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1.
PLoS Genet ; 19(12): e1011081, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38048317

RESUMEN

Haploid males of hymenopteran species produce gametes through an abortive meiosis I followed by meiosis II that can either be symmetric or asymmetric in different species. Thus, one spermatocyte could give rise to two spermatids with either equal or unequal amounts of cytoplasm. It is currently unknown what molecular features accompany these postmeiotic sperm cells especially in species with asymmetric meiosis II such as bees. Here we present testis single-cell RNA sequencing datasets from the honeybee (Apis mellifera) drones of 3 and 14 days after emergence (3d and 14d). We show that, while 3d testes exhibit active, ongoing spermatogenesis, 14d testes only have late-stage spermatids. We identify a postmeiotic bifurcation in the transcriptional roadmap during spermatogenesis, with cells progressing toward the annotated spermatids (SPT) and small spermatids (sSPT), respectively. Despite an overall similarity in their transcriptomic profiles, sSPTs express the fewest genes and the least RNA content among all the sperm cell types. Intriguingly, sSPTs exhibit a relatively high expression level for Hymenoptera-restricted genes and a high mutation load, suggesting that the special meiosis II during spermatogenesis in the honeybee is accompanied by phylogenetically young gene activities.


Asunto(s)
Semen , Espermatogénesis , Abejas/genética , Masculino , Animales , Espermatogénesis/genética , Espermátides/metabolismo , Testículo , Espermatocitos/metabolismo , Meiosis/genética
2.
EMBO Rep ; 24(8): e56635, 2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37358015

RESUMEN

Sepsis is a leading cause of in-hospital mortality resulting from a dysregulated response to infection. Novel immunomodulatory therapies targeting macrophage metabolism have emerged as an important focus for current sepsis research. However, understanding the mechanisms underlying macrophage metabolic reprogramming and how they impact immune response requires further investigation. Here, we identify macrophage-expressed Spinster homolog 2 (Spns2), a major transporter of sphingosine-1-phosphate (S1P), as a crucial metabolic mediator that regulates inflammation through the lactate-reactive oxygen species (ROS) axis. Spns2 deficiency in macrophages significantly enhances glycolysis, thereby increasing intracellular lactate production. As a key effector, intracellular lactate promotes pro-inflammatory response by increasing ROS generation. The overactivity of the lactate-ROS axis drives lethal hyperinflammation during the early phase of sepsis. Furthermore, diminished Spns2/S1P signaling impairs the ability of macrophages to sustain an antibacterial response, leading to significant innate immunosuppression in the late stage of infection. Notably, reinforcing Spns2/S1P signaling contributes to balancing the immune response during sepsis, preventing both early hyperinflammation and later immunosuppression, making it a promising therapeutic target for sepsis.


Asunto(s)
Macrófagos , Sepsis , Humanos , Proteínas de Transporte de Anión/metabolismo , Terapia de Inmunosupresión , Lactatos , Macrófagos/metabolismo , Especies Reactivas de Oxígeno/metabolismo
3.
Immunology ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38804253

RESUMEN

Retinopathy of prematurity (ROP) is a retinal disease-causing retinal neovascularization that can lead to blindness. Oxygen-induced retinopathy (OIR) is a widely used ROP animal model. Icariin (ICA) has anti-oxidative and anti-inflammation properties; however, whether ICA has a regulatory effect on OIR remains unclear. In this study, ICA alleviated pathological neovascularization, microglial activation and blood-retina barrier (BRB) damage in vivo. Further results indicated that endothelial cell tube formation, migration and proliferation were restored by ICA treatment in vitro. Proteomic microarrays and molecular mimicry revealed that ICA can directly bind to hexokinase 2 (HK2) and decrease HK2 protein expression in vivo and in vitro. In addition, ICA inhibited the AKT/mTOR/HIF1α pathway activation. The effects of ICA on pathological neovascularization, microglial activation and BRB damage disappeared after HK2 overexpression in vivo. Similarly, the endothelial cell function was revised after HK2 overexpression. HK2 overexpression reversed ICA-induced AKT/mTOR/HIF1α pathway inhibition in vivo and in vitro. Therefore, ICA prevented pathological angiogenesis in OIR in an HK2-dependent manner, implicating ICA as a potential therapeutic agent for ROP.

