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1.
Chin Med J (Engl) ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044816

RESUMO

BACKGROUND: Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology. METHODS: A retrospective study of patients' data was conducted using the Emergency Rescue Database of Chinese People's Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost, and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity, and the areas under receiver operator characteristic curves (ROC-AUC). RESULTS: The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the logistic regression were cardiac troponin T (CTnT) (coefficient = 0.346, OR = 1.413), temperature (T) (coefficient = 0.235, OR = 1.265), respiratory rate (RR) (coefficient= -0.206, OR = 0.814), serum kalium (K) (coefficient = 0.137, OR = 1.146), pulse oxygen saturation (SPO2) (coefficient = -0.101, OR = 0.904), and albumin (ALB) (coefficient = -0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heart rate, and systolic blood pressure. CONCLUSIONS: The main clinical indicators of concern included CTnT, RR, SPO2, T, ALB, and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.

2.
Nat Prod Bioprospect ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016770

RESUMO

A series of dearomatized isoprenylated acylphloroglucinols derivatives, hyperhenols A-E (1-5), as well as seven known analogues (6-12), were characterized from Hypericum henryi. Their structures were determined by combination of NMR, ECD spectroscopy, and X-ray diffraction analysis. Compounds 1 and 6-8 were tested to exhibit potential antitumor properties, of which 6 and 7 inhibited cell growth through inducing apoptosis and cell cycle arrest. In addition, these compounds could induce autophagy and PINK1/Parkin-mediated mitophagy in cancer cell lines, as well as suppress lung cancer A549 cells metastasis in vitro.

3.
Chemistry ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957072

RESUMO

We firstly use diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (HEH) as a visible-light photoredox catalyst for cross coupling of arylhalides and arylsulfinates without transition-metal, sacrificial agent and mediator. This method is compatible with various functional groups and provides diaryl sulfones in good to high yields. Mechanistic studies indicate that this reaction undergoes the stepwise light irradiation of HE - , single electron transfer (SET) in donor-acceptor complex (DAC) from * HE - to arylhalide, trapping of aryl radical with sulfinate, SET oxidation of sulfone radical anion by HE • to sulfone via the DAC method.

4.
Acta Pharmacol Sin ; 41(1): 82-92, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31371781

RESUMO

Metastasis causes the main lethality in esophageal cancer patient. Garcinol, a natural compound extracted from Gambogic genera, is a histone acetyltransferase (HAT) inhibitor that has shown anticancer activities such as cell cycle arrest and apoptosis induction. In this study, we investigated the effects of garcinol on the metastasis of esophageal cancer in vitro and in vivo. We found that garcinol (5-15 µM) dose-dependently inhibited the migration and invasion of human esophageal cancer cell lines KYSE150 and KYSE450 in wound healing, transwell migration, and Matrigel invasion assays. Furthermore, garcinol treatment dose-dependently decreased the protein levels of p300/CBP (transcriptional cofactors and HATs) and p-Smad2/3 expression in the nucleus, thus impeding tumor cell proliferation and metastasis. Knockdown of p300 could inhibit cell metastasis, but CBP knockdown did not affect the cell mobility. It has been reported that TGF-ß1 stimulated the phosphorylation of Smad2/3, which directly interact with p300/CBP in the nucleus, and upregulating HAT activity of p300. We showed that garcinol treatment dose-dependently suppressed TGF-ß1-activated Smad and non-Smad pathway, inhibiting esophageal cancer cell metastasis. In a tail vein injection pulmonary metastasis mouse model, intraperitoneal administration of garcinol (20 mg/kg) or 5-FU (20 mg/kg) significantly decreased the number of lung tumor nodules and the expression levels of Ki-67, p300, and p-Smad2/3 in lung tissues. In conclusion, our study demonstrates that garcinol inhibits esophageal cancer metastasis in vitro and in vivo, which might be related to the suppression of p300 and TGF-ß1 signaling pathways, suggesting the therapeutic potential of Garcinol for metastatic tumors.

