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Achieving ultrabright fluorogens is a key issue for fluorescence-guided surgery (FGS). Fluorogens with aggregation-induced emission (AIEgens) are potential agents for FGS on the benefit of the bright fluorescence in physiological conditions. Herein, the fluorescence brightness of AIEgen is further improved by preparing the nanoparticle using a polystyrene-based matrix and utilizing it for tumor FGS with a high signal-to-background ratio. After encapsulating AIEgen into polystyrene-poly (ethylene glycol) (PS-PEG), the fluorescence intensity of the prepared AIE@PS-PEG nanoparticles is multiple times that of nanoparticles in 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-poly (ethylene glycol) (DSPE-PEG), a commonly used polymer matrix for nanoparticle preparation. Molecular dynamics simulations suggest that higher free energy is required for the outer rings of AIEgen to rotate in polystyrene than in the DSPE, indicating that the benzene rings in polystyrene can restrict the intramolecular motions of AIEgen better than the alkyl chain in DSPE-PEG. Fluorescence correlation microscopy detections suggest that the triplet excited state of AIEgens is less in PS-PEG than in DSPE-PEG. The restricted intramolecular motions and suppressed triplet excited state result in ultrabright AIE@PS-PEG nanoparticles, which are more conducive to illuminating tumor tissues in the intestine for FGS. The illumination of metastatic tumors in lungs by AIE@PS-PEG nanoparticles is also tried.
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Poliestirenos , Poliestirenos/química , Fluorescência , Polietilenoglicóis/química , Humanos , Nanopartículas/química , Cirurgia Assistida por Computador/métodos , Simulação de Dinâmica Molecular , Animais , Corantes Fluorescentes/químicaRESUMO
Pitch canker caused by the fungus Fusarium circinatum is an important disease affecting pine trees in Europe and South Africa. Several countries, including China, have listed F. circinatum as a quarantine pathogen. Therefore, timely detection of F. circinatum could efficiently prevent its introduction into new areas or facilitate spread management in already infected sites. In this study, a recombinase polymerase amplification-lateral flow dipstick (RPA-LFD) assay was developed for rapid detection of F. circinatum based on a new target gene, Fcir2067, identified from whole-genome sequences. The assay was highly specific to F. circinatum. In fact, it exclusively detected F. circinatum isolates; 53 isolates of fungal and oomycete species and 2 nematodes of Bursaphelenchus xylophilus and B. mucronatus were not detected. By detecting as little as 10 pg of F. circinatum genomic DNA in a 50-µl reaction, the RPA-LFD assay was 10 times more sensitive than conventional PCR assays. F. circinatum was also detected in artificially inoculated pine needles of Cedrus deodara. These results demonstrated that the developed RPA-LFD assay has the potential for rapid detection of F. circinatum in regions at high risk of infection. The RPA-LFD assay might serve as an alternative method for the early detection of F. circinatum.
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Fusarium , Recombinases , Fusarium/genética , Reação em Cadeia da Polimerase , Técnicas de Amplificação de Ácido Nucleico/métodosRESUMO
Acute lung injury (ALI) is mostly relevant to acute and severe lung inflammation. We first utilized lipopolysaccharide (LPS) to induce mice for establishing a mouse model of ALI and detected decreased expression of GPR43 in the lung tissue in mice with ALI. Mice expressing increased GPR43 showed improvement in lung injury compared to LPS-treated mice. Additionally, ALI mice transfected with lenti-GPR43 significantly decreased the mRNA levels of TNF-α, IL-1ß, IL-6, MPO, COX2 and iNOS, and apoptosis levels in the lungs, as well as the phosphorylation levels of JNK and ELK1 compared to LPS-treated mice with lenti-vector infection. Subsequently, we employed LPS to induce alveolar type ii epithelial cells and observed that Ov-GPR43 infection markedly reduced the expression levels of inflammatory factors and apoptosis levels, while exposure of cells to anisomycin was also effective in blunting the effects of Ov-GPR43 on these processes. Taken together, these results demonstrate a role of GPR43 in mediating lung injury through JNK/ELK1 and imply the therapeutic potential of targeting GPR43 against ALI.
