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1.
Artigo em Inglês | MEDLINE | ID: mdl-31703838

RESUMO

Inflammasome mechanisms are recognized as a key pathophysiology of diabetic nephropathy (DN). The nucleotide-oligomerization domain-like receptor 3 (NLRP3) inflammasome has attracted the most attention. Autophagy as a conserved intracellular catabolic pathway plays essential roles in the maintenance of podocytes. Although autophagy was involved in preventing excessive inflammatory responses in kidney diseases, a clear understanding of the regulation of NLRP3 inflammasome on autophagy in glomerular damage in DN is still lacking. In this study, we focused on the effect of the activation of NLRP3 inflammasome on the suppression of podocyte autophagy and aimed to investigate the role of autophagy in podocyte injury in DN. Podocyte autophagy has been confirmed to be inhibited in high-fat diet/streptozotocin (HFD/STZ)-induced DN mice, and NLRP3 has been found to be upregulated in both mice and human DN biopsies and in vitro. Activation of NLRP3 inflammasome exacerbated podocyte autophagy and reduced podocyte nephrin expression, while silencing of NLRP3 efficiently restored podocyte autophagy and ameliorated podocyte injury induced by high glucose. The results showed that NLRP3 was a negative regulator of autophagy and suggested that restoration of podocyte autophagy by inactivation of NLRP3 under high glucose could reduce podocyte injury. Proper modification of autophagy and inflammasome has the potential to benefit the kidney in DN.

2.
Appl Opt ; 58(24): 6700-6705, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31503603

RESUMO

Titanium nitride (TiN) is a metal-like refractory material that can be used as a substitution for metals in many applications. In this paper, we report the use of an ultra-thin TiN film in the Salisbury screen structure to spectral selectively absorb visible light for forming an optical color filter. The ultra-thin TiN film functions as a partial reflector as well as a protection capping layer in the structure. Spectral selective perfect absorption color filters with TiN-ZnO-Al multilayer films were fabricated and characterized.

3.
Anal Chim Acta ; 1081: 51-58, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31446963

RESUMO

Mercury ions can significantly affect the organism and environment even at a very low concentration. Thus, great efforts have been devoted to developing high sensitive electrochemical sensors, especially the one that not only detect the mercury ions but also effective sensitive to thymine-Hg2+-thymine in aqueous solution. Metal-organic-frameworks (MOFs) possess hollow nature and are easy for grafting functional groups, however, there is still no attempts for working as electrochemical sensors in detecting mercury ions. Herein, we report a novel type sensor of Zr(IV)-based MOFs with specifically attached thioether side groups allowing mercury ions to be easily adsorbed and detected. The Zr(IV)-involved MOFs show strong binding to mercury ions compared with the bare MOFs, as confirmed by both experiment measurements and theoretical calculations. The as-prepared senor is sensitive ranging from 0.01 nM to 3 µM with detection limitation of 7.3 fM, which is better than most of T-Hg2+-T- and enzyme-based sensors reported so far. The high sensitivity could be due to the straightforward adsorption pathway and the biomolecule exclusion nature of the Zr(IV)-involved MOFs sensor. We anticipate that our findings could pave the way for MOFs-based sensor exploration towards its commercial applications.

