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1.
Theranostics ; 10(4): 1649-1677, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042328

RESUMO

Rationale: Autophagy in Schwann cells (SCs) is crucial for myelin debris degradation and clearance following peripheral nerve injury (PNI). Nerve growth factor (NGF) plays an important role in reconstructing peripheral nerve fibers and promoting axonal regeneration. However, it remains unclear if NGF effect in enhancing nerve regeneration is mediated through autophagic clearance of myelin debris in SCs. Methods: In vivo, free NGF solution plus with/without pharmacological inhibitors were administered to a rat sciatic nerve crush injury model. In vitro, the primary Schwann cells (SCs) and its cell line were cultured in normal medium containing NGF, their capable of swallowing or clearing degenerated myelin was evaluated through supplement of homogenized myelin fractions. Results: Administration of exogenous NGF could activate autophagy in dedifferentiated SCs, accelerate myelin debris clearance and phagocytosis, as well as promote axon and myelin regeneration at early stage of PNI. These NGF effects were effectively blocked by autophagy inhibitors. In addition, inhibition of the p75 kD neurotrophin receptor (p75NTR) signal or inactivation of the AMP-activated protein kinase (AMPK) also inhibited the NGF effect as well. Conclusions: NGF effect on promoting early nerve regeneration is closely associated with its accelerating autophagic clearance of myelin debris in SCs, which probably regulated by the p75NTR/AMPK/mTOR axis. Our studies thus provide strong support that NGF may serve as a powerful pharmacological therapy for peripheral nerve injuries.

2.
Medicine (Baltimore) ; 99(6): e19064, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028428

RESUMO

BACKGROUND: This meta-analysis is to evaluate the efficacy and safety of bivalirudin in patients with ST-elevation myocardial infarction (STEMI). METHODS: PubMed, Cochrane Library, Embase, CNKI, CBMdisc, and VIP database were searched. Randomized controlled trial (RCT) was selected and the meta-analysis was conducted by RevMan 5.1. The primary efficacy endpoint was the incidence of major adverse cardiovascular events (MACE) and the primary safety endpoint was the incidence of major bleeding. Secondary efficacy endpoints were myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST), stock, mortality, and thrombocytopenia. The pooled risk ratios (RRs) with the corresponding 95% confidence intervals (CI) were used to assess the efficacy and safety of bivalirudin vs heparin. RESULTS: Seven RCTs met the inclusion criteria, and 16,640 patients were included. We found that bivalirudin associated with lower risk of mortality (RR = 1.05; 95% CI = 0.74-1.49; P = .03; I = 2%), major bleeding (RR = 0.64; 95% CI = 0.54-0.75; P < .00001; I = 70%) and thrombocytopenia (RR = 0.39; 95% CI = 0.25-0.61; P < .0001; I = 0) compared with heparin. However, the use of bivalirudin increase the risk of MI(RR = 1.37; 95% CI = 1.10-1.71; P = .004; I = 25%) and ST(RR = 1.61; 95% CI = 1.05-2.47; P = .03; I = 70%) and has similar risk of MACE (RR = 1.00; 95% CI = 0.90-1.11; P = .97; I = 16%), TVR (RR = 1.43; 95% CI = 0.92-2.22; P = .11; I = 46%) and stock (RR = 1.43; 95% CI = 0.92-2.22; P = .11; I = 46%) compared with heparin used in STEMI patients. CONCLUSION: Bivalirudin associated with lower risk of mortality, major bleeding and thrombocytopenia compared with heparin. However, the use of bivalirudin increase the risk of MI and ST and has similar risk of MACE, TVR and stock compared with heparin used in STEMI patients.

