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2.
J Reconstr Microsurg ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553344

RESUMO

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are limited to flaps which carry a cutaneous paddle. As such, this useful and reliable technology has not previously been applicable to muscle-only free flaps where other modalities with substantial limitations continue to be utilized. METHODS: We present the first NIRS probe which allows continuous monitoring of local tissue oxygen saturation (StO2) directly within the substance of muscle tissue. This probe is flexible, subcentimeter in scale, waterproof, biocompatible, and is fitted with resorbable barbs which facilitate temporary autostabilization followed by easy atraumatic removal. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. During these experiments, the T.Ox device was affixed to the skin paddle, while the novel probe was within the muscle component of the same flap. RESULTS: The intramuscular NIRS device and skin-mounted ViOptix T.Ox devices produced very similar StO2 tracings throughout the vascular clamping events, with obvious and parallel changes occurring upon vascular clamping and release. The normalized cross-correlation at zero lag describing correspondence between the novel intramuscular NIRS and T.Ox devices was >0.99. CONCLUSION: This novel intramuscular NIRS probe offers continuous monitoring of oxygen saturation within muscle flaps. This experiment demonstrates the potential suitability of this intramuscular NIRS probe for the task of muscle-only free flap monitoring, where NIRS has not previously been applicable. Testing in the clinical environment is necessary to assess durability and reliability.

3.
J Reconstr Microsurg ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404105

RESUMO

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

4.
Nat Mater ; 20(11): 1559-1570, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34326506

RESUMO

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.

5.
Bioresour Technol ; 332: 125071, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33826982

RESUMO

Bioprocess, a biocatalysis-based technology, is becoming popular in many research fields and widely applied in industrial manufacturing. However, low bioconversion, low productivity, and high costs during industrial processes are usually the limitation in bioprocess. Therefore, many biocatalyst strategies have been developed to meet these challenges in recent years. In this review, we firstly discuss protein engineering strategies, which are emerged for improving the biocatalysis activity of biocatalysts. Then, we summarize metabolic engineering strategies that are promoting the development of microbial cell factories. Next, we illustrate the necessity of using the combining strategy of protein engineering and metabolic engineering for efficient biocatalysts. Lastly, future perspectives about the development and application of novel biocatalyst strategies are discussed. This review provides theoretical guidance for the development of efficient, sustainable, and economical bioprocesses mediated by novel biocatalysts.


Assuntos
Engenharia Metabólica , Engenharia de Proteínas , Biocatálise , Indústrias
6.
Appl Opt ; 60(8): 2190-2196, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690314

RESUMO

We experimentally report a low threshold soliton and a noise-like mode-locked fiber laser using an all-polarization-maintaining figure-eight cavity. We built a bidirectional pump structure without a phase shifter at the beginning of the experiment. The resonator has a high mode-locking threshold of 620 mW. Afterwards, we used a phase shifter in the resonator, and the laser can self-start in a conventional soliton (CS) mode-locked state when pump1 reaches the threshold of only 70 mW. The CS pulse with a duration of 863.8 fs can be observed at 1560 nm. When the two pump powers increase to 350 mW and 50 mW, the conventional soliton can convert to noise-like pulses. The central wavelength and pulse duration of noise-like mode-locked pulse are 1560.4 nm and 417.9 fs, respectively. The laser can realize conversion between ultrafast pulses and high-energy pulses, and have a low threshold that can be used for nonlinear frequency conversion, supercontinuum generation, sensing, etc.

8.
Nat Commun ; 11(1): 5990, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239608

RESUMO

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.


