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1.
J Clin Med ; 10(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34640500

RESUMO

BACKGROUND AND AIMS: The clinical significance of circulating tumor cells (CTCs) and TWIST expression in CTCs remains unelucidated in patients with gastric cancer (GC). Here, we evaluated CTCs and TWIST expression in CTCs and explored their correlation with prognosis in patients with metastatic GC. METHODS: Peripheral blood samples were prospectively obtained from 31 patients with metastatic GC between September 2017 and December 2018, prior to treatment. CTCs were detected using a centrifugal microfluidic system and CTCs positive for TWIST immunostaining were defined as TWIST (+) CTCs. RESULTS: CTCs and TWIST (+) CTCs were detected in 25 (80.6%) and 24 (77.4%) of the 31 patients, respectively. CTC count in patients with first diagnosis of metastatic cancer tended to be higher than that in those with recurrent metastatic cancer, but TWIST (+) CTC count was not different between the two groups. There was no difference in CTC and TWIST (+) CTC counts according to histopathologic type, peritoneal dissemination, hematogenous metastasis, serum tumor makers, or response to first-line chemotherapy. Patients with CTCs > 7.5/7.5 mL of blood showed shorter overall survival (OS) than those with CTCs ≤ 7.5/7.5 mL of blood (p = 0.049). Additionally, patients with TWIST (+) CTCs > 2.5/7.5 mL of blood tended to show shorter OS than those with TWIST (+) CTCs ≤ 2.5/7.5 mL of blood (p = 0.105). CONCLUSIONS: Our study demonstrated that high levels of CTCs and TWIST (+) CTCs were associated with worse OS.

2.
Acc Chem Res ; 54(19): 3643-3655, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34516092

RESUMO

Reliable, inexpensive, and rapid diagnostic tools are essential to control and prevent the spread of infectious diseases. Many commercial kits for coronavirus disease 2019 (COVID-19) diagnostics have played a crucial role in the fight against the COVID-19 pandemic. Most current standard in vitro diagnostic (IVD) protocols for infectious diseases are sensitive but time-consuming and require sophisticated laboratory equipment and specially trained personnel. Recent advances in biosensor technology suggest the potential to deliver point-of-care (POC) diagnostics that are affordable and provide accurate results in a short time. The ideal "sample-in-answer-out" type fully integrated POC infection diagnostic platforms are expected to be autonomous or easy-to-operate, equipment-free or infrastructure-independent, and high-throughput or easy to upscale. In this Account, we detail the recent progress made by our group and others in the development of centrifugal microfluidic devices or lab-on-a-disc (LOAD) systems. Unlike conventional pump-based fluid actuation, the centrifugal force generated by spinning the disc induces liquid pumping and no external fluidic interconnects are required. This allows a total fluidic network required for multiple steps of biological assays to be integrated on a disc, enabling fully automated POC diagnostics. Various applications have been demonstrated, including liquid biopsy for personalized cancer management, food applications, and environmental monitoring; here, we focus on IVD for infectious disease. First, we introduce various on-disc unit operation technologies, including reagent storage, sedimentation, filtration, valving, decanting, aliquoting, mixing, separation, serial dilution, washing, and calibration. Such centrifugal microfluidic technologies have already proved promising for micro-total-analysis systems for automated IVD ranging from molecular detection of pathogens to multiplexed enzyme-linked immunosorbent assays (ELISAs) that use raw samples such as whole blood or saliva. Some recent examples of LOAD systems for molecular diagnostics in which some or all steps of the assays are integrated on a disc, including pathogen enrichment, nucleic acid extraction, amplification, and detection, are discussed in detail. We then introduce fully automated ELISA systems with enhanced sensitivity. Furthermore, we demonstrate a toy-inspired fidget spinner that enables electricity-free and rapid analysis of pathogens from undiluted urine samples of patients with urinary tract infection symptoms and a phenotypic antimicrobial susceptibility test for an extreme POC diagnostics application. Considering the urgent need for cost-effective and reliable POC infection diagnostic tools, especially in the current pandemic crisis, the current limitations and future directions of fast and broad adaptation in real-world settings are also discussed. With proper attention to key challenges and leverage with recent advances in bio-sensing technologies, molecular biology, nanomaterials, analytical chemistry, miniaturization, system integration, and data management, LOAD systems hold the potential to deliver POC infection diagnostic tools with unprecedented performance regarding time, accuracy, and cost. We hope the new insight and promise of LOAD systems for POC infection diagnostics presented in this Account can spark new ideas and inspire further research and development to create better healthcare systems for current and future pandemics.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Técnicas Biossensoriais/métodos , COVID-19/virologia , Teste para COVID-19/instrumentação , Centrifugação , Humanos , Dispositivos Lab-On-A-Chip , RNA Viral/análise , RNA Viral/isolamento & purificação , RNA Viral/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação
3.
Biosens Bioelectron ; 194: 113584, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34474276

