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1.
Neuroreport ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31568209

RESUMO

Drug use among adolescents continues to be an area of concern because of the possibility of long-lasting physical and mental changes. The aim of this study was to determine whether methamphetamine exposure during adolescence results in long-lasting neurobehavioral alterations in adulthood. Sprague-Dawley rats were injected with methamphetamine (4 mg/kg/day) during postnatal days 28-37. Once rats reached postnatal days 150, they were placed in standard operant chambers, where they were trained to respond to a lever for sucrose pellets, the experimental reinforcement. Methamphetamine exposure during adolescence did not result in a noteworthy impairment in the development of the correct lever touch response in the autoshaped learning test with 4 seconds delayed reinforcement. These rats were also tested for the motivation to obtain sucrose pellets under a progressive ratio schedule of the reinforcement on postnatal days 170. Decreased lever-pressing response was noted in male rats exposed to methamphetamine during adolescence, but not in female rats. These results indicate that methamphetamine exposure during adolescence results in a decrease in the motivation for a natural reinforcer later in adulthood, particularly in male rats. From our data, we suggest that male brains are less capable of facilitating recovery than female brains after methamphetamine-induced perturbation of brain function during the adolescent period.

2.
Microsurgery ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31424589

RESUMO

Although a bipedicled deep inferior epigastric artery perforator (DIEP) flap is widely accepted for slim patients with large breasts, we suggest DIEP flap-based breast reconstruction in which the superficial inferior epigastric artery (SIEA) is supercharged to the branch of thoracodorsal vessel as an alternative, which has not previously been well described. We report the case of a 48-year-old breast cancer patient who had a normal body mass index of 23.01 and relatively thin abdominal tissue, with large and ptotic (grade II ptosis) breasts. The mastectomy specimen weighed ~890 g, and the harvested abdominal tissue weighed ~700 g with a size of 32 × 12 cm2 . The elliptical-shaped flap was inset with a 90° counterclockwise rotation, and the lower one-third of the flap was folded to create a projection. Perfusion of flap was augmented by microvascular anastomosis between the contralateral SIEA and the serratus branch of a thoracodorsal vessel. With a supercharged DIEP flap, nearly the whole lower abdominal tissue (696 g, 99.4% of the elevated flap) could be transferred to obtain a symmetric contour, and there were no complications such as vascular obstruction, flap necrosis, and delayed wound healing during the postoperative course. Using the SIEA pedicle for contralateral abdominal perfusion with elongated branch of the thoracodorsal vessel, aesthetic inset and contouring of the reconstructed breast could be technically enhanced. The DIEP flap with the contralateral SIEA supercharged to the serratus branch of thoracodorsal vessel may be a feasible option for large ptotic breast reconstruction in thin patients.

3.
Nanoscale ; 11(33): 15596-15604, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31403638

RESUMO

The fundamental unit of the nervous system is a synapse, which is involved in transmitting information between neurons as well as learning, memory, and forgetting processes. Two-terminal memristors can fulfil most of these requirements; however, their poor dynamic changes in resistance to input electric stimuli remain an obstacle, which must be improved for accurate and quick information processing. Herein, we demonstrate the synaptic properties of ZnO-based memristors, which were significantly enhanced (∼340 times) by geometrical modulation due to the localized electric field enhancement. Specifically, by inserting Ag-nanowires and Ag-dots into the ZnO/Si interface, the resistive switching could be controlled from a digital to analog mode. A finite element simulation revealed that the presence of Ag could enhance the localized electric field, which in turn improved the migration of ionic species. Further, the device showed a variety of comprehensive synaptic functions, for instance, paired-pulse facilitation and transformation from short-term plasticity to long-term plasticity, including the Pavlovian associative learning process in a human brain. Our study presents a novel architecture to enhance the synaptic sensitivity, and its uses in practical applications, including the artificial learning algorithm.

