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1.
Sci Total Environ ; 944: 173983, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-38876341

RESUMO

Integrated health risk assessment strategies for emerging organic pollutants and heavy metals that coexist in water/soil media are lacking. Contents of perfluoroalkyl compounds and potentially toxic elements in multiple media were determined by investigating a county where a landfill and a tungsten mine coexist. The spatial characteristics and sources of contaminants were predicted by Geostatistics-based and multivariate statistical analysis, and their comprehensive health risks were assessed. The average contents of perfluorooctane acid, perfluorooctanesulfonic acid, arsenic, and cadmium in groundwater were 3.21, 0.77, 1.69, and 0.14 µg L-1, respectively; the maximum content of cadmium in soils and rice highly reached 2.12 and 1.52 mg kg-1, respectively. In soils, the contribution of mine lag to cadmium was 99 %, and fertilizer and pesticide to arsenic was 59.4 %. While in groundwater, arsenic, cadmium and perfluoroalkyl compounds near the landfill mainly came from leachate leakage. Significant correlations were found between arsenic in groundwater and arsenic and cadmium in soils, as well as perfluoroalkyl compounds in groundwater and pH and sulfate. Based on these correlations, the geographically optimal similarity model predicted high-level arsenic in groundwater near the tungsten mine and cadmium/perfluoroalkyl compounds around the landfill. The combination of analytic network process, entropy weighting method and game theory-based trade-off method with risk assessment model can assess the comprehensive risks of multiple pollutants. Using this approach, a high health-risk zone located around the landfill, which was mainly attributed to the presence of arsenic, cadmium and perfluorooctanesulfonic acid, was found. Overall, perfluoroalkyl compounds in groundwater altered the spatial pattern of health risks in an arsenic­cadmium contaminated area.


Assuntos
Arsênio , Cádmio , Monitoramento Ambiental , Fluorocarbonos , Água Subterrânea , Poluentes Químicos da Água , Água Subterrânea/química , Poluentes Químicos da Água/análise , Fluorocarbonos/análise , Arsênio/análise , Cádmio/análise , Medição de Risco , Poluentes do Solo/análise , Ácidos Alcanossulfônicos/análise , Mineração , China
2.
J Cancer ; 15(11): 3242-3253, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817867

RESUMO

Bladder Cancer (BCa) is one of the most common cancers of the urinary system. Colony-stimulating factor 2 (CSF2) is involved in many cancers, but not BCa. We investigated the effect of CSF2 on BCa in this study and the underlying molecular mechanisms. CSF2 mRNA levels in BCa were analyzed using the Cancer Genome Atlas (TCGA) database. Western blot was conducted to verify CSF2 expression in BCa tissue samples and cell lines. The effect of CSF2 on the growth of BCa cells was assessed by CCK8 and colony formation. To determine the migration and invasion capabilities of BCa cells, transwell analysis and wound healing assays were conducted. Next, western blot was used to explore the underlying mechanism. In the end, a xenografted BCa mouse model was established to examine the effects of CSF2 on tumorigenesis in vivo. Results showed that CSF2 mRNA was upregulated in BCa samples. Knocking down CSF2 significantly inhibited the proliferation and tumorigenesis of BCa cells in vitro and in vivo. Mechanism analysis revealed that CSF2 knockdown inhibited the proliferation and invasion of BCa cells via AKT/mTOR signaling. Based on these results, CSF2 promotes the proliferation and tumorigenesis of BCa.

