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1.
J Clin Anesth ; 95: 111467, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38593491

RESUMO

STUDY OBJECTIVE: To assess the impact of preoperative infection with the contemporary strain of severe acute respiratory coronavirus 2 (SARS-CoV-2) on postoperative mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery. DESIGN: An ambidirectional observational cohort study. SETTING: A tertiary and teaching hospital in Shanghai, China. PATIENTS: All adult patients (≥ 18 years of age) who underwent elective, noncardiac surgery under general anesthesia at Huashan Hospital of Fudan University from January until March 2023 were screened for eligibility. A total of 2907 patients were included. EXPOSURE: Preoperative coronavirus disease 2019 (COVID-19) positivity. MEASUREMENTS: The primary outcome was 30-day postoperative mortality. The secondary outcomes included postoperative pulmonary complications (PPCs), myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), postoperative delirium (POD) and postoperative sleep quality. Multivariable logistic regression was used to assess the risk of postoperative mortality and morbidity imposed by preoperative COVID-19. MAIN RESULTS: The risk of 30-day postoperative mortality was not associated with preoperative COVID-19 [adjusted odds ratio (aOR), 95% confidence interval (CI): 0.40, 0.13-1.28, P = 0.123] or operation timing relative to diagnosis. Preoperative COVID-19 did not increase the risk of PPCs (aOR, 95% CI: 0.99, 0.71-1.38, P = 0.944), MINS (aOR, 95% CI: 0.54, 0.22-1.30; P = 0.168), or AKI (aOR, 95% CI: 0.34, 0.10-1.09; P = 0.070) or affect postoperative sleep quality. Patients who underwent surgery within 7 weeks after COVID-19 had increased odds of developing delirium (aOR, 95% CI: 2.26, 1.05-4.86, P = 0.036). CONCLUSIONS: Preoperative COVID-19 or timing of surgery relative to diagnosis did not confer any added risk of 30-day postoperative mortality, PPCs, MINS or AKI. However, recent COVID-19 increased the risk of POD. Perioperative brain health should be considered during preoperative risk assessment for COVID-19 survivors.


Assuntos
COVID-19 , Procedimentos Cirúrgicos Eletivos , Complicações Pós-Operatórias , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , COVID-19/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Idoso , China/epidemiologia , Estudos de Coortes , Adulto , Fatores de Risco , Período Pré-Operatório
2.
J Asian Nat Prod Res ; 25(12): 1217-1222, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37163366

RESUMO

A new abietane diterpenoid, 1ß, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2-4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [Figure: see text].


Assuntos
Antineoplásicos Fitogênicos , Lycopodium , Humanos , Abietanos/farmacologia , Abietanos/química , Estrutura Molecular , Lycopodium/química , Linhagem Celular Tumoral , Células MCF-7 , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química
3.
J Neurosurg ; 136(2): 350-357, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34359042

