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1.
Molecules ; 26(5)2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33668340

RESUMEN

Sigma-1 (σ-1) receptor agonists are considered as potential treatment for stroke. TS-157 is an alkoxyisoxazole-based σ-1 receptor agonist previously discovered in our group. The present study describes TS-157 profile in a battery of tests for cerebral ischemia. Initial evaluation demonstrated the compound's safety profile and blood-brain barrier permeability, as well as its ability to induce neurite outgrowth in vitro. The neurite outgrowth was shown to be mediated via σ-1 receptor agonism and involves upregulation of ERK phosphorylation (pERK). In particular, TS-157 also significantly accelerated the recovery of motor function in rats with transient middle cerebral artery occlusion (tMCAO). Overall, the results herein support the notion that σ-1 receptor agonists are potential therapeutics for stroke and further animal efficacy studies are warranted.

2.
Chem Commun (Camb) ; 2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33704314

RESUMEN

A donor-cell-assisted membrane biotinylation strategy was used to modify small extracellular vesicles (sEVs) while minimizing protein damage, and allowed the sEVs to be loaded onto carriers. Biotinylated programmed death-ligand 1 (PD-L1) positive sEVs were used to select for aptamers from a DNA library. PD-L1 negative sEVs from a homologous cell line were found to remove non-specific aptamer sequences to increase the specificity. After just four rounds, high-affinity aptamers for PD-L1 positive sEVs were selected as novel affinity reagents.

3.
Int J Mol Sci ; 22(4)2021 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-33672103

RESUMEN

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

4.
Genomics ; 113(3): 1114-1126, 2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33705885

RESUMEN

In the study, Methylated DNA immunoprecipitation sequencing, RNA sequencing, and whole-exome sequencing were employed to clinical small cell lung cancer (SCLC) patients. Then, we verified the therapeutic predictive effects of differentially methylated genes (DMGs) in 62 SCLC cell lines. Of 4552 DMGs between chemo-sensitive and chemo-insensitive group, coding genes constituted the largest percentage (85.08%), followed by lncRNAs (10.52%) and miRNAs (3.56%). Both two groups demonstrated two methylation peaks near transcription start site and transcription end site. Two lncRNA-miRNA-mRNA networks suggested the extensive genome connection between chemotherapy efficacy-related non-coding RNAs (ncRNAs) and mRNAs. Combing miRNAs and lncRNAs could effectively predict chemotherapy response in SCLC. In addition, we also verified the predictive values of mutated genes in SCLC cell lines. This study was the first to evaluate multiple drugs efficacy-related ncRNAs and mRNAs which were modified by methylation in SCLC. DMGs identified in our research might serve as promising therapeutic targets to reverse drugs-insensitivity by complex lncRNA-miRNA-mRNA mechanisms in SCLC.

5.
Proteomics ; : e2000211, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33634576

RESUMEN

Endometrial extracellular vesicles (EVs) are emerging as important players in reproductive biology. However, how their proteome is regulated throughout the menstrual cycle is not known. Such information can provide novel insights into biological processes critical for embryo development, implantation, and successful pregnancy. Using mass spectrometry-based quantitative proteomics, we show that small EVs (sEVs) isolated from uterine lavage of fertile women (UL-sEV), compared to infertile women, are laden with proteins implicated in antioxidant activity (SOD1, GSTO1, MPO, CAT). Functionally, sEVs derived from endometrial cells enhance antioxidant function in trophectoderm cells. Moreover, there was striking enrichment of invasion-related proteins (LGALS1/3, S100A4/11) in fertile UL-sEVs in the secretory (estrogen plus progesterone-driven, EP) versus proliferative (estrogen-driven, E) phase, with several players downregulated in infertile UL-sEVs. Consistent with this, sEVs from EP- versus E-primed endometrial epithelial cells promote invasion of trophectoderm cells. Interestingly, UL-sEVs from fertile versus infertile women carry known players/predictors of embryo implantation (PRDX2, IDHC), endometrial receptivity (S100A4, FGB, SERPING1, CLU, ANXA2), and implantation success (CAT, YWHAE, PPIA), highlighting their potential to inform regarding endometrial status/pregnancy outcomes. Thus, this study provides novel insights into proteome reprograming of sEVs and soluble secretome in uterine fluid, with potential to enhance embryo implantation and hence fertility.

