Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 95
Filtrar
1.
Mol Med Rep ; 23(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33846815

RESUMO

Arsenic trioxide (ATO)­induced hepatotoxicity limits the therapeutic effect of acute myelogenous leukemia treatment. Magnesium isoglycyrrhizinate (MgIG) is a natural compound extracted from licorice and a hepatoprotective drug used in liver injury. It exhibits anti­oxidant, anti­inflammatory and anti­apoptotic properties. The aim of the present study was to identify the protective action and underlying mechanism of MgIG against ATO­induced hepatotoxicity. A total of 50 mice were randomly divided into five groups (n=10/group): Control; ATO; MgIG and high­ and low­dose MgIG + ATO. Following continuous administration of ATO for 7 days, the relative weight of the liver, liver enzyme, histological data, antioxidant enzymes, pro­inflammatory cytokines, cell apoptosis and changes in Kelch­like ECH­associated protein 1/nuclear factor erythroid 2­related factor 2 (Keap1­Nrf2) signaling pathway were observed. MgIG decreased liver injury, decreased the liver weight and liver index, inhibited oxidative stress and decreased the activity of glutathione, superoxide dismutase and catalase, production of reactive oxygen species and levels of pro­inflammatory cytokines, including IL­1ß, IL­6 and TNF­α. Western blotting showed a decrease in Bax and caspase­3. There was decreased cleaved caspase­3 expression and increased Bcl­2 expression. MgIG notably activated ATO­mediated expression of Keap1 and Nrf2 in liver tissue. MgIG administration was an effective treatment to protect the liver from ATO­induced toxicity. MgIG maintained the level of Nrf2 in the liver and protected the antioxidative defense system to attenuate oxidative stress and prevent ATO­induced liver injury.

2.
Lipids Health Dis ; 20(1): 31, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845846

RESUMO

BACKGROUND: Hyperhomocysteinemia (HHcy) is associated with various health problems, but less is known about the gender differences in risk factors for high plasma homocysteine (Hcy) levels. METHODS: In this study, a retrospective study was carried out on 14,911 participants (7838 males and 7073 females) aged 16-102 years who underwent routine checkups between January 2012 and December 2017 in the Health Management Department of Xuanwu Hospital, China. Anthropometric measurements, including body mass index (BMI) and waist-to-hip ratio, were collected. Fasting blood samples were collected to measure the biochemical indexes. The outcome variable was Hcy level, and a generalized estimating equation (GEE) analysis was used to identify the associations of interest based on gender. RESULTS: Males exhibited increased Hcy levels (16.37 ± 9.66 vs 11.22 ± 4.76 µmol/L) and prevalence of HHcy (37.0% vs 11.3%) compared with females. Hcy levels and HHcy prevalence increased with age in both genders, except for the 16- to 29-year-old group. GEE analysis indicated that irrespective of gender, aspartate aminotransferase, creatinine, uric acid, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels were positively correlated with Hcy levels, and alanine aminotransferase, total cholesterol and glucose were negatively correlated with Hcy levels. However, age, BMI and triglycerides (TGs) were positively correlated with Hcy levels exclusively in females. CONCLUSIONS: Gender differences in risk factors for high plasma Hcy levels were noted. Although common correlational factors existed in both genders, age, BMI and TGs were independent risk factors for Hcy levels specifically in females.

3.
Drug Des Devel Ther ; 15: 543-556, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603344

RESUMO

Purpose: Magnesium isoglycyrrhizinate (MgIG), a single stereoisomer magnesium salt of glycyrrhizic acid, has beneficial effects on the cardiovascular system through anti-inflammatory, anti-oxidation, and anti-apoptotic actions. However, MgIG has not been shown to provide protection against cardiotoxicity induced by arsenic trioxide (ATO). This study aims to demonstrate the protection of MgIG against ATO-induced cardiac toxicity in mice and to investigate the underlying mechanism. Methods: A mouse cardiotoxicity model was established by administering 5 mg/kg ATO for 7 days. MgIG used in conjunction with the ATO to assess its cardioprotection. Results: MgIG administration could significantly reduce reactive oxygen species generation and the changes in tissue morphology. Also, MgIG administration increased the activity of antioxidase, such as superoxide dismutase, catalase, and glutathione peroxidase, and reduced malondialdehyde content and pro-inflammatory cytokine levels. Western blotting showed decreased expression of Bcl-2 associated X protein and Caspase-3, with increased expression of B-cell lymphoma 2. Importantly, MgIG administration increased nuclear factor-erythroid-2-related factor 2 (Nrf2) expression, while the expressions of nuclear factor kappa-B (NF-κB) and toll-like receptor-4 (TLR4) were significantly decreased. Conclusion: Our data showed that MgIG alleviates ATO-induced cardiotoxicity, which is associated to the anti-inflammation, anti-oxidation, and anti-apoptosis action, potentially through activation of the Nrf2 pathway and suppression of the TLR4/NF-κB pathway.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33608702