3.
Exp Cell Res ; 438(2): 114053, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38663476

RESUMO

Bladder cancer is a common tumor that impacts the urinary system and marked by a significant fatality rate and an unfavorable prognosis. Promising antineoplastic properties are exhibited by brusatol, which is obtained from the dried ripe fruit of Brucea javanica. The present study aimed to evaluate the influence of brusatol on the progression of bladder cancer and uncover the molecular mechanism involved. We used Cell Counting Kit-8, colony formation and EdU assays to detect cell numbers, viability and proliferation. We used transwell migration assay to detect cell migration ability. The mechanism of brusatol inhibition of bladder cancer proliferation was studied by flow cytometry and western blotting. It was revealed that brusatol could reduce the viability and proliferation of T24 and 5637 cells. The transwell migration assay revealed that brusatol was able to attenuate the migration of T24 and 5637 cells. We found that treatment with brusatol increased the levels of reactive oxygen species, malondialdehyde and Fe2+, thereby further promoting ferroptosis in T24 and 5637 cells. In addition, treatment with RSL3 (an agonistor of ferroptosis) ferrostatin-1 (a selective inhibitor of ferroptosis) enhanced or reversed the brusatol-induced inhibition. In vivo, treatment with brusatol significantly suppressed the tumor growth in nude mice. Mechanistically, brusatol induced ferroptosis by upregulating the expression of ChaC glutathione-specific gamma-glutamylcyclotransferase (Chac1) and decreasing the expression of SLC7A11 and Nrf2 in T24 and 5637 cells. To summarize, the findings of this research demonstrated that brusatol hindered the growth of bladder cancer and triggered ferroptosis via the Chac1/Nrf2/SLC7A11 pathway.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Movimento Celular , Proliferação de Células , Fator 2 Relacionado a NF-E2 , Quassinas , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Quassinas/farmacologia , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Espécies Reativas de Oxigênio/metabolismo , Progressão da Doença , Camundongos Endogâmicos BALB C , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
4.
Biomed Pharmacother ; 171: 116146, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38198952

RESUMO

The effectiveness and safety of traditional Chinese medicine's active ingredients in anti-tumor effects have attracted widespread attention worldwide. Solasonine is the main anti-tumor component of the traditional Chinese medicine Solanum nigrum L, which can inhibit tumor cell proliferation, induce apoptosis, induce ferroptosis in tumor cells, and inhibit of tumor cell metastasis, thereby inhibiting tumor progression. Therefore, we summarized anti-tumor mechanisms and targets of solasonine to provide new ideas and theoretical basis for its further development and application.


Assuntos
Neoplasias , Alcaloides de Solanáceas , Humanos , Alcaloides de Solanáceas/farmacologia , Apoptose , Medicina Tradicional Chinesa
5.
Biomed Pharmacother ; 165: 115107, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37423171

RESUMO

The antitumor effects of traditional drugs have received increasing attention and active antitumor components extracted from traditional drugs have shown good efficacy with minimal adverse events. Cepharanthine(CEP for short) is an active component derived from the Stephania plants of Menispermaceae, which can regulate multiple signaling pathways alone or in combination with other therapeutic drugs to inhibit tumor cell proliferation, induce apoptosis, regulate autophagy, and inhibit angiogenesis, thereby inhibiting tumor progression. Therefore, we retrieved studies concerning CEP's antitumor effects in recent years and summarized the antitumor mechanism and targets, in order to gain new insights and establish a theoretical basis for further development and application of CEP.


Assuntos
Antineoplásicos , Benzodioxóis , Benzilisoquinolinas , Benzilisoquinolinas/química , Benzilisoquinolinas/farmacologia , Benzodioxóis/química , Benzodioxóis/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Humanos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Tolerância a Radiação/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Angiogênese/efeitos dos fármacos
6.
Anal Bioanal Chem ; 415(12): 2185-2191, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36864308

RESUMO

Probes for detecting phosphate ions (Pi) are required for environmental monitoring and to protect human health. Here, novel ratiometric luminescent lanthanide coordination polymer nanoparticles (CPNs) were successfully prepared and used to selectively and sensitively detect Pi. The nanoparticles were prepared from adenosine monophosphate (AMP) and Tb3+, and lysine (Lys) was used as a sensitizer (through the antenna effect) to switch on Tb3+ luminescence at 488 and 544 nm while Lys luminescence at 375 nm was quenched because of energy transfer from Lys to Tb3+. The complex involved is here labeled AMP-Tb/Lys. Pi destroyed the AMP-Tb/Lys CPNs and therefore decreased the AMP-Tb/Lys luminescence intensity at 544 nm and increased the luminescence intensity at 375 nm at an excitation wavelength of 290 nm, meaning ratiometric luminescence detection was possible. The ratio between the luminescence intensities at 544 and 375 nm (I544/I375) was strongly associated with the Pi concentration between 0.1 and 6.0 µM, and the detection limit was 0.08 µM. The dual-emission reverse-change ratio luminescence sensing method can exclude environmental effects, so the proposed assay was found to be very selective. The method was successfully used to detect Pi in real water samples, and acceptable recoveries were found, suggesting that the method could be used in practice to detect Pi in water samples.


