RESUMO
Circular RNAs (circRNAs) represent an emerging category of endogenous transcripts characterized by long half-life time, covalently closed structures, and cell-/tissue-specific expression patterns, making them potential disease biomarkers. Herein, we demonstrate the construction of fluorescent G-quadruplex nanowires for label-free and accurate monitoring of circular RNAs in breast cancer cells and tissues by integrating proximity ligation-rolling circle amplification cascade with lighting up G-quadruplex. The presence of target circRNA facilitates the SplintR ligase-mediated ligation of the padlock probe. Upon the addition of primers, the ligated padlock probe can serve as a template to initiate subsequent rolling circle amplification (RCA), generating numerous long G-quadruplex nanowires that can incorporate with thioflavin T (ThT) to generate a remarkably improved fluorescence signal. Benefiting from good specificity of SplintR ligase-mediated ligation reaction and exponential amplification efficiency of RCA, this strategy can sensitively detect target circRNA with a limit of detection of 4.65 × 10-18 M. Furthermore, this method can accurately measure cellular circRNA expression with single-cell sensitivity and discriminate the circRNA expression between healthy para-carcinoma tissues and breast cancer tissues, holding great potential in studying the pathological roles of circRNA and clinic diagnostics.
Assuntos
Neoplasias da Mama , Nanofios , Humanos , Feminino , RNA Circular , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Corantes Fluorescentes/química , Ligases , Técnicas de Amplificação de Ácido Nucleico/métodosRESUMO
Intensive development of vanadium-titanium mines leads to an increasing discharge of vanadium (V) into the environment, imposing potential risks to both environmental system and public health. Microorganisms play a key role in the biogeochemical cycling of V, influencing its transformation and distribution. In addition, the characterization of microbial community patterns serves to assess potential threats imposed by elevated V exposure. However, the impact of V on microbial community remains largely unknown in alkaline V tailing areas with a substantial amounts of V accumulation and nutrient-poor conditions. This study aims to explore the characteristics of microbial community in a wet tailing pond nearby a large-scale V mine. The results reveal V contamination in both water (0.60 mg/L) and sediment tailings (340 mg/kg) in the tailing pond. Microbial community diversity shows distinctive pattern between environmental metrices. Genera with the functional potential of metal reduction\resistance, nitrogen metabolism, and carbon fixation have been identified. In this alkaline V tailing pond, V and pH are major drivers to induce community variation, particularly for functional bacteria. Stochastic processes primarily govern the assemblies of microbial community in the water samples, while deterministic process regulate the community assemblies of sediment tailings. Moreover, the co-occurrence network pattern unveils strong selective pattern for sediment tailings communities, where genera form a complex network structure exhibiting strong competition for limited resource. These findings reveal the patterns of microbial adaptions in wet vanadium tailing ponds, providing insightful guidelines to mitigate the negative impact of V tailing and develop sustainable management for mine-waste reservoir.
Assuntos
Bactérias , Vanádio , Titânio , Interações Microbianas , ÁguaRESUMO
The identification of cysteine enantiomers is of great significance in the biopharmaceutical industry and medical diagnostics. Herein, we develop an electrochemical sensor to discriminate cysteine (Cys) enantiomers based on the integration of a copper metal-organic framework (Cu-MOF) with an ionic liquid. Because the combine energy of D-cysteine (D-Cys) with Cu-MOF (-9.905 eV) is lower than that of L-cysteine (L-Cys) with Cu-MOF (-9.694 eV), the decrease in the peak current of the Cu-MOF/GCE induced by D-Cys is slightly higher than that induced by L-Cys in the absence of an ionic liquid. In contrast, the combine energy of L-Cys with an ionic liquid (-1.084 eV) is lower than that of D-Cys with an ionic liquid (-1.052 eV), and the ionic liquid is easier to cross-link with L-Cys than with D-Cys. When an ionic liquid is present, the decrease in the peak current of the Cu-MOF/GCE induced by D-Cys is much higher than that induced by L-Cys. Consequently, this electrochemical sensor can efficiently discriminate D-Cys from L-Cys, and it can sensitively detect D-Cys with a detection limit of 0.38 nM. Moreover, this electrochemical sensor exhibits good selectivity, and it can accurately measure the spiked D-Cys in human serum with a recovery ratio of 100.2-102.6%, with wide applications in biomedical research and drug discovery.