RESUMO

OBJECTIVE: Previous studies have suggested the use of 1.0 g/kg of 20% mannitol at the time of skin incision during neurosurgery in order to improve brain relaxation. However, the incidence of brain swelling upon dural opening is still high with this dose. In the present study, the authors sought to determine a better timing for mannitol infusion. METHODS: One hundred patients with midline shift who were undergoing elective supratentorial tumor resection were randomly assigned to receive early (immediately after anesthesia induction) or routine (at the time of skin incision) administration of 1.0 g/kg body weight of 20% mannitol. The primary outcome was the 4-point brain relaxation score (BRS) immediately after dural opening (1, perfectly relaxed; 2, satisfactorily relaxed; 3, firm brain; and 4, bulging brain). The secondary outcomes included subdural intracranial pressure (ICP) measured immediately before dural opening; serum osmolality and osmole gap (OG) measured immediately before mannitol infusion (T0) and at the time of dural opening (TD); changes in serum electrolytes, lactate, and hemodynamic parameters at T0 and 30, 60, 90, and 120 minutes thereafter; and fluid balance at TD. RESULTS: The time from the start of mannitol administration to dural opening was significantly longer in the early administration group than in the routine administration group (median 66 [IQR 55-75] vs 40 [IQR 38-45] minutes, p < 0.001). The BRS (score 1/2/3/4, n = 14/26/9/1 vs 3/25/18/4, p = 0.001) was better and the subdural ICP (median 5 [IQR 3-6] vs 7 [IQR 5-10] mm Hg, p < 0.001) was significantly lower in the early administration group than in the routine administration group. Serum osmolality and OG increased significantly at TD compared to levels at T0 in both groups (all p < 0.001). Intergroup comparison showed that serum osmolality and OG at TD were significantly higher in the routine administration group (p < 0.001 and = 0.002, respectively). Patients who had received early administration of mannitol had more urine output (p = 0.001) and less positive fluid balance (p < 0.001) at TD. Hemodynamic parameters, serum lactate concentrations, and incidences of electrolyte disturbances were comparable between the two groups. CONCLUSIONS: Prolonging the time interval between the start of mannitol infusion and dural incision from approximately 40 to 66 minutes can improve brain relaxation and decrease subdural ICP in elective supratentorial tumor resection.


Assuntos
Manitol , Neoplasias Supratentoriais , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Craniotomia/efeitos adversos , Humanos , Pressão Intracraniana , Ácido Láctico , Manitol/farmacologia , Manitol/uso terapêutico , Estudos Prospectivos , Neoplasias Supratentoriais/cirurgia
4.
Int J Mol Sci ; 22(20)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34681614

RESUMO

The l-type amino acid transporter 1 (LAT1) is a membranous transporter that transports neutral amino acids for cells and is dysregulated in various types of cancer. Here, we first observed increased LAT1 expression in pemetrexed-resistant non-small cell lung cancer (NSCLC) cells with high cancer stem cell (CSC) activity, and its mRNA expression level was associated with shorter overall survival in the lung adenocarcinoma dataset of the Cancer Genome Atlas database. The inhibition of LAT1 by a small molecule inhibitor, JPH203, or by RNA interference led to a significant reduction in tumorsphere formation and the downregulation of several cancer stemness genes in NSCLC cells through decreased AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) activation. The treatment of the cell-permeable leucine derivative promoted AKT/mTOR phosphorylation and reversed the inhibitory effect of JPH203 in the reduction of CSC activity in pemetrexed-resistant lung cancer cells. Furthermore, we observed that LAT1 silencing caused the downregulation of programmed cell death 1 ligand 1 (PD-L1) on lung cancer cells. The PD-L1+/LAT1+ subpopulation of NSCLC cells displayed great CSC activity with increased expression of several cancer stemness genes. These data suggest that LAT1 inhibitors can serve as anti-CSC agents and could be used in combination with immune checkpoint inhibitors in lung cancer therapy.


Assuntos
Antígeno B7-H1/metabolismo , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Benzoxazóis/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Transportador 1 de Aminoácidos Neutros Grandes/química , Transportador 1 de Aminoácidos Neutros Grandes/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Pemetrexede/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Tirosina/análogos & derivados , Tirosina/farmacologia
5.
Int J Clin Pract ; 75(11): e14570, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34165855