4.
Knee Surg Sports Traumatol Arthrosc ; 31(5): 2030-2037, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36038668

RESUMEN

PURPOSE: The aims of this study were (1) to develop a three-dimensional (3D) printed simulator that facilitates the simulation of surgical skills for portal placement, intra-articular identification of anatomical structures and arthroscope navigation for hip arthroscopy and (2) to concurrently examine the feasibility of using this simulator as an assessment tool to evaluate trainees' surgical competencies. METHODS: A simulator was developed using a combination of medical imaging, computer-aided design, and 3D printing. A cross-sectional study was conducted with 29 participants divided into 3 subgroups (novice, intermediate and experienced). All participants performed related skills on the simulator, and their performance was evaluated using different assessment parameters. The participants' qualitative feedback regarding the simulator was also collected. The data collated from each group of participants were subsequently compared. RESULTS: Significant differences were observed between the three subgroups of participants with regard to the total checklist score (F2,26 = 11.3), total Arthroscopic Surgical Skill Evaluation score (F2,26 = 92.1), overall final global rating scale score (F2,26 = 49), number of times the participants used fluoroscopy (F2,26 = 7.4), and task completion times (F2,26 = 23.5). The participants' performance in the simulated operation was correlated with their prior clinical experience. There was mainly positive feedback with regard to the fidelity and utility of the simulator in relation to the surgeons' prior clinical experience. CONCLUSIONS: This study demonstrated that a reliable hip arthroscopic simulator can be developed for use by orthopedic surgeons to evaluate their hip arthroscopic skills before performing actual surgical operations. LEVEL OF EVIDENCE: Level III.


Asunto(s)
Artroscopía , Cirujanos , Humanos , Estudios Transversales , Competencia Clínica , Simulación por Computador
5.
Molecules ; 28(22)2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-38005193

RESUMEN

Type 2 diabetes mellitus (T2DM) is an increasingly prevalent and serious health problem. Its onset is typically associated with metabolic disorders and disturbances in the gut microbiota. Previous studies have reported the anti-T2DM effects of Pueraria thomsonii Radix as a functional food. However, the mechanism of action is still unknown. In this study, rich polyphenols and polysaccharides from Pueraria Thomsonii Radix water extract (PTR) were quantitatively determined, and then the effects of PTR on db/db mice were evaluated by pharmacology, metabolomics, and 16S rRNA gene sequencing. The results showed that PTR could alleviate pancreatic tissue damage, significantly decrease fasting blood glucose (FBG), fasting serum insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), urinary glucose (UGLU), and urinary albumin/creatinine ratio (UACR). Metabolomics showed that the Diabetes Control (DM) group produced 109 differential metabolites, of which 74 could be regulated by PTR. In addition, 16S rRNA sequencing was performed in fecal samples and results showed that PTR could reduce the Firmicutes/Bacteroidetes(F/B) ratio and regulate three beneficial bacteria and one harmful bacterium. In conclusion, the results showed that PTR could ameliorate the T2DM symptoms, metabolic disorder, and gut microbiota imbalance of db/db mice, and it was superior to metformin in some aspects. We suggested for the first time that γ-aminobutyric acid (GABA) may be involved in the regulation of the microbiota-gut-brain axis (MGB) and thus affects the metabolic disorders associated with T2DM. This study will provide a scientific basis for the development of functional food with PTR.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Metformina , Pueraria , Ratones , Animales , Diabetes Mellitus Tipo 2/metabolismo , Pueraria/metabolismo , ARN Ribosómico 16S/genética , Metformina/farmacología , Bacterias/metabolismo , Glucemia/metabolismo
6.
Mol Biol Evol ; 38(2): 486-501, 2021 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-32946576

RESUMEN

Bumblebees are a diverse group of globally important pollinators in natural ecosystems and for agricultural food production. With both eusocial and solitary life-cycle phases, and some social parasite species, they are especially interesting models to understand social evolution, behavior, and ecology. Reports of many species in decline point to pathogen transmission, habitat loss, pesticide usage, and global climate change, as interconnected causes. These threats to bumblebee diversity make our reliance on a handful of well-studied species for agricultural pollination particularly precarious. To broadly sample bumblebee genomic and phenotypic diversity, we de novo sequenced and assembled the genomes of 17 species, representing all 15 subgenera, producing the first genus-wide quantification of genetic and genomic variation potentially underlying key ecological and behavioral traits. The species phylogeny resolves subgenera relationships, whereas incomplete lineage sorting likely drives high levels of gene tree discordance. Five chromosome-level assemblies show a stable 18-chromosome karyotype, with major rearrangements creating 25 chromosomes in social parasites. Differential transposable element activity drives changes in genome sizes, with putative domestications of repetitive sequences influencing gene coding and regulatory potential. Dynamically evolving gene families and signatures of positive selection point to genus-wide variation in processes linked to foraging, diet and metabolism, immunity and detoxification, as well as adaptations for life at high altitudes. Our study reveals how bumblebee genes and genomes have evolved across the Bombus phylogeny and identifies variations potentially linked to key ecological and behavioral traits of these important pollinators.