3.
Oxid Med Cell Longev ; 2020: 9741369, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998447

RESUMO

Spinal cord injury (SCI) is a devastating disease that may lead to lifelong disability. Thus, seeking for valid drugs that are beneficial to promoting axonal regrowth and elongation after SCI has gained wide attention. Metformin, a glucose-lowering agent, has been demonstrated to play roles in various central nervous system (CNS) disorders. However, the potential protective effect of metformin on nerve regeneration after SCI is still unclear. In this study, we found that the administration of metformin improved functional recovery after SCI through reducing neuronal cell apoptosis and repairing neurites by stabilizing microtubules via PI3K/Akt signaling pathway. Inhibiting the PI3K/Akt pathway with LY294002 partly reversed the therapeutic effects of metformin on SCI in vitro and vivo. Furthermore, metformin treatment weakened the excessive activation of oxidative stress and improved the mitochondrial function by activating the nuclear factor erythroid-related factor 2 (Nrf2) transcription and binding to the antioxidant response element (ARE). Moreover, treatment with Nrf2 inhibitor ML385 partially abolished its antioxidant effect. We also found that the Nrf2 transcription was partially reduced by LY294002 in vitro. Taken together, these results revealed that the role of metformin in nerve regeneration after SCI was probably related to stabilization of microtubules and inhibition of the excessive activation of Akt-mediated Nrf2/ARE pathway-regulated oxidative stress and mitochondrial dysfunction. Overall, our present study suggests that metformin administration may provide a potential therapy for SCI.

4.
Int Heart J ; 61(1): 153-159, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31956131

RESUMO

A previous study and a gene-annotation enrichment analysis for potential targets of the microRNA miR-202-3p both suggest that this microRNA might be implicated in cardiovascular and metabolic diseases. In the present study, the role of miR-202-3p in the pathogenesis of coronary heart disease (CHD) was explored. We conduct a case-control study to detect the expression levels of miR-202-3p in peripheral blood cells and found that miR-202-3p expression was significantly higher in CHD cases than in controls (P < 0.001). miR-202-3p levels were negatively correlated with platelet distribution width (r = -0.348, P = 0.002) and mean platelet volume (r = -0.29, P = 0.01). Further functional analyses suggested that stimulation with oxidized low-density lipoprotein (ox-LDL) induced miR-202-3p expression, and that this microRNA suppressed the formation of ox-LDL-induced macrophage foam cells derived from THP-1 cells in a feedback manner. In addition, miR-202-3p overexpression modulated the expression of several key genes involved in foam cell formation, including that of ABCG4, NCEH1I, and SCARB2. In summary, miR-202-3p was associated with CHD, exerting a protective role against CHD by feedback suppression of ox-LDL-induced macrophage foam cell formation.

5.
Hypertens Res ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31925339

RESUMO

This study evaluated the impact of ventricular rate (VR) in atrial fibrillation (AF) patients with oscillometric BP measurements. This study included 138 patients with AF and 112 patients with sinus rhythm (SR) who underwent coronary angiography. Left arm BP was measured three times with an oscillometric device, and the average was recorded as the final oscillometric value. At the same time, the average of three intra-aortic BP readings was used as invasive values. Delta BP was the difference between intra-aortic and oscillometric BP. Meanwhile, the BP percentage difference (PD-BP) was calculated with the following formula: PD-BP = (delta BP/intra-aortic BP) × 100%. Based on the VR, four subgroups of AF and SR patients, <80, 80-99, 100-120, and >120 bpm, were created, and the mean PD-BP for both systolic blood pressure (SBP) and diastolic blood pressure (DBP) was significantly higher in the AF group than in the SR group. Moreover, the mean PD-SBP values gradually increased as VR increased in both groups. More importantly, the difference in PD-SBP between the AF and SR groups increased as VR increased: when VR was <80 bpm, the levels were similar (-2.0 ± 3.5 vs. -1.4 ± 2.7 mm Hg, NS), but these values in AF patients were significantly higher when VR was 80-99 bpm (-3.7 ± 5.0 vs. -1.8 ± 2.3 mm Hg, p < 0.05), 100-120 bpm (-6.1 ± 4.3 vs. -2.3 ± 1.9 mm Hg, p < 0.05) and >120 bpm (-7.8 ± 4.9 vs. -2.9 ± 1.7 mm Hg, p < 0.05). The accuracy of oscillometric BP measurements are dependent on the ventricular rate in AF patients even after three measurements, and a higher ventricular rate may result in larger underestimations of oscillometric BP.