4.
J Phys Chem Lett ; 10(16): 4720-4724, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31369281

RESUMO

Probing the atomic details of intrinsically disordered proteins is crucial to understanding their biological function and relation to pathogenesis. Although amide-detected NMR experiments are widely employed in protein studies, 3JHNHα couplings between amide (1HN) and alpha (1Hα) protons impose an intrinsic limit on the achievable 1HN linewidth. Here, we present a homonuclear decoupling method that narrows the α-synuclein 1HN linewidths to 3-5 Hz. Tightly distributed 1JCαHα coupling values were employed to generate homogeneous antiphase coherences of 2HαzHNy and 4Hα(2)zHα(3)zHNy for nonglycine and glycine residues, respectively, which were combined with their in-phase HNy counterparts to achieve homonuclear decoupling. By reducing the multiplet structure to a singlet, the width of the 1HN cross-peak was reduced by ∼3-fold in the 2D HSQC and 3D intra-HNCA spectra, and good spectral quality was achieved without the need for postprocessing.


Assuntos
Ressonância Magnética Nuclear Biomolecular , alfa-Sinucleína/química , Amidas/química , Glicina/química , Prótons , Teoria Quântica , Soluções/química
5.
Mar Drugs ; 17(9)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438635

RESUMO

Four new peptides were isolated from the culture broths of the marine-derived fungi Aspergillus allahabadii and A. ochraceopetaliformis. Based on the results of chemical and spectroscopic analyses, two compounds (1 and 2) from A. allahabadii were determined to be cyclopentapeptides, while those from A. ochraceopetaliformis were a structurally-related cyclodepsihexapeptide (3) and its linear analog (4). In addition to the presence of a D-amino acid residue, the almost reversed sequence of peptides in 3 and 4, relative to those of the 1 and 2, is notable. These new compounds exhibited moderate inhibition against the enzyme sortase A as well as a weak inhibition against isocitrate lyase (2).

6.
Microsurgery ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31433073

RESUMO

BACKGROUND: Successful penoscrotal reconstruction requires proper resurfacing of the defect and maintenance of the original shape of the penis and scrotum. We examined the feasibility of using the superficial circumflex iliac artery perforator (SCIP) propeller flap to effectively reconstruct penoscrotal defects. METHODS: Eleven male patients with an average age of 62.2 years were retrospectively evaluated. The average defect size was 21.3 × 10.5 cm2 (range: 10 × 8-24 × 16 cm2 ). An eccentrically located elliptical flap was constructed using a handheld Doppler device after detecting the perforator as the pivot point. The medial branch of the superficial circumflex iliac artery was used for all cases. Flaps were designed to cover 70-80% of the defect area and the average rotation arc was 165°. RESULTS: The average flap dimension was 19.7 × 7.7 cm2 . Two cases showed partial necrosis in the flap tip area. There were no instances of total flap loss or lymphorrhea, or complications such as scar contracture, urination problems, erectile dysfunction, or discomfort during intercourse. CONCLUSIONS: The SCIP flap is an effective and ideal method for penoscrotal reconstruction considering the loose, elastic, and thin nature of the tissue. Elevation is easily facilitated, and the thickness of the SCIP flap can be adjusted without microsurgery.

7.
Sensors (Basel) ; 19(15)2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31362386

RESUMO

The Global Satellite Navigation System (GNSS) used in various location-based services is accurate and stable in outdoor environments. However, it cannot be utilized in an indoor environment because of low signal availability and degradation of accuracy due to the multipath distortion of satellite signals in urban areas. On the contrary, LTE signals are available almost everywhere in urban areas and are quite stable without much variation throughout the year. This is because of the fixed location of base stations and the well-maintained policy of mobile communication service providers. Its varied stability and reliability make LTE signals a more viable method for localization. However, there are some complexities in utilizing LTE signals including signal interference distortion phenomena during propagation multipath fading, and various types of noise. In this paper, we propose a surface correlation-based fingerprinting method to utilize LTE signals for localization in urban areas. The surface correlation converts timely measured signal strength into spatial pattern using the walking distance from a Pedestrian Dead-Reckoning (PDR). The surface correlation is carried out by comparing the spatial signal strength pattern of a pedestrian`s movement trajectory with a fingerprinting database to estimate the location. A reference trajectory of the moving pedestrian is chosen to have a greater correlation among the multiple trajectory candidates generated from a link-based fingerprinting database. By comparing spatial signal strength patterns, the proposed method can improve robustness in localization overcoming the accuracy degradation problem due to RF multipath and noise that are dominant in the conventional RSS measurement-based LTE localization scheme. The test results in urban areas demonstrate that the proposed surface correlation-based fingerprinting method has improved performance compared to the other conventional methods, thus proving to be a useful complementary method to the GNSS in urban areas.