5.
Restor Neurol Neurosci ; 37(6): 571-581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31796710

RESUMO

Many ocular diseases (such as glaucoma, diabetic retinopathy, age-related macular degeneration, and traumatic eye injuries) can result in the degeneration of retinal cells and the subsequent loss of vision. Some kinds of treatments, such as drugs, stem cell transplantation and surgery are reported to be effective in certain patients. However, no confirmatively effective, convenient and low-price intervention has been available so far. Physical exercise has been reported to exert neuroprotective effects on several neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Studies investigating the potential impacts of exercise on retinal diseases are rapidly emerging. Here we review these up-to-date findings from both human and animal studies, and discuss the possible mechanisms underlying exercise-elicited protection on retina.

6.
Int Rev Neurobiol ; 147: 281-294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31607358

RESUMO

Adiponectin, one kind of adipokines, has been shown to be neuroprotective in different neurodegenerative diseases. Adiponectin exerts its role through combination with its receptors and activates downstream molecular pathways. In the retinas, the expression of adiponectin can be detected and adiponectin receptors (AdipoRs) locate in different retinal cells. Adiponectin is mainly produced by adipose tissue, enters the circulation and passes through blood-brain barrier (BBB) without injury. It can also be produced locally in the brains as well as in the retinas. Therefore, it is possible that adiponectin from blood as well as that produced locally in the retinas take part in defense of different eye diseases. Here we have summarized the published data about the protective effects of adiponectin in eye diseases. Because exercise can increase the production of adiponectin systemically in the whole body and locally in the brain although no evidence has shown that exercise can increase the production of adiponectin in the eyes until now, we hypothesize that exercise will have a potential protective effect for the eyes via increasing the levels of adiponectin which needs further investigation.

7.
Nat Prod Res ; : 1-8, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31512485

RESUMO

One new xanthone, (±) garciesculenxanthone C (1), two new biphenyls, garciesculenbiphenyls A (2) and B (3), together with two known compounds, doitungbiphenyl B (4) and morusignin D (5), were isolated from Garcinia esculenta. The structures of new compounds were elucidated by spectroscopic analysis, and the absolute configuration of (±) garciesculenxanthone C (1) was assigned by a modified Mosher's method. All isolates were evaluated for their antistaphylococcal activities against Staphylococcus aureus Newman, USA300 LAC, USA400 MW2, and Mu50 strains. Among these, (±) garciesculenxanthone C (1) showed the best antistaphylococcal activity, and its effect was determined to be bactericidal by time-kill experiment.

8.
Chem Commun (Camb) ; 55(81): 12235-12238, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31552940

RESUMO

A new calixpyridinium-based light-responsive host-guest recognition motif was found in this work. This host-guest recognition motif was further discovered to be applied as a selective turn-on fluorescent sensor for lysine over other natural amino acids.


Assuntos
Corantes Fluorescentes/química , Lisina/química , Compostos Macrocíclicos/química , Fotólise , Compostos de Piridínio/química , Técnicas Biossensoriais/métodos , Interações Hidrofóbicas e Hidrofílicas , Conformação Molecular , Espectrometria de Fluorescência , Água
9.
Eur J Med Chem ; 181: 111536, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376561