6.
Exp Neurol ; 324: 113138, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31794745

RESUMO

After spinal cord injury (SCI), the inhibitory molecules derived from scars at the lesion sites and the limited regenerative capacity of neuronal axons pose difficulties for the recovery after SCI. Remodeling of cytoskeleton structures including microtubule assembly and tubulin post-translational modification are widely accepted to play a crucial role in initiation of growth cone and regrowth of injured axon. Although increasing studies have focused on the association between tubulin acetylation and autophagy due to the role of tubulin acetylation in organelles and substances transport, there are no studies exploring the effect of tubulin acetylation on autophagy after spinal cord injury (SCI). Here, we found that histone deacetylase 6 (HDAC6) was significantly up-regulated after SCI, while inhibition of HDAC6 by Tubastatin A induced functional recovery after SCI. In view of enzyme-dependent and -independent mechanisms of HDAC6 to adjust diverse cellular processes, such as autophagy, the ubiquitin proteasome system and post-translational modification of tubulin, we mainly focused on the significance of HDAC6 in axonal regeneration and autophagy after SCI. Western blotting, Co-immunoprecipitation and immunofluorescence staining were conducted to showed that Tubastatin A treatment in nocodazole-treated cells and mice suffering from SCI prompted acetylation and stabilization of microtubules and thus restored transport function, which may contribute to restored autophagic flux and increased axonal length. Whereas inhibition of degradation of autolysosomes by bafilomycin A1 (Baf-A1) reversed functional recovery caused by Tubastatin A, revealing the association between tubulin acetylation and autophagy, which supports HDAC6 inhibition as a potential target for SCI treatment.

7.
J Clin Hypertens (Greenwich) ; 22(1): 65-73, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31816157

RESUMO

We aimed to examine whether hypertension status modified the association between sleep duration and stroke among middle-aged and elderly population. This cross-sectional study included 10 516 participants aged ≥45 years from the China Hypertension Survey study. Sleep duration and history of stroke were assessed by questionnaires. Multivariate logistic regression analyses, a generalized additive model (GAM) and smooth curve fitting (penalized spline method) and a two-piecewise logistic regression models were performed to evaluate the association between sleep duration and stroke in different status of hypertension. 95% confidence interval (CI) for turning point was obtained by bootstrapping. Multiple logistic analyses showed that per 1 hour increase in sleep duration was associated with a 37% increased prevalence of stroke among participants without hypertension and associated with a 8% increased prevalence of stroke among hypertensive participants (without hypertension: odds ratio [OR] = 1.37, 95% CI 1.09-1.71; with hypertension: OR = 1.08, 95% CI 0.95-1.21; PInteraction  = .029). The fully adjusted smooth curves presented a linear association between sleep duration and stroke among participants without hypertension, but a threshold, nonlinear association among hypertensive participants. The turning point for the curve was found at a sleep duration of 8 (95% CI 5-9) h among hypertensive patients. The ORs (95% CIs) for stroke were 0.92 (0.79, 1.06) and 1.60 (1.23, 2.08) to the left and right of the turning point, respectively. In conclusion, we found a linear association between sleep duration and stroke among middle-aged and elderly participants without hypertension, but a threshold, nonlinear association among hypertensive participants.

8.
J Cell Mol Med ; 24(1): 488-510, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31680473

RESUMO

High plasma levels of homocysteine (Hcy) are regarded as a risk factor for atrial fibrillation (AF), which is closely associated with the pathological consequence of atrial fibrosis and can lead to heart failure with a high mortality rate; here, we show that atrial fibrosis is mediated by the relationship between canonical transient receptor potential 3 (TRPC3) channels and sirtuin type 1 (SIRT1) under the stimulation of Hcy. The left atrial appendage was obtained from patients with either sinus rhythm (SR) or AF and used to evaluate the relationship between the concentration of Hcy and a potential mechanism of cardiac fibrosis mediated by TRPC3 and SIRT1. We next performed transverse aortic constriction (TAC) in mouse to investigate the relationship. The mechanisms underlying atrial fibrosis involving TRPC3 and SIRT1 proteins were explored by co-IP, BLI and lentivirus transfection experiments. qPCR and WB were performed to analyse gene and protein expression, respectively. The higher level of atrial fibrosis was observed in the HH mouse group with a high Hcy diet. Such results suggest that AF patients may be more susceptible to atrial fibrosis and possess a high probability of progressing to hyperhomocysteinemia. Moreover, our findings are consistent with the hypothesis that TRPC3 channel up-regulation leads to abnormal accumulation of collagen, with the down-regulation of SIRT1 as an aetiological factor of high Hcy, which in turn predisposes to atrial fibrosis and strongly enhances the possibility of AF.

