RESUMO
Rectal toxicity is a significant concern in cervical cancer radiotherapy. Despite advancements in image-guided brachytherapy (IGBT), rectal morbidity remains a challenge. Injectable hydrogel showed promise in creating a space between the vagina and rectum, reducing rectal radiation dose; however, the traditional ultrasound-guided injection revealed some problems, such as the inadequate separation of the upper edge of the cervix, which can be mitigated through adopting CT-guided injection. This case report presents the successful use of computed tomography (CT)-guided hydrogel injection to limit rectal doses and improve treatment outcomes. A forty-year-old female with stage IIIC1r cervical cancer received external-beam radiotherapy and concurrent chemotherapy. Due to the proximity of the tumor to the rectum, a CT-guided hydrogel injection was performed to increase the distance between the cervix and rectum. Post-injection, magnetic resonance imaging (MRI) demonstrated increased distances between the cervix and rectum. Subsequent MRI-based IGBT achieved high clinical target volume doses while limiting rectal doses. During the six-month follow-up, the patient reported only mild adverse effects. CT-guided hydrogel injection offers advantages over ultrasound-guided injection in cervical cancer radiotherapy. The technique allows for better puncture position adjustment, reduced reliance on specialized ultrasound expertise, and shorter puncture distances. This case report highlights the potential of hydrogel injection as a viable method to reduce rectal morbidity and improve treatment outcomes in a broader range of cervical cancer patients. Further studies are warranted to validate these findings and explore its applicability in larger cohorts.
RESUMO
Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.
Assuntos
Gleditsia , Lignanas , Plântula , Lignanas/metabolismo , Gleditsia/química , Extratos Vegetais/metabolismo , Raízes de PlantasRESUMO
BACKGROUND: Dendrobium nobile has unique growth environment requirements, and unstable yields and high management costs are the key factors restricting the development of its imitation wild cultivation industry. The present study explored the effects of different associated bryophyte species on the yield and quality of D. nobile to clarify the dominant bryophyte species associated with D. nobile and to provide a scientific basis for the rational cultivation and quality evaluation of D. nobile. RESULTS: The growth of D. nobile was closely related to the microenvironment of the Danxia stone, and the different associated bryophytes had different effects on D. nobile growth. There was a rich variety of bryophytes associated with D. nobile, with a total of 15 families, 24 genera and 31 species of bryophytes identified in the study area, including 13 families, 22 genera and 29 species of mosses and 2 families, 2 genera and 2 species of liverworts, and mosses predominated in the association with D. nobile. Usually, 3-9 species of bryophytes were growing in association with D. nobile, among which associations of 5-6 bryophytes species were more common, and the bryophytes associated with D. nobile were only related to the species to which they belonged. The dry matter accumulation, quality and mineral content of D. nobile differed significantly among different bryophyte species. The coefficients of variation of dry matter accumulation, dendrobine content and content of 11 mineral elements of D. nobile in the 35 sample quadrats were 25.00%, 21.08%, and 11.33-57.96%, respectively. The biomass, dendrobine content and mineral content of D. nobile were analysed by principal component analysis (PCA) and membership function. The results showed that each evaluation method initially screened Trachycystis microphylla and Leucobryum juniperoideum as the dominant associated bryophytes in the preliminary identification analysis, and the frequency of occurrence and coverage of the two bryophytes were significantly higher than those of the remaining bryophytes. It was determined that T. microphylla and L. juniperoideum were the dominant associated bryophytes. CONCLUSIONS: There is a rich variety of bryophytes associated with D. nobile. The yield and quality of D. nobile differed significantly among different bryophyte species. T. microphylla and L. juniperoideum were the dominant associated bryophytes, and were the two bryophytes associated with D. nobile through mixed growth.
