Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 990
Filtrar
1.
Eur J Surg Oncol ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33934940

RESUMO

BACKGROUND & AIMS: Postoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC. METHODS: The data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (>2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity. RESULTS: Among 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P < 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P < 0.001) and TTR (median: 19.8 vs. 46.1 months; P < 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126-1.451; P < 0.001) and recurrence (1.187; 1.058-1.331; P = 0.004). CONCLUSION: This large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33939259

RESUMO

All-polymer solar cells (all-PSCs) have achieved tremendous progress due to the recent advances of polymerized small molecule acceptors (PSMAs) and their power conversion efficiencies (PCEs) have reached over 14%. However, the practical applications of all-PSCs are still severely restricted by the lack of PSMAs with a broad absorption spectrum, high electron mobility, low energy loss, and good batch-to-batch reproducibility. Herein, a multi-selenophene-containing PSMA, namely PFY-3Se, based on a selenophene-fused SMA framework and a selenophene π-spacer was designed and developed. Compared to its thiophene analog PFY-0Se, PFY-3Se possesses a significantly red-shifted absorption (~30 nm), increased electron mobility, and improved intermolecular aggregation and packing. When matched with polymer donor PBDB-T, the PFY-3Se-based all-PSCs achieved an impressive PCE of 15.1% with both high short-circuit current density of 23.6 mA cm-2 and high fill factor of 0.737, and a low energy loss, which are among the best values in all-PSCs field reported so far and much better than those of thiophene analogs (PCE=13.0%). More importantly, PFY-3Se maintains similarly good batch-to-batch properties which is very helpful for realizing reproducible device performance. This is the first reported and also is very rare for the PSMAs so far which provides a potential candidate for efficient all-PSCs toward practical applications.

3.
Genome Med ; 13(1): 57, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845891

RESUMO

BACKGROUND: Mutations in the DMD gene encoding dystrophin-a critical structural element in muscle cells-cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD. METHODS: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46-54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors. RESULTS: Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member ß-dystroglycan. CONCLUSIONS: We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.

4.
Chem Commun (Camb) ; 57(31): 3816-3819, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33876130

RESUMO

A dual-aptamer based AND logic cascade circuit is activated on cell membranes in response to the receptor-aptamer binding, affording enhanced specificity for cell subtype recognition and gene silencing.

5.
Medicine (Baltimore) ; 100(14): e25299, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832099

RESUMO

ABSTRACT: Intradialytic hypotension (IDH) may lead to a poor life quality and was associated with cardiovascular mortality in patients under hemodialysis. This study investigated the autonomic nerve and cardiovascular function in the IDH episodes.In this case-control study, 70 end stage renal disease patients (198 visits) were recruited. Pulse wave analysis and heart rate variability were evaluated before hemodialysis. Two definitions of IDH were confirmed by medical records. IDH-f indicated a drop of systolic blood pressure or mean arterial pressure, accompanied with symptoms; IDH-n indicated a low nadir systolic pressure during the hemodialysis. All parameters were evaluated for the possible predisposing factors under each definition.A total of 24 IDH-f and 37 IDH-n were noted in 177 visits. For both definitions, central pulse pressure seemed to be a consistent predisposing factor. Furthermore, lower sympathetic activity (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.35-0.87), lower pulse pressure (OR 0.95; 95% CI 0.92-0.98), and higher augmentation index (OR 17.36; 95% CI 1.48-204.10) were the possible predisposing factors for IDH-f. On the contrary, lower mean arterial pressure (OR 0.87; 95% CI 0.78-0.98) was identified as the possible factor for IDH-n.It was suggested that the lower central pulse pressure and sympathetic activity might be involved in the development of IDH.