RESUMO

BACKGROUND: Acute kidney injury (AKI) is one of the most serious perioperative complications. 20% to 40% of high-risk patients who undergo non-cardiac surgery have AKI and those with AKI are eight-times more likely to die within 30 days after surgery. It may be related to intraoperative hypotension, which is mainly caused by vasodilatory and cardiodepressant effects of anaesthesia, and/or hypovolemia. Strict intraoperative blood pressure management strategy (strict BP management) is a potential option to prevent postoperative AKI. This strategy refers to additional administration of vasoactive agents under the premise of a protocolised fluid delivery. The efficacy of strict BP management for preventing postoperative AKI in non-cardiac surgery patients was assessed by a meta-analysis. METHODS: We systematically retrieved randomised controlled trials (RCTs) and compared strict BP management with conventional therapy control on effect of postoperative AKI in non-cardiac surgery patients, which were published on PubMed, EMBASE, Cochrane library and Web of Science databases before October 5, 2020. Ultimately, a meta-analysis of all RCTs eligible for inclusion criteria was performed. RESULTS: Five RCTs, comprising 1485 patients, were included in the meta-analysis. Strict BP management was associated with a reduced incidence of postoperative AKI [relative risk (RR) = 0.73, 95% confidence interval (CI): 0.58-0.92, P = .007]. No significant difference was found between strict BP management group and conventional therapy control in mortality at longest follow-up available (RR = 0.92, 95% CI: 0.68-1.25, P = .60). In the subset analysis, the studies using supranormal BP management target was significantly lower in the incidence of postoperative AKI (RR = 0.65, 95% CI: 0.51-0.82, P = .0003) CONCLUSION: Strict BP management is significantly more effective than conventional therapy for the prevention of postoperative AKI. Supranormal target of intraoperative BP management may be considered a more appealing option for the prevention of AKI.


Assuntos
Injúria Renal Aguda , Hipotensão , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Pressão Sanguínea , Humanos , Hipotensão/etiologia , Hipotensão/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle
6.
Int J Clin Pharm ; 42(5): 1326-1334, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32686050

RESUMO

Background In most scenarios, anaesthesiologists titrate opioids to control nociceptive surgical stress based on intraoperative haemodynamic changes. Remifentanil was reported to cause more profound cardiovascular depression than sufentanil. A concern is that this direct cardiovascular depression might counteract the hypertension and tachycardia caused by surgical manipulation and mask inadequate analgesia. Objective To compare remifentanil and sufentanil, titrated to maintain a comparable haemodynamic range (within 20% of baseline) and combined with the same propofol regimen, in stress reduction measured as plasma levels of putative mediators of surgical stress. Setting Huashan Hospital of Fudan University, Shanghai, China. Method Forty-five patients undergoing supratentorial glioma resection were randomised to the remifentanil group or the sufentanil group. Main outcome measures Plasma concentrations of cortisol, epinephrine, norepinephrine, interleukin-6, interleukin-10 and lymphocyte counts were analysed before anaesthesia, 1 h after incision, at the end of surgery and 24 h after incision using enzyme-linked immunosorbent assay and an automatic haematology analyser. Recovery profiles during emergence from anaesthesia were also compared. Results Except for a lower epinephrine concentration in the remifentanil group 24 h after incision (median [interquartile range], 4.2 [3.4-6.1] vs. 8.4 [4.8-12.5] ng/ml; P = 0.003), stress biomarkers were not significantly different between the two groups. Patients in the sufentanil group had lower grades in coughing, restlessness (P = 0.001 and < 0.001, respectively) and a lower incidence of postoperative shivering (P = 0.007). Conclusion Compared to that of sufentanil, the direct cardiovascular depression of remifentanil does not mask the clinical manifestation of inadequate analgesia when both drugs are titrated according to haemodynamic variables in neurosurgery.


Assuntos
Procedimentos Neurocirúrgicos/métodos , Remifentanil/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Sufentanil/farmacologia , Adulto , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacologia , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/farmacologia , China , Método Duplo-Cego , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Propofol/administração & dosagem , Remifentanil/efeitos adversos
7.
Acta Anaesthesiol Scand ; 64(10): 1414-1421, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32659854

