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1.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(4): 412-416, 2019 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-31512836

RESUMO

OBJECTIVE: We aim to determine the thickness of the labial plate, the distance between the cement-enamel junction (CEJ) and alveolar crest, and the inclination angle of the long axis of healthy maxillary anterior teeth by using cone- beam computed tomography (CBCT). METHODS: A total of 345 CBCT volumes obtained by Newtom VGI® CBCT were analyzed by using the NNT software. The digital measurements of the labial bone plate thickness at level 4 mm below the CEJ, the midpoint of tooth root and the radiological tooth apex, the distance between the CEJ and alveolar crest, and the angle between the long axis of the teeth and the long axis of alveolar process were obtained from the mid-sagittal planes of maxillary incisors and canines. Plate thickness 4 mm below the CEJ was measured, and values below ≥1 mm were recorded. RESULTS: In the central incisor, 1) the angle between the long axis of the teeth and alveolar bone was 15.2°±6.2°, the distance between the CEJ and alveolar crest was (1.5±1.0) mm, labial bone plate thick-ness at 4 mm below the CEJ was (0.8±0.4) mm, the midpoint of tooth root was (0.6±0.4) mm, and the radiological tooth apex was (1.3±0.7) mm; in the lateral incisor, 16.2°±8.8°, (1.6±1.0) mm, (0.7±0.5) mm, (0.4±0.6) mm, and (1.1±0.7) mm, respectively; and in the canine, 19.0°±6.2°, (1.8±1.0) mm, (0.9±0.6) mm, (0.4±0.6) mm, and (1.2±0.7) mm, respectively. 2) The frequencies of plate thickness ≥1 mm were 28.3%, 25.8%, and 42.7% in the central incisor, lateral incisor, and canine, respectively. 3) The distance between the CEJ and alveolar crest was positively correlated with age. The correlation coefficients was 0.42 (P<0.01) in the central incisor, 0.50 (P<0.01) in the lateral incisor, and 0.62 (P<0.01) in the canine. CONCLUSIONS: The thickness of labial bone plate is thin, the distance from CEJ to alveolar crest increases with age, and the long axis of the teeth is more inclined than the long axis of alveolar process. Knowledge of these special morphological characteristics can improve the safety and result for many dental procedures.

2.
J Sports Sci ; : 1-9, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500501

RESUMO

To comprehensively shed light on whether viewing football games is associated with a higher risk of cardiovascular disease (CVD). Electronic databases were searched through 17 May 2018. All studies focusing on the association between viewing football matches and the fatal or non-fatal CVD were identified. Viewing football matches was associated with a higher risk of fatal overall CVD (RR: 1.06, 95%CI: 1.01-1.12) in both men (RR: 1.13, 95%CI: 1.004-1.28) and women (RR: 1.08, 95%CI: 1.01-1.15). Subgroup analysis showed that failure of the team has a higher risk of fatal overall CVD (RR: 1.29, 95%CI: 1.15-1.45). However, lower risk of fatal overall CVD from spectators was observed when team obtained a victory (RR: 0.80, 95%CI: 0.66-0.96). For non-fatal CVD, viewing football matches was associated with a higher risk of non-fatal overall CVD (RR: 1.24, 95%CI: 1.09-1.41) in both men (RR: 1.73, 95%CI: 1.12-2.69) and women (RR: 1.25, 95%CI: 1.08-1.45). Subgroup analysis showed that viewing football matches was associated with a higher risk of non-fatal myocardial infarction (RR: 1.20, 95%CI: 1.04-1.38) in both men and women (RR: 1.51, 95%CI: 0.99-2.28; RR: 1.21, 95%CI: 1.08-1.36, respectively). No significant increase was found in fatal or non-fatal stroke. Viewing football matches was associated with a higher risk of the fatal and non-fatal CVD, especially in male spectators. The victory of team could have a lower risk of fatal CVD. Therefore, precautionary measures should be required for the reduction of healthcare burden in football matches.