Assuntos
Líquidos Iônicos , Estruturas Metalorgânicas , Humanos , Cisteína , Cobre , Estereoisomerismo , Técnicas Eletroquímicas , Limite de DetecçãoRESUMO
High-risk human papillomavirus (HPV) persistent infection is the major tumorigenesis factor for cervical cancer (CC). However, the incidence of HPV-negative CC is 5% to 30% with different HPV detection methods. High-risk HPV E6/E7 mRNA in situ hybridization (RISH) can detect HPV-driven tumors. Our study aimed to explore whether HPV typing-negative CC was caused by HPV infection. The tissues of CC patients with HPV typing results, collected from cervical biopsies, conization, or hysterectomies, were submitted to RISH using RNAscope chromogenicin. Immunohistochemistry was performed to evaluate the expression of p16INK4a and Ki-67. A total of 308 women with HPV typing results were enrolled, and 30 (9.74%) cases of HPV typing were negative. In HPV typing-negative CCs, 28/30 (93.3%) were positive for RISH, which contained 22/22 (100%) squamous cell carcinomas and 6/8 (75%) adenocarcinomas. RISH was positive in 278/278 (100%) HPV typing-positive CCs, which included 232/232 (100%) squamous cell carcinomas and 46/46 (100%) adenocarcinomas. Positive RISH in HPV typing-negative CC was significantly lower than in the HPV typing-positive group ( P =0.002, 95% confidence interval: 0.848-1.027). However, this significant difference only existed in adenocarcinoma. No significant differences were seen in the expression of p16INK4a and Ki-67 (all P >0.05). HPV typing may cause misdiagnosis in 9.74% of CC patients, and HPV E6/E7 mRNA can detect HPV in CC with HPV typing-negative patients. This approach could provide a novel option to accurately detect high-risk HPVs in cervical tumors and help to eliminate the percentage of misdiagnosed HPV-related cases.
Assuntos
Carcinoma de Células Escamosas , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/patologia , Proteínas Oncogênicas Virais/genética , Antígeno Ki-67 , RNA Viral/genética , Inibidor p16 de Quinase Dependente de Ciclina , Carcinoma de Células Escamosas/diagnóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Papillomaviridae/genéticaRESUMO
Vanadium(V) is a redox-sensitive heavy-metal contaminant whose environmental mobility is strongly influenced by pyrrhotite, a widely distributed iron sulfide mineral. However, relatively little is known about microbially mediated vanadate [V(V)] reduction characteristics driven by pyrrhotite and concomitant mineral dynamics in this process. This study demonstrated efficient V(V) bioreduction during 210 d of operation, with a lifespan about 10 times longer than abiotic control, especially in a stable period when the V(V) removal efficiency reached 44.1 ± 13.8%. Pyrrhotite oxidation coupled to V(V) reduction could be achieved by an enriched single autotroph (e.g., Thiobacillus and Thermomonas) independently. Autotrophs (e.g., Sulfurifustis) gained energy from pyrrhotite oxidation to synthesize organic intermediates, which were utilized by the heterotrophic V(V) reducing bacteria such as Anaerolinea, Bacillus, and Pseudomonas to sustain V(V) reduction. V(V) was reduced to insoluble tetravalent V, while pyrrhotite oxidation mainly produced Fe(III) and SO42-. Secondary minerals including mackinawite (FeS) and greigite (Fe3S4) were produced synchronously, resulting from further transformations of Fe(III) and SO42- by sulfate reducing bacteria (e.g., Desulfatiglans) and magnetotactic bacteria (e.g., Nitrospira). This study provides new insights into the biogeochemical behavior of V under pyrrhotite effects and reveals the previously overlooked mineralogical dynamics in V(V) reduction bioprocesses driven by Fe(II)-bearing minerals.
