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1.
Talanta ; 207: 120287, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594575

RESUMO

The three-dimensional (3D) DNA nanostructure has been got much attention due to its excellent biocompatibility, enhanced structural stability, highly programmable and perfect cell-delivery performance. Here, a novel 3D DNA tetrahedron amplifier (DTA) has been developed for rapid and efficient mRNA imaging in living cells using target catalyzing spatial-confinement hairpin DNA assembly cascade reaction inside the DNA nanostructure. The DTA was constructed by assembling a DNA tetrahedron with four DNA strands at first, and then by assembling two metastable DNA hairpins H1 (Cy5) and H2 (Cy3) at specific locations of the DNA tetrahedron. In the presence of target mRNA, the catalyzed hairpin assembly (CHA) reaction on the DTA could be triggered and a H1-H2 duplexes nanostructure could be formed, which would obtain a significant fluorescence resonance energy transfer (FRET) signal, and release the target mRNA could trigger next H1-H2 duplexes formation. Due to the 3D DNA tetrahedral spatial-confinement effect, the circular reaction of DTA could achieve rapid and efficient amplification detection of target mRNA in living cells. Moreover, the DTA show excellent structural stability and non-cytotoxicity. This strategy presents a versatile method for the ultrasensitive detection of biomarkers in living system and gains a deeper development of the DNA nanostructures in biomedical functions.

2.
J Hazard Mater ; 382: 121090, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31476718

RESUMO

Fenton reaction is widely used for hazardous pollutant degradation. Reducing agents (RAs) have been proven to be efficient in promoting the generation of HO• in Fenton reaction by accelerating the redox cycle of Fe3+/Fe2+. However, the roles of different RAs in Fenton reaction remain unrevealed. In this work, the catalytic activity of three RAs, i.e., hydroxylamine (NH2OH), ascorbic acid (AA) and cysteine (Cys), on the degradation of benzoic acid (BA) and the hydroxyl radical formation in the Fenton-RAs system were investigated. Results show the catalytic performance of RAs in BA degradation by Fenton reaction followed an order of NH2OH > AA > Cys. Compared with the conventional Fenton system, the effective pH range in the Fenton-NH2OH system extended from 3.0 to 5.0, while the optimal pH in the Fenton-AA and Fenton-Cys systems ranged from 3.0 to 4.0. The Fenton-AA system exhibited a two-stage reaction toward BA degradation, which was different from the Fenton-NH2OH and Fenton-Cys systems. Furthermore, the dosing manner of AA was found to be a key factor governing its role in the Fenton-AA system. This observation suggests the different mechanisms behind the enhancement of the three RAs in Fenton system. Different from NH2OH and Cys, AA would inhibit the generation of HO•, especially at the fast stage of degradation process, where Fe3+ has not accumulated yet. In addition, the economic analysis using the electrical energy per order indicates Fenton-NH2OH system was economically feasible with the lowest energy input, compared to Fenton-AA and Fenton-Cys systems. These results are useful to better understand the roles of RAs in Fenton system, and also provide guidance about the selection and dosing manner of suitable RAs in the advanced oxidation processes.

3.
Anal Chim Acta ; 1093: 52-60, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31735215

RESUMO

A high performance miRNA biosensor based on effective click chemistry assembly of a Ru(bpy)32+ labeled DNA probe and efficient electrochemiluminescence (ECL) quenching of the Ru(bpy)32+/BDEA (BDEA = N-butyldiethanolamine) system by surface-confined electroactive methylene blue (MB) dye is reported. When the target miRNA was present, the ECL signal instantly changed from "light off" to "light on" status. Using the specific miRNA let-7d as the target analyte, this biosensor provided sensitive detection over approximately six orders of magnitude (10 fM-10 nM), with a limit of detection of 10 fM (S/N = 3). Detailed study of the ECL quenching behavior of the Ru(bpy)32+/BDEA system by MB in solution suggested that the ECL quenching involves a combination of photoluminescence dynamic quenching and quenching processes directly associated with the redox reactions, as well as resonance energy transfer. A large binding constant of 4.7 × 1011 M-1 between let-7d and the DNA hairpin was estimated using an ECL-based extended Langmuir isotherm model, suggesting remarkably strong binding of the target to the probe. Furthermore, our biosensor exhibited excellent specificity and reproducibility. Using the developed system, the concentration of the target miRNA extracted from the A549 cell line could be obtained, demonstrating the potential application of the developed biosensor to practical biological sample analysis.