4.
Environ Pollut ; 253: 429-438, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325888

RESUMO

Recently, the essentiality and fatalness of cardiovascular diseases is attracting much attention. Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants, which could induce the toxic effect and have been implicated in the occurrence and development of cardiovascular diseases. However, it is unclear how autophagy and apoptosis induced by BDE-209 in endothelial cells are regulated. The aim of the present study was to investigate the effects of BDE-209 on human umbilical vein endothelial cells (HUVECs) and elucidate the mechanisms involved. HUVECs were treated with a wide range concentration of BDE-209 for 24 h. The appearance of autophagy was tested by the testing index such as outcomes of monodansylcadaverine (MDC) staining and lysotracker staining, observation of autophagosomes and conversion between autophagy marker light chain 3 (LC3)-I and LC3-II. Besides, the apoptotic cell rate was detected with flow cytometry. In addition, BDE-209 induced endoplasmic reticulum (ER) stress was detected by transmission electron microscopy (TEM). Our data suggest that the exposure of BDE-209 could induce autophagy, which was confirmed by MDC staining, transmission electron microscopy observation, lysotracker staining and LC3-I/LC3-II conversion. Besides, the ER stress-related inositol-requiring enzyme 1α (IRE1α)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway could be activated by reactive oxygen species (ROS) to regulate autophagy. Moreover, the apoptosis of endothelial cells was alleviated when autophagy was blocked by 3-Methyladenine (3-MA). The results demonstrated that BDE-209 could induce the production of ROS and ER stress, activate autophagy through IRE1α/AKT/mTOR signaling pathway and ultimately induce apoptosis of vascular endothelial cells. These findings indicate that exposure to PBDE is possible to be a potential risk factor for cardiovascular diseases.


Assuntos
Poluentes Ambientais/toxicidade , Éteres Difenil Halogenados/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Inositol , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Testes de Toxicidade , Veias Umbilicais
5.
J Enzyme Inhib Med Chem ; 34(1): 1287-1297, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31288582

RESUMO

Inhibition of NF-κB signalling has been demonstrated as a therapeutic option in treating inflammatory diseases and cancers. Herein, we synthesized novel dissymmetric 3,5-bis(arylidene)-4-piperidones (BAPs, 83-102) and characterized fully. MTT and ELISA assay were performed to screen the anti-hepatoma and anti-inflammation properties. 96 showed the most potential bioactivity. 96 could promote HepG2 apoptosis through up-regulating the expression of C-Caspase-3 and Bax, down-regulating the expression of Bcl-2, while markedly inhibit LPS or TNF-α-induced activation of NF-κB through both inhibiting the phosphorylation of IκBα and p65, and preventing the p65 nuclear translocation to exhibit both anti-hepatoma and anti-inflammatory activities. Molecular docking verified that simulated 96 can effectively bond to the active site of Bcl-2 and NF-κB/p65 proteins. 96 inhibited xenografts growth by reducing the expression of TNF-α and Bcl-2 in the tumour tissue. This study suggested that 96 could be developed as a potential multifunctional agent for treatment of inflammatory diseases and cancers.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/prevenção & controle , Inflamação/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , NF-kappa B/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/patologia , Simulação de Acoplamento Molecular
6.
Zhongguo Zhen Jiu ; 39(6): 588-92, 2019 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-31190493

RESUMO

OBJECTIVE: To explore the effect of acupuncture at the "reflection points" of affected side on the peripheral facial paralysis in acute phase. METHODS: Ninety patients with peripheral facial paralysis in acute phase were randomly divided into a reflection group (group A), a conventional acupuncture group (group B) and a physiotherapy group (group C), 30 cases in each group. The same basic medication were given in all three groups. In the group A, acupuncture at "reflection points" of the affected side and local acupoints in acute phase, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group B, acupuncture at Yifeng (TE 17) of the affected side in acute phase and local acupoints, such as Dicang (ST 4), Jiache (ST 6), Quanliao (SI 18), Xiaguan (ST 7), Yangbai (GB 14), Taiyang (EX-HN 5), etc. were applied. The electroacupuncture was added in the stationary phase, and Zusanli (ST 36) was added in the recovery phase. In the group C, ultrashort wave on Yifeng (TE 17) of the affected side in acute phase was applied, and the treatment in the stationary phase and the recovery phase was the same as the group B. The treatment was given once every day, 5 times as one course for 4 courses. The House-Brackmann (H-B) grading scale, facial disability index scale, the symptom and physical score integral scale were used to score before and after treatment, and the clinical effects of the three groups were compared. RESULTS: After treatment, the functional grade of H-B facial nerve was better than that before treatment in the three groups (P<0.01). There was no significant difference among the three groups after treatment (P>0.05). After treatment, the course of treatment required to reflect the healing in the group A was shorter than that in the group B and the group C (P<0.01); the body function scores and social function scores in the three groups were better than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). The scores of symptoms and signs in the three groups were lower than those before treatment (P<0.01), there was no significant difference among the three groups after treatment (P>0.05). H-B facial nerve function grading scale and facial disability index (FDI) scale were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B and 46.7% (14/30) in the group C, the curative rate in the group A was better than the other two groups (P<0.05). The curative and markedly effective rate in the group A was 83.3% (25/30), 70.0% (21/30) in the group B and 63.3% (19/30) in the group C, the curative and markedly effective rate in the group A was better than the other two groups (P<0.05). The scores of symptoms and signs were used as the evaluation criteria, the curative rate was 66.7% (20/30) in the group A, 50.0% (15/30) in the group B, and 46.7% (14/30) in the group C. The curative rate in the group A was better than the other two groups (P<0.05). CONCLUSION: Compared with general acupuncture and physiotherapy, acupuncture at the "reflection points" of the affected side on the peripheral facial paralysis in acute phase could shorten the course of treatment and improve the curative effect.