3.
Curr Mol Med ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31453784

RESUMO

BACKGROUNDS: Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against the acetylcholine receptors (AChR) of the skeletal muscles. An imbalance in various T helper (Th) cells, including Th1, Th2, Th17, Th22 and follicular helper T (TFH) cells, has been found associated with immunological disturbances. OBJECTIVE: In this study, we aim to investigate the role of the Th cells in peripheral blood of MG patients. MATERIALS AND METHODS: A total of 33 MG patients and 34 age matched controls were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll-Paque density gradient centrifugation assay. The proportion of TFH cells in PBMC were analyzed using flow-cytometry assay by determining the levels of cellular markers CD4, CXCR5, CD45RO, CD45RA and ICOS and PD-1. The levels of IFN-γ, IL-4, IL-17 and IL-21 in serum were analyzed by Cytometric Bead Array. The serum IL-22 level were analyzed by ELISA. RESULTS: The frequency of TFH cells in PBMCs was higher than those in healthy subjects and correlated to the severity of MG patients. The levels of pro-inflammatory cytokines IFN-γ, IL-17 and IL-21 were elevated in the serum of MG patients, while there were no significant differences regarding the levels of IL-4 and IL-22 between MG patients and control subjects. CONCLUSION: Our findings suggest that Th cells and their cytokines balance of MG patients are involved in the clinical condition or severity of MG disease.

4.
Neuroscience ; 416: 268-280, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31425734

RESUMO

Intracranial hypertension (IH) is a medical or surgical emergency that can be the common ending of various neurological disorders, such as traumatic brain injury, cerebral vascular diseases and brain tumors. However, the molecular mechanisms underlying IH-induced neuronal apoptosis have not been fully determined, and the treatments are symptomatic, insufficient and complicated by side-effects. In this study, a cellular model induced by compressed gas treatment in primary cultured rat cortical neurons was performed to mimic IH-induced neuronal injury in vitro. We found that compression induced cytotoxicity and apoptosis in cortical neurons in a dose- and time-dependent manner. Compression resulted in oxidative stress, which could be prevented by the ROS scavenger N-acetylcysteine (NAC). Compression produced mitochondrial oxidative stress, ATP loss and mitochondrial fragmentation. The results of western blot showed that compression differently regulated the expression of mitochondrial dynamic proteins, and the Drp1 inhibitor mdivi-1 partially reversed the compression-induced cytotoxicity. Compression significantly increased the expression of ER stress-associated factors in a time-dependent manner. The results of calcium imaging showed that compression induced intracellular calcium overload via promoting ER calcium release. Furthermore, the results using inhibitors of each signaling pathway demonstrated that ROS mediated the compression-induced ER stress and mitochondrial dysfunction in cortical neurons. In conclusion, our results demonstrated that compression induced apoptosis in primary cultured cortical neurons, which was associated with ROS mediated ER stress and mitochondrial dysfunction. Pharmacological compounds or agents targeting mitochondrial dysfunction and ER stress associated oxidative stress might be ideal candidates for the treatment of IH-related neurological diseases.

5.
Neurochem Int ; 129: 104515, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31369778

RESUMO

Lysophosphatidic acid (LPA) is a glycerophospholipid that can be detected in serum, saliva and cerebrospinal fluid. However, the effect of LPA on neuronal death and survival has not been fully determined. In the present study, we investigated the potential neurotoxic effect of LPA in primary cultured cortical neurons. Treatment with LPA (0.5, 1 and 5 µM) markedly decreased neuronal viability, increased lactate dehydrogenase (LDH) release and promoted apoptosis in cortical neurons. The results of western blot showed that LPA increased the expression of endoplasmic reticulum (ER) stress associated factors, and the protein misfolding inhibitor 4-phenylbutyric acid (4-PBA) attenuated LPA-induced toxicity. In addition, treatment with LPA did not alter the expression and distribution of Homer1 in cortical neurons. The protein levels of metabotropic glutamate receptor 1 (mGluR1), but not metabotropic glutamate receptor 5 (mGluR5), were significantly increased by LPA at 12 and 24 h after treatment. Knockdown of Homer1 using specific siRNA partially prevented the LPA-induced neurotoxicity and ER stress. Furthermore, the results of Ca2+ imaging showed that treatment with LPA induced intracellular Ca2+ release, which could be partially prevented by 4-PBA and downregulation of Homer1. The LPA-induced intracellular Ca2+ release was associated with ER Ca2+ release through the Homer1-mGluR1 pathway. In summary, our results showed that LPA treatment induced ER stress and apoptosis in cortical neurons, and its neurotoxicity was partially mediated by Ca2+ release from the ER via the Homer1/mGluR1 pathway.

