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We report the reactivity, structures and spectroscopic characterization of reactions of phosphine-based ligands (mono-, di- and tri-dentate) with iron-carbide carbonyl clusters. Historically, the archetype of this cluster class, namely [Fe6(µ6-C)(µ2-CO)4(CO)12]2-, can be prepared on a gram-scale but is resistant to simple ligand substitution reactions. This limitation has precluded the relevance of iron-carbide clusters relating to organometallics, catalysis and the nitrogenase active site cluster. Herein, we aimed to derive a simple and reliable method to accomplish CO â L (where L = phosphine or other general ligands) substitution reactions without harsh reagents or multi-step synthetic strategies. Ultimately, our goal was ligand-based chelation of an Fe n (µ n -C) core to achieve more synthetic control over multi-iron-carbide motifs relevant to the nitrogenase active site. We report that the key intermediate is the PSEPT-non-conforming cluster [Fe6(µ6-C)(CO)16] (2: 84 electrons), which can be generated in situ by the outer-sphere oxidation of [Fe6(µ6-C)(CO)16]2- (1: closo, 86 electrons) with 2 equiv. of [Fc]PF6. The reaction of 2 with excess PPh3 generates a singly substituted neutral cluster [Fe5(µ5-C)(CO)14PPh3] (4), similar to the reported reactivity of the substitutionally active cluster [Fe5(µ5-C)(CO)15] with monodentate phosphines (Cooke & Mays, 1990). In contrast, the reaction of 2 with flexible, bidentate phosphines (DPPE and DPPP) generates a wide range of unisolable products. However, the rigid bidentate phosphine bis(diphenylphosphino)benzene (bdpb) disproportionates the cluster into non-ligated Fe3-carbide anions paired with a bdpb-supported Fe(ii) cation, which co-crystallize in [Fe3(µ3-CH)(µ3-CO)(CO)9]2[Fe(MeCN)2(bdpb)2] (6). A successful reaction of 2 with the tripodal ligand Triphos generates the first multi-iron-chelated, authentic carbide cluster of the formula [Fe4(µ4-C)(κ3-Triphos)(CO)10] (9). DFT analysis of the key (oxidized) intermediate 2 suggests that its (µ6-C)Fe6 framework remains fully intact but is distorted into an axially compressed, 'ruffled' octahedron distinct from the parent closo cluster 1. Oxidation of the cluster in non-coordinating solvent allows for the isolation and crystallization of the CO-saturated, intact closo-analogue [Fe6(µ6-C)(CO)17] (3), indicating that the intact (µ6-C)Fe6 motif is retained during initial oxidation with [Fc]PF6. Overall, we demonstrate that redox modulation beneficially 'bends' Wade-Mingo's rules via the generation of electron-starved (non-PSEPT) intermediates, which are the key intermediates in promoting facile CO â L substitution reactions in iron-carbide-carbonyl clusters.
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Social interactions between cows play a fundamental role in the daily activities of dairy cattle. Real-time location systems provide on a continuous and automated basis information about the position of individual cows inside barns, offering a valuable opportunity to monitor dyadic social contacts. Understanding dyadic social interactions could be applied to enhance the stability of the social structure promoting animal welfare and to model disease transmission in dairy cattle. This study aimed to identify the effect of different cow characteristics on the likelihood of the formation and persistence of social contacts in dairy cattle. The individual position of the lactating cows was automatically collected once per second for 2 wk, using an ultra-wideband system on a Swedish commercial farm consisting of almost 200 dairy cows inside a freestall barn. Social networks were constructed using the position data of 149 cows with available information on all characteristics during the study period. Social contacts were considered as a binary variable indicating whether a cow pair was within 2.5 m of each other for at least 10 min per day. The role of cow characteristics in social networks was studied by applying separable temporal exponential random graph models. Our results revealed that cows of the same parity interacted more consistently, as well as those born within 7 d of each other or closely related by pedigree. The repeatability of the topological parameters indicated a consistent short-term stability of the individual animal roles within the social network structure. Additional research is required to elucidate the underlying mechanisms governing the long-term evolution of social contacts among dairy cattle and to investigate the relationship between these networks and the transmission of diseases in the dairy cattle population.
