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1.
Article in Chinese | WPRIM | ID: wpr-879932

ABSTRACT

OBJECTIVE@#To investigate the regulatory effect of iridoid glycoside of radix scrophulariae (IGRS) on endoplasmic reticulum stress induced by oxygen-glucose deprivation and reperfusion @*METHODS@#Rat pheochromocytoma PC12 cells were pretreated with IGRS (50, 100, 200 μg/mL) for 24h, and the @*RESULTS@#The damage caused by OGD/R to PC12 cells was significantly reduced by IGRS, with significant effect on increasing survival rate and reducing LDH release (all @*CONCLUSIONS@#IGRS has neuroprotective effect, which may alleviate cerebral ischemia-reperfusion injury by regulating SERCA2, maintaining calcium balance, and inhibiting endoplasmic reticulum stress-mediated apoptosis.


Subject(s)
Animals , Cell Survival/drug effects , Down-Regulation/drug effects , Endoplasmic Reticulum Stress/drug effects , Glucose , In Vitro Techniques , Iridoid Glycosides/pharmacology , Oxygen , PC12 Cells , Rats , Reperfusion , Reperfusion Injury/prevention & control , Snails/chemistry
2.
Braz. j. med. biol. res ; 52(12): e8934, 2019. graf
Article in English | LILACS | ID: biblio-1055468

ABSTRACT

Baicalein (BAI) is an acknowledged flavonoids compound, which is regarded as a useful therapeutic pharmaceutical for numerous cancers. However, its involvement in melanoma is largely unknown. This study aimed to examine the anti-melanoma function of BAI and unraveled the regulatory mechanism involved. A375 and SK-MEL-28 were treated with BAI for 24 h. Then, CCK-8 assay, flow cytometry, and transwell assay were carried out to investigate cell growth, migration, and invasion. RT-qPCR was applied to detect the expression of colon cancer associated transcript-1 (CCAT1) in melanoma tissues and cells. The functions of CCAT1 in melanoma cells were also evaluated. Western blot was utilized to appraise Wnt/β-catenin or MEK/ERK pathways. BAI restrained cell proliferation and stimulated cell apoptotic capability of melanoma by suppressing cleaved-caspase-3 and cleaved-PARP. Cell migratory and invasive abilities were restrained by BAI via inhibiting MMP-2 and vimentin. CCAT1 was over-expressed in melanoma tissues and down-regulated by BAI in melanoma cells. Overexpressed CCAT1 reversed the BAI-induced anti-growth, anti-migratory, and anti-invasive effects. Furthermore, BAI inhibited Wnt/β-catenin and MEK/ERK pathways-axis via regulating CCAT1. Our study indicated that BAI blocked Wnt/β-catenin and MEK/ERK pathways via regulating CCAT1, thereby inhibiting melanoma cell proliferation, migration, and invasion.


Subject(s)
Humans , Gene Expression Regulation, Neoplastic/drug effects , Flavanones/pharmacology , RNA, Long Noncoding/metabolism , Melanoma/pathology , Down-Regulation/drug effects , Cell Movement/drug effects , Blotting, Western , Reverse Transcriptase Polymerase Chain Reaction , Cell Line, Tumor , Cell Proliferation/drug effects , Real-Time Polymerase Chain Reaction , Neoplasm Invasiveness
3.
Braz. j. med. biol. res ; 52(10): e8385, 2019. graf
Article in English | LILACS | ID: biblio-1039242

ABSTRACT

Malignant melanoma (MM) is one of the malignant tumors with highly metastatic and aggressive biological actions. Schizandrin A (SchA) is a bioactive lignin compound with strong anti-oxidant and anti-aging properties, which is stable at room temperature and is often stored in a cool dry place. Hence, we investigated the effects of SchA on MM cell line A375 and its underlying mechanism. A375 cells were used to construct an in vitro MM cell model. Cell viability, proliferation, apoptosis, and migration were detected by Cell Counting Kit-8, BrdU assay, flow cytometry, and transwell two-chamber assay, respectively. The cell cycle-related protein cyclin D1 and cell apoptotic proteins (Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9) were analyzed by western blot. Alteration of H19 expression was achieved by transfecting with pEX-H19. PI3K/AKT pathway was measured by detecting phosphorylation of PI3K and AKT. SchA significantly decreased cell viability in a dose-dependent manner. Furthermore, SchA inhibited cell proliferation and cyclin D1 expression. SchA increased cell apoptosis along with the up-regulation of pro-apoptotic proteins (cleaved-caspase-3, cleaved-caspase-9, and Bax) and the down-regulation of anti-apoptotic protein (Bcl-2). Besides, SchA decreased migration and down-regulated matrix metalloproteinases (MMP)-2 and MMP-9. SchA down-regulated lncRNA H19. Overexpression of H19 blockaded the inhibitory effects of SchA on A375 cells. SchA decreased the phosphorylation of PI3K and AKT while H19 overexpression promoted the phosphorylation of PI3K and AKT. SchA inhibited A375 cell growth, migration, and the PI3K/AKT pathway through down-regulating H19.