7.
J Exp Clin Cancer Res ; 38(1): 338, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382983

RESUMO

BACKGROUND: The GKN2 is a secretory protein, whose levels decrease in gastric cancer. The present study aimed to investigate the expression, function and mechanism of action of GKN2 in gastric cancer. METHODS: Molecular biology assays were performed to elucidate the function and underlying mechanisms of GKN2 in gastric cancer under stress-induced condition in vivo and in vitro. Clinical specimens were used to assess the correlation of GKN2 and prognosis. RESULTS: We found that overexpression of GKN2 significantly enhanced apoptosis and growth arrest in vitro. GKN2 expression increased in gastric cancer cells exposed to hydrogen peroxide and promoted reactive oxygen species-induced mitochondrial dysfunction and resulted in increased cell apoptosis via inhibition of NF-κB signaling pathway and activation of JNK signaling pathway through the direct interaction of GKN2 with Hsc70. Trefoil factor 1 might contribute to the tumor suppressing effects of GKN2. MiR-216a downregulated GKN2 expression. GKN2 also inhibited xenograft tumor growth and was an independent and significant prognostic factor for patients with gastric cancer treated with oxaliplatin. CONCLUSIONS: Taken together, our data indicate that GKN2 may increase sensitivity of GC cells to the drugs which increase ROS levels in tumors. Inhibition of the interaction between GKN2 and Hsc70 could attenuate the effects induced by GKN2. GKN2 overexpression could be used to determine the subgroup of patients to obtain the more favorable outcome of oxaliplatin treatment and may be used as biomarker of the prognosis of this cancer.

8.
J Biol Chem ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31406019

RESUMO

Collagens carry out critical extracellular matrix (ECM) functions by interacting with numerous cell receptors and ECM components. Single glycine substitutions in collagen III, which predominates in vascular walls, result in vascular Ehlers-Danlos syndrome (vEDS1), leading to arterial, uterine, and intestinal rupture and an average life expectancy of < 50 years. Collagen interactions with integrin α2ß1 are vital for platelet adhesion and activation; however, how these interactions are impacted by vEDS-associated mutations and by specific amino acid substitutions is unclear. Here, we designed collagen mimetic peptides (CMPs) with previously reported Gly→X (X = Ala, Arg, or Val) vEDS substitutions within a high-affinity integrin α2ß1 binding motif, GROGER. We used these peptides to investigate, at atomic-level resolution, how these amino acid substitutions affect the collagen III-integrin α2ß1 interaction. Using a multi-tiered approach combining biological adhesion assays, CD, NMR, and molecular dynamics (MD) simulations, we found that these substitutions differentially impede human mesenchymal stem cell spreading and integrin α2-inserted (α2I) domain binding to the CMPs and were associated with triple helix destabilization. Although an Ala substitution locally destabilized hydrogen bonding and enhanced mobility, it did not significantly reduce the CMP-integrin interactions. MD simulations suggested that bulkier Gly→X substitutions differentially disrupt the CMP-α2I interaction. The Gly→Arg substitution destabilized CMP-α2I side-chain interactions, and the Gly→Val change broke the essential Mg2+ coordination. The relationship between the loss of functional binding and the type of vEDS substitution provides a foundation for developing potential therapies for managing collagen disorders.

9.
J Cell Biochem ; 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31407397

RESUMO

BACKGROUND: In this study, we established both an animal model and a cellular model of hyperuricemia (HUC). Subsequently, we treated these models with allopurinol (ALLO) to study the effect of uric acid (UA) and ALLO on the differentiation and proliferation of osteoblasts and vascular smooth muscle cells (VSMC). METHODS: Western Blot, immunohistochemistry assay, and real-time polymerase chain reaction were conducted to measure the changes in the expression of differentiation-related factors in osteoblasts and VSMCs in HUC and HUC+ALLO groups. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry were utilized to observe the changes in the proliferation of osteoblasts in HUC and HUC+ALLO groups. Von Kossa staining was performed along with calcium content measurement to investigate the effect of HUC/ALLLO on vascular calcification. RESULTS: In this study, the levels of Wnt3a and differentiation-related factors, including Runx2, Sp7, Ibsp, Bglap, Dmp1, and Col1a1, were all evidently decreased in HUC rats, while the presence of ALLO increased the levels of above factors. In addition, the viability of osteoblasts was reduced while their apoptosis was elevated in the HUC group, and ALLO treatment reduced the apoptosis and increased the viability of osteoblasts to a certain extent. Moreover, HUC elevated the levels of Wnt3a, Runx2, Sp7, Bglap, Col1a1, SM22a, and Acta2 in VSMCs of HUC rats, leading to greatly increased calcium content and obvious vascular calcification. In contrary, ALLO treatment reduced the effect of HUC. Furthermore, the effect of UA and ALLO on osteoblasts and VSMCs was also validated in cellular models treated with monosodium urate (MSU) crystals or MSU+ALLO. CONCLUSIONS: HUC can suppress the differentiation and proliferation of osteoblasts while promoting the differentiation of VSMCs both in vivo and in vitro. The treatment by ALLO exhibited a therapeutic effect on HUC by promoting the differentiation and proliferation of osteoblasts while reducing vascular calcification.