Assuntos
Compostos Férricos , Vanadatos , Minerais , Ferro , Oxirredução , BactériasRESUMO
While microbial reduction has gained widespread recognition for efficiently remediating environments polluted by toxic metavanadate [V(V)], the pool of identified V(V)-reducing strains remains rather limited, with the vast majority belonging to bacteria and fungi. This study is among the first to confirm the V(V) reduction capability of Streptomyces microflavus, a representative member of ubiquitous actinomycetes in environment. A V(V) removal efficiency of 91.0 ± 4.35% was achieved during 12 days of operation, with a maximum specific growth rate of 0.073 d-1. V(V) was bioreduced to insoluble V(IV) precipitates. V(V) reduction took place both intracellularly and extracellularly. Electron transfer was enhanced during V(V) bioreduction with increased electron transporters. The electron-transfer pathways were revealed through transcriptomic, proteomic, and metabolomic analyses. Electrons might flow either through the respiratory chain to reduce intracellular V(V) or to cytochrome c on the outer membrane for extracellular V(V) reduction. Soluble riboflavin and quinone also possibly mediated extracellular V(V) reduction. Glutathione might deliver electrons for intracellular V(V) reduction. Bioaugmentation of the aquifer sediment with S. microflavus accelerated V(V) reduction. The strain could successfully colonize the sediment and foster positive correlations with indigenous microorganisms. This study offers new microbial resources for V(V) bioremediation and improve the understanding of the involved molecular mechanisms.
Assuntos
Streptomyces , Vanadatos , Oxirredução , Elétrons , ProteômicaRESUMO
Vanadium(V) is a highly toxic multivalent, redox-sensitive element. It is widely distributed in the environment and employed in various industrial applications. Interactions between V and (micro)organisms have recently garnered considerable attention. This Review discusses the biogeochemical cycling of V and its corresponding bioremediation strategies. Anthropogenic activities have resulted in elevated environmental V concentrations compared to natural emissions. The global distributions of V in the atmosphere, soils, water bodies, and sediments are outlined here, with notable prevalence in Europe. Soluble V(V) predominantly exists in the environment and exhibits high mobility and chemical reactivity. The transport of V within environmental media and across food chains is also discussed. Microbially mediated V transformation is evaluated to shed light on the primary mechanisms underlying microbial V(V) reduction, namely electron transfer and enzymatic catalysis. Additionally, this Review highlights bioremediation strategies by exploring their geochemical influences and technical implementation methods. The identified knowledge gaps include the particulate speciation of V and its associated environmental behaviors as well as the biogeochemical processes of V in marine environments. Finally, challenges for future research are reported, including the screening of V hyperaccumulators and V(V)-reducing microbes and field tests for bioremediation approaches.
Assuntos
Solo , Vanádio , Vanádio/análise , Vanádio/química , Biodegradação Ambiental , Minerais , OxirreduçãoRESUMO
The bioleaching process is widely used in the treatment of ores or solid wastes, but little is known about its application in the treatment of vanadium-bearing smelting ash. This study investigated bioleaching of smelting ash with Acidithiobacillus ferrooxidans. The vanadium-bearing smelting ash was first treated with 0.1 M acetate buffer and then leached in the culture of Acidithiobacillus ferrooxidans. Comparison between one-step and two-step leaching process indicated that microbial metabolites could contribute to the bioleaching. The Acidithiobacillus ferrooxidans demonstrated a high vanadium leaching potential, solubilizing 41.9% of vanadium from the smelting ash. The optimal leaching condition was determined, which was 1% pulp density, 10% inoculum volume, an initial pH of 1.8, and 3 Fe2+g/L. The compositional analysis showed that the fraction of reducible, oxidizable, and acid-soluble was transferred into the leaching liquor. Therefore, as the alternative to the chemical/physical process, an efficient bioleaching process was proposed to enhance the recovery of vanadium from the vanadium-bearing smelting ash.