RESUMO

PURPOSE: Circular RNAs (circRNAs) are involved in the development of diseases by regulating gene expression and become promising novel biomarkers for diseases. The aim of the present study was to identify the circulating circRNA biomarkers for early detection of type 2 diabetes (T2D). METHODS: circRNA expression profiles were screened by microarray between five new T2D cases and five healthy controls. The expression of candidate circRNAs that may be involved in the insulin PI3K/Akt signaling pathway were validated by RT-qPCR in a second sample with 30 T2D cases and 30 controls. The association between circRNAs and T2D and their clinical significances were further assessed by logistic regression model, correlation analysis and ROC curve in a large cohort composed of 313 subjects. The miRNA targets of circRNAs were verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Low expressed circ_0063425 and hsa_circ_0056891 were independent predictors of T2D, IFG and insulin resistance. The two-circRNA panel had a high diagnostic accuracy for discriminating T2D and IFG from healthy controls, especially when body mass index (BMI) was integrated. miR-19a-3p and miR-1-3p were identified as the miRNA targets of hsa_circ_0063425 and hsa_circ_0056891, respectively. Significantly positive correlations were found between the expression levels of AKT and hsa_circ_0063425, PI3K and hsa_circ_0056891, in the total sample and subgroups stratified by glucose levels. CONCLUSION: Downregulated hsa_circ_0063425 and hsa_circ_0056891 might contribute to the pathogenesis of T2D. They are valuable circulating biomarkers for early detection of T2D, which may be involved in regulation of PI3K/AKT signaling.

5.
Biomed Res Int ; 2021: 5545078, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628789

RESUMO

Objective: Psychological status plays a vital role in the recovery in young ischemic stroke patients. However, few reports on the psychological symptoms in Chinese young ischemic stroke patients have been published. In the present study, we aimed to outline the psychological status of young ischemic stroke patients and its risk factors at three months after their stroke. Methods: 364 patients with young ischemic stroke and 384 age-matched healthy controls were consecutively recruited from our study hospitals of the mainland of China between June 2018 and November 2020. Social demographic and clinical data were collected from all enrolled participants in the acute stage of their stroke, and their psychological variables were assessed via the Symptom Checklist 90 Revised (SCL-90-R) at three-month timepoint after their stroke. Multivariable logistic regression analyses were run to identify the independent factors for psychological variables in patients. Results: Compared with healthy controls, patients with young ischemic stroke had significantly higher total score of SCL-90-R and all subscale total scores (p < 0.01 or 0.05). 22.3% (81/364 cases) in young ischemic stroke patients had psychological abnormalities. Compared with young ischemic stroke patients without psychological symptoms (n = 283), patients with psychological symptoms (n = 81) had higher rate of married status (p = 0.03), rate of hypertension (p = 0.01), infarct size (p = 0.01), and the family dysfunction (p < 0.01). Multivariate logistic regression analyses revealed that the family dysfunction (odds ratio [OR], 2.50, 95% confidence interval [CI]: 1.71 to 3.54, p < 0.01), having hypertension (OR, 3.27, 95% CI: 1.92 to 4.27, p = 0.02), and ≥20mm3 infarct size (OR, 2.39, 95% CI: 1.53 to 3.45, p < 0.01) were independent factors for having psychological abnormalities in patients with young ischemic stroke at three months after their stroke. Single (OR, 1.23, 95% CI: 1.03 to 1.54, p = 0.01), poor family function (OR, 1.21, 95% CI: 1.05 to 1.45, p = 0.03), and ≥20mm3 infarct size (OR, 1.74, 95% CI: 1.14 to 3.13, p = 0.02) were independent factors for having depression in patents with psychological symptoms. The family dysfunction (OR, 2.32, 95% CI: 1.51 to 2.80, p < 0.01) and hypertension (OR, 2.41, 95% CI: 1.54 to 3.46, p = 0.03) were independent factors for emerging somatization and anxiety in patients with psychological symptoms, respectively. Conclusions: At three months after their stroke, young ischemic stroke patients had psychological problems and risk factors for developing them.