RESUMO

Cysteamine (CA) is a cystine depleting agent used in the treatment of cystinosis and many other diseases. However, high dose of CA can be toxic and thus point-of-care-test devices measuring blood CA level can be highly beneficial. Here, we report a highly sensitive, straightforward, and quantitative assay for the colorimetric and spectroscopic determination of CA concentration using plasmonic nanoparticles. The principle is based on the chemical etching-induced exchange of the surface ligands of plasmonic gold nanoparticles (AuNPs) upon the addition of CA. Moreover, destabilized particles can aggregate to generate the plasmonic couplings that trigger the redshift in the ultraviolet-visible (UV-vis) spectrum (the absorption band shifted from 526 to 732 nm) and the solution color change (wine-red to blackish-blue). This plasmonic AuNPs sensor displays a clear red-to-blue colorimetric transition in the presence of CA among various biothiols with high specificity and sensitivity within a short time (<15 s). Furthermore, a lab-on-a-disc platform was applied to the analysis of blood samples donated by healthy volunteers spiked with known amounts of the CA standard solution. This fully automated lab-on-a-disc platform approach for naked eye detecting the CA concentration in human blood samples (20 µL) is highly simple and time-efficient (<6 min), and it would be potentially useful for the careful selection of CA doses in the hospital industry.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Colorimetria , Cisteamina , Ouro , Humanos
4.
Ticks Tick Borne Dis ; 12(6): 101813, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34411795

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is caused by Dabie bandavirus that belongs to the genus Bandavirus in the family Phenuiviridae and order Bunyavirales and is transmitted by hard ticks. It has been detected in several tick species, various animals, and humans. The purpose of this study was to detect SFTS virus (SFTSV) antigen and antibody in wild boar in the Republic of Korea (ROK). A total of 768 sera samples were collected from wild boar in the ROK between January and December 2019. Viral RNA was extracted from sera using viral RNA extraction kit, and one-step RT-nested polymerase chain reaction (PCR) was performed to amplify the S segment of the SFTSV. The sequencing data were analyzed using Chromas and aligned using Clustal X. The phylogenetic tree was constructed using the maximum-likelihood method using MEGA7. In addition, wild boar sera were tested for IgG antibodies against SFTSV by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA). Of a total of 768 sera samples, 40 (5.2%) were positive for SFTSV by RT-PCR targeting the S segment. Two hundred twenty-one (28.8%) and 159 (20.7%) of 768 sera samples were seropositive by ELISA and IFA, respectively. Based on both ELISA and IFA tests of the same samples, 110 (14.3%) wild boar sera samples were positive for SFTSV antibodies. Of a total of 40 positive serum samples by RT-PCR, 33 (82.5%) and 7 (17.5%) sera were classified as the genotype B-3 and D, respectively, by sequence analysis,. These results provide useful information that demonstrates the detection of antigen and antibody in wild boar sera samples for every month of a certain year throughout the ROK.

5.
Lab Chip ; 21(17): 3263-3288, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34346466

RESUMO

Liquid biopsy has emerged as a complement to invasive tissue biopsy to guide cancer diagnosis and treatment. The common liquid biopsy biomarkers are circulating tumor cells (CTCs), extracellular vesicles (EVs), and circulating tumor DNA (ctDNA). Each biomarker provides specific information based on its intrinsic characteristics. Prostate cancer is the second most common cancer in males worldwide. In men with low-grade localized prostate cancer, the disease can often be managed by active surveillance. For men who require treatment, the 5-year survival rate of localized prostate cancer is the highest among all cancer types, but the metastatic disease remains incurable. Metastatic prostate cancer invariably progresses to involve multiple bone sites and develops into a castration-resistant disease that leads to cancer death. The need to appropriately diagnose and guide the serial treatment of men with prostate cancer has led to the implementation of many studies to apply liquid biopsies to prostate cancer management. This review describes recent advancements in isolation and detection technology and the strength and weaknesses of the three circulating biomarkers. The clinical studies based on liquid biopsy results are summarized to depict the future perspective in the role of liquid biopsy on prostate cancer management.