8.
ACS Appl Mater Interfaces ; 11(28): 25140-25146, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31259511

RESUMO

We demonstrated surface passivation of a black Si-based solar cell using an (NH4)2S solution to mitigate surface recombination velocity. Incorporated S at the interface between atomic-layer-deposited Al2O3 and black Si by (NH4)2S solution treatment boosted the density of negative fixed charges, S-enhanced field-effect passivation. Furthermore, NH4OH generated during (NH4)2S solution treatment removed the defective Si phase at the black Si surface, the surface cleaning effect. The optimized (NH4)2S solution treatment significantly enhanced the internal quantum efficiency up to ∼17.2% in the short wavelength region, suggesting suppressed surface recombination. As a result, photoconversion efficiency of the cell increased from 11.6 to 13.5%, by 16% compared to the control cells without (NH4)2S solution treatment.

9.
Sci Rep ; 9(1): 9132, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235765

RESUMO

The use of a photoelectrochemical device is an efficient method of converting solar energy into hydrogen fuel via water splitting reactions. One of the best photoelectrode materials is Si, which absorbs a broad wavelength range of incident light and produces a high photocurrent level (~44 mA·cm-2). However, the maximum photovoltage that can be generated in single-junction Si devices (~0.75 V) is much lower than the voltage required for a water splitting reaction (>1.6 V). In addition, the Si surface is electrochemically oxidized or reduced when it comes into direct contact with the aqueous electrolyte. Here, we propose the hybridization of the photoelectrochemical device with a thermoelectric device, where the Seebeck voltage generated by the thermal energy triggers the self-biased water splitting reaction without compromising the photocurrent level at 42 mA cm-2. In this hybrid device p-Si, where the surface is protected by HfOx/SiOx bilayers, is used as a photocathode. The HfOx exhibits high corrosion resistance and protection ability, thereby ensuring stability. On applying the Seebeck voltage, the tunneling barrier of HfOx is placed at a negligible energy level in the electron transfer from Si to the electrolyte, showing charge transfer kinetics independent of the HfOx thickness. These findings serve as a proof-of-concept of the stable and high-efficiency production of hydrogen fuel by the photoelectrochemical-thermoelectric hybrid devices.

10.
J Immunol ; 203(1): 127-136, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31142603

RESUMO

Mesenchymal stem cells (MSCs) can protect against cartilage breakdown in osteoarthritis (OA) via their immunomodulatory capacities. However, the optimization strategy for using MSCs remains challenging. This study's objective was to identify the in vivo effects of metformin-stimulated adipose tissue-derived human MSCs (Ad-hMSCs) in OA. An animal model of OA was established by intra-articular injection of monosodium iodoacetate into rats. OA rats were divided into a control group and two therapy groups (treated with Ad-hMSCs or metformin-stimulated Ad-hMSCs). Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Our data show that metformin increased IL-10 and IDO expression in Ad-hMSCs and decreased high-mobility group box 1 protein, IL-1ß, and IL-6 expression. Metformin increased the migration capacity of Ad-hMSCs with upregulation of chemokine expression. In cocultures, metformin-stimulated Ad-hMSCs inhibited the mRNA expression of RUNX2, COL X, VEGF, MMP1, MMP3, and MMP13 in IL-1ß-stimulated OA chondrocytes and increased the expression of TIMP1 and TIMP3. The antinociceptive activity and chondroprotective effects were greater in OA rats treated with metformin-stimulated Ad-hMSCs than in those treated with unstimulated Ad-hMSCs. TGF-ß expression in subchondral bone of OA joints was attenuated more in OA rats treated with metformin-stimulated Ad-hMSCs. Our findings suggest that metformin offers a promising option for the clinical application of Ad-hMSCs as a cell therapy for OA.