6.
Trials ; 22(1): 35, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413569

RESUMO

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia, which is closely related to cardiovascular morbidity and mortality. Although acupuncture is used in the treatment of AF, the evidence is insufficient. The objective of this pilot trial is to evaluate the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after catheter ablation (CA). METHODS AND DESIGN: This will be a multi-center, 3-arm, pilot randomized controlled trial in China. Sixty patients in total will be randomly assigned to the specific acupoints group, the non-specific acupoints group, or the non-acupoints group in a 1:1:1 ratio. The whole study period is 6 months, including a 3-month treatment period and a 3-month follow-up period. All patients will receive 18 sessions of acupuncture over 12 weeks after CA and appropriate post-ablation routine treatment. The primary outcome is AF burden at 6 months after CA measured by electrocardiography patch that can carry out a 7-day continuous ambulatory electrocardiographic monitoring. The secondary outcomes include AF burden at 3 months after CA, recurrence of AF, quality of life, etc. The adverse events will also be recorded. DISCUSSION: This pilot study will contribute to evaluating the feasibility, preliminary efficacy, and safety of acupuncture in reducing AF burden for persistent AF after CA. The results will be used for the sample size calculation of a subsequent large-scale trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030576 . Registered on 7 March 2020.

7.
Mol Med Rep ; 22(6): 4663-4674, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33173965

RESUMO

Arsenic trioxide (ATO) is a frontline chemotherapy drug used in the therapy of acute promyelocytic leukemia. However, the clinical use of ATO is hindered by its cardiotoxicity. The present study aimed to observe the potential effects and underlying mechanisms of tannic acid (TA) against ATO­induced cardiotoxicity. Male rats were intraperitoneally injected with ATO (5 mg/kg/day) to induce cardiotoxicity. TA (20 and 40 mg/kg/day) was administered to evaluate its cardioprotective efficacy against ATO­induced heart injury in rats. Administration of ATO resulted in pathological damage in the heart and increased oxidative stress as well as levels of serum cardiac biomarkers creatine kinase and lactate dehydrogenase and the inflammatory marker NF­κB (p65). Conversely, TA markedly reversed this phenomenon. Additionally, TA treatment caused a notable decrease in the expression levels of cleaved caspase­3/caspase­3, Bax, p53 and Bad, while increasing Bcl­2 expression levels. Notably, the application of TA decreased the expression levels of cytochrome c, second mitochondria­derived activator of caspases and high­temperature requirement A2, which are apoptosis mitochondrial­associated proteins. The present findings indicated that TA protected against ATO­induced cardiotoxicity, which may be associated with oxidative stress, inflammation and mitochondrial apoptosis.