Assuntos
Implantes Absorvíveis , Terapia por Estimulação Elétrica/instrumentação , Traumatismos dos Nervos Periféricos/terapia , Poliuretanos/química , Tecnologia sem Fio/instrumentação , Animais , Modelos Animais de Doenças , Terapia por Estimulação Elétrica/métodos , Feminino , Humanos , Teste de Materiais , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Ratos , Regeneração , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia
9.
Proc Natl Acad Sci U S A ; 116(31): 15368-15377, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31315983

RESUMO

Techniques for forming sophisticated, 3D mesostructures in advanced, functional materials are of rapidly growing interest, owing to their potential uses across a broad range of fundamental and applied areas of application. Recently developed approaches to 3D assembly that rely on controlled buckling mechanics serve as versatile routes to 3D mesostructures in a diverse range of high-quality materials and length scales of relevance for 3D microsystems with unusual function and/or enhanced performance. Nonlinear buckling and delamination behaviors in materials that combine both weak and strong interfaces are foundational to the assembly process, but they can be difficult to control, especially for complex geometries. This paper presents theoretical and experimental studies of the fundamental aspects of adhesion and delamination in this context. By quantifying the effects of various essential parameters on these processes, we establish general design diagrams for different material systems, taking into account 4 dominant delamination states (wrinkling, partial delamination of the weak interface, full delamination of the weak interface, and partial delamination of the strong interface). These diagrams provide guidelines for the selection of engineering parameters that avoid interface-related failure, as demonstrated by a series of examples in 3D helical mesostructures and mesostructures that are reconfigurable based on the control of loading-path trajectories. Three-dimensional micromechanical resonators with frequencies that can be selected between 2 distinct values serve as demonstrative examples.

10.
Chem Asian J ; 14(15): 2620-2628, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066179

RESUMO

The employment of a new rigid N-tridentate ligand, bis(1-chloroimidazo[1,5-a]pyridin-3-yl)pyridine (bcpp), in the construction of cobalt(II) single-ion magnets is reported. Two cobalt(II) complexes, [Co(bcpp)Cl2 ] (1) and [Co(bcpp)Br2 ] (2), have been prepared and characterized. Single-crystal XRD analyses reveal that complexes 1 and 2 are isostructural. They are pentacoordinated mononuclear cobalt(II) compounds with expected trigonal bipyramidal geometry. Both analysis of the magnetic data and ab initio calculations reveal easy-plane magnetic anisotropy (D>0) for 1 and 2. Detailed alternating current magnetic susceptibility measurements reveal the occurrence of slow magnetic relaxation behavior for the cobalt(II) centers of 1 and 2; thus indicating that both complexes are field-induced single-ion magnets.

11.
Nat Commun ; 10(1): 313, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30659184

RESUMO

Osteoarthritis (OA) has been recognized as the most common chronic age-related disease. Cartilage degeneration influences OA therapy. Here we report that hematopoietic pre-B cell leukemia transcription factor-interacting protein (HPIP) is essential for OA development. Elevated HPIP levels are found in OA patients. Col2a1-CreERT2/HPIPf/f mice exhibit obvious skeletal abnormalities compared with their HPIPf/f littermates. HPIP deficiency in mice protects against developing OA. Moreover, intra-articular injection of adeno-associated virus carrying HPIP-specific short hairpin RNA in vivo attenuates OA histological signs. Notably, in vitro RNA-sequencing and chromatin immunoprecipitation sequencing profiles identify that HPIP modulates OA cartilage degeneration through transcriptional activation of Wnt target genes. Mechanistically, HPIP promotes the transcription of Wnt targets by interacting with lymphoid enhancer binding factor 1 (LEF1). Furthermore, HPIP potentiates the transcriptional activity of LEF1 and acetylates histone H3 lysine 56 in the promoters of Wnt targets, suggesting that HPIP is an attractive target in OA regulatory network.