Asunto(s)
Adaptación Biológica/genética , Abejas/genética , Evolución Biológica , Genoma de los Insectos , Animales , Uso de Codones , Elementos Transponibles de ADN , Dieta , Conducta Alimentaria , Componentes del Gen , Tamaño del Genoma , Selección Genética
7.
BMC Plant Biol ; 22(1): 37, 2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35039017

RESUMEN

BACKGROUND: Nicotianamine (NA), 2'-deoxymugineic acid (DMA), and mugineic acid (MA) are chelators required for iron uptake and transport in plants. Nicotianamine aminotransferase (NAAT), 2'-deoxymugineic acid synthase (DMAS), transporter of MAs (TOM), and efflux transporter of NA (ENA) are involved in iron uptake and transport in rice (Oryza sativa), wheat (Triticum aestivum), and barley (Hordeum vulgare); however, these families have not been fully identified and comprehensively analyzed in maize (Zea mays L.). RESULTS: Here, we identified 5 ZmNAAT, 9 ZmDMAS, 11 ZmTOM, and 2 ZmENA genes by genome mining. RNA-sequencing and quantitative real-time PCR analysis revealed that these genes are expressed in various tissues and respond differently to high and low iron conditions. In particular, iron deficiency stimulated the expression of ZmDMAS1, ZmTOM1, ZmTOM3, and ZmENA1. Furthermore, we determined protein subcellular localization by transient expression of green fluorescent protein fusions in maize mesophyll protoplasts. ZmNAAT1, ZmNAAT-L4, ZmDMAS1, and ZmDMAS-L1 localized in the cytoplasm, whereas ZmTOMs and ZmENAs targeted to plasma and tonoplast membranes, endomembranes, and vesicles. CONCLUSIONS: Our results suggest that the different gene expression profiles and subcellular localizations of ZmNAAT, ZmDMAS, ZmTOM, and ZmENA family members may enable specific regulation of phytosiderophore metabolism in different tissues and under different external conditions, shedding light on iron homeostasis in maize and providing candidate genes for breeding iron-rich maize varieties.


Asunto(s)
Genoma de Planta/genética , Hierro/metabolismo , Familia de Multigenes/genética , Proteínas de Plantas/genética , Zea mays/genética , Ácido Azetidinocarboxílico/análogos & derivados , Ácido Azetidinocarboxílico/metabolismo , Transporte Biológico , Cromosomas de las Plantas/genética , Regulación de la Expresión Génica de las Plantas , Genes Reporteros , Homeostasis , Deficiencias de Hierro , Filogenia , Proteínas de Plantas/metabolismo , Transporte de Proteínas , Proteínas Recombinantes de Fusión , Sideróforos/metabolismo , Transaminasas/genética , Transaminasas/metabolismo , Zea mays/enzimología , Zea mays/fisiología
8.
Exp Cell Res ; 405(2): 112678, 2021 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-34171351

RESUMEN

Tumor cell apoptosis evasion is one of the main reasons for easy metastasis occurrence, chemotherapy resistance, and the low five-year survival rate of digestive system tumors. Current research has shown that non-apoptotic cell death plays an important role in tumors of the digestive system. Therefore, increasing the proportion of non-apoptotic tumor cells is one of the effective methods of improving therapeutic efficacies for digestive system tumors. Non-apoptotic cell death modes mainly include autophagic cell death, pyroptosis, ferroptosis, in addition to other cell death modes. This review covers a systematic review relating to the research progress made into autophagic cell death, pyroptosis, ferroptosis, and other cell death modes in the treatment of digestive system tumors. It also highlights how treatment is a reasonable prospect based on clinical experience and provides reliable guidance for the further development of digestive system tumor treatments.