RESUMO

Nine new and unique xanthone derivatives, including one novel hybrid monoterpene-tetrahydroxanthone (1), three dihydro-xanthone derivatives (2-4), and five skeleton-rearranged xanthone derivatives (5-9), were obtained from a 95% EtOH extract of Garcinia oligantha leaves by a LC-MS-guided fractionation procedure. The structures of the new compounds were elucidated by analysis of their 1D and 2D NMR and MS data. The relative configurations of 2 and 8 were determined via X-ray crystallographic data analysis, while the absolute configurations of 1-2, 5-9 were assigned based on a comparison of calculated and experimental ECD and/or OR data. In SRB, PI-exclusion and Hoechst staining assays, 6 showed strong cytotoxic activities which could dose-dependently induce Taxol-insensitive quiescent LNCaP cell death. Additionally, a preliminary mechanism investigation using immunoblotting and Caspase-3 activity assay, indicated that 6 induced quiescent LNCaP cell death potentially through caspase-dependent mitochondrial apoptosis pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inibidores Enzimáticos/farmacologia , Garcinia/química , Folhas de Planta/química , Xantonas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Xantonas/química , Xantonas/isolamento & purificação
10.
J Am Chem Soc ; 141(32): 12804-12814, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31348651

RESUMO

Programming the hierarchical self-assembly of small molecules has been a fundamental topic of great significance in biological systems and artificial supramolecular systems. Precise and highly programmed self-assembly can produce supramolecular architectures with distinct structural features. However, it still remains a challenge how to precisely control the self-assembly pathway in a desirable way by introducing abundant structural information into a limited molecular backbone. Here we disclose a strategy that directs the hierarchical self-assembly of sodium thioctate, a small molecule of biological origin, into a highly ordered supramolecular layered network. By combining the unique dynamic covalent ring-opening-polymerization of sodium thioctate and an evaporation-induced interfacial confinement effect, we precisely direct the dynamic supramolecular self-assembly of this simple small molecule in a scheduled hierarchical pathway, resulting in a layered structure with long-range order at both macroscopic and molecular scales, which is revealed by small-angle and wide-angle X-ray scattering technologies. The resulting supramolecular layers are found to be able to bind water molecules as structural water, which works as an interlayer lubricant to modulate the material properties, such as mechanical performance, self-healing capability, and actuating function. Analogous to many reversibly self-assembled biological systems, the highly dynamic polymeric network can be degraded into monomers and reformed by a water-mediated route, exhibiting full recyclability in a facile, mild, and environmentally friendly way. This approach for assembling commercial small molecules into structurally complex materials paves the way for low-cost functional supramolecular materials based on synthetically simple procedures.

11.
Pharmacol Res ; 147: 104328, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288080

RESUMO

A global transcriptional regulator, MgrA, was previously identified as a key determinant of virulence in Staphylococcus aureus. An 80% EtOH extract of Uncaria gambier was found to attenuate the virulence of S. aureus via its effects on MgrA. Using bioassay-guided fractionation, a polyphenolic polymer, uncariitannin, was found to be the main bioactive constituent of the extract, and its structure was characterized using spectral and chemical analysis. The molecular weight and polydispersity of uncariitannin were determined by gel permeation chromatography-refractive index-light scattering analysis. An electrophoretic mobility shift assay showed that uncariitannin could effectively inhibit the interaction of MgrA with DNA in a dose-dependent manner. Treatment with uncariitannin could decrease the mRNA and protein levels of Hla in both the S. aureus Newman and USA300 LAC strains. Further analysis of Hla expression levels in the Newman ΔmgrA and Newman ΔmgrA/pYJ335-mgrA strains indicated that uncariitannin altered Hla expression primarily in an MgrA-dependent manner. A mouse model of infection indicated that uncariitannin could attenuate MRSA virulence. In conclusion, uncariitannin may be a potential candidate for further development as an antivirulence agent for the treatment of S. aureus infection.