Assuntos
Cartilagem Articular/patologia , Proteínas Correpressoras/genética , Osteoartrite/genética , Osteoartrite/patologia , Animais , Cartilagem Articular/metabolismo , Células Cultivadas , Condrócitos/metabolismo , Imunoprecipitação da Cromatina , Proteínas Correpressoras/metabolismo , Dependovirus , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Interferente Pequeno/genética , Saccharomyces cerevisiae , Análise de Sequência de RNA
12.
Ann Rheum Dis ; 78(1): 100-110, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30026257

RESUMO

OBJECTIVES: Understanding the molecular mechanisms underlying human cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). Here, we report the molecular programmes and lineage progression patterns controlling human OA pathogenesis using single-cell RNA sequencing (scRNA-seq). METHODS: We performed unbiased transcriptome-wide scRNA-seq analysis, computational analysis and histological assays on 1464 chondrocytes from 10 patients with OA undergoing knee arthroplasty surgery. We investigated the relationship between transcriptional programmes of the OA landscape and clinical outcome using severity index and correspondence analysis. RESULTS: We identified seven molecularly defined populations of chondrocytes in the human OA cartilage, including three novel phenotypes with distinct functions. We presented gene expression profiles at different OA stages at single-cell resolution. We found a potential transition among proliferative chondrocytes, prehypertrophic chondrocytes and hypertrophic chondrocytes (HTCs) and defined a new subdivision within HTCs. We revealed novel markers for cartilage progenitor cells (CPCs) and demonstrated a relationship between CPCs and fibrocartilage chondrocytes using computational analysis. Notably, we derived predictive targets with respect to clinical outcomes and clarified the role of different cell types for the early diagnosis and treatment of OA. CONCLUSIONS: Our results provide new insights into chondrocyte taxonomy and present potential clues for effective and functional manipulation of human OA cartilage regeneration that could lead to improved health.


Assuntos
Condrócitos/metabolismo , Osteoartrite do Joelho/genética , Análise de Sequência de RNA , Cartilagem Articular/citologia , Condrogênese/genética , Biologia Computacional , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Fenótipo , Células-Tronco/metabolismo , Transcriptoma
13.
Appl Microbiol Biotechnol ; 103(3): 1339-1350, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30539257

RESUMO

Efflux pumps are recognized as an important mechanism for decreased susceptibility of benzalkonium chloride (BC) in Listeria monocytogenes. Previous studies showed that the efflux pump MdrL was overexpressed in L. monocytogenes exposed to BC. In the present work, we aimed to clarify the role of MdrL in tolerance to BC and environmental stresses including acid, alkali, osmotic, ethanol, and oxidative stresses, as well as resistance to other antimicrobial agents in L. monocytogenes EGD-e. In addition, regulation of the expression of mdrL by LadR was investigated. Gene deletion mutants were constructed by homologous recombination strategy. For the wild-type and mutant strains, minimum inhibitory concentrations (MICs) of antimicrobial agents were determined by the agar dilution, and the growth and survival analysis were also performed. LadR was expressed and the interaction between LadR and the mdrL promoter was investigated by electrophoretic mobility shift assay (EMSA). Compared to the wild-type strain, the growth of ΔmdrL deletion mutant strain was impaired in the presence of sublethal concentration of BC. Moreover, the mutant showed a lower level of survival than that of the wild-type strain in the presence of lethal concentration of BC. However, the deletion of mdrL had no impact on cefotaxime resistance and ethidium bromide efflux. BC could induce the expression of mdrL in L. monocytogenes and the mdrL expression was regulated by LadR instead of SigmaB. LadR was able to specifically bind to the mdrL promoter. The results showed that efflux pump MdrL was associated with BC tolerance in L. monocytogenes EGD-e. Moreover, our results also provided strong evidence that LadR negatively regulated the expression of mdrL. Since BC is commonly used in the food industry, efflux pump MdrL is beneficial for L. monocytogenes to survive this stress in food processing environments.