Assuntos
Hemodinâmica/fisiologia , Hipotensão/etiologia , Hipotensão/fisiopatologia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Análise de Onda de Pulso
6.
Thorac Cancer ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829674

RESUMO

BACKGROUND: Lung cancer stage has a significant impact on prognosis, and early detection of lung cancer relies on screenings. Despite the strong relationship between screening and lung cancer staging, the role of healthcare expenditure in lung cancer outcomes remains unknown. The aim of this study was to evaluate the relationship between economic status and clinical outcomes in lung cancer. METHODS: Data were obtained from GLOBOCAN and the World Health Organization. Mortality-to-incidence ratios (MIRs) and their change over time, calculated as the difference between the MIRs of 2012 and 2018 (δMIR), were used to evaluate their correlation to expenditures on healthcare and human development index (HDI) disparities via Spearman's rank correlation coefficient. RESULTS: Regions such as North America have relatively high crude incidence rates but low MIR values. Furthermore, countries with lower crude incidence rates spent less on healthcare. The results show significant negative associations between HDI, current health expenditure (CHE) per capita, CHE as a percentage of gross domestic product (CHE/GDP), and MIR. As for MIR and δMIR, countries with favorable MIRs also showed improving MIRs based on δMIR. CONCLUSIONS: HDI, CHE per capita, CHE/GDP, and development status play noticeable roles in the prognosis of lung cancer, leading to large disparities in clinical outcomes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33792691

RESUMO

BACKGROUND: The optimal antibiotic regimen for the medical management of acute appendicitis remains unknown due to a lack of head-to-head comparisons between different antibiotic regimens. METHODS: We systematically searched the PubMed, EMBASE, Scopus and Cochrane Central Register of Controlled Trials databases from their inception through to August 2020. We selected randomized controlled trials (RCTs) or observational studies comparing antibiotic therapy and appendectomy as the initial treatment for adult or paediatric patients with acute appendicitis. We performed a Bayesian network meta-analysis (NMA) to obtain the indirect comparison results between different antibiotic regimens by employing the group managed by surgery as a common comparator. Antibiotic regimens were classified into three categories: those including a carbapenem; those including a cephalosporin; and those including a ß-lactam/ß-lactamase inhibitor combination. RESULTS: A total of 9 RCTs (adults, n = 8; paediatrics, n = 1) and 12 observational studies (adults, n = 3; paediatrics, n = 9) were included in the NMA, with a total of 4551 patients. The most commonly administered regimen was a ß-lactam/ß-lactamase inhibitor combination (9/21; 43%), followed by a cephalosporin (7/21; 33%) or a carbapenem (5/21; 24%). The NMA indicated that surgery significantly increased 1 year treatment success, compared with cephalosporins [OR: 16.79; 95% credible interval: 3.8-127.64] or ß-lactam/ß-lactamase inhibitor combinations (OR: 19.99; 95% credible interval: 4.87-187.57), but not carbapenems (OR: 3.50, 95% credible interval: 0.55-38.63). In contrast, carbapenems were associated with fewer treatment-related complications compared with surgery (OR: 0.12; 95% credible interval: 0.01-0.85). CONCLUSIONS: Carbapenems might be recommended as the initial antibiotic regimen for the non-operative management of adult patients with acute appendicitis. Nevertheless, due to the imprecise estimates in our NMA, additional RCTs are needed to corroborate these findings, especially for paediatric patients.

9.
J Neurochem ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882624

RESUMO

Cognitive deficits are the core feature of schizophrenia and effective treatment strategies are still missing. Previous studies have reported that fisetin promotes long-term potentiation (LTP) and cognitive function in normal rodents and other model animals of neurological diseases. The aim of the present study was to assess the effect of fisetin on synaptic plasticity and cognitive deficits caused by a brief disruption of N-methyl-D-aspartate receptors (NMDARs) with dizocilpine (MK-801) during early development in rats. The cognitive performance was examined by the Morris water maze task and a fear conditioning test. Hippocampal synaptic plasticity was investigated by field potential recording. The expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and cognition-related proteins were measured by Western blotting. We found that intraperitoneal administration of fisetin rescued hippocampus-dependent spatial and contextual fear memory in MK-801 rats. In parallel with these behavioral results, fisetin treatment in MK-801 rats reversed the impairment of hippocampal LTP. At the molecular level, fisetin treatment selectively increased the phosphorylation and surface expression of AMPA receptor subunit 1 (GluA1) in MK-801-treated rats. Moreover, fisetin restored the phosphorylation levels of calcium-calmodulin-dependent kinaseII (CaMKII), cAMP response element-binding protein (CREB) and the extracellular signal-regulated kinase (ERK1/2) in MK-801-treated rats. Collectively, our findings demonstrate that fisetin treatment can reverse the deficits of hippocampal synaptic plasticity and memory in a male rat model of schizophrenia by restoring the phosphorylation and surface expression of AMPAR GluA1 subunit, suggesting fisetin as a promising therapeutic candidate for schizophrenia-associated cognitive deficits.

