RESUMO
The parasitic wasp Cotesia congregata suppresses feeding in its host, the caterpillar Manduca sexta, during specific periods of wasp development. We examined both feeding behaviour and the neurophysiology of the mandibular closer muscle in parasitized and unparasitized control M. sexta to determine how the wasp may accomplish this. To test whether the wasps activated a pre-existing host mechanism for feeding cessation, we examined the microstructure of feeding behaviour in caterpillars that stopped feeding due to illness-induced anorexia or an impending moult. These microstructures were compared with that shown by parasitized caterpillars. While there were overall differences between parasitized and unparasitized caterpillars, the groups showed similar progression in feeding microstructure as feeding ended, suggesting a common pattern for terminating a meal. Parasitized caterpillars also consumed less leaf area in 100 bites than control caterpillars at around the same time their feeding microstructure changed. The decline in food consumption was accompanied by fewer spikes per burst and shorter burst durations in chewing muscle electromyograms. Similar extracellular results were obtained from the motorneuron of the mandibular closer muscle. However, chewing was dramatically re-activated in non-feeding parasitized caterpillars if the connectives posterior to the suboesophageal ganglion were severed. The same result was observed in unparasitized caterpillars given the same treatment. Our results suggest that the reduced feeding in parasitized caterpillars is not due to damage to the central pattern generator (CPG) for chewing, motor nerves or chewing muscles, but is more likely to be due to a suppression of chewing CPG activity by ascending or descending inputs.
Assuntos
Manduca , Vespas , Animais , Vespas/fisiologia , Manduca/fisiologia , Mastigação , Comportamento Alimentar/fisiologia , Larva/fisiologia , Interações Hospedeiro-Parasita/fisiologiaRESUMO
BACKGROUND: We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). METHODS: We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. RESULTS: We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. CONCLUSION: EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).
Assuntos
Adenoma , Neoplasias Colorretais , Vesículas Extracelulares , MicroRNAs , Humanos , Estudos Prospectivos , MicroRNAs/genética , Adenoma/diagnóstico , Adenoma/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genéticaRESUMO
Applying machine learning methods to resolve the cadmium (Cd) uptake characteristics of regional soil-wheat systems can contribute to the accuracy and rationality of risk decisions. Based on a regional survey, we constructed a Freundlich-type transfer equation, random forest (RF) model, and neural network (BPNN) model to predict wheat Cd enrichment factor (BCF-Cd); verified the prediction accuracy; and assessed the uncertainty of different models. The results showed that both RF (R2=0.583) and BPNN (R2=0.490) were better than the Freundlich transfer equation (R2=0.410). The RF and BPNN were further trained repeatedly, and the results showed that the mean absolute error (MAE) and root mean square error (RMSE) of RF and BPNN were close to each other. Additionally, the accuracy and stability of RF (R2=0.527-0.601) was higher than that of BPNN (R2=0.432-0.661). Feature importance analysis showed that multiple factors led to the heterogeneity of wheat BCF-Cd, in which soil phosphorus (P) and zinc (Zn) were the key variables affecting the change in wheat BCF-Cd. Parameter optimization can further improve the accuracy, stability, and generalization ability of the model.