Assuntos
Acidithiobacillus , Vanádio , Acidithiobacillus/metabolismoRESUMO
This study investigated groundwater hexavalent chromium (Cr(VI)) decontamination by a biological permeable reactive barrier (bio-PRB), where a woodchip-elemental sulfur [S(0)] based mixotrophic process was established. 89.0 ± 0.27% of Cr(VI) was removed from the synthetic groundwater after 72 h at a concentration of 50 mg/L during the preliminary batch experiment. The impact of geochemical and hydrodynamic conditions Cr(VI) removal was investigated in the bio-PRB over 225 days. Although elevated Cr(VI) (i.e., 75 mg/L), addition of nitrate and short hydraulic retention time reduced the Cr(VI) removal, 87.2 ± 2.09% of Cr(VI) removal was accomplished. Characterization of the solids indicated that the soluble Cr(VI) was converted and immobilized as the insoluble trivalent chromium [Cr(III)]. 16S rRNA gene based sequencing results suggested that micromolecules produced by woodchip cellulose hydrolyzing- and sulfur oxidizing bacteria were further used by functional Cr(VI) removal bacteria (e.g., Geobacteraceae and Pseudomonas). The extracellular protein and humic-like substances in extracellular polymeric substances (EPS) can bind toxic Cr(VI) through carboxyl and hydroxyl groups, and reduce Cr(VI) in an enzymatic manner. The preliminary finding of this study provided a potential way to utilize agricultural waste for in-situ Cr(VI) contaminated-groundwater remediation.
Assuntos
Água Subterrânea , Poluentes Químicos da Água , RNA Ribossômico 16S , Poluentes Químicos da Água/análise , Água Subterrânea/química , Cromo/análise , Enxofre , BiotecnologiaRESUMO
Steroid-induced osteonecrosis of the femoral head (SIONFH) has been a common disease following corticosteroid therapy. Presently, we aim to explore the functions of circular RNA (circ) PVT1 in SIONFH rats and the underlying mechanism. Glucocorticoid (GC) was used to treat SD rats and bone marrow-derived mesenchymal stem cells (BMSCs) to construct SIONFH model in vitro and in vivo, respectively. The pathological injury of the femoral head in the SIONFH rats was detected via haematoxylin-eosin (HE) staining and immunohistochemistry (IHC). The osteogenic differentiation, proliferation and apoptosis of BMSCs were detected. Western blot was used to detect Smad7, Bax, Bcl2 and Smad2/3. The potential targets of circPVT1 and miR-21-5p were validated through luciferase reporter gene assay and RNA pull-down assay, respectively. We found that CircPVT1 was decreased in the femoral head of SIONFH rats and GC-treated BMSCs, while miR-21-5p was markedly up-regulated. Overexpressed circPVT1 attenuated the apoptosis and cell viability inhibition of BMSCs induced by GC, while miR-21-5p up-regulation had the opposite effects. What's more, the in vivo experiments confirmed that up-regulating circPVT1 repressed osteonecrosis in SIONFH rats through repressing apoptosis. Mechanistically, circPVT1 functioned as a ceRNA of miR-21-5p, which targeted at the 3'untranslated region of Smad7. CircPVT1 enhancing Smad7 and mitigating GC activated TGFß/Smad2/3 pathway through inhibiting miR-21-5p. In conclusion, CircPVT1 exerts protective effects against SIONFH via modulating miR-21-5p-mediated Smad7/TGFß pathway.
