Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 116
Filtrar
1.
Cell ; 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35777355

RESUMO

The host-seeking activity of hematophagous arthropods is essential for arboviral transmission. Here, we demonstrate that mosquito-transmitted flaviviruses can manipulate host skin microbiota to produce a scent that attracts mosquitoes. We observed that Aedes mosquitoes preferred to seek and feed on mice infected by dengue and Zika viruses. Acetophenone, a volatile compound that is predominantly produced by the skin microbiota, was enriched in the volatiles from the infected hosts to potently stimulate mosquito olfaction for attractiveness. Of note, acetophenone emission was higher in dengue patients than in healthy people. Mechanistically, flaviviruses infection suppressed the expression of RELMα, an essential antimicrobial protein on host skin, thereby leading to the expansion of acetophenone-producing commensal bacteria and, consequently, a high acetophenone level. Given that RELMα can be specifically induced by a vitamin A derivative, the dietary administration of isotretinoin to flavivirus-infected animals interrupted flavivirus life cycle by reducing mosquito host-seeking activity, thus providing a strategy of arboviral control.

2.
J Cell Biochem ; : e30614, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884354

RESUMO

Currently, the clinical outcomes of peripheral nerve injuries are suboptimal, highlighting the urgent need to understand the mechanisms of nerve injury to enhance treatment strategies. Muscle-derived stem cells (MDSCs) are a diverse group of multipotent cells that hold promise for peripheral nerve regeneration due to their strong antioxidant and regenerative properties. Our research has revealed that severe ferroptosis occurs in the sciatic nerve and ipsilateral dorsal root ganglion following sciatic nerve injury. Interestingly, we have observed that MDSC-derived exosomes effectively suppress cell ferroptosis and enhance cell viability in Schwann cells and dorsal root ganglion cells. Treatment with exosomes led to increased expression of BDNF and P62 in Schwann cells, decreased expression of Keap1, Nrf2, and HO-1 in Schwann cells, and upregulated dorsal root ganglion cells. Rats treated with exosomes exhibited improvements in sciatic nerve function, sensitivity to stimuli, and reduced muscle atrophy, indicating a positive impact on post-injury recovery. In conclusion, our findings demonstrate the occurrence of ferroptosis in the sciatic nerve and dorsal root ganglion post-injury, with MDSC exosomes offering a potential therapeutic strategy by inhibiting ferroptosis, activating the Keap1-Nrf2-HO-1 pathway, and optimizing the post-injury repair environment.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38290448

RESUMO

Objective: Multimodal cocktail analgesic injection (CAI) is widely used as an adjunct pain-reliever in the postoperative phase of patients undergoing total knee arthroplasty (TKA) due to intense postoperative pain accompanying the procedure leading to complications, thereby extending hospital stays. The aim of this study is to establish the clinical efficacy and effects of utilizing CAI regimens during the TKA procedure and the corresponding postoperative patient outcomes. Methods: A database search for pertinent articles literature search was performed in Embase, PubMed, Cochrane Library, Web of Science, and MEDLINE databases. RevMan version 5.4 was used to perform a meta-analysis on the included studies. Results: Data screening and selection produced 15 relevant articles that met the eligibility criteria of this study. The meta-analysis revealed insignificant difference between cocktail injected and control groups in VAS postoperative pain scores both at rest and during activity (OR 0.79, 95% CI 0.59 to 1.05; I2 = 0%; P = .93) and (OR 0.79, 95% CI 0.57 to 1.10; I2 = 0%; P = .75), respectively. Similarly, there was insignificant differences in postoperative knee flexion ROM, postoperative narcotic consumption, and length of stays between the two groups, (OR 1.20, 95% CI 1.03 to 1.40; P = .53), (OR 0.62, 95% CI 0.36 to 1.07; P = .09), and (OR 0.45, 95% CI 0.29 to 0.70; P = .21), respectively. However, the postoperative complications reveal statistical significance between the cocktail injected and the control group (OR 0.45, 95% CI 0.29 to 0.70; P = .004). Conclusion: It is concluded that CAI can play a crucial role in minimizing post-operative complications for patients undergoing TKA.