9.
J Cell Mol Med ; 24(2): 1220-1232, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31840938

RESUMO

Blood-brain barrier (BBB) disruption and neuronal apoptosis are important pathophysiological processes after traumatic brain injury (TBI). In clinical stroke, Dl-3n-butylphthalide (Dl-NBP) has a neuroprotective effect with anti-inflammatory, anti-oxidative, anti-apoptotic and mitochondrion-protective functions. However, the effect and molecular mechanism of Dl-NBP for TBI need to be further investigated. Here, we had used an animal model of TBI and SH-SY5Y/human brain microvascular endothelial cells to explore it. We found that Dl-NBP administration exerts a neuroprotective effect in TBI/OGD and BBB disorder, which up-regulates the expression of tight junction proteins and promotes neuronal survival via inhibiting mitochondrial apoptosis. The expressions of autophagy-related proteins, including ATG7, Beclin1 and LC3II, were significantly increased after TBI/OGD, and which were reversed by Dl-NBP treatment both in vivo and in vitro. Moreover, rapamycin treatment had abolished the effect of Dl-NBP for TBI recovery. Collectively, our current studies indicate that Dl-NBP treatment improved locomotor functional recovery after TBI by inhibiting the activation of autophagy and consequently blocking the junction protein loss and neuronal apoptosis. Dl-NBP, as an anti-inflammatory and anti-oxidative drug, may act as an effective strategy for TBI recovery.

10.
Aging Dis ; 10(6): 1233-1245, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788335

RESUMO

Autophagy is a lysosome-dependent cellular catabolic mechanism that mediates the turnover of dysfunctional organelles and aggregated proteins. It has a neuroprotective role on neurodegenerative diseases. Here, we hypothesized that autophagy may also have a neuroprotective role in diabetes-associated cognitive decline (DACD). In current study, we found that db/db mice display cognitive decline with inferior learning and memory function. The accumulation of ß-amyloid1-42 (Aß1-42), which is a characteristic of Alzheimer's disease (AD), was markedly higher in the prefrontal cortex (PFC), cornu ammon1 (CA1), and dentate gyrus (DG) areas of the hippocampus in db/db mice. Moreover, BDNF and microtubule associated protein 2 (MAP2) levels were lower in the hippocampus of db/db mice. However, there was no noticeable differences in the level of apoptosis in the hippocampus between control (CON) mice and db/db mice. Markers of autophagy in the hippocampus were elevated in db/db mice. The expression levels of ATG5, ATG7, and LC3B were higher, and the level of P62 was lower. An autophagy inhibitor, 3-MA, and ATG7 siRNA significantly reversed the activation of autophagy in vitro, which was accompanied with a higher level of apoptosis. Taken together, our current study suggests that diabetes is associated with cognitive decline, and activation of autophagy has a neuroprotective role in DACD.

11.
Int J Hypertens ; 2019: 9473182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781383

RESUMO

Background: Association between age at menarche (AAM) and hypertension remains a controversial topic, and data in China were sparse. Therefore, we aimed to investigate the association between AAM and hypertension in Chinese female population. Methods: In this cross-sectional study, 5,102 females aged ≥15 years were enrolled. Self-reported AAM was assessed by the questionnaire. Multiple linear regression analysis was used to evaluate the association between systolic blood pressure (SBP), diastolic blood pressure (DBP), and AAM. Logistic regression analysis was performed to evaluate the association between hypertension and AAM. Generalized additive model (GAM) and smooth curve fitting (penalized spline method) were conducted to explore the exact shape of curve between them. Results: The overall mean of AAM was 15.5 years. Each additional year of AAM was associated with a 15% higher risk of hypertension (odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.11-1.19). Among females with hypertension, there was a significant positive association between AAM and SBP (ß = 0.88, 95% CI: 0.29-1.46) and DBP (ß = 0.80, 95% CI: 0.47-1.13). A significantly higher risk of hypertension was found in younger subjects (15-44 y: OR = 1.37, 95% CI: 1.21-1.55; P for interaction = 0.009) compared with those aged between 62 and 97 y. Conclusions: AAM was positively associated with hypertension and blood pressure, especially among females in early adulthood from southern China.