6.
Life Sci ; 272: 119208, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33582177

RESUMEN

AIMS: The efficacy of anti-osteoporotic treatments is still limited. Our study aimed to investigate the effect of extracellular vesicles (EVs) derived from bone marrow-derived MSCs (BMSCs) overexpressing glycoprotein non-melanoma clone B (GPNMB) on osteoporosis (OP). MAIN METHODS: Lentiviral vector for GPNMB overexpression or its negative control was generated and transfected into BMSCs. EVs enriched with GPNMB (GPNMB-EVs) were extracted from GPNMB-modified BMSC-conditioned medium and then identified. Cellular uptake and proliferation were analyzed using the Dil-labeled assay and CCK-8 assay, respectively. Cytochemical staining, western blot, and RT-qPCR analysis were performed to assess the effect of GPNMB-EVs on osteogenic differentiation of BMSCs in vitro. Dickkopf-1 (DKK1) as the inhibitor was applied to explore the Wnt/ß-catenin signaling pathway involved in the GPNMB-EV-induced osteogenic differentiation. In vivo experiments were conducted using an ovariectomized (OVX) rat model of postmenopausal osteoporosis, and then assessed the effect of GPNMB-EVs by micro-CT, and histological and immunohistochemical assays. KEY FINDINGS: GPNMB-EVs were taken up by BMSCs, and they noticeably promoted the proliferation of BMSCs. Additionally, GPNMB-EVs activated the Wnt/ß-catenin signaling to stimulate osteogenesis in BMSCs. In vivo examination showed that GPNMB-EVs remarkably improved trabecular bone regeneration and alleviated the osteoporotic phenotype in the OVX-induced rat model of OP. SIGNIFICANCE: EVs derived from GPNMB-modified BMSCs significantly stimulated the proliferation and osteogenic differentiation of BMSCs via the activation of Wnt/ß-catenin signaling and attenuated the bone loss in the OVX-induced rat model of OP. Our findings suggest the promising potential of GPNMB-EVs as cell-free therapy for the treatment of OP.


Asunto(s)
Vesículas Extracelulares/metabolismo , Glicoproteínas de Membrana/farmacología , Osteoblastos/metabolismo , Animales , Médula Ósea/metabolismo , Células de la Médula Ósea/metabolismo , Huesos/metabolismo , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Células Cultivadas , Femenino , Glicoproteínas de Membrana/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Osteoblastos/fisiología , Osteogénesis/efectos de los fármacos , Osteoporosis/metabolismo , Ovariectomía , Ratas , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 86-90, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33554802