4.
Nat Commun ; 10(1): 5380, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772164

RESUMO

Despite the efficacy of current starvation therapies, they are often associated with some intrinsic drawbacks such as poor persistence, facile tumor metastasis and recurrence. Herein, we establish an extravascular gelation shrinkage-derived internal stress strategy for squeezing and narrowing blood vessels, occluding blood & nutrition supply, reducing vascular density, inducing hypoxia and apoptosis and eventually realizing starvation therapy of malignancies. To this end, a biocompatible composite hydrogel consisting of gold nanorods (GNRs) and thermal-sensitive hydrogel mixture was engineered, wherein GRNs can strengthen the structural property of hydrogel mixture and enable robust gelation shrinkage-induced internal stresses. Systematic experiments demonstrate that this starvation therapy can suppress the growths of PANC-1 pancreatic cancer and 4T1 breast cancer. More significantly, this starvation strategy can suppress tumor metastasis and tumor recurrence via reducing vascular density and blood supply and occluding tumor migration passages, which thus provides a promising avenue to comprehensive cancer therapy.

5.
J Speech Lang Hear Res ; : 1-10, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747532

RESUMO

Purpose The purpose of this study was to investigate how the distinctive establishment of 2nd language (L2) vowel categories (e.g., how distinctively an L2 vowel is established from nearby L2 vowels and from the native language counterpart in the 1st formant [F1] × 2nd formant [F2] vowel space) affected L2 vowel perception. Method Identification of 12 natural English monophthongs, and categorization and rating of synthetic English vowels /i/ and /ɪ/ in the F1 × F2 space were measured for Chinese-native (CN) and English-native (EN) listeners. CN listeners were also examined with categorization and rating of Chinese vowels in the F1 × F2 space. Results As expected, EN listeners significantly outperformed CN listeners in English vowel identification. Whereas EN listeners showed distinctive establishment of 2 English vowels, CN listeners had multiple patterns of L2 vowel establishment: both, 1, or neither established. Moreover, CN listeners' English vowel perception was significantly related to the perceptual distance between the English vowel and its Chinese counterpart, and the perceptual distance between the adjacent English vowels. Conclusions L2 vowel perception relied on listeners' capacity to distinctively establish L2 vowel categories that were distant from the nearby L2 vowels.

6.
Cell Rep ; 29(8): 2489-2504.e4, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31747615

RESUMO

Hair follicle stem cells (HFSCs) and subsequent generations of matrix progeny make lineage choices by responding to spatiotemporal signals; however, the cues driving that specification are not well understood. Here, we demonstrate that the dynamics of microRNA (miR)-29 expression are inversely proportional to HFSC lineage progression. Furthermore, we show that sustained miR-29a/b1 overexpression in anagen or telogen in mice causes a short-hair phenotype and eventual hair loss by inhibiting the proliferation of HFSCs and matrix cells and likely preventing their differentiation. Conversely, in a loss-of-function in vivo model, miR-29a/b1 deficiency accelerates HFSC lineage progression in telogen. Mechanistically, miR-29a/b1 blocks HFSC lineage specification by spatiotemporally targeting Ctnnb1, Lrp6, Bmpr1a, and Ccna2. We further show that skin-specific Lrp6 or Bmpr1a ablation partially accounts for the short-hair phenotype. Overall, these synergistic targets reveal miR-29a/b1 as a high-fidelity antagonist of HFSC lineage progression and a potential therapeutic target for hair loss.