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Enfermedades de los Bovinos , Leche , Femenino , Bovinos , Animales , Lactancia , Conducta Animal , Enfermedades de los Bovinos/epidemiología , Relaciones Interpersonales , Industria Lechera/métodos , Vivienda para AnimalesRESUMEN
Extracellular vesicles (EVs) are small, membrane-enclosed vesicles released by cells into the extracellular milieu. They are found in all body fluids and contain a variety of functional cargo including DNA, RNA, proteins, glycoproteins and lipids, able to provoke phenotypic responses in cells, both locally and at distant sites. They are implicated in a wide array of physiological and pathological processes and hence have attracted considerable attention in recent years as potential therapeutic targets, drug delivery vehicles and biomarkers of disease. In this review we summarise the major functions of EVs in health and disease and discuss their translational potential, highlighting opportunities of - and challenges to - capitalising on our rapidly increasing understanding of EV biology for patient benefit.
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Vesículas Extracelulares , Humanos , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Comunicación Celular/fisiología , Biomarcadores/metabolismo , ProteínasRESUMEN
Melatonin confers protection against myocardial injury by reducing inflammation and inhibiting apoptosis. In the present study, we investigated whether melatonin regulates cardiomyocyte proliferation and improves cardiac function in rats with myocardial infarction (MI). Two MI models were established in vitro (H9c2 cells were cultured under hypoxia) and in vivo (the left anterior descending coronary artery of rats was surgically ligated). miR-200b-3p and high mobility group box 1 (HMGB1) levels were detected. Cell proliferation and apoptosis were analyzed in vitro, and cardiac function, inflammatory cytokines, and myocardial injury markers in vivo were tested. The experimental results reported that melatonin promoted proliferation and impaired apoptosis of H9c2 cells cultured in hypoxia. In vivo, melatonin improved cardiac function and inhibited the inflammation and myocardial injury of rats with MI. miR-200b-3p was downregulated and HMGB1 was upregulated in MI, while melatonin could upregulate miR-200b-3p and downregulate HMGB1. The HMGB1 was targeted by miR-200b-3p. Upregulating miR-200b-3p or downregulating HMGB1 could further promote the therapeutic effect of melatonin, and downregulating miR-200b-3p or upregulating HMGB1 could abolish the therapeutic effect of melatonin. In conclusion, melatonin alleviates inflammation and cardiac dysfunction after MI by regulating the miR-200b-3p/HMGB1 axis, offering a new therapeutic strategy for MI.
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Proteína HMGB1 , Melatonina , MicroARNs , Infarto del Miocardio , Ratas , Animales , MicroARNs/genética , MicroARNs/metabolismo , Melatonina/farmacología , Melatonina/uso terapéutico , Melatonina/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Proteína HMGB1/farmacología , Transducción de Señal/fisiología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Apoptosis , Hipoxia , Miocitos Cardíacos/metabolismoRESUMEN
The article "Overexpression of long non-coding RNA TUG1 alleviates TNF-α-induced inflammatory injury in interstitial cells of Cajal", by K. Zhao, J.-Y. Tan, Q.-D. Mao, K.-Y. Ren, B.-G. He, C.-P. Zhang, L.-Z. Wei published in Eur Rev Med Pharmacol Sci 2019; 23 (1): 312-320-DOI: 10.26355/eurrev_201901_16778-PMID: 30657572 has been retracted by the authors for the following reasons: We are still conducting research in the effect of long non-codingRNA TUG1 in interstitial cells of Cajal recently. It turned out that some of the current experimental results are inconsistent with the previous results. Some data cannot be repeated by further research. We need to further confirm the effect of long non-coding RNA TUG1 on alleviating TNF-α-induced inflammatory injury in interstitial cells of Cajal and for this reason, the authors all agreed to withdraw the manuscript. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16778.
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In modern freestall barns where large groups of cows are housed together, the behavior displayed by herd mates can influence the welfare and production of other individuals. Therefore, understanding social interactions in groups of dairy cows is important to enhance herd management and optimize the outcomes of both animal health and welfare in the future. Many factors can affect the number of social contacts in a group. This study aimed to identify which characteristics of a cow are associated with the number of contacts it has with other group members in 2 different functional areas (feeding and resting area) to increase our understanding of the social behavior of dairy cows. Inside 2 herds housed in freestall barns with around 200 lactating cows each, cow positions were recorded with an ultra-wideband real-time location system collecting all cows' positions every second over 2 wk. Using the positioning data of the cows, we quantified the number of contacts between them, assuming that cows spending time in proximity to one another (within a distance of 2.5 m for at least 10 min per day) were interacting socially. We documented in which barn areas these interactions occurred and used linear mixed models to investigate if lactation stage, parity, breed, pregnancy status, estrus, udder health, and claw health affect the number of contacts. We found variation in the number of contacts a cow had between individuals in both functional areas. Cows in later lactation had more contacts in the feeding area than cows in early lactation. Furthermore, in one herd, higher parity cows had fewer contacts in the feeding area than first parity cows, and in the other herd, cows in third parity or higher had more contacts in the resting area. This study indicates that cow characteristics such as parity and days in milk are associated with the number of contacts a cow has daily to its herd mates and provides useful information for further research on social interactions of dairy cows.