10.
Int J Nanomedicine ; 14: 5339-5353, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409991

RESUMO

Background: Like most protein macromolecular drugs, the half-life of rhIFNɑ-2b is short, with a low drug utilization rate, and the preparation and release conditions significantly affect its stability. Methods: A nanoporous ion-responsive targeted drug delivery system (PIRTDDS) was designed to improve drug availability of rhIFNα-2b and target it to the lung passively with sustained release. Chitosan rhIFNα-2b carboxymethyl nanoporous microspheres (CS-rhIFNα-2b-CCPM) were prepared by the column method. Here, an electrostatic self-assembly technique was undertaken to improve and sustain rhIFNα-2b release rate. Results: The size distribution of the microspheres was 5~15 µm, and the microspheres contained nanopores 300~400 nm in diameter. The in vitro release results showed that rhIFNα-2b and CCPM were mainly bound by ionic bonds. After self-assembling, the release mechanism was transformed into being membrane diffusion. The accumulative release amount for 24 hrs was 83.89%. Results from circular dichrogram and SDS-PAGE electrophoresis showed that there was no significant change in the secondary structure and purity of rhIFNα-2b. Results from inhibition rate experiments for A549 cell proliferation showed that the antitumor activity of CS-rhIFNα-2b-CCPM for 24 hrs retained 91.98% of the stock solution, which proved that the drug-loaded nanoporous microspheres maintained good drug activity. In vivo pharmacokinetic experimental results showed that the drugs in CS-rhIFNα-2b-CCPM can still be detected in vivo after 24 hrs, equivalent to the stock solution at 6 hrs, which indicated that CS-rhIFNα-2b-CCPM had a certain sustained-release effect in vivo. The results of in vivo tissue distribution showed that CS-rhIFNα-2b-CCPM was mainly concentrated in the lungs of mice (1.85 times the stock solution). The pharmacodynamics results showed that CS-rhIFNα-2b-CCPM had an obvious antitumor effect, and the tumor inhibition efficiency was 29.2%. Conclusion: The results suggested a novel sustained-release formulation with higher drug availability and better lung targeting from CS-rhIFNα-2b-CCPM compared to the reference (the stock solution of rhIFNα-2b), and, thus, should be further studied.

11.
J Clin Neurosci ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31420274

RESUMO

Sleep disturbance is a common psychiatric complication after stroke. Oxidative stress has been an important pathophysiological mechanism of sleep disturbance. However, no study has explored the relationship between uric acid (UA) and post-stroke sleep quality. This prospective study included 191 patients who were followed up for two months after acute ischemic stroke. Serum UA levels were measured at admission and divided into 3 tertiles (≤251 µmol/L, 252-326 µmol/L, ≥327 µmol/L). Patients in the 3rd tertile of UA levels had a lower incidence of poor sleep quality than those belonging to 2nd or 1st tertile, respectively (9.7% vs. 27.7% vs. 35.9%; P = 0.002). Furthermore, high UA levels (≥327 µmol/L) were independently associated with low risk of poor sleep quality (OR = 0.129, 95%CI = 0.031-0.528, P = 0.004) after adjusting for demographics, cardiovascular risk factors, stroke severity, functional outcome and depressive symptoms. High modified Rankin Scale score and depressive symptoms were associated with increased risk of poor sleep quality after stroke (OR = 1.836, 95%CI = 1.035-3.354, P = 0.038) and (OR = 5.082, 95%CI = 1.709-15.115, P = 0.003). In conclusion, high UA levels may reduce the risk of poor sleep quality after acute ischemic stroke. Further randomized controlled trials are necessary in examining whether appropriate UA supplement could provide a potential prevention or therapeutic target for sleep disturbance after stroke.