Assuntos
Terapia por Acupuntura , Eletroacupuntura , Paralisia Facial , Pontos de Acupuntura , Paralisia Facial/terapia , Humanos
7.
Appl Biochem Biotechnol ; 189(4): 1304-1317, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31254227

RESUMO

Feruloyl esterases (FAEs) have great potential applications in paper and breeding industry. A new thermo-stable feruloyl esterase gene, TtfaeB was identified from the thermophilic fungus Thielavia terrestris h408. Deduced protein sequence shares the identity of 67% with FAEB from Neurospora crassa. The expression vector pPIC9K-TtfaeB was successfully constructed and electro-transformed into GS115 strain of Pichia pastoris. One transformant with high feruloyl esterase yield was obtained through plate screening and named TtFAEB1. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of fermentation supernatant from transformant TtFAEB1 showed a distinct protein band appearing at the position of about 35-kDa, indicating that TtfaeB gene has been successfully expressed in P. pastoris. The recombinant TtFAEB was purified by affinity chromatography and the specific activity of purified TtFAEB was 6.06 ± 0.72 U/mg. The optimal temperature and pH for purified recombinant TtFAEB was 60 °C and 7.0, respectively. TtFAEB was thermostable, retaining 96.89 and 84.16% of the maximum activity after being treated for 1 h at 50 °C and 60 °C, respectively. Additionally, the enzyme was stable in the pH range 4.5-8.0. The homology model of TtFAEB showed that it consists of a single domain adopting a typical α/ß-hydrolase fold and contains a catalytic triad formed by Ser117, Asp201, and His260. TtFAEB in association with xylanase from Trichoderma reesei could release 77.1% of FA from destarched wheat bran. The present results indicated that the recombinant TtFAEB with excellent enzymatic properties is a promising candidate for potential applications in biomass deconstruction and biorefinery.

8.
Cell Biol Int ; 43(8): 899-909, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31081266

RESUMO

Previous studies have shown that the ovarian failure in autoimmune-induced premature ovarian failure (POF) mice could be improved by the transplantation of human placenta-derived mesenchymal stem cells (hPMSCs); however, the protective mechanism of hPMSCs transplantation on ovarian dysfunction remains unclear. Ovarian dysfunction is closely related to the apoptosis of granulosa cells (GCs). To determine the effects of hPMSCs transplantation on GCs apoptosis, an autoimmune POF mice model was established with zona pellucida glycoprotein 3 (ZP3) peptide. It is reported that the inositol-requiring enzyme 1α (IRE1α) and its downstream molecules play a central role in the endoplasmic reticulum (ER) stress-induced apoptosis pathway. So the aim of this study is to investigate whether hPMSCs transplantation attenuated GCs apoptosis via inhibiting ER stress IRE1α signaling pathway. The ovarian dysfunction, follicular dysplasia, and GCs apoptosis were observed in the POF mice. And the IRE1α pathway was activated in ovaries of POF mice, as demonstrated by, increased X-box binding protein 1 (XBP1), up-regulated 78 kDa glucose-regulated protein (GRP78) and caspase-12. Following transplantation of hPMSCs, the ovarian structure and function were significantly improved in POF mice. In addition, the GCs apoptosis was obviously attenuated and IRE1α pathway was significantly inhibited. Transplantation of hPMSCs suppressed GCs apoptosis-induced by ER stress IRE1α signaling pathway in POF mice, which might contribute to the hPMSCs transplantation-mediating ovarian function recovery.


