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Background: Electroacupuncture (EA) has been shown to promote functional recovery after cerebral ischemia-reperfusion (I/R) injury. However, the contribution of mitochondrial dynamics to recovery remains unclear. The aim of this study was to investigate whether mitochondrial dynamics are involved in the effects of EA on cerebral I/R injury. Methods: The rats with cerebral I/R injury were established by the middle cerebral artery occlusion/reperfusion. Subsequently, EA was applied to Baihui (GV20) and Dazhui (GV14) acupoints, with 2 Hz/5 Hz in frequency, 1.0 mA in intensity, 20 min each time, once a day for seven consecutive days. The therapeutic outcomes were assessed by modified neurological severity score (mNSS), 2,3,5-Triphenyte-trazolium chloride (TTC) staining, and hematoxylin-eosin (HE) staining. Mitochondrial morphology was observed under transmission electron microscopy. Adenosine triphosphate (ATP) content and ATP synthases (ATPases) activity were evaluated to measure mitochondrial function using ELISA. Finally, mitochondrial dynamics-related molecules, including dynamin-related protein 1 (Drp1), fission 1 (Fis1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (OPA1), were detected by Western blot and immunofluorescence staining. Results: Cerebral I/R injury induced neurological dysfunction, cerebral infarction and neuronal injury, all of which were ameliorated by EA. And EA improved mitochondrial morphology and function. Moreover, EA altered the balance of mitochondrial dynamics. Specifically, the data showed a significant decrease in the expression of Drp1 and Fis1, leading to the inhibition of mitochondrial fission. Additionally, Mfn1, Mfn2 and Opa1, which are related to mitochondrial fusion, were effectively promoted after EA treatment. However, sham EA did not show any neuroprotective effects in rats with cerebral I/R injury. Conclusions: In summary, our study indicates that the balance of mitochondrial dynamics is crucial for EA therapy to treat cerebral I/R injury.
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BACKGROUND: Colorectal polyps are frequently observed in patients with type 2 diabetes mellitus (DM), posing a significant risk for colorectal cancer. Metformin, a widely prescribed biguanidine drug for type 2 DM, has been suggested to have potential chemoprophylactic effects against various cancers. AIM: To explore the correlation between colorectal polyps and metformin use in type 2 DM patients. METHODS: Type 2 DM patients were categorized into polyp and non-polyp groups. Following this, all patients were categorized into the type 2 DM-metformin, type 2 DM-non-metformin, and non-type 2 DM groups. Based on the baseline colonoscopy results, we performed pairwise comparisons of the incidence of colorectal polyps among the three groups. Additionally, we analyzed the relationship between colorectal polyps and the duration of metformin use and between the size and number of polyps and metformin use. Simultaneously, we focused on the specific pathological types of polyps and analyzed their relationship with metformin use. Finally, we compared the incidence of polyps between metformin and non-metformin groups according to the interval colonoscopy results. RESULTS: The rate of metformin use in patients with colorectal polyps was 0.502 times that of patients without colorectal polyps [odds ratio (OR) = 0.502, 95% confidence interval (CI): 0.365-0.689; P < 0.001]. The incidence of colorectal polyps did not differ significantly between the type 2 DM-metformin and non-type 2 DM groups (P > 0.05). Furthermore, the correlations between the duration of metformin use and the incidence of colorectal polyps and between the size and number of polyps and metformin use were not statistically significant (P > 0.05). Metformin use did not affect the incidence of colorectal polyps during interval colonoscopy (P > 0.05). CONCLUSION: Metformin use and colorectal polyp incidence in type 2 DM patients showed a negative correlation, independent of the hypoglycemic effect of metformin.