RESUMEN

OBJECTIVE: To investigate the clinical features and prognostic factors of patients with extranodal NK/T cell lymphoma (ENKTL). METHODS: The clinical data of patients with ENKTL from November 2009 to November 2019 was collected and retrospectively analyzed to clarify the clinical features of ENKTL, and evaluate the factors that affected survival and prognosis. RESULTS: Forty-seven patients with ENKTL were collected, median age was 40 (12-82) years old, and more common in males than females, at the ratio of 1.47∶ 1. The median follow-up was 28 (1-112) months, and 5-year overall survival (OS) rate was 49.3%. The 5-year OS rates of the subjects with ECOG performance stage 0-1 and ≥2 were 51.6% and 0 (P=0.001), respectively. The 5-year OS rates of International Prognostic Index (IPI) score 0-1 and ≥2 were 60.0% and 40.6% (P=0.027), respectively. The 5-year OS rates of Ann Arbor staging Ⅰ/Ⅱ and stage Ⅲ/Ⅳ were 61.3% and 31.7% (P=0.005), respectively. The 5-year OS rates of the patients with presentation of B symptoms and without presentation of B symptoms were 79.0% and 30.1% (P=0.013), respectively. The 5-year OS rates of plasma EBV-DNA level < 5×102/ml and ≥ 5×102/ml were 60.4% and 33.3% (P=0.003), respectively. The 5-year OS rates of the patients receiving chemotherapy alone, combined chemotherapy and radiotherapy, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) were 12.9%, 86.5%, and 62.5% (P=0.001), respectively. Univariate analysis showed that ECOG score, IPI score, Ann Arbor staging, B symptoms, the copy number of EBV-DNA, and treatment regimens were statistically significant for OS. Multivariate analysis showed that ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens were independent factors of ENKTL OS. CONCLUSION: ECOG score, B symptoms, the copy number of EBV-DNA, and treatment regimens are independent prognostic factors for OS of patients with ENKTL.


Asunto(s)
Linfoma Extranodal de Células NK-T , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma Extranodal de Células NK-T/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Autólogo
8.
Insect Sci ; 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33634599

RESUMEN

Halloween genes are involved in the biosynthesis of the molting hormone, which plays a key role in insect ecdysis, development, metamorphosis, and reproduction. Our previous work identified five Halloween genes from Locusta migratoria, but their functions are currently unknown. In this study, the sequences of these five Halloween genes were analyzed and characterized. LmCYP307a2, LmCYP306a1, LmCYP302a1, and LmCYP315a1 were primarily expressed in the prothoracic glands, while LmCYP314a1 was universally expressed in peripheral tissues, especially in the ovaries and Malpighian tubules. All five Halloween genes were mainly expressed from the 5th to the 7th d in 5th-instar nymphs. RNA interference (RNAi) silencing of LmCYP307a2 resulted in severe molting delays and molting failure, which could be rescued by supplementary 20-hydroxyecdysone. A hematoxylin and eosin staining analysis suggested that the RNAi of LmCYP307a2 inhibited the ecdysis process by inhibiting the apolysis and degradation of the old cuticle, and by promoting the synthesis of a new cuticle. Quantitative reverse transcription polymerase chain reaction results showed that the expressions of LmE74, LmCht5, and LmCht10 were dramatically down-regulated, while that of LmChsI was substantially up-regulated, after knockdown of LmCYP307a2. The results suggest that LmCYP307a2 is related to the molt process via regulation of chitin synthesis and degradation.

9.
Artículo en Inglés | MEDLINE | ID: mdl-33480836

RESUMEN

A bacterial strain, designated TRM 80801T, was isolated from the Karelinea in Taklamakan desert, Xinjiang Uygur Autonomous Region, north-west China. Cells were Gram-stain-positive, aerobic, non-motile, short rods. Strain TRM 80801T grew at 4-50 °C, with optimum growth at 28 °C, and grew at pH 6.0-11.0 and 1-15 % (w/v) NaCl. Phylogenetic analyses of the 16S rRNA gene sequences placed strain TRM 80801T within the genus Microbacterium with the highest similarities to Microbacterium suaedae YZYP 306T (98.97 %) and Microbacterium indicum BBH6T (98.17 %), respectively. The DNA G+C content of TRM 80801T is 69.38 mol%. The cell-wall peptidoglycan contained the amino acids ornithine, glutamic acid, glycine and alanine, the diagnostic diamino acid was ornithine. The acyl type of the peptidoglycan was glycolyl. Whole-cell sugars were ribose, mannose, glucose, rhamnose and galactose. The major cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The predominant menaquinones were MK-10, MK-11 and MK-12. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol. The whole-genome average nucleotide identity (ANI) value between strain TRM 80801T and Microbacterium suaedae YZYP 306T is 70.2 %. On the basis of the evidence presented in this study, strain TRM 80801T is representative of a novel species in the genus Microbacterium, for which the name Microbacterium karelineae sp. nov. is proposed. The type strain is TRM 80801T (=CCTCC AB 2019248T=KCTC 49357T).