11.
J Nat Prod ; 82(4): 937-946, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-30896942

RESUMO

Tuberculosis is an infectious disease of global concern. Members of the diazaquinomycin (DAQ) class of natural products have shown potent and selective activity against drug-resistant Mycobacterium tuberculosis. However, poor solubility has prevented further development of this compound class. Understanding DAQ biosynthesis may provide a viable route for the generation of derivatives with improved properties. We have sequenced the genomes of two actinomycete bacteria that produce distinct DAQ derivatives. While software tools for automated biosynthetic gene cluster (BGC) prediction failed to detect DAQ BGCs, comparative genomics using MAUVE alignment led to the identification of putative BGCs in the marine Streptomyces sp. F001 and in the freshwater Micromonospora sp. B006. Deletion of the identified daq BGC in strain B006 using CRISPR-Cas9 genome editing abolished DAQ production, providing experimental evidence for BGC assignment. A complete model for DAQ biosynthesis is proposed based on the genes identified. Insufficient knowledge of natural product biosynthesis is one of the major challenges of productive genome mining approaches. The results reported here fill a gap in knowledge regarding the genetic basis for the biosynthesis of DAQ antibiotics. Moreover, identification of the daq BGC shall enable future generations of improved derivatives using biosynthetic methods.

12.
Am J Sports Med ; : 363546518810517, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30485118

RESUMO

BACKGROUND:: There is a lack of knowledge about the changes in perianchor cysts over time and the factors related to perianchor cysts. PURPOSE:: To evaluate the changes in perianchor cyst formation and anchor absorption over time after arthroscopic rotator cuff repair with a biocomposite suture anchor and to evaluate the factors affecting perianchor cyst persistence and their relationship with patient outcomes. STUDY DESIGN:: Case-control study; Level of evidence, 3. METHODS:: Forty consecutive patients (mean age, 61.10 ± 5.79 years) who underwent arthroscopic repair for medium- to large-sized rotator cuff tears using a single type of biocomposite (poly-L-lactic acid/polyglycolic acid-beta tricalcium phosphate) medial-row anchor were prospectively enrolled. Postoperative magnetic resonance imaging (MRI) at 2 different time points (6 and 18 months) was performed, and perianchor cyst formation, anchor absorption, and healing failures were evaluated using postoperative MRI. Demographic and clinical data were collected, and functional outcomes at a minimum of 18 months after surgery were assessed. RESULTS:: Perianchor cysts were observed in 24 patients (60.0% total; grade 1: 35.0%; grade 2: 10.0%; grade 3: 7.5%; grade 4: 7.5%) at 6 months, and 7 patients (18.4% total; grade 1: 7.9%; grade 2: 5.3%; grade 3: 2.6%; grade 4: 2.6%) had a persistent perianchor cyst at 18 months after surgery. No anchors were absorbed at 6 months, but 73.7% of patients revealed complete or near-full absorption at 18 months. Patients with persistent perianchor cysts showed a significantly larger tear size in the anteroposterior dimension ( P = .002) and greater retraction ( P < .001). There were no differences in healing failures and functional outcomes between patients with and without persisting perianchor cysts (all P > .05). No differences were found in perianchor cyst formation and anchor absorption between anchors inserted in the greater tuberosity and the lesser tuberosity (all P > .05). CONCLUSION:: The incidence and severity of perianchor cysts decreased with time, and most biocomposite suture anchors were absorbed at 18 months after surgery. Persisting perianchor cysts correlated with a larger tear size in the anteroposterior dimension and greater retraction.

