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1.
mSystems ; 9(5): e0122223, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38564711

RESUMEN

Rapid and accurate sequencing of the entire viral genome, coupled with continuous monitoring of genetic changes, is crucial for understanding the epidemiology of coronaviruses. We designed a novel method called micro target hybrid capture system (MT-Capture) to enable whole-genome sequencing in a timely manner. The novel design of probes used in target binding exhibits a unique and synergistic "hand-in-hand" conjugation effect. The entire hybrid capture process is within 2.5 hours, overcoming the time-consuming and complex operation characteristics of the traditional liquid-phase hybrid capture (T-Capture) system. By designing specific probes for these coronaviruses, MT-Capture effectively enriched isolated strains and 112 clinical samples of coronaviruses with cycle threshold values below 37. Compared to multiplex PCR sequencing, it does not require frequent primer updates and has higher compatibility. MT-Capture is highly sensitive and capable of tracking variants.IMPORTANCEMT-Capture is meticulously designed to enable the efficient acquisition of the target genome of the common human coronavirus. Coronavirus is a kind of virus that people are generally susceptible to and is epidemic and infectious, and it is the virus with the longest genome among known RNA viruses. Therefore, common human coronavirus samples are selected to evaluate the accuracy and sensitivity of MT-Capture. This method utilizes innovative probe designs optimized through probe conjugation techniques, greatly shortening the time and simplifying the handwork compared with traditional hybridization capture processes. Our results demonstrate that MT-Capture surpasses multiplex PCR in terms of sensitivity, exhibiting a thousandfold increase. Moreover, MT-Capture excels in the identification of mutation sites. This method not only is used to target the coronaviruses but also may be used to diagnose other diseases, including various infectious diseases, genetic diseases, or tumors.


Asunto(s)
Genoma Viral , Secuenciación Completa del Genoma , Humanos , Genoma Viral/genética , Secuenciación Completa del Genoma/métodos , Coronavirus/genética , Coronavirus/aislamiento & purificación , SARS-CoV-2/genética
2.
Artículo en Inglés | MEDLINE | ID: mdl-37971472

RESUMEN

Objective: The objective of this study is to investigate the effects of emergency nursing interventions, specifically those based on the Pediatric Early Warning Score (PEWS), on children diagnosed with acute asthma, to promote the recovery of children with asthma and improve the quality of care for children with asthma. Methods: A total of 80 children, Acute asthma attacks under the age of 12, diagnosed with acute asthma and admitted to the Emergency Department of Hebei Children's Hospital between June 2018 and June 2019 were selected as participants for this study. They were randomly assigned to either the control group or the PEWS group. There was no significant statistical difference in age, gender, course of disease, and disease severity between the two groups of children. In the control group, children received standard emergency nursing interventions, while in the PEWS group, children received emergency nursing interventions based on the Pediatric Early Warning Score (PEWS). To evaluate the effectiveness of these interventions, several outcome measures were compared between the two groups. This included assessing the duration for symptoms to disappear, analyzing pulmonary function indicators and respiratory dynamics indicators, measuring scores from the Pediatric Asthma Quality of Life Questionnaire (PAQLQ), and evaluating nursing satisfaction. Results: Following the implementation of the nursing interventions, 1. The average cough disappearance time of children in the PEWS group was 1.97 days shorter than that in the control group, the average wheezing disappearance time was 0.97 days shorter, the average dyspnea disappearance time was 0.64 days shorter, and the average lung wheezing disappearance time was 1.19 days shorter, which indicated that emergency care based on PEWS shortened the duration of symptoms in children with asthma. 2. The average FEV1 of children in the PEWS group was 9.87% higher than the control group, the average FVC was 0.62L higher, the average PEF was 9.84% higher, the average V70 was 0.91% higher, the average V50 was 0.43% higher , and the average V25 was 0.37% higher, when compared with control group. These results indicates that emergency care based on PEWS enhances the lung function of children with asthma. 3. The average respiratory rate of children in the PEWS group was 8.05 times/min lower, and the average dynamic respiratory system compliance was 6.91 mL/cmH2O higher, than that in the control group, which indicated that emergency care based on PEWS improved respiratory dynamics indicators in children with asthma. 4. The average PAQLQ symptom dimension score of children in the PEWS group was 0.84 points higher, the average activity dimension score was 0.34 points higher, and the average emotional dimension score was 0.47 points higher when compared with the control group. This indicated that emergency care based on PEWS improves the quality of life of children with asthma. 5. The nursing satisfaction of children in the PEWS group was 95%, higher than 72.5% in the control group, indicating that emergency care based on PEWS improved the satisfaction of asthma children with the nursing process. Conclusion: The implementation of PEWS based emergency care in pediatric asthma patients has important clinical significance in promoting recovery and improving the quality of care for asthma patients. The implementation of emergency nursing interventions based on the Pediatric Early Warning Score (PEWS) for children with acute asthma has been found to be effective in promoting the recovery of their condition, enhancing their quality of life, and improving nursing satisfaction.