8.
Mol Med Rep ; 22(6): 5271-5281, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33173984

RESUMO

Arsenic trioxide (ATO) is commonly used to treat patients with acute promyelocytic leukemia since it was authorized by the U.S. Food and Drug Administration in the 1970s, but its applicability has been limited by its cardiotoxic effects. Therefore, the aim of the present study was to investigate the cardioprotective effects and underlying mechanism of crocetin (CRT), the critical ingredient of saffron. Sprague­Dawley rats were then randomly divided into four groups (n=10/group): i) Control group; ii) ATO group, iii) CRT­low (20 mg/kg) group; and iv) CRT­high (40 mg/kg) group. Rats in the Control and ATO groups were intraperitoneally injected with equal volumes of 0.9% sodium chloride solution, and CRT groups were administered with either 20 and 40 mg/kg CRT. Following 6 h, all groups except the Control group were intraperitoneally injected with 5 mg/kg ATO over 10 days. Cardiotoxicity was indicated by changes in electrocardiographic (ECG) patterns, morphology and marker enzymes. Histomorphological changes in the heart tissue were observed by pathological staining. The levels of superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase in the serum were analyzed using colometric commercial assay kits, and the levels of reactive oxygen species in the heart tissue were detected using the fluorescent probe dihydroethidium. The expression levels of inflammatory factors and activities of apoptosis­related proteins were analyzed using immunohistochemistry. The protein expression levels of silent information regulator of transcription 1 were measured using western blotting. Cardiotoxicity was induced in male Sprague­Dawley rats with ATO (5 mg/kg). CRT (20 and 40 mg/kg) and ATO were co­administered to evaluate possible cardioprotective effects. CRT significantly reduced the heart rate and J­point elevation induced by ATO in rats. Histological changes were evaluated via hematoxylin and eosin staining. CRT decreased the levels of creatine kinase and lactate dehydrogenase, increased the activities of superoxide dismutase, glutathione­peroxidase and catalase, and decreased the levels of malondialdehyde and reactive oxygen species. Moreover, CRT downregulated the expression levels of the pro­inflammatory factors IL­1, TNF­α, IL­6, Bax and p65, as well as increased the expression of Bcl­2. It was also identified that CRT enhanced silent information regulator of transcription 1 protein expression. Thus, the present study demonstrated that CRT treatment effectively ameliorated ATO­induced cardiotoxicity. The protective effects of CRT can be attributed to the inhibition of oxidative stress, inflammation and apoptosis. Therefore, CRT represents a promising therapeutic method for improving the cardiotoxic side effects caused by ATO treatment, and additional clinical applications are possible, but warrant further investigation.

9.
Oncol Rep ; 44(5): 2306-2316, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000240

RESUMO

The present study was performed to investigate the protective effects of tannic acid (TA) on liver injury induced by arsenic trioxide (ATO) and to elucidate the mechanism involved as related to the Kelch­like ECH­associated protein 1 (Keap1)­nuclear factor erythroid 2­related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. Adult rats were intraperitoneally injected with TA, while ATO was administered 1 h later. On the 11th day, the rats were euthanized to determine any liver histological changes, liver function, and the activities of antioxidant, antiapoptosis and proinflammatory cytokines in the liver. Furthermore, the protein expression levels of nuclear Nrf2, total Nrf2, Keap1, Heme oxygenase­1 (HO­1), NADPH quinine oxidoreductase­1 (NQO1), and γ­glutamylcysteine synthetase (γ­GCS) were determined using western blot analysis. The results showed that TA treatment ameliorated ATO­induced liver histological changes and decreased the ATO­induced increased alanine aminotransferase (ALT) and aspartate transaminase (AST) serum levels. Activities of the antioxidant enzymes significantly were increased, while the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were attenuated following TA treatment. In addition, TA treatment inhibited ATO­induced liver apoptosis and inflammatory responses, increased Bcl­2 protein expression level and reduced the levels of Bax, caspase­3, interleukin (IL)­1ß, IL­6 and tumor necrosis factor (TNF)­α. Furthermore, TA treatment increased the protein expression levels of Nrf2 and Keap1, HO­1, NQO1 and γ­GCS. The results demonstrated that TA has a protective effect on ATO­treated hepatic toxicity and that its underlying mechanism could be due to TA activation of the Keap1­Nrf2/ARE signaling pathway, to reduce oxidative stress, apoptosis and inflammation in ATO­intoxicated rats.

10.
Gen Physiol Biophys ; 39(5): 491-498, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33084602

RESUMO

The main active components of saffron are crocin, crocetin, picrocrocin, and safranal. There are many studies on their cardioprotective effects, but their cardiotoxicities have not been reported. The human ether-a-go-go-related gene (hERG) K+ channels are of considerable pharmaceutical interest as the target responsible for acquired long QT syndromes. The aim of this study is to explore the effects of crocin, crocetin, picrocrocin, and safranal on the K+ channels encoded by hERG. The interaction of these components with the rapid delayed rectification of K+ currents (IKr) were studied using the perforated patch recording technique. Crocin and picrocrocin had no significant effects on IKr, but crocetin and safranal inhibited hERG K+ currents in a concentration-dependent manner, with IC50 values of 36.35 µM and 37.86 µM, respectively. The maximum inhibitory effects were 37.74 ± 4.14% and 33.74 ± 4.81%, respectively, and the effects were reversible upon washout. The results demonstrate that crocetin and safranal significantly inhibit hERG K+ current, but crocin and picrocrocin do not. This suggests that crocetin and safranal may increase the risk of cardiac arrhythmias by inhibiting IKr.