Assuntos
Cádmio , Triticum , Aprendizado de Máquina , Fósforo , SoloRESUMO
The interaction of zinc (Zn) and cadmium (Cd) is an important research direction in the prevention and control of Cd pollution of wheat in recent years. In this study, a typical wheat field in North China was selected as the object to explore the control effect and application risk of Zn fertilizer on Cd pollution in a soil-wheat system through field experiments. The results showed that under the treatment of a low dosage of Zn, the Cd concentrations in wheat grains in Jiyuan City and Kaifeng City decreased by 33.4% and 25.3% compared with those in the control, respectively. By contrast, Cd concentrations in wheat grains treated with a high dosage of Zn increased by 22.4% and 34.2% compared with that of the low-dosage Zn treatment. After the application of Zn, the total amount and available Zn concentrations increased significantly, and Cd was partially activated in these two locations. Canonical correlation analysis (CCA) showed that when the Zn concentrations in the soils were less than 200 mg·kg-1, soil Zn was the main factor affecting Cd accumulation in the soil-wheat system, whereas when Zn concentrations in soils were greater than 200 mg·kg-1, the activation of soil Cd was the main factor affecting Cd accumulation in wheat grains. Regression analysis showed that when the soil Cd/Zn ratio decreased to 0.0089 (low dosage of Zn), Zn and Cd showed an antagonistic effect, whereas when the soil Cd/Zn ratio decreased to 0.0078 (high dosage of Zn), Zn and Cd showed a synergistic effect. According to the characteristics of regional Cd pollution, adjusting the amount of Zn fertilizer can improve the efficiency of pollution control and avoid aggravating the harm of Cd pollution.
Assuntos
Cádmio , Poluentes do Solo , Cádmio/análise , Zinco , Triticum , Fertilizantes/análise , Poluentes do Solo/análise , Grão Comestível/química , SoloRESUMO
Importance: The efficacy of laparoscopic vs open surgery for patients with low rectal cancer has not been established. Objective: To compare the short-term efficacy of laparoscopic surgery vs open surgery for treatment of low rectal cancer. Design, Setting, and Participants: This multicenter, noninferiority randomized clinical trial was conducted in 22 tertiary hospitals across China. Patients scheduled for curative-intent resection of low rectal cancer were randomized at a 2:1 ratio to undergo laparoscopic or open surgery. Between November 2013 and June 2018, 1070 patients were randomized to laparoscopic (n = 712) or open (n = 358) surgery. The planned follow-up was 5 years. Data analysis was performed from April 2021 to March 2022. Interventions: Eligible patients were randomized to receive either laparoscopic or open surgery. Main Outcomes and Measures: The short-term outcomes included pathologic outcomes, surgical outcomes, postoperative recovery, and 30-day postoperative complications and mortality. Results: A total of 1039 patients (685 in laparoscopic and 354 in open surgery) were included in the modified intention-to-treat analysis (median [range] age, 57 [20-75] years; 620 men [59.7%]; clinical TNM stage II/III disease in 659 patients). The rate of complete mesorectal excision was 85.3% (521 of 685) in the laparoscopic group vs 85.8% (266 of 354) in the open group (difference, -0.5%; 95% CI, -5.1% to 4.5%; P = .78). The rate of negative circumferential and distal resection margins was 98.2% (673 of 685) vs 99.7% (353 of 354) (difference, -1.5%; 95% CI, -2.8% to 0.0%; P = .09) and 99.4% (681 of 685) vs 100% (354 of 354) (difference, -0.6%; 95% CI, -1.5% to 0.5%; P = .36), respectively. The median number of retrieved lymph nodes was 13.0 vs 12.0 (difference, 1.0; 95% CI, 0.1-1.9; P = .39). The laparoscopic group had a higher rate of sphincter preservation (491 of 685 [71.7%] vs 230 of 354 [65.0%]; difference, 6.7%; 95% CI, 0.8%-12.8%; P = .03) and shorter duration of hospitalization (8.0 vs 9.0 days; difference, -1.0; 95% CI, -1.7 to -0.3; P = .008). There was no significant difference in postoperative complications rate between the 2 groups (89 of 685 [13.0%] vs 61 of 354 [17.2%]; difference, -4.2%; 95% CI, -9.1% to -0.3%; P = .07). No patient died within 30 days. Conclusions and Relevance: In this randomized clinical trial of patients with low rectal cancer, laparoscopic surgery performed by experienced surgeons was shown to provide pathologic outcomes comparable to open surgery, with a higher sphincter preservation rate and favorable postoperative recovery. Trial Registration: ClinicalTrials.gov Identifier: NCT01899547.