11.
Nano Lett ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830766

RESUMO

The genetic heterogeneities in cancer cells pose challenges to achieving precise drug treatment in a widely applicable manner. Most single-cell gene analysis methods rely on cell lysis for gene extraction and identification, showing limited capacity to provide the correlation of genetic properties and real-time cellular behaviors. Here, we report a single living cell analysis nanoplatform that enables interrogating gene properties and drug resistance in millions of single cells. We designed a Domino-probe to identify intracellular target RNAs while releasing 10-fold amplified fluorescence signals. An on-chip addressable microwell-nanopore array was developed for enhanced electro-delivery of the Domino-probe and in situ observation of cell behaviors. The proof-of-concept of the system was validated in primary lung cancer cell samples, revealing the positive-correlation of the ratio of EGFR mutant cells with their drug susceptibilities. This platform provides a high-throughput yet precise tool for exploring the relationship between intracellular genes and cell behaviors at the single-cell level.

12.
Mol Oncol ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811456

RESUMO

Glioma cells are characterized by high migration and invasion ability; however, the molecular mechanism behind both processes still remains to be investigated. Several studies have demonstrated that ubiquitin-specific protease 39 (USP39) plays an oncogenic role in various cancer types. Here, we investigated the expression and function of USP39 in patients with glioma. Oncomine database analysis revealed that high USP39 expression was significantly correlated with poor overall survival in patients with glioma. Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro. Gene expression profiling of glioma cells transduced with short hairpin RNA (shRNA) against USP39 revealed that disintegrin and metalloproteinase domain-containing protein 9 (ADAM9), a molecule previously related to tumor cell migration and invasion, was significantly downregulated. Furthermore, USP39 induced ADAM9 messenger RNA (mRNA) maturation and decreased the expression of integrin ß1. Additionally, overexpression of ADAM9 inhibited the migration and invasion of glioma cells caused by USP39 depletion in vitro. USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice. Altogether, our data show that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered potential target for treating patients with glioma.

13.
Leuk Res ; 105: 106566, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33848709

RESUMO

Angiogenesis is an integral part of the multiple myeloma (MM) microenvironment, and affects tumorigenesis, progression, invasion, and metastasis. Exosomes are essential for cell-cell communication and help in regulating the bone marrow microenvironment. Herein, we investigated macrophage polarization and angiogenesis in MM in vitro via exosome-derived miR-let-7c. We observed that exosomal miR-let-7c secreted by mesenchymal stem cells promoted M2 macrophage polarization, thereby enhancing angiogenesis in the bone marrow microenvironment. Suppressing miR-let-7c expression significantly inhibited vascular endothelial cell function in myeloma. Thus, exosomal miR-let-7c may be a reliable biomarker for early prediction of tumor progression and a promising therapeutic target for MM.

14.
Waste Manag ; 126: 706-718, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33878675

RESUMO

This is the first study integrate the flameless oxidation (FO) and in-chamber melting (ICM) processes in a primary chamber of a laboratory waste incinerator to improve energy and emission performances. Two liquid burners created a twin-cyclonic fluid field that achieved the FO and ICM in the same chamber. The first cyclone provided a well-mixed and lower temperature FO to reduce auxiliary diesel consumption, NOx and PM emissions by 25.8%, 30.9%, and 79.2%, respectively, from the original system. The hot gases produced by FO enhance the ICM process and transformed the bottom ashes to stabler slags, in turn meeting the regulations for nonhazardous wastes. The other cyclone enhanced the drying and water-gas shift reaction in the drying zone by recirculating the CO and enthalpy from FO and ICM. Eventually, the residual CO, hydrocarbons, and H2 were sent to the secondary chamber for further oxidation. A computational fluid dynamic simulation supported the fluid field assumption posed in this study. Moreover, advanced scrubbers were employed after thermal treatments to reduce HCl and SO2 by 81.8% and 38.8% and further retarded the corrosion rate in the baghouse supporting cage by 87.7%. The precursors of condensable particulate matter were reduced by condensation and finally removed in the baghouse. Nevertheless, the emissions of the high- and mid-molecular-weight polycyclic aromatic hydrocarbons were greatly reduced by 60.8-93.1% and 80.2-99.9%, respectively. Consequently, the new system reduced annual emissions by 40.7-87.6% and operating costs by 41.5%, allowing recovery of the remodification investment in 20.5 months.