7.
J Mater Chem B ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750849

RESUMO

Optimal integration between the polyethylene terephthalate (PET) graft and host bone is a prerequisite to obtain a satisfactory outcome after graft implantation for ligament reconstruction. Recent studies indicate that complex biosignals including immunoregulation, cell recruitment, and osteogenic differentiation provided by the extracellular matrix (ECM) are conducive to promoting osseointegration. In the present study, a chondroitin sulfate (CS)/polydopamine-modified PET graft was developed to regulate the local immune microenvironment, guide stem cell behavior, and promote new bone formation. We found that CS-modified PET grafts significantly regulated the macrophage phenotype switching from M1 to M2 and promoted the expression of pro-repair cytokines including interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-ß1. Moreover, the immunoregulatory function of CS-modified PET guided stem cell behaviors, including recruitment, adhesion, and proliferation, and enhanced the osteogenic differentiation of stem cells. In vivo experiments confirmed that CS-modified PET switched the local immune microenvironment status from pro-inflammatory to anti-inflammatory, up-regulated osteogenic marker expression, and promoted the bone regeneration process, so as to achieve graft-bone osseointegration. These results indicate that an ECM-biomimetic immunoregulatory coating is an effective approach to promote graft integration. This study proposes an effective strategy for an artificial graft to achieve graft-bone osseointegration through immunoregulatory osteogenesis.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31750975

RESUMO

Near-infrared (NIR) light triggered amplified photodynamic therapy (PDT) is highly desirable for tumor treatment. Herein, we report the design and synthesis of a mitochondria-specific, 808 nm NIR light-activated PDT system based on the combination of metal-organic frameworks (MOFs) and upconversion photochemistry with organelle-targeted strategy. The system was synthesized through growth of porphyrinic MOF on Nd 3+ -sensitized upconversion nanoparticles to achieve Janus nanostructures with further asymmetric functionalization of the surface of MOF domain. Of note, the designed PDT nanoplatform allows for photosensitizing with 808 nm NIR light, which has minimized absorption of biological tissue and thus could effectively avoid the laser irradiation-induced overheating effect. Furthermore, mitochondria-targeted capability could amplify PDT efficacy through the depolarization of the mitochondrial membrane and the initiation of intrinsic apoptotic pathway. This work not only presents the first 808 nm NIR light-activated MOFs for organelle-targeted PDT, but also sheds light on the hybrid engineering of MOFs to combat their current limitations for PDT.

9.
BMC Genomics ; 20(1): 842, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718558

RESUMO

BACKGROUND: Recent advances in genomic technologies have facilitated genome-wide investigation of human genetic variations. However, most efforts have focused on the major populations, yet trio genomes of indigenous populations from Southeast Asia have been under-investigated. RESULTS: We analyzed the whole-genome deep sequencing data (~ 30×) of five native trios from Peninsular Malaysia and North Borneo, and characterized the genomic variants, including single nucleotide variants (SNVs), small insertions and deletions (indels) and copy number variants (CNVs). We discovered approximately 6.9 million SNVs, 1.2 million indels, and 9000 CNVs in the 15 samples, of which 2.7% SNVs, 2.3% indels and 22% CNVs were novel, implying the insufficient coverage of population diversity in existing databases. We identified a higher proportion of novel variants in the Orang Asli (OA) samples, i.e., the indigenous people from Peninsular Malaysia, than that of the North Bornean (NB) samples, likely due to more complex demographic history and long-time isolation of the OA groups. We used the pedigree information to identify de novo variants and estimated the autosomal mutation rates to be 0.81 × 10- 8 - 1.33 × 10- 8, 1.0 × 10- 9 - 2.9 × 10- 9, and ~ 0.001 per site per generation for SNVs, indels, and CNVs, respectively. The trio-genomes also allowed for haplotype phasing with high accuracy, which serves as references to the future genomic studies of OA and NB populations. In addition, high-frequency inherited CNVs specific to OA or NB were identified. One example is a 50-kb duplication in DEFA1B detected only in the Negrito trios, implying plausible effects on host defense against the exposure of diverse microbial in tropical rainforest environment of these hunter-gatherers. The CNVs shared between OA and NB groups were much fewer than those specific to each group. Nevertheless, we identified a 142-kb duplication in AMY1A in all the 15 samples, and this gene is associated with the high-starch diet. Moreover, novel insertions shared with archaic hominids were identified in our samples. CONCLUSION: Our study presents a full catalogue of the genome variants of the native Malaysian populations, which is a complement of the genome diversity in Southeast Asians. It implies specific population history of the native inhabitants, and demonstrated the necessity of more genome sequencing efforts on the multi-ethnic native groups of Malaysia and Southeast Asia.