Asunto(s)
Clima Desértico , Filogenia , Plantas Tolerantes a la Sal/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Glucolípidos/química , Hibridación de Ácido Nucleico , Peptidoglicano/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/química
10.
Cancer Treat Res Commun ; 26: 100297, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33385734

RESUMEN

BACKGROUND: This study aimed to deconvolve the levels of infiltrating immune cells in non-small cell lung cancer (NSCLC) and to identify specific gene co-expression modules associated with prognosis of NSCLC. MATERIALS AND METHODS: CIBERSORT algorithm was employed to infer the relative abundance of 22 immune cell subtypes in 1751 NSCLC subjects. The patterns of immune infiltration were identified for NSCLC with different clinical and genomic features and were used to construct an immunoscore by LASSO regression associated with NSCLC survival. Weighted gene co-expression network analysis (WGCNA) was employed to identify specific modules related to immunoscore and NSCLC survival. An integrated prognostic model was constructed with immunoscore combined with the available clinical variables and the selected gene modules to predict the prognosis of NSCLC. RESULTS: We found distinct immune infiltration patterns for NSCLC with different genotype. EGFR-mutant NSCLC was characterized by enriched resting memory CD4+ T cell. An immunoscore was established based on the infiltration abundance of 17 selected immune cell subtypes. Patients with a low immunoscore had a prolonged survival and higher abundance of CD4+ T cell, resting dendritic cells and resting mast cells. The WGCNA analysis identified the gene modules significantly associated with immunoscore and the prognosis of NSCLC. The immunoscore was further incorporated with clinical parameters and selected gene modules to fit a predictive model which stratified patients into subgroups with significantly different survival. CONCLUSION: The distinct immune profiles are associated with differential overall survival of NSCLC and the integrated model can robustly predict the prognosis of NSCLC.

11.
Methods Mol Biol ; 2261: 105-149, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33420988

RESUMEN

Extracellular vesicles (EVs) are membrane-enclosed vesicles released by cells. They carry proteins, nucleic acids, and metabolites which can be transferred to a recipient cell, locally or at a distance, to elicit a functional response. Since their discovery over 30 years ago, the functional repertoire of EVs in both physiological (e.g., organ morphogenesis, embryo implantation) and pathological (e.g., cancer, neurodegeneration) conditions has cemented their crucial role in intercellular communication. Moreover, because the cargo encapsulated within circulating EVs remains protected from degradation, their diagnostic as well as therapeutic (such as drug delivery tool) applications have garnered vested interest. Global efforts have been made to purify EV subtypes from biological fluids and in vitro cell culture media using a variety of strategies and techniques, with a major focus on EVs of endocytic origin called exosomes (30-150 nm in size). Given that the secretome comprises of soluble secreted proteins, protein aggregates, RNA granules, and EV subtypes (such as exosomes, shed microvesicles, apoptotic bodies), it is imperative to purify exosomes to homogeneity if we are to perform biochemical and biophysical characterization and, importantly, functional dissection. Besides understanding the composition of EV subtypes, defining molecular bias of how they reprogram target cells also remains of paramount importance in this area of active research. Here, we outline a systematic "how to" protocol (along with useful insights/tips) to obtain highly purified exosomes and perform their biophysical and biochemical characterization. This protocol employs a mass spectrometry-based proteomics approach to characterize the protein composition of exosomes. We also provide insights on different isolation strategies and their usefulness in various downstream applications. We outline protocols for lipophilic labeling of exosomes to study uptake by a recipient cell, investigating cellular reprogramming using proteomics and studying functional response to exosomes in the Transwell-Matrigel™ Invasion assay.