Subject(s)
Humans , Polycyclic Compounds/pharmacology , Down-Regulation/drug effects , Cell Movement/drug effects , Apoptosis/drug effects , Lignans/pharmacology , Cyclooctanes/pharmacology , Cell Proliferation/drug effects , Melanoma/pathology , Signal Transduction/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Blotting, Western , MicroRNAs/metabolism , Cell Line, Tumor , Real-Time Polymerase Chain Reaction , RNA, Long Noncoding
4.
Acta cir. bras ; 33(12): 1061-1066, Dec. 2018. tab
Article in English | LILACS | ID: biblio-973491

ABSTRACT

Abstract Purpose: To investigate the role of atenolol in the gene expression of caspase 1 (Casp1) and Bcl2L1 on vascular endothelium of rat intestine after ischemia and reperfusion (IR). Methods: Eighteen adult male Wistar rats were randomly divided into 3 groups (n=6): SG (Sham group): no clamping of the superior mesenteric artery; IRG: IR plus saline group: IRG+At: IR plus Atenolol group. Rats from IRG and IRG+At were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. Atenolol (2mg/kg) or saline were injected in the femoral vein 5 min before ischemia, 5 min and 55 min after reperfusion. Thereafter, intestinal segments were appropriately removed and processed for Endothelial Cell Biology Rat RT2 Profiler PCR Array. Results: the anti-apoptotic Bcl2L1 gene expression was significantly down-regulated (-1.10) in the IRG and significantly up-regulated in the IRG+At (+14.15). Meanwhile, despite Casp1 gene expression was upregulated in both groups, it was significantly higher in the IRG (+35.06) than the IRG+At (+6.68). Conclusions: Atenolol presents antiapoptotic effects on rat intestine subjected to IR partly by the up-regulation of the anti-apoptotic Bcl2L1 gene expression. Moreover, atenolol can mitigate the pro-apoptotic and pro-inflammatory effects of Casp1 gene on rat intestine after IR.


Subject(s)
Animals , Male , Atenolol/pharmacology , Reperfusion Injury/prevention & control , Gene Expression/drug effects , Protective Agents/pharmacology , Caspase 1/drug effects , bcl-X Protein/drug effects , Intestine, Small/blood supply , Time Factors , Endothelium, Vascular , Random Allocation , Down-Regulation/drug effects , Up-Regulation/drug effects , Polymerase Chain Reaction , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Mesenteric Artery, Superior , Apoptosis/drug effects , Constriction , Cytoprotection/drug effects , Caspase 1/genetics , bcl-X Protein/genetics , Mesenteric Ischemia/prevention & control
5.
Acta cir. bras ; 33(7): 556-564, July 2018. tab, graf
Article in English | LILACS | ID: biblio-949368

ABSTRACT

Abstract Purpose: To investigate the effects of baicalin on inflammatory reaction, oxidative stress and protein kinase D1 (PKD1) and nuclear factor-kappa B (NF-κB) protein expressions in severe acute pancreatitis (SAP) rats. Methods: Sixty rats were divided into sham operation, model, and low-, medium- and high-dose baicalin group. SAP model was established in later 4 groups. The later 3 groups were injected with 0.1, 0.2 and 0.4 ml/100 g 5% baicalin injection, respectively. At 12 h, the serum SAP related indexes and inflammatory factors, peripheral blood CD3 and γδT cell percentages, wet/dry ratio and pancreas ascites volume, oxidative stress indexes and PKD1 and NF-κB protein expressions in pancreatic tissue were determined. Results: Compared with model group, in high-dose baicalin group the wet/dry ratio and ascites volume, serum amylase level, phospholipase A2 activity, TNF-α, IL-1 and IL-6 levels, and pancreatic malondialdehyde level and PKD1 and NF-κB protein expression were significantly decreased (P < 0.05), and peripheral blood CD3 and γδT cell percentages and pancreatic superoxide dismutase and glutathione peroxidase levels were significantly increased (P < 0.05). Conclusion: Baicalin can resist the inflammatory reaction and oxidative stress, and down-regulate protein kinase D1 and nuclear factor-kappa B protein expressions, thus exerting the protective effects on severe acute pancreatitis in rats.


Subject(s)
Animals , Pancreatitis/drug therapy , Flavonoids/pharmacology , Protein Kinase C/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , NF-kappa B/metabolism , Oxidative Stress/drug effects , Pancreatitis/metabolism , Superoxide Dismutase/drug effects , Protein Kinase C/drug effects , Random Allocation , Down-Regulation/drug effects , Reproducibility of Results , NF-kappa B/drug effects , Interleukin-6/blood , Interleukin-1/blood , Tumor Necrosis Factor-alpha/blood , Treatment Outcome , Rats, Sprague-Dawley , CD3 Complex/drug effects , CD3 Complex/blood , Glutathione Peroxidase/drug effects , Glutathione Peroxidase/metabolism , Amylases/drug effects , Amylases/blood , Malondialdehyde/metabolism
6.
Acta cir. bras ; 33(6): 491-498, June 2018. graf
Article in English | LILACS | ID: biblio-949359

ABSTRACT

Abstract Purpose: To investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Methods: The mouse model of vincristine-induced peripheral neuropathy and interleukin (IL)-4 knockout mice were utilized to investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Vincristine induced increased sensitivity to mechanical stimulation was measured by von Frey hair test 7 and 14 days after intraperitoneal administration of 0.1 mg/kg vincristine in mice. Relative expression levels of cytokines were detected by quantitative real-time PCR. STAT6 expression following vincristine treatment was assessed with western blotting. Results: We discovered that IL-4/STAT6 signaling was down-regulated in vincristine-treated mice. Deletion of IL-4 in mice increased the sensitivity to mechanical allodynia. IL-4 knockout mice also produced more pro-inflammatory cytokines, including IL-1β and TNF-α. Notably, co-administration of exogenous recombination IL-4 significantly prevented vincristine-induced mechanical allodynia. Conclusion: Anti-inflammatory cytokine IL-4 protects rodent model from vincristine-induced peripheral neuropathy via the stimulation of IL-4/STAT6 signaling and inhibition of the pro-inflammatory cytokines.