10.
Fungal Genet Biol ; : 103313, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31751775

RESUMO

MicroRNAs (miRNAs in animals and plants or milRNAs in fungi) are endogenous noncoding RNAs that can regulate gene expression. However, little information is known about milRNAs and their target genes in Ganoderma lucidum. Here, we systematically predicted and characterised the milRNAs and their target genes across the three developmental stages of G. lucidum. A total of 168 unique milRNAs were predicted using a small RNA sequencing method. For them, 1,612 target sequences corresponding to 1,311 unique genes were predicted by degradome sequencing. We selected 42 predicted milRNAs and performed RT-PCR amplification and Sanger sequencing of the products. Five products were found to have sequences similar to those predicted, confirming the presence of milRNAs in G. lucidum, but demonstrating the difficulty in their validation. Among the 168 milRNAs, 111 were found to be significantly differentially expressed across the three developmental stages (q ≤ 0.05). The expression levels of 12 milRNAs were measured by stem-loop quantitative real-time polymerase chain reaction. Eight of them were in line with the sequencing results (r ≥ 0.9, p ≤ 0.05). These 12 milRNAs and their target genes form 16 milRNA-target gene pairs. The expression profiles of 8 of these 16 miRNA-target pairs were negatively correlated, according to real-time quantitative analysis, whereas the other eight pairs were positively correlated. Furthermore, the results of functional enrichment analysis showed that the target genes of milRNAs mapped to the Gene Ontology terms 'GTP binding' and 'FAD binding' were enriched in specific developmental stages. These target genes were related to the biosynthesis of triterpenes and polysaccharides and lignin degradation pathway in G. lucidum. In summary, this study has indicated that milRNAs may play crucial regulatory roles in various biological processes of G. lucidum for the first time and open up new avenues for research on milRNAs' biosyntheses and functions in basidiomycetes.

11.
Int J Biol Macromol ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739054

RESUMO

Foot and mouth disease virus (FMDV) is a highly contagious pathogen propagating among cloven-hoofed animals. As a major immunogenic protein, VP1 plays a pivotal role in the induction of neutralizing antibodies, which therefore is an ideal target for developing subunit vaccines. In current study, four prokaryotic expression clones (rV4C, rC4V, rV5F and rF5V) were constructed by fusing truncated calreticulin (CRT) (120-250 aa or 120-308 aa) at the N/C terminal of vp1 gene, and co-expressed with chaperone trigger factor 16 (Tf16) in E.coli, respectively. The soluble recombinant CRT-fused VP1 proteins could form into homogeneous reactive polymers with average hydrodynamic diameters around 100 nm according to the dynamic light scattering (DLS) data. Immunization of guinea pigs with 10 µg purified CRT-fused VP1 proteins induced high levels of antibodies against naked-VP1 through indirect ELISA. Sandwich ELISA showed that only rC4V could elicit the same level of antibody against FMD virus as commercial inactivated vaccine after booster. The lymphocyte cytokines secretion of immunized rC4V was higher than the other CRT-fused VP1 proteins in guinea pigs. These results showed that the soluble CRT-fused VP1 proteins, especially rC4V, expressed with Tf16 in E. coli might have potential to be used as subunit vaccine candidate against FMDV.

12.
Mol Med Rep ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31746390

RESUMO

Intervertebral disc degeneration (IDD) and ligamentum flavum hypertrophy (LFH) are major causes of degenerative spinal disorders. Comparative and proteomic analysis was used to identify differentially expressed proteins (DEPs) in IDD and LFH discs compared with normal discs. Subsequent gene ontology term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DEPs in human IDD discs or LFH samples were performed to identify the biological processes and signaling pathways involved in IDD and LFH. The PI3K­AKT signaling pathway, advanced glycation endproducts­receptor for advanced glycation endproducts signaling pathway, p53 signaling pathway, and transforming growth factor­b signaling pathway were activated in disc degeneration. This review summarizes the recently identified DEPs, including prolargin, fibronectin 1, cartilage intermediate layer protein, cartilage oligomeric matrix protein, and collagen types I, II and IV, and their pathophysiological roles in degenerative spinal disorders, and may provide a deeper understanding of the pathological processes of human generative spinal disorders. The present review aimed to summarize significantly changed proteins in degenerative spinal disorders and provide a deeper understanding to prevent these diseases.