12.
Front Pharmacol ; 10: 1224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680984

RESUMO

The process of axonal regeneration after peripheral nerve injury (PNI) is slow and mostly incomplete. Previous studies have investigated the neuroprotective effects of fibroblast growth factor 10 (FGF10) against spinal cord injury and cerebral ischemia brain injury. However, the role of FGF10 in peripheral nerve regeneration remains unknown. In this study, we aimed to investigate the underlying therapeutic effects of FGF10 on nerve regeneration and functional recovery after PNI and to explore the associated mechanism. Our results showed that FGF10 administration promoted axonal regeneration and functional recovery after nerve damage. Moreover, exogenous FGF10 treatment also prevented SCs from excessive oxidative stress-induced apoptosis, which was probably related to the activation of phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling. The inhibition of the PI3K/Akt pathway by the specific inhibitor LY294002 partially reversed the therapeutic effects of FGF10 both in vivo and in vitro. Thus, from our perspective, FGF10 may be a promising therapeutic drug for repairing sciatic nerve damage through countering excessive oxidative stress-induced SC apoptosis.

13.
J Neurochem ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602651

RESUMO

In recent years, many studies have focused on autophagy, an evolutionarily conserved mechanism that relies on lysosomes to achieve cellular metabolic requirements and organelle turnover, and revealed its important role in animal models of traumatic injury. Autophagy is a double-edged sword. Appropriate levels of autophagy can promote the removal of abnormal proteins or damaged organelles, while hyperactivated autophagy can induce autophagic apoptosis. However, recent studies suggest that autophagic flux seems to be blocked after traumatic brain injury (TBI), which contributes to the apoptosis of brain cells. In this study, valproic acid (VPA), which was clinically used for epilepsy treatment, was used to treat TBI. The Morris water maze test, hematoxylin & eosin staining and Nissl staining were first conducted to confirm that VPA treatment had a therapeutic effect on mice after TBI. Western blotting, enzyme-linked immunosorbent assay and immunofluorescence staining were then performed to reveal that VPA treatment reversed TBI-induced blockade of autophagic flux, which was accompanied by a reduced inflammatory response. In addition, the variations in activation and phenotypic polarization of microglia were observed after VPA treatment. Nevertheless, the use of the autophagy inhibitor 3-methyladenine partially abolished VPA-induced neuroprotection and the regulation of microglial function after TBI, resulting in the deterioration of the central nervous system microenvironment and neurological function. Collectively, VPA treatment reversed the TBI-induced blockade of autophagic flux in the mouse brain cortex, subsequently inhibiting brain cell apoptosis and affecting microglial function to achieve the promotion of functional recovery in mice after TBI.

14.
ACS Appl Mater Interfaces ; 11(44): 41482-41489, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31597432

RESUMO

The field of neuromorphic computing systems has been through enormous progress in recent years, whereas some issues are still remaining to be solved. One of the biggest challenges in neuromorphic circuit designing is the lack of a robust device with functions comparable to or even better than the metal-oxide-semiconductor field-effect transistor (MOSFET) used in traditional integrated circuits. In this work, we demonstrated a MoS2 neuristor using a dual-gate transistor structure. An ionic top gate is designed to control the migration of ions, while an electronic back gate is used to control electronic migration. By applying different driving signals, the MoS2 neuristor can be programmed as a neuron, a synapse, or an n-type MOSFET, which can be seen as a fundamental building block in the neuromorphic circuit design. The MoS2 neuristor provides viable solutions for future reconfigurable neuromorphic systems and can be a promising candidate for future neuromorphic computing.