RESUMO

BACKGROUND: In the monitored anesthesia care (MAC) setting for awake craniotomy (AC), maintaining airway patency in sedated patients remains challenging. This randomized controlled trial aimed to compare the validity of the below-epiglottis transnasal tube insertion (the tip of the tube placed between the epiglottis and vocal cords) and the nasopharyngeal airway (simulated by the above-epiglottis transnasal tube with the tip of the tube placed between the epiglottis and the free edge of the soft palate) with respect to maintaining upper airway patency for moderately sedated patients undergoing AC. METHODS: Sixty patients scheduled for elective AC were randomized to receive below-epiglottis (n = 30) or above-epiglottis (n = 30) transnasal tube insertion before surgery. Moderate sedation was maintained in the pre- and post-awake phases. The primary outcome was the upper airway obstruction (UAO) remission rate (relieved obstructions after tube insertion/the total number of obstructions before tube insertion). RESULTS: The UAO remission rate was higher in the below-epiglottis group [100% (12/12) vs 45% (5/11); P = .005]. The tidal volume values monitored through the tube were greater in the below-epiglottis group during the pre-awake phase (P < .001). End-tidal carbon dioxide (EtCO2 ) monitored through the tube was higher in the below-epiglottis group at bone flap removal (P < .001). During the awake phase, patients' ability to speak was not impeded. No patient had serious complications related to the tube. CONCLUSION: The below-epiglottis tube insertion is a more effective method to maintain upper airway patency than the nasopharyngeal airway for moderately sedated patients undergoing AC.


Assuntos
Manuseio das Vias Aéreas , Vigília , Sedação Consciente , Craniotomia , Epiglote , Humanos , Intubação Intratraqueal
8.
Eur J Cancer Prev ; 26(4): 314-323, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27192048

RESUMO

Cinnamomum verum has been used as a Chinese herbal medication. We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human lung squamous cell carcinoma NCI-H520 cells. The effects of 2-MCA on cell growth, cytotoxicity, apoptosis, and topoisomerase I and II activities in human lung squamous cell carcinoma NCI-H520 cells were evaluated in vitro and in vivo. The results showed that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm) loss, activation of both caspase 3 and caspase 9, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated volume of acidic compartment and cytotoxicity, and inhibited topoisomerase I as well as II activities. Additional study showed the antiproliferative effect of 2-MCA in a nude mice model. In short, our data imply that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of proapoptotic molecules, associated with increased lysosomal vacuolation. In vivo, 2-MCA reduced the tumor size, which could have had a significant clinical impact. Our data imply that 2-MCA may be a potential agent for chemoprevention as well as anticancer therapy.


Assuntos
Acroleína/análogos & derivados , Carcinoma de Células Escamosas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Cinnamomum/química , DNA Topoisomerases Tipo I/química , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Ligação a Poli-ADP-Ribose/antagonistas & inibidores , Acroleína/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , DNA Topoisomerases Tipo II , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Food Nutr Res ; 60: 31607, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27281694

RESUMO

BACKGROUND: Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the plant has been used as a Chinese herbal medication. METHODS: We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human colorectal adenocarcinoma COLO 205 cells. Specifically, cell viability was evaluated by colorimetric assay; apoptosis was determined by flow cytometry and morphological analysis with bright field, acridine orange, and neutral red stainings, as well as comet assay; topoisomerase I activity was determined by assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VACs) were determined by neutral red staining. RESULTS: The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm) loss, activation of both caspase-3 and -9, increase of annexin V(+)PI(+) cells, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated VAC, cytotoxicity, and inhibitions of topoisomerase I as well as II activities. Additional study demonstrated the antiproliferative effect of 2-MCA found in a nude mice model. CONCLUSIONS: Our data implicate that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of pro-apoptotic molecules, associated with increased lysosomal vacuolation. In vivo 2-MCA reduced the tumor burden that could have significant clinical impact. Indeed, similar effects were found in other tested cell lines, including human hepatocellular carcinoma SK-Hep-1 and Hep 3B, lung adenocarcinoma A549 and squamous cell carcinoma NCI-H520, and T-lymphoblastic MOLT-3 (results not shown). Our data implicate that 2-MCA could be a potential agent for anticancer therapy.