Assuntos
Nanopartículas , Térbio , Humanos , Luminescência , Polímeros , Lisina , Monofosfato de Adenosina , Água
8.
Environ Res ; 212(Pt A): 113133, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35337834

RESUMO

Characteristic sexual hormones (SHs) and the factors that dominantly influence their occurrence in coastal ecosystems are less understood. This study verified the relationships between SHs and environmental factors and further inferred the possible controlling mechanisms of SH distribution. A characteristic pollutant of SHs was first proposed by determining the contamination level and ecological risks of SHs (seven species) in a coastal river adjacent to the Bohai Sea. The results showed that the 17ß-oestradiol (17ß-E2), estriol (E3), and 17α-ethynylestradiol (EE2) had high mean concentrations of 11.20 (±1.31), 10.17 (±4.91), and 16.71 (±0.88) ng L-1, respectively, in the river water. The concentration of estrone (E1) was positively related to microbial substances of DOMs (p < 0.05). The humification index (HIX) had a negative relationship with E3 (p < 0.05). In water, the distribution of total SHs was regulated by the HIX and fluorescence index (FI), which might be related to photodegradation reactions. The 17α-oestradiol (17α-E2) and EE2 were related to humified organic matter, while E3 and androstenedione (ADD) were influenced by sewage input. The 17ß-E2, E1, and 17α-E2 may be derived from animal sources, while E3, ADD, EE2, and progesterone were from human activities. Oestrogens, including E1, 17α-E2, 17ß-E2, and EE2, displayed higher ecological risks than androgens and progesterone, with medium to high risk in most sites. The 17ß-E2 was regarded as a characteristic pollutant of SHs throughout the river system, which displayed the highest risk. This paper may provide a reference for SH risk management and control.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Animais , Ecossistema , Estradiol/metabolismo , Estrogênios/metabolismo , Etinilestradiol/análise , Etinilestradiol/metabolismo , Progesterona , Rios , Água , Poluentes Químicos da Água/análise
9.
Biomed Pharmacother ; 146: 112506, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34883450

RESUMO

Ascites is one of the common complications in patients with decompensated liver cirrhosis and liver cancer. Wuling powder (WLP) is a classic prescription for the treatment of water retention caused by bladder gasification. It is also widely used in the treatment of ascites. This systematic review aimed to evaluate the clinical efficacy of WLP and determine its effective chemical components based on a large number of related pieces of literature. The pharmacological effects and chemical constituents of WLP were summarized. Besides, the clinical research status of WLP in the treatment of ascites caused by liver cancer and cirrhosis was analyzed. The key targets and pathways of WLP in the treatment of ascites based on network pharmacology analysis were also discussed. Furthermore, the core components and core targets of WLP in the treatment of ascites using molecular docking were verified and the interaction sites were predicted, to provide a theoretical and scientific basis for the clinical application of WLP.


Assuntos
Ascite/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Pós , Transdução de Sinais/efeitos dos fármacos
10.
Braz J Anesthesiol ; 71(4): 352-357, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34229861

RESUMO

BACKGROUND: The role of intravenous lidocaine infusion in endoscopic surgery has been previously evaluated for pain relief and recovery. Recently, it has been shown to reduce postoperative pain and opioid in patients undergoing endoscopic submucosal dissection. Similar to endoscopic submucosal dissection, operative hysteroscopy is also an endoscopic surgical procedure within natural lumens. The present study was a randomized clinical trial in which we evaluated whether intravenous lidocaine infusion would reduce postoperative pain in patients undergoing hysteroscopic surgery. OBJECTIVE: To evaluate whether intravenous lidocaine infusion could reduce postoperative pain in patients undergoing operative hysteroscopy. METHODS: Eighty-five patients scheduled to undergo elective hysteroscopy were randomized to receive either an intravenous bolus of lidocaine 1.5 mg.kg-1 over 3 minutes, followed by continuous infusion at a rate of 2 mg.kg-1. h-1 during surgery, or 0.9% normal saline solution at the same rate. The primary outcome was to evaluate postoperative pain by Visual Analog Scale (VAS). Secondary outcomes included remifentanil and propofol consumption. RESULTS: In the lidocaine group, the VAS was significantly lower at 0.5 hour (p = 0.008) and 4 hours (p = 0.020). Patients in the lidocaine group required less remifentanil than patients in the control group (p < 0.001). However, there was no difference between the two groups in the propofol consumption. The incidence of throat pain was significantly lower in the lidocaine group (p = 0.019). No adverse events associated with lidocaine infusion were discovered. CONCLUSION: Intravenous lidocaine infusion as an adjuvant reduces short-term postoperative pain in patients undergoing operative hysteroscopy.