Assuntos
Necrose da Cabeça do Fêmur/prevenção & controle , MicroRNAs/genética , Osteogênese , RNA Circular/genética , Proteína Smad7/metabolismo , Esteroides/toxicidade , Fator de Crescimento Transformador beta1/metabolismo , Animais , Apoptose , Biomarcadores/metabolismo , Proliferação de Células , Células Cultivadas , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/patologia , Regulação da Expressão Gênica , Masculino , Ratos , Ratos Sprague-Dawley , Proteína Smad7/genética , Fator de Crescimento Transformador beta1/genéticaRESUMO
Uncovering the linkages between community assembly and species diversity is a fundamental issue in microbial ecology. In this study, a large-scale (transect intervals of 1257.6 km) cross-biome soil survey was conducted, which ranged over agricultural fields, forests, wetlands, grasslands and desert, in the arid regions of northwest China. The aim was to investigate the biogeographic distribution, community assembly and species co-occurrence of soil fungi. The fungal communities in agricultural soils exhibited a steeper distance-decay slope and wider niche breadths, and were more strongly affected by stochastic assembly processes, than fungi in other natural habitats. A strong relationship was revealed between soil fungal richness and community assembly in arid ecosystems, with the influence of stochastic assembly processes decreasing with increasing fungal richness. Moreover, aridity was the most important environmental factor influencing fungal richness, ß-diversity and species co-occurrence patterns. Specifically, the predicted increase in arid conditions will probably reduce fungal richness and network complexity. These findings represent a considerable advance in linking fungal richness to mechanisms underlying the biogeographic patterns and assembly processes of fungal communities in arid ecosystems. These results can thus be used to forecast species co-occurrence and diversities pattern of soil fungi under climate aridity and land-use change scenarios.
Assuntos
Ecossistema , Solo , Clima Desértico , Fungos/genética , Microbiologia do SoloRESUMO
BACKGROUND: There are differences in survival between high-and low-grade Upper Tract Urothelial Carcinoma (UTUC). Our study aimed to develop a nomogram to predict overall survival (OS) of patients with high- and low-grade UTUC after tumor resection, and to explore the difference between high- and low-grade patients. METHODS: Patients confirmed to have UTUC between 2004 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. The UTUCs were identified and classified as high- and low-grade, and 1-, 3- and 5-year nomograms were established. The nomogram was then validated using the Chinese multicenter dataset (patients diagnosed in Shandong, China between January 2010 and October 2020). RESULTS: In the high-grade UTUC patients, nine important factors related to survival after tumor resection were identified to construct nomogram. The C index of training dataset was 0.740 (95% confidence interval [CI]: 0.727-0.754), showing good calibration. The C index of internal validation dataset was 0.729(95% CI:0.707-0.750). On the other hand, Two independent predictors were identified to construct nomogram of low-grade UTUC. The C index was 0.714 (95% CI: 0.671-0.758) for the training set,0.731(95% CI:0.670-0.791) for the internal validation dataset. Encouragingly, the nomogram was clinically useful and had a good discriminative ability to identify patients at high risk. CONCLUSION: We constructed a nomogram and a corresponding risk classification system predicting the OS of patients with an initial diagnosis of high-and low-grade UTUC.
Assuntos
Modelos Estatísticos , Nomogramas , Programa de SEER/estatística & dados numéricos , Neoplasias da Bexiga Urinária/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
Hexavalent chromium [Cr(VI)] is one of the common heavy-metal contaminants in groundwater, and the availability of electron donors is considered to be a key parameter for Cr(VI) biotransformation. During the autotrophic remediation process, however, much remains to be illuminated about how complex syntrophic microbial communities couple Cr(VI) reduction with other elemental cycles. Two series of Cr(VI)-reducing groundwater bioreactors were independently amended by elemental sulfur and iron and inoculated with the same inoculum. After 160 days of incubation, both bioreactors showed similar archaea-dominating microbiota compositions, whereas a higher Cr(VI)-reducing rate and more methane production were detected in the Fe0-driven one. Metabolic reconstruction of 23 retrieved genomes revealed complex symbiotic relationships driving distinct elemental cycles coupled with Cr(VI) reduction in bioreactors. In both bioreactors, these Cr(VI) reducers were assumed to live in syntrophy with oxidizers of sulfur, iron, hydrogen, and volatile fatty acids and methane produced by carbon fixers and multitrophic methanogens, respectively. The significant difference in methane production was mainly due to the fact that the yielded sulfate greatly retarded acetoclastic methanogenesis in the S-bioreactor. These findings provide insights into mutualistic symbioses of carbon, sulfur, iron, and chromium metabolisms in groundwater systems and have implications for bioremediation of Cr(VI)-contaminated groundwater.