Asunto(s)
Métodos Analíticos de la Preparación de la Muestra , Exosomas/metabolismo , Proteínas/aislamiento & purificación , Proteómica , Espectrometría de Masas en Tándem , Animales , Reactores Biológicos , Técnicas de Cultivo de Célula/instrumentación , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Exosomas/ultraestructura , Fibroblastos/metabolismo , Humanos , Neoplasias/metabolismo , Proteolisis
12.
Mikrochim Acta ; 187(12): 667, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33211195

RESUMEN

A new nucleic acid detection technique, termed Nano-SAMRS-RPA, is reported which employed carbon nanomaterial (graphene oxide, GO) and self-avoiding molecular recognition systems (SAMRS) to improve the specificity of recombinase polymerase amplification (RPA). In the presence of GO and SAMRS primers, the assay artifacts, including primer-dimers, nonspecific products, off-target hybrids, and non-canonical folds, are completely suppressed and eliminated, which makes the creation of RPA-based methods faster by simplifying the primer design and eliminating the need for primer optimization and complex probe. Moreover, a lateral flow bioassay (LFB) was also devised for simply and rapidly indicating the Nano-SAMRS-RPA results. Particularly, the new detection system only requires a single-labeled primer, eliminating the false-positive result from hybridization (the labeled probe and reverse primer) and the use of real-time instrument, more complex enzymatic solutions, and probes. As a result, GO, SAMRS primers, and LFB convert RPA from a technique suited only for the research laboratory into one that has a practical value in clinical settings, field environments, and at points-of-care testing. Human papillomaviruses (HPV) genotypes 16 and 18 were applied as model analytes to test the assay's availability. The initial data indicated that Nano-SAMRS-RPA could detect down to 10 copies per reaction, and the sensitivity (14/14 samples collected from HPV16 and HPV 18 patients) and specificity (75/75 samples collected from non-HPV patients) for clinical sample detection were 100%. The proof-of-concept technique can be reconfigured to detect various nucleic acid sequences by redesigning the specific RPA primers.Graphical abstract.

13.
Chem Commun (Camb) ; 56(94): 14909-14912, 2020 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-33179640

RESUMEN

The water oxidation reaction is the pivotal half-reaction for photo-/electro-catalytic water splitting. Fabrication of high-efficiency and robust water oxidation is essential to realize wide-scale artificial photosynthesis. Here, we report an efficient strategy to improve the water oxidation activity of iridium oxide by a nitrogen-coordination method. Due to the coordination effect, the iridium oxide can be well dispersed to generate ultra-small nanoparticles and the intrinsic activity can be improved for the water oxidation reaction. This study suggests that high-performance water oxidation catalysts can be constructed based on a nitrogen-coordination strategy.