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Enfermedades de los Bovinos , Lactancia , Femenino , Embarazo , Bovinos , Animales , Vivienda para Animales , Industria Lechera , Paridad , LecheRESUMEN
Objective: To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients. Results: Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs(P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion: HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.
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Insuficiencia Hepática Crónica Agudizada/diagnóstico , Hepatitis B Crónica/complicaciones , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/virología , Femenino , Virus de la Hepatitis B , Hepatitis B Crónica/mortalidad , Humanos , Masculino , Pronóstico , Curva ROC , Estudios Retrospectivos , Factores de RiesgoRESUMEN
We previously reported the presence of vasculogenic mimicry (VM) in human osteosarcoma. However, the mechanistic basis of osteosarcoma VM remains unclear. Three hundred eighty-one upregulated differentially expressed genes (DEGs) and 526 downregulated DEGs between human osteosarcoma cell line 143B and HOS cell exposed to Matrigel were screened out by microarray. GO categories such as "cell adhesion", "angiogenesis" were enriched in 143B group. PATHWAY analysis showed enriched TGF-beta, Wnt and VEGF signaling pathway in 143B group. The hub gene ITGA2 in signal-network of DEGs exhibited pro-VM and pro-metastasis effect. Our study provides fundamental data for further studies regarding molecules involved in osteosarcoma VM.
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Neoplasias Óseas/genética , Neovascularización Patológica/genética , Osteosarcoma/genética , Transcriptoma , Neoplasias Óseas/patología , Línea Celular Tumoral , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Análisis por Micromatrices , Osteosarcoma/patología , Transducción de SeñalRESUMEN
OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional disorder in the gastrointestinal tract. Inflammatory response has been found to participate in the pathogenesis of IBS. This study aimed to explore the effects of long non-coding RNA taurine upregulated gene 1 (TUG1) on tumor necrosis factor alpha (TNF-α)-induced interstitial cells of Cajal (ICC) inflammatory injury, which was relevant to the pathogenesis of IBS. PATIENTS AND METHODS: The expression levels of TUG1 and microRNA-127 (miR-127) were analyzed by qRT-PCR. Viability, apoptosis and the expression of apoptosis-associated factors were analyzed by CCK-8 assay, flow cytometry and Western blot, respectively. The mRNA and protein levels of pro-inflammatory cytokines were detected by qRT-PCR and Western blot, respectively. Finally, activations of nuclear factor kappa-B (NF-κB) and Notch pathways were evaluated by Western blot. RESULTS: TNF-α treatment inhibited ICC viability, induced ICC apoptosis and promoted an inflammatory response in ICC. TUG1 was downregulated in TNF-α-treated ICC. TUG1 overexpression protected ICC from TNF-α-induced apoptosis and pro-inflammatory cytokines expression. TUG1 suppression showed opposite effects. MiR-127 was negatively regulated by TUG1 and implicated in the action of TUG1 in ICC. MiR-127 up-regulation largely reversed the effects of TUG1 on TNF-α-treated ICC. Mechanistically, TUG1 inhibited TNF-α-induced activation of NF-κB and Notch pathways in ICC by down-regulating miR-127. CONCLUSIONS: TUG1 attenuated TNF-α-caused apoptosis and inflammatory response in ICC by down-regulating miR-127 and then inactivating NF-κB and Notch pathways.