Assuntos
DNA Tumoral Circulante , Células Neoplásicas Circulantes , Neoplasias da Próstata , Biomarcadores Tumorais , Humanos , Biópsia Líquida , Masculino , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia
6.
J Am Chem Soc ; 143(28): 10582-10589, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34213897

RESUMO

Despite the enormous application potential, methods for conformal few-atomic-layer deposition on colloidal nanocrystals (NCs) are scarce. Similar to the process of lamination, we introduce a "confine and shine" strategy to homogeneously modify the different surface curvatures of plasmonic NCs with ultrathin conformal layers of diverse catalytic noble metals. This self-limited epitaxial skinlike metal growth harvests the localized surface plasmon resonance to induce reduction chemistry directly on the NC surface, confined inside hollow silica. This strategy avoids any kinetic anisotropic metal deposition. Unlike the conventional thick, anisotropic, and dendritic shells, which show severe nonradiative damping, the skinlike metal lamination preserves the key plasmonic properties of the core NCs. Consequently, the plasmonic-catalytic hybrid nanoreactors can carry out a variety of organic reactions with impressive rates.

7.
Front Bioeng Biotechnol ; 9: 669537, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34164385

RESUMO

Extracellular vesicles (EVs) have been lauded as next-generation medicines, but very few EV-based therapeutics have progressed to clinical use. Limited clinical translation is largely due to technical barriers that hamper our ability to mass produce EVs, i.e., to isolate, purify, and characterize them effectively. Technical limitations in comprehensive characterization of EVs lead to unpredicted biological effects of EVs. Here, using a range of optical and non-optical techniques, we showed that the differences in molecular composition of EVs isolated using two isolation methods correlated with the differences in their biological function. Our results demonstrated that the isolation method determines the composition of isolated EVs at single and sub-population levels. Besides the composition, we measured for the first time the dry mass and predicted sedimentation of EVs. These parameters were likely to contribute to the biological and functional effects of EVs on single cell and cell cultures. We anticipate that our new multiscale characterization approach, which goes beyond traditional experimental methodology, will support fundamental understanding of EVs as well as elucidate the functional effects of EVs in in vitro and in vivo studies. Our findings and methodology will be pivotal for developing optimal isolation methods and establishing EVs as mainstream therapeutics and diagnostics. This innovative approach is applicable to a wide range of sectors including biopharma and biotechnology as well as to regulatory agencies.

8.
ACS Appl Mater Interfaces ; 13(25): 29313-29324, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34137258

RESUMO

Extracellular vesicles (EVs) with native membrane proteins possess a variety of functions. EVs have become increasingly important platforms for incorporating a new peptide/protein with additional functions on their membranes using genetic manipulation of producer cells. Although directly harnessing native membrane proteins on EVs for functional studies is promising, limited studies have been conducted to confirm its potential. This study reports bioengineered EVs with CD14, a natural glycosylphosphatidylinositol (GPI)-anchored protein and a selectively enriched native membrane protein on EVs. We demonstrated that producer cells transfected with genes encoding for GPI-anchored and transmembrane glycoproteins selectively display the former over the latter on bioengineered EVs. Furthermore, using specific enzyme cleavage studies, we characterized and validated that CD14 is indeed GPI-anchored on bioengineered EV membranes. Natural GPI-anchored proteins are conserved receptors for bacterial toxins; for example, CD14 is an innate immune receptor for lipopolysaccharide (LPS), a gram-negative bacterial endotoxin. We reported that unlike soluble CD14, bioengineered EVs harboring CD14 reduce (50-90%) LPS-induced cytokine responses in mouse macrophages, including primary cells, possibly by reduced cell surface binding of LPS. These findings highlight the importance of harnessing the native EV membrane proteins, like GPI-anchored proteins, for functional studies such as toxin neutralization. The GPI-anchoring platform can display various natural GPI-anchored proteins and other full-length proteins as GPI-anchored proteins on EV membranes.