4.
J Biol Chem ; 298(12): 102620, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36272645

RESUMO

Fission protein 1 (FIS1) and dynamin-related protein 1 (DRP1) were initially described as being evolutionarily conserved for mitochondrial fission, yet in humans the role of FIS1 in this process is unclear and disputed by many. In budding yeast where Fis1p helps to recruit the DRP1 ortholog from the cytoplasm to mitochondria for fission, an N-terminal "arm" of Fis1p is required for function. The yeast Fis1p arm interacts intramolecularly with a conserved tetratricopeptide repeat core and governs in vitro interactions with yeast DRP1. In human FIS1, NMR and X-ray structures show different arm conformations, but its importance for human DRP1 recruitment is unknown. Here, we use molecular dynamics simulations and comparisons to experimental NMR chemical shifts to show the human FIS1 arm can adopt an intramolecular conformation akin to that observed with yeast Fis1p. This finding is further supported through intrinsic tryptophan fluorescence and NMR experiments on human FIS1 with and without the arm. Using NMR, we observed the human FIS1 arm is also sensitive to environmental changes. We reveal the importance of these findings in cellular studies where removal of the FIS1 arm reduces DRP1 recruitment and mitochondrial fission similar to the yeast system. Moreover, we determined that expression of mitophagy adapter TBC1D15 can partially rescue arm-less FIS1 in a manner reminiscent of expression of the adapter Mdv1p in yeast. These findings point to conserved features of FIS1 important for its activity in mitochondrial morphology. More generally, other tetratricopeptide repeat-containing proteins are flanked by disordered arms/tails, suggesting possible common regulatory mechanisms.


Assuntos
Dinaminas , GTP Fosfo-Hidrolases , Proteínas de Membrana , Proteínas Mitocondriais , Humanos , Dinaminas/genética , Dinaminas/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Membrana/metabolismo , Dinâmica Mitocondrial , Proteínas Mitocondriais/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
5.
EMBO Rep ; 22(7): e52891, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34184813

RESUMO

Fusobacterium nucleatum (Fn) is a Gram-negative oral commensal, prevalent in various human diseases. It is unknown how this common commensal converts to a rampant pathogen. We report that Fn secretes an adhesin (FadA) with amyloid properties via a Fap2-like autotransporter to enhance its virulence. The extracellular FadA binds Congo Red, Thioflavin-T, and antibodies raised against human amyloid ß42. Fn produces amyloid-like FadA under stress and disease conditions, but not in healthy sites or tissues. It functions as a scaffold for biofilm formation, confers acid tolerance, and mediates Fn binding to host cells. Furthermore, amyloid-like FadA induces periodontal bone loss and promotes CRC progression in mice, with virulence attenuated by amyloid-binding compounds. The uncleaved signal peptide of FadA is required for the formation and stability of mature amyloid FadA fibrils. We propose a model in which hydrophobic signal peptides serve as "hooks" to crosslink neighboring FadA filaments to form a stable amyloid-like structure. Our study provides a potential mechanistic link between periodontal disease and CRC and suggests anti-amyloid therapies as possible interventions for Fn-mediated disease processes.


Assuntos
Adesinas Bacterianas , Fusobacterium nucleatum , Adesinas Bacterianas/metabolismo , Animais , Transporte Biológico , Camundongos , Sinais Direcionadores de Proteínas , Virulência
6.
Anim Biotechnol ; 34(5): 1786-1795, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35302433