Assuntos
Briófitas , Dendrobium , Humanos , Biomassa , MineraisRESUMO
Purpose: Endometrial carcinoma (EC) is a common gynecological malignancy. Vaginal cuff brachytherapy (VBT) is an adjuvant treatment for EC. Since a single-channel cylinder sometimes delivers inadequate dose coverage to the vaginal apex, three-dimensional (3D) printing technology can be used to achieve satisfactory dose distribution. Here, we report the first case of an EC patient with Herlyn-Werner-Wunderlich syndrome (HWWS) treated with VBT using 3D-printed applicators. Case Presentation: Here, we present a case study of an endometrial cancer patient with HWWS who underwent surgery. During adjuvant radiotherapy, 3D-printed applicators were used in VBT. To accomplish the reconstruction of the source pathways on magnetic resonance imaging, catheters with copper sulfate were placed in two 3D-printed applicators. The early tolerance of this treatment was positive. During the 6-month follow-up, locoregional recurrence was not detected. Conclusion: Our findings strongly indicate that VBT with 3D-printed applicators may be a reasonable treatment option for EC with HWWS.
RESUMO
Objective: Readiness for hospital discharge is an important indicator of patients' transition from illness to health and can predict rehabilitation and prognosis. Identifying factors that influence readiness for discharge is crucial for developing effective nursing interventions. Therefore, this study aims to investigate the current status of discharge readiness and its influencing factors in elderly patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 311 elderly inpatients diagnosed with COPD were enrolled in this investigation at a tertiary hospital in Chengdu between December 2021 and June 2022. Questionnaires were designed to collect general information, disease-related information, and responses to the Readiness for Hospital Discharge Scale (RHDS) and the Quality of Discharge Teaching Scale (QDTS). Univariate and multivariate linear regression analyses were employed to further analyze factors related to discharge readiness and the correlation between discharge readiness and the quality of discharge guidance. Results: The total score of discharge readiness of elderly COPD patients was 77.72 ± 11.86 with a mean score of 6.48 ± 0.19 for each item. The quality of discharge instructions was 110.54 ± 15.66, with a mean score of 6.12 ± 0.15 for each item. Discharge preparation was positively correlated with the quality of discharge guidance. Multivariate analysis showed that marital status, admission mode, length of stay in hospital, Classification of Severity of Airflow Limitation, mMRC classification, number of medications taken with discharge, presence of inhalers in medication orders, mode of home oxygen therapy, and quality of discharge guidance were independent factors of discharge readiness in elderly COPD patients (P < 0.05). Conclusion: Both discharge readiness and the quality of discharge guidance for elderly COPD patients in China are currently suboptimal and need further improvement. The survey findings provide valuable insights that can guide future management practices and interventions aimed at improving discharge readiness.
RESUMO
This study explored the feasibility of mineral element content and ratios of nitrogen isotopes to discriminate the cultivation mode of Dendrobium nobile in order to provide theoretical support for the discrimination of the cultivation mode of D. nobile. The content of 11 mineral elements(N, K, Ca, P, Mg, Na, Fe, Cu, Zn, Mn, and B) and nitrogen isotope ratios in D. nobile and its substrate samples in three cultivation methods(greenhouse cultivation, tree-attached cultivation, and stone-attached cultivation) were determined. According to the analysis of variance, principal component analysis, and stepwise discriminant analysis, the samples of different cultivation types were classified. The results showed that the nitrogen isotope ratios and the content of elements except for Zn were significantly different among different cultivation types of D. nobile(P<0.05). The results of correlation analysis showed that the nitrogen isotope ratios, mineral element content, and effective component content in D. nobile were correlated with the nitrogen isotope ratio and mineral element content in the corresponding substrate samples to varying degrees. Principal component analysis can preliminarily classify the samples of D. nobile, but some samples overlapped. Through stepwise discriminant analysis, six indicators, including δ~(15)N, K, Cu, P, Na, and Ca, were screened out, which could be used to establish the discriminant model of D. nobile cultivation methods, and the overall correct discrimination rates after back-substitution test, cross-check, and external validation were all 100%. Therefore, nitrogen isotope ratios and mineral element fingerprints combined with multivariate statistical analysis could effectively discriminate the cultivation types of D. nobile. The results of this study provide a new method for the identification of the cultivation type and production area of D. nobile and an experimental basis for the quality evaluation and quality control of D. nobile.