Subject(s)
Animals , Male , Vincristine/adverse effects , Interleukin-4/pharmacology , Peripheral Nervous System Diseases/prevention & control , STAT6 Transcription Factor/drug effects , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/adverse effects , Time Factors , Down-Regulation/drug effects , Blotting, Western , Reproducibility of Results , Cytokines/analysis , Cytokines/drug effects , Treatment Outcome , Mice, Knockout , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/metabolism , Neuroprotective Agents , Disease Models, Animal , STAT6 Transcription Factor/analysis , Real-Time Polymerase Chain Reaction , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Mice, Inbred C57BL
7.
Biol. Res ; 51: 14, 2018. graf
Article in English | LILACS | ID: biblio-950900

ABSTRACT

BACKGROUND: Neurokinin1 (NK1) receptor has played a vital role in the development of tumor. However, NKP608 as a NK1 receptor antagonist whether has the effect of the resistance of colorectal cancer is still unclear. Thereby, in this study, we investigated the role of NKP608 on human colorectal cancer and explored the underlying mechanism. METHODS: The cell proliferation of colorectal cancer cells was detected by cell counting kit-8 (CCK8) assay, cell migration and invasion were assessed by transwell assay, the apoptotic ratio of cells was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide stained and flow cytometry. The involvement of molecular mechanisms was examined by western blot. RESULTS: In this study, we found that NKP608 inhibited the proliferation, migration/invasion of HCT116 cells. In addition, NKP608 reduced expressions of Wnt-3a, ß-catenin, Cyclin D1, and (vascular endothelial growth factor) VEGF while induced expression of E-Cadherin. Furthermore, flow cytometry analyzed that NKP608 induced apoptosis of HCT116 cells, consistently, western blotting detecting of apoptosis-related proteins revealed that NKP608 downregulated Bcl-2 while upregulated Bax and Active-Caspase-3. CONCLUSIONS: Taken together, our results demonstrated that NKP608 inhibited colorectal cancer cell proliferation, migration and invasion via suppressing the Wnt/ß-catenin signaling pathway. Therefore, NKP608 might represent a promising therapeutic agent in the treatment of colorectal cancer.


Subject(s)
Humans , Piperidines/pharmacology , Quinolines/pharmacology , Colorectal Neoplasms/pathology , Cell Movement/drug effects , Cell Proliferation/drug effects , Wnt Signaling Pathway/drug effects , Neurokinin-1 Receptor Antagonists/pharmacology , Down-Regulation/drug effects , Blotting, Western , Cell Line, Tumor , HCT116 Cells , Flow Cytometry
8.
Biol. Res ; 51: 11, 2018. graf
Article in English | LILACS | ID: biblio-950897

ABSTRACT

BACKGROUND: Gastric cancer occupies the fourth highest morbidity rate of cancers worldwide. Clinical therapies of gastric cancer remain limited because of uncertainty of mechanisms and shortness of effective medicine. Thus, new drug candidates for gastric cancer treatment is urgently needed. RESULTS: In this study, CMPD1 as a wildly used MK2 phosphorylation inhibitor was employed to find its impact on gastric cancer cell proliferation, apoptosis and cell cycle using colony formation assay and flow cytometry analysis. Along with its anti-proliferation effect on gastric cancer cell line MKN-45 and SGC7901, CMPD1 also induced massive apoptosis and significant G2/M phase arrest in a time-dependent and dose-dependent manner in MKN-45 cells respectively. Furthermore, Western blot confirmed that the expression of anti-apoptotic proteins Bcl-2 was decreased while BAX, cytochrome c release and cleaved PARP were increased. In addition, oncogene c-Myc was downregulated in response to CMPD1 treatment. CONCLUSIONS: Our results demonstrated that CMPD1 has anti-tumor effect on human gastric cancer cell line MKN- 45 possibly via downregulating oncogene c-Myc expression and CMPD1 could be applied as a potential candidate for treating gastric malignancy. To the best of our knowledge, it is the first report of anti-tumor effect of CMPD-1 on human gastric cancer cells.