15.
Biochem Biophys Res Commun ; 557: 334-341, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33915432

RESUMO

Atherosclerosis is a chronic lipid disfunction and inflammatory disease, which is characterized with enriched foam cells and necrotic core underneath the vascular endothelium. Therefore, the inhibition of foam cell formation is a critical step for atherosclerosis treatment. Metformin, a first-line treatment for Type 2 diabetes, is reported to be beneficial to cardiovascular disease. However, the mechanism underlying the antiatherogenic effect of metformin remains unclear. Macrophage autophagy is reported to be a highly anti-atherogenic process that promotes the catabolism of cytosolic lipid to maintain cellular lipid homeostasis. Notably, dysfunctional autophagy in macrophages plays a detrimental role during atherogenesis. Krueppel-like factor 2 (KLF2) is an important transcription factor that functions as a key regulator of the autophagy-lysosome pathway. While the role of KLF2 in foam cell formation during the atherogenesis remains elusive. In this study, we first investigated whether metformin could protect against atherogenesis via enhancing autophagy in high fat diet (HFD)-induced apoE-/- mice. Subsequently, we further determined the molecular mechanism that whether metformin could inhibit foam cell formation by activating KLF2-mediated autophagy. We show that metformin protected against HFD-induced atherosclerosis and enhanced plaque stability in apoE-/- mice. Metformin inhibits foam cell formation and cellular apoptosis partially through enhancing autophagy. Mechanistically, metformin promotes autophagy via modulating KLF2 expression. Taken together, our study demonstrates a novel antiatherogenic mechanism of metformin by upregulating KLF2-mediated autophagy.

16.
Biol Reprod ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33899078

RESUMO

Three major pathogenic states of the prostate, including benign prostatic hyperplasia, prostate cancer, and prostatitis, are related to the local inflammation. However, the mechanisms underlying the initiation of prostate inflammation remain largely unknown. Given that the innate immune responses of the tissue-specific cells to microbial infection or auto-antigens contribute to local inflammation, this study focused on pattern recognition receptor (PRR)-initiated innate immune responses in mouse prostatic epithelial cells (PECs). Primary mouse PECs abundantly expressed Toll-like receptor 3 (TLR3), TLR4, TLR5, melanoma differentiation-associated protein 5 (MDA5) and p204. These PRRs can be activated by their respective ligands: lipopolysaccharide (LPS) and flagellin of Gram-negative bacteria for TLR4 and TLR5, polyinosinic-polycytidylic acid (poly(I:C)) for TLR3 and MDA5, and herpes simplex virus DNA analog (HSV60) for p204. LPS and flagellin predominantly induced the expression of inflammatory cytokines, including TNFA, IL6, MCP1, and CXCL10. Poly(I:C) and HSV60 predominantly induced the expression of type 1 interferons (IFNA and IFNB) and antiviral proteins: Mx GTPase 1, 2',5'-oligoadenylate synthetase 1, and IFN-stimulated gene 15. The replication of mumps virus in PECs was inhibited by type 1 IFN signaling. These findings provide insights into the mechanisms underlying innate immune response in the prostate.

17.
BMC Mol Cell Biol ; 22(1): 21, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827416

RESUMO

BACKGROUND: Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. RESULTS: We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvß3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvß3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. CONCLUSIONS: In this study, we found that Cyr61 promotes SC proliferation and migration via αvß3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC's function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