Assuntos
Apoptose/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Células-Tronco Mesenquimais/imunologia , Placenta/citologia , Insuficiência Ovariana Primária , Animais , Caspase 12/metabolismo , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Endorribonucleases/metabolismo , Feminino , Células da Granulosa/citologia , Proteínas de Choque Térmico/metabolismo , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Ovário/metabolismo , Gravidez , Insuficiência Ovariana Primária/metabolismo , Insuficiência Ovariana Primária/terapia , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína 1 de Ligação a X-Box/metabolismo , Glicoproteínas da Zona Pelúcida/metabolismo
9.
Biochem Biophys Res Commun ; 513(1): 147-153, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-30948157

RESUMO

OBJECTIVE: We investigated whether Piezo1 could regulate oxygen-glucose deprivation/reoxygenation injury of neurons through Ca2+/calpain signaling. METHODS: Piezo1 expression in rat brain cortex and PC12 cells were confirmed by immunohistochemistry, immunofluorescence and Western blotting. The effects of Yoda1 and GsMTx4 on OGD/R-induced decrease in cell viability, increase in cell apoptosis and activation of downstreaming Ca2+/calpain signaling were investigated. Furthermore, calpain signaling was inhibited by PD151746 to see whether Ca2+/calpain signaling participated in the neurotoxic effects of Piezo1 activation. RESULTS: Piezo1 expression was increased in rat cerebral cortex after ischemia/reperfusion and in PC12 cells after OGD/R. Activation of Piezo1 by Yoda1 enhanced OGD/R-induced cell viability inhibition, apoptosis, increase intracellular calcium levels and enhanced calpain activity while GsMTx4 showed the opposite effects. The effects of Piezo1 activation on cell viability and apoptosis were reversed by PD151746. CONCLUSION: Piezo1 could regulate neuron oxygen-glucose deprivation/reoxygenation injury via activation of Ca2+/calpain signaling.

10.
Bioelectrochemistry ; 128: 9-16, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30884361

RESUMO

Bioelectrochemical systems (BESs) have shown great potential for azo dye removal. However, comprehensive evaluation of the bioelectrochemical decolorization performance for reactive diazo dyes remains limited, particularly the kinetics and operation parameter optimization. This study evaluated the decolorization of the diazo dye Reactive Black 5 (RB5) in BESs, particularly with regard to kinetics, parameter optimization using response surface methodology (RSM), and the degradation pathway. The results indicated that the pseudo-first-order kinetic rate constant of RB5 decolorization increased from 0.023 ±â€¯0.001 to 0.146 ±â€¯0.008 h-1 with a decrease in cathode potential from -400 mV to -500 mV. RSM optimization suggested that the linear effects of RB5 concentration, cathode potential and hydraulic retention time (HRT), interaction of RB5 concentration with cathodic HRT, and the quadratic effect of cathodic HRT were most influential on the bioelectrochemical decolorization of RB5. Further, the decolorized RB5 products in the BESs were characterized by ultraviolet-visible spectrophotometry, Fourier-transform infrared spectroscopy, and liquid chromatograph-mass spectrometry. From this, a potential decolorization mechanism is proposed based on cleavage of azo bonds.