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Lesão Pulmonar Aguda , Lipopolissacarídeos , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Apoptose , Inflamação , Pulmão/metabolismo , CamundongosRESUMO
Dianthus chinensis is a popular ornamental plant that is widely cultivated in China. In May 2020, a disease was found at several landscape sites in Xuanwu District, Nanjing, China, causing symptoms of foliage blight and root discoloration on approximately 52% of one-year old D. chinensis plants. To recover the causal pathogen, samples of infected roots and leaves were cut into 5×5 mm2 pieces, surface-disinfected in 75% ethanol for 30 sec, followed by 1% NaClO for 90 sec, rinsed with sterile water three times and placed on potato dextrose agar (PDA) with 0.1 mg/mL of ampicillin at 25 °C. Hyphae growing on PDA were visible from both root and leaf tissues after three days. Individual hyphal tips were transferred to new PDA plates to obtain pure isolates. Three representative isolates were deposited in the China Forestry Culture Collection Center (CFCC 57545,57546, 57547). The hyphae grew radially, densely, and the aerial hyphae were velvety, white, yellow-white, or pink-white. Representative isolate Facu-DCY5 produced three types of conidia (microconidia, macroconidia, and chlamydospores). Macroconidia were sickle-shaped, measuring 25.7-55.4 µm × 3.2-4.6 µm (n=50). Microconidia were numerous, oval or kidney-shaped, measuring 6.8-11.9 µm × 3.5-4.8 µm (n=50). Conidia produced in the aerial mycelium were 16-34 × 2.2-5.3 µm (n=50). The ITS region, TEF1, calmodulin (CMDA), and RNA polymerase II second largest subunit (RPB2) were amplified with primers ITS1/ITS4, EF1/EF2, CL1/CL2A and 5F2/7CR , respectively and sequenced at Sangon Biotech (Nanjing, China). The ITS sequence of isolate Facu-DCY5 (GenBank No. ON307073.1) was identical to HQ165938.1, ON306850.1, OM964482.1. TEF1 (ON331997.1) was identical to LC546967.1, HQ165866.1, MZ158155.1. CMDA (ON331996.1) was identical to HQ412345.1, MZ921595.1 and MZ921597.1. RPB2 (ON331995.1) was identical to MZ997370.1. Maximum parsimony and maximum likelihood phylogenies of the Facu-DCY5 multilocus sequence data and those of several species within the F. tricinctum species complex identified the isolate from D. chinensis as F. acuminatum . Pathogenicity tests were performed using a conidial suspension (104 conidia/mL). Each plant (approx. 0.3 m in -height) was inoculated with 1 mL of the conidial suspension by mixing it into the potting soil (500 g). Control plants were treated with sterile distilled water. All inoculated plants (n=9) in three repeats of the assay exhibited foliage blight and root rot after 15 days, whereas all control plants (n=9) remained asymptomatic. Fusarium isolates with identical morphological features and molecular marker sequences to those of Facu-DCY5 were recovered from foliage blight and root tissues of all the inoculated plants. In China, F. acuminatum has been reported as a pathogen of Cucurbita maxima, Actinidia arguta, Polygonatum odoratumand Schisandra chinensis. This is the first report of F. acuminatum on D. chinensis in China. Considering the importance of D. chinensis to both ornamental nurseries and landscaping industries, we recommend that diseased plants be removed to prevent the spread of F. acuminatum, and that identification of the infecting isolates from D. chinensis at other sites and landscape locations be performed.
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INTRODUCTION: Arthrodesis of the proximal interphalangeal (PIP) joint at 40° angle has been proposed by many authors. A smaller angle of arthrodesis results in weaker grip strength of the hand from the quadriga effect. However, arthrodesis at 40° compromises other aspects of hand function including poor aesthetic appearance. This paper aims to quantify the decrease in grip strength at 40°, 20°, and 0° of arthrodesis. MATERIALS AND METHODS: Grip strengths of the hand were measured using a BASELINE dynamometer at settings II, III, and IV. Baseline grip strength of the subjects were first measured without wearing a splint. Thereafter, subjects wore thermoplastic splints to simulate arthrodesis of the middle and ring finger PIP joint at 40°, 20°, and 0°, and grip strengths were measured again. The grip strength of the hand with simulated arthrodesis was then calculated as a ratio of the baseline. RESULTS: There were 50 subjects yielding 100 sets of results. The results show that average grip strength ratio of the hand decreases progressively from 40° and 20° and to 0° of arthrodesis for both the middle and ring finger. However, the difference in grip strength ratio between 40° and 20° of arthrodesis was minimal. Simulated arthrodesis of the middle finger affected the grip strength ratio more than arthrodesis of the ring finger, and compromised gripping of a smaller handle more than a wider one. CONCLUSION: The decrease in grip strength from 40° to 20° simulated fusion of PIP joint was minimal. Therefore, in so far as grip strength loss is concerned, arthrodesis of the PIP joint at an angle less than 40° can be considered for patients with individual functional and aesthetic concerns.