Assuntos
Histeroscopia , Lidocaína , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Histeroscopia/efeitos adversos , Infusões Intravenosas , Lidocaína/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Gravidez , Remifentanil/uso terapêutico
11.
Ann Vasc Surg ; 72: 445-453, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33157247

RESUMO

BACKGROUND: To evaluate morphologic features of symptomatic and ruptured abdominal aortic aneurysms in Asian patients. METHODS: Two hundred sixty four continuous candidates with an abdominal aortic aneurysm (AAA) were retrospectively identified from a tertiary hospital database between January 2017 and May 2019. The patients meeting inclusion criteria were divided into symptomatic or ruptured AAA (srAAA) and asymptomatic AAA (asAAA) groups. Their computed tomography angiographies were reconstructed using centerline technique and the geometric features of AAAs between the 2 groups were compared. RESULTS: One hundred two patients fulfilled selection criteria (mean age 71 years, 80 men), comprising 35 srAAAs and 67 asAAAs. There was no essential association between gender, smoking or hypertension, and AAA-associated symptoms or rupture. The maximum diameter (5.8 ± 1.4 cm vs. 5.0 ± 0.9 cm; P = 0.001), length (8.8 ± 0.6 cm vs. 7.0 ± 0.3 cm; P = 0.002), and intraluminal thrombus (ILT) thickness (1.7 ± 0.2 cm vs. 1.3 ± 0.1 cm; P = 0.039) of AAAs were independent risk factors for AAA-associated symptoms or rupture (binary logistic regression, P < 0.05), but AAA length and ILT were strongly correlated with the AAA diameter (Pearson correlation coefficient value of 0.591 and 0.444) whereas other factors such as aneurysmal tortuosity, aneurysmal neck anatomy, or common iliac artery geometry were nonsignificant. CONCLUSIONS: AAA diameter, length, and intraluminal thrombus thickness were identified as risk factors for AAA-associated symptoms in Asian patients. While the diameter is regarded as the most important predictor for symptoms and rupture, AAA length and ILT thickness should also be taken into consideration when contemplating intervention, particularly for borderline and smaller aneurysms.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Ruptura Aórtica/diagnóstico por imagem , Aortografia , Angiografia por Tomografia Computadorizada , Idoso , Aneurisma da Aorta Abdominal/etnologia , Ruptura Aórtica/etnologia , Povo Asiático , China/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombose/diagnóstico por imagem
12.
J Environ Qual ; 49(5): 1322-1333, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33016441

RESUMO

Antibiotics and estrogens are recognized as emerging contaminants in the water environment because of their potentially adverse effects on aquatic ecosystems. The concentrations of four steroid estrogens (17α-estradiol, 17ß-estradiol, estrone, and estriol) and eight antibiotics (norfloxacin, levofloxacin, ciprofloxacin, enrofloxacin, metronidazole, sulfapyridine, doxycycline, and sulfamethoxazole) in the Chaohu Lake basin in Anhui province, China, were analyzed along with adjacent wastewater. The levels of the target antibiotics and estrogens were below detection limits (not detected [nd])-89.86 and nd-118.09 ng L-1 , respectively, in the lake water. All of the target antibiotics and estrogens were detected in sediment, and the concentrations ranged widely (nd-35,544 and nd-16,344 ng kg-1 , respectively). Antibiotics and estrogens varied spatially in the study area and mostly came from untreated wastewater. Antibiotics and estrogens were associated with water parameters such as pH and total nitrogen. A significant positive correlation was observed between estriol and levofloxacin concentrations (r = .65; p < .01), indicating that levofloxacin from the same source might have inhibited the microbiological degradation of estriol in the surface water. Overall, the estrogens pose a more severe risk than antibiotics to the Chaohu Lake system. However, co-occurrence of antibiotics may affect the fate of estrogens in the same lake media. More attention should be given to estrogens than to antibiotics in wastewater-affected lake systems.