Assuntos
Dendrobium , Minerais , Análise Discriminante , Análise Multivariada , Isótopos de NitrogênioRESUMO
Subsequently to the publication of this paper, an interested reader drew to the authors' attention that the same control ßactin bands had apparently been included in the western blots featured in Fig. 5E and F, even though different experiments were presented in these figure parts. The authors have reexamined their data and realized that Fig. 5G was assembled incorrectly. The results from all the originally performed experiments were presented to the Editorial Office for our perusal. The revised version of Fig. 5, containing the correct ßactin data for the western blots in Fig. 5F, is shown on the next page. The authors regret the inadvertent error that was made during the preparation of Fig. 5, and confirm that this error did not seriously affect the conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologise to the readership for any inconvenience caused.[Oncology Reports 41: 26892702, 2019; DOI: 10.3892/or.2019.7054].
RESUMO
Subsequently to the publication of this paper, an interested reader drew to the authors' attention that western blots featured in Figs. 4B and 5G (representing the 'AR' experiments in both cases) appeared to be the same, albeit that the bands were flipped vertically in Fig. 5G relative to Fig. 4B. The authors have reexamined their data and realized that Fig. 5 was assembled incorrectly. The results from all the originally performed experiments were presented to the Editorial Office for our perusal. The revised version of Fig. 5, containing the correct data for the 'AR' experiment in Fig. 5G, is shown on the next page. The authors regret the inadvertent error that was made during the preparation of Fig. 5, and confirm that this error did not seriously affect the conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologise to the readership for any inconvenience caused. [Oncology Reports 43: 13971412, 2020; DOI: 10.3892/or.2020.7520].
RESUMO
Flexible pressure sensors still face difficulties achieving a constantly adaptable micronanostructure of substrate materials. Interlinked microcone resistive sensors were fabricated by polydimethylsiloxane (PDMS) nanocone array. PDMS nanocone array was achieved by the second transferring tapered polymethyl methacrylate (PMMA) structure. In addition, self-assembly 2D carbon nanotubes (CNTs) networks as a conducting layer were prepared by a low-cost, dependable, and ultrafast Langmuir−Blodgett (LB) process. In addition, the self-assembled two-dimensional carbon nanotubes (CNTs) network as a conductive layer can change the internal resistance due to pressure. The results showed that the interlinked sensor with a nanocone structure can detect the external pressure by the change of resistivity and had a sensitive resistance change in the low pressure (<200 Pa), good stability through 2800 cycles, and a detection limit of 10 kPa. Based on these properties, the electric signals were tested, including swallowing throat, finger bending, finger pressing, and paper folding. The simulation model of the sensors with different structural parameters under external pressure was established. With the advantages of high sensitivity, stability, and wide detection range, this sensor shows great potential for monitoring human motion and can be used in wearable devices.
RESUMO
Following the publication of the above article, an interested reader drew to the authors' attention that the western blotting data shown in Figs. 2F and 5E were strikingly similar, even though they were intended to show the results from differently performed experiments; furthermore, the migration assay images shown for the 24 h 'Blank' and 'Vector' experiments in Fig. 3C were apparently the same. The authors have consulted their original data, and realized that the errors in the presentation of these figures arose inadvertently as a consequence of selecting the wrong images for the 24 h 'Blank' experiement in Fig. 3C and the western blot for the AR / Nucleus experiment in Fig. 5E. The revised versions of Figs. 3 and 5 are shown on the next two pages. All the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. The authors regret that these errors were included in the paper, and also apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 21152124, 2019; DOI: 10.3892/mmr.2019.9841].