Asunto(s)
Muerte Celular/efectos de los fármacos , Neoplasias del Sistema Digestivo/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Gastrointestinales/tratamiento farmacológico , Animales , Autofagia/efectos de los fármacos , Neoplasias del Sistema Digestivo/metabolismo , Neoplasias Gastrointestinales/metabolismo , Humanos , Piroptosis/efectos de los fármacos
9.
Knee Surg Sports Traumatol Arthrosc ; 30(7): 2492-2499, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35079844

RESUMEN

PURPOSE: The purpose of this study is to describe rotator cuff muscle stiffness in patients with different degrees of rotator cuff tear (RCT) severity and to assess its predictive ability for RCT reparability. METHODS: One hundred and thirty-three consecutive patients who were scheduled to undergo arthroscopic shoulder surgery were prospectively enrolled. Tendon retraction, fatty infiltration, and muscle atrophy were evaluated using magnetic resonance imaging. Shear modulus of supraspinatus (SSP) and infraspinatus (ISP) muscles were measured by ultrasound shear wave elastography (SWE). The tear size and reparability were determined intraoperatively. RESULTS: There were 97 patients in RCT group and 36 patients in control group. Bilateral shear modulus discrepancy (Δshear modulus) was used to represent rotator cuff stiffness. Severely fatty-infiltrated rotator cuff muscles possessed a significantly higher stiffness compared with their counterparts (SSP: CI 27.8-31.8 vs. 13.5-15.6 kPa, ISP: CI 33.2-38.1 vs. 8.8-11.2 kPa, p < 0.001). The same trend applied to muscles with distinct tendon retraction (SSP: CI 27.7-32.3 vs. 10.9-14.9 kPa, ISP: CI 33.2-38.6 vs. 6.5-11.0 kPa, p < 0.001) and obvious muscle atrophy (SSP: CI 27.9-32.1 vs. 13.6-15.8 kPa, ISP: CI 32.9-38.2 vs. 9.0-11.7 kPa, p < 0.001). Irreparable massive RCT (MRCT) patients had significantly stiffer SSP (CI 27.7-31.9 vs. 13.5-16.5 kPa, p < 0.001) and ISP (CI 33.5-37.8 vs. 10.3-14.8 kPa, p < 0.001) than reparable MRCT. The Δshear modulus of the ISP was a highly accurate predictor of RCT reparability. A cutoff value of 18.0 kPa had a sensitivity of 100% and specificity of 98.8% for irreparable MRCT. CONCLUSION: Ultrasound SWE-derived rotator cuff muscle stiffness is closely correlated with RCT size and severity. LEVEL OF EVIDENCE: I.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Lesiones del Manguito de los Rotadores , Artroscopía/métodos , Diagnóstico por Imagen de Elasticidad/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Atrofia Muscular/diagnóstico por imagen , Atrofia Muscular/etiología , Manguito de los Rotadores/diagnóstico por imagen , Manguito de los Rotadores/patología , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/diagnóstico por imagen , Lesiones del Manguito de los Rotadores/patología , Lesiones del Manguito de los Rotadores/cirugía , Rotura/patología
10.
Nano Lett ; 21(13): 5627-5632, 2021 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-34160228

RESUMEN

Using chemically synthesized silver nanowires with 5-fold twinning planes as a model system, a bottom-up process to generate a bulk nanostructured metal has been demonstrated. Although the nanowires would be shortened and deformed during densification, they are chosen as a model system because they are currently the most scalable and convenient way to obtain Ag particles with high twinning densities. Direct cold pressing of a silver nanowire filter cake did not generate a sufficiently cohesive sample, while hot pressing at 190 °C for 8 h resulted in extensive sintering, eliminating the nanowire morphology. Copper was then electroplated on the silver nanowires as a binder and filler to increase the densification upon hot pressing; despite nonuniform plating across the thickness of the filter cake, the thermal stability of the nanowires was increased, allowing hot pressing at 390 °C. Finally, a uniform copper coating on silver nanowires was achieved by electroless plating, leading to cohesive bulk metal after hot pressing.