10.
Nutrients ; 8(6)2016 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-27231935

RESUMO

Cinnamomum verum, also called true cinnamon tree, is employed to make the seasoning cinnamon. Furthermore, the plant has been used as a traditional Chinese herbal medication. We explored the anticancer effect of cuminaldehyde, an ingredient of the cortex of the plant, as well as the molecular biomarkers associated with carcinogenesis in human colorectal adenocarcinoma COLO 205 cells. The results show that cuminaldehyde suppressed growth and induced apoptosis, as proved by depletion of the mitochondrial membrane potential, activation of both caspase-3 and -9, and morphological features of apoptosis. Moreover, cuminaldehyde also led to lysosomal vacuolation with an upregulated volume of acidic compartment and cytotoxicity, together with inhibitions of both topoisomerase I and II activities. Additional study shows that the anticancer activity of cuminaldehyde was observed in the model of nude mice. Our results suggest that the anticancer activity of cuminaldehyde in vitro involved the suppression of cell proliferative markers, topoisomerase I as well as II, together with increase of pro-apoptotic molecules, associated with upregulated lysosomal vacuolation. On the other hand, in vivo, cuminaldehyde diminished the tumor burden that would have a significant clinical impact. Furthermore, similar effects were observed in other tested cell lines. In short, our data suggest that cuminaldehyde could be a drug for chemopreventive or anticancer therapy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Benzaldeídos/farmacologia , Cinnamomum zeylanicum , Neoplasias Colorretais/tratamento farmacológico , DNA Topoisomerases Tipo II/metabolismo , DNA Topoisomerases Tipo I/metabolismo , Extratos Vegetais/farmacologia , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase II/farmacologia , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Benzaldeídos/isolamento & purificação , Caspase 3/metabolismo , Caspase 9/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cinnamomum zeylanicum/química , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Cimenos , Relação Dose-Resposta a Droga , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Transdução de Sinais/efeitos dos fármacos , Inibidores da Topoisomerase I/isolamento & purificação , Inibidores da Topoisomerase II/isolamento & purificação , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Curr Cancer Drug Targets ; 16(9): 796-806, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27113744

RESUMO

Cinnamomum verum is used to make the spice cinnamon and has been used for more than 5000 years by both of the two most ancient forms of medicine in the words: Ayurveda and traditional Chinese herbal medicines for various applications such as adenopathy, rheumatism, dermatosis, dyspepsia, stroke, tumors, elephantiasis, trichomonas, yeast, and virus infections. We evaluated the anticancer effect of cuminaldehyde (CuA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that cuminaldehyde suppressed proliferation and induced apoptosis as indicated by mitochondrial membrane potential loss, activation of caspase 3 and 9, increase in annexin V+PI+ cells, and morphological characteristics of apoptosis, including blebbing of plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. In addition, cuminaldehyde also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of both topoisomerase I & II as well as telomerase activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of cuminaldehyde was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of cuminaldehyde against A549 cells is accompanied by downregulations of proliferative control involving apoptosis, both topoisomerase I & II as well as telomerase activities, together with an upregulation of lysosomal vacuolation and VAC. Similar effects (including all of the above-mentioned effects) were found in other cell lines, including human lung squamous cell carcinoma NCI-H520 and colorectal adenocarcinoma COLO 205 (results not shown). Our data suggest that cuminaldehyde could be a potential agent for anticancer therapy.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Benzaldeídos/farmacologia , Cinnamomum zeylanicum/química , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão , Animais , Apoptose/efeitos dos fármacos , Cimenos , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular/métodos , Telomerase/antagonistas & inibidores , Telomerase/metabolismo , Inibidores da Topoisomerase I/farmacologia , Inibidores da Topoisomerase II/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Cancer ; 7(3): 251-61, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26918037