13.
J Phys Chem Lett ; 9(18): 5412-5418, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30179502

RESUMO

The open-circuit potential ( Voc) represents the maximum thermodynamic potential in a device, and achieving a high Voc is crucial for self-biased photoelectrochemical (PEC) devices that use only solar energy to produce chemical energy. In general, Voc is limited by the photovoltage ( Vph), which is a potential difference generated by light-induced thermodynamic processes at semiconductor photoelectrodes, such as the generation and recombination of charge carriers. Therefore, low light intensity and nanostructured semiconductor materials degrade Vph (and Voc) by inefficient carrier generation and by enhancing recombination loss, respectively. Here, we report that Voc in dynamic PEC devices employing a porous NiO x/Si photocathode is insensitive to thermodynamic losses, which was clarified by varying the carrier generation and recombination rates. The Voc values were observed to be unchanged even under a low light intensity of 0.1 sun, as well as for different morphologies such as nanostructured and polycrystalline Si. These findings shed light on the potential merit of dynamically operated PEC systems.

14.
J Nat Prod ; 81(9): 1962-1967, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30199256

RESUMO

The use of botanical dietary supplements is becoming increasingly popular for the alleviation of hormonal-based conditions such as hot flashes, premenstrual syndrome, and fertility. Estrogen and progesterone receptors (ER and PR) play an essential role in these processes. However, despite the fact that many therapies used to alleviate gynecological conditions act through PR-mediated mechanisms, few studies have investigated or identified any herbal natural product components that act on this receptor. In the current study, we used a progesterone response element (PRE)-luciferase (Luc) reporter assay to identify four phytoprogestins present in a standardized red clover ( Trifolium pratense) extract. We found that the component irilone (1) potentiated the effect of progesterone in both endometrial and ovarian cancer cell lines. In these cancers, progesterone action is generally associated with positive outcomes; thus the potentiating effect of 1 may provide entirely new strategies for enhancing progesterone signaling as a means of mitigating conditions such as fibroids and endometriosis. Formononetin (3) and biochanin A (4) exhibited mixed agonist activity, while prunetin (2) acted only as an antagonist. Collectively, these results suggest that the effects of red clover extract repeatedly observed in cultured cells and the inverse correlation between risk of various cancers and flavonoid intake may be due, in part, to altered progesterone signaling.

15.
World Neurosurg ; 120: 185-189, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30201577

RESUMO

BACKGROUND: Combined revascularization is the preferred surgical management of adult Moyamoya disease. However, postoperative flap necrosis of the scalp is not an uncommon complication. We investigated the role of scalp incision design on the basis of the course of the superficial temporal artery (STA) to prevent postoperative scalp necrosis. The utility of tissue expander in wide scalp defect repair is explored. CASE DESCRIPTION: A 13-year-old female patient underwent STA-to-middle cerebral artery anastomosis and encephaloduroarteriosynangiosis due to ischemic symptoms. However, she suffered from wide scalp necrosis measuring 10.5 × 10 cm after bypass surgery. Conventional rotational scalp flap reconstruction was impossible due to the wide defect, and therefore split thickness skin graft was considered. However, aesthetic compromise or hair loss is a psychologic burden in an adolescent female. Two tissue expanders were inserted under the contralateral normal scalp, and a gradual expansion was achieved by saline infusion for 3 months. Finally, a wide scalp flap, which covered the large defect, was obtained using this procedure. The patient underwent rotational flap advancement and was discharged without any hair loss wound. CONCLUSIONS: Miserable scalp flap design results in a large scalp defect during combined bypass surgery. However, tissue expanders aided the reconstruction of a large scalp defect. Reconstruction using tissue expanders and advancement of local rotation flap is recommended in case of large scalp necrosis. The procedure yields cosmetically superior outcomes due to scalp hair conservation and concealment of postoperative scar behind the hair line.