15.
Hypertens Res ; 42(12): 1971-1978, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31562418

RESUMO

In the treatment of resistant hypertension, physiologically individualized therapy based on phenotyping with plasma renin activity (PRA) and plasma aldosterone significantly improves blood pressure control. Patients with a low-renin/low aldosterone (Liddle) phenotype respond best to amiloride, while those with low-renin/high aldosterone respond best to aldosterone antagonists, and those with high renin/high aldosterone (renal phenotype) respond best to angiotensin receptor blockers (ARB). However, it is important to measure PRA in a stimulated condition to distinguish between low levels due to high salt intake, licorice or nonsteroidal inflammatory drugs and low levels due to suppression by excess aldosterone secretion or renal tubular genetic variants causing retention of salt and water (Liddle phenotype). In the past, both diuretics and angiotensin converting inhibitors (ACEi) have been used for this purpose, and it has been assumed that these classes of drugs are equivalent. In this study of 2896 patients with hypertension, we evaluated that assumption. We found important differences among diuretics alone, ACEi/ARB alone, and ACEi/ARB + diuretics, which all stimulated PRA. However, ACEi/ARB lowers plasma aldosterone, and beta blockers lower PRA. Among patients with systolic pressure ≥ 180 mmHg ± diastolic pressure ≥ 100 mmHg stimulated only by diuretics, the phenotypes were 25% Liddle, 38% IA, 8.7% renal, and 28.3% mixed. In choosing physiologically individualized therapy based on PRA and aldosterone, it is important to consider the classes of stimulating drugs. Phenotypes are best distinguished by taking into account the aldosterone/PRA ratio in addition to the levels of PRA and aldosterone.

16.
Drug Des Devel Ther ; 13: 2619-2632, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534311

RESUMO

Objective: The aim was to investigate the role and potential mechanism of geranylgeranylacetone (GGA) in the development of atherosclerosis, and to explore the role of heat shock protein 22 (HSP22) in mediating GGA effect. Methods: Human coronary artery endothelial cell (HCAEC) was used for in vitro study. RNA interference was applied to suppress HSP22 in the cells. Cellular apoptosis and intracellular level of reactive oxygen species (ROS) were detected by flow cytometer, and proteins of HSP22, NF-κB, eNOS, and ICAM-1 were assessed by immunoblotting. HSP22-/-//ApoE-/-, and HSP22+/+//ApoE-/- mice were used to investigate the effect of GGA in the animal model of atherosclerosis. Atherosclerotic lesion of the mice aortas was evaluated by Oil Red O staining and H&E staining. Results: GGA significantly inhibited HCAEC apoptosis in response to oxidized-LDL (ox-LDL), but stimulated HSP22 synthesis in the cells. Transfection of HSP22-siRNA in the cells resulted in complete blockage of the GGA effect on apoptosis. GGA also significantly inhibited ROS, NF-κB, and ICAM-1 in the cells transfected control siRNA, but not in the cells transfected with HSP22-siRNA. Atherosclerotic plaque in the aorta was significantly less in the wild type (WT) animals treated with GGA as stained either by Oil Red O or by H&E staining, but not in the HSP22-KO mice. GGA significantly inhibited expression of NF-κB and ICAM-1 in the WT mice, but not in the HSP22-KO mice. Conclusion: GGA-induced HSP22, and inhibited ox-LDL-induced apoptosis as well as expression of NF-κB and ICAM-1 in the HCAECs. GGA also attenuated formation of atherosclerotic plaques in mice aorta. Suppression of HSP22 by siRNA resulted in blockage of the GGA inhibition on apoptosis or stimulation on NF-κB and ICAM-1. These findings suggested that GGA protects endothelial cells from injury in response to ox-LDL and block atherosclerotic development in mice aorta through induction of HSP22.

17.
Chin Med J (Engl) ; 132(18): 2229-2236, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31478927

RESUMO

OBJECTIVE: Anabolic-androgenic steroids (AAS) represents a group of synthetic testosterone derivatives that play an important role in clinical treatment. These drugs are widely abused among the general public to increase lean weight and improve athletic performance. It has been reported that AAS use can produce many adverse effects, especially the occurrence of cardiovascular risk. Although there are many related studies, there has been no consensus on AAS use and cardiovascular risk. The present study was to review the effect of AAS on the cardiovascular system. DATA SOURCES: The data in this review were obtained from articles included in PubMed and the National Center for Biotechnology Information database. STUDY SELECTION: Original articles, case reports, and systematic reviews about AAS were selected for the article. RESULTS: The use/abuse of AAS is correlated with higher cardiovascular risks, and many AAS users/abusers had cardiovascular diseases. However, there are many confounding factors in the studies that explored the causality between AAS intake and disease development, and additional studies are required to determine AAS toxicity. CONCLUSION: AAS produces toxic effects on the cardiovascular system, and it is necessary to ensure that more people know this about AAS, including medical personnel.