Subject(s)
Humans , Stomach Neoplasms/drug therapy , Protein-Serine-Threonine Kinases/pharmacology , Apoptosis/drug effects , Intracellular Signaling Peptides and Proteins/pharmacology , Cell Proliferation/drug effects , SOX9 Transcription Factor/pharmacology , G2 Phase Cell Cycle Checkpoints/drug effects , Antineoplastic Agents/pharmacology , Stomach Neoplasms/pathology , Down-Regulation/drug effects , Up-Regulation/drug effects , Blotting, Western , Reproducibility of Results , Cytochromes/drug effects , Cell Line, Tumor , Apoptosis Regulatory Proteins/pharmacology , Flow Cytometry/methods
9.
Yonsei Medical Journal ; : 43-50, 2018.
Article in English | WPRIM | ID: wpr-742506

ABSTRACT

PURPOSE: Tripartite-motif-containing protein 56 (TRIM56) has been found to exhibit a broad antiviral activity, depending upon E3 ligase activity. Here, we attempted to evaluate the function of TRIM56 in multiple myeloma (MM) and its underlying molecular basis. MATERIALS AND METHODS: TRIM56 expression at the mRNA and protein level was measured by qRT PCR and western blot analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry analysis was performed to investigate the effect of TRIM56 on MM cell proliferation and apoptosis. The concentrations of interferon (IFN)-β, interleukin (IL)-6, and tumor necrosis factor-α in MM cell culture supernatants were detected with respective commercial ELISA kits. Western blot was employed to determine the effect of TRIM56 on toll-like receptor 3 (TLR3)/toll-IL-1 receptor (TIR) domain-containing adaptor inducing IFN-β (TRIF) signaling pathway. RESULTS: TRIM56 expression was prominently decreased in MM cells. Poly (dA:dT)-induced TRIM56 overexpression in U266 cells suppressed proliferation, induced apoptosis, and enhanced inflammatory cytokine production, while TRIM56 knockdown improved growth, diminished apoptosis, and inhibited inflammatory cytokine secretion in RPMI8226 cells. Moreover, TRIM56 knockdown blocked TLR3 signaling pathway. Furthermore, poly (I:C), a TLR3 agonist, markedly abolished TRIM56 depletion-induced increase of proliferation, decrease of apoptosis, and reduction of inflammatory factor in MM cells. CONCLUSION: TRIM56 may act as a tumor suppressor in MM through activation of TLR3/TRIF signaling pathway, contributing to a better understanding of the molecular mechanism of TRIM56 involvement in MM pathogenesis and providing a promising therapy strategy for patients with MM.


Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cytokines/metabolism , Disease Progression , Down-Regulation/drug effects , Gene Knockdown Techniques , Humans , Multiple Myeloma/metabolism , Multiple Myeloma/pathology , Poly I-C/pharmacology , Signal Transduction/drug effects , Toll-Like Receptor 3/metabolism , Tripartite Motif Proteins/deficiency , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/deficiency , Ubiquitin-Protein Ligases/metabolism
10.
Braz. j. infect. dis ; 21(4): 386-390, July-Aug. 2017. graf
Article in English | LILACS | ID: biblio-888886

ABSTRACT

Abstract Mycobacterium tuberculosis (MTB) adopts a special survival strategy to overcome the killing mechanism(s) of host immune system. Amongst the many known factors, small heat shock protein 16.3 (sHSP16.3) of MTB encoded by gene hspX has been reported to be critical for the survival of MTB. In the present study, the effect of recombinant murine interferon-gamma (rmIFN-γ) and recombinant murine interleukin-10 (rmIL-10) on the expression of gene hspX of MTB in murine macrophage RAW264.7 has been investigated. By real-time RT-PCR, it was observed that three increasing concentrations (5, 25 and 50 ng/ml) of rmIFN-γ significantly up-regulated the expression of hspX whereas similar concentrations of rmIL-10 (5, 25 and 50 ng/ml) significantly down-regulated the hspX expression. This effect was not only dependent on the concentration of the stimulus but this was time-dependent as well. A contrasting pattern of hspX expression was observed against combinations of two different concentrations of rmIFN-γ and rmIL-10. The study results suggest that rIL-10 mediated down-regulation of hspX expression, in the presence of low concentration of rIFN-γ, could be used as an important strategy to decrease the dormancy of MTB in its host and thus making MTB susceptible to the standard anti-mycobacterial therapy used for treating tuberculosis. However, as these are only preliminary results in the murine cell line model, this hypothesis needs to be first validated in human cell lines and subsequently in animal models mimicking the latent infection using clinical isolates of MTB before considering the development of modified regimens for humans.


Subject(s)
Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial/physiology , Interferon-gamma/pharmacology , Interleukin-10/pharmacology , Macrophages/microbiology , Mycobacterium tuberculosis/genetics , Antigens, Bacterial/metabolism , Time Factors , Bacterial Proteins/genetics , Recombinant Proteins/pharmacology , Down-Regulation/drug effects , Dose-Response Relationship, Drug , Antigens, Bacterial/genetics
11.
Braz. j. med. biol. res ; 50(7): e5974, 2017. graf
Article in English | LILACS | ID: biblio-951702

ABSTRACT

microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 μg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 μg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.