3.
Sci Total Environ ; 903: 166961, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-37696402

RESUMEN

In natural waters, hydroxyl radical (OH) can initiate many free radical-induced reactions, oxidizing various inorganic and organic compounds through electron transfer reactions, dehydrogenation reactions, addition reactions, and self-quenching reactions. However, due to its extremely low concentration and short lifetime in natural waters, studies on the quantitative measurement of OH levels are insufficient. In this work, we developed the first quinolinium-based fluorescence probe containing fluoride substituted donor that could detect hydroxyl radicals in the water system. This probe exhibits excellent selectivity towards OH with a large Stokes shift (114 nm) and 23-fold enhancement in fluorescence. Additionally, this probe has been proven to be low toxicity and applied to detect OH in living cells, zebrafish, and natural water samples with good recovery (over 92 %).

4.
bioRxiv ; 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37645936

RESUMEN

CRISPR prime editing (PE) requires a Cas9 nickase-reverse transcriptase fusion protein (known as PE2) and a prime editing guide RNA (pegRNA), an extended version of a standard guide RNA (gRNA) that both specifies the intended target genomic sequence and encodes the desired genetic edit. Here we show that sequence complementarity between the 5' and the 3' regions of a pegRNA can negatively impact its ability to complex with Cas9, thereby potentially reducing PE efficiency. We demonstrate this limitation can be overcome by a simple pegRNA refolding procedure, which improved ribonucleoprotein-mediated PE efficiencies in zebrafish embryos by up to nearly 25-fold. Further gains in PE efficiencies of as much as 6-fold could also be achieved by introducing point mutations designed to disrupt internal interactions within the pegRNA. Our work defines simple strategies that can be implemented to improve the efficiency of PE.

5.
Sci Rep ; 13(1): 8558, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37236998

RESUMEN

The incorporation of energy conservation measures into production efficiency is widely recognized as a crucial aspect of contemporary industry. This study aims to develop interpretable and high-quality dispatching rules for energy-aware dynamic job shop scheduling (EDJSS). In comparison to the traditional modeling methods, this paper proposes a novel genetic programming with online feature selection mechanism to learn dispatching rules automatically. The idea of the novel GP method is to achieve a progressive transition from exploration to exploitation by relating the level of population diversity to the stopping criteria and elapsed duration. We hypothesize that diverse and promising individuals obtained from the novel GP method can guide the feature selection to design competitive rules. The proposed approach is compared with three GP-based algorithms and 20 benchmark rules in the different job shop conditions and scheduling objectives considered energy consumption. Experiments show that the proposed approach greatly outperforms the compared methods in generating more interpretable and effective rules. Overall, the average improvement over the best-evolved rules by the other three GP-based algorithms is 12.67%, 15.38%, and 11.59% in the meakspan with energy consumption (EMS), mean weighted tardiness with energy consumption (EMWT), and mean flow time with energy consumption (EMFT) scenarios, respectively.

6.
Biol Reprod ; 108(5): 791-801, 2023 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-36721997

RESUMEN

Increasing evidences showed that ovulatory dysfunction, possibly caused by luteinized unruptured follicular follicle syndrome (LUFS), is one of the reasons for endometriosis-related infertility. The present study was conducted to explore the potential effect of elevated progesterone in follicular fluid (FF) on ovulation in endometriosis. A prospective study including 50 ovarian endometriosis patients and 50 control patients with matched pairs design was conducted with alterations in FF and peritoneal fluid (PF) components identified by metabolomics analyses and differentially expressed genes in granulosa cells (GCs) identified by transcriptome analysis. Patients with endometriosis exhibited a significantly higher progesterone level in serum, FF, and PF. Granulosa cells from endometriosis patients revealed decreased expression of HPGD, COX-2, and suppressed NF-ĸB signaling. Similarly, progesterone treatment in vitro downregulated HPGD and COX2 expression and suppressed NF-ĸB signaling in granulosa tumor-like cell line KGN (Bena Culture Collection, China) and primarily cultured GCs, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIĸBα/IĸBα ratio, and nucleus translocation of p65. On the contrary, TNF-α treatment increased expression of IL1R1, IRAK3, pIĸBα, p65, and HPGD in GCs. One potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation. In conclusion, we found that intrafollicular progesterone might downregulate HPGD and COX-2 in GCs via suppressing the NF-ĸB signaling pathway, shedding light on the mechanism underlying the endometriosis-related ovulatory dysfunction.


Asunto(s)
Endometriosis , Infertilidad Femenina , Femenino , Humanos , Progesterona/farmacología , Progesterona/metabolismo , Líquido Folicular/metabolismo , Endometriosis/genética , Endometriosis/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Estudios Prospectivos , Células de la Granulosa/metabolismo , Infertilidad Femenina/metabolismo
7.
Nurs Open ; 10(6): 4083-4092, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36807562

RESUMEN

AIM: To determine the potential profile classes of anxiety reported by ischaemic stroke survivors in rural China, and to explore the characteristics of patients having different types of post-stroke anxiety. DESIGN: A cross-sectional survey. METHODS: A cross-sectional survey was conducted by using convenience sampling to collect data from 661 ischaemic stroke survivors in rural Anyang city, Henan Province, China, from July 2021 to September 2021. The parameters included in the study were the socio-demographic characteristics, self-rating anxiety scale (SAS), self-rating depression scale (SDS) and the Barthel index of daily activity ability. Potential profile analysis was done to recognize subgroups of post-stroke anxiety. The Chi-square test was performed to explore the characteristics of individuals with different types of post-stroke anxiety. RESULTS: The model fitting indices of stroke survivors supported three classes of anxiety models which were as follows: (a) Class 1, low-level, stable group (65.3%, N = 431); (b) Class 2, moderate-level, unstable group (17.9%, N = 118) and (c) Class 3, high-level, stable group (16.9%, N = 112). The risk factors associated with post-stroke anxiety were female patients, lower levels of education, living alone, lower monthly household income, other chronic diseases, impaired daily activity ability and depression. CONCLUSIONS: This study identified three different subgroups of post-ischaemic stroke anxiety and their characteristics in patients in rural China. IMPACT: This study has significance in providing evidence for the development of targeted intervention measures to reduce negative emotions in different subgroups of post-stroke anxiety patients. PATIENT OR PUBLIC CONTRIBUTION: In this study, the researchers arranged the time of questionnaire collection with the village committee in advance, gathered the patients to the village committee for face-to-face questionnaire survey and collected the household data of the patients with mobility difficulties.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Accidente Cerebrovascular/epidemiología , Estudios Transversales , Depresión/epidemiología , Depresión/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Sobrevivientes/psicología
8.
Biomed Pharmacother ; 154: 113647, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36067570

RESUMEN

As a global mental disorder, depression is associated with oxidative stress in the brain. Cysteine, a reductive biothiols, regulates the oxidative situation in many biological events including the stress that occurs in the tissues. Exploring the pathology and physiology of depression is still a challenge and always in an urgent need. Thus, developing a new method that could track Cys level without the interferes from other competing substances is of great importance. Herein, we developed a fluorescence probe that could selectively sensing Cys over other biothiols. Besides, we have demonstrated its desirable performance in cellular applications and mouse brain. This work provides a new method for Cys imaging and understanding pathogenesis of depression. We hope the work described here could be used as a potential chemical approach for the diagnosis of Cys associated diseases in clinical applications.


Asunto(s)
Depresión , Colorantes Fluorescentes , Animales , Cisteína , Colorantes Fluorescentes/química , Glutatión , Células HeLa , Homocisteína , Humanos , Ratones , Espectrometría de Fluorescencia
9.
Front Endocrinol (Lausanne) ; 13: 818888, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35250874

RESUMEN

Female fertility declines with age, and this natural variation culminates in reproductive senescence. Human follicular fluids are rich in low-molecular weight metabolites which are responsible for the maturation of oocytes. The metabolomic approaches are powerful tools to study biochemical markers of oocyte quality in the follicular fluids. It is necessary to identify and quantify the reliable metabolites in follicular fluids reflecting oocyte developmental potential. The goal of this study is to conduct a metabolomic analysis of the follicular fluids in women of different ages and study the metabolomic profile of the follicular fluids in relationship with oocyte quality in assisted reproductive technology (ART) treatment. A total of 30 women seeking for ART treatment at the Women's Hospital, Zhejiang University School of Medicine from October 2014 to April 2015 were recruited for the present study. Fifteen women aged from 39 to 47 were grouped as advanced maternal age, and the other 15 women aged from 27 to 34, as young controls. Ovarian stimulation and oocyte retrieval were conducted using a regular protocol involving mid-luteal pituitary down-regulation and controlled ovarian stimulation. Follicular fluids from mature follicles were collected and centrifuged for analyses. Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography-Mass Spectroscopy (GC-MS) were used to perform the quantitative metabolomic analysis. The follicular fluid levels of 311 metabolites and the metabolic significance were assessed. 70 metabolites showed significant differences between women with young and advanced ages. Follicular fluids from women with advanced age showed significantly higher levels of creatine, histidine, methionine, trans-4-hydroxyproline, choline, mevalonate, N2,N2-dimethylguanosine and gamma-glutamylvaline, as compared to those from the young age group. 8 metabolites were found significantly correlated with maternal age positively. Moreover, 3 metabolites were correlated with the number of oocytes retrieved, and 5 metabolites were correlated with cleaved embryo numbers, both negatively. The follicular fluids from women undergoing ART treatment exhibited age-dependent metabolomic profile. Metabolites associated with oocyte quality were identified, suggesting them as potential biomarkers for oocyte maturation and ART outcomes.


Asunto(s)
Líquido Folicular , Recuperación del Oocito , Femenino , Líquido Folicular/metabolismo , Humanos , Masculino , Metabolómica , Oocitos/fisiología , Técnicas Reproductivas Asistidas
10.
Ecotoxicol Environ Saf ; 233: 113340, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35228029

RESUMEN

Thiophenol, which is a highly toxic sulfhydryl compound widely used in chemical industry, is an environmental pollutant that threatens human health significantly. It is of great importance to detect highly toxic thiophenols in both environmental and biological system. Thus, the need to develop rapid response, selective and sensitive probes is urgent. In this study, a novel probe was presented for the detection of thiophenols based on an intramolecular charge transfer (ICT) mechanism. This probe exhibits rapid response, broad pH adaptation (2-10), highly selectivity, a large Stokes shift (131 nm) and 40-fold enhancement in fluorescence. Besides, this probe showed low toxicity towards human cell HEK293 and could be applied to detect thiophenol both in living cells, zebrafish and environmental water samples with good recovery (over 94%). All the results indicated that this probe could be a promising sensor for applications for thiophenol derivatives detection in both environmental and biological sciences.


Asunto(s)
Colorantes Fluorescentes , Pez Cebra , Animales , Colorantes Fluorescentes/química , Células HEK293 , Humanos , Concentración de Iones de Hidrógeno , Fenoles , Compuestos de Sulfhidrilo , Agua
12.
Nat Biotechnol ; 40(2): 189-193, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33927418

RESUMEN

Prime editors have been delivered using DNA or RNA vectors. Here we demonstrate prime editing with purified ribonucleoprotein complexes. We introduced somatic mutations in zebrafish embryos with frequencies as high as 30% and demonstrate germline transmission. We also observed unintended insertions, deletions and prime editing guide RNA (pegRNA) scaffold incorporations. In HEK293T and primary human T cells, prime editing with purified ribonucleoprotein complexes introduced desired edits with frequencies of up to 21 and 7.5%, respectively.


Asunto(s)
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Pez Cebra , Animales , Sistemas CRISPR-Cas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Edición Génica , Células HEK293 , Humanos , ARN Guía de Kinetoplastida/genética , Ribonucleoproteínas/genética , Pez Cebra/genética
13.
Biomater Res ; 25(1): 40, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34819167

RESUMEN

Intrauterine adhesion (IUA) is a common gynaecological disease that develops from infection or trauma. IUA disease may seriously affect the physical and mental health of women of childbearing age, which may lead to symptoms such as hypomenorrhea or infertility. Presently, hysteroscopic transcervical resection of adhesion (TCRA) is the principal therapy for IUAs, although its function in preventing the recurrence of adhesion and preserving fertility is limited. Pharmaceuticals such as hormones and vasoactive agents and the placement of nondegradable stents are the most common postoperative adjuvant therapy methods. However, the repair of injured endometrium is relatively restricted due to the different anatomical structures of the endometrium. Recently, the treatment outcome of IUAs has improved with the advancement of hysteroscopic techniques. In particular, the application of bioactive scaffolds combined with tissue engineering technology has proven to have high therapeutic potential or endometrial repair in IUA treatment. Herein, this review has summarized past therapeutic strategies, including postoperative adjuvant therapy, cell or therapeutic molecular delivery therapy methods and bioactive scaffold-based tissue engineering methods. Therefore, this review presented the recent therapeutic strategies for repairing endometrium treatment and pointed out the issues of clinical concern to provide alternative methods for the management of IUAs.

14.
Bioorg Chem ; 116: 105391, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34607279

RESUMEN

The development of novel fluorescent dyes for bio-thiol is of great importance in biological, clinical and pharmaceutical sciences. Given the importance of bio-thiol anticipating in numerous physiological processes, there is a great need to construct fluorescent biosensors with high quality to detect them. Fluorophores, especially those used in bio-system, usually require high-quality properties such as high brightness, good water solubility, bio-compatible and photostability. Herein, we reported a novel fluorescent probe based on piperazine-coumarin scaffold with enhanced brightness and solubility. To further demonstrate the potential clinical applications, we performed living cell fluorescence image and human esophageal carcinoma diagnosis. The result indicated that we were able to distinguish pathological tissue from normal tissue by applying this probe. Thus, we hope this design will be helpful to develop high-quality fluorophores for clinical diagnosis.


Asunto(s)
Cumarinas/química , Neoplasias Esofágicas/diagnóstico por imagen , Carcinoma de Células Escamosas de Esófago/diagnóstico por imagen , Colorantes Fluorescentes/química , Piperazina/química , Colorantes Fluorescentes/síntesis química , Células HEK293 , Humanos , Estructura Molecular , Solubilidad , Espectrometría de Fluorescencia
15.
Turk J Gastroenterol ; 32(4): 382-392, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-34231485

RESUMEN

BACKGROUND: Ulcerative colitis, as a kind of inflammatory bowel disease (IBD) is characterized by abdominal pain. This study aimed to investigate the effect of icariin (ICA) on the intestinal microflora of colitis mice. METHODS: Fifteen female C57BL/6 mice were randomly divided into the Control group, dextran sodium sulfate (DSS)-induced colitis (DSS) group, and ICA treatment (DSS+ICA) group. The severity of inflammation in DSS-induced colitis mice was evaluated using disease activity scoring (considering weight-loss percentage, stool-shape change, and stool-bleeding scoring). Pathological changes of mice intestinal tract were evaluated using hematoxylin-eosin (HE) staining. Serum levels of TNF-α and IL-6 were detected with enzyme-linked immunosorbent assay. Expressions of p65 and p-p65 (p-p65/p65 ratio) were analyzed using Western blot assay. 16S rDNA sequencing was used to analyze the abundance and composition of intestinal microflora. RESULTS: Compared with DSS group, ICA significantly improved disease activity (P < .05) and reduced inflammatory damage of colon tissues (P < .05) in DSS-induced colitis mice. Compared with the DSS group, mice in the ICA group demonstrated significant weight and colon length (P < .05). ICA significantly inhibited expressions of IL-6 and TNF-α compared to the DSS group (P < .05). p-p65/ p65 ratio in the DSS + ICA group was remarkably enhanced compared to the DSS group (P < .05). ICA significantly reduced the proportion and activity of Bacteroides, Helicobacteraceae, Turicibacter, and significantly increased that of beneficial microflora (Lactobacillus, Lachnospiraceae, Akkermansia), so as improved damages of colon tissues. CONCLUSION: ICA can improve intestinal flora abundance and composition of DSS-induced colitis mice, and inhibit tissue damage and inflammatory response through modulating the p-p65/p65 expression.


Asunto(s)
Colon/efectos de los fármacos , Sulfato de Dextran/toxicidad , Flavonoides/farmacología , Microbioma Gastrointestinal , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Modelos Animales de Enfermedad , Femenino , Inflamación , Interleucina-6/sangre , Ratones , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/sangre
16.
Cell Biosci ; 11(1): 125, 2021 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-34233737

RESUMEN

BACKGROUND: Endometriosis is an oestrogen-dependent disease with an unclear aetiology and pathogenesis affecting 6-10% of the global female population, predominantly those of reproductive age. Herein, we profile the transcriptomes of approximately 55,000 single cells from three groups including ectopic endometrium, eutopic endometrium from women with endometriosis, and eutopic endometrium from healthy women to create a single-cell transcriptome atlas of endometriosis. RESULTS: We have identified 9 cell types and performed single-cell analysis of fibroblasts, and determined a potential developmental trajectory associated with endometriosis. We also identified fibroblast subpopulations related to endometriosis development and found that StAR played an important role in this process. Moreover, T cells in endometriosis were less activated or inflammatory with decreased effector CD8 + T cells, while the composition ratio of natural killer cells decreased and the percentage of monocytes/macrophages increased in endometriosis cysts. In addition, the effectiveness of immune cells in endometriosis lesions, eutopic endometrium from women with endometriosis, and eutopic endometrium from healthy women was distinct. Cell-cell interaction analyses highlighted the imbalanced immune environment in endometriosis lesions and immune cells in endometriosis could promote the development of the disease. CONCLUSION: Our study provided a systematic characterisation of endometriosis and insights into the aetiology and pathology of endometriosis.

17.
Reprod Biol Endocrinol ; 19(1): 111, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-34266426

RESUMEN

BACKGROUND: Endometriosis is a benign gynecological disease that shares some characteristics with malignant tumors and affects approximately 10% of women of reproductive age. Endometrioma refers to endometriosis that appears in the ovary. Metallopanstimulin-1 (MPS-1) is a component of the 40S subunit of ribosomes that has extra-ribosomal functions that contribute to the development of diseases. This study aimed to explore the expression pattern and role of MPS-1 in endometrioma development. METHODS: Quantitative real time polymerase chain reaction, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay were used to determine the expression of MPS-1 in patients with endometrioma. Following the successful knockdown of MPS-1 by siRNA, CCK-8 assays, flow cytometry, and transwell assays were performed to detect ectopic endometrial stromal cells (EcESCs) proliferation, the rate of apoptosis, and cell cycle, migration, and invasion, respectively. Western blotting was used to explore the effect of MPS-1 knockdown on protein levels in the NF-κB signaling pathway. RESULTS: The expression of MPS-1 was significantly higher in endometrioma and the serum of endometrioma patients than in the patients without endometriosis. In addition, the downregulation of MPS-1 expression inhibited EcESCs proliferation, migration, and invasion. This downregulation led to the arrest of the EcESCs cycle in the G0/G1 phase and apoptosis and depressed the NF-κB signaling pathway. CONCLUSION: MPS-1 can regulate EcESCs proliferation, motility, invasion, apoptosis, and cell cycle via the NF-κB signaling pathway in endometrioma. This may contribute to the formation or development of endometriotic foci. This study suggests the potential role of MPS-1 in the pathogenesis of endometriosis and enabled further research into the use of MPS-1 in the clinical diagnosis of endometrioma.


Asunto(s)
Proteínas de Ciclo Celular/biosíntesis , Endometriosis/metabolismo , Endometrio/metabolismo , FN-kappa B/biosíntesis , Proteínas Serina-Treonina Quinasas/biosíntesis , Proteínas Tirosina Quinasas/biosíntesis , Transducción de Señal/fisiología , Adulto , Proteínas de Ciclo Celular/genética , Células Cultivadas , Endometriosis/genética , Endometriosis/patología , Endometrio/patología , Femenino , Expresión Génica , Humanos , FN-kappa B/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Tirosina Quinasas/genética , Adulto Joven
18.
RNA ; 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33863818

RESUMEN

Thiamine pyrophosphate (TPP) riboswitches regulate thiamine metabolism by inhibiting the translation of enzymes essential to thiamine synthesis pathways upon binding to thiamine pyrophosphate in cells across all domains of life. Recent work on the Arabidopsis thaliana TPP riboswitch suggests a multi-step TPP binding process involving multiple riboswitch configurational ensembles and that Mg2+ dependence underlies the mechanism of TPP recognition and subsequent transition to the expression-inhibiting state of the aptamer domain followed by changes in the expression platform. However, details of the relationship between TPP riboswitch conformational changes and interactions with TPP and Mg2+ ¬¬in the aptamer domain constituting this mechanism are unknown. Therefore, we integrated single-molecule multiparameter fluorescence and force spectroscopy with atomistic molecular dynamics simulations and found that conformational transitions within the aptamer domain's sensor helices associated with TPP and Mg2+ ligand binding occurred between at least five different ensembles on timescales ranging from µs to ms. These dynamics are orders of magnitude faster than the 10 second-timescale folding kinetics associated with expression-state switching in the switch sequence. Together, our results show that a TPP and Mg2+ dependent mechanism determines dynamic configurational state ensemble switching of the aptamer domain's sensor helices that regulates the stability of the switch helix, which ultimately may lead to the expression-inhibiting state of the riboswitch. Additionally, we propose that two pathways exist for ligand recognition and that this mechanism underlies a kinetic rheostat-like behavior of the Arabidopsis thaliana TPP riboswitch.

19.
Nutr Cancer ; 73(10): 1849-1855, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33016141

RESUMEN

Although the relationship between tea consumption and the risk of endometrial cancer has been previously analyzed in certain studies, the resulting information is still conflicting, and a previous meta-analysis yielded inconsistent results. Therefore, here, we aimed to perform an updated meta-analysis of studies on this subject in order to elucidate this relationship.We searched the literature on the PubMed, Web of Science, Scopus, and Chinese National Knowledge Infrastructure databases for studies that were published prior to September 25, 2019, and all the relevant references were examined. Ultimately, we included eight studies, and seven of them were on black tea. We used the overall relative risk values (RR) and 95% confidence intervals (CI) to evaluate the risk. The synthetic RR of the eight eligible studies demonstrated that tea consumption was not relevant to the incidence rate of endometrial cancer (RR 1.06, 95% CI 0.96, 1.18). No publication bias was found. We detected significant heterogeneity among the studies (Q = 15.84, p = 0.027, I2 = 55.8%). In conclusion, the results of this meta-analysis indicate that tea consumption is not relevant to the incidence of endometrial cancer. Further research and cohort studies should be conducted to validate our result.


Asunto(s)
Camellia sinensis , Neoplasias Endometriales , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/etiología , Humanos , Incidencia , Riesgo , Factores de Riesgo ,
20.
PeerJ ; 8: e10171, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33354413

RESUMEN

The purpose of this study was to integrate the existing expression profile data on endometriosis (EM)-related tissues in order to identify the differentially expressed genes. In this study, three series of raw expression data were downloaded from GEO database. Differentially expressed genes (DEGs) in three tissue types were screened. GO, KEGG pathway enrichment analysis, core differential genes (CDGs) protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA) were performed, finally, the dysregulation of Hippo pathway in ectopic endometrium (EC) was detected by Western blotting. A total of 1,811 DEGs between eutopic (EU) and normal endometrium (NE), 5,947 DEGs between EC and EU, and 3,192 DEGs between EC and NE datasets were identified. After screening, 394 CDGs were obtained, and 5 hub genes identified in the PPI network. CDGs enrichment and WGCNA network analysis revealed cell proliferation, differentiation, migration and other biological processes, Hippo and Wnt signaling pathways, and a variety of tumor-related pathways. Western blotting results showed that YAP/TAZ was upregulated, and MOB1, pMOB1, SAV1, LATS1 and LATS2 were downregulated in EC. Moreover, CDGs, especially the hub genes, are potential biomarkers and therapeutic targets. Finally, the Hippo pathway might play a key role in the development of endometriosis.

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