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1.
J Cell Mol Med ; 28(8): e18303, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38613362

RESUMEN

Curcuma longa, best known for its culinary application as the main constituent of curry powder, has shown potential impact on the reproductive system. This study aimed to investigate the efficacy of Curcuma longa extract (CLE) on Kidney-Yang deficiency mice induced by hydrocortisone and the possible roles in testosterone secretion in Leydig cells. We evaluated male sexual behaviour, reproductive organ weight, testosterone levels, and histological tissue changes in hydrocortisone-induced mice. CLE effectively reversed hydrocortisone-induced Kidney-Yang deficiency syndrome by improving sexual behaviour, testis and epididymis weight, testosterone levels and reducing pathological damage. Our in vitro study further indicated that CLE stimulated testosterone production via upregulating the mRNA and protein expression of steroidogenic enzymes in Leydig cells. It significantly improved H89-inhibited protein expression of StAR and cAMP-response element-binding (CREB), as well as melatonin-suppressed StAR protein expression. The data obtained from this study suggest that CLE could alleviate Kidney-Yang deficiency symptoms and stimulate testosterone production by upregulating the steroidogenic pathway. This research identifies CLE as a potential nutraceutical option for addressing testosterone deficiency diseases.


Asunto(s)
Glomerulonefritis , Extractos Vegetales , Testosterona , Masculino , Animales , Ratones , Células Intersticiales del Testículo , Curcuma , Hidrocortisona , Deficiencia Yang
2.
Twin Res Hum Genet ; 27(2): 80-84, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38634508

RESUMEN

Gestational diabetes mellitus (GDM) is a frequent complication of pregnancy. The specific mechanisms underlying GDM have not yet been fully elucidated. Contemporary research indicates a potential association between liver enzyme irregularities and an increased risk of metabolic disorders, including diabetes. The alanine aminotransferase (ALT) level is recognized as a sensitive marker of liver injury. An increase in ALT levels is hypothesized to be linked to the pathogenesis of insulin resistance and diabetes. Nonetheless, the definitive causal link between ALT levels and GDM still needs to be determined. This investigation utilized two-sample Mendelian randomization (MR) to examine the genetic causation between alanine aminotransferase (ALT) and GDM. We acquired alanine aminotransferase (ALT)-related GWAS summary data from the UK Biobank, Million Veteran Program, Rotterdam Study, and Lifeline Study. Gestational diabetes data were obtained from the FinnGen Consortium. We employed various MR analysis techniques, including inverse-variance weighted (IVW), MR Egger, weighted median, simple, and weighted weighting. In addition to MR-Egger intercepts, Cochrane's Q test was also used to assess heterogeneity in the MR data, and the MR-PRESSO test was used to assess horizontal pleiotropy. To assess the association's sensitivity, a leave-one-out approach was employed. The IVW results confirmed the independent risk factor for GDM development, as indicated by the ALT level (p = .011). As shown by leave-one-out analysis, horizontal pleiotrophy did not significantly skew the causative link (p > .05). Our dual-sample MR analysis provides substantiated evidence of a genetic causal relationship between alanine aminotransferase (ALT) levels and gestational diabetes.


Asunto(s)
Alanina Transaminasa , Diabetes Gestacional , Análisis de la Aleatorización Mendeliana , Humanos , Femenino , Diabetes Gestacional/genética , Diabetes Gestacional/sangre , Diabetes Gestacional/epidemiología , Alanina Transaminasa/sangre , Alanina Transaminasa/genética , Embarazo , Estudio de Asociación del Genoma Completo , Factores de Riesgo , Adulto , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad
3.
J Obstet Gynaecol Res ; 50(8): 1317-1333, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38923718