Subject(s)
Humans , Bleomycin/pharmacology , Down-Regulation/drug effects , Apoptosis/drug effects , MicroRNAs/metabolism , Cyclooxygenase 2/metabolism , Lung/cytology , Transfection , Cell Line , Lung/drug effects , Lung/metabolism
12.
Braz. j. med. biol. res ; 50(2): e5801, 2017. graf
Article in English | LILACS | ID: biblio-839250

ABSTRACT

We determined the effect of N-acetylcysteine (NAC) on the expression of the phosphorylated p38 (p-p38) protein and superoxide anion generation (SAG), two important players in the processing of neuropathic pain, in the lumbosacral spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain. The sciatic functional index (SFI) was also measured to assess the functional recovery post-nerve lesion. Thirty-six male Wistar rats were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received 2, 4, or 8 intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline beginning 4 h after CCI. Rats were sacrificed 1, 3, and 7 days after CCI. The SFI was measured on these days and the lumbosacral spinal cord was used for analysis of p-p38 expression and SAG. CCI induced a decrease in SFI as well as an increase in p-p38 expression and SAG in the spinal cord. The SFI showed a partial recovery at day 7 in saline-treated CCI rats, but recovery was improved in NAC-treated CCI rats. NAC induced a downregulation in p-p38 expression at all time-points evaluated, but did not reverse the increased SAG induced by CCI. Since p-p38 is a mediator in neuropathic pain and/or nerve regeneration, modulation of this protein may play a role in NAC-induced effects in CCI rats.


Subject(s)
Animals , Male , Rats , Acetylcysteine/therapeutic use , Neuralgia/drug therapy , p38 Mitogen-Activated Protein Kinases/drug effects , Spinal Cord/drug effects , Superoxides/metabolism , Blotting, Western , Constriction, Pathologic , Disease Models, Animal , Down-Regulation/drug effects , Neuralgia/etiology , p38 Mitogen-Activated Protein Kinases/metabolism , Pain Threshold , Phosphorylation/drug effects , Rats, Wistar , Spinal Cord/metabolism
13.
Rev. bras. anestesiol ; 66(1): 29-36, Jan.-Feb. 2016. graf
Article in Portuguese | LILACS | ID: lil-773481

ABSTRACT

BACKGROUND: Intra-articular injections of local anesthetics are commonly used to enhance post-operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra-articular local anesthetic have raised concerns. OBJECTIVES: The study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics - ropivacaine, bupivacaine and lidocaine - on human chondrocytes. METHODS: The chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500 µM was determined by LIVE/DEAD assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species. RESULTS: On exposure to the local anesthetics, chondrotoxicity was found in the order ropivacaine < bupivacaine < lidocaine. Vitamin C effectively improved the reduced chondrocyte viability and decreased the raised apoptosis levels following exposure to anesthesia. At higher doses, vitamin C was found efficient in reducing the generation of reactive oxygen species and as well down-regulate the expressions of caspases 3 and 9. CONCLUSIONS: Vitamin C was observed to effectively protect chondrocytes against the toxic insult of local anesthetics ropivacaine, bupivacaine and lidocaine.


JUSTIFICATIVA: Injeções de anestésicos locais por via intra-articular são comumente usadas para melhorar a analgesia no período pós-operatório de cirurgia ortopédica como artroscopia. No entanto, relatos recentes de complicações graves devido ao uso de anestésico local por via intra-articular causou preocupações. OBJETIVOS: O objetivo do estudo foi avaliar o uso de vitamina C para reduzir os efeitos adversos dos anestésicos mais comumente usados (ropivocaína, bupivacaína e lidocaína) sobre condrócitos humanos. MÉTODOS: A viabilidade dos condrócitos após a exposição à bupivacaína a 0,5% ou ropivacaína a 0,75% ou lidocaína a 1,0% e/ou vitamina C em doses de 125, 250 e 500 µM foi determinada pelo ensaio Vivo/Morto e coloração com anexina V. Os níveis de expressão das caspases 3 e 9 foram avaliados com o uso de anticorpos pela técnica Western blotting. Citometria de fluxo foi feita para analisar a geração de espécies reativas ao oxigênio. RESULTADOS: Na exposição aos anestésicos locais, condrotoxicidade foi encontrada na seguinte ordem: ropivacaína < bupivacaína < lidocaína. A vitamina C efetivamente melhorou a redução da viabilidade dos condrócitos e diminuiu os níveis elevados de apoptose após a exposição à anestesia. Em doses mais altas, a vitamina C foi eficiente para reduzir a geração de espécies reativas ao oxigênio e assim regular negativamente a expressão das caspases 3 e 9. CONCLUSÕES: Observamos que a vitamina C foi eficaz na proteção dos condrócitos contra a agressão tóxica dos anestésicos locais ropivacaína, bupivacaína e lidocaína.


Subject(s)
Humans , Ascorbic Acid/pharmacology , Reactive Oxygen Species/metabolism , Chondrocytes/drug effects , Anesthetics, Local/toxicity , Ascorbic Acid/administration & dosage , Bupivacaine/toxicity , Down-Regulation/drug effects , Cells, Cultured , Apoptosis/drug effects , Chondrocytes/pathology , Dose-Response Relationship, Drug , Caspase 3/genetics , Caspase 9/genetics , Flow Cytometry , Ropivacaine , Amides/toxicity , Lidocaine/toxicity , Antioxidants/administration & dosage , Antioxidants/pharmacology
14.
Clin. biomed. res ; 36(4): 179-186, 2016. ilus
Article in English | LILACS | ID: biblio-831517