Assuntos
Águas Residuárias , Poluentes Químicos da Água/análise , Antibacterianos/análise , China , Ecossistema , Monitoramento Ambiental , Estrogênios/análise , Lagos/análise
13.
J Coll Physicians Surg Pak ; 30(4): 407-411, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32513362

RESUMO

ABATRACT Controversy exists in the effect of general anesthesia and non-general anesthesia on postoperative cognitive dysfunction (POCD). The authors aimed to perform this systematic review to comprehensively assess the effect of general anesthesia or non-general anesthesia on POCD. Relative studies from the online literature database were retrieved. Seven studies with 1,031 patients were included. Odds ratio and 95% confidence interval were calculated. The results showed that the POCD incidence was significantly lower in the patients underwent non-general anesthesia than those underwent general anesthesia in one and three days after surgery (p<0.05). However, no remarkable difference existed between the two anesthesia in seven days and three months after surgery (p>0.05). In conclusion, when compared with the non-general anesthesia, general anesthesia increases the incidence of POCD in patients within three days after surgery, but makes no difference after seven days. It suggests that early intervention should be conducted on patients undergoing general anesthesia. Key Words: General anesthesia, Postoperative cognitive dysfunction, Meta-analysis.


Assuntos
Complicações Cognitivas Pós-Operatórias , Anestesia Geral/efeitos adversos , Humanos , Incidência , Testes Neuropsicológicos , Complicações Pós-Operatórias/epidemiologia
14.
Biomed Pharmacother ; 129: 110380, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32554250

RESUMO

Baoyuan Jiedu (BYJD for short) decoction, a traditional Chinese medicine formula, is composed of Astragalus, Ginseng, Aconite root, Honeysuckle, Angelica, Licorice, which has the functions of nourishing qi and blood, enhancing immune function, improving quality of life and prolonging survival time of tumor patients. The present study aimed to investigate the effect and mechanism of BYJD decoction on reversing the pre-metastatic niche. We showed that BYJD decoction could prolong the survival time of 4T1 tumor-bearing mice. Moreover, we found that the BYJD decoction inhibited the formation of lung pre-metastatic niche and inhibited recruitment of myeloid derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and genes expression of TGF-ß, Smad2, Smad3, p-Smad2/3, Smad4, CCL9 in the TGF-ß/CCL9 signaling pathway were suppressed by BYJD decoction. In line with the above findings, our results confirm that BYJD decoction inhibits the accumulation of MDSC in pre-metastatic niche of lung via TGF-ß/CCL9 pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Quimiocinas CC/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/prevenção & controle , Pulmão/efeitos dos fármacos , Proteínas Inflamatórias de Macrófagos/metabolismo , Células Supressoras Mieloides/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Quimiocinas CC/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Proteínas Inflamatórias de Macrófagos/genética , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Carga Tumoral/efeitos dos fármacos
15.
Yonsei Med J ; 60(12): 1195-1202, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769251

RESUMO

PURPOSE: The aim of this study was to investigate whether propofol could attenuate hypoxia/reoxygenation-induced apoptosis and autophagy in human renal proximal tubular cells (HK-2) by inhibiting JNK activation. MATERIALS AND METHODS: HK-2 cells were treated with or without propofol or JNK inhibitor SP600125 for 1 hour and then subjected to 15 hours of hypoxia and 2 hours of reoxygenation (H/R). Cell viability and LDH release were measured with commercial kits. Cell apoptosis was evaluated by flow cytometry. The expressions of p-JNK, cleaved-caspase-3, Bcl-2, and autophagy markers LC3 and p62 were measured by Western blot or immunofluorescence. RESULTS: HK-2 cells exposed to H/R insult showed higher cell injury (detected by increased LDH release and decreased cell viability), increased cell apoptosis index and expression of cleaved-caspase-3, a decrease in the expression of Bcl-2 accompanied by increased expression of p-JNK and LC3II, and a decrease in expression of p62. All of these alterations were attenuated by propofol treatment. Similar effects were provoked upon treatment with the JNK inhibitor SP600125. Moreover, the protective effects were more obvious with the combination of propofol and SP600125. CONCLUSION: These results suggest that propofol could attenuate hypoxia/reoxygenation induced apoptosis and autophagy in HK-2 cells, probably through inhibiting JNK activation.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Propofol/farmacologia , Antracenos/farmacologia , Western Blotting , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , L-Lactato Desidrogenase/metabolismo , Oxigênio
16.
Life Sci ; 238: 116938, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593704