RESUMO
Acute lymphoblastic leukaemia (ALL) is diagnosed by the presence of at least 20% lymphoblasts in the bone marrow. ALL may be aggressive and include the lymph nodes, liver, spleen, central nervous system (CNS), and other organs. Without early recognition and timely treatment, ALL will progress quickly and may have poor prognosis in clinical scenarios. ALL is a rare type of leukaemia in adults but is the most common type in children. Precipitating factors such as environmental radiation or chemical exposure, viral infection, and genetic factors can be associated with ALL. We report a rare case of ALL with symptomatic hypercalcaemia in an adult woman. The patient presented with general weakness, poor appetite, bilateral lower limbs oedema, consciousness disturbance, and lower back pain for 3 weeks. She had a history of cervical cancer and had undergone total hysterectomy, chemotherapy, and radiation therapy. Her serum calcium level was markedly increased, at 14.1 mg/dl at admission. Neck magnetic resonance imaging, abdominal sonography, abdominal computed tomography, and bone marrow examination were performed. Laboratory data, including intact parathyroid hormone (i-PTH), peripheral blood smear, and 25-(OH) D3, were checked. Bone marrow biopsy showed B cell lymphoblastic leukaemia. Chemotherapy was initiated to be administered but was discontinued due to severe sepsis. Finally, the patient died due to septic shock. This was a rare case of B cell ALL in an adult complicated by hypercalcaemic crisis, which could be a life-threatening emergency in clinical practice. Physicians should pay attention to the associated risk factors. Early recognition and appropriate treatment may improve clinical outcomes.
RESUMO
It has been demonstrated Inhibitor Kappa B Kinase ß (IKKß) facilitates autophagy, which in turn mediates p-Tau protein clearance. However, the specific regulatory mechanism in Alzheimer's disease (AD) remains unclear. Firstly, AD model was generated by the intracerebroventricular (ICV) injection of the Β-amyloid 1-42 (Aß1-42) peptide. Subsequently, mice were injected with shRNA adenoviral transduction particles designed to target DJ-1 or Aß1-42 or Aß1-42â¯+â¯shNC or Aß1-42â¯+â¯shRNA against DJ-1. shRNA against DJ-1 were injected into hippocampus of mice (8â¯×â¯104 viral particles for each mice) for seven consecutive days. Immunohistochemistry was performed to detect the accumulation of Aß in the hippocampus of mice, and Hematoxylin-Eosin (HE) staining assay was carried to detect pathological changes in the hippocampus of mice. Further, sh-IKKß, shDJ-1, pcDNA-IKKß and pcDNA-DJ-1 plasmids were transfected into HT-22 cells, MTT assay, TUNEL staining and Hoechst staining were performed to detect cell viability and apoptosis, respectively. Western blotting was carried to measure the relative expression of proteins. Findings indicated that Aß1-42 inhibited autophagy and up-regulated p-Tau protein expression; Overexpression of IKKß and DJ-1 all rescued the autophagy inhibited by Aß1-42 and down-regulated p-Tau protein expression induced by Aß1-42; DJ-1 up-regulated IKKß via p-VHL, further promoted autophagy and reduced the expression of p-Tau protein; DJ-1 knockdown inhibited autophagy and up-regulated p-Tau protein expression, resulting in delayed behavior in mice. In conclusion, IKKß, modulated by DJ-1/p-VHL, reduces p-Tau accumulation via autophagy in AD's disease model. This study may provide theoretical basis for the treatment of AD.