Asunto(s)
Nanoestructuras , Nanocables , Cobre , Plata
11.
J Environ Manage ; 301: 113856, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34626948

RESUMEN

The conventional sintering process of municipal solid waste incineration (MSWI) fly ash is always energy intensive. The process forms a cracked structure because of the difficulty in forming the liquid phase to enhance the mass transfer process. Therefore, exploring a new disposal method to simultaneously decrease the sintering temperature and improve the mechanical and heavy metal leaching properties of sintered samples is necessary. In this study, a pressure-assisted sintering treatment was introduced to dispose fly ash by varying the chemical composition and mechanical pressure at relatively low temperatures (300-500 °C). The results revealed that the compressive strength of treated samples increased with the CaO/SiO2 molar ratio increasing from 0.5 to 1.0, and a maximum value of 238.28 ± 8.50 MPa was obtained. The heavy metal leaching concentration results demonstrated a low risk of contamination in the treated samples. Microstructure analyses suggested that the densification process was enhanced with increased mechanical pressure, and the formed calcium silicates and aluminosilicates positively affected the compressive strength. Moreover, smaller crystal lattices were observed during aggregation formation, suggesting the restraint of anomalous crystal growth, which accelerated the densification process and increased the compressive strength. Moreover, the mass transfer process during the pressure-assisted sintering process was enhanced compared with the conventional thermal process, which was reflected by the transformation of elements from homogeneous to heterogeneous distribution. Therefore, the improved mechanical properties and leaching behavior of heavy metals were attributed to the densified microstructure, formation of new minerals, and enhanced driving force during the pressure-assisted sintering process. These findings suggest that pressure-assisted sintering is a promising method for maximizing the reutilization and minimizing the energy consumption simultaneously to dispose fly ash.


Asunto(s)
Metales Pesados , Eliminación de Residuos , Carbono , Ceniza del Carbón , Incineración , Metales Pesados/análisis , Material Particulado , Dióxido de Silicio , Residuos Sólidos/análisis
12.
Pharm Biol ; 60(1): 384-393, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35188856

RESUMEN

CONTEXT: Therapeutic lymphangiogenesis is a new treatment for cardiovascular diseases. Our previous study showed M2b macrophages can alleviate myocardial ischaemia/reperfusion injury (MI/RI). However, the relation between M2b macrophages and lymphangiogenesis is not clear. OBJECTIVE: To investigate the effects of M2b macrophages on lymphangiogenesis after MI/RI. MATERIALS AND METHODS: Forty male Sprague-Dawley (SD) rats were randomized into Sham operation group (control, n = 8), MI/RI group (n = 16) and M2b macrophage transplantation group (n = 16). M2b macrophages (1 × 106) in 100 µL of normal saline or the same volume of vehicle was injected into the cardiac ischaemic zone. Two weeks later, echocardiography and lymphatic counts were performed, and the extent of myocardial fibrosis and the expression of vascular endothelial growth factor C (VEGFC) and VEGF receptor 3 (VEGFR3) were determined. In vitro, lymphatic endothelial cells (LECs) were cultured with M2b macrophages for 6-24 h, and the proliferation, migration and tube formation of the LECs were assessed. RESULTS: In vivo, M2b macrophage transplantation increased the level of lymphangiogenesis 2.11-fold, reduced 4.42% fibrosis, improved 18.65% left ventricular ejection fraction (LVEF) and upregulated the expressions of VEGFC and VEGFR3. In vitro, M2b macrophage increased the proliferation, migration, tube formation and VEGFC expression of LECs. M2b macrophage supernatant upregulated VEGFR3 expression of LECs. DISCUSSION AND CONCLUSIONS: Our study shows that M2b macrophages can promote lymphangiogenesis to reduce myocardial fibrosis and improve heart function, suggesting the possible use of M2b macrophage for myocardial protection therapy.


Asunto(s)
Linfangiogénesis/fisiología , Macrófagos/trasplante , Daño por Reperfusión Miocárdica/terapia , Animales , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Modelos Animales de Enfermedad , Ecocardiografía , Células Endoteliales/metabolismo , Fibrosis , Masculino , Daño por Reperfusión Miocárdica/fisiopatología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiología
13.
Foot Ankle Surg ; 28(3): 347-353, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33903004

RESUMEN

BACKGROUND: The medial longitudinal arch (MLA) improves with age in childhood. However, it still causes parents to worry that children have flat feet. Due to the lack of a standard to quantitatively assess the arch development in kids at certain age, the pediatricians judge the flat feet by experience, causing many cases to be overtreated. The aim of this study was to plot the distribution of MLA parameters in children. METHODS: Children without lower limb deformity and lower limb pain were recruited from 12 primary schools and kindergartens in Chongqing province-level city. Foot length (FL) and navicular height (NH) was measured manually, arch index (AI) and arch volume (AV) were measured with the Foot Plantar Scanner. Each parameter was measured in both weight-bearing and non-weight-bearing positions. Significant differences were also compared between the measurements of consecutive years. RESULTS: This study was the first to use a three-dimensional laser surface scanner to measure the MLA parameters of children aged 3-12 years in China. 1744 children (871 girls, 873 boys) participated in this study. FL, NH, AI and AV varied significantly with age in both the weight-bearing and non-weight-bearing positions. These parameters have significant differences between the weighted and non-weighted positions (p < 0.05). CONCLUSIONS: The age distribution characteristics of these parameters indicated that the MLA improves with age. The establishment of a developmental scale for the children's MLA is necessary.