16.
Knee ; 25(6): 1016-1026, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30115591

RESUMO

BACKGROUND: The aim of this study was to identify the correlations between the single-leg vertical jump (SLVJ) test and subjective and objective tests which were used widely for determining return-to-sports (RTS) after anterior cruciate ligament reconstruction (ACLR). METHODS: Seventy-five patients (29.5 ±â€¯9.2 years) who underwent ACLR between May 2012 and Jan 2014 were included. Subjective knee scoring systems including subjective International Knee Documentation Committee (IKDC) score, Lysholm score, Tegner activity scale, and ACL-Return to Sports after Injury (ACL-RSI) scale were assessed. Objective tests were also performed. RESULTS: The limb symmetry index (LSI) for SLVJ test and single-leg hop for distance (SLHD) test was 89.4 ±â€¯14.9% and 90.7 ±â€¯11.7%. LSI for SLVJ test was correlated to subjective IKDC scores (r = 0.26, P = 0.024), Tegner activity scale (r = 0.64, P < 0.001), ACL-RSI scale (r = 0.61, P < 0.001), LSI for SLHD (r = 0.45, P < 0.001), Co-contraction (r = -0.57, P < 0.001), Shuttle run (r = -0.52, P < 0.001), and Carioca (r = -0.54, P < 0.001) tests. In isokinetic strength tests, extensor peak torque (r = 0.30, P = 0.009) and extensor strength deficit (r = -0.41, P < 0.001) were correlated with LSI for SLVJ test. CONCLUSION: There were considerable correlations between SLVJ test and subjective IKDC scores, Tegner activity scale, ACL-RSI scale, isokinetic extensor muscle strength, and all other functional tests. SLVJ test could be used conveniently to determine RTS after ACLR in outpatient clinics. LEVEL OF EVIDENCE: Level IV, case series.

17.
Nanoscale ; 10(32): 15285-15293, 2018 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-30067253

RESUMO

Two-dimensional group-10 transition metal dichalcogenides have recently attracted increasing research interest because of their unique electronic and optoelectronic properties. Herein, we present vertical hybrid heterojunctions of multilayered PtSe2 and Si, which take advantage of large-scale homogeneous PtSe2 films grown directly on Si substrates. These heterojunctions show obvious rectifying behavior and a pronounced photovoltaic effect, enabling them to function as self-driven photodetectors operating at zero bias. The photodetectors can operate in both photovoltage and photocurrent modes, with responsivity values as high as 5.26 × 106 V W-1 and 520 mA W-1 at 808 nm, respectively. The Ilight/Idark ratio, specific detectivity, and response speed are 1.5 × 105, 3.26 × 1013 Jones, and 55.3/170.5 µs, respectively. Furthermore, the heterojunctions are highly sensitive in a broad spectral region ranging from deep ultraviolet to near-infrared (NIR) (200-1550 nm). Because of the strong NIR light absorption of PtSe2, the heterojunctions exhibit photocurrent responsivities of 33.25 and 0.57 mA W-1 at telecommunication wavelengths of 1310 and 1550 nm, respectively. Considering the excellent performance of the PtSe2/Si heterojunctions, they are highly suitable for application in high-performance broadband photodetectors. The generality of the above results also signifies that the proposed in situ synthesis method has great potential for future large-scale optoelectronic device integration.

18.
Molecules ; 23(8)2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30060484

RESUMO

Inflammation is considered the root cause of various inflammatory diseases, including cancers. Decursinol angelate (DA), a pyranocoumarin compound obtained from the roots of Angelica gigas, has been reported to exhibit potent anti-inflammatory effects. In this study, the anti-inflammatory effects of DA on the MAP kinase and NFκB signaling pathways and the expression of pro-inflammatory cytokines were investigated in phorbol 12-myristate 13-acetate (PMA)-activated human promyelocytic leukemia (HL-60) and lipopolysaccharide (LPS)-stimulated macrophage (Raw 264.7) cell lines. PMA induced the activation of the MAP kinase-NFκB pathway and the production of pro-inflammatory cytokines in differentiated monocytes. Treatment with DA inhibited the activation of MAP kinases and the translocation of NFκB, and decreased the expression and exogenous secretion of IL-1ß and IL-6. Furthermore, LPS-stimulated Raw 264.7 cells were found to have increased expression of M1 macrophage-associated markers, such as NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS), and the M2 macrophage-associated marker CD11b. LPS also activated pro-inflammatory cytokines and Erk-NFκB. Treatment with DA suppressed LPS-induced macrophage polarization and the inflammatory response by blocking Raf-ERK and the translocation of NFκB in Raw 264.7 cells. Treatment with DA also inhibited the expression of pro-inflammatory cytokines, such as IL-1ß and IL-6, NOX, and iNOS in Raw 264.7 cells. These results suggest that DA has the potential to inhibit macrophage polarization and inflammation by blocking the activation of pro-inflammatory signals. These anti-inflammatory effects of DA may contribute to its potential use as a therapeutic strategy against various inflammation-induced cancers.