RESUMO

The main component of donkey meat is skeletal muscle, and different muscle fibers have been found to be associated with meat quality. However, RNA-seq technology has yet to be used to profile the transcriptomic changes of different muscles of the donkey. In this study, the characterizations of different muscles on the gene expression profiles of Dezhou donkey were obtained, the aim was to identify the important genes in donkey muscles, and aid in improving donkey meat quality via RNA-seq. In the donkey gluteus (DG) and donkey longissimus dorsi (DL) group, GO enrichment indicated that DEGs were mainly involved in the biological regulation and metabolic process, and KEGG analysis shows that a total of 427 DEGs were mapped to 216 KEGG pathways and 23 KEGG pathways were significantly enriched such as the ribosome, glycolysis/gluconeogenesis, glucagon signaling pathway and biosynthesis of amino acids pathways. Meanwhile, 504 DEGs were mapped to 223 KEGG pathways, in which 17 were significantly enriched including cardiac muscle contraction and oxytocin signaling pathway in donkey hamstring muscles (DH) and DL group. In addition, the tenderness in donkey meat might involve muscle fiber type and glucose metabolism, which might profit from the DEGs including MYH1, MYH7, TNNC1, TNNI3, TPM3, ALDOA, ENO3, and PGK1. The genes found in this study will provide some ideas for further understanding the molecular mechanism of donkey meat quality.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Animais , RNA-Seq , Perfilação da Expressão Gênica/veterinária , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas
7.
Int J Mol Sci ; 24(10)2023 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-37240056

RESUMO

Seed germination is a complex, multistage developmental process that is an important step in plant development. In this study, RNA-Seq was conducted in the embryo and endosperm of unshelled germinating rice seeds. A total of 14,391 differentially expressed genes (DEGs) were identified between the dry seeds and the germinating seeds. Of these DEGs, 7109 were identified in both the embryo and endosperm, 3953 were embryo specific, and 3329 were endosperm specific. The embryo-specific DEGs were enriched in the plant-hormone signal-transduction pathway, while the endosperm-specific DEGs were enriched in phenylalanine, tyrosine, and tryptophan biosynthesis. We categorized these DEGs into early-, intermediate-, and late-stage genes, as well as consistently responsive genes, which can be enriched in various pathways related to seed germination. Transcription-factor (TF) analysis showed that 643 TFs from 48 families were differentially expressed during seed germination. Moreover, 12 unfolded protein response (UPR) pathway genes were induced by seed germination, and the knockout of OsBiP2 resulted in reduced germination rates compared to the wild type. This study enhances our understanding of gene responses in the embryo and endosperm during seed germination and provides insight into the effects of UPR on seed germination in rice.


Assuntos
Endosperma , Oryza , Humanos , Endosperma/metabolismo , Sementes/metabolismo , Germinação/genética , Oryza/genética , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica , Transcriptoma
8.
BMC Surg ; 21(1): 224, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931045

RESUMO

BACKGROUND: Adenosquamous carcinoma (ASC) of the ampulla of Vater (AmV) is exceedingly rare with more aggressive behavior and worse prognosis than adenocarcinoma. The finding of ASC at the AmV in combination to the gastric adenocarcinoma has never been reported in the literature before. CASE PRESENTATION: An old lady was diagnosed as gastric adenocarcinoma at stage IV with enlargement of supraclavicular lymph nodes by gastroscopy and histopathological evaluation 3 years ago. Afterwards, the patient achieved complete remission after regular chemotherapy. However, the patient manifested yellow sclera and skin, choluria and clay colored stool 3 months ago. Preoperative contrast-enhanced CT, ERCP, MRCP, and PET/CT revealed the presence of an ampullary tumor. The patient then underwent laparoscopic radical gastrectomy and pancreaticoduodenectomy with regional lymph node dissection. Postoperative cytological analyses confirmed the diagnosis of gastric ulcer with complete response to neoadjuvant therapy and ASC at the AmV. The patient's postoperative outcome was uneventful. CONCLUSION: Drawing firm conclusions about the diagnosis of ampullary ASC is difficult because of the difficulty in acquiring both adenocarcinoma and SCC components by fine needle biopsy. The rarity of ASC of the AmV coexistent with gastric carcinoma makes it difficult to elucidate their clinicopathological characteristics, therapeutic strategies and overall prognosis. Surgical resection still remains the main treatment method.