Assuntos
Água Subterrânea , Poluentes Químicos da Água , Biodegradação Ambiental , Reatores Biológicos , Cromo , OxirreduçãoRESUMO
Whereas prospects of bioremediation for a vanadium(V) [V(V)]-contaminated environment are widely recognized, reported functional species are extremely limited, with the vast majority of Gram-negative bacteria in Proteobacteria. Herein, the effectiveness of V(V) reduction is proved for the first time by Lactococcus raffinolactis, a Gram-positive bacterium in Firmicutes. The V(V) removal efficiency was 86.5 ± 2.17% during 10-d operation, with an average removal rate of 4.32 ± 0.28 mg/L·d in a citrate-fed system correspondingly. V(V) was bio-reduced to insoluble vanadium(IV) and distributed both inside and outside the cells. Nitrite reductase encoded by gene nirS mainly catalyzed intracellular V(V) reduction, revealing a previously unrecognized pathway. Oxidative stress induced by reactive oxygen species from dissimilatory V(V) reduction was alleviated through strengthened superoxide dismutase and catalase activities. Extracellular polymeric substances with chemically reactive hydroxyl (-OH) and carboxyl (-COO-) groups also contributed to V(V) binding and reduction as well as ROS scavenging. This study can improve the understanding of Gram-positive bacteria for V(V) bio-detoxification and offer microbial resources for bioremediation of a V(V)-polluted environment.
Assuntos
Lactococcus , Vanádio , Biodegradação Ambiental , Oxirredução , Vanádio/análiseRESUMO
Cu2+ ions are required by all living organisms and play important roles in many bactericides and fungicides. We previously reported that Cu2+ can elicit defense responses, which are dependent on the ethylene signaling pathway in Arabidopsis However, the mechanism by which Cu2+ elicits the biosynthesis of ethylene remains unclear. Here, we show that CuSO4 treatment rapidly increases the production of ethylene. In addition, it upregulates the expression of several defense-related genes and ethylene biosynthesis genes, including genes encoding S-adenosylmethionine synthase, 1-aminocyclopropane-1-carboxylate (ACC) synthase (ACS) and ACC oxidase. Among these genes, Arabidopsis thaliana (At)ACS8 was identified as essential for the defense response and early ethylene biosynthesis induced by Cu2+ Furthermore, Cu2+-induced AtACS8 expression depended on the copper-response cis-element (CuRE) in the promoter of AtACS8 Our study indicates that Cu2+ specifically activates the expression of AtACS8 to promote the early biosynthesis of ethylene that elicits plant immunity in Arabidopsis plants.
Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Cobre/farmacologia , Etilenos/biossíntese , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Fluorescência Verde/metabolismo , Íons , Mutação/genética , Regiões Promotoras Genéticas/genética , Elementos de Resposta/genéticaRESUMO
Lung cancer is the leading cause of cancer-related death, and adenocarcinoma is the most common histological type of lung cancer. Syntaxin-binding protein 1 (STXBP1) is essential for exocytosis of secretory vesicles. Since exocytosis is the basic cellular process of cells, we investigated STXBP1 expression and clinical significance in lung adenocarcinoma. We performed quantitative real-time polymerase chain reaction in 20 pairs of lung adenocarcinoma and paired normal tissues, and demonstrated that the relative expression levels of STXBP1 mRNA in lung adenocarcinoma was significantly higher than those in normal lung tissues. We then carried out immunohistochemistry (IHC) to determine the expression profile of STXBP1 in 276 lung adenocarcinoma specimens, and categorized patients into subgroups with low or high STXBP1 expression, based on the IHC score. Moreover, STXBP1 expression phenotypes were categorized as membrane, cytoplasm, and mixed expression (both membrane and cytoplasm) expression. High STXBP1 protein accounted for 58.0% of all the 276 cases (160/276), and membrane, cytoplasm or mixed STXBP1 accounted for 28.75%, 25.63% and 45.63% in the 160 cases of high STXBP1 expression. The clinical significances of these phenotypes were evaluated by analyzing their correlation with clinicopathological factors, as well as their prognostic values. Consequently, the whole STXBP1 expression or membranal STXBP1 expression were correlated with poor prognosis and were independent prognostic factors of lung adenocarcinoma. The whole and membranal STXBP1 expression are independent prognostic factors of lung adenocarcinoma. STXBP1 detection is capable to help screen patients who may have poor prognosis and strengthen the adjuvant therapy more precisely.