13.
J Mol Endocrinol ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31710594

RESUMO

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women. Women with PCOS have a 2.7-fold increased risk for developing endometrial cancer (EC). The study was performed to investigate the potential stimulatory effects of serum exosomes isolated from patients with PCOS on EC cell lines and to explore the underlying mechanism. EC cell lines exposed to exosomes derived from PCOS patients serum exhibited a phenotype of enhanced migration and invasion. Next, sequence-based analysis of exosomal miRNA was conducted to screen the differentially expressed miRNAs in serum exosomes from PCOS patients and normal controls. The levels of 55 mature miRNAs significantly differed in serum exosomes from PCOS patients compared with normal controls. Real time PCR was used to verify the expression of 8 of these miRNAs, among which miR-27a-5p was the most significantly elevated in PCOS patients serum exosomes. The role of miR-27a-5p in EC migration and invasion was further investigated via transfection with miR-27a-5p mimics or inhibitor in Ishikawa and HEC-1A EC cell lines. In addition, the SMAD4 gene was identified as the target of miR-27a-5p by several target prediction databases and validated by a luciferase assay. SMAD4 messenger RNA (mRNA) and protein levels were decreased in EC cells transfected with the miR-27a-5p mimics but increased when transfected with the miR-27a-5p inhibitor. Furthermore, the results of in vitro experiments confirmed that miR-27a-5p prohibited migration and invasion via SMAD4 downregulation. Thus, serum exosomal miR-27a-5p may play a role in EC development in PCOS patients.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31677784

RESUMO

Oxidative stress and cardiomyocyte apoptosis contributed to the progression of doxorubicin (Dox)-induced cardiotoxicity. Recent studies identified microRNA-22 (miR-22) as a cardiac- and skeletal muscle-enriched microRNA that functioned as a key regulator in stress-induced cardiac injury. The present study aimed to investigate the role and possible mechanism of miR-22 on Dox-induced oxidative stress and cardiomyocyte apoptosis. Mice were exposed to reduplicative injections of Dox (i.p., 4 mg/kg) weekly for consecutive 4 weeks to generate Dox-induced cardiotoxicity. Herein, we found that miR-22 level was significantly increased in murine hearts subjected to chronic Dox treatment. MiR-22 inhibition attenuated oxidative stress and cardiomyocyte apoptosis in vivo and in vitro, thereby preventing Dox-induced cardiac dysfunction. Mechanistically, we observed that miR-22 directly bound to the 3'-UTR of Sirt1 and caused SIRT1 downregulation. Conversely, miR-22 antagomir upregulated SIRT1 expression and SIRT1 inhibitor abolished the beneficial effects of miR-22 antagomir. In conclusion, miR-22 inhibition prevented oxidative stress and cardiomyocyte apoptosis via upregulating SIRT1 and miR-22 might be a new target for treating Dox-induced cardiotoxicity.

15.
Curr Biol ; 29(21): 3635-3646.e5, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31668619

RESUMO

Both the structure and the amount of sleep are important for brain function. Entry into deep, restorative stages of sleep is time dependent; short sleep bouts selectively eliminate these states. Fragmentation-induced cognitive dysfunction is a feature of many common human sleep pathologies. Whether sleep structure is normally regulated independent of the amount of sleep is unknown. Here, we show that in Drosophila melanogaster, activation of a subset of serotonergic neurons fragments sleep without major changes in the total amount of sleep, dramatically reducing long episodes that may correspond to deep sleep states. Disruption of sleep structure results in learning deficits that can be rescued by pharmacologically or genetically consolidating sleep. We identify two reciprocally connected sets of ellipsoid body neurons that form the heart of a serotonin-modulated circuit that controls sleep architecture. Taken together, these findings define a circuit essential for controlling the structure of sleep independent of its amount.