Assuntos
Compostos Azo/química , Cor , Corantes/química , Técnicas Eletroquímicas/métodos , Cromatografia Líquida , Eletrodos , Estudos de Viabilidade , Cinética , Microscopia Eletrônica de Varredura , Naftalenossulfonatos/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Espectrometria de Massas em Tandem
11.
World Neurosurg ; 127: e346-e352, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30904799

RESUMO

BACKGROUND: Neuronal apoptosis plays a pivotal role in spinal cord injury (SCI)-induced secondary cellular events. Caspase-dependent and -independent pathways are involved in neuronal apoptosis. Caspase-3 is the final effector of caspase-dependent apoptosis, whereas poly-ADP-ribose polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) are key executors of caspase-independent apoptosis. However, it remains unclear whether simultaneous inhibition of the 2 apoptosis pathways will be more beneficial for neuronal survival. Therefore, this study investigated the ability of coadministration of the PARP-1 inhibitor 3-aminobenzamide (3-AB) and caspase-3 inhibitor z-DEVD-fmk to attenuate apoptosis in a rat SCI model. METHODS: The rats were subjected to moderate contusive SCI. Locomotor function was measured using the Basso, Beattie, and Bresnahan rating scales; neuronal apoptosis was detected using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling; and immunohistochemistry and Western blotting were used to measure protein expression. RESULTS: We found the locomotor function of rats was weakened within 7 days post-SCI. At day 7 post-SCI, neuronal apoptosis dramatically increased and the expression of PARP-1, AIF, and cleaved caspase-3 was significantly upregulated. Further, Bcl-2 expression was significantly downregulated. The highest locomotor function recovery was recorded after the combined administration of 3-AB and z-DEVD-fmk for 7 days post-SCI when compared with 3-AB or z-DEVD-fmk administered alone. In addition, this combination therapy significantly reduced neuronal apoptosis by preventing upregulation of PARP-1 and AIF, inhibiting caspase-3 activation, and elevating Bcl-2 expression. CONCLUSIONS: These results suggest that combination therapy is beneficial for neuronal function recovery in rats with SCI. The underlying mechanism may be associated with cosuppression of caspase-dependent and caspase-independent apoptosis pathways.

12.
Chem Commun (Camb) ; 55(35): 5091-5094, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30924482

RESUMO

To boost the design of microporous solids, we integrated a two-faced shape (as in cucurbiturils and cyclodextrins) into the building blocks of framework materials. Reported herein is a planar tritopic carboxyl linker with secondary tripod donors sprouting off both sides at the core region. The two-faced, barrel-like core region imparts a rugged 3D character to the linker architecture, obviating close packing and creating complex-shaped cavities in an Eu(iii)-carboxylate network. The merits extend beyond the interesting shape of the multiple tripod: e.g., the two sets of sulfur tripods at the barrel region, together with the triazine center, offer a rich array of donors for adsorbing Hg(ii) ions. The microporous solid also removes iodine from vapor and water, and can be easily cycled in column chromatography.

13.
J Enzyme Inhib Med Chem ; 34(1): 264-271, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30734613

RESUMO

Novel hydroxyl-substituted double Schiff-base 4-piperidone/cyclohexanone derivatives, 3a-e, 4a-e, 5a-d, and 6a-c, were synthesized and fully characterized by 1H NMR, IR and elemental analysis. The cytotoxicity against human carcinoma cell lines A549, SGC7901, HePG2, HeLa, K562, THP-1 and non-malignant LO2 cell lines were evaluated. The results showed 4-piperidinone derivatives displayed better cytotoxicity than cyclohexanone derivatives, especially for 3,4,5-trihydroxyphenyl-substituted BAP 5c. The western blot and flow cytometry results proved 5c can effectively promote cell apoptosis through up-regulating Bax protein and down-regulating Bcl-2 protein expression. Molecular docking modes showed that 5c could reasonably bind to the active site of Bcl-2 protein through strong intermolecular hydrogen bonds and significant hydrophobic effect. In vivo, 5c can effectively suppress the growth of HepG2 xenografts without apparent body weight changes. This study indicates that 5c can be a potential anticancer agent for early treatment of liver cancers.


Assuntos
Antineoplásicos/farmacologia , Cicloexanonas/farmacologia , Hidróxidos/química , Piperidonas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cicloexanonas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Simulação de Acoplamento Molecular , Estrutura Molecular , Piperidonas/química , Bases de Schiff/química , Relação Estrutura-Atividade
14.
Org Biomol Chem ; 17(5): 1141-1153, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30638238

RESUMO

The first solution-phase total synthesis of the cyclic depsipeptide teixobactin is described. Stereoselective construction of l-allo-enduracididine was established, and the protective groups for the peptide coupling reactions and conditions for the assembly of the fragments were also optimised. The longest linear sequence for the total synthesis was 20 steps from the known l-cis-4-hydroxyproline derivative and gave a 5.6% overall yield. This solution-phase total synthesis could serve as a complement to the current solid-phase synthesis of teixobactin.

15.
Iran J Basic Med Sci ; 21(10): 1013-1019, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30524674

RESUMO

Objectives: The purpose of this study was to detect the protective effects of adiponectin on coagulation dysfunction and its mechanism in sepsis of rats. Materials and Methods: The experimental samples were composed of sham group, model group that was underwent cecal ligation and puncture (CLP) and three adiponectin treatment groups that treated by adiponectin with different dose (72 µg/kg, 96 µg/kg and 120 µg/kg) after CLP. The prothrombin time (PT), activated partial thromboplastin time (APTT) was measured, respectively, the level of malondialdehyde (MDA), tissue factor (TF), activated coagulation factor VIIa and Xa, p-selectin were detected, the histology structure of vascular was observed, the expressions of Caspase 9, Caspase 3, Bax, Bcl-2 and vWF in vascular were measured. Results: The results demonstrated that adiponectin treatment lengthened PT and APTT, reduced the expression of MDA, TF, activated coagulation factor VIIa, Xa and p-selectin in plasma of septic rats. Additionally, adiponectin treatment alleviated endothelial cell apoptosis and oxidative stress, down-regulated the levels of Caspase 3, Caspase 9, Bax, Bcl-2 and vWF in vascular. Conclusion: These findings suggest that adiponectin treatment might be a promising therapeutic strategy for relieving septic endothelial cell injury and coagulation dysfunction via inhibiting endothelial cell apoptosis in septic rats.

16.
Braz J Med Biol Res ; 51(12): e7747, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30462773

RESUMO

Endoplasmic reticulum (ER) stress is a critical molecular mechanism involved in the pathogenesis of sepsis. Hence, strategies for alleviating this stress may be essential for preventing cardiovascular injuries under sepsis. Adiponectin is secreted by adipocytes and its levels are decreased in sepsis. The purpose of this study was to investigate the protective effects of adiponectin treatment on endothelial cells and its mechanism. Male Wistar rats underwent cecal ligation and puncture (CLP) before being treated with adiponectin (72 and 120 µg/kg). The levels of malondialdehyde (MDA) in plasma, histological structure, and apoptosis of endothelial cells were evaluated. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with adiponectin at 10 and 20 µg/mL for 24 h after stimulation by lipopolysaccharide (LPS). The levels of reactive oxygen species (ROS), ultrastructure, rate of apoptosis, the expression of inositol-requiring enzyme 1α (IRE1α) protein, and its downstream molecules (78 kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and caspase-12) were detected. The results showed that the levels of MDA and ROS induced by CLP or LPS stimulation were increased. Furthermore, endothelial cell apoptosis was increased under sepsis. The IRE1α pathway was initiated, as evidenced by activated IRE1α, increased GRP78, and up-regulated CHOP and caspase-12 in HUVECs. Following treatment with adiponectin, the number of apoptotic endothelial cells was markedly decreased. These findings demonstrated that treatment with adiponectin decreased apoptosis of endothelial cells caused by sepsis by attenuating the ER stress IRE1α pathway activated by oxidative stress.