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Células Intersticiales de Cajal/inmunología , Síndrome del Colon Irritable/genética , MicroARNs/genética , ARN Largo no Codificante/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Apoptosis/genética , Apoptosis/inmunología , Supervivencia Celular/genética , Supervivencia Celular/inmunología , Células Cultivadas , Femenino , Perfilación de la Expresión Génica , Humanos , Células Intersticiales de Cajal/patología , Síndrome del Colon Irritable/inmunología , Síndrome del Colon Irritable/patología , Ratones , MicroARNs/metabolismo , Cultivo Primario de Células , ARN Largo no Codificante/agonistas , ARN Largo no Codificante/antagonistas & inhibidores , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo , Receptores Notch/inmunología , Receptores Notch/metabolismo , Transducción de Señal/genética , Transducción de Señal/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Regulación hacia ArribaRESUMEN
OBJECTIVE: Accounting for 25% of all the cancers and 20% of the cancer-related mortality, lung cancer is one of the devastating types of cancers. Due to an increase in the incidence of lung cancer and limited treatment options, there is a pressing need to look for novel drug options and to identify potential therapeutic targets. Long non-coding RNAs (LncRNAs) have been considered to be important therapeutic targets due to their plethora of cellular roles. Herein, we investigated the therapeutic potential of UCA1 in lung cancer and also attempted to examine the underlying mechanism through UCA1 exerts its growth inhibitory effects on cancer cells. MATERIALS AND METHODS: The quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR) was used to perform the expression analysis. The CCK-8 assay was used to monitor the growth of the cells. The AO/EB assay was used to check apoptosis and flow cytometry was used for cell cycle distribution. The wound heal and transwell assays were used to monitor the cell migration and invasion. RESULTS: It was found that the lncRNA UCA was significantly (p < 0.05) upregulated in the lung cancer cells and silencing of UCA1 could inhibit the proliferation of the SK-MES-1 lung cancer cells via induction of G2/M cell cycle arrest and apoptosis. Moreover, UCA1 silencing could also suppress the migration and invasion of the SK-MES-1 cells. The LncRNA UCA1 was also found to upregulate the expression of miR-143, and overexpression of miR-143 could also suppress the proliferation, migration, and invasion of the SK-MES-1 lung cancer cells. Both UCA1 silencing and miR-143 overexpression could cause a significant decrease in the expression of mitogen-activated protein kinase 1 (MAPK1). Therefore, it is concluded that UCA1 regulates the growth of the SK-MES-1 lung cancer by inhibition of MAPK1 via miR-143 upregulation. CONCLUSIONS: UCA1, as well as miR-143, may be essential therapeutic targets for the management of lung cancer and warrant further investigations.
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Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , ARN Largo no Codificante/metabolismo , Células A549 , Apoptosis , Puntos de Control del Ciclo Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , MicroARNs/genética , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Invasividad Neoplásica , ARN Largo no Codificante/genética , Transducción de SeñalRESUMEN
OBJECTIVE: Lung cancer is one of the deadliest cancers responsible for significant mortality and morbidity across the globe. The unavailability of efficient treatments, lack of reliable biomarkers and potent therapeutic targets, limit the treatment of lung cancer. In this study, we explored the potential of long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) as the therapeutic target for lung cancer. MATERIALS AND METHODS: The expression analysis was carried out by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cell viability was monitored by cell counting kit 8 (CCK-8) assay. The 4',6-diamidino-2-phenylindole (DAPI), annexin-V/Propidium iodide staining and comet assays were used to detect apoptosis. Boyden chamber and wound heal assays were used for cell to asses cell invasion and migration respectively. Protein expression was determined by immunoblotting. RESULTS: The expression of lncRNA UCA1 was determined by qRT-PCR in six different types of lung cancer cell lines. It was observed that lncRNA UCA1 was significantly (p < 0.05) upregulated in all the lung cancer cell lines. To investigate the role of lncRNA UCA1 in lung cancer, its expression was suppressed by transfection of the lung cancer NCI-H23 cells by si-UCA1. The results showed that suppression of lncRNA UCA1 significantly (p < 0.05) reduced the viability of NCI-H23 cancer cells via induction of the apoptosis. Furthermore, the lncRNA UCA1 suppression (p < 0.05) significantly inhibited the migration and invasion of the NCI-H23 lung cancer at least in part via inhibition of mitogen-activated protein kinase 1 (MAPK1). Additionally, the suppression of MAPK1 exhibited similar effects on the proliferation, migration, and invasion of the NCI-H23 cells as that of UCA1 silencing. Finally, the co-suppression of lncRNA UCA1 and MAPK1 exhibited synergistic effects on cell proliferation, migration, and invasion. CONCLUSIONS: We demonstrated that lncRNA UCA1 could be an important therapeutic target for curbing lung cancer.