12.
Exp Ther Med ; 18(1): 366-372, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31258674

RESUMO

The present study evaluated the effectiveness and safety of the removal of unilateral staghorn renal stones with concurrent infections by retroperitoneal laparoscopic pyelolithotomy (RLP) with prolonged renal posterior lower segment incision. Patients with staghorn renal stone and concurrent urinary tract infection (UTI) who underwent RLP with prolonged renal posterior lower segment incision as the primary, one-session treatment at our institution between March 2014 and December 2017 were retrospectively reviewed. Routine laboratory tests were performed and the patients received broad-spectrum intravenous antibiotics from at least 3 days prior to the operation. All patients were examined pre-operatively by urinary ultrasonography, computed tomography or intravenous urography. UTI was confirmed by laboratory tests with or without radiographic evidence by an experienced urologist. All patients (18 females and 10 males) successfully underwent the procedures and there was no conversion to open surgery in any case. The mean age was 57.0±10.81 years (age range, 40-74 years) and the mean calculus size was 3.3±0.79 cm. The mean operation time, warm ischemia time and post-operative hospital stay were 114.4±12.09 min, 28.1±4.23 min and 5.8±1.42 days, respectively. The mean hemoglobin drop on day 3 following surgery was 0.5±0.38 g/dl and there was no requirement for blood transfusion in any patient. The mean change of serum creatinine levels between pre-operative baseline and post-operative day 3 or post-operative month 6 was 6.0±20.03 or -4.5±15.13 µmol/l, respectively. The stone-free rate was 100% at 3 days and at 6 months. Mild post-operative complications (Grade I or II) occurred in 6 patients, including temporary and constant elevated body temperature (>38.5°C). No severe complications, including urine leakage, sepsis, residual stones requiring auxiliary procedures, were noted and there were no circumstances requiring further surgical intervention in any of the patients. In conclusion, RLP with prolonged renal posterior lower segment incision is an effective and safe procedure for patients with staghorn renal stones and concurrent UTI, and its feasible application as a single-session monotherapy is particularly convenient considering the financial and medical situation, as well as the patients' preference.

13.
Opt Express ; 27(8): 11510-11515, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31052994

RESUMO

In this paper, we proposed and numerically demonstrated a novel method to effectively minimize Fresnel reflection from a perpendicularly cleaved fiber using a uniform fiber Bragg grating (FBG) inscribed at the fiber end. By matching the reflectivity of an in-line FBG with the reflectivity caused by the glass-air boundary, the FBG acts as a virtual boundary, which provides destructive interference and suppresses Fresnel reflection. We achieved an anti-reflection FBG with a return loss of more than 80 dB by ensuring that the product of the index contrast and grating period number is almost constant, with a value of 0.2695.

14.
Phytomedicine ; 58: 152874, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30889421

RESUMO

BACKGROUND: The fruits of Psoralea corylifolia L. (Fructus Psoraleae, FP) has a long history and a wide range of applications in the treatment of osteoporosis and leukoderma. Although it is well known that FP could cause hepatotoxicity and reproductive toxicity, less is known about its potential toxicity on multiple organs. PURPOSE: This study aims to determine the multiorgan toxicity of EtOH extract of FP (EEFP) and to investigate the underlying mechanisms through a systematic evaluation in Wistar rats. STUDY DESIGN AND METHODS: Wistar rats were orally administered with the EEFP at doses of 1.5, 1.0 and 0.5 g/kg for 28 days. Histopathologic and clinicopathologic analyses were performed, and the hormone levels in serum and the mRNA levels of enzymes related to the production of steroid hormones in adrenal glands were detected. The area of each band of adrenal glands and the steroid levels in the adrenal glands were also measured. RESULTS: After the treatment, both the histopathologic and clinicopathologic examination showed that EEFP caused liver, prostate, seminal vesicle and adrenal gland damage. Among the enzymes involved in the regulation of adrenal steroid hormone production, NET, VMAT2, and CYP11B1 were upregulated, while CYP17A1 was downregulated. Among the adrenal steroid hormones, COR and NE were upregulated, while levels of DHT and serum ACRH and CRH decreased. CONCLUSION: Our results indicated that adrenal gland, prostate, and seminal vesicles could also be the target organs of FP-induced toxicity. Abnormal enzyme and hormone production related to the hypothalamic pituitary adrenal (HPA) axis caused by the EEFP may be the potential toxic mechanism for changes in the adrenal gland and secondary sex organs of male rats.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Enzimas/metabolismo , Extratos Vegetais/toxicidade , Esteroides/metabolismo , Administração Oral , Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/patologia , Animais , Enzimas/genética , Etanol/química , Feminino , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos Wistar , Testes de Toxicidade/métodos
15.
Chem Commun (Camb) ; 55(24): 3532-3535, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30840002