Assuntos
Bioengenharia/métodos , Vesículas Extracelulares , Glicosilfosfatidilinositóis , Lipopolissacarídeos/metabolismo , Proteínas de Membrana , Animais , Técnicas de Visualização da Superfície Celular , Células Cultivadas , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Feminino , Glicosilfosfatidilinositóis/química , Glicosilfosfatidilinositóis/metabolismo , Células HEK293 , Humanos , Macrófagos/citologia , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C
9.
Ticks Tick Borne Dis ; 12(4): 101689, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33676201

RESUMO

Ticks are considered important vectors among arthropods and are linked to serious medical and veterinary health problems. In this study, we investigated tick-borne pathogens (TBPs) of Ornithodoros (Carios) sawaii and a newly identified Ornithodoros species from migratory bird nests in the uninhabited islands of the Republic of Korea (ROK). Ticks were collected from seabird nests with soil using a Tullgren funnel. Polymerase chain reaction (PCR) was performed using specific primer sets targeting genes of Borrelia spp., Rickettsia sp., Anaplasma phagocytophilum, Anaplasma bovis, and Bartonella spp. for molecular identification of TBPs, and two pathogens, Borrelia sp. and Rickettsia sp. were detected via PCR. Sequence data were analyzed and a phylogenetic analysis was conducted using the maximum-likelihood method in MEGA v.7. The detection rate of Borrelia sp. in O.(C.) sawaii was 6.8 % (5/74), and that of Rickettsia sp. in O. sawaii and the newly identified Ornithodoros species. was 36.5 % (27/74). Sequencing analysis revealed that the 16S ribosomal (r) RNA and flagellin genes of Borrelia sp., and the citrate synthase (gltA) and 17-kDa antigen gene of Rickettsia sp. were closely phylogenetically related to those of Borrelia turicatae and Rickettsia asembonensis. This is the first report identifying Borrelia sp. and Rickettsia sp. from O. sawaii, and Rickettsia sp. from the newly identified Ornithodoros species in the ROK, and these results imply that soft ticks (O. sawaii, and the newly identified Ornithodoros species) may function as pathogen carriers with important implications for public health throughout their distribution areas in Asia.


Assuntos
Borrelia/isolamento & purificação , Ornithodoros/microbiologia , Rickettsia/isolamento & purificação , Animais , Feminino , Masculino , Ninfa/crescimento & desenvolvimento , Ninfa/microbiologia , Ornithodoros/crescimento & desenvolvimento , República da Coreia , Especificidade da Espécie
10.
ACS Appl Mater Interfaces ; 13(13): 15837-15846, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33689266

RESUMO

Patterning wrinkles on three-dimensional curved or enclosed surfaces can be challenging due to difficulties in application of uniform films and stresses on such structures. In this study, we demonstrate a simple one-step wrinkle-formation method on various hydrogel structures utilizing the oil-water interfaces. By diffusion of the photoinitiator from the oil phase to the prepolymer solution in water through the interface, a characteristic cross-linking gradient is set up in the hydrogel. Then, after photopolymerization, we observe diverse patterns of wrinkles upon changing the concentration of the hydrogel or photoinitiator. As the wrinkle formation via photoinitiator diffusion through the interface requires only UV exposure for polymerization, while taking advantage of the oil-water interfacial tension, wrinkles can be developed easily on various curved structures. In addition, we illustrate the formation of wrinkles on surfaces underneath another layer of polymer or on completely enclosed surfaces, which is difficult with conventional methods. We expect that our results will lead to production of novel microstructures and provide a platform for studying the morphogenesis of wrinkles found in nature such as in curved substrates and multilayers.

11.
Science ; 371(6526)2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33446529

RESUMO

Günther et al report that their control experiment using randomized magnetic field gradient sequences disagreed with findings we had reported using linear gradients. However, we show that measurements in our laboratory are consistent using both methods.

12.
Nano Lett ; 21(1): 337-343, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33227203

RESUMO

Since the emergence of the COVID-19 pandemic outbreak, the increasing demand and disposal of surgical masks has resulted in significant economic costs and environmental impacts. Here, we applied a dual-channel spray-assisted nanocoating hybrid of shellac/copper nanoparticles (CuNPs) to a nonwoven surgical mask, thereby increasing the hydrophobicity of the surface and repelling aqueous droplets. The resulting surface showed outstanding photoactivity (combined photocatalytic and photothermal properties) for antimicrobial action, conferring reusability and self-sterilizing ability to the masks. Under solar illumination, the temperature of this photoactive antiviral mask (PAM) rapidly increased to >70 °C, generating a high level of free radicals that disrupted the membrane of nanosized (∼100 nm) virus-like particles and made the masks self-cleaning and reusable. This PAM design can provide significant protection against the transmission of viral aerosols in the fight against the COVID-19 pandemic.