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Artrodese , Articulações dos Dedos , Artrodese/métodos , Articulações dos Dedos/cirurgia , Dedos , Força da Mão , Humanos , Amplitude de Movimento ArticularRESUMO
BACKGROUND: Nowadays, there is no approved targeted agent for lung injury induced by sepsis. S1PR2 is confirmed to be a promising diagnosis and treatment target. JTE-013 as S1PR2 antagonists may be an agent of great potential. In this research, we sought to determine the functional role of JTE-013 in lung injury induced by sepsis. MATERIALS AND METHODS: Seventy-two rats were assigned into normal group, sepsis model group and JTE-013 group. The animal model of lung injury induced by sepsis was constructed by cecal ligation and puncture. The human pulmonary microvascular endothelial cells (HPMECs) were divided into control, LPS and LPS + JTE-013 group. HPMECs induced by LPS served as the cell model of lung injury induced by sepsis. HE staining assay was performed for assessment of the pathological condition and Evans blue was applied for assessment of pulmonary tissue permeability. Wet/dry ratio was measured as indicators of pulmonary edema degree and neutrophil count was measured as indicators of infection status. The levels of inflammatory factors were detected by corresponding kits, cell survival by CCK-8 assay and protein expression level by western blot. RESULTS: S1PR2 was highly expressed in vivo model of lung injury induced by sepsis. It was observed that JTE-013 as antagonist of S1PR2 alleviated the lung tissue injury, endothelial dysfunction and pulmonary edema induced by sepsis. In addition, JTE-013 reduced neutrophil count and levels of inflammatory factors. Moreover, results confirmed that JTE-013 enhanced cell viability and mitigated inflammatory response in cell model of sepsis. CONCLUSIONS: Overall, JTE-013 as an antagonist of S1PR2 could relieve inflammatory injury and endothelial dysfunction induced by sepsis in vivo and vitro, resulting in attenuation of lung injury. These findings elucidated that JTE-013 may be a promising targeted agent for lung injury induced by sepsis.
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Lesão Pulmonar Aguda/tratamento farmacológico , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Sepse/complicações , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Humanos , Masculino , Pirazóis/farmacologia , Piridinas/farmacologia , Ratos Sprague-Dawley , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores , Receptores de Esfingosina-1-Fosfato/metabolismoRESUMO
BACKGROUND: Primary ovarian failure (POF) is defined as follicular failure in women of reproductive age. Although many factors are speculated to contribute to the occurrence of POF, the exact aetiology remains unclear. Moreover, alterations in the microbiome of patients with POF are poorly studied. RESULTS: This study investigated the vaginal microbiota of 22 patients with POF and 29 healthy individuals. High-throughput Illumina MiSeq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene was used to evaluate the relationships between the vaginal flora and clinical characteristics of POF. Different from results of previous studies, we found that the diversity and richness of the vaginal flora of patients with POF was significantly different from those of healthy controls. Comparison of the vaginal flora of patients with POF with that of menopausal women revealed that the relative abundance of Lactobacillus was significantly reduced in the latter. A reduced abundance of Lactobacillus was furthermore associated with a lower pregnancy success rate. Of particular interest is that L. gallinarum especially appeared to be beneficially associated with reproductive-related indicators (FSH, E2, AMH, PRL) whilst L. iners appeared to have a detrimental effect. The result of the present study may enable the identification of microbiota associated with POF, however, further investigations of differences in the microbiota in the context of POF will enable a deeper understanding of the disease pathogenesis that involves modification of the vaginal microbiota. CONCLUSIONS: The present study identified the microbiota associated with POF. Further investigations on the differences in the microbiota in the context of POF will improve our understanding of the pathogenesis of the disease which involves modification of the vaginal microbiota.