11.
Biol Pharm Bull ; 43(9): 1367-1374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879211

RESUMO

Crocetin is a major bioactive ingredient in saffron (Crocus sativus L.) and has favorable cardiovascular effects. Here, the effects of crocetin on L-type Ca2+ current (ICa-L), contractility, and the Ca2+ transients of rat cardiomyocytes, were investigated via patch-clamp technique and the Ion Optix system. A 600 µg/mL dose of crocetin decreased ICa-L 31.50 ± 2.53% in normal myocytes and 35.56 ± 2.42% in ischemic myocytes, respectively. The current voltage nexus of the calcium current, the reversal of the calcium current, and the activation/deactivation of the calcium current was not changed. At 600 µg/mL, crocetin abated cell shortening by 28.6 ± 2.31%, with a decrease in the time to 50% of the peak and a decrease in the time to 50% of the baseline. At 600 µg/mL, crocetin abated the crest value of the ephemeral Ca2+ by 31.87 ± 2.57%. The time to half maximal of Ca2+ peak and the time constant of decay of Ca2+ transient were both reduced. Our results suggest that crocetin inhibits L-type Ca2+ channels, causing decreased intracellular Ca2+ concentration and contractility in adult rat ventricular myocytes. These findings reveal crocetin's potential use as a calcium channel antagonist for the treatment of cardiovascular disease.

12.
Int Immunopharmacol ; 88: 106959, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32919218

RESUMO

Arsenic trioxide (ATO)-induced renal toxicity through oxidative stress and apoptosis restricts the therapeutic action of acute myelogenous leukemia. Crocetin (Crt) possesses antioxidant and antiapoptosis properties, and has certain renal protective effects, but it has not been reported that it has protective effect on renal injury caused by ATO. The current study explored the effects and mechanisms of Crt on kidney damage induced by ATO. Fifty Sprague-Dawley rats were randomly divided into five groups. Adult rats were given Crt concurrently with ATO for 1 week. On the 8th day, rats were killed and blood and kidney tissues were collected. Histopathological changes were measured, and kidneytissues and serum were used to determine renal function and antioxidant enzyme activity. In addition, the protein expression levels of P-PI3K, PI3K, P-AKT, AKT, CytC, Bax, Bcl-2 and Caspase-3 were determined via western blot analysis. Results revealed ATO induced renal morphological alterations and activated serum BUN and CRE. Compared with the control group, ROS, MDA, IL-1ß, TNF-α, protein carbonyls (PC), lipid hydroperoxides (LOOH) and arsenic concentration levels were found to be significantly increased and SOD, CAT, GSH-Px, GSH and total sulphydryl groups (TSH) levels were attenuated in the ATO group. Crt markedly reduced oxidative stress in ATO-induced nephrotoxicity. Further, ATO induced apoptosis by significantly enhancing CytC, Bax and Caspase-3 and inhibiting Bcl-2. Administration with Crt markedly improved the expression of apoptosis factor. Moreover, Crt treatment stimulated the expressions of P-PI3K, PI3K, P-AKT, AKT induced by ATO. This study indicates Crt could prevent renal injury caused by ATO through inhibiting oxidative stress, inflammation and apoptosis, and its mechanism may be related to activation of PI3K/Akt signaling pathway.