Assuntos
Adenocarcinoma , Ampola Hepatopancreática , Carcinoma Adenoescamoso , Adenocarcinoma/terapia , Carcinoma Adenoescamoso/cirurgia , Feminino , Humanos , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
9.
Phys Rev Lett ; 125(6): 060405, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32845667

RESUMO

The manipulation of quantum "resources" such as entanglement, coherence, and magic states lies at the heart of quantum science and technology, empowering potential advantages over classical methods. In practice, a particularly important kind of manipulation is to "purify" the quantum resources since they are inevitably contaminated by noise and thus often lose their power or become unreliable for direct usage. Here we prove fundamental limitations on how effectively generic noisy resources can be purified enforced by the laws of quantum mechanics, which universally apply to any reasonable kind of quantum resource. More explicitly, we derive nontrivial lower bounds on the error of converting any full-rank noisy state to any target pure resource state by any free protocol (including probabilistic ones)-it is impossible to achieve perfect resource purification, even probabilistically. Our theorems indicate strong limits on the efficiency of distillation, a widely used type of resource purification routine that underpins many key applications of quantum information science. In particular, this general result induces the first explicit lower bounds on the resource cost of magic state distillation, a leading scheme for realizing scalable fault-tolerant quantum computation. Implications for the standard error-correction-based methods are specifically discussed.

10.
Phys Rev Lett ; 125(6): 060404, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32845691

RESUMO

Quantum coherence is a fundamental resource that quantum technologies exploit to achieve performance beyond that of classical devices. A necessary prerequisite to achieve this advantage is the ability of measurement devices to detect coherence from the measurement statistics. Based on a recently developed resource theory of quantum operations, here we quantify experimentally the ability of a typical quantum-optical detector, the weak-field homodyne detector, to detect coherence. We derive an improved algorithm for quantum detector tomography and apply it to reconstruct the positive-operator-valued measures of the detector in different configurations. The reconstructed positive-operator-valued measures are then employed to evaluate how well the detector can detect coherence using two computable measures. As the first experimental investigation of quantum measurements from a resource theoretical perspective, our work sheds new light on the rigorous evaluation of the performance of a quantum measurement apparatus.

11.
Chemistry ; 26(31): 7092-7108, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32037581

RESUMO

Many cancer cells critically rely on antioxidant systems for cell survival and are vulnerable to further oxidative impairment triggered by agents generating reactive oxygen species (ROS). Therefore, the classical design and development of inhibitors that target antioxidant defense enzymes such as thioredoxin reductase (TrxR) can be a promising anticancer strategy. Herein, it is shown that a gold(I) complex containing an oleanolic acid derivative (4 b) induces apoptosis of ovarian cancer A2780 cells by activating endoplasmic reticulum stress (ERS). It can inhibit TrxR enzyme activity to elevate ROS, mediate ERS and mitochondrial dysfunction, and finally leads to cell cycle arrest and apoptosis of A2780 cells. Notably, this complex inhibits A2780 xenograft tumor growth accompanied by increased ERS level and decreased TrxR activity in tumor tissues.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Ouro/química , Ácido Oleanólico/química , Neoplasias Ovarianas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/química , Estresse do Retículo Endoplasmático , Feminino , Ouro/farmacologia , Humanos , Oxirredução , Tiorredoxina Dissulfeto Redutase/química
12.
World J Surg ; 44(12): 4142-4148, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32918103

RESUMO

BACKGROUND: Lymph node metastasis (LNM) often occurs in papillary thyroid carcinoma (PTC); the efficacy of ultrasound for predicting high-volume lymph node metastases (LNMs) in patients with PTC remains unexplored. METHODS: The medical records of 2073 consecutive PTC patients were reviewed. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to evaluate the efficacy of ultrasound. Risk factors for LNM/high-volume LNMs and lymph node involvement on ultrasound (usLNM) were identified by univariate and multivariate analyses. RESULTS: Of all the patients, 936 (45.2%) patients had LNMs, and 254 (12.3%) patients had high-volume LNMs. The sensitivity of ultrasound for detecting LNM/high-volume LNMs was 27.9% and 63.8%, respectively; the specificity was 93.1% and 90.3%, respectively. The NPV for ultrasound in detecting high-volume LNMs was 94.7%. In multivariate analysis, male sex (OR = 2.108, p < 0.001), tumor diameter > 1.0 cm (OR = 2.304, p < 0.001) and usLNM (+) (OR = 12.553, p < 0.001) were independent clinical risk factors for high-volume LNMs. Tumor diameter > 1 cm (OR = 3.036, p < 0.001) and male sex (OR = 1.642, p < 0.001) were independent clinical risk factors for usLNM; a skilled sonographer (OR = 1.121, p = 0.358) was not significantly associated with usLNM. CONCLUSIONS: Lymph node involvement found by ultrasound has great predictive value for high-volume LNMs; the NPV is very high for patients without lymph node involvement on ultrasound. The ultrasound results do not appear to be influenced by the experience of the sonographer.