Assuntos
Antivirais/química , COVID-19/prevenção & controle , Cobre/química , Máscaras/virologia , Nanopartículas Metálicas/química , Esterilização/métodos , Catálise , Humanos , Interações Hidrofóbicas e Hidrofílicas , Processos Fotoquímicos , SARS-CoV-2/isolamento & purificação , Temperatura
13.
Nano Lett ; 21(1): 279-287, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33306397

RESUMO

Next-generation catalysts are urgently needed to tackle the global challenge of antimicrobial resistance. Existing antimicrobials cannot function in the complex and stressful chemical conditions found in biofilms, and as a result, they are unable to infiltrate, diffuse into, and eradicate the biofilm and its associated matrix. Here, we introduce mixed-FeCo-oxide-based surface-textured nanostructures (MTex) as highly efficient magneto-catalytic platforms. These systems can produce defensive ROS over a broad pH range and can effectively diffuse into the biofilm and kill the embedded bacteria. Because the nanostructures are magnetic, biofilm debris can be scraped out of the microchannels. The key antifouling efficacy of MTex originates from the unique surface topography that resembles that of a ploughed field. These are captured as stable textured intermediates during the oxidative annealing and solid-state conversion of ß-FeOOH nanocrystals. These nanoscale surfaces will advance progress toward developing a broad array of new enzyme-like properties at the nanobio interface.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Biofilmes , Óxidos , Espécies Reativas de Oxigênio
14.
Cancers (Basel) ; 12(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007940

RESUMO

The detection of epidermal growth factor receptor (EGFR) mutation, based on tissue biopsy samples, provides a valuable guideline for the prognosis and precision medicine in patients with lung cancer. In this study, we aimed to examine minimally invasive bronchial washing (BW)-derived extracellular vesicles (EVs) for EGFR mutation analysis in patients with lung cancer. A lab-on-a-disc equipped with a filter with 20-nm pore diameter, Exo-Disc, was used to enrich EVs in BW samples. The overall detection sensitivity of EGFR mutations in 55 BW-derived samples was 89.7% and 31.0% for EV-derived DNA (EV-DNA) and EV-excluded cell free-DNA (EV-X-cfDNA), respectively, with 100% specificity. The detection rate of T790M in 13 matched samples was 61.5%, 10.0%, and 30.8% from BW-derived EV-DNA, plasma-derived cfDNA, and tissue samples, respectively. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. The EGFR mutations can be readily detected in BW-derived EVs, which demonstrates their clinical potential as a liquid-biopsy sample that may aid precise management, including assessment of the treatment response and drug resistance in patients with lung cancer.

15.
J Parasitol ; 106(5): 546-563, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32916707

RESUMO

Ticks and tick-borne diseases are important issues worldwide because of their effects on animal and human health. The genus Ornithodoros, which is included in the family Argasidae, is typically associated with wild animals, including seabirds. In this study, samples from the nests of seabirds and surrounding soil were collected to investigate Ornithodoros spp. from 9 uninhabited islands in the western, eastern, and southern parts of Korea from April 2017 to October 2018. The islands are known as the breeding places of migratory and resident birds. Ticks were collected from soil and nest material of seabirds using a Tullgren funnel and identified using 16S rRNA and the cytochrome c oxidase 1 gene (COI), and host animals of soft ticks were identified using the mitochondrial DNA cytochrome b gene by a polymerase chain reaction. In the sequence identity of the 16S rRNA gene fragment of Ornithodoros sp., Ornithodoros sawaii was identified as the closest homologous sequence, and the new Ornithodoros sp. was newly identified. We found that the newly identified Ornithodoros sp. in the Republic of Korea was located in uninhabited islands used as breeding places by the black-tailed gull, Larus crassirostris.