RESUMO

AIMS: To investigate the effect of 7-O-geranylquercetin (GQ), a derivative of quercetin (Q), on reversing drug resistance in breast cancer MCF-7/ADR cells and reveal the mechanisms related to P-glycoprotein (P-gp). MAIN METHODS: Cell viability was determined by MTT assay. Accumulation of adriamycin (ADR) in cells was determined by confocal fluorescence microscope and microplate reader while that of rhodamine (Rh) was measured by flow cytometry. Expression levels of P-gp and MDR1 gene in cells were detected by western blot and Real-Time PCR, respectively. Molecular docking of GQ and Q with P-gp was conducted using AutoDock program. Xenograft model was established by inoculating MCF-7/ADR cells in BALB/c-nude mice. Tumor bearing mice were administered with ADR via tail vein injection and/or GQ (Q) by gavage. Expression levels of P-gp in tissues were detected by western blot and immunohistochemistry. KEY FINDINGS: GQ could reverse drug resistance of MCF-7/ADR cells to ADR. GQ inhibited the efflux of ADR by down-regulating the expression of P-gp protein and its encoding gene MDR1 in MCF-7/ADR cells. Molecular modeling showed that GQ matched with P-gp better than Q. GQ enhanced the antitumor effects of ADR and decreased the expression of P-gp in mice and its activities were higher than that of Q. GQ could reverse drug resistance of MCF-7/ADR cells by down-regulating the expression of P-gp in vitro and in vivo. SIGNIFICANCES: The reversal effect of GQ on P-gp-mediated drug resistance indicates its potential as a reversal agent for drug resistance in cancer chemotherapy.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Quercetina/análogos & derivados , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Quercetina/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Cancer ; 10(2): 293-304, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30719123

RESUMO

In the treatment of lung cancer, the multidrug resistance to chemotherapeutic drugs is one of the reasons of low rates for cure and treatment failure, the combination of chemotherapeutic drugs and traditional Chinese medicine can increase the sensitivity of chemotherapy and reduce its adverse effects. Our previous study has proved that Chinese herbal medicine (CHM) Wenxia Changfu Formula (WCF for short) effectively enhances chemotherapeutic efficacy in lung cancer treatment and reverses multidrug resistance in lung cancer cells in vitro. The present study aims to investigate the effect and mechanism of WCF in reversing cell adhesion-mediated drug resistance of lung cancer by using A549 three-dimensional cell culture and nude mouse model of the A549 cell line with Integrin ß1 overexpression. We show that the combination of WCF with DDP can decrease proliferation of lung cancer cells by inducing cell cycle arrest and apoptosis. Moreover, we find that the combination of WCF with DDP suppresses the expression of certain molecules which regulate cell cycle and apoptosis. Mechanistically, we show that the Integrin ß1, FAK, PI3K, and AKT protein expressions are suppressed by DDP and even more responses are observed when DDP and WCF are combined, showing WCF treatment enhances the effect of commonly used anticancer drugs. In line with the above findings, our results confirm that WCF reverses cell adhesion-mediated drug resistance of lung cancer via inactivating Integrin ß1/PI3K/AKT and apoptosis induction.

18.
J Coll Physicians Surg Pak ; 29(1): 4-7, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30630559

RESUMO

OBJECTIVE: To analyse the impact of dezocine-remifentanil intravenous anaesthesia on perioperative signs, serum tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in liver cancer patients undergoing radiofrequency ablation (RFA). STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Renmin Hospital of Wuhan University, Wuhan, China, from January 2017 to February 2018. METHODOLOGY: Eighty patients with small hepatocellular carcinoma (SHCC) were selected as the research object. They were divided into Group A and Group B with the random number table method, with 40 cases in each group. Group A were given dezocine-remifentanil intravenous anaesthesia and Group B were given midazolam-remifentanil intravenous anaesthesia. Patients' situations in the surgery were compared between the two groups. Changes in heart rate (HR), mean arterial pressure (MAP) and blood oxygen saturation (SpO2) were recorded before the surgery (T0), at 5 minutes after the RFA (T1) and at the end of the RFA (T2). Levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on the 12 day after the RFA were compared between the two groups. RESULTS: The wake-up time in Group A was shorter than Group B (p<0.001), and the VAS pain score in Group A was lower than Group B (p<0.001). At T1, the MAP in Group A was higher than Group B (p<0.001). There was no significant difference in MAP between the two groups at T0 and T2 (p=0.881, 0.696, respectively). At T1 and T2, the HR in Group A was lower than Group B (all p<0.001). There was no significant difference in HR between the two groups at T0 (p=0.684). There was no significant difference in SpO2 between the two groups at T0, T1 and T2 (p=0.654, 0.884 and 0.798, respectively). On the 1st day after the RFA, the level of TNF-α, IL-6 in Group A were lower than those of Group B (all p<0.001). There was no significant difference in the incidence of intraoperative complications between the two groups (p=0.644). CONCLUSION: Compared with midazolam-remifentanil intravenous anaesthesia, the dezocine-remifentanil method has a better analgesic effect, shorter wake-up time, and can effectively regulate the expression of inflammatory cytokines TNF-α and IL-6. However, the effect of remifentanil on the respiratory function is dose-dependent. Therefore, respiratory cycle monitoring and management should be strengthened during the surgery.