Assuntos
Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Cirurgiões/psicologia , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Sensibilidade e Especificidade , Adulto Jovem
13.
J Cell Physiol ; 234(9): 16238-16251, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30741413

RESUMO

Tafazzin has been found to be associated with tumor progression. Mitochondrial homeostasis regulates cancer cell viability and metastasis. However, the roles of Tafazzin and mitochondrial homeostasis in thyroid cancer have not been explored. The aim of our study is to investigate the influences of Tafazzin on thyroid cancer apoptosis with a focus on mitochondrial fission. Our results indicated that Tafazzin deletion induced death in thyroid cancer via apoptosis. Biological analysis demonstrated that mitochondrial stress, including mitochondrial bioenergetics disorder, mitochondrial oxidative stress, and mitochondrial apoptosis, was activated by Tafazzin deletion. Furthermore, we found that Tafazzin affected mitochondrial stress by triggering inverted formin 2 (INF2)-related mitochondrial fission. The loss of INF2 sustained mitochondrial function and promoted cancer cell survival. Molecular investigation illustrated that Tafazzin regulated INF2 expression via the JNK signaling pathway; moreover, the blockade of JNK prevented Tafazzin-mediated INF2 expression and improved cancer cell survival. Taken together, our results highlight the key role of Tafazzin as a master regulator of thyroid cancer viability via the modulation of INF2-related mitochondrial fission and the JNK signaling pathway. These findings defined Tafazzin deletion and INF2-related mitochondrial fission as tumor suppressors that act by promoting cancer apoptosis via the JNK signaling pathway, with potential implications for new approaches to thyroid cancer therapy.

14.
Phys Rev Lett ; 123(2): 020401, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31386487

RESUMO

A fundamental approach for the characterization and quantification of all kinds of resources is to study the conversion between different resource objects under certain constraints. Here we analyze, from a resource-nonspecific standpoint, the optimal efficiency of resource formation and distillation tasks with only a single copy of the given quantum state, thereby establishing a unified framework of one-shot quantum resource manipulation. We find general bounds on the optimal rates characterized by resource measures based on the smooth max- or min-relative entropies and hypothesis testing relative entropy, as well as the free robustness measure, providing them with general operational meanings in terms of optimal state conversion. Our results encompass a wide class of resource theories via the theory-dependent coefficients we introduce, and the discussions are solidified by important examples, such as entanglement, coherence, superposition, magic states, asymmetry, and thermal nonequilibrium.

15.
Phys Rev Lett ; 122(14): 140402, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-31050492

RESUMO

One of the central problems in the study of quantum resource theories is to provide a given resource with an operational meaning, characterizing physical tasks in which the resource can give an explicit advantage over all resourceless states. We show that this can always be accomplished for all convex resource theories. We establish in particular that any resource state enables an advantage in a channel discrimination task, allowing for a strictly greater success probability than any state without the given resource. Furthermore, we find that the generalized robustness measure serves as an exact quantifier for the maximal advantage enabled by the given resource state in a class of subchannel discrimination problems, providing a universal operational interpretation to this fundamental resource quantifier. We also consider a wider range of subchannel discrimination tasks and show that the generalized robustness still serves as the operational advantage quantifier for several well-known theories such as entanglement, coherence, and magic.