RESUMO

Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the effects and the molecular mechanisms of cuminaldehyde (CuA), a constituent of the bark of Cinnamomum verum, on human lung squamous cell carcinoma NCI-H520 cells. Specifically, cell viability was evaluated by colorimetric assay; cytotoxicity by LDH release; apoptosis was determined by Western blotting, and morphological analysis with, acridine orange and neutral red stainings and comet assay; topoisomerase I activity was assessed using assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VAC) were evaluated with neutral red staining. The results show that CuA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and a down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, and morphological characteristics of apoptosis, including blebbing of the plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. In addition, CuA also induced lysosomal vacuolation with increased VAC, cytotoxicity, as well as suppressions of both topoisomerase I and II activities in a dose-dependent manner. Further study revealed the growth-inhibitory effect of CuA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of CuA against NCI-H520 cells is accompanied by downregulations of proliferative control involving apoptosis and both topoisomerase I and II activities, and upregulation of lysosomal with increased VAC and cytotoxicity. Similar effects were found in other cell lines, including human lung adenocarcinoma A549 cells and colorectal adenocarcinoma COLO 205 (results not shown). Our data suggest that CuA could be a potential agent for anticancer therapy.

13.
Phytother Res ; 30(2): 331-40, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26676220

RESUMO

Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an upregulation of pro-apoptotic Bax and Bak genes and downregulation of anti-apoptotic Bcl-2 and Bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase-3 and -9, and morphological characteristics of apoptosis, including plasma membrane blebbing and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartment (VAC) and suppressions of nuclear transcription factors nuclear factor-κB (NF-κB) and both topoisomerase I and II activities. Further study reveals that the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against A549 cells is accompanied by downregulations of NF-κB binding activity and proliferative control involving apoptosis and both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy.


Assuntos
Acroleína/análogos & derivados , Antineoplásicos Fitogênicos/farmacologia , Cinnamomum zeylanicum/química , Inibidores da Topoisomerase/farmacologia , Acroleína/farmacologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Citocromos c/metabolismo , DNA Topoisomerases Tipo I/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Nus , NF-kappa B/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Am J Emerg Med ; 30(1): 45-50, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20970297

RESUMO

OBJECTIVE: The study aimed to assess the clinical efficacy of pigtail catheter drainage for patients with a first episode of secondary spontaneous pneumothorax (SSP) and different associated conditions. METHODS: We retrospectively reviewed the records of patients with SSP who received pigtail catheter drainage as their initial management between July 2002 and October 2009. A total of 168 patients were included in the analysis; 144 (86%) males and 24 (14%) females with a mean age of 60.3 ± 18.3 years (range, 17-91 years). Data regarding demographic characteristics, pneumothorax size, complications, treatments, length of hospital stay, and associated conditions were analyzed. RESULTS: In total, 118 (70%) patients were successfully treated with pigtail catheter drainage, and 50 (30%) patients required further management. Chronic obstructive lung disease was the most common underlying disease (57% of cases). Secondary spontaneous pneumothorax associated with infectious diseases had a higher rate of treatment failure than SSP associated with obstructive lung conditions (19/38 [50%] successful vs 78/104 [75%] successful, P = .004) and malignancy (19/38 [50%] successful vs 13/16 [81%] successful, P = .021). Moreover, patients with SSP associated with infectious diseases had a longer length of hospital stay than those with obstructive lung conditions (23.8 vs 14.5 days, P = .003) and malignancy (23.8 vs 12.1 days, P = .017). No complications were associated with pigtail catheter drainage. CONCLUSIONS: A higher rate of treatment failure was noted in SSP patients with infectious diseases; thus, pigtail catheter drainage is appropriate as an initial management for patients with SSPs associated with obstructive lung conditions and malignancy.