Assuntos
Doença de Alzheimer , Proteínas tau , Peptídeos beta-Amiloides/metabolismo , Animais , Autofagia , Hipocampo/metabolismo , Camundongos , Fragmentos de Peptídeos , Proteínas tau/metabolismoRESUMO
The simulation analysis of the migration path and soil accumulation trend of Cd in paddy soil systems could contribute to improved scientific and reasonable risk decision-making. In this study, based on a regional survey of environmental media in Youxian County, Hunan Province, a pollutant accumulation model (PAM) was built to predict the cumulative trend of Cd in paddy soils. Combined with Monte Carlo simulation, the PAM model was used to evaluate the effectiveness and sustainability of various remediation measures. Results showed that the probability of Cd accumulation in paddy soils in Youxian County exceeded that of the national soil environmental quality standard by 2-fold and was up to 82.1%, and the average accumulation rate reached 4.28 µg·(kg·a)-1 after 50 years of cultivation under current input pattern. Sensitivity analysis results showed that atmospheric deposition and rice uptake were the key processes affecting Cd accumulation in paddy soils. Results of a multi-scenario simulation showed that the comprehensive measures, such as reducing the straw returning, optimizing the layout of industrial and mining enterprises that reduce the atmospheric deposition of Cd, and cleaning irrigation water, could reduce the Cd accumulation in paddy soils by 43.7% and reduce the probability of light Cd pollution by 80.6% after 50 years, which would be an effective long-term measure to prevent and control Cd pollution risk in paddy soils.
RESUMO
Aim: We aimed to evaluate the capacity of the bilayer polylactic-co-glycolic acid (PLGA)/TGF-ß3/adipose-derived mesenchymal stem cell (ADSC) construct used to repair cartilage defects and the role of ADSCs in the repair process in vivo. Materials & methods: Defects were created surgically on the femoropatellar groove of knee joints in 64 rabbits. All the rabbits were randomly divided into four groups: defect group, PLGA group, PLGA/TGF-ß3 group and PLGA/TGF-ß3/ADSC group. In vivo MRI and Prussian blue staining were applied. Quantitative real-time PCR and western blot methods were used to analyze the gene and protein expression. Results & conclusion: The result showed that TGF-ß3 could effectively stimulate the expressions of aggrecan, collagen type II and SRY-related HMG box 9 (SOX9). The bilayer PLGA/TGF-ß3/ADSC construct showed a promising repair effect.
Assuntos
Doenças das Cartilagens/terapia , Cartilagem Articular/fisiologia , Nanopartículas Magnéticas de Óxido de Ferro/química , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Fator de Crescimento Transformador beta3/metabolismo , Animais , Cartilagem Articular/lesões , Diferenciação Celular , Células Cultivadas , Bicamadas Lipídicas/química , Coelhos , Engenharia Tecidual , Alicerces Teciduais/química , Fator de Crescimento Transformador beta3/químicaRESUMO
Early warning of soil environmental quality is an important basis for implementing classified and graded soil risk management measures. To quickly understand the regional soil environmental quality and take effective measures in time to prevent continuous soil pollution before deterioration of soil environmental quality, a simple, effective, and quantifiable early warning system for soil environmental quality of agricultural land and development land was respectively established based on environmental capacity and pollutant input-output flux theory. Furthermore, corresponding method and mechanism for early warning were defined based on soil environmental quality standards, food safety standards, and carcinogenic risk coefficients. The agricultural land in Youxian county and the development area within the fifth-ring in Beijing were chosen to assess the soil environmental quality and predict risks of heavy metals exceeding standards in different scenarios. The results show that the soil environmental quality of the agricultural land in Wangling and Taoshui Town both can be classified to the fifth early warning level. Compared with other remediation measures, the Cd contents of soil can be lowered to risk screening levels in the short term by the scenario of "paddy straw not returned to the field". The soil quality in the development area within the fifth-ring in Beijing belongs to the first early warning level under both the "no intervention" and the "decreased input" scenarios, which means that Cd, Cu, Pb, and Zn all need more than 50 years to reach their threshold values to pose potential health risks.