16.
BMC Surg ; 19(1): 89, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296197

RESUMO

BACKGROUNDS: The clinicopathologic features and biological behaviors of pancreatic mixed adenoneuroendocrine carcinoma (pMANEC) and its impacts on survival are poorly known. METHODS: We retrospectively reviewed seven pMANEC cases from a single institution from September 2010 to January 2017 along with twenty-one previously reported cases from the literature. Survival and prognostic analyses were conducted using Kaplan-Meier estimates and Cox regression, respectively. RESULTS: Seven pMANEC cases were identified during the study interval. Among the six patients who underwent operations, five reached R0 resections, one experienced postoperative pancreatic fistula, and two suffered other complications. The median progression-free survival (PFS) and disease-specific survival (DSS) were 7.5 months (2 to 36 months) and 15 months (6 to 36 months), respectively. A total analysis of twenty-eight pMANEC cases showed that patients were mostly older (median age, 59.5 years) and male (64.3%). The two most common symptoms were abdominal pain (53.6%) and obstructive jaundice (35.7%). The majority of pMANECs were non-functional (89.3%) and located in the pancreatic head (64.3%). The median diameter of pMANEC was 3.0 cm, with a wide range (0.5 to 19.0 cm). Lymph node metastasis (P = 0.015) was associated with decreased DSS, while age (P = 0.414), sex (P = 0.125), tumor size (P = 0.392), location (P = 0.913), functional status (P = 0.313), CA19-9 level (P = 0.608), and liver metastasis (P = 0.935) did not show significant prognoses on DSS. CONCLUSIONS: We reported seven pMANEC cases and outlined their clinical behaviors and prognoses with a review of twenty-one cases from the literature. Lymph node metastasis was found to be a negative prognostic factor of DSS based on the present study.


Assuntos
Adenocarcinoma/patologia , Carcinoma Neuroendócrino/patologia , Neoplasias Pancreáticas/patologia , Dor Abdominal/etiologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Carcinoma Neuroendócrino/cirurgia , Intervalo Livre de Doença , Feminino , Hospitais com Alto Volume de Atendimentos , Humanos , Icterícia Obstrutiva/etiologia , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
17.
Anal Chem ; 90(22): 13451-13458, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30234974

RESUMO

Exosomes are membrane-enclosed phospholipid extracellular vesicles, which can act as mediators of intercellular communication. Although the original features endow tumor-derived exosomes great potential as biomarkers, efficient isolation and detection methods remain challenging. Here, we presented a two-stage microfluidic platform (ExoPCD-chip), which integrates on-chip isolation and in situ electrochemical analysis of exosomes from serum. To promote exosomes capture efficiency, an improved staggered Y-shaped micropillars mixing pattern was designed to create anisotropic flow without any surface modification. By combining magnetic enrichment based on specific phosphatidylserine-Tim4 protein recognition with a new signal transduction strategy in a chip for the first time, the proposed platform enables highly sensitive detection for CD63 positive exosomes as low as 4.39 × 103 particles/mL with a linear range spanning 5 orders of magnitude, which is substantially better than the existing methods. The reduced volume of sample (30 µL) and simple affinity method also make it ideal for rapid downstream analysis of complex biofluids within 3.5 h. As a proof-of-concept, we performed exosomes analysis in human serum and liver cancer patients can be well discriminated from the healthy controls by the ExoPCD-chip. These results demonstrate that this proposed ExoPCD-chip may serve as a comprehensive exosome analysis tool and potential noninvasive diagnostic platform.


Assuntos
Biomarcadores Tumorais/sangue , Técnicas Eletroquímicas/métodos , Exossomos/metabolismo , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/métodos , Aptâmeros de Nucleotídeos/química , Carcinoma/diagnóstico , DNA Catalítico/química , Técnicas Eletroquímicas/instrumentação , Desenho de Equipamento , Hemina/química , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Fenômenos Magnéticos , Técnicas Analíticas Microfluídicas/instrumentação , Tetraspanina 30/química
18.
Cell Physiol Biochem ; 46(2): 579-590, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29617677