15.
Front Oncol ; 10: 1719, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33042816

RESUMEN

Purpose: To explore the value of ultrasound radiomics in the preoperative identification of true and pseudo gallbladder polyps and to evaluate the associated diagnostic accuracy. Methods: Totally, 99 pathologically proven gallbladder polyps in 96 patients were enrolled, including 58 cholesterol polyps (55 patients) and 41 gallbladder tubular adenomas (41 patients). Features on preoperative ultrasound images, including spatial and morphological features, were acquired for each lesion. Following this, two-stage feature selection was adopted using Fisher's inter-intraclass variance ratios and Z-scores for the selection of intrinsic features important for differential diagnosis achievement with support vector machine use. Results: Eighty radiomic features were extracted from each polyp. Eight intrinsic features were identified after two-stage selection. The contrast 14 (Cont14) and entropy 6 (Entr6) values in the cholesterol polyp group were significantly higher than those in the gallbladder adenoma group (4.063 ± 1.682 vs. 2.715 ± 1.867, p < 0.001 for Cont14; 4.712 ± 0.427 vs. 4.380 ± 0.720, p = 0.003 for Entr6); however, the homogeneity 13 (Homo13) and energy 8 (Ener8) values in the cholesterol polyp group were significantly lower (0.500 ± 0.069 vs. 0.572 ± 0.057, p < 0.001 for Homo13; 0.050 ± 0.023 vs. 0.068 ± 0.038, p = 0.002 for Ener8). These results indicate that the pixel distribution of cholesterol polyps was more uneven than that of gallbladder tubular adenomas. The dispersion degree was also significantly lower in the cholesterol polyp group than the gallbladder adenoma group (0.579 ± 0.054 vs. 0.608 ± 0.041, p = 0.005), indicating a lower dispersion of high-intensity areas in the cholesterol polyps. The long axis length of the fitting ellipse (Maj.Len), diameter of a circle equal to the lesion area (Eq.Dia) and perimeter (Per) values in the cholesterol polyp group were significantly lower than those in the gallbladder adenoma group (0.971 ± 0.485 vs. 1.738 ± 0.912, p < 0.001 for Maj.Len; 0.818 ± 0.393 vs. 1.438 ± 0.650, p < 0.001 for Eq.Dia; 2.637 ± 1.281 vs. 5.033 ± 2.353, p < 0.001 for Per), demonstrating that the cholesterol polyps were smaller and more regular in terms of morphology. The classification accuracy, sensitivity, specificity, and area under the curve values were 0.875, 0.885, 0.857, and 0.898, respectively. Conclusions: Ultrasound radiomic analysis based on the spatial and morphological features extracted from ultrasound images effectively contributed to the preoperative diagnosis of true and pseudo gallbladder polyps and may be valuable in their clinical management.

16.
PeerJ ; 8: e10035, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33024644

RESUMEN

Insect olfaction and vision play important roles in survival and reproduction. Diurnal butterflies mainly rely on visual cues whereas nocturnal moths rely on olfactory signals to locate external resources. Histia rhodope Cramer (Lepidoptera: Zygaenidae) is an important pest of the landscape tree Bischofia polycarpa in China and other Southeast Asian regions. As a diurnal moth, H. rhodope represents a suitable model for studying the evolutionary shift from olfactory to visual communication. However, only a few chemosensory soluble proteins have been characterized and information on H. rhodope chemoreceptor genes is currently lacking. In this study, we identified 45 odorant receptors (ORs), nine ionotropic receptors (IRs), eight gustatory receptors (GRs) and two sensory neuron membrane proteins (SNMPs) from our previously acquired H. rhodope antennal transcriptomic data. The number of chemoreceptors of H. rhodope was less compared with that found in many nocturnal moths. Some specific chemoreceptors such as OR co-receptor (ORco), ionotropic receptors co-receptor, CO2 receptors, sugar receptors and bitter receptors were predicted by phylogenetic analysis. Notably, two candidate pheromone receptors (PRs) were identified within a novel PR lineage. qRT-PCR results showed that almost all tested genes (22/24) were predominantly expressed in antennae, indicating that they may be important in olfactory function. Among these antennae-enriched genes, six ORs, five IRs and two GRs displayed female-biased expression, while two ORs displayed male-biased expression. Additionally, HrhoIR75q.2 and HrhoGR67 were more highly expressed in heads and legs. This study enriches the olfactory gene inventory of H. rhodope and provides the foundation for further research of the chemoreception mechanism in diurnal moths.

17.
J Biol Chem ; 2020 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-33067357

RESUMEN

Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (MTB), is one of the leading causes of death worldwide, especially in children. However, the mechanisms by which MTB infects its cellular host, activates an immune response and triggers inflammation remain unknown. Mitochondria play important roles in the initiation and activation of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) inflammasome, where mitochondria associated endoplasmic reticulum membranes (MAMs) may serve as the platform for inflammasome assembly and activation. Additionally, mitofusin 2 (MFN2) is implicated in the formation of MAMs, but, the roles of mitochondria and MFN2 in MTB infection have not been elucidated. Using mircroarry profiling of TB patients and in vitro MTB stimulation of macrophages, we observed an upregulation of MFN2 in the peripheral blood mononuclear cells of active TB patients. Furthermore, we found that MTB stimulation by MTB-specific antigen ESAT-6 or lysate of MTB promoted MFN2 interaction with NLRP3 inflammasomes, resulting in the assembly and activation of the inflammasome and, subsequently, IL-1ß secretion. These findings suggest that MFN2 and mitochondria play important role in the pathogen-host interaction during MTB infection.