Assuntos
Antibacterianos/farmacologia , Compostos de Benzalcônio/farmacologia , Listeria monocytogenes/genética , Listeria monocytogenes/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Transporte Biológico/genética , Farmacorresistência Bacteriana/genética , Regulação Bacteriana da Expressão Gênica/genética , Listeria monocytogenes/efeitos dos fármacos , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana
14.
Adv Mater ; 31(2): e1805615, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30370605

RESUMO

Capabilities for controlled formation of sophisticated 3D micro/nanostructures in advanced materials have foundational implications across a broad range of fields. Recently developed methods use stress release in prestrained elastomeric substrates as a driving force for assembling 3D structures and functional microdevices from 2D precursors. A limitation of this approach is that releasing these structures from their substrate returns them to their original 2D layouts due to the elastic recovery of the constituent materials. Here, a concept in which shape memory polymers serve as a means to achieve freestanding 3D architectures from the same basic approach is introduced, with demonstrated ability to realize lateral dimensions, characteristic feature sizes, and thicknesses as small as ≈500, 10, and 5 µm simultaneously, and the potential to scale to much larger or smaller dimensions. Wireless electronic devices illustrate the capacity to integrate other materials and functional components into these 3D frameworks. Quantitative mechanics modeling and experimental measurements illustrate not only shape fixation but also capabilities that allow for structure recovery and shape programmability, as a form of 4D structural control. These ideas provide opportunities in fields ranging from micro-electromechanical systems and microrobotics, to smart intravascular stents, tissue scaffolds, and many others.

15.
Mol Ther Nucleic Acids ; 13: 154-163, 2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30290307

RESUMO

Lung cancers, the leading cause of cancer mortality worldwide, are characterized by a high metastatic potential. Growing evidence reveals that Spindlin 1 (SPIN1) is involved in tumor progression and carcinogenesis. However, the role of SPIN1 in non-small-cell lung cancer (NSCLC) and the molecular mechanisms underlying SPIN1 in human NSCLC remain undetermined. Here we examined the function of SPIN1 in human NSCLC and found that the expression of SPIN1 was closely correlated with the overall survival and poor prognosis of NSCLC patients. Aberrant regulation of microRNAs (miRNAs) has an important role in cancer progression. We revealed that miR-409 inhibits the expression of SPIN1 by binding directly to the 3' UTR of SPIN1 using dual-luciferase reporter assays. Overexpression of miR-409 significantly suppressed cell migration, growth, and proliferation by inhibiting SPIN1 in vitro and in vivo. SPIN1 overexpression in miR-409-transfected NSCLC cells effectively rescued the suppression of cell migration, growth, and proliferation regulated by miR-409. miR-409 regulates the PI3K/AKT (protein kinase B) pathway in NSCLC. Moreover, clinical data showed that NSCLC patients with high levels of miR-409 experienced significantly better survival. miR-409 expression was also negatively associated with SPIN1 expression. Taken together, these findings highlight that the miR-409/SPIN1 axis is a useful pleiotropic regulatory network and could predict the metastatic potential in NSCLC patients early, indicating the possibility that miR-409 and SPIN1 might be attractive prognostic markers for treating NSCLC patients.

16.
Mol Ther Nucleic Acids ; 11: 170-179, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29858052

RESUMO

Cryptotanshinone (CTS) has emerged as an anti-inflammatory agent in osteoarthritis (OA). However, the molecular mechanism underlying its potent therapeutic effect on OA remains largely unknown. MicroRNAs (miRNAs) act as crucial regulators in maintaining cartilage homeostasis. To investigate whether CTS protects against developing OA through regulation of miRNAs, we examined the potential CTS-mediated miRNA molecules using microarray analysis. We found that CTS significantly promoted miR-106a-5p expression in chondrocytes. Using the OA mouse model created by anterior cruciate ligament transection, we revealed that intra-articular injection of miR-106a-5p agomir attenuated OA. In addition, miR-106a-5p inhibited GLI-similar 3 (GLIS3) production by directly targeting the 3' untranslated region. CTS promoted miR-106a-5p expression through recruitment of a member of the paired box (PAX) family of transcription factors, PAX5, to the miR-106a-5p promoter. Inhibition of PAX5 mimicked the effect of miR-106a-5p and abolished the CTS ability to regulate miR-106a-5p expression. In OA patients, miR-106-5p is downregulated which is accompanied by downregulation of PAX5 and upregulation of GLIS3. Collectively, these data highlight that the PAX5/miR-106a-5p/GLIS3 axis acts as a novel pleiotropic regulator in CTS-mediated OA cartilage protection, suggesting that miR-106a-5p and PAX5 activation and GLIS3 inhibition might be useful and attractive for therapeutic strategies to treat OA patients.