RESUMO
The aim of this study was to observe dynamic changes in immunological parameters and levels of inflammatory factors from pre-radiotherapy to post-radiotherapy in patients with esophageal cancer, and to evaluate the related clinical prognosis. In all, 110 patients with esophageal cancer who underwent radiotherapy were enrolled. Before radiotherapy, post-radiotherapy, and 3 months after radiotherapy, the percentages of T lymphocyte subsets and natural killer (NK) cells in peripheral blood were detected using flow cytometry. The levels of serum inflammatory factors were measured with the enzyme-linked immunosorbent assay (ELISA). Thirty peripheral blood samples from healthy people were similarly analysed as the control. Before radiotherapy, the percentages of CD4+ and CD8+ T cells and NK cells, and the CD4+/CD8+ rate in esophageal cancer patients were significantly different from those in the healthy control group (P < 0.001); the levels of inflammatory factors were increased significantly (P < 0.001). The percentages of the above cells and the levels of inflammatory factors also differed statistically significantly between pre- and post-radiotherapy (P < 0.001) in the esophageal cancer patients. Three months after radiotherapy, the percentages of CD3+ (P = 0.453), CD4+ (P = 0.108), and CD8+ T cells (P = 0.163) and NK cells (P = 0.103) had recovered to the level before radiotherapy; and the levels of TNF-α (P = 0.101), IL-6 (P = 0.302) and IL-8 (P = 0.250) were also restored. After radiotherapy, alterations in immunological parameters were associated with the irradiation volume and the myelosuppression condition. Patients with recovered immunological parameters showed a longer median survival time than those with poor recovery of immunological parameters. For esophageal cancer patients who were immunosuppressive and had an activated inflammatory response before radiotherapy, radiotherapy aggravated these symptoms, and this aggravation was positively associated with myelosuppression and irradiation volume. In addition, recovery of the immunological parameters indicated better prognosis.
Assuntos
Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/radioterapia , Mediadores da Inflamação/metabolismo , Inflamação/patologia , Adulto , Idoso , Neoplasias Esofágicas/patologia , Feminino , Humanos , Terapia de Imunossupressão , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Subpopulações de Linfócitos T/imunologiaRESUMO
BACKGROUND: The expression of follistatin-like protein 1 (FSTL1) is closely associated with diseases of the musculoskeletal system. However, despite being a well characterized inflammatory mediator, the effects of FSTL1 on chondrocytes are not completely understood. In this study, we investigated the effects of FSTL1 on the expression of inflammatory and catabolic factors in rat chondrocytes. METHODS: Rat chondrocytes were treated directly with various concentrations of FSTL1 in vitro. The levels of matrix metalloproteinases (MMPs), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1ß, tumour necrosis factor (TNF)-α and IL-6 were measured by polymerase chain reaction, ELISA and Western blotting. In addition, activation of the nuclear factor kappa B (NF-κB) pathway was explored to identify potential regulatory mechanisms. RESULTS: Follistatin-like protein 1 directly increased the expression of MMP-1, MMP-13, iNOS, COX-2, IL-1ß, TNF-α and IL-6 at both gene and protein level in a dose-dependent manner. Activation of NF- κB and phosphorylation of p65 were also promoted by FSTL1 stimulation. CONCLUSIONS: Follistatin-like protein 1 exerts pro-inflammatory and catabolic effects on cultured chondrocytes via activation of the NF-κB signalling pathway. FSTL1 may therefore be a target in the treatment of OA.
Assuntos
Condrócitos/efeitos dos fármacos , Proteínas Relacionadas à Folistatina/farmacologia , Mediadores da Inflamação/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Condrócitos/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Expressão Gênica/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The effect of attapulgite (magnesium aluminium phyllosilicate) and its modified materials on the extractability of soil Cd and the accumulation of Cd in lettuce (Lactuca sativa) were investigated using a pot-culture experiment, and the immobilization mechanism of attapulgite and its modified materials was explored through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The results showed that attapulgite and its modified materials could significantly reduce the Cd concentration in Lactuca sativa, with maximum reductions of 41.0% and 56.5%, respectively, and attapulgite modified materials treatments appeared more efficient than attapulgite treatments in reducing Cd uptake of Lactuca sativa. The saturated adsorption capacity for the adsorption of Cd2+ on attapulgite rose distinctly after being modified. Attapulgite and its modified materials could significantly reduce Cd content in soil CaCl2 extract at the dosage of 1%, with the maximum reduction rates of 34.2% and 34.3%, respectively. The attapulgite formed a complex to immobilize Cd mainly through the surface silanol and Cd2+ complexation reaction, while the modified attapulgite formed a complex mainly through the complexation of Cd2+ with carboxyl groups which existed in addition to the complexation with surface hydroxyl, thus reducing the mobility of Cd2+ and achieving remediation of Cd-contaminated soil. In summary, attapulgite and its modified materials can both be used for remediation of Cd-contaminated soil, and the mechanisms for this function were found to be different.