RESUMEN

BACKGROUND: Gestational Diabetes Mellitus (GDM) poses significant risks to maternal and fetal health. Current diagnostic methods based on glucose tolerance tests have limitations for early detection. tRNA-derived small RNAs (tsRNAs) have emerged as potential molecular regulators in various diseases, including metabolic disorders. However, the diagnostic value of tsRNAs in plasma for early GDM or postpartum remains unclear. METHODS: This longitudinal study profiled the expression of tsRNAs across different gestational stages and postpartum in women with GDM (n = 40) and healthy control gestational women (HCs, n = 40). High-throughput small RNA sequencing identified candidate tsRNAs, which were then validated and correlated with clinical biochemical markers such as fasting blood glucose (FBG), HOMA-IR, and GHbA1c. RESULTS: tRF-1:32-Val-AAC-1-M6, tRF-1:31-Glu-CTC-1-M2, and tRF-1:30-Gly-CCC-1-M4 were consistently upregulated in the GDM group compared to HCs during the second trimester (p < 0.05). Only tRF-1:31-Glu-CTC-1-M2 was highly expressed during the first trimester, and tRF-1:30-Gly-CCC-1-M4 increased during postpartum. tRF-1:31-Glu-CTC-1-M2 showed a significant correlation with FBG levels in the first trimester (R = 0.317, p = 0.047). The expression of tRF-1:30-Gly-CCC-1-M4 was significantly correlated with HOMA-IR (r = 0.65, p < 0.001) and GHBA1c (r = 0.33, p = 0.037) during postpartum. A joint diagnostic model incorporating tsRNAs expression and clinical markers demonstrated enhanced predictive power for GDM (ROC AUC = 0.768). CONCLUSION: Our results revealed distinct expression patterns of specific tsRNAs in GDM, showcasing their correlation with key metabolic parameters. This underscores their promising role as biomarkers for early prediction and diagnosis of GDM. The integration of tRFs into a composite biomarker panel holds the potential to improve clinical outcomes by enabling personalized risk assessment and targeted interventions.


Asunto(s)
Diabetes Gestacional , ARN de Transferencia , Humanos , Femenino , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/metabolismo , Diabetes Gestacional/sangre , Embarazo , Adulto , Estudios Longitudinales , ARN de Transferencia/sangre , ARN de Transferencia/genética , Biomarcadores/sangre , Biomarcadores/metabolismo
4.
J Clin Lab Anal ; 37(3): e24826, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36701562

RESUMEN

OBJECTIVE: To explore the relationship between 25(OH)D3 and circular RNAs (circRNAs) in the early diagnosis of gestational diabetes mellitus (GDM) and to screen for biological markers for early prediction of GDM. METHODS: A cohort study was conducted using samples and data collected from pregnant women registered at the Li Huili hospital in China between April 2018 and January 2020. Four circRNAs (hsa_circ_0003218, hsa_circ_0002968, hsa_circ_0007430, and hsa_circ_0006260) were selected as potential biomarkers, and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure their concentration in the serum and to analyze their correlation with 25(OH)D3. The Pearson correlation test was used to assess the correlation between the 25(OH)D3, circRNAs, and various clinical variables. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic value of circRNAs and 25(OH)D3 in the early stage of pregnancy. RESULTS: Weight, body mass index (BMI), triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and 25(OH)D3 were found to be risk factors for GDM. The level of 25(OH)D3 correlated significantly with HDL-C with a correlation coefficient of 0.298 (p < 0.05). The expression of hsa_circ_0003218 was significantly downregulated in the GDM group (p < 0.05). Hsa_circ_0002968, hsa_circ_0007430, and hsa_circ_0006260 did not show any differential expression between the two groups (p > 0.05). Furthermore, hsa_circ_0003218 level correlated significantly with 25(OH)D3 and the correlation coefficient was 0.357 (p < 0.05). The AUC of hsa_circ_0003218 combined with 25(OH)D3 was 0.789 ([0.700-0.877], p < 0.001), with sensitivity and specificity of 63.04% and 80.65%, respectively. CONCLUSIONS: Hsa_circ_0003218 and 25(OH)D3 may jointly participate in the metabolic process of GDM. Thus, the combination of 25(OH)D3 and hsa_circ_0003218 represents a potential biomarker for the prediction of GDM in the early stages of pregnancy.


Asunto(s)
Diabetes Gestacional , ARN Circular , Humanos , Femenino , Embarazo , Estudios de Cohortes , Biomarcadores , Diagnóstico Precoz , Colesterol
5.
Int J Mol Sci ; 24(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37175755

RESUMEN

Thyroid cancer (TC) is the most common endocrine malignancy. Recently, the global incidence of TC has increased rapidly. Differentiated thyroid cancer includes papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), which are the most common types of TC. Although PTCs and FTCs exert good prognoses and high survival rates, FTCs tend to be more aggressive than PTCs. There is an urgent need to improve patient outcomes by developing effective therapeutic agents for FTCs. Piperlongumine exerts anti-cancer effects in various human carcinomas, including human anaplastic TCs and PTCs. However, the anti-cancer effects of piperlongumine in FTCs and the underlying mechanisms are yet to be elucidated. Therefore, in the present study, we evaluated the effect of piperlongumine on cell proliferation, cell cycle, apoptosis, and autophagy in FTC cells with flowcytometry and Western blot. We observed that piperlongumine caused growth inhibition, cell cycle arrest, apoptosis induction, and autophagy elevation in FTC cells. Activities of reactive oxygen species and the downstream PI3K/Akt pathway were the underlying mechanisms involved in piperlongumine mediated anti-FTC effects. Advancements in our understanding of the effects of piperlongumine in FTC hold promise for the development of novel therapeutic strategies.