ABSTRACT

Caffeine consumption during pregnancy has been shown in the scientific literature to be associated with teratogenicity such as low birth weight, fetal malformations, and miscarriage. However, the morphological alterations of the offspring of dams exposed during pregnancy have not been consistently described, and the mechanisms why they occur remain elusive. Thus, we aimed to characterize the offspring malformations induced by moderate and high doses of caffeine during pregnancy. Dams were divided into three groups: control, moderate (0.3 g/L), and high dose (1.0 g/L) of caffeine, which was provided in the drinking water beginning on gestational day 1 and continuing throughout the entire gestation. At moderate doses, only one of the dams had stillborn pups, although no macroscopic malformations were observed. High doses of caffeine induced significantly more malformations (P<0.001) and early death (before P4). The malformations observed were related to fetal development and cardiovascular alterations, namely bruises, macrocephaly with short limbs, abnormal development (or absence) of head structures and limbs, labial malformations, hydrops fetalis, and poor placental formation. We discussed the proposed mechanisms by which caffeine might induce these phenotypes, which may involve down-regulation of adenosine A1 receptors, and increased mothers' catecholamines. Our findings further confirm the evidence of the teratogenic effects of high doses of caffeine administered during pregnancy. These findings support the recommendation to avoid caffeine exposure during pregnancy (AU)


Subject(s)
Animals , Female , Pregnancy , Rats , Caffeine/toxicity , Congenital Abnormalities , Heart Defects, Congenital/chemically induced , Pregnancy , Caffeine/administration & dosage , Down-Regulation/drug effects , Maternal-Fetal Exchange/drug effects , Receptor, Adenosine A1
15.
Braz. j. med. biol. res ; 49(12): e5717, 2016. graf
Article in English | LILACS | ID: biblio-828174

ABSTRACT

Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. A previous study has found that propofol can inhibit invasion and induce apoptosis of ovarian cancer cells. However, the underlying mechanisms are not known. miR-9 has been reported to be little expressed in ovarian cancer cells, which has been related to a poor prognosis in patients with ovarian cancer. Studies have also demonstrated that propofol could induce microRNAs expression and suppress NF-κB activation in some situations. In the present study, we assessed whether propofol inhibits invasion and induces apoptosis of ovarian cancer cells by miR-9/NF-κB signaling. Ovarian cancer ES-2 cells were transfected with anti-miR-9 or p65 cDNA or p65 siRNA for 24 h, after which the cells were treated with different concentrations of propofol (1, 5, and 10 μg/mL) for 24 h. Cell growth and apoptosis were detected using MTT assay and flow cytometry analysis. Cell migration and invasion were detected using Transwell and Wound-healing assay. Western blot and electrophoretic mobility shift assay were used to detect different protein expression and NF-κB activity. Propofol inhibited cell growth and invasion, and induced cell apoptosis in a dose-dependent manner, which was accompanied by miR-9 activation and NF-κB inactivation. Knockdown of miR-9 abrogated propofol-induced NF-κB activation and MMP-9 expression, reversed propofol-induced cell death and invasion of ES-2 cells. Knockdown of p65 inhibited NF-κB activation rescued the miR-9-induced down-regulation of MMP-9. In addition, overexpression of p65 by p65 cDNA transfection increased propofol-induced NF-κB activation and reversed propofol-induced down-regulation of MMP-9. Propofol upregulates miR-9 expression and inhibits NF-κB activation and its downstream MMP-9 expression, leading to the inhibition of cell growth and invasion of ES-2 cells.


Subject(s)
Humans , Female , MicroRNAs/drug effects , Neoplasm Invasiveness/prevention & control , NF-kappa B/drug effects , Ovarian Neoplasms/drug therapy , Propofol/therapeutic use , Protective Agents/therapeutic use , Apoptosis/drug effects , Blotting, Western , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Matrix Metalloproteinase 9/metabolism , MicroRNAs/genetics , NF-kappa B/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Polymerase Chain Reaction
16.
Cad. saúde pública ; 31(3): 517-530, 03/2015. tab, graf
Article in English | LILACS | ID: lil-744825

ABSTRACT

A territorial analysis of Aedes aegypti density was conducted in two Colombian cities using an ecosystem and chorematic approach. Entomological and behavioral data (by cluster) and information on the urban context were used to analyze the relationship between territorial structures and dynamics and vector density. The results were represented in graphic (chorematic) models. Arauca showed higher vector density than Armenia. Higher density was related to unplanned urbanization, flood-prone areas, low socioeconomic strata, household water tanks, higher temperature, and recall of control measures for adult mosquitos. Zones with low density indices coincided with diverse socioeconomic, ecological, and behavioral conditions. The study found a relationship between territorial structures and dynamics and vector density in both Arauca and Armenia, where the interaction between ecological and social systems shape areas with high and low A. aegypti density.


Foi realizada uma análise territorial da densidade do Aedes aegypti em duas cidades da Colômbia, desde um enfoque ecossistêmico e da coremática. Com base em informação entomológica e comportamental (por conglomerados) e informação do contexto urbano, foi indagada a relação de estruturas dinâmicas do território com a densidade vetorial. Foram apresentados os resultados com modelos gráficos (coremática). Identificou-se maior densidade vetorial em Arauca do que na Armênia. Maiores densidades foram relacionadas à urbanização não planejada, zonas de alagamento, estratos socioeconômicos baixos, tanques baixos (reservatórios), maior temperatura e relatório de ações contra os mosquitos adultos. Zonas de densidades baixas coincidiram com diversas condições socioeconômicas, ecológicas e comportamentais. Foi encontrada uma relação das estruturas e dinâmicas do território com a densidade vetorial para Arauca e Armênia, onde a interação entre sistemas ecológicos e sociais configura zonas particulares de alta e baixa densidades de A. aegypti.