Assuntos
Disponibilidade Biológica , Cádmio/análise , Compostos de Magnésio/química , Compostos de Silício/química , Poluentes do Solo/análise , Lactuca/química , SoloRESUMO
Pollution from organochlorine (OCP) and organophosphorus (OPP) pesticides in groundwater is a key issue for water resource protection. Sixteen kinds of OCP and six kinds of OPP pesticides were detected in 18 groundwater samples determined by GC-MS. Results showed that seven kinds of OPCs and two kinds of OPPs were found in the groundwater in Beijing. Among the OCPs, there were mainly hexachlorobenzene (HCB), hemochromatosis (HCH), and dichlorodiphenyltrichloroethane (DDT), with maximum values of, respectively, 82.4, 193, and 158 ng·L-1. Among the OPPs, there were o, o-dimethyl-o-2,2-dichlorovinylphosphate and o,o-dimethyl methylcarbamoylmethyl phosphorodithioate, with maximum values of 7.1 ng·L-1 and 17.7 ng·L-1, respectively. The OCPs and OPPs were found in the sewage irrigation areas. The results of a probabilistic risk assessment showed that the non-carcinogenic and carcinogenic risks of OCPs and OPPs within the drinking water in Beijing had been controlled, that risks from OCPs were higher, and that women were more sensitive to the toxicity of the pesticides. The monitoring of HCH and DDT in the groundwater should be implemented.
Assuntos
Água Subterrânea/análise , Hidrocarbonetos Clorados/análise , Praguicidas/análise , Poluentes Químicos da Água/análise , Pequim , Monitoramento Ambiental , Medição de RiscoRESUMO
Apoptosis serves a pivotal role in the pathogenesis of osteoarthritis (OA). Increasing evidence has demonstrated that paeoniflorin exerts key properties (including anticancer, anti-inflammation and neuroprotective) for clinical applications. However, the precise role of paeoniflorin in articular cartilage apoptosis remains unknown. The present study explored the effects and potential molecular mechanism of paeoniflorin on rat chondrocyte apoptosis. Rat articular chondrocytes were cultured in monolayers. The lactate dehydrogenase (LDH) release rate of cells was determined by an LDH release assay. Annexin V-fluorescein isothiocyanate and propidium iodide staining were performed to detect early and advanced apoptotic cells by flow cytometry. The activity of caspase-3 in chondrocytes was determined using a caspase-3 activity assay. The expression of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) was examined by reverse transcriptionquantitative polymerase chain and western blotting. The present study also examined the protein kinase B (Akt) signaling pathway by western blotting. Treatment with 25 or 50 µM paeoniflorin markedly decreased the release of LDH and the ratio of apoptotic cells in interleukin (IL)-1ß-induced rat chondrocytes. Paeoniflorin treatment decreased the mRNA and protein levels of Bax, and increased the level of Bcl-2. Paeoniflorin also reduced the activity of caspase-3 in chondrocytes. Furthermore, paeoniflorin was determined to regulate the Akt signaling pathway by increasing Akt phosphorylation. Therefore, paeoniflorin may exert its protective effect by inhibiting apoptosis in IL-1ß-induced rat chondrocytes and thus, may be an effective agent in the prevention and treatment of OA.