18.
Chemosphere ; 278: 130489, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33839388

RESUMO

Graphene photocatalysis is receiving increased attention for its potential to be used as a novel green technology for mitigating harmful algae in highly eutrophic waters. However, graphene is seldom applied to in situ aquatic ecosystems for environmental applications. Here, the impacts of graphene photocatalysis on phytoplankton and environmental conditions were evaluated through an in situ macrocosm experiment in the eutrophic Lake Xingyun, southwestern China. The graphene photocatalysis treated area had significantly reduced conductivity, total nitrogen (TN), total phosphorus (TP) and dissolved phosphorus concentrations, as well as increased dissolved oxygen (DO) concentrations. The abundances of all species of the genus Microcystis were significantly reduced in the graphene photocatalysis-treated area; in contrast, the abundances of all species of the diazotrophic genera, including Anabaena and Aphanizomenon, greatly increased after treatment with graphene photocatalysis. Eukaryotic algae, especially Chlorophyta, Euglenophyta and Pyrrophyta, as well as Cryptophyta, had significantly higher abundances in the graphene photocatalysis-treated area, whereas most of the eutrophic diatom species had lower abundances in the treated area. These observed differences in eukaryotic algae between the two groups might be related to their sensitivity to graphene photocatalysis and their tolerance of nutrients. Generally, graphene photocatalysis can make a great contribution to the improvement of eutrophic water, as evidenced by the reduction in cyanobacteria abundance and phosphorus concentration, as well as the increase in species richness and the dissolved oxygen concentration in the treated area. However, the mechanisms underlying these differences in phytoplankton community structure and environmental conditions require further study.

19.
Front Immunol ; 12: 582946, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815357

RESUMO

The causative agent of mumps is a single-stranded, non-segmented, negative sense RNA virus belonging to the Paramyxoviridae family. Besides the classic symptom of painfully swollen parotid salivary glands (parotitis) in mumps virus (MuV)-infected men, orchitis is the most common form of extra-salivary gland inflammation. Mumps orchitis frequently occurs in young adult men, and leads to pain and swelling of the testis. The administration of MuV vaccines in children has been proven highly effective in reducing the incidence of mumps. However, a recent global outbreak of mumps and the high rate of orchitis have recently been considered as threats to male fertility. The pathogenesis of mumps orchitis remains largely unclear due to lack of systematic clinical data analysis and animal models studies. The alarming increase in the incidence of mumps orchitis and the high risk of the male fertility have thus become a major health concern. Recent studies have revealed the mechanisms by which MuV-host cells interact and MuV infection induces inflammatory responses in testicular cells. In this mini-review, we highlight advances in our knowledge of the clinical aspects and possible mechanisms of mumps orchitis.

20.
J Cell Mol Med ; 25(8): 3724-3734, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33724642

RESUMO

Several studies reported the role of endoplasmic reticulum stress (ERS) in vascular calcification. High-mobility group box-1 (HMGB-1) plays a substantial role in diabetes and its complications. However, relatively little information is available regarding the association between HMGB-1 and calcification, and the underlying mechanism has still remained elusive. Therefore, in the present study, we attempted to indicate whether HMGB-1 could promote vascular calcification via ERS in diabetes. After induction of diabetes by Streptozotocin (STZ), mice were treated with glycyrrhizin (Gly) or 4-phenylbutyrate (4-PBA). Mineral deposition was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and calcium assay. In cell experiments, calcification of vascular smooth muscle cells (VSMCs) was performed with Alizarin Red staining, alkaline phosphatase (ALP) activity and RT-PCR. Expression and location of HMGB-1 in aortic tissue were detected by Western blotting, immunocytochemistry (ICC) and immunohistochemistry (IHC). Diabetic mice demonstrated increased HMGB-1 expression, ERS and vascular calcification. However, inhibition of HMGB-1 with Gly or inhibition of ERS with 4-PBA ameliorated the enhanced vascular calcification and ERS in diabetic mice. In vitro experiments unveiled that inhibition of HMGB-1 attenuated advanced glycation end products (AGEs)-induced ERS in VSMCs. In addition, AGEs promoted translocation and secretion of HMGB-1 in VSMCs, which was reversed by 4-PBA. Moreover, VSMCs exhibited increased mineralization and osteogenic gene expressions in response to HMGB-1 and AGEs. However, inhibition of ERS with 4-PBA partially, although noticeably, attenuated VSMC calcification induced by HMGB-1. Thus, diabetes induced translocation and secretion of HMGB-1 via ERS, which resulted in calcification in diabetic mice and in AGEs-treated VSMCs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...