Asunto(s)
Pie Plano , Huesos Tarsianos , Niño , China , Femenino , Pie Plano/etiología , Pie/diagnóstico por imagen , Humanos , Masculino , Soporte de Peso
14.
J Cell Mol Med ; 25(14): 6800-6814, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34080298

RESUMEN

Bacterial products can stimulate inflammatory reaction and activate immune cells to enhance the production of inflammatory cytokines, and finally promote osteoclasts recruitment and activity, leading to bone destruction. Unfortunately, effective preventive and treatment measures for inflammatory osteolysis are limited and usually confuse the orthopedist. Astragalus polysaccharide (APS), the main extractive of Astragali Radix, has been widely used for treating inflammatory diseases. In the current study, in vitro and in vivo experimental results demonstrated that APS notably inhibited osteoclast formation and differentiation dose-dependently. Moreover, we found that APS down-regulated RANKL-related osteoclastogenesis and levels of osteoclast marker genes, such as NFATC1, TRAP, c-FOS and cathepsin K. Further underlying mechanism investigation revealed that APS attenuated activity of MAPK signalling pathways (eg ERK, JNK and p38) and ROS production induced by RANKL. Additionally, APS was also found to suppress LPS-related inflammatory osteolysis by decreasing inflammatory factors' production in vivo. Overall, our findings demonstrate that APS effectively down-regulates inflammatory osteolysis due to osteoclast differentiation and has the potential to become an effective treatment of the disorders associated with osteoclast.


Asunto(s)
Antiinflamatorios/uso terapéutico , Planta del Astrágalo/química , Sistema de Señalización de MAP Quinasas , Osteoclastos/metabolismo , Osteogénesis , Osteólisis/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Animales , Catepsina K/metabolismo , Células Cultivadas , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Lipopolisacáridos/toxicidad , Ratones , Ratones Endogámicos C57BL , Factores de Transcripción NFATC/metabolismo , Osteoclastos/efectos de los fármacos , Osteólisis/etiología , Osteólisis/metabolismo , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ligando RANK/metabolismo , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Fosfatasa Ácida Tartratorresistente/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos
15.
J Transl Med ; 19(1): 391, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34526059

RESUMEN

BACKGROUND: EMT is an important biological process in the mechanism of tumor invasion and metastasis. However, there are still many unknowns about the specific mechanism of EMT in tumor. At present, a comprehensive analysis of EMT-related genes in colorectal cancer (CRC) is still lacking. METHODS: All the data were downloaded from public databases including TCGA database (488 tumor samples and 52 normal samples) as the training set and the GEO database (GSE40967 including 566 tumor samples and 19 normal samples, GSE12945 including 62 tumor samples, GSE17536 including 177 tumor samples, GSE17537 including 55 tumor samples) as the validation sets. One hundred and sixty-six EMT-related genes (EMT-RDGs) were selected from the Molecular Signatures Database. Bioinformatics methods were used to analyze the correlation between EMT-RDGs and CRC prognosis, metastasis, drug efficacy, and immunity. RESULTS: We finally obtained nine prognostic-related EMT-RDGs (FGF8, NOG, PHLDB2, SIX2, SNAI1, TBX5, TIAM1, TWIST1, TCF15) through differential expression analysis, Unicox and Lasso regression analysis, and then constructed a risk prognosis model. There were significant differences in clinical characteristics, 22 immune cells, and immune functions between the high-risk and low-risk groups and the different states of the nine prognostic-related EMT-RDGs. The methylation level and mutation status of nine prognostic-related EMT-RDGs all affect their regulation of EMT. The Cox proportional hazards regression model was also constructed by the methylation sites of nine prognostic-related EMT-RDGs. In addition, the expression of FGF8, PHLDB2, SIX2, and SNAIL was higher and the expression level of NOG and TWIST1 was lower in the non-metastasis CRC group. Nine prognostic-related EMT-RDGs also affected the drug treatment response of CRC. CONCLUSIONS: Targeting these nine prognostic-related EMT-RDGs can regulate CRC metastasis and immune, which is beneficial for the prognosis of CRC patients, improve drug sensitivity in CRC patients.