12.
Neurobiol Dis ; 132: 104567, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394202

RESUMO

Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aß) accumulation. However, the mechanism by which Aß induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aß and mediates Aß neurotoxicity, implying that p75NTR may mediate Aß-induced tau phosphorylation in AD. Here, we showed that Aß-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3ß (GSK3ß) significantly changed Aß/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aß to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aß-induced tau pathology and is a potential druggable target for AD and other tauopathies.

13.
J Immunol ; 203(6): 1548-1559, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31383742

RESUMO

Long noncoding RNAs are important regulators of gene expression in innate immune responses. Antisense IL-7 (IL-7-AS) is a newly discovered long noncoding RNA in human and mouse that has been reported to regulate the expression of IL-6. However, the potential function of IL-7-AS in innate immune system is not fully understood. In this study, we found that the expression of IL-7-AS is primarily dependent on the NF-κB and MAPK signaling pathways in macrophages and intestinal epithelial cells. Functionally, IL-7-AS promotes the expression of several inflammatory genes, including CCL2, CCL5, CCL7, and IL-6, in cells in response to LPS. Specifically, IL-7-AS physically interacts with p300 to regulate histone acetylation levels around the promoter regions of these gene loci. Moreover, IL-7-AS and p300 complex modulate the assembly of SWI/SNF complex to the promoters. IL-7-AS regulates chemotaxis activity of monocytes to intestine epithelial cells with involvement of CCL2. Therefore, our data indicate a new promoting role for NF-κB/MAPK-responsive IL-7-AS in the transcriptional regulation of inflammatory genes in the innate immune system although modulation of histone acetylation around the promoters of related genes.

14.
Curr Alzheimer Res ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31368873

RESUMO

BACKGROUND: Alzheimer's disease (AD) is characterized by the presence of extracellular amyloid-ß (Aß) plaques and intraneuronal neurofibrillary tangles assembled by the microtubule-associated protein tau. Increasing evidences demonstrated that tau pathology played an important role in AD progression. Resveratrol (RSV) has been previously proved to exert neuroprotective effect against AD by inhibiting Aß generation and Aß-induced neurocytotoxicity, while its effect on tau pathology is still unknown. METHOD: The effect of RSV on tau aggregation was measured by Thioflavin T fluorescence and Transmission electron microscope imaging; The effect of RSV on tau oligomer-induced cytotoxicity was assessed by MTT assay; The uptake of extracellular tau by N2a cells was determined by immunocytochemistry. 6-month-old male PS19 mice were treated with RSV or vehicle by oral administration (gavage) once a day for 5 weeks. The cognitive performance was determined using Morris water maze test, object recognition test and Y-maze test. The levels of phosphorylated-tau, gliosis, proinflammatory cytokines such as TNF-α and IL-1ß, and synaptic proteins including synaptophysin and PSD95 in the mouse brains were evaluated by immunoblotting, immunostaining and ELISA, respectively. RESULTS: RSV significantly inhibited tau aggregation and tau oligomer-induced cytotoxicity, and blocked the uptake of extracellular tau oligomers by N2a cells. When applied to PS19 mice, RSV treatment effectively rescued cognitive deficits, reduced the levels of phosphorylated tau, neuroinflammation and synapse loss in the brains of mice. CONCLUSION: These findings suggest that RSV has promising therapeutic potential for AD and other tauopathies.