RESUMO
At present, the addition of dimethylcyclosiloxanes (DMCs) in cosmetics is being debated and no substantial progress has been made in their safety risk assessment because of the lack of a suitable analytical method. Therefore, it is of theoretical and practical significance to establish a method suitable for the determination of DMCs in cosmetics with different formulation systems. Accordingly, a method based on gel permeation chromatography (GPC) purification combined with gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed for the determination of seven DMCs in cosmetics. The cosmetic samples were extracted by ethyl acetate-cyclohexane (1â¶1, v/v), purified by gel permeation chromatography, separated on a DB-5ms column (30.0 m×0.25 mm×0.25 µm), confirmed and detected by gas chromatography-tandem mass spectrometry in the selected reaction monitoring (SRM) mode, and quantified by the internal standard method with n-hexadecane as the internal standard. Experiments were carried out using n-tetradecane, n-hexadecane, and n-octadecane as the internal standards, and based on the retention time in GPC and GC, n-hexadecane was found to be the suitable choice for further analyses. The extraction efficiency for the target compounds was tested in different solvents such as methanol, n-hexane, acetonitrile, ethyl acetate, and ethyl acetate-cyclohexane (1â¶1, v/v). Given the high recovery, ethyl acetate-cyclohexane (1â¶1, v/v) was selected as the extraction solvent for analyses. Among the three purification methods (analysis without purification, solid-phase extraction (SPE), and GPC purification), GPC was selected as the best method because of the minimal matrix interference to the target compounds. Under the optimized conditions, the seven DMCs showed good linearities in the range of 0.05-1.0 mg/L. The correlation coefficients (r) were 0.994-0.998, which were greater than the required of the specification (r≥0.990). The limits of detection (LODs, S/N=3) were 0.04-0.08 mg/kg, and the limits of quantification (LOQs, S/N=3) were 0.12-0.24 mg/kg. According to the cosmetic matrix in different formulation systems, standard addition recovery tests at three levels of low, medium, and high were carried out. The average recovery rates of the targets were 85.3%-108.8%. The relative standard deviations (RSDs, n=6) were 3.1%-9.4%. The established method was also employed for the analysis of cosmetics in the market, and octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) were detected at various levels in the cosmetics. The method established in this study has the advantages of operational simplicity, high sensitivity, and good reproducibility, and it allows for the determination of seven DMCs in cosmetics with different formulation systems. The establishment of this method provides a basis for the quality supervision and inspection of DMCs in cosmetics in China, in addition to providing technical support for follow-up health and safety evaluation.
Assuntos
Cosméticos , Espectrometria de Massas em Tandem , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Cosméticos/análise , Cicloexanos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Reprodutibilidade dos Testes , Extração em Fase Sólida , Solventes/análiseRESUMO
Enzalutamide is an effective drug for the treatment of castration-resistant prostate cancer (CRPC), but acquired enzalutamide resistance is usually unavoidable within the short term in many patients. Lycopene, a safe and effective phytochemical, has been documented to have anticancer activity in a variety of tumors, especially for prostate cancer (PCa). The aim of this study was to provide data support for the combination of lycopene and enzalutamide in the treatment of CRPC. To this end, tissues from patients with primary prostate cancer (PPC) and CRPC were examined by immunohistochemical analysis and found that p-AKT and p-EZH2 were overexpressed in CRPC. Furthermore, Kaplan-Meier survival analysis showed that the high expression of p-AKT and p-EZH2 may be related to the poor prognosis of patients. In addition, the expression of p-AKT, p-EZH2 and androgen receptor (AR) were significantly down-regulated in 22RV1 and C4-2B cells and the proliferation and invasion of CRPC cells were inhibited after treatment with lycopene, while SC79 (an AKT agonist) markedly rescue this effect. Of note, a combination of lycopene and enzalutamide significantly inhibited the proliferation and invasion of CRPC cells in vitro, as well as tumor growth and bone metastasis in vivo. These results suggest that the enhanced antitumor effects of enzalutamide by lycopene may be related to the reduction of AR protein levels through lycopene-mediated inhibition of AKT/EZH2 pathway, which may provide a new approach to improve the efficacy of enzalutamide in CRPC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Benzamidas , Proteína Potenciadora do Homólogo 2 de Zeste , Licopeno , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração , Proteínas Proto-Oncogênicas c-akt , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzamidas/administração & dosagem , Benzamidas/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Licopeno/administração & dosagem , Licopeno/farmacologia , Masculino , Nitrilas/administração & dosagem , Nitrilas/farmacologia , Feniltioidantoína/administração & dosagem , Feniltioidantoína/farmacologia , Neoplasias de Próstata Resistentes à Castração/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Androgênicos/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: The investigation of molecular mechanisms involved in polysaccharides and saponin metabolism is critical for genetic engineering of Polygonatum cyrtonema Hua to raise major active ingredient content. Up to now, the transcript sequences are available for different tissues of P. cyrtonema, a wide range scanning about temporal transcript at different ages' rhizomes was still absent in P. cyrtonema. RESULTS: Transcriptome sequencing for rhizomes at different ages was performed. Sixty-two thousand six hundred thirty-five unigenes were generated by assembling transcripts from all samples. A total of 89 unigenes encoding key enzymes involved in polysaccharide biosynthesis and 56 unigenes encoding key enzymes involved in saponin biosynthesis. The content of total polysaccharide and total saponin was positively correlated with the expression patterns of mannose-6-phosphate isomerase (MPI), GDP-L-fucose synthase (TSTA3), UDP-apiose/xylose synthase (AXS), UDP-glucose 6-dehydrogenase (UGDH), Hydroxymethylglutaryl CoA synthase (HMGS), Mevalonate kinase (MVK), 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (ispF), (E)-4-hydroxy-3-methylbut-2-enyl-diphosphate synthase (ispG), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (ispH), Farnesyl diphosphate synthase (FPPS). Finally, a number of key genes were selected and quantitative real-time PCR were performed to validate the transcriptome analysis results. CONCLUSIONS: These results create the link between polysaccharides and saponin biosynthesis and gene expression, provide insight for underlying key active substances, and reveal novel candidate genes including TFs that are worth further exploration for their functions and values.