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Microbiota , Insuficiência Ovariana Primária/microbiologia , Vagina/microbiologia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Lactobacillus/classificação , Lactobacillus/genética , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Menopausa , Insuficiência Ovariana Primária/sangue , RNA Ribossômico 16S/genética , ReproduçãoRESUMO
Chimeric antigen receptor modified T cell-based immunotherapy is revolutionizing the field of cancer treatment. However, its potential in treating bile duct carcinoma has not been fully explored. Herein, we developed the second-generation mesothelin-targeting chimeric antigen receptor-modified T cells with the 4-1BB co-stimulatory module by the piggyBac transposon system. Mesothelin-targeting chimeric antigen receptor was expressed by 66.0% of mesothelin-targeting chimeric antigen receptor-modified T cells post electrophoretic transfection and stimulation with K562-meso cells; the expressions of activation markers were tested by flow cytometry assay and showed greater activation of mesothelin-targeting chimeric antigen receptor-modified T cells than control T cells (CD107α: 71.9% vs 48.6%; CD27: 92.1% vs 61.8%; CD137: 55.5% vs 8.4%; CD28: 98.0% vs 82.1%; CD134: 37.5% vs 10.4%). Furthermore, mesothelin-targeting chimeric antigen receptor-modified T cells exerted cytotoxicity toward mesothelin-expressing EH-CA1b and EH-CA1a cells in an effector-to-target ratio-dependent manner, while leaving mesothelin-negative GSC-SD and EH-GB1 cells and normal liver L02 cells almost unharmed. Mesothelin-targeting chimeric antigen receptor-modified T cells secreted cytokines at higher levels when co-cultured with mesothelin-positive EH-CA1a and EH-CA1b cells than with mesothelin-negative GSC-SD and EH-GB1 cells. Enhanced cytotoxicity and cytokine secretion of mesothelin-targeting chimeric antigen receptor-modified T cells compared to control T cells were also observed when co-cultured with 293-meso cells (interferon γ: 85.1% ± 1.47% vs 8.3% ± 2.50%, p = 0.000; tumor necrosis factor α: 90.9% ± 4.67% vs 18.5% ± 3.62%, p = 0.0004; interleukin 2: 60.8% ± 2.00% vs 15.6% ± 2.06%, p = 0.002; interleukin 6: 6.4% ± 2.95% vs 1.7% ± 0.63%, p = 0.055). In addition, mesothelin-targeting chimeric antigen receptor-modified T cells showed greater inhibitory and proliferative capability than control T cells within EH-CA1a cell xenografts. This study shows the potential of mesothelin-targeting chimeric antigen receptor-modified T cells in treating bile duct carcinoma.
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Neoplasias dos Ductos Biliares/terapia , Elementos de DNA Transponíveis , Proteínas Ligadas por GPI/imunologia , Imunoterapia/métodos , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Animais , Neoplasias dos Ductos Biliares/patologia , Células Cultivadas , Humanos , Mesotelina , Camundongos , Proteínas Recombinantes de FusãoRESUMO
Abnormal activation of synovial fibroblasts (SFs) plays an important role in rheumatoid arthritis (RA), the mechanism of which remains unknown. The purpose of our study is to comprehensively and systematically explore the mechanism for Semaphorin 5A-mediated abnormal SF activation in RA. Here, we found that Semaphorin 5A levels were significantly higher in synovial fluid and synovial tissue from RA patients compared with osteoarthritis patients. We further found that the mRNA level and protein abundance of Plexin-A1 was elevated in RA SFs compared with OA SFs, while Plexin-B3 expression showed no significant difference. The increased Semaphorin 5A in RA synovial fluid was mainly derived from CD68+ synovial macrophages, and the elevation led to increased binding between Semaphorin 5A and its receptors, thereby promoting cytokine secretion, proliferation, and migration, and decreasing apoptosis. Moreover, the effect of Semaphorin 5A on enhancing activation (cytokine secretion, cell proliferation and migration) and reducing apoptosis of SFs was significantly abolished after knockdown of Plexin-A1 and Plexin-B3 by small interfering RNA. Transcriptome sequencing and protein array detection revealed that Semaphorin 5A activated the PI3K/AKT/mTOR signaling pathway and inhibited ferroptosis. Morphologically, transmission electron microscopy results showed that Semaphorin 5A could significantly eliminate the mitochondrial diminution, membrane density increased and crest ruptured of SFs induced by ferroptosis inducer RSL3. Mechanistically, Semaphorin 5A enhanced GPX4 expression and SREBP1/SCD-1 signaling by activating the PI3K/AKT/mTOR signaling pathway, thus suppressing ferroptosis of RA SFs. In conclusion, our study provided the first evidence that elevated Semaphorin 5A in RA synovial fluid promotes SF activation by suppressing ferroptosis through the PI3K/AKT/mTOR signaling pathway.