Assuntos
Anti-Inflamatórios/farmacologia , Benzopiranos/farmacologia , Butiratos/farmacologia , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/citologia , NF-kappa B/metabolismo , Animais , Polaridade Celular/efeitos dos fármacos , Citocinas/metabolismo , Células HL-60 , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Ésteres de Forbol/farmacologia , Transporte Proteico/efeitos dos fármacos , Células RAW 264.7
19.
Mol Cells ; 41(7): 676-683, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-29983040

RESUMO

Cilia are highly specialized antennae-like organelles that extend from the cell surface and act as cell signaling hubs. Intraflagellar transport (IFT) is a specialized form of intracellular protein trafficking that is required for the assembly and maintenance of cilia. Because cilia are so important, mutations in several IFT components lead to human disease. Thus, clarifying the molecular functions of the IFT proteins is a high priority in cilia biology. Live imaging in various species and cellular preparations has proven to be an important technique in both the discovery of IFT and the mechanisms by which it functions. Live imaging of Drosophila cilia, however, has not yet been reported. Here, we have visualized the movement of IFT in Drosophila cilia using time-lapse live imaging for the first time. We found that NOMPB-GFP (IFT88) moves according to distinct parameters depending on the ciliary segment. NOMPB-GFP moves at a similar speed in proximal and distal cilia toward the tip (~0.45 µm/s). As it returns to the ciliary base, however, NOMPB-GFP moves at ~0.12 µm/s in distal cilia, accelerating to ~0.70 µm/s in proximal cilia. Furthermore, while live imaging NOMPB-GFP, we observed one of the IFT proteins required for retrograde movement, Oseg4 (WDR35), is also required for anterograde movement in distal cilia. We anticipate our time-lapse live imaging analysis technique in Drosophila cilia will be a good starting point for a more sophisticated analysis of IFT and its molecular mechanisms.


Assuntos
Cílios/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Imagem com Lapso de Tempo , Animais , Cílios/ultraestrutura , Drosophila melanogaster/ultraestrutura , Proteínas de Fluorescência Verde/metabolismo , Audição , Mutação/genética , Neurônios/metabolismo , Neurônios/ultraestrutura , Transporte Proteico
20.
Front Immunol ; 9: 1611, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30042768

RESUMO

Objective: Systemic sclerosis (SSc) is a progressive fibrotic disease that affects the skin and internal organs. Despite evidence implicating increased interleukin-17 (IL-17) activity in SSc, the role of IL-17 in SSc remains uncertain. The purpose of this study was to investigate whether IL-17 plays a pathophysiological role in SSc in two different murine models of SSc. Methods: Bleomycin (BLM)-induced fibrosis and chronic graft-versus-host disease (cGVHD) models were used. Histological analysis was performed using Masson's trichrome and immunohistochemical staining. Quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunoassays were used to quantify the messenger RNA and protein levels of inflammatory mediators in dermal fibroblasts. Results: IL-1 receptor antagonist-deficient (IL-1Ra-KO) mice were more severely affected by BLM injection, as shown by dermal and pulmonary fibrosis, compared with wild-type (WT) mice. Increased tissue fibrosis was reversed by knocking down IL-17. In vitro experiments showed that IL-1 and IL-17 exerted synergistic effects on the expression of profibrotic and inflammatory mediators. In the cGVHD model, C57BL/6 mice receiving splenocytes of IL-1Ra-KO BALB/c mice developed more severe cGVHD than did those receiving cells from WT mice. Knockdown of IL-17 in IL-1Ra-KO donor mice significantly attenuated the IL-1-induced acceleration of cGVHD severity. Conclusion: Targeting IL-1 and its downstream IL-17 activity may be a novel treatment strategy for inhibiting inflammation and tissue fibrosis in SSc.

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