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Apoptosis , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares/metabolismo , ARN Largo no Codificante/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Invasividad Neoplásica , ARN Largo no Codificante/genética , Transducción de SeñalRESUMEN
OBJECTIVE: To investigate the effects of ulinastatin on inflammatory response and cognitive function after hip arthroplasty for the elderly patients with femoral neck fracture. PATIENTS AND METHODS: A total of 80 patients with femoral neck fracture receiving hip arthroplasty in our hospital from August 2016 to February 2017 were selected and divided into observation group (n=40) and control group (n=40) using a random number table. The control group was treated with hip arthroplasty and symptomatic and supportive treatment after operation, while the observation group was treated with ulinastatin based on the treatment means of control group. The changes in antioxidant capacities, plasma noradrenaline (NA) and adrenaline (A) levels between the two groups before and after intervention were compared. The changes in neuron-specific enolase (NSE) and plasma S-100B protein levels before intervention and at 48 h after intervention were also compared. Moreover, the changes in mini-mental state examination (MMSE) scores during intervention and the Harris hip scores before intervention and at discharge between the two groups were compared. Finally, the off-bed walking time and postoperative discharge time of the two groups were recorded. RESULTS: After intervention, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) and the total antioxidant capacity in observation group were significantly superior to those in observation group before intervention and control group after intervention (p<0.05). After intervention, the levels of NA and A in observation group were lower than those in control group (p<0.05), and the levels of interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) in observation group were also lower than those in control group (p<0.05). At 48 h after intervention, the levels of NSE and plasma S-100B protein in observation group were significantly lower than those in observation group before intervention and control group at 48 h after intervention (p<0.05). At 12 h, 24 h and 48 h after intervention, the MMSE scores of observation group were superior to those of control group in the same period (p<0.05). After intervention, the Harris hip score of observation group was superior to that of control group before and after intervention (p<0.05). The postoperative discharge time of observation group was earlier than that of control group (p<0.05), and the off-bed walking time was also earlier than that of control group (p<0.05). CONCLUSIONS: The combined application of ulinastatin could effectively reduce the oxidative stress and inflammatory response, improve the neurological functions, and promote the postoperative recovery in the elderly patients with femoral neck fracture after hip arthroplasty.
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Artroplastia de Reemplazo de Cadera/psicología , Cognición/efectos de los fármacos , Fracturas del Cuello Femoral/tratamiento farmacológico , Glicoproteínas/uso terapéutico , Mediadores de Inflamación/sangre , Estrés Oxidativo/efectos de los fármacos , Adulto , Anciano , Artroplastia de Reemplazo de Cadera/tendencias , Cognición/fisiología , Femenino , Fracturas del Cuello Femoral/cirugía , Glicoproteínas/farmacología , Humanos , Mediadores de Inflamación/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Alta del Paciente/tendencias , Resultado del Tratamiento , Inhibidores de Tripsina/farmacología , Inhibidores de Tripsina/uso terapéuticoRESUMEN
AIMS: (i) To obtain and identify the predatory bacteria for the control of contaminated bacteria and to promote the autotrophic growth of Chlorella USTB-01. (ii) To identify and measure the different cell numbers in microalgal culture using flow cytometer. METHODS AND RESULTS: A predatory bacterial strain was isolated using Escherichia coli BL21 as a sole prey host, which was identified as Bdellovibrio USTB-06 by the analysis of 16S rDNA sequence. A flow cytometer was successfully used to identify and measure the cell numbers of Chlorella USTB-01, the contaminated bacteria and Bdellovibrio USTB-06 simultaneously in the autotrophic culture of Chlorella USTB-01 according to the identification of the different cell sizes. With the addition of Bdellovibrio USTB-06 at initial 104 plaque-forming units per ml, the contaminated bacteria severely decreased by about five counts (in log10 CFU per ml) and the growth of Chlorella USTB-01 was greatly increased by 37·0% compared with those of control respectively. CONCLUSIONS: Bdellovibrio USTB-06 could effectively promote the growth of Chlorella USTB-01 via the killing of the contaminated bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study reveals a good biotechnology method to increase the growth of Chlorella USTB-01 which is very important in the industry of microalgal culture.
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Bdellovibrio/fisiología , Chlorella/crecimiento & desarrollo , Chlorella/microbiología , Procesos Autotróficos , Bdellovibrio/aislamiento & purificación , Escherichia coli/fisiología , Interacciones MicrobianasRESUMEN
Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference (P=0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P=0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results (P=0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients(P<0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast, knockdown NS1-BP in KYSE510 cells induced c-Myc expression, increased cell proliferation and repressed apoptosis. Conclusions: NS1-BP is an independent favorable prognostic factor in ESCC. It inhibits cell proliferation and enhances cell apoptosis via repressing c-Myc. Targeting NS1-BP may be a new therapeutic strategy for ESCC patients.