Se realizó un análisis territorial de la densidad de Aedes aegypti en dos ciudades de Colombia desde un enfoque ecosistémico y la coremática. A partir de información entomológica y comportamental (por conglomerados) e información del contexto urbano, se indagó la relación de estructuras y dinámicas del territorio con la densidad vectorial. Se representaron los resultados con modelos gráficos (coremática). Se identificó mayor densidad vectorial en Arauca que en Armenia. Mayores densidades se relacionaron con urbanización no planeada, zonas de inundación, estratos socioeconómicos bajos, tanques bajos (alberca), mayor temperatura y reporte de acciones hacia los mosquitos adultos. Zonas de densidades bajas coincidieron con diversas condiciones socioeconómicas, ecológicas y comportamentales. Se encontró relación de las estructuras y dinámicas del territorio con la densidad vectorial para Arauca y Armenia, donde la interacción entre sistemas ecológicos y sociales configuran zonas particulares de alta y baja densidad de A. aegypti.


Subject(s)
Animals , Rats , Apoptosis/drug effects , Benzamides/pharmacology , Enzyme Inhibitors/pharmacology , Fatty Acids, Nonesterified/pharmacology , Insulin-Secreting Cells/enzymology , Phenanthrenes/pharmacology , Poly(ADP-ribose) Polymerases/biosynthesis , Cell Line , Down-Regulation/drug effects , Homeodomain Proteins/biosynthesis , Insulin , Poly(ADP-ribose) Polymerases/antagonists & inhibitors , Trans-Activators/biosynthesis
17.
Salud colect ; 11(1): 99-114, ene.-mar. 2015. ilus, tab
Article in Spanish | LILACS | ID: lil-746687

ABSTRACT

El Consejo Federal de Medicina de Brasil (CFM) -órgano normativo y fiscalizador del ejercicio ético de la medicina- prohibió, en 2008, la participación de médicos brasileños en investigaciones que utilizaran placebo para enfermedades con tratamiento eficaz y efectivo, en contraposición a la Declaración de Helsinki, que permite su uso en condiciones metodológicamente justificadas. Con el objetivo de verificar si la normativa ética del CFM modificó el uso de placebo en ensayos clínicos de fase III en Brasil, se analizaron varias características de sus registros en el ClinicalTrials.gov, en los períodos de 2003 a 2007 y de 2009 a 2013. Se concluye que: a) la normativa promulgada por el CFM en 2008 fue ineficaz y prevaleció la posición adoptada por la Declaración de Helsinki; b) el patrocinio de ensayos con placebo por parte de la industria farmacéutica multinacional fue significativo; c) predominaron las investigaciones de fármacos para enfermedades crónicas, y fueron poco significativas para las enfermedades postergadas, de importancia para Brasil.


In 2008, Brazil's Federal Council of Medicine [Conselho Federal de Medicina] (CFM) - regulatory and supervisory agency on the ethical practice of medicine - banned the participation of Brazilian doctors in studies using placebos for diseases with efficient and effective treatment. This position differs with the Helsinki Declaration, which allows the use of placebos in methodologically justified conditions. To ascertain whether the CMF's ethical regulation modified the use of placebos in phase III clinical trials in Brazil, characteristics of the records in ClinicalTrials.gov were researched in the periods from 2003 to 2007 and from 2009 to 2013. The conclusions reached were: a) the regulations issued by the CFM in 2008 were ineffective and the position adopted by the Helsinki Declaration prevails; b) there was significant sponsorship by the multinational pharmaceutical industry of trials with placebos; c) the research was predominantly on new drugs for chronic diseases, with little study done of the neglected diseases which are of great importance to Brazil.


Subject(s)
Animals , Rats , Apoptosis/genetics , Gene Expression Regulation, Enzymologic/genetics , Heme/deficiency , Nerve Degeneration/genetics , Neurons/metabolism , Porphyrias/complications , Apoptosis/drug effects , Caspases/drug effects , Caspases/metabolism , Cell Survival/drug effects , Cell Survival/genetics , Collagen Type XI/drug effects , Collagen Type XI/metabolism , Cyclic AMP Response Element-Binding Protein/drug effects , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP Response Element-Binding Protein/metabolism , Down-Regulation/drug effects , Down-Regulation/physiology , Enzyme Inhibitors , Gene Expression Regulation, Enzymologic/drug effects , Heptanoates , Heme/biosynthesis , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/physiology , Membrane Proteins/drug effects , Membrane Proteins/genetics , Membrane Proteins/metabolism , Nerve Degeneration/metabolism , Nerve Degeneration/physiopathology , Nerve Tissue Proteins/drug effects , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neural Cell Adhesion Molecules/drug effects , Neural Cell Adhesion Molecules/genetics , Neural Cell Adhesion Molecules/metabolism , Neurons/drug effects , Neurons/pathology , Poly(ADP-ribose) Polymerases , Porphyrias/metabolism , Porphyrias/physiopathology , RNA, Messenger/drug effects , RNA, Messenger/metabolism , RNA-Binding Proteins/drug effects , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , SMN Complex Proteins , Up-Regulation/drug effects , Up-Regulation/physiology , Vesicular Transport Proteins/drug effects , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolism
18.
Clinics ; 70(3): 157-161, 03/2015. tab
Article in English | LILACS | ID: lil-747105