18.
J Integr Neurosci ; 19(3): 429-436, 2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-33070521

RESUMEN

MicroRNAs are reportedly involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease and multiple system atrophy. We previously identified 7 differentially expressed microRNAs in Parkinson's disease patients and control sera (miR-30c, miR-31, miR-141, miR-146b-5p, miR-181c, miR-214, and miR-193a-3p). To investigate the expression levels of the 7 serum microRNAs in Parkinson's disease and multiple system atrophy, 23 early Parkinson's disease patients (who did not take any anti- Parkinson's disease drugs), 23 multiple system atrophy patients, and 24 normal controls were recruited at outpatient visits in this study. The expression levels of the 7 microRNAs in serum were detected using quantitative real-time polymerase chain reaction. A receiver operating characteristic curve was used to evaluate whether microRNAs can differentially diagnose Parkinson's disease and multiple system atrophy. Clinical scales were used to analyze the correlations between serum microRNAs and clinical features. The results indicated that miR-214 could distinguish Parkinson's disease from the controls, and another 3 microRNAs could differentiate multiple system atrophy from the controls (miR-141, miR-193a-3p, and miR-30c). The expression of miR-31, miR-141, miR-181c, miR-193a-3p, and miR-214 were lower in multiple system atrophy than in Parkinson's disease (all P < 0.05). Combinations of microRNAs accurately discriminated Parkinson's disease from multiple system atrophy (area under the receiver operating characteristic curve = 0.951). For the correlation analysis, negative correlations were discovered between the expression of miR-214 and the Hamilton Anxiety Scale and Parkinson's Disease Non-Motor Symptom scores (all P < 0.05). Our results demonstrate that the distinctive characteristics of microRNAs differentiate Parkinson's disease and multiple system atrophy patients from healthy controls and may be used for the early diagnosis of Parkinson's disease and multiple system atrophy.

19.
J Comp Neurol ; 2020 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-33029803

RESUMEN

Recovery of responses to cutaneous stimuli in the area 3b hand cortex of monkeys after dorsal column lesions (DCLs) in the cervical spinal cord relies on neural rewiring in the cuneate nucleus (Cu) over time. To examine whether the corticocuneate projections are modified during recoveries after the DCL, we injected cholera toxin subunit B into the hand representation in Cu to label the cortical neurons after various recovery times, and related results to the recovery of neural responses in the affected area 3b hand cortex. In normal New World monkeys, labeled neurons were predominately distributed in the hand regions of contralateral areas 3b, 3a, 1 and 2, parietal ventral (PV), secondary somatosensory cortex (S2), and primary motor cortex (M1), with similar distributions in the ipsilateral cortex in significantly smaller numbers. In monkeys with short-term recoveries, the area 3b hand neurons were unresponsive or responded weakly to touch on the hand, while the cortical labeling pattern was largely unchanged. After longer recoveries, the area 3b hand neurons remained unresponsive, or responded to touch on the hand or somatotopically abnormal parts, depending on the lesion extent. The distributions of cortical labeled neurons were much more widespread than the normal pattern in both hemispheres, especially when lesions were incomplete. The proportion of labeled neurons in the contralateral area 3b hand cortex was not correlated with the functional reactivation in the area 3b hand cortex. Overall, our findings indicated that corticocuneate inputs increase during the functional recovery, but their functional role is uncertain.

20.
J Fungi (Basel) ; 6(4)2020 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-33080826

RESUMEN

Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in A. fumigatus killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against A. fumigatus conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients.

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