17.
Mol Ther ; 26(5): 1299-1312, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29628305

RESUMO

Cadherin-6 (CDH6) is aberrantly expressed in cancer and closely associated with tumor progression. However, the functions of CDH6 in human osteosarcoma and the molecular mechanisms underlying CDH6 in osteosarcoma oncogenesis remain poorly understood. In this work, we assessed the role of CDH6 in human osteosarcoma and identified that the expression of CDH6 was closely related with the overall survival and poor prognosis of osteosarcoma patients. MicroRNAs (miRNAs) have been implicated as important epigenetic regulators during the progression of osteosarcoma. Using dual-luciferase reporter assays, we showed that miR-223-3p suppresses CDH6 expression by directly binding to the 3' UTR of CDH6. miR-223-3p overexpression significantly inhibited cell invasion, migration, growth, and proliferation by suppressing the CDH6 expression in vivo and in vitro. Besides, CDH6 overexpression in the miR-223-3p-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion, migration, growth, and proliferation mediated by miR-223-3p. Additionally, Kaplan-Meier analysis suggests that the expression of miR-223-3p predicts favorable clinical outcomes for osteosarcoma patients. Moreover, the expression of miR-223-3p was downregulated in osteosarcoma patients and was negatively associated with the expression of CDH6. Collectively, these data highlight that miR-223-3p/CDH6 axis is an important novel pleiotropic regulator and could early predict the metastatic potential in human osteosarcoma treatments.


Assuntos
Neoplasias Ósseas/genética , Caderinas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Osteossarcoma/genética , Interferência de RNA , Regiões 3' não Traduzidas , Animais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Camundongos , Metástase Neoplásica , Estadiamento de Neoplasias , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico , Recidiva , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Cell Death Dis ; 8(10): e3103, 2017 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-29022909

RESUMO

Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated. Here we found that CDK14 expression was closely associated with poor prognosis and overall survival of OS patients. Using dual-luciferase reporter assays, we also found that miR-216a inhibits CDK14 expression by binding to the 3'-untranslated region of CDK14. Overexpression of miR-216a significantly suppressed cell proliferation, migration and invasion in vivo and in vitro by inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected OS cells effectively rescued the suppression of cell proliferation, migration and invasion caused by miR-216a. In addition, Kaplan-Meier analysis indicated that miR-216a expression predicted favourable clinical outcomes for OS patients. Moreover, miR-216a expression was downregulated in OS patients and was negatively associated with CDK14 expression. Overall, these data highlight the role of the miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the associated molecular mechanisms, thus suggesting the intriguing possibility that miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic strategies for treating OS patients.


Assuntos
Neoplasias Ósseas/patologia , Proliferação de Células/genética , Quinases Ciclina-Dependentes/biossíntese , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Osteossarcoma/patologia , Regiões 3' não Traduzidas/genética , Animais , Sítios de Ligação/genética , Neoplasias Ósseas/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Quinases Ciclina-Dependentes/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Camundongos Endogâmicos BALB C , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Transplante de Neoplasias , Osteossarcoma/genética , Transplante Heterólogo
19.
Int J Food Microbiol ; 258: 12-17, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-28738194