Asunto(s)
Adenocarcinoma Folicular , Neoplasias de la Tiroides , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Adenocarcinoma Folicular/patología , Transducción de Señal , Neoplasias de la Tiroides/patología , Apoptosis , Autofagia
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(5): 582-587, 2023 May 10.
Artículo en Zh | MEDLINE | ID: mdl-37102294

RESUMEN

OBJECTIVE: To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome (MNS). METHODS: A fetus with MNS diagnosed at Ningbo Women and Children's Hospital in November 2020 was selected as the study subject. Clinical data was collected. Pathogenic variant was screened by using trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation, bilateral femur curvature, omphalocele, single umbilical artery, and oligohydramnios. Trio-WES revealed that the fetus has harbored hemizygous c.3562G>A (p.A1188T) missense variant of the FLNA gene. Sanger sequencing confirmed that the variant was maternally derived, whilst its father was of a wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION: The hemizygous c.3562G>A (p.A1188T) variant of the FLNA gene probably underlay the structural abnormalities in this fetus. Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.


Asunto(s)
Anomalías Múltiples , Osteocondrodisplasias , Niño , Femenino , Humanos , Embarazo , Anomalías Múltiples/genética , Retardo del Crecimiento Fetal , Feto , Filaminas/genética , Asesoramiento Genético , Mutación
7.
Gynecol Endocrinol ; 38(1): 50-54, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34665686

RESUMEN

OBJECTIVE: To explore the relationship between circular RNA (circRNA) in gestational diabetes mellitus (GDM) and the metabolic profile at the molecular level, and find a biological marker that can predict GDM early. METHODS: A retrospective case-control study was conducted using data and samples from women treated at a hospital in China between January 10 2018 and February 20 2019. Reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of hsa_circRNA_102682 in serum and analyze its correlation with lipid metabolism parameters. RESULTS: Advanced age and higher pre-pregnancy body mass index (BMI) during pregnancy are risk factors for GDM. The expression level of hsa_circ_102682 was lower among the cases than the controls (p=.000). The levels of triglyceride, apolipoprotein A1 (APOA1), APOB, and high-density lipoprotein cholesterol (HDL-C) were different between the controls and cases (p<.05). Hsa_circRNA_102682 was significantly correlated with triglycerides, APOA1, APOB, 1-h blood glucose in the serum of GDM patients, and the correlation coefficients were 0.319, 0.314, 0.286, and 0.311, respectively (p<.05). The area under the receiver operating characteristic curve is 0.684 (95% confidence interval 0.611-0.756, p=.0001). CONCLUSIONS: Hsa_circRNA_102682 may regulate lipid metabolism, participate in the pathogenesis of GDM. It can be used as a marker to predict GDM.


Asunto(s)
Diabetes Gestacional/sangre , Metabolismo de los Lípidos/genética , ARN Circular/sangre , Albúmina Sérica Humana/genética , Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Glucemia/análisis , Estudios de Casos y Controles , China , HDL-Colesterol/sangre , Diabetes Gestacional/genética , Femenino , Expresión Génica , Humanos , Embarazo , ARN Circular/genética , Estudios Retrospectivos , Triglicéridos/sangre
8.
Reprod Biol Endocrinol ; 19(1): 158, 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34641897

RESUMEN

BACKGROUND: Synchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol. METHODS: This RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate. RESULTS: Both groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0-13.0] vs. 11.0 [7.0-14.8], P = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups. CONCLUSION: This large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800019730 . Registered 26 November 2018.


Asunto(s)
Fertilización In Vitro , Antagonistas de Hormonas/administración & dosificación , Inducción de la Ovulación/métodos , Inyecciones de Esperma Intracitoplasmáticas , Aborto Espontáneo/epidemiología , Adulto , Esquema de Medicación , Femenino , Fertilización In Vitro/métodos , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Humanos , Recién Nacido , Infertilidad/epidemiología , Infertilidad/terapia , Masculino , Ovulación/efectos de los fármacos , Ovulación/fisiología , Embarazo , Resultado del Embarazo/epidemiología , Índice de Embarazo , Inyecciones de Esperma Intracitoplasmáticas/métodos
9.
Gynecol Endocrinol ; 37(7): 665-671, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34126831