17.
Onco Targets Ther ; 11: 7827-7840, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464530

RESUMO

Background and aims: HOXD antisense growth-associated long noncoding RNA (HOXD-AS1) was reported to be upregulated in various cancers, such as gastric cancer, hepatocellular carcinoma, colorectal cancer, and glioma. Here, we conducted a meta-analysis and The Cancer Genome Atlas data review to investigate the clinicopathologic and prognostic value of HOXD-AS1 in patients with malignant tumors. Materials and methods: Systematic literatures were searched from PubMed, Medline, Cochrane Library, Web of Science, EMBASE database, Ovid, Chinese CNKI, and the Chinese WanFang database. The role of HOXD-AS1 in cancers was evaluated by pooled ORs and HRs with 95% CIs. The Cancer Genome Atlas dataset was used to explore the prognostic value of HOXD-AS1 in various cancers. Results: Fifteen studies with 1,678 patients were included in this meta-analysis. The results indicated that HOXD-AS1 was associated with tumor size, differentiation, lymph node metastasis, and TNM stage. Moreover, the high HOXD-AS1 expression indicated a poor overall survival (OS) rate and can be an independent predictive factor for OS. The TCGA dataset, which included 9,502 cancer patients, showed that the expression of HOXD-AS1 was related to poor OS and disease-free survival. We also analyzed the prognostic role in different kinds of cancers such as digestive cancers, female reproductive system cancers, respiratory system cancers, and urinary system cancers. Conclusion: This study demonstrated that HOXD-AS1 was closely correlated with tumor size, lymph node metastasis, distant metastasis, and TNM stage, and an increased HOXD-AS1 expression could be a reliable prognostic biomarker in human cancers. However, more studies are needed to confirm this conclusion.

18.
Nutrients ; 10(11)2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30360498

RESUMO

A low carbohydrate diet (LCD), with some staple food being replaced with nuts, has been shown to reduce weight, improve blood glucose, and regulate blood lipid in patients with type 2 diabetes mellitus (T2DM). These nuts include tree nuts and ground nuts. Tree nut consumption is associated with improved cardio-vascular and inflammatory parameters. However, the consumption of tree nuts is difficult to promote in patients with diabetes because of their high cost. As the main ground nut, peanuts contain a large number of beneficial nutrients, are widely planted, and are affordable for most patients. However, whether peanuts and tree nuts in combination with LCD have similar benefits in patients with T2DM remains unknown; although almonds are the most consumed and studied tree nut. This study sought to compare the effect of peanuts and almonds, incorporated into a LCD, on cardio-metabolic and inflammatory measures in patients with T2DM. Of the 32 T2DM patients that were recruited, 17 were randomly allocated to the Peanut group (n = 17) and 15 to the Almond group (n = 15) in a parallel design. The patients consumed a LCD with part of the starchy staple food being replaced with peanuts (Peanut group) or almonds (Almond group). The follow-up duration was three months. The indicators for glycemic control, other cardio-metabolic, and inflammatory parameters were collected and compared between the two groups. Twenty-five patients completed the study. There were no significant differences in the self-reported dietary compliance between the two groups. Compared with the baseline, the fasting blood glucose (FBG) and postprandial 2-h blood glucose (PPG) decreased in both the Peanut and Almond groups (p < 0.05). After the intervention, no statistically significant differences were found between the Peanut group and the Almond group with respect to the FBG and PPG levels. A decrease in the glycated hemoglobin A1c (HbA1c) level from the baseline in the Almond group was found (p < 0.05). However, no significant difference was found between the two groups with respect to the HbA1c level at the third month. The peanut and almond consumption did not increase the body mass index (BMI) and had no effect on the blood lipid profile or interleukin-6 (IL-6).In conclusion, incorporated into a LCD, almonds and peanuts have a similar effect on improving fasting and postprandial blood glucose among patients with T2DM. However, more studies are required to fully establish the effect of almond on the improvement of HbA1c.