Assuntos
Tubos Torácicos , Drenagem/métodos , Pneumotórax/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Pneumopatias/complicações , Neoplasias Pulmonares/complicações , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/complicações , Pneumotórax/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Zhong Yao Cai ; 33(5): 763-7, 2010 May.
Artigo em Chinês | MEDLINE | ID: mdl-20873562

RESUMO

OBJECTIVE: To study The protective effect of puerarin on Abeta(25-35)-induced PC12 cell injury. METHODS: PC12 cells were treated with puerarin for 0.5 h, then incubated with Abeta(25-35) (50 micromol/L) for 24 h to investigate the production of reactive oxygen species (ROS), mitochondrial membrane potential levels and Caspase-3 activation; The expressions of Bax, bcl-2 were measured by Western Blotting. RESULTS: Preincubation of the cell with puerarin could inhibit the ROS and increase mitochondrial membrane potential levels. Puerarin was also found to increase the Bcl-2/Bax ratio and reduce Caspase-3 activation. CONCLUSION: Puerarin may act as an intracellular ROS scavenger, and its antioxidant properties may protect against Abeta(25-35)-induced cell injury.


Assuntos
Doença de Alzheimer/prevenção & controle , Antioxidantes/farmacologia , Isoflavonas/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 3/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Fragmentos de Peptídeos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Proteína X Associada a bcl-2/metabolismo
16.
Am J Emerg Med ; 28(8): 915-21, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20825924

RESUMO

OBJECTIVE: Little is known about the efficacy and safety of ultrasound-guided pigtail catheters for the management of various pleural diseases in the emergency department, ward, and intensive care unit. METHODS: We conducted a retrospective study in a university hospital during a 1-year interval. RESULTS: A total of 276 patients (178 men and 98 women) underwent 332 pigtail catheters (the drain size ranged from 10F to 16F) under ultrasound guidance. The mean ± SEM patient age was 59 ± 18 years, and mean duration of drainage was 6.1 ± 2 days. A total of 64 drains (19.2%) were inserted for pneumothoraces; 98 drains (29.5%), for malignant effusions; 119 drains (35.8%), for parapneumonic effusions/empyemas; and 38 drains (11.4%), for massive transudate pleural effusions. The overall success rate was 72.9%. The success rate was highest when the drain was used to treat massive transudate effusions (81.6%) and malignant pleural effusions (75.5%), followed by parapneumonic effusions/empyemas (72.2%), hemothoraces (66.6%), and pneumothoraces (64.0%). Only 10 (3.0%) drains had complications due to the procedure, including infection (n = 4, 1.2%), dislodgment (n = 4, 1.2%), wound bleeding at the pigtail catheter puncture area complicated with hemothoraces (n = 1, 0.3%), and lung puncture (n = 1, 0.3%). There was no significant difference in success rate when different catheter sizes were used to treat pleural diseases. CONCLUSIONS: Ultrasound-guided pigtail catheters provide a safe and effective method of draining various pleural diseases. We strongly suggest that ultrasound-guided pigtail catheters be considered as the initial draining method for a variety of pleural diseases.


Assuntos
Cateterismo/instrumentação , Drenagem/instrumentação , Doenças Pleurais/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo/efeitos adversos , Drenagem/efeitos adversos , Empiema Pleural/terapia , Feminino , Hemotórax/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/terapia , Derrame Pleural Maligno/terapia , Pneumotórax/terapia , Estudos Retrospectivos , Ultrassonografia/instrumentação , Adulto Jovem
17.
Zhong Yao Cai ; 32(7): 1090-3, 2009 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19873738