Asunto(s)
Neoplasias Colorrectales , Preparaciones Farmacéuticas , ARN Largo no Codificante , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico
16.
FASEB J ; 34(7): 9678-9693, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32469121

RESUMEN

Glioblastoma multiforme is the most common and aggressive glial tumor with poor prognosis. Importantly, effective treatment options for glioblastoma are unmet needs. Obesity and low physical activity have been linked with a high risk of cancer, and exercise is related to delayed cancer development and progression. Epidemiological studies have revealed a correlation between exercise and the survival rate of patients with glioblastoma. Nevertheless, the mechanisms by which exercise exerts its anticancer effects in glioblastoma remain unclear. Here, we found that irisin, an exercise-induced myokine, induced G2 /M cell cycle arrest and increased p21 levels in glioblastoma cells, leading to the inhibition of cell proliferation. In addition, irisin inhibited glioblastoma cell invasion by upregulating TFPI-2 and even reversed the aggressive tumor phenotype promoted by co-cultivation with cancer-associated adipocytes. Furthermore, irisin retarded xenograft glioblastoma tumor growth, and radiolabeled irisin demonstrated specific tumor-targeting capability in vivo. Therefore, this study identified one potential molecular mechanism by which exercise prevents cancer progression via irisin. Intriguingly, irisin has the potential to be developed as a molecular imaging and therapeutic anticancer agent.


Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular , Ejercicio Físico , Fibronectinas/farmacología , Glioma/tratamiento farmacológico , Neuropéptidos/farmacología , Animales , Apoptosis , Ciclo Celular , Movimiento Celular , Glioma/metabolismo , Glioma/patología , Humanos , Masculino , Ratones , Ratones Desnudos , Invasividad Neoplásica , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Heredity (Edinb) ; 126(1): 163-177, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32855546

RESUMEN

When selection favours rare alleles over common ones (balancing selection in the form of negative frequency-dependent selection), a locus may maintain a large number of alleles, each at similar frequency. To better understand how allelic richness is generated and maintained at such loci, we assessed 201 sequences of the complementary sex determiner (csd) of the Asian honeybee (Apis cerana), sampled from across its range. Honeybees are haplodiploid; hemizygotes at csd develop as males and heterozygotes as females, while homozygosity is lethal. Thus, csd is under strong negative frequency-dependent selection because rare alleles are less likely to end up in the lethal homozygous form. We find that in A. cerana, as in other Apis, just a few amino acid differences between csd alleles in the hypervariable region are sufficient to trigger female development. We then show that while allelic lineages are spread across geographical regions, allelic differentiation is high between populations, with most csd alleles (86.3%) detected in only one sample location. Furthermore, nucleotide diversity in the hypervariable region indicates an excess of recently arisen alleles, possibly associated with population expansion across Asia since the last glacial maximum. Only the newly invasive populations of the Austral-Pacific share most of their csd alleles. In all, the geographic patterns of csd diversity in A. cerana indicate that high mutation rates and balancing selection act together to produce high rates of allele genesis and turnover at the honeybee sex locus, which in turn leads to its exceptionally high local and global polymorphism.


Asunto(s)
Alelos , Abejas , Selección Genética , Procesos de Determinación del Sexo , Animales , Asia , Abejas/genética , Femenino , Polimorfismo Genético
18.
J Immunol ; 202(1): 249-259, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30510067

RESUMEN

The peptidoglycan recognition protein SAs (PGRP-SAs) from Bombus ignitus (Bi-PGRP-SA), Apis mellifera (Am-PGRP-SA), and Megachile rotundata PGRP-SA (Mr-PGRP-SA) exhibit an intrinsic ability to preferentially bind to Dap-type peptidoglycan (PGN) from Bacillus subtilis rather than Lys-type PGN from Micrococcus luteus This ability is more analogous to the binding exhibited by PGRP-LCx and PGRP-SD than to that exhibited by PGRP-SA in Drosophila Moreover, Bi-PGRP-SA and Am-PGRP-SA share greater sequence identity with Drosophila PGRP-LCx than with PGRP-SD and retain several conserved contact residues, including His37/His38, His60/His61, Trp66/Trp67, Ala150/Ala151, and Thr151/Thr152 However, the corresponding contact residue Arg85 is not a major anchor residue in bees (e.g., bumblebees, honeybees, and leaf-cutting bees), and an in silico analysis indicated that the residues Thr151/Thr152 and Ser153/Ser154 of Bi-PGRP-SA and Am-PGRP-SA are deduced to be anchor residues. In addition, the nonconserved residues Asp67 in Bi-PGRP-SA and Mr-PGRP-SA and His68 in Am-PGRP-SA are deduced to be involved in the binding to Dap-type PGNs in bumblebees, honeybees, and leaf-cutting bees. We conclude that the structures and specificities of PGRP-SAs in bees are more analogous to those of PGRP-LCx than to those of Drosophila PGRP-SA. This phenomenon might be explained by the fact that the evolutionary clade of Hymenoptera is more ancient than that of Diptera.