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Artrite Reumatoide , Ferroptose , Osteoartrite , Semaforinas , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Fibroblastos/metabolismo , Humanos , Osteoartrite/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Transdução de Sinais , Membrana Sinovial/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
OBJECTIVES: The purpose of this study was to determine the incidence of myositis-specific autoantibodies (MSAs) in a cohort of Chinese patients with idiopathic inflammatory myopathies (IIMs) and to examine their associations with clinical characteristics and long-term prognosis. METHODS: Adult patients with confirmed IIMs (n = 515) were studied using the EUROLINE Autoimmune Inflammatory Myopathies 16 Ag (IgG) commercial line blot test to detect MSAs/myositis-associated autoantibodies. We collected the laboratory data and clinical features. The frequencies of MSAs and their associations with clinical phenotypes were evaluated using SPSS 25.0 software. RESULTS: At least one MSA was found in 88.2% of the 515 IIM patients studied. The most frequently detected MSAs were anti-MDA5 (25.4%), anti-Jo-1(15.1%), and anti-EJ (9.5%). Autoantibodies against MDA5, TIF1-γ, and NXP2 were significantly correlated with cutaneous involvement (P < 0.001 or P < 0.01). Anti-TIF1-γ-positive patients had an enhanced risk of malignancy (OR = 3.51). Rapidly progressive interstitial lung disease (RP-ILD) was significantly correlated with anti-MDA5 (P < 0.0001). Anti-MDA5-positive patients had increased risks of elevated ferritin and decreased lymphocyte counts (OR = 5.65 and OR = 5.74, respectively). Kaplan-Meier survival revealed that individuals positive for anti-MDA5, especially anti-MDA5 combined with anti-Ro52, had the worst prognosis (P = 0.03). Male, old age, RP-ILD, and elevated ferritin were identified as predictors of poor prognosis in IIM patients. CONCLUSIONS: MSAs were present in the majority of the IIM patients. Numerous MSAs were independent factors for identifying exceptional clinical phenotypes. Key Points ⢠This is a large Chinese cohort of IIM patients to analyze possible associations of MSA profiles with clinical characteristics, aiming to provide valuable data for clinical work. ⢠MSAs were present in approximately 90% of IIM patients with distinct clinical subsets. Patients with anti-Jo-1 and non-anti-Jo-1 ASAs exhibited similar characteristics. ⢠The association of anti-TIF1-γ with malignancy was confirmed in adult patients. Patients with IIMs who were positive for both anti-Ro52 and anti-MDA5 had a worse prognosis. ⢠Male, RP-ILD, and heliotrope rash were independent risk factors for a poor prognosis in patients with IIMs.
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Doenças Pulmonares Intersticiais , Miosite , Neoplasias , Autoanticorpos , Ferritinas , Humanos , Imunoglobulina G , Doenças Pulmonares Intersticiais/etiologia , Masculino , Neoplasias/complicaçõesRESUMO
PROBLEM: For women of reproductive age, achieving a successful pregnancy requires both the normal functioning of reproductive endocrine and the health of the reproductive tract environment. We aimed to study how these fertility factors, such as female age, baseline sexual hormone levels, tubal patency, and vaginal pH, affect the composition of vaginal microbiome. METHOD OF STUDY: The 16S rRNA sequencing was carried on vaginal microbiome samples from 85 women of reproductive age without vaginal infections or reproductive endocrine diseases. The detailed correlations between fertility factors and vaginal microbiome were quantified by Spearman's rank tests. A linear discriminant analysis was carried out to explore the effects of fertility factors on the relative abundances of vaginal bacterial species. RESULTS: The vaginal pH, levels of basal E2, LH, and FSH all had significant effects on the distribution of vaginal microbiome. The relative abundances of vaginal bacterial species, including Escherichia coli, Streptococcus agalactiae, and Prevotella intermedia, were significantly different due to the host's state of reproductive endocrine and tubal patency. It was worth noting that women with tubal obstruction, or prolonged menstrual cycle, or antral follicle count >15, or vaginal pH > 4.5 all had a higher abundance of Escherichia coli in vagina. CONCLUSION: The fertility factors associated with the reproductive endocrine and the genital tract environment affected vaginal microbiome in women of reproductive age. The species Escherichia coli, Streptococcus agalactiae, Prevotella intermedia, etc could be used as biomarkers to reflect the pathological state of reproductive endocrine and genital tract.