Assuntos
Polygonatum , Saponinas , Perfilação da Expressão Gênica , Genes de Plantas , Polygonatum/genética , Polissacarídeos , Saponinas/genéticaRESUMO
Energy metabolism reprogramming is becoming an increasingly important hallmark of cancer. Specifically, cancers tend to undergo metabolic reprogramming to upregulate a celldependent glutamine (Gln) metabolism. Notably, hepatocellular cell adhesion molecule (HepaCAM) has been previously reported to serve a key role as a tumour suppressor. However, the possible regulatory role of HepaCAM in Gln metabolism in prostate cancer (PCa) remains poorly understood. In the present study, bioinformatics analysis predicted a significant negative correlation among the expression of HepaCAM, phosphatidylinositol4,5bisphosphate 3kinase catalytic subunit α (PIK3CA), glutaminase (GLS) and solute carrier family 1 member 5 (SLC1A5), components of Gln metabolism, in clinical and genomic datasets. Immunohistochemistry results verified a negative correlation between HepaCAM and PIK3CA expression in PCa tissues. Subsequently, liquid chromatographytandem mass spectrometry (LCMS/MS) and gas chromatographymass spectrometry (GCMS) assays were performed, and the results revealed markedly reduced levels of Gln and metabolic flux in the blood samples of patients with PCa and in PCa cells. Mechanistically, overexpression of HepaCAM inhibited Gln metabolism and proliferation by regulating PIK3CA in PCa cells. In addition, Gln metabolism was discovered to be stressresistant in PCa cells, since the expression levels of GLS and SLC1A5 remained high for a period of time after Gln starvation. However, overexpression of HepaCAM reversed this resistance to some extent. Additionally, alpelisib, a specific inhibitor of PIK3CA, effectively potentiated the inhibitory effects of HepaCAM overexpression on Gln metabolism and cell proliferation through mass spectrometry and CCK8 experiments. In addition, the inhibitory effect of PIK3CA on the growth of tumor tissue in nude mice was also confirmed by immunohistochemistry in vivo. To conclude, the results from the present study revealed an abnormal Gln metabolic profile in the blood samples of patients with PCa, suggesting that it can be applied as a clinical diagnostic tool for PCa. Additionally, a key role of the HepaCAM/PIK3CA axis in regulating Gln metabolism, cell proliferation and tumour growth was identified. The combination of alpelisib treatment with the upregulation of HepaCAM expression may serve as a novel method for treating patients with PCa.
Assuntos
Proliferação de Células/genética , Glutamina/metabolismo , Transdução de Sinais/genética , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral/metabolismo , Proliferação de Células/fisiologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Modelos Animais de Doenças , Glutamina/genética , Masculino , Camundongos , Camundongos Nus/genética , Camundongos Nus/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/prevenção & controleRESUMO
Compared with the available drugs for the treatment of fibrosis in other organs, the development of intestinal antifibrosis drugs is limited. Therefore, it is of practical significance to examine novel drugs to delay or block the development of intestinal fibrosis. The present study aimed to investigate the effect of atractylenolide III (ATLIII) on intestinal fibrosis. An MTT assay was used to detect the effect of ATLIII on the activity of IEC6 cells. The migration and invasion of fibrotic cells stimulated with TGFß were determined via wound healing and Transwell assays. An immunofluorescence assay and western blotting were conducted to assess the expression levels of protein associated with epithelialmesenchymal transition (EMT). The role of the AMPactivated protein kinase (AMPK) pathway was verified using compound C (an AMPK inhibitor) treatment. The results of the present study indicated that ATLIII had no effect on the cells at a dose of 120 µmol/l. Moreover, ATLIII can inhibit the invasion and migration of cells induced by TGFß1, as well as block the EMT process. It was found that ATLIII could also activate the AMPK pathway. Furthermore, compound C reduced the inhibitory effect of ATLIII on stimulated cells, which indicated that the AMPK pathway plays a role in the inhibition process. In conclusion, ATLIII may inhibit the EMT of IEC6 cells stimulated with TGFß1 by activating the AMPK signaling pathway.