Assuntos
Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Glucosídeos/farmacologia , Interleucina-1beta/metabolismo , Monoterpenos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Animais , Cartilagem Articular/citologia , Células Cultivadas , Interleucina-1beta/farmacologia , L-Lactato Desidrogenase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Ratos , Proteína X Associada a bcl-2/genéticaRESUMO
Objective To study the effect of Water Extract of Ginseng (WEG) on the prolifera- tion/metastasis of lung cancer A549 cells and the expression of F-actin in co-culture system of tumor as- sociated macrophages (TAMs) and A549 cells. Methods Human acute leukemia mononuclear strain THP-1 was induced to become TAMs using Phorbol-12-myristate-13-acetate (PMA) combined IL-4 and IL- 13. The supernant of TAMs and A549 cells were co-cultured. A co-culture model was set up by simulating microenvironment of lung cancer. Then cells were divided into the blank control group (A549) , the co- culture group (A549 +TAMs) , high, middle, and low dose WEG groups (TAMs +A549 + high, middle, and low dose WEG). The effects of WEG on the proliferation/metastasis of lung cancer A549 cells and the expression of F-actin under various conditions were detected using MTT method, Real time cell analysis (RTCA) , and high content screening (HCS). Results Compared with the blank control group, the pro- liferation of A549 cells was obviously increased, cell migration was obviously elevated, and the area of cell skeleton was markedly enlarged in the TAMs + A549 group, with statistical difference (P <0. 05). Compared with the TAMs +A549 group, the proliferation and migration of A549 cells were inhibited, the area of cell skeleton and the number of microfilaments were reduced dose-dependently (P <0. 05). Conclusion WEG could effectively inhibit the proliferation and migration of A549 cells, which might be a- chieved by adjusting immunoactivities of TAMs, and further it affected biological behaviors of tumor cells.
Assuntos
Actinas , Neoplasias Pulmonares , Panax , Extratos Vegetais , Células A549 , Citoesqueleto de Actina , Actinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Cocultura , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Macrófagos/metabolismo , Extratos Vegetais/farmacologia , ÁguaRESUMO
The consumption of vegetables is a probable cause of Cd exposure in several world areas including China.In this study,we selected the prefecture of Youxian,southern China,as a case to analyze the influences of various environmental factors on Cd accumulation in vegetables based on a large scale agricultural and climatologically survey and collection of 585 irrigation water and 625 paired soil-vegetables samples.The results showed the concentration of Cd differed greatly in the irrigation water,soil and vegetables.The average daily dose for the adult populations consumed vegetables cropping in affected areas was slightly above the tolerable daily intake level,suggesting a potential health risk.The vegetables Cd uptake factor followed the natural lognormal distribution,and had a 10 percentile probability of higher than 1.The PUF values exhibited comparable results and appeared to define a reasonable and consistent Cd risk assessment.Many environmental variables (soil pH,soil organic matter,cation-exchange capacity,rainfall,water pH,and nitrogenous fertilizer usage) exhibited significant correlations with the concentrations of Cd in the soil-vegetable system.The canonical corresponding analysis and path model analysis found that soil pH and soil organic matter (SOM) had major direct effects on PUF.The close correlations between rainfall,water pH,nitrogen fertilizer usage and PUF were mainly resuled from the direct effect of soil pH and SOM.The high field-moisture capacity in the study area generated a rapid acidification causing the migration of Cd to weaker bounding sites thus promoting the vegetables uptake.The excessive application of nitrogen fertilizers led to a substantial loss of SOM and worsening of soil acidification ultimately causing increasing Cd accumulation in vegetables.Considering that the soil pH and SOM in the study area were maintained at a low level,the accumulation risk of Cd in soil-vegetable system needs to be addressed.The influence of environmental factors on vegetables accumulating Cd needs to be fully considered for better and safer vegetables production.
Assuntos
Cádmio/análise , Exposição Dietética/análise , Poluentes do Solo/análise , Verduras/química , Adulto , China , Monitoramento Ambiental , Humanos , SoloRESUMO
Cadmium (Cd) can cause adverse health effects and is a subject of concern in rice consumption. The uncertainty analysis helps improve the accuracy in the risk assessment for Cd in soil-rice system. A regional investigation on Youxian prefecture, southern China, was conducted to analyze the Cd concentration in rice. Based on the species sensitivity distribution model (SSD), health risk assessment model, and Monte Carlo simulation, the accumulation characteristic of Cd in soil-rice system, accumulation risk of Cd in soil, and health risk of Cd concentration in rice were determined. The results showed that the plant uptake factor (PUF) of Cd of rice was well fitted by the SSD model. The mean level of PUF was 1.86, with a significant spatial heterogeneity. The rice produced in WL county tended to accumulate a high level of Cd. There was no significant relationship between concentrations of Cd in soil and rice, suggesting that of rice renders the Cd risk management very difficult. The pollution load index of Cd in soil was 2.4, which belonged to a moderate contamination level. Under current accumulation condition of Cd in soil, there would be a 90.4% probability for soil Cd concentration to be higher than the national soil quality standard after 10 years. Health risk assessment showed that the average daily dose (ADD) was 2.9 µg·(kg·d)-1, 3.5 fold higher than the WHO limit. About 93.9% of the adult populations consuming rice cropping in affected areas had the risk that the daily Cd intake was above the WHO limit. The health risk index (HRI) was around 2.1 to 4.7. The probability for health risk index (HRI) higher than 5 was 21.5%, suggesting a high health risk. When the soil pH was lower than 5.5, the probability for HRI higher than 1 was 95.3%, and when the soil pH was higher than 6, the probability for HRI higher than 1 reduced to 68.1%. An improved management of soil pH values would be needed for a better and safer rice production. The combination of uncertainty analysis, species sensitivity model and health risk assessment model was validated to be feasible and reliable in the risk analysis.
Assuntos
Cádmio/análise , Exposição Ambiental/análise , Oryza , Poluentes do Solo/análise , Adulto , China , Humanos , Medição de Risco , Solo , IncertezaRESUMO
This paper was aimed to investigate the microRNA associated with multidrug resistance gene MDR1 of salvianolic acid A reversal in lung cance. Human lung cancer A549 cells were divided into normal control group and drug group, and the MDR1 expression levels were determined by real-time quantitative PCR. MicroRNA expression profiling of normal control group and drug group were detected by using the latest microRNA microarray. Quantitative RT-PCR was used to validate the differentially expressed miRNA. Forecast of miRNA associated with MDR1 multi-resistant genes of up-regulated miRNA. Experimental results showed that the dosage of MDR1 expression level significantly lowered compared with control group. The miRNA expression spectrum analyses of human lung cancer A549 cells to drug group and the control group were detected by microRNA microarray, 426 differentially expressed miRNA were screened out. Then target prediction were performed for difference up-expression of miRNA and found that there were four obvious increase of miRNA associated with MDR1 multi-resistant genes. Real-time quantitative PCR for 4 microRNA verification, the results were consistent with the chip. So the author considered that salvianolic acid A down lung cancer multidrug resistance gene MDR1 is likely to be affected by the miRNA expression and regulation of target genes, to further clarify the traditional Chinese medicine to reverse multi-drug resistant mechanism provides the experimental basis.
Assuntos
Ácidos Cafeicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Genes MDR , Lactatos/farmacologia , Neoplasias Pulmonares/genética , MicroRNAs/genética , Células A549 , Resistência a Múltiplos Medicamentos/genética , HumanosRESUMO
It is well known that rheumatoid arthritis (RA) is an autoimmune joint disease in which fibroblast-like synoviocytes (FLSs) play a pivotal role. In this study, we investigated the anti-arthritic properties of acacetin in FLSs. The expression of matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13 were investigated by quantitative RT-PCR and western blot at gene and protein levels. At the same time, the phosphorylation of mitogen-activated protein kinases (MAPK) was investigated. The DNA-binding activity of NF-κB was investigated by electrophoretic mobility shift assay. We found that acacetin inhibits p38 and JNK phosphorylation and reduces MMP-1, MMP-3 and MMP-13 expression in interleukin-1ß-induced FLSs. Our results suggest that acacetin has antiarthritic effects in FLSs. Thus, acacetin should be further studied for the treatment of arthritis.