18.
Chin Med J (Engl) ; 132(18): 2150-2156, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31490268

RESUMO

BACKGROUND: The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran. METHODS: A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. RESULTS: During 6-month follow-up, 87 participants occurred bleeding events. For every 1 × 10/L increase in leukocyte count, the risk of bleeding increased by 11% (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99-1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75 × 10/L. For leukocyte counts < 6.75 × 10/L, the HR (95% CI) was 0.88 (0.69-1.13), and for leukocyte counts ≥ 6.75 × 10/L, the HR (95% CI) was 1.28 (1.09-1.51). CONCLUSION: This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran. CLINICAL TRIAL REGISTRATION: NCT02414035, https://clinicaltrials.gov.

19.
Nat Mater ; 18(10): 1091-1097, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31406368

RESUMO

Although indium tin oxide (ITO) is widely used in optoelectronics due to its high optical transmittance and electrical conductivity, its degenerate doping limits exploitation as a semiconduction material. In this work, we created short-channel active transistors based on an ultra-thin (down to 4 nm) ITO channel and a high-quality, lanthanum-doped hafnium oxide dielectric of equivalent oxide thickness of 0.8 nm, with performance comparative to that of existing metal oxides and emerging two-dimensional materials. Short-channel immunity, with a subthreshold slope of 66 mV per decade, off-state current <100 fA µm-1 and on/off ratio up to 5.5 × 109, was measured for a 40-nm transistor. Logic inverters working in the subthreshold regime exhibit a high gain of 178 at a low-supply voltage of 0.5 V. Moreover, radiofrequency transistors, with as-measured cut-off frequency fT and maximum oscillation frequency fmax both >10 GHz, have been demonstrated. The unique wide bandgap and low dielectric constant of ITO provide prospects for future scaling below the 5-nm regime for advanced low-power electronics.

20.
Environ Pollut ; 253: 1021-1029, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31434179

RESUMO

Permeable reactive bio-barriers (Bio-PRBs) are a new and developing technique for in situ remediation of groundwater contamination. Some remediation technologies have often been impeded by insufficient understanding of contaminant transport and transformation in the subsurface environment. Therefore, advanced knowledge in contaminant transport and reactions in Bio-PRBs will be crucial to the successful practical application of this technique. A two-dimensional reaction model C1 was developed for predicting the multi-path chain kinetic reaction of 1,1,1-trichloroethane (1,1,1-TCA) in Bio-PRBs. This study demonstrates that model C1 is able to predict the 1,1,1-TCA breakthrough time and rapidly evaluate the Bio-PRBs retardation performance. The results show that microbial growth and immobilization are the key factors that affect the retardation and remediation performance of Bio-PRBs. The free growth of microorganisms had significant negative effects on hydraulic conductivity (K) in the zero-valent iron (ZVI) region of free microorganism Bio-PRBs (FM-PRBs). The total head loss in the FM-PRB was 9.0 cm, which was significantly greater than the head loss (6.5 cm) of immobilized microorganism Bio-PRBs (IM-PRBs). Compared to ZVI-PRBs and FM-PRBs, the numerical simulation results reveal that microbial immobilization significantly improves the remediation performance of IM-PRBs by 550.9% and 32.7%, respectively. The dual effect of microorganisms leads to significant differences in the 1,1,1-TCA and daughter products (1,1-dichloroethane, 1,1-dichloroethene, chloroethane and vinyl chloride) contaminant-plume evolution between FM-PRBs and IM-PRBs. In addition, model C1 can be utilized to design standard Bio-PRBs for real site of 1,1,1-TCA contanminated groundwater. To meet the safety standard of groundwater as potable water, the width of IM-PRBs needs to be increased by 24 cm. However, in FM-PRBs, the width needs to be increased by 42 cm. Therefore, IM-PRBs save costs significantly. This work has successfully used a model to optimize Bio-PRBs and to predict 1,1,1-TCA and daughter products contaminant-plume evolution in different Bio-PRBs.


Assuntos
Modelos Químicos , Tricloroetanos/química , Poluentes Químicos da Água/química , Monitoramento Ambiental , Cloreto de Etil , Água Subterrânea , Ferro , Cinética , Poluentes Químicos da Água/análise
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