15.
Neurosci Lett ; : 134416, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31398456

RESUMO

Levo-tetrahydropalmatine (L-THP) is the main active ingredient of traditional Chinese herbal medicine Corydalis and Stephania, which have been used for sedative, neuroleptic, and analgesic purposes. Previous studies have demonstrated that L-THP has antagonistic activation on dopamine receptors. Despite its effectiveness on treating drug addiction, L-THP's underlying molecular mechanisms in modulating methamphetamine (METH) reward behavior remain unclear. In order to clarify the mechanisms behind, we designed an experiment of conditioned place preference (CPP) to investigate the effects of L-THP on METH-induced CPP in mice. We then dissected the underlying molecular mechanisms of L-THP in modulating METH-induced CPP by evaluating accompanying changes in expression of phosphorylated extracellular signal-regulated kinase (p-ERK) in reward-relevant brain regions, including nucleus accumbens (NAc), prefrontal cortex (PFc), caudate putamen (CPu), and hippocampus (Hip), which may mediate the effects of L-THP on METH-induced CPP. The results showed that 1.0 mg/kg METH could induce obvious CPP in mice; 10.0 mg/kg L-THP could significantly attenuate METH-induced CPP in mice, though it could not induce CPP or conditioned place aversion by itself. Moreover, the levels of p-ERK in NAc and PFc of the METH group were significantly higher than that of the saline group. Although there was no evident difference between the levels of p-ERK of the L-THP group with that of the saline group, the levels of p-ERK in NAc and PFc of the M + T group were significantly lower than that of the METH group. There was no striking difference among the levels of p-ERK in CPu and Hip of all experimental groups. Our research suggested that NAc and PFc function as circuits contributing to METH addiction, and the activation of the ERK phosphorylation plays an important role in the mechanisms of METH addiction. Besides, L-THP significantly decreased ERK phosphorylation's high expression induced by METH, which suggested that the inhibitory effect of L-THP on modulating METH reward behavior may be related to the suppression of ERK phosphorylation in NAc and PFc of mice. In conclusion, L-THP could suppress the reward properties of METH, therefore, it may be a promising candidate for the treatment of METH addiction.

16.
Food Funct ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31432066

RESUMO

The antidiabetic activity and potential underlying mechanism of a polysaccharide-protein (PSP) complex from Corbicula fluminea were determined in streptozotoxin (STZ)-induced diabetic rats. PSP exhibited inhibitory activity (in vitro) against α-glucosidase and α-amylase via a reversible competitive inhibition pattern with a stronger inhibition for α-glucosidase. Dietary administration of PSP had potential antidiabetic activities in vivo, which was evidenced by the fact that PSP alleviates body weight loss and organ injuries, reduced fasting blood glucose levels, elevated glucose tolerance, and ameliorated lipid metabolism and hepatic functions, as well as attenuated oxidative stress in STZ-treated diabetic rats. Furthermore, our results demonstrated that the antidiabetic activities of PSP were associated with the activation of the phosphoinositide 3-kinase/protein kinase B signaling pathway in STZ-treated rats. These findings supported the potential of PSP to be used as a functional ingredient in the preparation of functional and medicinal foods to inhibit diabetes mellitus and its complications.

17.
Cardiovasc Res ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31397837

RESUMO

AIMS: Circular RNAs (circRNAs) are involved in gene regulation in a variety of physiological and pathological processes. The present study aimed to investigate the effect of circRNA_000203 on cardiac hypertrophy and the potential mechanisms involved. METHODS AND RESULTS: CircRNA_000203 was found to be upregulated in the myocardium of Ang-II-infused mice and in the cytoplasma of Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Enforced-expression of circRNA_000203 enhances cell size and expression of atrial natriuretic peptide (ANP) and ß-myosin heavy chain (MHC) in NMVCs. In vivo, heart function was impaired and cardiac hypertrophy was aggravated in Ang-II-infused myocardium-specific circRNA_000203 transgenic mice (Tg-circ203). Mechanistically, we found that circRNA_000203 could specifically sponge miR-26b-5p, -140-3p in NMVCs. Further, dual luciferase reporter assay showed that miR-26b-5p, -140-3p could interact with 3'UTRs of Gata4 gene, and circRNA_000203 could block the above interactions. Additionally, Gata4 expression is transcriptionally inhibited by miR-26b-5p, -140-3p mimic in NMVCs, but enhanced by over-expression of circRNA_000203 in vitro and in vivo. Functionally, miR-26b-5p, -140-3p, and Gata4 siRNA, could reverse the hypertrophic growth in Ang-II-induced NMVCs, as well as eliminate the pro-hypertrophic effect of circRNA_000203 in NMVCs. Furthermore, we demonstrated that NF-κB signaling mediates the upregulation of circRNA_000203 in NMVCs exposed to Ang-II treatment. CONCLUSIONS: Our data demonstrated that circRNA_000203 exacerbates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p leading to enhanced Gata4 levels.