Asunto(s)
Bacillus subtilis/fisiología , Abejas , Proteínas Portadoras/genética , Proteínas de Insectos/metabolismo , Micrococcus luteus/fisiología , Peptidoglicano/metabolismo , Dominios y Motivos de Interacción de Proteínas/genética , Animales , Sitios de Unión/genética , Evolución Biológica , Proteínas Portadoras/química , Proteínas Portadoras/metabolismo , Cristalografía por Rayos X , Drosophila , Proteínas de Insectos/química , Proteínas de Insectos/genética , Modelos Químicos , Peptidoglicano/química , Filogenia , Unión Proteica , Homología de Secuencia , Relación Estructura-Actividad
19.
Proc Natl Acad Sci U S A ; 115(22): 5703-5708, 2018 05 29.
Artículo en Inglés | MEDLINE | ID: mdl-29760075

RESUMEN

Cresols are a group of naturally occurring and massively produced methylphenols with broad use in the chemical industry. Here, we report that m-cresol and its liquid mixtures with other isomers are surprisingly good solvents for processing carbon nanotubes. They can disperse carbon nanotubes of various types at unprecedentedly high concentrations of tens of weight percent, without the need for any dispersing agent or additive. Cresols interact with carbon nanotubes by charge transfer through the phenolic hydroxyl proton and can be removed after processing by evaporation or washing, without altering the surface of carbon nanotubes. Cresol solvents render carbon nanotubes polymer-like rheological and viscoelastic properties and processability. As the concentration of nanotubes increases, a continuous transition of four states can be observed, including dilute dispersion, thick paste, free-standing gel, and eventually a kneadable, playdough-like material. As demonstrated with a few proofs of concept, cresols make powders of agglomerated carbon nanotubes immediately usable by a broad array of material-processing techniques to create desirable structures and form factors and make their polymer composites.

20.
Ecotoxicol Environ Saf ; 223: 112555, 2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34332249

RESUMEN

As a highly effective plant hormone, the overuse of 6-benzylaminopurine (6-BA) may pose potential threats to organisms and the environment. Melatonin is widely known for its regulation of sleep rhythm, and it also shows a beneficial effect in a variety of adverse situations. In order to investigate the harm of 6-BA to vertebrates and whether melatonin can reverse the toxicity induced by 6-BA, we analyzed the circadian rhythm and cardiovascular system of zebrafish, and further clarified the role of the thyroid endocrine system. The exposure of well-developed embryos started at 2 hpf, then 6-BA and/or melatonin were carried out. The results indicated that 6-BA disturbed the rhythmic activities of the larvae, increased wakefulness, correspondingly reduced their rest, and induced disrupted clock gene expression. Video analysis and qRT-PCR data found that zebrafish under 6-BA exposure showed obvious cardiovascular morphological abnormalities and dysfunction, and the mRNA levels of cardiovascular-related genes (nkx2.5, gata4, myl7, vegfaa and vegfab) were significantly down-regulated. In addition, altered thyroid hormone content and hypothalamus-pituitary-thyroid (HPT) axis-related gene expression were also clearly observed. 1umol/L of melatonin had little effect on zebrafish, but its addition could significantly alleviate the circadian disturbance and cardiovascular toxicity caused by 6-BA, and simultaneously played a regulatory role in thyroid system. Our research revealed the adverse effects of 6-BA on zebrafish larvae and the protective role of melatonin in circadian rhythm, cardiovascular and thyroid systems.


Asunto(s)
Sistema Cardiovascular , Melatonina , Animales , Compuestos de Bencilo , Hipotálamo , Purinas , Pez Cebra
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