Assuntos
Proteínas Quinases Ativadas por AMP , Transição Epitelial-Mesenquimal , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Células Epiteliais/metabolismo , Intestino Delgado/metabolismo , Lactonas , Ratos , Sesquiterpenos , Transdução de SinaisRESUMO
Increased expression of histone deacetylases (HDACs) affiliated to the epigenetic regulation is common aberration in prostate cancer (PCa). We have confirmed that hepatocyte cell adhesion molecule (hepaCAM), acting as a tumor suppressor gene, is rarely expressed in PCa previously, However, the mechanisms of which is still unknown. The level of histone acetylation reportedly may involve anti-oncogene transcription and expression. In this study, we investigated the effect of panobinostat, the broad-spectrum histone deacetylases inhibitor, on PCa LNCaP and DU145 cell growth, and observed re-expression of hepaCAM when treated with panobinostat. We demonstrated that intranuclear acetylation of lys9 of histone H3 (Ac-H3K9) were increased, while that of both mRNA and protein of HDAC1, HDAC3, and HDAC4 were decreased when the treating concentration of panobinostat increased. We confirmed the relationship between histone acetylation and the expression of hepaCAM and AR in prostate cancer tissues. We also confirmed that panobinostat could overcome the resistance for androgen deprivation therapy (ADT). Further, we combined panobinostat with Ad-hepaCAM, which resulted in significantly increased antitumor activity and significant attenuation of the proliferation-associated genes CCND1 and PCNA compared to each single treatment. In conclusion, panobinostat may enhance the acetylation of lys9 of histone 3 and reverse the hepaCAM expression through its inhibitory effect on HDACs activity in PCa LNCaP and DU145 cells; Ad-hepaCAM combined with panobinostat may synergistically inhibit the growth of LNCaP and DU145 cells, via a potential mechanism associated with the down-regulation of the expression of CCND1 and PCNA. These findings suggest that this therapeutic strategy should be further developed in clinical trials.
Assuntos
Proteínas de Ciclo Celular/genética , Panobinostat/farmacologia , Neoplasias da Próstata/genética , Antagonistas de Androgênios/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , China , Epigênese Genética/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Histonas/metabolismo , Humanos , Masculino , Panobinostat/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos , Transdução de Sinais/efeitos dos fármacosRESUMO
Resistive pressure sensors are appealing due to having several advantages, such as simple reading mechanisms, simple construction, and quick dynamic response. Achieving a constantly changeable microstructure of sensing materials is critical for the flexible pressure sensor and remains a difficulty. Herein, a flexible, tunable resistive pressure sensors is developed via simple, low-cost microsphere self-assembly and graphene/carbon nanotubes (CNTs) solution drop coating. The sensor uses polystyrene (PS) microspheres to construct an interlocked dome microstructure with graphene/CNTs as a conductive filler. The results indicate that the interlocked microdome-type pressure sensor has better sensitivity than the single microdome-type and single planar-type without surface microstructure. The pressure sensor's sensitivity can be adjusted by varying the diameter of PS microspheres. In addition, the resistance of the sensor is also tunable by adjusting the number of graphene/CNT conductive coating layers. The developed flexible pressure sensor effectively detected human finger bending, demonstrating tremendous potential in human motion monitoring.