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Escherichia coli/fisiologia , Fertilidade/fisiologia , Microbiota/genética , Prevotella intermedia/fisiologia , RNA Ribossômico 16S/genética , Streptococcus/fisiologia , Vagina/microbiologia , Adulto , Fatores Etários , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Gravidez , Reprodução , Adulto JovemRESUMO
OBJECTIVE: To identify different microbial species in women with polycystic ovary syndrome (PCOS) and reveal a possible relationship between gut dysbiosis and pathological changes. DESIGN: Cross-sectional study. SETTING: Academic institution. PATIENT(S): Reproductive-aged women with PCOS (n = 14) and controls (n = 14) from the Centre for Reproductive Medicine. INTERVENTION(S): Shotgun metagenomic sequencing on fecal samples from patients, and clinical parameters (including body mass index, endocrine hormone levels, and glycemia level) gathered for correlation analysis. MAIN OUTCOME MEASURE(S): Identification of different gut microbial strains and relativity between microbiota and clinical parameters. RESULT(S): We found several microbial strains were statistically significantly more abundant in the PCOS group, including Parabacteroides merdae, Bacteroides fragilis, and strains of Escherichia and Shigella, whereas Faecalibacterium prausnitzii was enriched in the control group. Metagenomic species (MGS) analysis revealed that the microbes of the PCOS group were negatively correlated with those of the control group. Of note, we observed a positive correlation between MGS relevant to PCOS and endocrine disorders, including body mass index and elevated levels of serum testosterone, luteinizing hormone, and antimüllerian hormone. Functional alterations, reflected by Kyoto Encyclopedia of Genes and Genomes orthologues, could imply potential mechanisms of microbial involvement in the developmental progress of PCOS. CONCLUSION(S): Our findings suggest an intimate association and potential mechanisms linking microbial dysbiosis and the pathophysiologic changes of PCOS. We address the importance of monitoring and modulating microbial composition and functional shifts in future clinical practice.
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Bactérias/genética , Microbioma Gastrointestinal/genética , Intestinos/microbiologia , Síndrome do Ovário Policístico/microbiologia , Adulto , Bactérias/classificação , Estudos de Casos e Controles , Estudos Transversais , Disbiose , Fezes/microbiologia , Feminino , Humanos , Metagenômica , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Adulto JovemRESUMO
The interplay between genetic and environmental risk factors contributes to the pathogenesis of metabolic disease. Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Circadian rhythm disruption is an important risk factor for PCOS. In this study, we evaluated the effect of circadian disorder on reproduction as well as metabolism, and determined its influence on gut microbiota in a rat model. Female Sprague Dawley (SD) rats were kept under continuous light exposure (12-h:12-h light/light cycle, L/L group) or a control cycle (12-h:12-h light/dark cycle, L/D group) for four consecutive weeks. Manifestations in endocrine hormones and metabolism were detected and gut microbiota were analyzed with the 16s rRNA gene sequencing technique. To our knowledge, this is the first study to report PCOS-like reproductive manifestation, such as anti-Müllerian hormone (AMH) elevation induced by continuous light exposure. Moreover, continuous light resulted in abnormal glucose metabolism and gut microbial community variations, including enrichment of the microbial genus of Parasutterella and reduced abundance of genus Corynebacterium, genus Odoribacter, and genus Acinetobacter. Increased Parasutterella abundance was positively correlated with serum testosterone level. A PICRUSt analysis revealed that reproductive and metabolic-related genes were enriched in rats of L/D group. In conclusion, the present study demonstrates that continuous light exposure, an important environmental factor, contributes to the occurrence and developmental progress of PCOS and changes in microbial component and structure. Continuous light exposure is one of vital causes of PCOS, which is closely related to microbial structure and functions.