16.
Comput Intell Neurosci ; 2019: 9027803, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687008

RESUMO

BOLD-fMRI technology provides a good foundation for the research of human brain dynamic functional connectivity and brain state analysis. However, due to the complexity of brain function connectivity and the high dimensionality expression of brain dynamic attributions, more research studies are focusing on tracking the time-varying characteristics through the transition between different brain states. The transition process is considered to occur instantaneously at some special time point in the above research studies, whereas our work found the brain state transition may be completed in a time section gradually rather than instantaneously. In this paper, a brain state conversion rate model is constructed to observe the procedure of brain state transition trend at each time point, and the state change can be observed by the values of conversion rate. According to the results, the transition of status always lasts for a few time points, and a brain state network model with both steady state and transition state is presented. Network topological overlap coefficient is built to analyze the features of time-varying networks. With this method, some common regular patterns of time-varying characteristics can be observed strongly in healthy children but not in the autism children. This distinct can help us to distinguish children with autism from healthy children.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31702518

RESUMO

Excessive bone resorption has been recognized as a major role in the development of bone-related diseases such as osteoporosis, rheumatoid arthritis, Paget's disease of bone, and cancer metastasis to bone. Phospholipase Cγ (PLCγ) family members PLCγ1 and PLCγ2 are critical regulators of signaling pathways downstream of growth factor receptors, integrins, and immune complexes and play a crucial role in the osteoclastogenesis. Ca2+ signaling has been recognized as an essential pathway to the differentiation of osteoclasts. With growing attention and research about natural occurring compounds, the therapeutic use of natural active plant-derived products has been widely recognized in recent years. In this review, we summarized the recent research on PLCγ signaling in bone marrow stem cells and the use of several natural compounds that were proven to inhibit RANKL-mediated osteoclastogenesis via modulating PLCγ signaling pathways.

18.
Bioanalysis ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729243

RESUMO

Organophosphorus nerve agents inhibit the cholinesterase activity by phosphylation of the active site serine. The resulting phosphylated cholinesterase and adducts on human serum albumin (HSA) are appropriate biomarkers for nerve agents exposure. Several methods have been developed for the detection of nerve agents, including fluoride reactivation or alkaline cleavage. It was previously thought that some nerve agents adducts to HSA could not be detected via fluoride regeneration. In our study, the results showed that tabun (GA) adducts of HSA could be detected by fluoride regeneration. The sample preparation included acetone precipitation, washing and SPE. Deuterated tabun (d5-GA) was applied as the internal standard. The product of regenerated fluorotabun is detected with a good linearity (R2 > 0.997) in the concentration range from 0.02 to 100.0 ng/ml, small relative standard deviation (≤6.89%) and favorable recoveries between 94.8 and 106.3%. The established preparation confirmed the fluorotabun was regenerated from the GA-HSA adducts.

19.
Aesthetic Plast Surg ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667548

RESUMO

BACKGROUND: Capsular contracture (CC) is a complication of breast augmentation that frequently requires revision surgery. The axillary approach reduces the visibility of the postoperative scar. It is unclear whether the previous incision can be used to repair the deformity caused by CC. METHODS: This study analyzed 21 patients (42 breasts) with grade III-IV CC during 2012-2017. The mean age of the patients was 32 years (range 23-48). Previous axillary scars were used to expose, and CCs were taken out completely or partially. Breast implants were removed. The dissection was performed with endoscopic assistance, using electrocautery under direct visualization. RESULTS: The mean follow-up period was 13 months (range 6-24 months). The dissection plane was changed to dual plane. Thirty-five CCs were taken out completely. Thirty-eight breast implants taken out remained intact. None of the patients required additional surgery. CONCLUSION: Endoscopic-assisted treatment may be an effective technique for treating CC and avoiding the additional scar. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

20.
Artigo em Inglês | MEDLINE | ID: mdl-31668922

RESUMO

Increasing evidence indicates some G protein-coupled receptors function as a heterodimer, which provide a novel target for therapeutics investigation. However, study on the receptor-receptor interaction interface, a potent target on interfering dimer formation, are still limited. Here, using bioluminescence resonance energy transfer (BRET) combined with co-immunoprecipitation (Co-IP), we found a new constitutive GPCR heterodimer, apelin receptor (APJ)-orexin receptor type 1 (OX1R). Both APJ and OX1R co-internalized when constantly subjected to cognate agonist (apelin-13 or orexin-A) specific to either protomer. Combined with BRET and immunostaining, the in vitro synthesized transmembrane peptides (TMs) interfering experiments suggests that TM4 and 5 of APJ act as the interaction interface of the APJ-OX1R heterodimer, and co-internalization could be disrupted by these peptides as well. Our study not only provide new evidence on GPCR heterodimerization, but address a novel heterodimerization interface, which can be severed as a potential pharmacological target.

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