Assuntos
Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Membrana Celular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Munc18/metabolismo , Estudos de Coortes , Feminino , Humanos , Espaço Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
PTMC-PEG-PTMC triblock copolymers were prepared by ring-opening polymerization of trimethylene carbonate (TMC) in the presence of dihydroxylated poly(ethylene glycol) (PEG) with Mn of 6000 and 10,000 as macro-initiator. The copolymers with different PTMC block Lengths and the two PEGs were end functionalized with acryloyl chloride. The resulting diacrylated PEG-PTMC-DA and PEG-DA were characterized by using NMR, GPC and DSC. The degree of substitution of end groups varied from 50.0 to 65.1%. Hydrogels were prepared by photo-crosslinking PEG-PTMC-DA and PEG-DA in aqueous solution using a water soluble photo-initiator under visible light irradiation. The effects of PTMC and PEG block lengths and degree of substitution on the swelling and weight loss of hydrogels were determined. Higher degree of substitution leads to higher crosslinking density, and thus to lower degree of swelling and weight loss. Similarly, higher PTMC block length also leads to lower degree of swelling and weight loss. Freeze dried hydrogels exhibit a highly porous structure with pore sizes from 20 to 100 µm. The biocompatibility of hydrogels was evaluated by MTT assay, hemolysis test, and dynamic clotting time measurements. Results show that the various hydrogels present outstanding cyto- and hemo-compatibility. Doxorubicin was taken as a model drug to evaluate the potential of PEG-PTMC-DA and PEG-DA hydrogels as drug carrier. An initial burst release was observed in all cases, followed by slower release up to more than 90%. The release rate is strongly dependent on the degree of swelling. The higher the degree of swelling, the faster the release rate. Finally, the effect of drug loaded hydrogels on SKBR-3 tumor cells was evaluated in comparison with free drug. Similar cyto-toxicity was obtained for drug loaded hydrogels and free drug at comparable drug concentrations. Therefore, injectable PEG-PTMC-DA hydrogels with outstanding biocompatibility and drug release properties could be most promising as bioresorbable carrier of hydrophilic drugs.
Assuntos
Actinas , Neoplasias da Mama , Calgranulina A , Calgranulina B , Movimento Celular , Transição Epitelial-Mesenquimal , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Feminino , Actinas/metabolismo , Calgranulina B/metabolismo , Calgranulina B/genética , Calgranulina A/metabolismo , Calgranulina A/genética , Linhagem Celular Tumoral , Invasividade Neoplásica , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/genética , PolimerizaçãoRESUMO
MAIN CONCLUSION: A rice allele of PSKR1 functioning in resistance to bacterial leaf streak was identified. Phytosulfokine (PSK), a disulfated pentapeptide encoded by precursor genes that are ubiquitously present in higher plants, belongs to the group of plant peptide growth factors. The PSK receptor PSKR1 in Arabidopsis thaliana is an active kinase and has guanylate cyclase activity resulting in dual-signaling outputs. Here, the LOC_Os02g41890 out of three candidates completely rescued root growth and susceptible to Pseudomonas syringae pv. DC3000 in the Arabidopsis pskr1-3 mutant and was identified as OsPSKR1. This protein was localized to plasma membrane similar to AtPSKR1. The expression of OsPSKR1 was upregulated upon inoculation with RS105, a strain of Xanthomonas oryzae pv. oryzicola (Xoc) that cause bacterial leaf streak in rice. OsPSKR1 overexpression (OE) lines had greater resistance to RS105 than the wild type. Consistently, the expression of pathogenesis-related genes involved in the salicylic acid (SA) pathway was upregulated in the transgenic lines. Overall, OsPSKR1 functions as a candidate PSK receptor and regulates resistance to Xoc by activating the expression of pathogenesis-related genes involved in the SA pathway in rice.