Assuntos
Analgésicos Opioides/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Carcinoma Hepatocelular/cirurgia , Frequência Cardíaca/efeitos dos fármacos , Interleucina-6/sangue , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência , Remifentanil/uso terapêutico , Tetra-Hidronaftalenos/uso terapêutico , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Anestesia Intravenosa/efeitos adversos , Anestesia Intravenosa/métodos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Carcinoma Hepatocelular/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Remifentanil/administração & dosagem , Tetra-Hidronaftalenos/administração & dosagem , Resultado do Tratamento
19.
Acta cir. bras ; 34(1): e20190010000003, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-983683

RESUMO

Abstract Purpose: To investigate the influence of lycium barbarum polysaccharides (LBP), a functional derivative from lycium barbarum, on septic kidney injury. Methods: The SD male rats were randomly divided into 8 groups. The concentration of IL-1β, IL-6, IL-8, TNF-α, NF-κB and ROS, in kidney cortex homogenates after 12 h treatments were determined by enzyme-linked immunosorbent assay and ROS test kit, respectively. Morphology observation of kidney tissue was conducted with HE staining. The mRNA and protein expression levels of Nrf2, HO-1, NQO1, NF-κB, and Keap1 in kidney tissues were determined by qRT-PCR and Western blot, respectively. Results: LPS treatment significantly increased the oxidative stress. After LBP treatment, the ROS content reduced significantly in a dose-depend manner. However, the levels of HO-1, NQO1 and Nrf2 as molecular elements that respond to oxidative stress were further increased. Also, administration of LBP increased the levels of NF-κB and Keap1, and decreased the levels of Nrf2 in the Keap 1-Nrf2∕ARE signaling pathway. By administrating the brusatol, the inhibition of Nrf2 enhanced the expression of NF-κB, inhibits the antioxidant responses, and further reverse the protective effect of LBP on the LPS induced septic kidney injury. Conclusion: Lycium barbarum polysaccharides can reduce inflammation and activate the antioxidant responses via regulating the level of pro-inflammatory cytokines and the Keap1-Nrf2/ARE signaling pathway.


Assuntos
Animais , Masculino , Ratos , Medicamentos de Ervas Chinesas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças
20.
Sci Rep ; 8(1): 7051, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728592

RESUMO

The aging of many mammalian tissues is associated with loss of functional adult stem cells, especially bone marrow-derived mesenchymal stem cells (BMSCs). This study was aimed to analyze the biological effect of chick embryo (CE) and nutrient mixture (NM) on the BMSCs of aging rats. The aging rat model was established to be induced by D-galactose (500 mg/kg/d) for 90 days. Meanwhile, aging rats were fed with CE and NM in different dose manner by intragastric administration. At the end of the experimental period, serum was collected from rats and used for BMSCs culture. Flow cytometric analysis was used to investigate the BMSCs surface markers. Alizarin Red and oil red O staining were performed to evaluate the multi-lineage differentiation of BMSCs. The results showed that CE plus NM increased the telomere length of BMSCs and promoted BMSCs proliferation. Moreover, CE plus NM administration promoted BMSCs differentiation into osteoblasts and suppressed differentiation into adipocytes. High-throughput sequencing analysis revealed that there were 326 genes were up-regulated and 59 genes were down-regulated in BMSCs of aging rats treated with CE plus NM. In conclusion, CE plus NM supplement had potential to delay aging through the recovery of BMSCs senescence and could be used as a safe effective approach for nutritional therapy of anti-aging.


Assuntos
Comunicação Celular , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Nutrientes/farmacologia , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Fatores Etários , Animais , Biomarcadores , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Técnicas de Cocultura , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Imunofenotipagem , Células-Tronco Mesenquimais/citologia , Nutrientes/química , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Ratos , Homeostase do Telômero
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