RESUMO

OBJECTIVE: To observe the effects of total flavonoids from Rhizoma Drynariae medicated serum on cell proliferation, differentiation, cell cycle and apoptosis of rats' osteoblasts cultured in vitro. METHODS: The osteoblasts from cranium of newborn SD rats were cultured by collagenase method. MTT, PNPP, PI and Annexin V/PI methods were used to observe the proliferation, activity of alkaline phosphatase (ALP), every stage cells in the cell cycle, and the ratio of apoptosis cells by different concentrations of total flavonoids from Rhizoma Drynariae medicated serum at different time points. RESULTS: Different concentrations of total flavonoids from Rhizoma Drynariae medicated serum could significantly enhance the cell proliferation rate and ALP activity (P < 0.05), more cells in S stage and less cells apoptosised than that of the untreated osteoblasts (P < 0.05). CONCLUSION: Total flavonoids from Rhizoma Drynariae medicated serum could promote the proliferation, differentiation, increase S stage cells, and reduce the ratio of apoptosis cells, which reveals that they have anti-osteoporosis activity.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Flavonoides/farmacologia , Osteoblastos/citologia , Polypodiaceae/química , Fosfatase Alcalina/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Flavonoides/isolamento & purificação , Osteoblastos/efeitos dos fármacos , Osteoblastos/enzimologia , Osteoporose/prevenção & controle , Ratos , Ratos Sprague-Dawley
19.
Cell Biol Int ; 32(10): 1230-7, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18675923

RESUMO

beta-Amyloid protein (Abeta), a major protein component of brain senile plaques in Alzheimer's disease, is known to be directly responsible for the production of reactive oxygen species (ROS) and induction of apoptosis. In this study, the protective effect of puerarin, an isoflavone purified from the radix of the Chinese herb Pueraria lobata, on Abeta-induced rat pheochromocytoma (PC12) cultures was investigated. Although exposure of PC12 cells to 50 microM Abeta25-35 caused significant viability loss and apoptotic rate increase, pretreatment of the cells with puerarin for 24h reduced the viability loss and apoptotic rate. Puerarin (1 microM) significantly inhibited Abeta25-35-induced apoptosis of PC12 cells. Preincubation of the cell with puerarin also restored the ROS and mitochondrial membrane potential levels that had been altered as a result of Abeta25-35 treatment. Puerarin was also found to increase the Bcl-2/Bax ratio and reduce caspase-3 activation. These results suggest that puerarin could attenuate Abeta25-35-induced PC12 cell injure and apoptosis and could also promote the survival of PC12 cells. Therefore, puerarin may act as an intracellular ROS scavenger, and its antioxidant properties may protect against Abeta25-35-induced cell injury.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Isoflavonas/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Caspase 3/metabolismo , Humanos , Marcação In Situ das Extremidades Cortadas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neurônios/fisiologia , Células PC12 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Vasodilatadores/farmacologia , Proteína X Associada a bcl-2/metabolismo
20.
Zhong Yao Cai ; 31(4): 543-6, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18661826

RESUMO

OBJECTIVE: To establish a nerve cell injury model by incubating PC12 cell line in the presence of Abeta25-35 to study the effect of puerarin on apoptosis of nerve cells. METHODS: PC12 cells were incubated with Abeta25-35 and puerarin. Cell viability was detected by MTT. The cellular morphology was observed with electron microscopy. FITC-labeled Annexin V and propidium iodide were adopted to evaluate the rate of cell apoptosis in different groups by means of flow cytometry. RESULTS: Following incubation Abeta25-35, the cells were induced to undergo apoptosis. The viability of PC12 cells decreased in a time-dependent manner. Morphological evidences for apoptosis nuclear condensation were observed in PC12 cells. Cells incubated in the presence of Abeta25-35 showed increasing apoptotic rates, but cells treated with puerarin and Abeta25-35 revealed decreasing apoptotic rates, it demonstrated that puerarin had a significant protective action against Abeta25-35 evoked apoptosis. CONCLUSION: Puerarin can resist the adverse effects of Abeta25-35 on increasing apoptotic rates, and it has the protective function towards nerve cells.


Assuntos
Doença de Alzheimer/patologia , Apoptose/efeitos dos fármacos , Isoflavonas/farmacologia , Fármacos Neuroprotetores/farmacologia , Peptídeos beta-Amiloides , Animais , Sobrevivência Celular/efeitos dos fármacos , Fabaceae/química , Citometria de Fluxo , Células PC12 , Fragmentos de Peptídeos , Ratos , Vasodilatadores/farmacologia
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