RESUMO

BACKGROUND/AIM: Mammalian target of rapamycin (mTOR) plays an important role in papillary thyroid carcinoma (PTC) cell progression. CZ415 is a novel, highly-efficient and specific mTOR kinase inhibitor. The current study tested the potential anti-tumor activity of CZ415 in human PTC cells. METHODS: The established (TPC-1 cell line) and primary human PTC cells were treated with CZ415. Cell survival and growth were tested by Cell Counting Kit-8 assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by caspase-3/-9 activity assay, Hoechst-33342 staining assay and single-stranded DNA ELISA assay. Cell cycle progression was tested by propidium iodide-FACS assay. The mTOR signaling was tested by Western blotting assay and co-immunoprecipitation assay. The mouse xenograft tumor model was applied to study the effect of CZ415 in vivo. RESULTS: In cultured human PTC cells, treatment with CZ415 at nM concentrations significantly inhibited cell survival and growth. CZ415 induced apoptosis activation and cell cycle arrest in human PTC cells. CZ415 disrupted assembling of mTORC1 (mTOR-Raptor association) and mTORC2 (mTOR-Rictor-GßL association) in TPC-1 cells, which led to de-phosphorylation of the mTORC1 substrates (S6K1 and 4E-BP1) and the mTORC2 substrate AKT (Ser-473). Further studies show that the autophagy inhibitor 3-methyladenine (3-MA) or Beclin-1 shRNA aggravated CZ415-induced cytotoxicity against PTC cells. In vivo, CZ415 oral administration inhibited TPC-1 xenograft tumor growth in mice. CONCLUSION: Our results show that mTOR blockage by CZ415 inhibits PTC cell growth in vitro and in vivo.


Assuntos
Proliferação de Células/efeitos dos fármacos , Óxidos S-Cíclicos/toxicidade , Compostos de Fenilureia/toxicidade , Inibidores de Proteínas Quinases/toxicidade , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Beclina-1/antagonistas & inibidores , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Carcinoma Papilar/tratamento farmacológico , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Óxidos S-Cíclicos/química , Óxidos S-Cíclicos/uso terapêutico , Feminino , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Camundongos , Camundongos SCID , Compostos de Fenilureia/química , Compostos de Fenilureia/uso terapêutico , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Especificidade por Substrato , Serina-Treonina Quinases TOR/metabolismo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
19.
Phys Rev Lett ; 120(13): 130502, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29694167

RESUMO

The entanglement properties of random quantum states or dynamics are important to the study of a broad spectrum of disciplines of physics, ranging from quantum information to high energy and many-body physics. This Letter investigates the interplay between the degrees of entanglement and randomness in pure states and unitary channels. We reveal strong connections between designs (distributions of states or unitaries that match certain moments of the uniform Haar measure) and generalized entropies (entropic functions that depend on certain powers of the density operator), by showing that Rényi entanglement entropies averaged over designs of the same order are almost maximal. This strengthens the celebrated Page's theorem. Moreover, we find that designs of an order that is logarithmic in the dimension maximize all Rényi entanglement entropies and so are completely random in terms of the entanglement spectrum. Our results relate the behaviors of Rényi entanglement entropies to the complexity of scrambling and quantum chaos in terms of the degree of randomness, and suggest a generalization of the fast scrambling conjecture.

20.
Phys Rev Lett ; 118(6): 060502, 2017 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-28234509

RESUMO

Resource theory is a widely applicable framework for analyzing the physical resources required for given tasks, such as computation, communication, and energy extraction. In this Letter, we propose a general scheme for analyzing resource theories based on resource destroying maps, which leave resource-free states unchanged but erase the resource stored in all other states. We introduce a group of general conditions that determine whether a quantum operation exhibits typical resource-free properties in relation to a given resource destroying map. Our theory reveals fundamental connections among basic elements of resource theories, in particular, free states, free operations, and resource measures. In particular, we define a class of simple resource measures that can be calculated without optimization, and that are monotone nonincreasing under operations that commute with the resource destroying map. We apply our theory to the resources of coherence and quantum correlations (e.g., discord), two prominent features of nonclassicality.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA