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Ovarian endometriosis is a common gynecological disease, and one of its most significant symptoms is infertility. In patients with endometriosis, defects in endometrial decidualization lead to impaired endometrial receptivity and embryo implantation, thus affecting early pregnancy and women's desire to have children. However, the mechanisms underlying the development of endometriosis and its associated defective decidualization are unclear. We find that NEK2 expression is increased in the ectopic and eutopic endometrium of patients with endometriosis. Meanwhile, NEK2 interacts with FOXO1 and phosphorylates FOXO1 at Ser184, inhibiting the stability of the FOXO1 protein. Importantly, NEK2-mediated phosphorylation of FOXO1 at Ser184 promotes cell proliferation, migration, invasion and impairs decidualization. Furthermore, INH1, an inhibitor of NEK2, inhibits the growth of ectopic lesions in mouse models of endometriosis and promotes endometrial decidualization in mouse models of artificially induced decidualization. Taken together, these findings indicate that NEK2 regulates the development of endometriosis and associated disorders of decidualization through the phosphorylation of FOXO1, providing a new therapeutic target for its treatment.
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Proliferação de Células , Endometriose , Endométrio , Proteína Forkhead Box O1 , Quinases Relacionadas a NIMA , Feminino , Endometriose/metabolismo , Endometriose/patologia , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Humanos , Animais , Fosforilação , Camundongos , Quinases Relacionadas a NIMA/metabolismo , Quinases Relacionadas a NIMA/genética , Endométrio/metabolismo , Endométrio/patologia , Movimento Celular , Decídua/metabolismo , Decídua/patologia , Adulto , Modelos Animais de DoençasRESUMO
The structure-property relationship of poly(vinyl chloride) (PVC)/CaCO3 nanocomposites is investigated by all-atom molecular dynamics (MD) simulations. MD simulation results indicate that the dispersity of nanofillers, interfacial bonding, and chain mobility are imperative factors to improve the mechanical performance of nanocomposites, especially toughness. The tensile behavior and dissipated work of the PVC/CaCO3 model demonstrate that 12 wt % CaCO3 modified with oleate anion and dodecylbenzenesulfonate can impart high toughness to PVC due to its good dispersion, favorable interface interaction, and weak migration of PVC chains. Under the guidance of MD simulation, we experimentally prepared a transparent PVC/CaCO3 nanocomposite with good mechanical properties by in situ polymerization of monodispersed CaCO3 in vinyl chloride monomers. Interestingly, experimental tests indicate that the optimum toughness of a nanocomposite (a 368% increase in the elongation at break and 204% improvement of the impact strength) can be indeed realized by adding 12 wt % CaCO3 modified with oleic acid and dodecylbenzenesulfonic acid, which is remarkably consistent with the MD simulation prediction. In short, this work provides a proof-of-concept of using MD simulation to guide the experimental synthesis of PVC/CaCO3 nanocomposites, which can be considered as an example to develop other functional nanocomposites.
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In the recent decade, chimeric antigen receptor (CAR)-T cell therapy has revolutionized strategies for cancer treatments due to its highly effective clinical efficacy and response for B cell malignancies. The success of CAR-T cell therapy has stimulated the increase in the research and development of various CAR constructs to target different tumor types. Therefore, a robust and efficient in vitro potency assay is needed to quickly identify potential CAR gene design from a library of construct candidates. Image cytometry methodologies have been utilized for various CAR-T cell-mediated cytotoxicity assay using different fluorescent labeling methods, mainly due to their ease-of-use, ability to capture cell images for verification, and higher throughput performance. In this work, we employed the Celigo Image Cytometer to evaluate and compare two CAR-T cell-mediated cytotoxicity assays using GFP-expressing or fluorescent dye-labeled myeloma and plasmacytoma cells. The GFP-based method demonstrated higher sensitivity in detecting CAR-T cell-mediated cytotoxicity when compared to the CMFDA/DAPI viability method. We have established the criteria and considerations for the selection of cytotoxicity assays that are fit-for-purpose to ensure the results produced are meaningful for the specific testing conditions.
Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T , Linhagem Celular Tumoral , Imunoterapia Adotiva/métodosRESUMO
Ovarian endometriosis is a common gynecological condition that can cause infertility in women of childbearing age. However, the pathogenesis is still unknown. We demonstrate that the carboxyl terminus of Hsc70-interacting protein (CHIP) is a negative regulator in the development of endometriosis and reduces HMGB1 expression in endometriotic cells. Meanwhile, CHIP interacts with HMGB1 and promotes its ubiquitinated degradation, thereby inhibiting aerobic glycolysis and the progression of endometriosis. Furthermore, the CHIP agonist YL-109 effectively suppresses the growth of ectopic endometrium in endometriosis mouse model, which could be a potential therapeutic approach for endometriosis. In conclusion, our data suggest that CHIP may inhibit the development of endometriosis by suppressing the HMGB1-related glycolysis.
Assuntos
Endometriose , Proteína HMGB1 , Ubiquitina-Proteína Ligases , Animais , Feminino , Humanos , Camundongos , Endometriose/patologia , Glicólise , Proteína HMGB1/metabolismo , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Morchella esculenta (L.) Pers., referred to as Morel, is a medicinal and edible homologous fungus, which contains many bioactive substances. In Morel, polysaccharides are the most abundant and have various bioactivities. In the present work, two novel polysaccharides, Se-MPS and MPS, were prepared and purified from selenium-enriched (Se-enriched) and common Morel mycelia, respectively, and their structural and immunomodulatory properties were evaluated. The results show that Se-enriched treatment significantly changed the polysaccharides' chemical composition, molecular weight, and sugar chain configuration. In addition, the Se-enriched treatment also improved the polysaccharides' fragmentation and thermal stability. Importantly, Se-enriched Morel polysaccharide (Se-MPS) could significantly enhance phagocytosis of RAW 264.7 macrophage cells and, remarkably, activate their immune response via activating the TLR4-TRAF6-MAPKs-NF-κB cascade signaling pathway, finally exerting an immunomodulatory function. Based on these findings, selenium-enriched Morel polysaccharide appears to have more potential for development and utilization in functional foods or medicines than ordinary Morel polysaccharide.
Assuntos
Selênio , Selênio/química , Antioxidantes/química , Polissacarídeos/farmacologia , Polissacarídeos/química , FagocitoseRESUMO
Inulin is a naturally soluble dietary fiber that is widely distributed and primarily derived from plants. As a reserve biopolysaccharide in plants, inulin is considered an indigestible carbohydrate of fructan because of its unique ß-(2,1)-glycosidic bond structure. Numerous recent animal and human experimental studies have shown that functional inulin possesses multiple bioactivities, including immunomodulatory, antioxidant, antitumor, hepatoprotective, hypoglycemic, and gastrointestinal protective activities. Due to its increasing popularity, people tend to consume foods containing inulin. Moreover, inulin holds promise as a bioactive compound for use in the development of various food products. Therefore, this paper provides a detailed review of the extraction method, physicochemical properties, functional activity, and application development of inulin polysaccharides, to provide a theoretical foundation for further advancements in the fields of preparation and application of functional foods.
Assuntos
Inulina , Polissacarídeos , Animais , Humanos , Inulina/farmacologia , Polissacarídeos/farmacologia , Polissacarídeos/química , Frutanos , Carboidratos , Alimento FuncionalRESUMO
OBJECTIVE: To explore the practicality and effectiveness of a flexible low-dose protocol in the fresh embryo transfer cycle: reducing the total amount of antagonist by increasing the interval between administrations of Cetrotide. METHODS: A total of 211 patients with normal ovarian reserve who accepted GnRH-ant protocol for IVF-ET were selected, and they were randomized to the flexible low-dose antagonist group (test group, n = 101) or the conventional dose antagonist group (control group, n = 110). The initial dose of Cetrotide in the test group was 0.25 mg every other day, and then the dose was adjusted to 0.25 mg every day based on the subsequent luteinizing hormone (LH) levels. The dosage of Cetrotide in the control group was 0.25 mg per day. The primary outcome was the clinical pregnancy rate. Secondary outcomes included the incidence of premature LH rise, total dosage of Cetrotide, number of oocytes retrieved, number of fertilized oocytes, number of high-quality embryos, biochemical pregnancy rate and ongoing pregnancy rate. RESULTS: There was no significant difference in the general condition of the two groups. There was no significant difference in the clinical pregnancy rate (51.49% vs. 48.18%, p = 0.632) or the incidence of premature LH rise (18.81% vs. 15.45%, p = 0.584) between the two groups. However, the amount of Cetrotide used in the test group was significantly lower than that in the conventional dose antagonist group (1.13 ± 0.41 vs. 1.61 ± 0.59 mg, p < 0.001). CONCLUSION: The flexible low-dose antagonist protocol and the conventional dose antagonist protocol were equally effective in people with a normal ovarian reserve in the fresh embryo transfer cycle of IVF-ET.
Assuntos
Indução da Ovulação , Resultado da Gravidez , Transferência Embrionária , Feminino , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina , Humanos , Indução da Ovulação/métodos , GravidezRESUMO
BACKGROUND: Long non-coding RNA plasmacytoma variant translocation 1 (lnc-PVT1) exacerbates inflammation and induces T helper (Th) 1/Th2 imbalance in allergic diseases, but its clinical role in allergic rhinitis (AR) remains unclear. Hence, we conducted this study to compare lnc-PVT1 expression among AR children, disease controls (DCs), and health controls (HCs), aiming to investigate its clinical application in AR children. METHODS: Sixty AR children, 30 DCs, and 30 HCs were enrolled in the study, and then, their lnc-PVT1 expression in peripheral blood mononuclear cell was detected. Serum interferon-gamma (IFN-γ), interleukin 10 (IL-10), Th1, and Th2 cells in AR children were also analyzed. Besides, lnc-PVT1 was also detected at Week (W)4 after treatment in AR patients. RESULTS: Lnc-PVT1 was upregulated in AR children compared with DCs and HCs (both p < 0.001). Lnc-PVT1 was positively related to nasal rhinorrhea score, itching score, congestion score, and total nasal symptom score (TNSS) in AR children (all p < 0.050), instead of sneezing score (p = 0.115). Lnc-PVT1 negatively associated with Th1 cells in AR children (p = 0.028) also exhibited a negative correlation trend with IFN-γ (but without statistical significance) (p = 0.065). Differently, lnc-PVT1 was positively related to Th2 cells (p = 0.012) and IL-10 (p = 0.021) in AR children. Besides, lnc-PVT1 and TNSS were reduced at W4 after treatment in AR children (both p < 0.001); notably, lnc-PVT1 expression decline was correlated with TNSS decline during treatment (p = 0.013). CONCLUSION: Lnc-PVT1 works as a biomarker, whose aberrant expression is related to disease severity, Th1/Th2 imbalance, and its decrement can reflect treatment outcome in AR children.
Assuntos
RNA Longo não Codificante , Rinite Alérgica , Criança , Citocinas/metabolismo , Humanos , Interleucina-10 , Leucócitos Mononucleares/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Rinite Alérgica/genética , Células Th2/metabolismoRESUMO
Photoperiod and thermo-sensitive genic male sterile (PTGMS) rice is an important resource for two line hybrid rice production. The SQUAMOSA-promoter binding, such as the (SPL) gene family, encode the plant specific transcription factors that regulate development and defense responses in plants. However, the reports about SPLs participating in male fertility regulation are limited. Here, we identified 19 OsSPL family members and investigated their involvement in the fertility regulation of the PTGMS rice lines, PA2364S and PA2864S, with different fertility transition temperatures. The results demonstrated that OsSPL2, OsSPL4, OsSPL16 and OsSPL17 affect male fertility in response to temperature changes through the MiR156-SPL module. WGCNA (weighted gene co-expression network analysis) revealed that CHI and APX1 were co-expressed with OsSPL17. Targeted metabolite and flavonoid biosynthetic gene expression analysis revealed that OsSPL17 regulates the expression of flavonoid biosynthesis genes CHI, and the up regulation of flavanones (eriodictvol and naringenin) and flavones (apigenin and luteolin) content contributed to plant fertility. Meanwhile, OsSPL17 negatively regulates APX1 to affect APX (ascorbate peroxidase) activity, thereby regulating ROS (reactive oxygen species) content in the tapetum, controlling the PCD (programmed cell death) process and regulating male fertility in rice. Overall, this report highlights the potential role of OsSPL for the regulation of male fertility in rice and provides a new insight for the further understanding of fertility molecular mechanisms in PTGMS rice.
Assuntos
Oryza , Fertilidade/genética , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/metabolismo , Fotoperíodo , TemperaturaRESUMO
Two-line hybrid rice systems represent a new technical approach to utilizing the advantages of rice hybrids. However, the mechanism underlying the male sterile-line fertility transition in rice remains unclear. Peiai 64S (PA64S) is a photoperiod- and thermo-sensitive genic male sterile (PTGMS) line in which male sterility manifests at an average temperature above 23.5 °C under long-day (LD) conditions. Nongken 58S (NK58S) is a LD-sensitive genic male sterile (PGMS) rice that is sterile under LD conditions (above 13.75 h-day). In contrast, D52S is a short-day (SD)-PGMS line that manifests male sterility under SD conditions (below 13.5 h-day). In this study, we obtained fertile and sterile plants from all three lines and performed transcriptome analyses on the anthers of the plants. Gene ontology (GO) analysis suggested that the differentially expressed genes identified were significantly enriched in common terms involved in the response to jasmonic acid (JA) and in JA biosynthesis. On the basis of the biochemical and molecular validation of dynamic, tissue-specific changes in JA, indole-3-acetic acid (IAA) levels, gibberellin (GA) levels, and JA biosynthetic enzyme activities and expression, we proposed that JA could play a pivotal role in viable pollen production through its initial upregulation, constant fluctuation and leaf-spikelet signaling under certain fertility-inducing conditions. Furthermore, we also sprayed methyl jasmonate (MEJA) and salicylhydroxamic acid (SHAM) on the plants, thereby achieving fertility reversal in the PGMS lines NK58S and D52S, with 12.91-63.53% pollen fertility changes. Through qPCR and enzyme activity analyses, we identified two key enzymes-allene oxide synthase (AOS) and allene oxide cyclase (AOC)-that were produced and upregulated by 20-500-fold in PGMS in response to spraying; the activities of these enzymes reversed pollen fertility by influencing the JA biosynthetic pathway. These results provide a new understanding of hormone interactions and networks in male-sterile rice based on the role of JA that will help us to better understand the potential regulatory mechanisms of fertility development in rice in the future.
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Ciclopentanos/metabolismo , Oxirredutases Intramoleculares/genética , Oryza/metabolismo , Oxilipinas/metabolismo , Pólen/crescimento & desenvolvimento , Transdução de Sinais , Acetatos/farmacologia , Ciclopentanos/farmacologia , Fertilidade , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/fisiologia , Oxilipinas/farmacologia , Proteínas de Plantas/genética , Pólen/metabolismo , Salicilamidas/farmacologiaRESUMO
A photoperiod- and thermo-sensitive genic male sterile (PTGMS) line is the basic material for two-hybrid rice and is an important genetic breeding resource. Peiai64S (PA64S) is an important germplasm resource of PTGMS rice, and it has been applied to two-line hybrid rice systems in China. Pollen fertility in PA64S is regulated by the temperature and photoperiod, but the mechanism of the fertility transition is unclear. In this study, we obtained the male fertile plant PA64S(F) and the male sterile plant PA64S(S) by controlling different temperatures under long light conditions and used the male fertile and sterile plants to investigate the role of microRNAs (miRNAs) in regulating male fertility in rice. We performed the small RNA library sequencing of anthers from PA64S(S) and PA64S(F). A total of 196 miRNAs were identified-166 known miRNAs among 27 miRNA families and 30 novel miRNAs. In the transcriptome analysis, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes revealed significant enrichment in the synthesis and metabolism of fatty acids and some secondary metabolism pathways such as fatty acid metabolism and phenylalanine metabolism. With a comprehensive analysis of miRNA, transcriptome, and degradome sequencing, we identified that 13 pairs of miRNA/target genes regulated male fertility in rice by responding to temperature change, among which the miR156, miR5488, and miR399 affect the male fertility of PA64S by influencing SPLs, the lignin synthesis of anther walls, and the flavonoid metabolism pathway. The results provide a new understanding of PTGMS rice, which will help us better understand the potential regulatory mechanisms of male sterility in the future.
Assuntos
Fertilidade/genética , MicroRNAs/genética , Oryza/genética , Desenvolvimento Vegetal/genética , Proteínas de Plantas/genética , Pequeno RNA não Traduzido/genética , Transcriptoma , Regulação da Expressão Gênica de Plantas , Redes e Vias Metabólicas , Oryza/crescimento & desenvolvimento , Fotoperíodo , Melhoramento Vegetal , Análise de Sequência de RNA , TemperaturaRESUMO
BACKGROUND: During the onset of osteoarthritis (OA), certain biochemical events have been shown to accelerate cartilage degradation, including the dysregulation of cartilage ECM anabolism, abnormal generation of reactive oxygen species (ROS) and overproduction of proteolytic enzymes and inflammatory cytokines. The potency of aucubin in protecting cellular components against oxidative stress, inflammation and apoptosis effects are well documented, which makes it a potential candidate for OA treatment. In this study, we aimed to evaluate the protective benefits of aucubin against OA using H2O2 and compression induced OA-like chondrocyte models. METHODS: The effects of aucubin were studied in porcine chondrocytes after 1 mM H2O2 stimulation for 30 min or sustained compression for 24 h. Effects of aucubin on cell proliferation and cytotoxicity of chondrocytes were measured with WST-1 and LDH assays. ROS production was evaluated by the Total ROS/Superoxide Detection Kit. Caspase-3 activity was evaluated by the CaspACE assay system. The levels of apoptosis were evaluated by the Annexin V-FITC apoptosis detection kit. OA-related gene expression was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Total DNA quantification was evaluated by the DNeasy Blood and Tissue kit. Sulfated-glycosaminoglycans (sGAGs) production and content were evaluated by DMMB assay and Alcian blue staining. RESULTS: The results showed that the ROS scavenge effects of aucubin appeared after 1 h of pretreatment. Aucubin could reduce the caspase-3 activity induced by H2O2, and reduced the apoptosis cell population in flowcytometry. In RT-qPCR results, aucubin could maintain ACAN and COL2A1 gene expressions, and prevent IL6 and MMP13 gene up-regulation induced by H2O2 and compression stimulations. In the DMMB assay and Alcian blue staining, aucubin could maintain the sGAG content and protect chondrocytes against compressive stress, but not oxidative stress from H2O2. CONCLUSIONS: These results indicated that aucubin has protective effects in an osteoarthritic chondrocyte model induced by H2O2 and mechanical stimulus.
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Condrócitos/efeitos dos fármacos , Glucosídeos Iridoides/uso terapêutico , Osteoartrite/tratamento farmacológico , Agrecanas/genética , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo II/genética , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Peróxido de Hidrogênio , Técnicas In Vitro , Interleucina-6/genética , Glucosídeos Iridoides/toxicidade , Metaloproteinase 13 da Matriz/genética , Osteoartrite/genética , Estimulação Física , Espécies Reativas de Oxigênio/metabolismo , SuínosRESUMO
Hericium erinaceus is an important mushroom with edible values and medicinal properties. Both the mycelium and the fruiting bodies contain many bioactive compounds with drug efficacy. Recent evidence demonstrates that it is helpful to various diseases, such as Alzheimer's disease, immunoregulatory, and many types of cancer. Furthermore, emerging pieces of evidence have shown that different active molecules in H. erinaceus have different functions on different organs in different diseases via the different mechanisms. Drawing on current research results, this review mainly focuses on the therapeutic effects of H. erinaceus on various diseases of multiple physiological systems, including the nervous system, digestive system, circulatory system, and immune system. This paper also discusses systematically the efficient protection of H. erinaceus against the diseases from the intricate experimental proofs by using the systematic viewpoints, which provides a framework for future research directions.
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Agaricales/química , Química Farmacêutica , Animais , Citocinas , HumanosRESUMO
Although Morchella esculenta (L.) Pers. is an edible and nutritious mushroom with significant selenium (Se)-enriched potential, its biological response to selenium stimuli remains unclear. This study explored the effect of selenium on mushroom growth and the global gene expression profiles of M. esculenta. While 5 µg mL-1selenite treatment slightly promoted mycelia growth and mushroom yield, 10 µg mL-1significantly inhibited growth. Based on comparative transcriptome analysis, samples treated with 5 µg mL-1 and 10 µg mL-1 of Se contained 16,061 (452 upregulated and 15,609 downregulated) and 14,155 differentially expressed genes (DEGs; 800 upregulated and 13,355 downregulated), respectively. Moreover, DEGs were mainly enriched in the cell cycle, meiosis, aminoacyl-tRNA biosynthesis, spliceosome, protein processing in endoplasmic reticulum pathway, and mRNA surveillance pathway in both selenium-treated groups. Among these, MFS substrate transporter and aspartate aminotransferase genes potentially involved in Se metabolism and those linked to redox homeostasis were significantly upregulated, while genes involved in isoflavone biosynthesis and flavonoid metabolism were significantly downregulated. Gene expression levels increased alongside selenite treatment concentration, suggesting that high Se concentrations promoted M. esculenta detoxification. These results can be used to thoroughly explain the potential detoxification and Se enrichment processes in M. esculenta and edible fungi.
Assuntos
Selênio , Transcriptoma , Selênio/farmacologia , Selênio/administração & dosagem , Selênio/metabolismo , Transcriptoma/efeitos dos fármacos , Ascomicetos/efeitos dos fármacos , Ascomicetos/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica/efeitos dos fármacosRESUMO
Various genetic variants have been found to be associated with the clinical onset of premature ovarian insufficiency (POI). However, when measured in vitro, the functional influence of the variants can be difficult to determine. By whole-exome sequencing (WES) of 93 patients with sporadic POI, we found a missense variant c.623G > A;p.R208H in the EIF4ENIF1 gene. In silico prediction of the variant using different algorithms suggested it might be a damaging variant. We compared the property of EIF4ENIF1 R208H and Q842P, a POI-related mutant that we reported previously, with wildtype (WT) protein using 293FT cells in vitro. Surprisingly, a change in subcellular distribution and granule forming ability (Q842P) and nuclear import capacity (R208H) was not observed, despite domain prediction evidences. Since EIF4ENIF1 was reported to inhibit translation, we employed T&T-seq, a translation-transcription dual-omics sequencing method, to profile gene expression upon overexpression of EIF4ENIF1 WT and mutants. EIF4ENIF1 WT overexpression group exhibited significantly (P < 0.0001) lower translation efficiency (TE) than empty vector or GFP overexpression control group. Surprisingly, EIF4ENIF1 Q842P overexpression failed to repress global translation, showing an overall TE significantly higher than WT group. Overexpression R208H significantly (P < 0.0001) lowered the overall TE, whereas exhibiting a reduced translation inhibitory effect on high-TE genes (TE > 2 in GFP control group). Several fertility-associated genes, such as AMH in Q842P group and SERPINE1 and THBS1 in R208H group, was translationally up-regulated in mutant groups versus WT control, suggesting a potential mechanism of mutated EIF4ENIF1 causing POI via impaired translation repression. It is further proposed that T&T-seq can be a sensitive evaluation tool for the measurement of functional alteration by variants in many other translational regulator genes, not only EIF4ENIF1, helping to eliminate misinterpretation of clinical significance of genetic variants.
Assuntos
Proteínas de Transporte Nucleocitoplasmático , Insuficiência Ovariana Primária , Biossíntese de Proteínas , Adulto , Feminino , Humanos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Sequenciamento do Exoma/métodos , Células HEK293 , Mutação , Mutação de Sentido Incorreto , Proteínas de Transporte Nucleocitoplasmático/genética , Insuficiência Ovariana Primária/genéticaRESUMO
Ovarian endometriosis (EMs) is a benign, estrogen-dependent gynecological disorder. Estrogen receptor beta (ERß), a nuclear receptor for estradiol, plays an important role in the development of ovarian EMs. Here, we investigated the biological significance of aurora kinase A (AURKA) in ovarian EMs and the mechanism by which it regulates ERß. We used immunohistochemical assays to verify that AURKA and ERß were highly expressed in ectopic endometrial tissues. Cell proliferation and colony formation assays were used to demonstrate that AURKA promoted the proliferation of EMs cells. Wound-healing assay, Transwell migration assay, and Matrigel invasion assay further showed that AURKA enhanced the ability of EMs cells to migrate and invade. In addition, AURKA was shown to stimulate glycolysis in EMs cells by measuring the concentration of glucose and lactate in the cell supernatants. Moreover, the AURKA inhibitor alisertib was found to inhibit the progression of ovarian EMs and glycolysis in a mouse model of EMs by measuring ectopic tissues as well as by testing the peritoneal fluid of mice. Furthermore, coimmunoprecipitation assay showed that AURKA interacted with ERß. The rescue experiments confirmed that AURKA regulated the development and glycolysis of ovarian EMs in an ERß-dependent manner. AURKA contributed to the development of ovarian EMs by upregulating of ERß. AURKA may represent a new target for the treatment of ovarian EMs.
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Endometriose , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Aurora Quinase A/genética , Aurora Quinase A/metabolismo , Receptor beta de Estrogênio/metabolismo , GlicóliseRESUMO
PURPOSE: Early diagnosis of benign and malignant vertebral compression fractures by analyzing imaging data is crucial to guide treatment and assess prognosis, and the development of radiomics made it an alternative option to biopsy examination. This systematic review and meta-analysis was conducted with the purpose of quantifying the diagnostic efficacy of radiomics models in distinguishing between benign and malignant vertebral compression fractures. METHODS: Searching on PubMed, Embase, Web of Science and Cochrane Library was conducted to identify eligible studies published before September 23, 2023. After evaluating for methodological quality and risk of bias using the Radiomics Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), we selected studies providing confusion matrix results to be included in random-effects meta-analysis. RESULTS: A total of sixteen articles, involving 1,519 vertebrae with pathological-diagnosed tumor infiltration, were included in our meta-analysis. The combined sensitivity and specificity of the top-performing models were 0.92 (95 % CI: 0.87-0.96) and 0.93 (95 % CI: 0.88-0.96), respectively. Their AUC was 0.97 (95 % CI: 0.96-0.99). By contrast, radiologists' combined sensitivity was 0.90 (95 %CI: 0.75-0.97) and specificity was 0.92 (95 %CI: 0.67-0.98). The AUC was 0.96 (95 %CI: 0.94-0.97). Subsequent subgroup analysis and sensitivity test suggested that part of the heterogeneity might be explained by differences in imaging modality, segmentation, deep learning and cross-validation. CONCLUSION: We found remarkable diagnosis potential in correctly distinguishing vertebral compression fractures in complex clinical contexts. However, the published radiomics models still have a great heterogeneity, and more large-scale clinical trials are essential to validate their generalizability.
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Fraturas por Compressão , Fraturas da Coluna Vertebral , Neoplasias da Coluna Vertebral , Humanos , Fraturas por Compressão/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Diagnóstico Diferencial , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/complicações , Sensibilidade e Especificidade , RadiômicaRESUMO
Antibiotics overuse and misuse increase the emergence of multidrug-resistant bacterial strains, which often leads to the failure of conventional antibiotic therapies. Even worse, the tendency of bacteria to form biofilms further increases the therapeutic difficulty, because the extracellular matrix prevents the penetration of antibiotics and triggers bacterial tolerance. Therefore, developing novel antibacterial agents or therapeutic strategies with diverse antibacterial mechanisms and destruction of bacteria biofilm is a promising way to combat bacterial infections. In the present study, the combination of quaternary ammonium compound poly(diallyl dimethyl ammonium chloride) (PDDA) with Cu2+ was screened out to fight common pathogenic Staphylococcus aureus (S. aureus) through multi-mechanisms. This combination appeared strong synergistic antibacterial activity, and the fractional inhibitory concentration index was as low as 0.032. The synergistic antibacterial mechanism involved the destruction of the membrane function, generation of intracellular reactive oxygen, and promotion more Cu2+ into the cytoplasm. Further, the combination of PDDA and Cu2+ reduced the extracellular polysaccharide matrix, meanwhile killing the bacteria embedded in the biofilm. The biocompatibility study in vitro revealed this combination exhibited low cytotoxicity and hemolysis ratio even at 8 times of minimum bactericidal concentration. This work provides a novel antibacterial agents combination with higher efficiency to fight planktonic and biofilm conditions of S. aureus.
Assuntos
Cobre , Staphylococcus aureus Resistente à Meticilina , Cobre/farmacologia , Staphylococcus aureus , Compostos de Amônio Quaternário/farmacologia , Antibacterianos/farmacologia , Bactérias , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
As one of the important timber species in China, Cunninghamia lanceolata is widely distributed in southern China. The information of tree individuals and crown plays an important role in accurately monitoring forest resources. Therefore, it is particularly significant to accurately grasp such information of individual C. lanceolata tree. For high-canopy closed forest stands, the key to correctly extract such information is whether the crowns of mutual occlusion and adhesion can be accurately segmented. Taking the Fujian Jiangle State-owned Forest Farm as the research area and using the UAV image as the data source, we developed a method to extract crown information of individual tree based on deep learning method and watershed algorithm. Firstly, the deep learning neural network model U-Net was used to segment the coverage area of the canopy of C. lanceolata, and then the traditional image segmentation algorithm was used to segment the individual tree to obtain the number and crown information of individual tree. Under the condition of maintaining the same training set, validation set and test set, the extraction results of the canopy coverage area by the U-Net model and traditional machine learning methods [random forest (RF) and support vector machine (SVM)] were compared. Then, two individual tree segmentation results were compared, one using the marker-controlled watershed algorithm, and the other using the combination of the U-Net model and marker-controlled watershed algorithm. The results showed that the segmentation accuracy (SA), precision, IoU (intersection over union) and F1-score (harmonic mean of precision and recall) of the U-Net model were higher than those of RF and SVM. Compared with RF, the value of those four indicators increased by 4.6%, 14.9%, 7.6% and 0.05, respectively. Compared with SVM, the four indicators increased by 3.3%, 8.5%, 8.1% and 0.05, respectively. In terms of extracting the number of trees, the overall accuracy (OA) of the U-Net model combined with the marker-controlled watershed algorithm was 3.7% higher than that of the marker-controlled watershed algorithm, with the mean absolute error (MAE) being decreased by 3.1%. In terms of extracting crown area and crown width of individual tree, R2 increased by 0.11 and 0.09, mean squared error decreased by 8.49 m2 and 4.27 m, and MAE decreased by 2.93 m2 and 1.72 m, respectively. The combination of deep learning U-Net model and watershed algorithm could overcome the challenges in accurately extracting the number of trees and the crown information of individual tree of high-density pure C. lanceolata plantations. It was an efficient and low-cost method of extracting tree crown parameters, which could provide a basis for developing intelligent forest resource monitoring.