RESUMEN

OBJECTIVES: MicroRNAs (miRNAs) are potentially involved in the regulation of glucose and lipid metabolism. The aim of this study was to investigate potential miRNA regulators for serum lipids and blood glucose in gestational diabetes mellitus. METHODS: Plasma samples were obtained from 53 women with GDM and 46 normal pregnant women. Fasting blood glucose and a blood lipid profile were measured. Plasma miRNA expression profiles were analyzed using microarray. To verify the microarray data, the expression of miRNAs was evaluated by real-time PCR. Gene ontology (GO) and genes and genomics (KEGG) pathway enrichment of the predicted target genes of miRNAs were analyzed. RESULTS: The miRNA expression profiles of plasma samples from healthy and GDM women are distinct. We identified 93 differently expressed miRNAs. Compared with healthy pregnant women, 48 miRNAs including miR-574-5p and miR-3135b exhibited significantly lower expression in plasma samples from GDM patients. The expression of miR-574-5p was significantly correlated with levels of blood glucose and LDL-C; miR-3135b was significantly correlated with HDL-C. Some predicted common target genes of these two miRNAs are associated with the metabolism of glucose and lipids as well as the insulin signaling pathway. CONCLUSIONS: miR-574-5p and miR-3135b may serve as metabolic regulators of glucose and lipids for GDM.


Asunto(s)
Glucemia/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Diabetes Gestacional/metabolismo , MicroARNs/metabolismo , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Metabolismo de los Lípidos , Embarazo , Estudios Retrospectivos , Transcriptoma
11.
Materials (Basel) ; 17(6)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38541396

RESUMEN

To enhance the performance of ultra-high voltage power fittings in severe weather conditions without altering their current structure, the high-strength and toughness aluminum alloys were rationally selected to study the optimization of the die-casting process. This approach aims to improve the overall longevity and function of the power fittings in extreme climates. First of all, the propose of this study is to use the material's strength-toughness product (STP) concept to evaluate the material stability of the power fitting impact resistance and fatigue toughness in order to determine the appropriate material selection. Secondly, the location of the mold's sprue and gate was optimized through finite element simulation to prevent gas volume and flow defects during the casting process. This improves the material's toughness and anti-fatigue failure characteristics of the product. Then, vacuum equipment and a vacuum valve auxiliary system were added based on the existing die-casting machine, and the mold structure was optimized to enable the vacuum die-casting process. Finally, a water-based boron nitride environmentally friendly mold release agent was used to solve demolding difficulties with an A356 aluminum alloy and improve mold lubrication and surface quality. The production of quad-bundled spacers using A356 and vacuum die casting has resulted in parts with a tensile strength of at least 250 MPa and an elongation of no less than 7%. This improvement has laid a foundation for enhancing the operational reliability of existing overhead transmission line fittings.

12.
PeerJ ; 12: e17751, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006037

RESUMEN

Background: Tumor deposits (TD) was a significant risk factor impacting the prognosis of patients diagnosed with gastric cancer (GC), yet it was not currently incorporated into TNM staging systems. The objective of this research was to develop a predictive model for assessing the prognosis of patients with TD-positive GC. Methods: Retrospective analysis was performed on the data of 4,972 patients treated for GC with D2 radical gastrectomy at Wannan Medical College's Yijishan Hospital between January 2012 and December 2021. The patients were categorized based on the number of TD (L1: 1, L2: 2-3, L3: ≥4) and the anatomical location of TD (Q1: single area, Q2: multiple areas). In a 3:1 ratio, patients were randomly assigned to one of two groups: training or validation. Results: The study included a total of 575 patients who were divided into the training group (n = 432) and validation group (n = 143). Survival analysis showed that the number and anatomical location of TD had a significant impact on the prognosis of patients with TD-positive GC. Univariate analysis of the training group data revealed that tumor size, T-stage, N-stage, histological grade, number and distribution of TD, neural invasion, and postoperative chemotherapy were associated with prognosis. Multivariate Cox regression analysis identified poor histological grade, T4 stage, N3 stage, number of TD, neural invasion, and postoperative chemotherapy as independent prognostic factors for GC patients with TD. A nomogram was developed using these variables, demonstrating well predictive ability for 1, 3, and 5-year overall survival (OS) in the validation set. The DCA curve shows that the constructed model shows a large positive net gain compared to the eighth edition Tumour, Node, Metastasis (TNM) staging system. Conclusion: The prognostic model developed for patients with TD-positive GC has a higher clinical utility compared to the eighth edition of TNM staging.