19.
Ying Yong Sheng Tai Xue Bao ; 29(10): 3367-3376, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30325162

RESUMO

Construction of ecological network is important for improving urban ecological environment under the scenarios of rapid urbanization. We extracted the core area with good connectivity as the ecological sources with the methods of morphological spatial pattern analysis (MSPA) and landscape index with Guangzhou City as the study area. The ecological network was then constructed by minimal cumulative resistance (MCR) model and was quantitatively analyzed by gravity model and connectivity indices. After that, an optimized ecological network was finally constructed. The results showed that ten core patches could be used as ecological sources. In addition, eighteen important corridors as well as twenty-seven general corridors were identified, which were mainly distributed in the northeast part of the city. Five more ecological sources and thirteen more planning corridors were suggested under the optimized ecological network. Our results indicated that forests were the main composition of ecological corridors. The appropriate width for the important corridor and planning corridor was 60-100 m and 30-60 m, respectively. Our results provide scientific guidance for designing urban ecological network.


Assuntos
Ecossistema , China , Cidades , Planejamento de Cidades , Conservação dos Recursos Naturais , Florestas , Análise Espacial , Urbanização
20.
Acta Crystallogr C Struct Chem ; 74(Pt 10): 1171-1179, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30284984

RESUMO

3,5-Bis(arylidene)-4-piperidone (BAP) derivatives display good antitumour and anti-inflammatory activities because of their double α,ß-unsaturated ketone structural characteristics. If N-benzenesulfonyl substituents are introduced into BAPs, the configuration of the BAPs would change significantly and their anti-inflammatory activities should improve. Four N-benzenesulfonyl BAPs, namely (3E,5E)-1-(4-methylbenzenesulfonyl)-3,5-bis[4-(trifluoromethyl)benzylidene]piperidin-4-one dichloromethane monosolvate, C28H21F6NO3S·CH2Cl2, (4), (3E,5E)-1-(4-fluorobenzenesulfonyl)-3,5-bis[4-(trifluoromethyl)benzylidene]piperidin-4-one, C27H18F7NO3S, (5), (3E,5E)-1-(4-nitrobenzenesulfonyl)-3,5-bis[4-(trifluoromethyl)benzylidene]piperidin-4-one, C27H18F6N2O5S, (6), and (3E,5E)-1-(4-cyanobenzenesulfonyl)-3,5-bis[4-(trifluoromethyl)benzylidene]piperidin-4-one dichloromethane monosolvate, C28H18F6N2O3S·CH2Cl2, (7), were prepared by Claisen-Schmidt condensation and N-sulfonylation. They were characterized by NMR, FT-IR and HRMS (high resolution mass spectrometry). Single-crystal structure analysis reveals that the two 4-(trifluoromethyl)phenyl rings on both sides of the piperidone ring in (4)-(7) adopt an E stereochemistry of the olefinic double bonds. Molecules of both (4) and (6) are connected by hydrogen bonds into one-dimensional chains. In (5) and (7), pairs of adjacent molecules embrace through intermolecular hydrogen bonds to form a bimolecular combination, which are further extended into a two-dimensional sheet. The anti-inflammatory activity data reveal that (4)-(7) significantly inhibit LPS-induced interleukin (IL-6) and tumour necrosis factor (TNF-α) secretion. Most importantly, (6) and (7), with strong electron-withdrawing substituents, display more potential inhibitory effects than (4) and (5).


Assuntos
Anti-Inflamatórios/química , Derivados de Benzeno/química , Piperidonas/química , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Derivados de Benzeno/síntese química , Derivados de Benzeno/farmacologia , Cristalografia por Raios X , Ligações de Hidrogênio , Interleucina-6/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Piperidonas/síntese química , Piperidonas/farmacologia , Células RAW 264.7 , Sulfonas/síntese química , Sulfonas/química , Sulfonas/farmacologia , Fator de Necrose Tumoral alfa/imunologia
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