RESUMO

The aim of this study was to examine the presence of genes responsible for resistance to quaternary ammonium compounds (QACs) and the association of qac genes with class 1 integrons in Escherichia coli isolated from retail meats. Among the 179 E. coli isolates tested, the minimum inhibitory concentrations (MICs) of benzalkonium chloride (BC) ranged from 4 to 64µg/mL. PCR assays indicated that QAC-resistance genes sugE(c), ydgE/ydgF, mdfA, emrE and qacEΔ1 were commonly present (40.2%-88.3%) in these isolates, but qacE, qacF, qacH and sugE(p) were less prevalent (2.2%-28.5%). Seven different gene cassette arrangements were identified in 31 intI1-positive isolates. Three types of qacH-sul3-associated non-classic integrons were observed in four isolates: dfrA12-orfF-aadA2-cmlA1-aadA1-qacH-IS440-sul3, aadA2-cmlA1-aadA1-qacH-IS440-sul3 and dfrA1-aadA1-qacH-IS440-sul3. Non-classic class 1 integrons were located on plasmids of 100-150kb in these four isolates. Our results demonstrated that the qacH-associated integrons located on 100 kb plasmids in two isolates could be transferred to an E. coli recipient, indicating the co-existence and co-dissemination of disinfectant and antimicrobial resistance genes among bacterial species.


Assuntos
Antibacterianos/farmacologia , Compostos de Benzalcônio/farmacologia , Desinfetantes/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Transferência Genética Horizontal/genética , Escherichia coli/isolamento & purificação , Contaminação de Alimentos , Integrons/genética , Carne/microbiologia , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Reação em Cadeia da Polimerase
20.
J Mol Med (Berl) ; 94(7): 771-85, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27067395

RESUMO

UNLABELLED: The proinflammatory cytokine interleukin-1ß (IL-1ß) is involved in the initiation and progression of osteoarthritis (OA) by stimulating the expression of matrix-degrading proteinases, such as a disintegrin metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), a key player in OA pathogenesis. However, how IL-1ß induces ADAMTS-5 overexpression is poorly understood. We demonstrate that IL-1ß regulates ADAMTS-5 expression by suppressing microRNA-30a (miR-30a). Bioinformatics was performed to predict miRNAs targeting ADAMTS-5. miR-30a inhibited ADAMTS-5 expression by directly targeting its 3'-untranslated region. miR-30a expression was downregulated in OA patients and was negatively correlated with ADAMTS-5 expression and positively correlated with Hospital for Special Surgery (HSS) scores. IL-1ß suppressed miR-30a expression by recruiting the activator protein (AP-1) transcription factor c-jun/c-fos to the miR-30a promoter. IL-1ß-induced c-jun/c-fos expression regulated ADAMTS-5 expression and cartilage matrix degradation via miR-30a in human chondrocytes. These data indicate that the IL-1ß/AP-1/miR-30a/ADAMTS-5 pathway contributes to IL-1ß-induced cartilage matrix degradation in human OA chondrocytes. miR-30a may act as a pivotal regulator of cartilage homeostasis and a potential diagnostic and therapeutic target for OA. KEY MESSAGES: ADAMTS-5 was identified as a novel direct target of miR-30a. IL-1ß suppresses miR-30a expression through activation of AP-1 (c-jun/c-fos). AP-1/miR-30a is essential for IL-1ß-induced ADAMTS-5 upregulation in OA. Downregulation of miR-30a in OA is negatively correlated with ADAMTS-5 expression.


Assuntos
Proteína ADAMTS5/genética , Cartilagem Articular/metabolismo , Interleucina-1beta/genética , MicroRNAs/genética , Osteoartrite do Joelho/genética , Fator de Transcrição AP-1/genética , Regiões 3' não Traduzidas , Proteína ADAMTS5/metabolismo , Idoso , Artroplastia do Joelho , Sequência de Bases , Sítios de Ligação , Cartilagem Articular/patologia , Cartilagem Articular/cirurgia , Condrócitos/metabolismo , Condrócitos/patologia , Biologia Computacional , Feminino , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Articulação do Joelho/cirurgia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Transdução de Sinais , Fator de Transcrição AP-1/metabolismo
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