RESUMO

Solvothermal reaction of Zn(NO3)2 with 2,9-bis-(2-pyridine-3-yl-vinyl)-[1,10]phenanthroline (3-bpep) and furan-2,5-dicarboxylic acid (2,5-H2FDC) afforded a one-dimensional (1D) coordination polymer {[Zn2(3-bpep)2(2,5-FDC)2]·1.5H2O}n (1), which undergoes regioselective photocycloaddition to yield another 1D coordination polymer {[Zn2(3-bpep)(trans,rctt-3-bpbpycb)0.5(2,5-FDC)2]·H2O}n (2) in a single-crystal-to-single-crystal manner under UV light irradiation. The reverse process from 2 to 1 can be achieved by heating 2 at 240 °C. Such a photocycloaddition/thermocycloreversion cycle results in an interesting reversible dielectric switching.

16.
Dalton Trans ; 48(15): 5072-5082, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30920560

RESUMO

Seven new chelated cyclometalated Ir complexes of ABON,P, ABON,O, and ABON,C(carbene) based on a rigid and tunable 2-arylbenzo[d]oxazole backbone have been prepared for the N-methylation of amines. Among these three coordinated modes, ABON,C(carbene)-chelated iridium-based catalysts exhibited good performance in the monomethylation of aromatic amines with methanol (MeOH) as the green methylation reagent. The steric-modified synthesis of ABON,C(carbene) complexes was described. The most active ABON,C(carbene) complex with marginal steric hindrance as a catalyst was obtained from the benzoxazole ring without a substituent and methyl group of the benzimidazole ring on the N-heterocyclic carbene (NHC) ligand. A variety of amines including para- and meta-substituted aromatic amines, as well as heterocyclic amines, were formulated as suitable substrates. Importantly, this catalyst considerably promoted the yield of the N-methylation of ortho-substituted aromatic amines. Controlled kinetic experiments and deuterium-labeling reactions of these ortho-substituted amines were conducted under optimized conditions. On the basis of the experimental results, a plausible mechanism was proposed.

17.
Org Biomol Chem ; 17(14): 3567-3574, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30899931

RESUMO

The challenge in the C-C cross-coupling of secondary and primary alcohols using acceptorless dehydrogenation coupling (ADC) is the difficulty in accurately controlling product selectivities. Herein, we report a controlled approach to a diverse range of ß-alkylated secondary alcohols, α-alkylated ketones and α,ß-unsaturated ketones using the ADC methodology employing a Ni(ii) 4,6-dimethylpyrimidine-2-thiolate cluster catalyst under different reaction conditions. This catalyst could tolerate a wide range of substrates and exhibited a high activity for the annulation reaction of secondary alcohols with 2-aminobenzyl alcohols to yield quinolines. This work is an example of precise chemoselectivity control by careful choice of reaction conditions.

18.
Cell Transplant ; 28(5): 607-618, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30838886

RESUMO

The rat partial optic nerve transection (PONT) model has been used for studying secondary degeneration of retinal ganglion cells (RGCs) in recent years. In this study, we carried out PONT of the temporal side of rat optic nerves, whereas PONT was carried out of the superior side in the previous publication. We found that this surgery is better and easier than the previous method and can produce a repeatable and reliable model. We detected significant changes in the polarization of microglia/macrophages and the level of autophagy in optic nerves after PONT. We also used this model to detect the effects of the polysaccharides extracted from Lycium barbarum (LBP) on the survival of RGCs and the changes in the polarization of microglia/macrophages and the level of autophagy after PONT. We find that LBP can delay secondary degeneration of RGCs after temporal injury of optic nerves, promote the M2 polarization of microglia/macrophages, and down-regulate the level of autophagy after PONT. In conclusion, we find that the polarization of microglia/macrophages and the autophagy level change after PONT; LBP treatment delays secondary degeneration of RGCs; and the polarization of microglia/macrophages and the level of autophagy are also altered after LBP treatment.