Assuntos
Doenças das Aves/parasitologia , Ornithodoros/classificação , Infestações por Carrapato/veterinária , Animais , Aves , Clonagem Molecular , DNA/química , DNA/isolamento & purificação , Complexo IV da Cadeia de Transporte de Elétrons/genética , Ilhas , Funções Verossimilhança , Microscopia Eletrônica de Varredura , Ornithodoros/genética , Ornithodoros/ultraestrutura , Filogenia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , República da Coreia , Solo/parasitologia , Infestações por Carrapato/parasitologia
16.
ACS Nano ; 14(11): 14971-14988, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-32880442

RESUMO

The liver is one of the most common sites of breast cancer metastasis and is associated with high lethality. Although the interaction between tumor cells and their microenvironment at metastatic sites has been recognized as a key regulator of tumor progression, the underlying mechanism is not fully elucidated. Here, we describe a three-dimensional (3D) microfluidic human liver-on-a-chip (liver-chip) that emulates the formation of a premetastatic niche to investigate the roles of breast cancer-derived extracellular vesicles (EVs) in liver metastasis. We demonstrate that breast cancer-derived EVs activate liver sinusoidal endothelial cells (LSECs) in the liver-chip, inducing endothelial to mesenchymal transition and destruction of vessel barriers. In addition, we show that transforming growth factor ß1 (TGFß1) in breast cancer-derived EVs upregulates fibronectin, an adhesive extracellular matrix protein, on LSECs, which facilitates the adhesion of breast cancer cells to the liver microenvironment. Furthermore, we observed that EVs isolated from triple-negative breast cancer (TNBC) patients with liver metastasis contain higher TGFß1 levels and induce adhesion of more breast cancer cells to the 3D human liver-chip than do EVs isolated from healthy donors or nonmetastatic TNBC patients. These findings provide a better understanding of the mechanisms through which breast cancer-derived EVs guide secondary metastasis to the liver. Furthermore, the 3D human liver-chip described in this study provides a platform to investigate the mechanisms underlying secondary metastasis to the liver and possible therapeutic strategies.


Assuntos
Vesículas Extracelulares , Fígado , Neoplasias de Mama Triplo Negativas , Células Endoteliais , Humanos , Dispositivos Lab-On-A-Chip , Fígado/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Microambiente Tumoral
17.
Science ; 369(6503): 537-541, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32732420

RESUMO

Mobility of reactants and nearby solvent is more rapid than Brownian diffusion during several common chemical reactions when the energy release rate exceeds a threshold. Screening a family of 15 organic chemical reactions, we demonstrate the largest boost for catalyzed bimolecular reactions, click chemistry, ring-opening metathesis polymerization, and Sonogashira coupling. Boosted diffusion is also observed but to lesser extent for the uncatalyzed Diels-Alder reaction, but not for substitution reactions SN1 and SN2 within instrumental resolution. Diffusion coefficient increases as measured by pulsed-field gradient nuclear magnetic resonance, whereas in microfluidics experiments, molecules in reaction gradients migrate "uphill" in the direction of lesser diffusivity. This microscopic consumption of energy by chemical reactions transduced into mechanical motion presents a form of active matter.

18.
Cells ; 9(6)2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32527037

RESUMO

The shape of epithelial tissue supports physiological functions of organs such as intestinal villi and corneal epithelium. Despite the mounting evidence showing the importance of geometry in tissue microenvironments, the current understanding on how it affects biophysical behaviors of cells is still elusive. Here, we cultured cells on various protruded convex structure such as triangle, square, and circle shape fabricated using two-photon laser lithography and quantitatively analyzed individual cells. Morphological data indicates that epithelial cells can sense the sharpness of the corner by showing the characteristic cell alignments, which was caused by actin contractility. Cell area was mainly influenced by surface convexity, and Rho-activation increased cell area on circle shape. Moreover, we found that intermediate filaments, vimentin, and cytokeratin 8/18, play important roles in growth and adaptation of epithelial cells by enhancing expression level on convex structure depending on the shape. In addition, microtubule building blocks, α-tubulin, was also responded on geometric structure, which indicates that intermediate filaments and microtubule can cooperatively secure mechanical stability of epithelial cells on convex surface. Altogether, the current study will expand our understanding of mechanical adaptations of cells on out-of-plane geometry.


Assuntos
Células Epiteliais/metabolismo , Diferenciação Celular , Humanos , Imageamento Tridimensional
20.
Theranostics ; 10(12): 5181-5194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32373206

RESUMO

Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy.

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