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Green finance (GF) has emerged as a promising tool to promote low-carbon development, while knowledge is rather limited regarding the underlying mechanism. This article aims to address this void by constructing a city-level GF index covering seven dimensions and identifying the main pathways through which GF can facilitate the low-carbon development of cities. Using a balanced panel data covering 277 Chinese cities from 2010 to 2020, the results show that: (1) China's GF development exhibits an overall spatial differentiation of 'high in the east and low in the west', while the distribution of carbon intensity (CI) displays an overall spatial differentiation of 'high in the north and low in the south'; (2) GF significantly decreases CI of cities, which is robust to employing DID strategies and IV estimations; (3) The role of GF on CI varies with the level of CI whereas not with the level of GF. Specifically, the mitigating effect of GF on CI is significant in both high GF and low GF groups, but only in high CI group; and (4) GF promotes low-carbon transition of cities through mainly on adjusting industrial structure rather than stimulating technological innovation. Despite we also demonstrate green finance enhances green innovation, due to multi-factors, such technology progress it brings may not always translate into a tangible improvement in green productivity. For most developing countries including China, the future policy objective of green finance should focus on enhancing sustainable technological progress.
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PURPOSE: We evaluated the value of copy number variation sequencing (CNV-seq) and quantitative fluorescence (QF)-PCR for analyzing chromosomal abnormalities (CA) in spontaneous abortion specimens. METHODS: A total of 650 products of conception (POCs) were collected from spontaneous abortion between April 2018 and May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. The clinical features of the patients were recorded. RESULTS: Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, of which 217 (33.4%) were autosomal trisomies, 42(6.5%) were chromosomal monosomies and 40 (6.2%) were pathogenic CNVs (pCNVs). Chromosomal trisomy occurs mainly on chromosomes 15, 16, 18, 21and 22. Monosomy X was not associated with the maternal or gestational age. The frequency of chromosomal abnormalities in miscarriages from women with a normal live birth history was 55.3%; it was 54.4% from women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and with ≥ 2 previous miscarriages regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 and 30-34 years (P < 0.05). CONCLUSION: Chromosomal abnormalities are the most common cause of pregnancy loss, and maternal and gestational ages are strongly associated with fetal autosomal trisomy aberrations. Embryo chromosomal examination is recommended regardless of the gestational age, modes of conception or previous abortion status.
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Aborto Espontâneo , Síndrome de Turner , Gravidez , Humanos , Feminino , Aborto Espontâneo/genética , Variações do Número de Cópias de DNA , Trissomia/genética , Aberrações CromossômicasRESUMO
As a new type of progressive energy release propellant, nitro gradiently distributed propellant (NGDP) was prepared by a denitration reaction between a denitration reagent and the propellant to remove the energy-containing functional group (-O-NO2) from the surface of the propellant. The kinetics of the denitration reaction determines distribution of the nitrate group in the surface layer of NGDP, which further affects the combustion progressivity. In this paper, the kinetic model for the denitration reaction process of the cylindrical single-base gun propellant was studied by the shrinking unreacted core model (SUC model). The energy change of the propellant particles before and after the denitration reaction was used to evaluate the denitration rates, which were used to fit the proposed SUC cylindrical model. The results show that the rate-controlling step of the denitration reaction process is largely dependent on the concentration of the denitration reagent. At low concentrations (the concentration of the denitration reagent was 6%), the denitration reaction process was controlled by the chemical reaction, and the activation energy was found to be 48.40 kJ·mol-1. When the concentration increased (the concentration of the denitration reagent was 15%), the rate-controlling step changed to a solid product layer diffusion control with an activation energy of 84.77 kJ·mol-1. The kinetic models obtained in this study can provide theoretical guidance for the controlled preparation of NGDP with good combustion progressivity.
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Environmental attitude, value and awareness are widely believed to help reach the goal of cutting global food waste, but these psychological and cognitive factors are not always good predictors of wasteful behaviours. Notably, it is still unclear how the role of pro-environmental attitude (PEA) in reducing household food waste (HFW) changes with grocery shopping distance. To this end, using 7319 households survey data from China, this study investigates the moderating effect of shopping distance on the link between PEA and HFW behaviour. The results of Tobit regressions show that PEA is an important predictor of actual HFW behaviour in the absence of the constraint of shopping distance. However, the expansion of shopping distance will weaken the positive role of PEA in reducing HFW. It indicates that, due to the temporal and financial constraints generated by shopping distance, there is a certain degree of hypothetical deviation between the wasteful behaviours that individuals actually exhibit and their stated PEA. Our findings, from the perspective of the moderating effect of shopping distance, explain why some individuals deviate from their stated PEA in HFW behaviour, which provides a new insight into the generation of 'attitude-behaviour' gap. Therefore, policy interventions that merely enhancing environmental education may have limited effect on reducing food waste; instead, the promotion of citizen environmental ethics should be combined with efforts to improve the accessibility of retail infrastructures.
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The existing evidence on the environmental effects of vehicular emissions regulation almost comes from developed countries, but the effectiveness of this policy tool in developing countries, especially in China, remains unclear. This study, for the first time, examined the mitigating effects of China's vehicular emissions regulation on air pollution at the prefecture level cities, by using the latest implementation of China's National Vehicular Emissions Standard VI (CHINA-VI) as a quasi-natural experimental process of policy shocks. To this end, monthly data from 2018 to 2020 was applied to construct a difference-in-differences (DID) model. The results showed that pilot cities' air quality index (AQI) significantly decreased by 4.74 compared to non-pilot cities after the implementation of CHINA-VI. Also, the concentration of PM2.5, PM10, and O3 has decreased by 3.6 µg∕m3, 6.4 µg∕m3, and 3.0 µg∕m3, respectively, which means the new China's vehicular emissions regulation has comprehensively improved air quality. The findings are still valid after a series of robustness tests using different estimation methods such as PSM-DID and IV-2SLS. In addition, we also found heterogeneity in the environmental performance of CHINA-VI across cities. Specifically, cities with lower levels of green finance development and public environmental concern showed a greater emissions reduction effect, but smart cities showed a greater emissions reduction effect than non-smart cities.
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Poluentes Atmosféricos , Poluição do Ar , Emissões de Veículos/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , CidadesRESUMO
OBJECTIVE: To observe the effect of electroacupunctureï¼EAï¼preconditioning on ferroptosis in rats with cerebral ischemia-reperfusion injury ï¼CIRIï¼, so as to explore the neuroprotective mechanism of EA preconditioning. METHODS: Male SD rats were randomly divided into sham operation, model, EA, inhibitor and inducer groups with 20 rats in each group. The CIRI model was established by modified Zea Longa occlusion of the middle cerebral artery. Before modeling, EA treatment ï¼2 Hz/15 Hz, 1-2 mAï¼ was applied to "Baihui"ï¼GV20ï¼, "Fengfu"ï¼GV16ï¼ and "Dazhui"ï¼GV14ï¼ for rats of the EA group, 20 min a day for 7 consecutive days. Rats of the inhibitor group were intraperitoneally injected with ferristatin-1ï¼25 mg/kgï¼at a slow and uniform rate. Rats of the inducer group were intraperitoneally injected with Erastinï¼100 mg/kgï¼ after 7 days of EA preconditioning, once every 2 h for a total of 4 times. The CIRI models were prepared 2 d later after the above interventions finished by thread-occlusion. The degree of neurological impairment was evaluated by modified Zea Longa score. The percentage of infarct size was calculated by TTC staining. The ultrastructure of neurons in hippocampus was observed by transmission electron microscope. The contents of ferrous ion ï¼Fe2+ï¼, malondialdehyde ï¼MDAï¼ and glutathione ï¼GSHï¼ in cerebral tissue and reactive oxygen species ï¼ROSï¼ in serum were determined by biochemical method. The changes of mitochondrial membrane potential in rats brain tissues were detected by flow cytometry. The mRNA and protein expression levels of glutathione peroxidase 4 ï¼GPX4ï¼, acyl-CoA synthetase long-chain family member 4 ï¼ACSL4ï¼, transferrin receptor ï¼TFRCï¼, 15-lipoxygenase ï¼15-LOXï¼ and cyclooxygenase-2 ï¼COX-2ï¼ in the ischemic hippocampal region of CIRI rats were detected by real-time quantitative PCR and Western blot, respectively. RESULTS: Compared with the sham operation group, the neurological impairment score, the percentage of cerebral infarction area, the contents of MDA and Fe2+ in cerebral tissue as well as ROS in serum, the protein and mRNA expression levels of ACSL4, TFRC, 15-LOX, COX-2 in hippocampal tissue were increased ï¼P<0.01ï¼, while the content of GSH in cerebral tissue, the protein and mRNA expression levels of GPX4 in hippocampal tissue were decreased ï¼P<0.01ï¼, and mitochondria in brain tissue were significantly damaged ï¼P<0.01ï¼ in the model group. Compared with the model group, the above indexes were all reversed ï¼P<0.05, P<0.01ï¼ in the EA group and inhibitor group. Compared with the EA group, the neurological impairment score, the percentage of cerebral infarction area, the contents of MDA and Fe2+ in cerebral tissue as well as ROS in serum, the protein and mRNA expression le-vels of ACSL4, TFRC, 15-LOX, COX-2 in hippocampal tissue were increased ï¼P<0.05, P<0.01ï¼, while the content of GSH in cerebral tissue, the protein and mRNA expression levels of GPX4 in hippocampal tissue were decreased ï¼P<0.01, P<0.05ï¼, and mitochondria in brain tissue were significantly damaged ï¼P<0.05ï¼ in the inducer group. CONCLUSION: EA preconditioning has neuroprotective effect on CIRI rats, which may be related to inhibiting ACSL4/TFRC/15-LOX/COX-2 expression and increasing GSH/GPX4 expression.
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Eletroacupuntura , Ferroptose , Traumatismo por Reperfusão , Animais , Masculino , Ratos , Infarto Cerebral , Ciclo-Oxigenase 2 , Ferroptose/genética , Neurônios , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/terapiaRESUMO
OBJECTIVE: To observe the effect of Tongdu Tiaoshen (promoting the circulation of the governor vessel and regulating the spirit) electroacupuncture (EA) pretreatment on pyroptosis mediated by peroxisome proliferators-activated receptor γ (PPARγ) of the cerebral cortex in rats with cerebral ischemia reperfusion injury (CIRI) and explore the potential mechanism of EA for the prevention and treatment of CIRI. METHODS: A total of 110 clean-grade male SD rats were randomly divided into a sham-operation group, a model group, an EA group, an EA + inhibitor group and an agonist group, 22 rats in each group. In the EA group, before modeling, EA was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14), with disperse-dense wave, 2 Hz/5 Hz in frequency, 1 to 2 mA in intensity, lasting 20 min; once a day, consecutively for 7 days. On the base of the intervention as the EA group, on the day 7, the intraperitoneal injection with the PPARγ inhibitor, GW9662 (10 mg/kg) was delivered in the EA + inhibitor group. In the agonist group, on the day 7, the PPARγ agonist, pioglitazone hydrochloride (10 mg/kg) was injected intraperitoneally. At the end of intervention, except the sham-operation group, the modified thread embolization method was adopted to establish the right CIRI model in the rats of the other groups. Using the score of the modified neurological severity score (mNSS), the neurological defect condition of rats was evaluated. TTC staining was adopted to detect the relative cerebral infarction volume of rat, TUNEL staining was used to detect apoptosis of cerebral cortical nerve cells and the transmission electron microscope was used to observe pyroptosis of cerebral cortical neural cells. The positive expression of PPARγ and nucleotide-binding to oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex was detected with the immunofluorescence staining. The protein expression of PPARγ, NLRP3, cysteinyl aspartate specific protease-1 (caspase-1), gasdermin D (GSDMD) and GSDMD-N terminal (GSDMD-N) in the cerebral cortex was detected with Western blot. Using the quantitative real-time fluorescence-PCR, the mRNA expression of PPARγ, NLRP3, caspase-1 and GSDMD of the cerebral cortex was detected. The contents of interleukin (IL)-1ß and IL-18 in the cerebral cortex of rats were determined by ELISA. RESULTS: Compared with the sham-operation group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.01), pyroptosis was severe, the protein and mRNA expression levels of PPARγ, NLRP3, caspase-1 and GSDMD were elevated (P<0.01); and the protein expression of GSDMD-N and contents of IL-1ß and IL-18 were increased (P<0.01) in the model group. When compared with the model group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1ß and IL-18 were lower (P<0.01) in the EA group and the agonist group; while, in the EA + inhibitor group, the protein expression of PPARγ was increased (P<0.01), the protein and mRNA expression levels of NLRP3 and GSDMD were decreased (P<0.01, P<0.05), the mRNA expression of caspase-1 was reduced (P<0.01); and the contents of IL-1ß and IL-18 were lower (P<0.01). When compared with the EA + inhibitor group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.05, P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1ß and IL-18 were declined (P<0.01) in the EA group. Compared with the agonist group, in the EA group, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.05, P<0.01), the mRNA expression of PPARγ was decreased (P<0.01) and the protein expression of GSDMD-N was elevated (P<0.05); and the contents of IL-1ß and IL-18 were higher (P<0.01). CONCLUSION: Tongdu Tiaoshen EA pretreatment can attenuate the neurological impairment in the rats with CIRI, and the underlying mechanism is related to the up-regulation of PPARγ inducing the inhibition of NLRP3 in the cerebral cortex of rats so that pyroptosis is affected.
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Eletroacupuntura , PPAR gama , Masculino , Animais , Ratos , Ratos Sprague-Dawley , PPAR gama/genética , Piroptose , Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Córtex Cerebral , Infarto Cerebral/genética , Infarto Cerebral/terapia , Caspases , RNA MensageiroRESUMO
BACKGROUND: The incidence of blunt abdominal injury has significantly increased, and the liver is one of the most commonly damaged organs. In this study, we explored and established a nomogram model for patients with liver ruptures undergoing surgical treatment. METHODS: A retrospective analysis was conducted for 66 adult patients with liver rupture, who were admitted to our hospital from January 2011 to October 2018. These patients were classified into two groups, according to whether the patient had surgery: surgery group (41 cases) and non-surgical group (25 cases). The following data were collected from these two groups of patients: gender, age, injury mechanism, liver damage, laboratory test results, and hospitalization. Multivariate logistic regression analysis was performed to screen the risk factors of patients who require surgical treatment, establish a predictive model based on the selected indicators, and draw the nomogram. Receiver operating characteristic curves and the calibration curve were used to evaluate the predictive value of the model. RESULTS: Compared to the non-surgical group, the body temperature decreased, the heart rate increased, the injury severity score grade increased, the blood urea nitrogen, blood uric acid, creatinine (Cr), arterial partial pressure of oxygen, alkali excess, blood lactic acid and creatine kinase isoenzymes MB (CK-MB) increased, and the HCO- and Glasgow Coma Scale (GCS) coma scores decreased for patients in the surgical group (all, p<0.05). The logistic regression analysis revealed that Cr, arterial partial pressure of oxygen, HCO3-, CK-MB, and the Glasgow coma score were the influencing factors for surgical intervention for liver rupture. The nomo-gram model constructed based on these five indicators had a good degree of discrimination (area under the curve = 0.971, 95% CI: 0.896-0.997) and accuracy. CONCLUSION: A nomogram model established based on Cr, arterial partial pressure of oxygen, HCO3-, CK-MB, the GCS, and other parameters can accurately predict the surgical treatment of patients with liver rupture.
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Hepatopatias , Nomogramas , Adulto , Humanos , Estudos Retrospectivos , Coma , Curva ROCRESUMO
The annual burden of severe acute respiratory infection (SARI) is enormous, and environmental factors may have a vital role in respiratory infections. This study aimed to investigate the potential effects of the atmospheric environment on SARI. A time-series analysis was performed on the relationship between atmospheric environment and 136,989 SARI cases by distributed lag non-linear model. Wind speed, PM10, PM2.5, O3, and CO exhibited differential effects at a range of lag times or exposure ranges. Air pressure, temperature, and diurnal temperature range showed risk effects in the full range. The lag effect of high pollution was stronger, appeared earlier, and lasted longer than that of low pollution. Most environmental factors had a certain non-linear lag relationship with SARI. Low wind speed and high air pollution may be increasing risk factors for SARI.
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Poluentes Atmosféricos , Poluição do Ar , Pneumonia , Infecções Respiratórias , Humanos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/induzido quimicamente , Material Particulado/toxicidade , Material Particulado/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análiseRESUMO
Background and Objectives: Oxytocin (OT) is a neuropeptide hormone which is known for its classical effects in pregnancy and lactation. Recently, growing evidence demonstrated a close relation between OT and bone. The present study aimed to explore the relationship between OT, bone and osteoporosis risk in Chinese adult females. Materials and Methods: in total, 149 adult females were enrolled. The serum OT levels were measured using ELISA kits. Bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry (DXA). The study subjects were divided into two groups according to their menopause status and then divided into tertiles based on their serum OT level. Results: Serum OT, serum estradiol and BMD at three skeletal sites were significantly higher in the premenopausal group than in the postmenopausal group (p < 0.001, p = 0.008 and p < 0.001, respectively). In the tertile analysis, relative to tertile 1, significant associations were found for tertile 3 for OT levels and higher BMD in the femoral neck and total hip, in both pre- and postmenopausal groups. Using logistic regression analysis, tertile 3 appeared less likely to have low-BMD osteoporosis than tertile 1 (OR = 0.257, 95% CI = 0.073, 0.910). In multivariate stepwise regression analysis, OT and total lean mass were two positive determinants of BMD in the femoral neck and total hip in the premenopausal group (adjusted R2 for the model = 0.232 and 0.199, respectively; both p < 0.001). Conclusion: Our study demonstrated positive associations between serum OT levels and BMD in a Chinese (non-Caucasian) population. OT appeared to be more strongly associated with hip BMD in premenopausal females. These results may suggest a protective role and potential therapeutic use of OT in osteoporosis, especially for premenopausal women.
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Densidade Óssea , Osteoporose , Adulto , Feminino , Humanos , Ocitocina , Composição Corporal , ChinaRESUMO
Trichoderma isolates were collected from moist soils near a water source in different areas of China. ITS sequences were submitted to MIST (Multiloci Identification System for Trichoderma) and meets the Trichoderma [ITS76] standard. Combined analyses of phylogenetic analyses of both phylograms (tef1-α and rpb2) and morphological characteristics, revealed five new species of Trichoderma, namely Trichodermahailarense, T.macrofasciculatum, T.nordicum, T.shangrilaense and T.vadicola. Phylogenetic analyses showed T.macrofasciculatum and T.shangrilaense belong to the Polysporum clade, T.hailarense, while T.nordicum and T.vadicola belong to the Viride clade. Each new taxon formed a distinct clade in phylogenetic analysis and have unique sequences of tef1-α and rpb2 that meet the Trichoderma new species standard. The conidiation of T.macrofasciculatum typically appeared in white pustules in concentric rings on PDA or MEA and its conidia had one or few distinctly verrucose. Conidiophores of T.shangrilaense are short and rarely branched, phialides usually curved and irregularly disposed. The aerial mycelium of T.hailarense and T.vadicola formed strands to floccose mat, conidiation tardy and scattered in tufts, conidiophores repeatedly rebranching in dendriform structure. The phialides of T.nordicum lageniform are curved on PDA and its conidia are globose to obovoidal and large.
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BACKGROUND: Cancer stem cells (CSCs), responsible for cancer metastasis and recurrence, are generated from non-CSCs after chemo-radiation therapy. This study investigated the induction of CSC potential in non-stem breast cancer cells and the underlying molecular mechanisms in detachment culture. METHODS: Bulk breast cancer cells, or sorted non-CSCs and CSCs were cultured under an attached or detached condition to assess CSC numbers, ability to form tumor spheres, expression of stemness markers, and chemoresistance. Lentivirus carrying CD147 shRNA or cDNA was used to manipulate CD147 expression, while CD147 ligand recombinant cyclophilin A (CyPA) or its inhibitor was used to activate or inhibit CD147 signaling. RESULTS: Detachment promoted anoikis resistance, chemoresistance, sphere formation, self-renewal, and expression of stemness markers in breast cancer cells. Detachment increased functional ALDH+ or CD44highCD24-/low CSCs, and induced CSC potential in ALDH- or CD44 low CD24high non-CSCs. Upon detachment, both CD147 expression and CyPA secretion were enhanced, and CyPA-CD147 activation mediated detachment induced CSC potential in non-CSCs via STAT3 signaling. Clinically, CD147 and pSTAT3 were highly co-expressed and correlated with poor overall survival and tumor recurrence in breast cancer patients. CONCLUSION: This study demonstrates that detachment induces the generation of CSCs from non-stem breast cancer cells via CyPA-CD147 signaling, indicating that targeting CD147 may serve as a potential novel therapeutic strategy for lethal metastatic breast cancer by eliminating induced CSCs.
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Proteínas de Arabidopsis , RNA Polimerases Dirigidas por DNA , Proteínas de Arabidopsis/metabolismo , Metilação de DNA , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Regulação da Expressão Gênica de Plantas , Crescimento e Desenvolvimento , RNA de Plantas/metabolismo , RNA Interferente Pequeno/metabolismoRESUMO
In this study, a series of 4-aniline quinazoline derivatives bearing hydrogen sulfide (H2S) donors were designed, synthesized and evaluated for biological activities. The synthesized compounds were screened for the enzymatic activities against EGFR and EGFR mutants by kinase target-based cell screening method. The results demonstrate that most compounds exhibit selectively inhibitory activities against TEL-EGFR-L858R-BaF3, especially compound 9h with GI50 = 0.008 µM (TEL-EGFR-L858R-BaF3), 0.0069 µM (TEL-EGFR-C797S-BaF3), >10 µM (BaF3), >10 µM (TEL-EGFR-BaF3) and 6.03 µM (TEL-EGFR-T790M-L858R-BaF3). The results from anti-proliferative assays in two NSCLC cell lines indicate that synthetic derivatives (9g, 9h, 15e and 15f) with H2S donor ACS81 display greater anti-proliferative potency against NSCLC cell line H3255 bearing EGFR mutant (L858R) with GI50 values ranging from 0.3486 to 1.348 µM. In addition, compound 9h exhibits weak anti-proliferative effects on other tumor cells (HepG2, MCF-7, HT-29 and A431) and has lower toxic effect on HUVEC cells than AZD9291 (positive control). Meanwhile, compound 9h inhibits the phosphorylation of EGFR in H3255 cells in a dose-dependent manner. Cell cycle analysis reveals that compound 9h suppresses the proliferation of cells by inducing cell cycle arrest in G0-G1 phase. The result of H2S release evaluation suggests that the H2S release of compound 9h is significantly more and faster than other compounds.
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Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Desenho de Fármacos , Sulfeto de Hidrogênio/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Compostos de Anilina/síntese química , Compostos de Anilina/química , Antineoplásicos/síntese química , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Sulfeto de Hidrogênio/química , Estrutura Molecular , Mutação , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-AtividadeRESUMO
We have previously demonstrated that anti-CD44s H4C4 or liposomal-delivered STAT3 inhibitor FLLL32 sensitized pancreatic cancer cells to radiotherapy through the elimination or inhibition of cancer stem cells (CSCs) and that HAb18G/CD147 promoted STAT3-mediated pancreatic tumor development by forming a signaling complex with CD44s. In this paper, we therefore explored whether anti-CD147 HAb18IgG sensitized pancreatic cancer cells to chemoradiotherapy via the targeting of CSCs. We tested the influence of HAb18IgG on the sensitivity of pancreatic cancer cells to chemoradiotherapy by clonogenic and MTT assays and on pancreatic CSCs by colony and sphere formation assays, flow cytometry, quantitative real-time RT-PCR (qRT-PCR) and stem cell transcription factors PCR array analysis. Changes in CD147 signaling were examined by immunoblot and reporter assays. We found that HAb18IgG sensitized pancreatic cancer cells to chemoradiotherapy by dose-dependently decreasing colony and sphere formation. Furthermore, HAb18IgG reduced the pancreatic CSC subpopulation and the expression of stem cell transcription factors OCT4, SOX2 and NANOG. Mechanistically, HAb18IgG inhibited CSCs by blocking CD44s-pSTAT3 signaling. The present findings indicated the promising therapeutic role of anti-CD147 HAb18IgG in suppressing pancreatic tumor initiation and overcoming post-chemoradiotherapy recurrence through the direct targeting of CSCs.
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The present study aimed to examine the effects of sodium selenite on the SW982 human synovial sarcoma cell line in relation to cell viability, apoptosis and autophagy. The results indicated that sodium selenite reduced cell viability and induced apoptosis by activating caspase3 and members of the poly (ADPribose) polymerase and Bcl2 protein families in SW982 cells. Furthermore, autophagy was also suppressed by sodium selenite treatment in SW982 cells, and apoptosis was upregulated in cells cotreated with sodium selenite and the autophagy inhibitor 3methyladenine. By contrast, apoptosis was downregulated when sodium selenite was combined with rapamycin, an inducer of autophagy. The results indicated that autophagy may protect cells from the cytotoxicity of sodium selenite. The present study results demonstrated that sodium selenite induced apoptosis and inhibited autophagy and autophagyprotected cells from death by antagonizing sodium seleniteinduced apoptosis in SW982 cells in vitro.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sarcoma Sinovial/metabolismo , Selenito de Sódio/farmacologia , Caspase 3/biossíntese , Linhagem Celular Tumoral , Humanos , Poli(ADP-Ribose) Polimerases/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Sarcoma Sinovial/patologiaRESUMO
The phytohormone abscisic acid (ABA) controls many developmental and physiological processes. Here, we report that PHOSPHATE1 (PHO1) participates in ABA-mediated seed germination and early seedling development. The transcription of PHO1 was obviously enhanced during seed germination and early seedling development and repressed by exogenous ABA. The pho1 mutants (pho1-2, pho1-4, and pho1-5) showed ABA-hypersensitive phenotypes, whereas the PHO1-overexpressing lines were ABA-insensitive during seed germination and early seedling development. The expression of PHO1 was repressed in the ABI5-overexpressing line and elevated in the abi5 mutant, and ABI5 can bind to the PHO1 promoter in vitro and in vivo, indicating that ABI5 directly down-regulated PHO1 expression. Disruption of PHO1 abolished the ABA-insensitive germination phenotypes of abi5 mutant, demonstrating that PHO1 was epistatic to ABI5 Together, these data demonstrate that PHO1 is involved in ABA-mediated seed germination and early seedling development and transcriptionally regulated by ABI5.