13.
Biomed Pharmacother ; 131: 110713, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32920515

RESUMO

Arsenic trioxide (ATO) is an excellent therapy for acute promyelocytic leukemia; however, its use is limited due to its cardiotoxicity. Crocin (CRO) possesses abundant pharmacological and biological properties, including antioxidant, anti-inflammatory, and anti-apoptotic. This study examined the cardioprotective effects of crocin and explored their mechanistic involvement in ATO-induced cardiotoxicity. Forty-eight male rats were treated with ATO to induce cardiotoxicity. In combination with ATO, CRO were given to evaluate its cardioprotection. The results demonstrated that CRO administration not only diminished QTc prolongation, myocardial enzymes and Troponin T levels but also improved histopathological results. CRO administration reduced reactive oxygen species generation. However, the CRO administration caused an increase in glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and total sulphydryl levels and a decrease in malondialdehyde content, gamma glutamyl transferase and lipid hydroperoxides levels and proinflammatory cytokines. Importantly, immunohistochemical analysis, real time PCR and western blotting showed a reduction in Caspase-3 and Bcl-2-associated X protein expressions and enhancement of B cell lymphoma-2 expression. Real time PCR and western blotting showed a reduction in proinflammatory cytokines. Moreover, CRO caused an activation in nuclear factor erythroid-2 related factor 2, leading to enhanced Kelch-like ECH-associated protein 1, heme oxygenase-1 and nicotinamide adenine dinucleotide quinone dehydrogenase 1 expressions involved in Nrf2 signaling during ATO-induced cardiotoxicity. CRO was shown to ameliorate ATO-induced cardiotoxicity. The mechanisms for CRO amelioration of cardiotoxicity due to inflammation, oxidative damage, and apoptosis may occur via an up-regulated Keap1-Nrf2/HO-1 signaling pathway.

14.
J Comp Neurol ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32949023

RESUMO

The relatively large primary olfactory center of the insect brain, the antennal lobe (AL), contains several heterogeneous neuronal types. These include projection neurons (PNs), providing olfactory information to higher-order neuropils via parallel pathways, and local interneurons (LNs), which provide lateral processing within the AL. In addition, various types of centrifugal neurons (CNs) offer top-down modulation onto the other AL neurons. By performing iontophoretic intracellular staining, we collected a large number of AL neurons in the moth, Helicoverpa armigera, to examine the distinct morphological features of PNs, LNs, and CNs. We characterize 190 AL neurons. These were allocated to 25 distinct neuronal types or sub-types, which were reconstructed and placed into a reference brain. In addition to six PN types comprising 15 sub-types, three LN and seven CN types were identified. High-resolution confocal images allowed us to analyze AL innervations of the various reported neurons, which demonstrated that all PNs innervating ventroposterior glomeruli contact a protocerebral neuropil rarely targeted by other PNs, that is the posteriorlateral protocerebrum. We also discuss the functional roles of the distinct CNs, which included several previously uncharacterized types, likely involved in computations spanning from multisensory processing to olfactory feedback signalization into the AL.

15.
Chin Med J (Engl) ; 133(18): 2229-2235, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32826614

RESUMO

BACKGROUND: The predictive value of hemoglobin A1c (HbA1c) levels in non-diabetic patients with myocardial infarction undergoing percutaneous coronary intervention (PCI) is still controversial. This study aimed to evaluate whether HbA1c levels were independently associated with adverse clinical outcomes in non-diabetic patients with coronary artery disease (CAD) who had undergone PCI by performing a meta-analysis of cohort studies. METHODS: This meta-analysis included non-diabetic patients with CAD who had undergone PCI. A systematic search for publications listed in the PubMed, Embase, and Cochrane Library databases from commencement to December 2018 was conducted. Studies evaluating the adverse clinical outcomes according to abnormal HbA1c levels in non-diabetic patients diagnosed with CAD who had undergone PCI were eligible. The primary outcomes were long-term all-cause deaths and long-term major adverse cardiac events, and the secondary outcome was short-term all-cause deaths. The meta-analysis was conducted with RevMan 5.3 and Stata software 14.0. Odds ratios (ORs) were pooled using a random or fixed-effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary. RESULTS: Six prospective cohort studies involving 10,721 patients met the inclusion criteria. From the pooled analysis, abnormal HbA1c levels were associated with increased risk for long-term all-cause death (OR 1.39, 95% confidence interval [CI] 1.16-1.68, P = 0.001, I = 45%). Sub-group analysis suggested that abnormal HbA1c levels between 6.0% and 6.5% predicted higher long-term major adverse cardiac event (including all-cause deaths, non-fatal myocardial infarction, target lesion revascularization, target vessel revascularization, recurrent acute myocardial infarction, heart failure requiring hospitalization, and stent thrombosis) risk (OR 2.05, 95% CI 1.46-2.87, P < 0.001, I = 0). Contrarily, elevated HbA1c levels were not associated with increased risk of short-term all-cause death (OR 1.16, 95% CI 0.88-1.54, P = 0.300, I = 0). CONCLUSIONS: An abnormal HbA1c level is an independent risk factor for long-term adverse clinical events in non-diabetic patients with CAD after PCI. Strict control of HbA1c levels may improve patient survival. Further studies in different countries and prospective cohort studies with a large sample size are required to verify the association.