ABSTRACT

OBJECTIVE: To determine whether Tai Chi Chuan or ballroom dancing promotes better performance with respect to postural balance, gait, and postural transfer among elderly people. METHODS: We evaluated 76 elderly individuals who were divided into two groups: the Tai Chi Chuan Group and the Dance Group. The subjects were tested using the NeuroCom Balance Master¯ force platform system with the following protocols: static balance tests (the Modified Clinical Tests of Sensory Interaction on Balance and Unilateral Stance) and dynamic balance tests (the Walk Across Test and Sit-to-stand Transfer Test). RESULTS: In the Modified Clinical Test of Sensory Interaction on Balance, the Tai Chi Chuan Group presented a lower sway velocity on a firm surface with open and closed eyes, as well as on a foam surface with closed eyes. In the Modified Clinical Test of Sensory Interaction on Unilateral Stance, the Tai Chi Chuan Group presented a lower sway velocity with open eyes, whereas the Dance Group presented a lower sway velocity with closed eyes. In the Walk Across Test, the Tai Chi Chuan Group presented faster walking speeds than those of the Dance Group. In the Sit-to-stand Transfer Test, the Tai Chi Chuan Group presented shorter transfer times from the sitting to the standing position, with less sway in the final standing position. CONCLUSION: The elderly individuals who practiced Tai Chi Chuan had better bilateral balance with eyes open on both types of surfaces compared with the Dance Group. The Dance Group had better unilateral postural balance with eyes closed. The Tai Chi Chuan Group had faster walking speeds, shorter transfer times, and better postural balance in the final standing position during the Sit-to-stand Test. .


Subject(s)
/metabolism , Cyclic AMP/metabolism , Dictyostelium/enzymology , Dictyostelium/genetics , GTP-Binding Protein alpha Subunits, Gi-Go/metabolism , Protozoan Proteins/metabolism , /genetics , Dictyostelium/growth & development , Dictyostelium/metabolism , Down-Regulation/drug effects , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Folic Acid/pharmacology , /deficiency , /genetics , /metabolism , GTP-Binding Protein alpha Subunits, Gi-Go/deficiency , GTP-Binding Protein alpha Subunits, Gi-Go/genetics , Mutation , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Protozoan Proteins/genetics , Signal Transduction , Spores, Protozoan/enzymology , Spores, Protozoan/genetics , Vitamin B Complex/pharmacology
19.
Article in English | WPRIM | ID: wpr-64643

ABSTRACT

BACKGROUND/AIMS: Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. METHODS: Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. RESULTS: Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. CONCLUSIONS: Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Down-Regulation/drug effects , Drug Screening Assays, Antitumor , Drug Synergism , Humans , Liver Neoplasms/metabolism , Niacinamide/analogs & derivatives , Phenylurea Compounds/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Quinazolines/pharmacology , ErbB Receptors/metabolism , Signal Transduction/drug effects , Silymarin/pharmacology
20.
Article in English | WPRIM | ID: wpr-149086

ABSTRACT

Pentraxin 3 (PTX3) was identified as a marker of the inflammatory response and overexpressed in various tissues and cells related to cardiovascular disease. Honokiol, an active component isolated from the Chinese medicinal herb Magnolia officinalis, was shown to have a variety of pharmacological activities. In the present study, we aimed to investigate the effects of honokiol on palmitic acid (PA)-induced dysfunction of human umbilical vein endothelial cells (HUVECs) and to elucidate potential regulatory mechanisms in this atherosclerotic cell model. Our results showed that PA significantly accelerated the expression of PTX3 in HUVECs through the IkappaB kinase (IKK)/IkappaB/nuclear factor-kappaB (NF-kappaB) pathway, reduced cell viability, induced cell apoptosis and triggered the inflammatory response. Knockdown of PTX3 supported cell growth and prevented apoptosis by blocking PA-inducted nitric oxide (NO) overproduction. Honokiol significantly suppressed the overexpression of PTX3 in PA-inducted HUVECs by inhibiting IkappaB phosphorylation and the expression of two NF-kappaB subunits (p50 and p65) in the IKK/IkappaB/NF-kappaB signaling pathway. Furthermore, honokiol reduced endothelial cell injury and apoptosis by regulating the expression of inducible NO synthase and endothelial NO synthase, as well as the generation of NO. Honokiol showed an anti-inflammatory effect in PA-inducted HUVECs by significantly inhibiting the generation of interleukin-6 (IL-6), IL-8 and monocyte chemoattractant protein-1. In summary, honokiol repaired endothelial dysfunction by suppressing PTX3 overexpression in an atherosclerotic cell model. PTX3 may be a potential therapeutic target for atherosclerosis.


Subject(s)
Apoptosis/drug effects , Atherosclerosis/chemically induced , Biphenyl Compounds/chemistry , C-Reactive Protein/genetics , Down-Regulation/drug effects , Drugs, Chinese Herbal/chemistry , Human Umbilical Vein Endothelial Cells , Humans , I-kappa B Kinase/immunology , Lignans/chemistry , Magnolia/chemistry , Palmitic Acid , Protein-Serine-Threonine Kinases/immunology , Serum Amyloid P-Component/genetics , Signal Transduction/drug effects
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