOR), intolerable ventilatory depression (IVD), and loss of response to esophageal instrumentation (LREI) were then estimated. Accuracy of prediction is assessed by calculating the difference between the true response and the model-predicted probability. Clinical events such as interruption of TEE were recorded. The average procedure time was 11 minutes. Accuracy for prediction of LOR and LREI is 63.6% and 38.5%, respectively. There were four patients experienced desaturation for less than 1 minute, which were not predicted by IVD model, and one interruption of TEE due to involuntary movement. The previous published drug-interaction RSMs predict LOR well but not LREI for TEE sedation. Further studies using response surface methodology are needed to improve quality for TEE sedation and clinical implementation.


Subject(s)
Alfentanil/administration & dosage , Anesthetics, Intravenous/administration & dosage , Conscious Sedation/methods , Echocardiography, Transesophageal , Esophagus/drug effects , Propofol/administration & dosage , Aged , Alfentanil/therapeutic use , Anesthetics, Intravenous/therapeutic use , Cross-Sectional Studies , Drug Interactions , Female , Humans , Male , Middle Aged , Propofol/therapeutic use , Taiwan
20.
BMC Genomics ; 19(Suppl 10): 904, 2018 Dec 31.
Article in English | MEDLINE | ID: mdl-30598081

ABSTRACT

BACKGROUND: Human gut microbiome has an essential role in human health and disease. Although the major dominant microbiota within individuals have been reported, the change of gut microbiome caused by external factors, such as antibiotic use and bowel cleansing, remains unclear. We conducted this study to investigate the change of gut microbiome in overweight male adults after bowel preparation, where none of the participants had been diagnosed with any systemic diseases. METHODS: A total of 20 overweight, male Taiwanese adults were recruited, and all participants were omnivorous. The participants provided fecal samples and blood samples at three time points: prior to bowel preparation, 7 days after colonoscopy, and 28 days after colonoscopy. The microbiota composition in fecal samples was analyzed using 16S ribosome RNA gene amplicon sequencing. RESULTS: Our results demonstrated that the relative abundance of the most dominant bacteria hardly changed from prior to bowel preparation to 28 days after colonoscopy. Using the ratio of Prevotella to the sum of Prevotella and Bacteroides in the fecal samples at baseline, the participants were separated into two groups. The fecal samples of the Type 1 group was Bacteroides-dominant, and that of the Type 2 group was Prevotella-dominant with a noticeable presence Bacteroides. Bulleidia appears more in the Type 1 fecal samples, while Akkermensia appears more in the Type 2 fecal samples. Of each type, the gut microbial diversity differed slightly among the three collection times. Additionally, the Type 2 fecal microbiota was temporarily susceptible to bowel cleansing. Predictive functional analysis of microbial community reveals that their activities for the mineral absorption metabolism and arachidonic acid metabolism differed significantly between the two types. Depending on their fecal type, the variance of triglycerides and C-reactive protein also differed between the two types of participants. CONCLUSIONS: Depending upon the fecal type, the microbial diversity and the predictive functional modules of microbial community differed significantly after bowel preparation. In addition, blood biochemical markers presented somewhat associated with fecal type. Therefore, our results might provide some insights as to how knowledge of the microbial community could be used to promote health through personalized clinical treatment.


Subject(s)
Feces/microbiology , Gastrointestinal Microbiome , Overweight/microbiology , Adult , Biodiversity , Humans , Male , Middle Aged , Young Adult
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