16.
Front Cell Neurosci ; 14: 147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581719

RESUMO

Even though insects have comparably small brains, they achieve astoundingly complex behaviors. One example is flying moths tracking minute amounts of pheromones using olfactory circuits. The tracking distance can be up to 1 km, which makes it essential that male moths respond efficiently and reliably to very few pheromone molecules. The male-specific macroglomerular complex (MGC) in the moth antennal lobe contains circuitry dedicated to pheromone processing. Output neurons from this region project along three parallel pathways, the medial, mediolateral, and lateral tracts. The MGC-neurons of the lateral tract are least described and their functional significance is mainly unknown. We used mass staining, calcium imaging, and intracellular recording/staining to characterize the morphological and physiological properties of these neurons in the noctuid moth, Helicoverpa armigera. All lateral-tract MGC neurons targeted the column, a small region within the superior intermediate neuropil. We identified this region as a unique converging site for MGC lateral-tract neurons responsive to pheromones, as well as a dense congregating site for plant odor information since a substantial number of lateral-tract neurons from ordinary glomeruli (OG) also terminates in this region. The lateral-tract MGC-neurons responded with a shorter peak latency than the well-described neurons in the medial tract. Different from the medial-tract MGC neurons encoding odor quality important for species-specific signal identification, those in the lateral tract convey a more robust and rapid signal-potentially important for fast control of hard-wired behavior.

17.
Drug Des Devel Ther ; 14: 1921-1931, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32546959

RESUMO

Purpose: Arsenic trioxide (ATO) has been shown to induce hepatic injury. Crocetin is a primary constituent of saffron, which has been verified to have antioxidant and anti-inflammatory effects. In the current experiment, we evaluated the efficacy of crocetin against ATO-induced hepatic injury and explored the potential molecular mechanisms in rats. Methods: Rats were pretreated with 25 or 50 mg/kg crocetin 6 h prior to treating with 5 mg/kg ATO to induce hepatic injury daily for 7 days. Results: Treatment with crocetin attenuated ATO-induced body weight loss, decreases in food and water consumption, and improved ATO-induced hepatic pathological damage. Crocetin significantly inhibited ATO-induced alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) increases. Crocetin prevented ATO-induced liver malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Crocetin abrogated the ATO-induced decrease of catalase (CAT) and superoxide dismutase (SOD) activity. Crocetin was found to significantly restore the protein levels of interleukin 6 (IL-6), interleukin 1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α). Furthermore, crocetin promoted the expression of nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADP(H): quinone oxidoreductase 1 (NQO1). Conclusion: These findings suggest that crocetin ameliorates ATO-induced hepatic injury in rats. In addition, the effect of crocetin might be related to its role in antioxidant stress, as an anti-inflammatory agent, and in regulating the Nrf2 signaling pathway.

18.
Int Immunopharmacol ; 84: 106548, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32388215

RESUMO

Doxorubicin (DOX) is widely used to treat multiple of tumors, but its clinical trials are allied with some serious adverse events mainly cardiac functional abnormalities. So the objective of our investigation is to identify the cardioprotective action of crocin (CRO), a natural compound derived from saffron, against DOX-induced cardiotoxicity. CRO was injected intraperitoneally (i.p.) to rats for sixconsecutive days and DOX (i.p.) was administered on the fourth day. H9c2 cells were treated with DOX for 24 h after being pre-treated by CRO for 2 h. CROreduced tachycardiaand J-point elevation,decreased the levelsof serum creatine kinase, lactate dehydrogenase,glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase.CRO exerted positive effect on DOX-induced ROS productionand changes of oxidative stress biomarkers. CRO significantlydecreased intracellular Ca2+ concentration andincreased mitochondria membrane potentialin H9c2 cells. CRO also resisted the DOX-induced high expressionof tumor necrosis factor-αand interleukin-6, inhibitedapoptosisand improved the abnormal expression levels of Bcl-2, Bax and Caspase-3 proteins.CRO obviously restrained DOX-mediatedhigh expression of toll-like receptor-2 (TLR-2) and nuclear factor kappa-B (NF-κB) in ventricular tissue. Inbrief,CRO distinctly restrained DOX-mediated cardiotoxicity by inhibiting oxidative stress, inflammation, apoptoticandredressingcardiomyocyte calcium dyshomeostasis and mitochondria damage.These cardioprotective effects may berelated closely with the TLR2/NF-κB pathway.