18.
Langmuir ; 35(34): 11157-11166, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31347852

RESUMO

It is expected that the widely dispersed ions in seawater would have strong influence on the performance of polymeric marine antibiofouling materials through the modulation of enzymatic degradation of the materials. In this work, poly(ε-caprolactone)-based polyurethane and poly(triisopropylsilyl methacrylate-co-2-methylene-1,3-dioxepane) have been employed as model systems to explore the specific ion effects on the enzymatic degradation of polymeric marine antibiofouling materials. Our study demonstrates that the specific ion effects on the enzymatic degradation of the polymer films are closely correlated with the ion-specific enzymatic hydrolysis of the ester. In the presence of different cations, the effectiveness of the enzyme to degrade the polymer films is dominated by the direct specific interactions between the cations and the negatively charged enzyme molecules. In the presence of different anions, the kosmotropic anions give rise to a high enzyme activity in the degradation of polymer films induced by the salting-out effect, whereas the chaotropic anions lead to a low enzyme activity in the degradation of the polymer films owing to the salting-in effect. This work highlights the opportunities available for the use of specific ion effects to modulate the enzymatic degradation of polymeric antibiofouling materials in the marine environment.

19.
Acc Chem Res ; 52(8): 2256-2265, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31328502

RESUMO

Indazoles are an important class of nitrogen heterocycles because of their excellent performance in biologically relevant applications, such as in chemical biology and medicinal chemistry. In these applications, convenient synthesis using commercially available and diverse building blocks is highly desirable. Within this broad class, 2H-indazoles are relatively underexploited when compared to 1H-indazole, perhaps because of regioselectivity issues associated with the synthesis of 2H-indazoles. This Account describes our unfolding of the synthetic utility of the Davis-Beirut reaction (DBR) for the construction of 2H-indazoles and their derivatives; parallel unfoldings of mechanistic models for these interrelated N-N bond forming reactions are also summarized. The Davis-Beirut reaction is a robust method that exploits the diverse chemistries of a key nitroso imine or nitroso benzaldehyde intermediate generated in situ under redox neutral conditions. The resulting N-N bond-forming heterocyclization between nucleophilic and electrophilic nitrogens can be leveraged for the synthesis of multiple classes of indazoles and their derivatives, such as simple or fused indazolones, thiazolo-indazoles, 3-alkoxy-2H-indazoles, 2H-indazole N-oxides, and 2H-indazoles with various substitutions on the ring system or the nitrogens. These diverse products can all be synthesized under alkaline conditions and the various strategies for accessing these heterocycles are discussed. Alternatively, we have also developed methods involving mild photochemical conditions for the nitrobenzyl → aci-nitro → nitroso imine sequence. Solvent consideration is especially important for modulating the chemistry of the reactive intermediates in these reactions; the presence of water is critically important in some cases, but water's beneficial effect has a ceiling because of the alternative reaction pathways it enables. Fused 2H-indazoles readily undergo ring opening reactions to give indazolones when treated with nucleophiles or electrophiles. Furthermore, palladium-catalyzed cross coupling, the Sonagashira reaction, EDC amide coupling, 1,3-dipolar cycloadditions with nitrile oxides, copper-catalyzed alkyne-azide cycloadditions (click reaction), as well as copper-free click reactions, can all be used late-stage to modify 2H-indazoles and indazolones. The continued development and applications of the Davis-Beirut reaction has provided many insights for taming the reactivity of highly reactive nitro and nitroso groups, which still has a plethora of underexplored chemistries and challenges. For example, there is currently a limited number of nonfused 2H-indazole examples containing an aryl substitution at nitrogen. This is caused by relatively slow N-N bond formation between N-aryl imine and nitroso reactants, which allows water to add to the key nitroso imine intermediate causing imine bond cleavage to be a competitive reaction pathway rather than proceeding through the desired N-N bond-forming heterocyclization.

20.
Food Chem ; 300: 125221, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31351256

RESUMO

In this study, water-soluble curdlan products (Cur and Cur-D) were prepared by an alkali-neutralization treatment process, after which ferulic acid (FA)-grafted Cur conjugates (Cur-g-FA and Cur-D-g-FA) were fabricated in the presence and absence of salt by adopting an approach involving free-radicals generated by the ascorbic acid/hydrogen peroxide redox pair under an inert atmosphere. Results showed that FA was successfully grafted onto the C-6 and C-4 positions of the Cur chains through covalent linkages and that the presence of salt exerted minor influences on the grafting ratios and structural characterizations of the products. Cur-g-FA and Cur-D-g-FA showed decreased crystallinity, thermal stability, and rheological properties, as well as a distinct surface morphology, when compared with those of native Cur. However, Cur-g-FA and Cur-D-g-FA also exhibited remarkably enhanced free-radical scavenging ability and antioxidant capacity in vitro. These results indicate that FA-grafted Cur conjugates have great potential application in the field of functional foods.

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