19.
Int J Oncol ; 54(5): 1676-1690, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30816490

RESUMO

The aim of the present study was to investigate the effects of lysyl oxidase­like 2 (LOXL2) on the invasion, migration and epithelial­to­mesenchymal transition (EMT) of renal cell carcinoma (RCC) cells through the steroid receptor coactivator (Src)/focal adhesion kinase (FAK) signaling pathway. RCC tissues and adjacent normal tissues were collected from 80 patients with RCC. Immunohistochemistry was used to determine the positive expression rate of the LOXL2 protein. The expression levels of LOXL2 in the HK­2, 786­O, ACHN, Caki1 and A498 cell lines were detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The high LOXL2­expressing 786­O cells were selected for gene silencing experiments, whereas Caki1 cells, which exhibited low LOXL2 expression, were used for overexpression experiments. RT­qPCR and western blot analysis were applied to determine the expression of LOXL2, FAK, Src, matrix metalloproteinase (MMP)­9, epithelial (E)­cadherin, neuronal (N)­cadherin and vimentin. A MTT assay, a Transwell assay, a wound healing assay and flow cytometry were performed to detect cell proliferation, invasion, migration, cell cycle distribution and apoptosis, respectively. The protein expression rate of LOXL2 in RCC tissues was higher compared with that in adjacent normal tissues. Compared with adjacent normal tissues, the mRNA and protein expression levels of LOXL2, FAK, Src, MMP­9, N­cadherin and vimentin and the levels of FAK and Src phosphorylation were increased, while the mRNA and protein expression levels of E­cadherin were decreased in RCC tissues. Following the transfection of 786­O cells with small interfering (si) RNA against LOXL2, the mRNA and protein expression levels of FAK, Src, MMP­9, N­cadherin and vimentin and the levels of phosphorylated FAK and Src were notably decreased in the si­LOXL2 and PP2 inhibitor treated groups, while that of E­cadherin was substantially increased. Additionally, cell proliferation, invasion, migration and the percentage of RCC cells in the G1 phase were reduced, and cell apoptosis was increased. Additionally, Caki1 cells transfected with LOXL2 exhibited an opposite trend. In summary, these results indicate that LOXL2 silencing inhibits the invasion, migration and EMT in RCC cells through inhibition of the Src/FAK signaling pathway.


Assuntos
Aminoácido Oxirredutases/genética , Aminoácido Oxirredutases/metabolismo , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Transdução de Sinais , Adolescente , Adulto , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Feminino , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Regulação para Cima , Adulto Jovem , Quinases da Família src/metabolismo
20.
Org Lett ; 21(5): 1534-1537, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30775925

RESUMO

Garsubelone A (1), the first dimeric polycyclic polyprenylated acylphloroglucinols type metabolite featuring a complicated 6/6/6/6/6/6/6 heptacyclic architecture containing 10 stereogenic centers, was isolated from Garcinia subelliptica. Biogenetically, this compound was constructed by the plausible monomeric precursor, garsubelone B (2) and secohyperforin, via a key Diels-Alder cycloaddition to form an unique 2-oxabicyclo[3.3.1]nonane core. Their structures and absolute configurations were determined by comprehensive spectroscopic and X-ray diffraction techniques. The cytotoxic activities of these isolates were also evaluated.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/metabolismo , Garcinia/química , Floroglucinol/análogos & derivados , Compostos Policíclicos/química , Compostos Policíclicos/metabolismo , Terpenos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Floroglucinol/química , Compostos Policíclicos/isolamento & purificação , Difração de Raios X
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