19.
J Pharmacol Sci ; 143(3): 156-164, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32278466

RESUMO

Safranal (SFR) is the major constituent of saffron. The purpose of this study was to observe the effect of SFR on myocardial ischemia induced by isoprenaline (ISO) and to explore its possible mechanism. The myocardial ischemia rat model was established by subcutaneous injection of ISO (85 mg/kg/d) on the 8th and 9th day of the experiment. Serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured, as were changes in calcium concentration, reactive oxygen species (ROS) and cardiac morphology of the myocardial tissue. The effects of SFR on cell contraction, Ca2+ transient and L-type Ca2+ current (ICa-L) in isolated rat myocardial cells were measured using the Ion Optix detection system and the whole-cell patch-clamp technique. SFR can decrease the activity of serum CK, LDH and MDA, and increase the activity of serum SOD, reduce intracellular calcium concentration and the manufacture of ROS. In addition, SFR can improve changes in heart morphology. SFR can significantly inhibit contraction, Ca2+ transients and ICa-L in isolated ventricular myocytes. SFR has a cardioprotective role in ISO-induced MI rats, and the underling mechanism is related to the inhibition of oxidative stress, myocardial contractility, ICa-L and the regulation of Ca2+ homeostasis.


Assuntos
Cálcio/metabolismo , Crocus/química , Cicloexenos/farmacologia , Cicloexenos/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Terpenos/farmacologia , Terpenos/uso terapêutico , Animais , Cardiotônicos , Células Cultivadas , Cicloexenos/isolamento & purificação , Modelos Animais de Doenças , Isoproterenol/efeitos adversos , Masculino , Malondialdeído/metabolismo , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica/induzido quimicamente , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Terpenos/isolamento & purificação
20.
Neural Regen Res ; 15(10): 1920-1930, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32246641

RESUMO

Hydrogen sulfide, which can be generated in the central nervous system from the sulfhydryl-containing amino acid, L-cysteine, by cystathionine-ß-synthase, may exert protective effects in experimental subarachnoid hemorrhage; however, the mechanism underlying this effect is unknown. This study explored the mechanism using a subarachnoid hemorrhage rat model induced by an endovascular perforation technique. Rats were treated with an intraperitoneal injection of 100 mM L-cysteine (30 µL) 30 minutes after subarachnoid hemorrhage. At 48 hours after subarachnoid hemorrhage, hematoxylin-eosin staining was used to detect changes in prefrontal cortex cells. L-cysteine significantly reduced cell edema. Neurological function was assessed using a modified Garcia score. Brain water content was measured by the wet-dry method. L-cysteine significantly reduced neurological deficits and cerebral edema after subarachnoid hemorrhage. Immunofluorescence was used to detect the number of activated microglia. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the levels of interleukin 1ß and CD86 mRNA in the prefrontal cortex. L-cysteine inhibited microglial activation in the prefrontal cortex and reduced the mRNA levels of interleukin 1ß and CD86. RT-PCR and western blot analysis of the complement system showed that L-cysteine reduced expression of the complement factors, C1q, C3α and its receptor C3aR1, and the deposition of C1q in the prefrontal cortex. Dihydroethidium staining was applied to detect changes in reactive oxygen species, and immunohistochemistry was used to detect the number of NRF2- and HO-1-positive cells. L-cysteine reduced the level of reactive oxygen species in the prefrontal cortex and the number of NRF2- and HO-1-positive cells. Western blot assays and immunohistochemistry were used to detect the protein levels of CHOP and GRP78 in the prefrontal cortex and the number of CHOP- and GRP78-positive cells. L-cysteine reduced CHOP and GRP78 levels and the number of CHOP- and GRP78-positive cells. The cystathionine-ß-synthase inhibitor, aminooxyacetic acid, significantly reversed the above neuroprotective effects of L-cysteine. Taken together, L-cysteine can play a neuroprotective role by regulating neuroinflammation, complement deposition, oxidative stress and endoplasmic reticulum stress. The study was approved by the Animals Ethics Committee of Shandong University, China on February 22, 2016 (approval No. LL-201602022).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...