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BACKGROUND: Disordered folliculogenesis is a key feature of polycystic ovary syndrome (PCOS), but the underlying molecular mechanism remains unclear. METHODS: Long non-coding RNA (lncRNA) expression in luteinized granulosa cells (hLGCs) derived from women with and without PCOS were analyzed using microarray and qRT-PCR. Immortalized human granulosa cell lines were cultured for proliferation assays after transfection with the LINC-01572:28 over-expression vector in the presence or absence of p27 siRNA. Protein expression analysis, rescue assays, and RNA immunoprecipitation (RIP) were used to confirm the LINC-01572:28 substrate. FINDINGS: LINC-01572:28 and p27 protein were elevated whereas proliferating cell nuclear antigen protein was decreased in the hLGCs of women with PCOS. LINC-01572:28 expression was positively correlated with basal testosterone levels. Over-expression of LINC-01572:28 inhibited cell proliferation and impeded G1/S transition, which were partially reversed by siRNA-mediated p27 knockdown. INTERPRETATION: Our findings, therefore, suggest that LINC-01572:28 suppresses cell proliferation and cell cycle progression by reducing the degradation of p27 protein via SKP2 binding.
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Single-wall carbon nanotubes (SWNTs) have been extensively explored as an ultrafast nonlinear optical material. However, due to the numerous electronic and morphological arrangements, a simple and self-contained physical model that can unambiguously account for the rich photocarrier dynamics in SWNTs is still absent. Here, by performing broadband degenerate and non-degenerate pump-probe experiments on SWNTs of different chiralities and morphologies, we reveal strong evidences for the existence of bandgap renormalization in SWNTs. In particularly, it is found that the broadband transient response of SWNTs can be well explained by the combined effects of Pauli blocking and bandgap renormalization, and the distinct dynamics is further influenced by the different sensitivity of degenerate and non-degenerate measurements to these two concurrent effects. Furthermore, we attribute optical-phonon bath thermalization as an underlying mechanism for the observed bandgap renormalization. Our findings provide new guidelines for interpreting the broadband optical response of carbon nanotubes.
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BACKGROUND: Suoyang originates from a psammophyte named Cynomorium songaricum Rupr and has been known as a phenolic-antioxidant-enriched traditional Chinese herbal medicine. The present study attempted to investigate the protective effect of phenolic antioxidants in Suoyang towards â¢OH-mediated MSCs and then further discusses the chemical mechanisms. METHODS: The lyophilized aqueous extract of Suoyang (LAS) was prepared and characterized using HPLC. Then, two phenolic antioxidant references, epicatechin and luteolin-7-O-ß-D-glucoside, along with LAS, were investigated for their effects on the viability of â¢OH-treated MSCs using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The comparison and mechanistic chemistry of epicatechin and luteolin-7-O-ß-D-glucoside were further explored using various antioxidant assays, including PTIOâ¢-scavenging, FRAP (ferric ion reducing antioxidant power), ABTS+â¢-scavenging, and DPPHâ¢-scavenging. Their Fe2+-binding capacities were also compared using ultraviolet (UV) spectra. RESULTS: The HPLC analysis indicated that there are 8 phenolic antioxidants in LAS, including epicatechin, luteolin-7-O-ß-D-glucoside, gallic acid, protocatechuic acid, catechin, isoquercitrin, phlorizin, and naringenin. The MTT assay revealed that epicatechin could more effectively increase the survival of â¢OH-treated MSCs than luteolin-7-O-ß-D-glucoside. Similarly, epicatechin exhibited higher antioxidant abilities than luteolin-7-O-ß-D-glucoside in the DPPHâ¢-scavenging, ABTS+â¢-scavenging, FRAP, and PTIOâ¢-scavenging assays. In the Fe2+-binding assay, luteolin-7-O-ß-D-glucoside gave a stronger UV peak at 600 nm, with ε = 2.62 × 106 M-1 cm-1, while epicatechin produced two peaks at 450 nm (ε = 8.47 × 105 M-1 cm-1) and 750 nm (ε = 9.68 × 105 M-1 cm-1). CONCLUSION: As two reference antioxidants in Suoyang, epicatechin and luteolin-7-O-ß-D-glucoside can enhance the viability of â¢OH-damaged MSCs. Such a beneficial effect may be from their antioxidant effects, including direct-antioxidant and indirect-antioxidant (i.e., Fe2+-binding) processes. In the direct-antioxidant process, proton (H+), one electron (e), or even hydrogen-atom (â¢H) transfer may occur to fulfill radical-scavenging (especially â¢OH-scavenging); in this aspect, epicatechin is superior to luteolin-7-O-ß-D-glucoside due to the presence of more phenolic -OHs. The additional -OHs can also be responsible for the better cytoprotective effect. In terms of indirect-antioxidant potential, however, epicatechin is inferior to luteolin-7-O-ß-D-glucoside due to the absence of a hydroxyl-keto moiety. These findings will provide new information about medicinal psammophytes for MSC transplantation.