RESUMO
OBJECTIVE: Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men which is associated with profound metabolic changes. Systematic analysis of the metabolic alterations and identification of new biomarkers may benefit PCa diagnosis and a deep understanding of the pathological mechanism. The purpose of this study was to determine the metabolic features of PCa. METHODS: Plasma and urine metabolites from 89 prostate cancer (PCa) patients, 84 benign prostatic hyperplasia (BPH) patients, and 70 healthy males were analyzed using LC-MS/MS and GC-MS. The Orthogonalised Partial Least Squares Discriminant Analysis (OPLS-DA) was used to find the significantly changed metabolites. The clinical value of the candidate markers was examined by receiver operating characteristic curve analysis and compared with prostate-specific antigen (PSA). RESULTS: Multivariate statistical analyses found a series of altered metabolites, which related to the urea cycle, tricarboxylic acid cycle (TCA), fatty acid metabolism, and the glycine cleavage system. Plasma Glu/Gln showed the highest predictive value (AUC = 0.984) when differentiating PCa patients from healthy controls, with a higher sensitivity than PSA (96.6% vs. 94.4%). Both Glu/Gln and PSA displayed a low specificity when differentiating PCa patients from BPH patients (<53.2%), while the combination of Glu/Gln and PSA can further increase the diagnostic specificity to 66.9%. CONCLUSIONS: The present study showed the metabolic features of PCa, provided strong evidence that the amide nitrogen and the energy metabolic pathways could be a valuable source of markers for PCa. Several candidate markers identified in this study were clinically valuable for further assessment.
Assuntos
Cromatografia Líquida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Nitrogênio/metabolismo , Próstata , Hiperplasia Prostática , Neoplasias da Próstata , Idoso , Metabolismo Energético , Humanos , Masculino , Redes e Vias Metabólicas , Metabolômica/métodos , Tamanho do Órgão , Próstata/diagnóstico por imagem , Próstata/metabolismo , Próstata/patologia , Antígeno Prostático Específico/análise , Hiperplasia Prostática/sangue , Hiperplasia Prostática/patologia , Hiperplasia Prostática/urina , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/urina , Reprodutibilidade dos TestesRESUMO
The present study aimed to explore the therapeutic effects of the main active ingredients of Atractylodes macrocephala on the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced mouse colitis model. TNBS-induced colitis was established in mice, which were treated with 8-ß-Hydroxyasterolide (Atractylenolideâ III) for 14â days. The body weight of the mice in the middle and high dose groups of Atractylenolideâ III was increased compared with that of the model group. The disease activity index score was significantly reduced. The activity levels of myeloperoxidase were significantly decreased following increase in the dosage of Atractylenolideâ III, as determined by histological analysis. Moreover, Atractylenolideâ III downregulated the expression levels of the inflammatory factors interleukin-1ß and tumor necrosis factor-α, and greatly suppressed the levels of the pro-oxidant markers, reactive oxygen species and malondialdehyde, while enhancing the expression levels of the antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase. The protein expression levels of formyl peptide receptorâ 1 (FPR1) and nuclear respiratory factorâ 2 (Nrf2) were upregulated in the colonic tissues of TNBS-treated mice. This effect was effectively reversed by Atractylenolide III treatment. In vivo studies indicated that TNBS alone induced a decrease in the abundance of lactobacilli and in the biodiversity of the colon. In conclusion, the present study suggested that Atractylenolide III attenuated TNBS-induced acute colitis by regulating oxidative stress via the FPR1 and Nrf2 pathways and by affecting the development of intestinal flora.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Lactonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/patologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Interleucina-1beta/metabolismo , Lactonas/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Ácido Trinitrobenzenossulfônico/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
The treatment of castration-resistant prostate cancer (CRPC) remains challenging due to the failure of androgen deprivation therapy (ADT); hence the search for other molecular therapeutic targets besides androgen receptor signaling is ongoing. This study systematically investigated the expression of SOX17 and Notch receptors in CRPC tissues and cells in vitro, showing that consistent clinical CRPC, SOX17/Notch1, and Notch4 were responsible for enzalutamide resistance in CRPC cells. The γ secretase inhibitors, BMS-708163, GSI-IX, PF-3084014, and RO4929097 abrogated the enzalutamide resistance by inhibiting Notch1 or/and Notch4 in vitro, with GSI-IX and RO4929097 being more effective than BMS-708163 and PF-3084014 in reliving bone metastasis in vivo. In conclusion, the Notch1 and Notch4 inhibitors GSI-IX and RO4929097 are promising therapeutic agents for the treatment of CRPC.