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Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Apoptosis , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Línea Celular Tumoral , Proliferación Celular , Quimioradioterapia , Supervivencia sin Enfermedad , Regulación hacia Abajo , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas de Unión al ARN , TransfecciónRESUMEN
BACKGROUND: Current medical treatments for chemotherapy-induced pain (CIP) are either ineffective or have adverse side effects. Acupuncture may alleviate CIP, but its effectiveness against this condition has not been studied. Paclitaxel causes neuropathic pain in cancer patients. METHODS: We evaluated the effects of electroacupuncture (EA) on paclitaxel-induced CIP in a rat model. Paclitaxel (2 mg/kg) or vehicle was injected (i.p.) on alternate days of 0-6. The resulting pain was treated with 10 Hz/2 mA/0.4 ms pulse EA for 30 min at the equivalent of human acupoint GB30 (Huantiao) once every other day between days 14 and 26. For sham control, EA needles were inserted into GB30 without stimulation. Von Frey filaments with bending forces of 2-8 g and 15 g were used to assess mechanical allodynia and hyperalgesia, respectively, on day 13 and once every other day between 14-26 days and then for 2-3 weeks after EA treatment. RESULTS: Compared to sham control, EA significantly alleviated paclitaxel-induced mechanical allodynia and hyperalgesia, as shown by less frequent withdrawal responses to the filaments. The alleviation of allodynia/hyperalgesia lasted up to 3 weeks after the EA treatment. EA significantly inhibited phosphorylation of Ca2+ /calmodulin-dependent protein kinase II (CaMKII) in the spinal cord. KN-93, a selective inhibitor of p-CaMKII, inhibited mechanical allodynia/hyperalgesia and p-CaMKII. 5-HT1A receptor antagonist blocked EA inhibition of allodynia/hyperalgesia and p-CaMKII. CONCLUSIONS: Electroacupuncture activates 5-HT 1A receptors in the spinal cord and inhibits p-CaMKII to alleviate both allodynia and hyperalgesia. The data support acupuncture/EA as a complementary therapy for CIP. SIGNIFICANCE: Electroacupuncture (EA) activates spinal 5-HT1A receptors to inhibit p-CaMKII to alleviate paclitaxel-induced pain. Acupuncture/EA may be used as a complementary therapy for CIP.
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Antineoplásicos Fitogénicos/efectos adversos , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Electroacupuntura/métodos , Hiperalgesia/terapia , Neuralgia/terapia , Paclitaxel/efectos adversos , Médula Espinal/metabolismo , Puntos de Acupuntura , Animales , Hiperalgesia/inducido químicamente , Hiperalgesia/metabolismo , Masculino , Neuralgia/inducido químicamente , Neuralgia/metabolismo , Fosforilación , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Gastric cancer (GC) is one of the most prevalent types of malignant disease Worldwide. Mounting evidence has demonstrated the involvement of miRNAs in the development of GC. One of these miRNAs, miR-144 has been found aberrantly expressed in a variety of human malignancies. PATIENTS AND METHODS: GC tissues were collected from patients, and the level of miR-144 was determined by qRT-PCR. GC cell lines SGC7901 and AGS were used as model cell lines and the anti-tumor effect of miR-144 in both cells were examined. The level of miR-144 was restored in GC cells using miR-144 mimic. Moreover, the target gene of miR-144 wad identified. RESULTS: In this study, our results showed that low miR-144 level significantly correlated with lymph node metastasis stage, TNM stage and differentiation degree. In addition, we found that miR-144 acted as a tumor suppressor in GC. Moreover, our findings showed that miR-144 exerted an anti-tumor effect by directly targeting RLIP76. CONCLUSIONS: miR-144 acts as a tumor suppressor in GC and it is a potential therapeutic target for GC treatment.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Proteínas Activadoras de GTPasa/genética , Genes Supresores de Tumor , MicroARNs/genética , Neoplasias Gástricas/metabolismo , Transportadoras de Casetes de Unión a ATP/biosíntesis , Anciano , Diferenciación Celular/fisiología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Proteínas Activadoras de GTPasa/biosíntesis , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Metástasis Linfática/fisiopatología , Masculino , MicroARNs/agonistas , MicroARNs/antagonistas & inhibidores , MicroARNs/farmacología , Persona de Mediana Edad , Invasividad Neoplásica/fisiopatologíaRESUMEN
This article has been withdrawn at the request authors.