Asunto(s)
Gastrectomía , Estadificación de Neoplasias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Masculino , Femenino , Estudios Retrospectivos , Pronóstico , Persona de Mediana Edad , Anciano , Nomogramas , Análisis de Supervivencia , Adulto , Factores de Riesgo
13.
Artículo en Inglés | MEDLINE | ID: mdl-38743109

RESUMEN

RATIONALE: Clinical and preclinical studies have demonstrated that estradiol withdrawal after delivery is one of important factors involved in the pathogenesis of postpartum depression (PPD). The infralimbic cortex (IL) is related to anxiety and mood disorders. Whether IL neurons mediate PPD is still unclear. OBJECTIVES: This study was to observe the antidepressant effect and expression of BDNF and ß-catenin in IL by allopregnanolone (ALLO) treatment or the selective activation or inhibition of IL neurons using a chemogenetic approach in a pseudopregnancy model of PPD. METHODS: Administration of estradiol combined with progesterone and the abrupt withdrawal of estradiol simulated the pregnancy and early postpartum periods to induce depression in ovariectomized rats. The relative expression levels of ß-catenin and BDNF were observed by western blotting. RESULTS: Immobility time was significantly increased in the forced swim test and open-arm movement was reduced in the elevated plus maze test in the estradiol-withdrawn rats. After ALLO treatment, the immobility time were lower and open-arm traveling times higher than those of the estradiol-withdrawn rats. Meanwhile, the expression level of BDNF or ß-catenin in the IL was reduced significantly in estradiol-withdrawn rats, which was prevented by treatment with ALLO. The hM3Dq chemogenetic activation of pyramidal neurons in the IL reversed the immobility and open-arm travel time trends in the estradiol-withdrawal rat model, but chemogenetic inhibition of IL neurons failed to affect this. Upregulated BDNF and ß-catenin expression and increased c-Fos in the basolateral amygdala were found following IL neuron excitation in model rats. CONCLUSIONS: Our results demonstrated that pseudopregnancy and estradiol withdrawal produced depressive-like behavior and anxiety. ALLO treatment or specific excitement of IL pyramidal neurons relieved abnormal behaviors and upregulated BDNF and ß-catenin expression in the IL in the PPD model, suggesting that hypofunction of IL neurons may be involved in the pathogenesis of PPD.

14.
Clin Epigenetics ; 16(1): 51, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38576048

RESUMEN

BACKGROUND: The intriguing connection between selenium and cancer resembles a captivating puzzle that keeps researchers engaged and curious. While selenium has shown promise in reducing cancer risks through supplementation, its interaction with epigenetics in cervical cancer remains a fascinating yet largely unexplored realm. Unraveling the intricacies of selenium's role and its interaction with epigenetic factors could unlock valuable insights in the battle against this complex disease. RESULT: Selenium has shown remarkable inhibitory effects on cervical cancer cells in various ways. In in vitro studies, it effectively inhibits the proliferation, migration, and invasion of cervical cancer cells, while promoting apoptosis. Selenium also demonstrates significant inhibitory effects on human cervical cancer-derived organoids. Furthermore, in an in vivo study, the administration of selenium dioxide solution effectively suppresses the growth of cervical cancer tumors in mice. One of the mechanisms behind selenium's inhibitory effects is its ability to inhibit histone demethylases, specifically JMJD3 and UTX. This inhibition is observed both in vitro and in vivo. Notably, when JMJD3 and UTX are inhibited with GSK-J4, similar biological effects are observed in both in vitro and in vivo models, effectively inhibiting organoid models derived from cervical cancer patients. Inhibiting JMJD3 and UTX also induces G2/M phase arrest, promotes cellular apoptosis, and reverses epithelial-mesenchymal transition (EMT). ChIP-qPCR analysis confirms that JMJD3 and UTX inhibition increases the recruitment of a specific histone modification, H3K27me3, to the transcription start sites (TSS) of target genes in cervical cancer cells (HeLa and SiHa cells). Furthermore, the expressions of JMJD3 and UTX are found to be significantly higher in cervical cancer tissues compared to adjacent normal cervical tissues, suggesting their potential as therapeutic targets. CONCLUSIONS: Our study highlights the significant inhibitory effects of selenium on the growth, migration, and invasion of cervical cancer cells, promoting apoptosis and displaying promising potential as a therapeutic agent. We identified the histone demethylases JMJD3 and UTX as specific targets of selenium, and their inhibition replicates the observed effects on cancer cell behavior. These findings suggest that JMJD3 and UTX could be valuable targets for selenium-based treatments of cervical cancer.


Asunto(s)
Selenio , Neoplasias del Cuello Uterino , Femenino , Humanos , Animales , Ratones , Selenio/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética , Metilación de ADN , Histona Demetilasas con Dominio de Jumonji/genética , Histona Demetilasas/genética
15.
Front Med (Lausanne) ; 11: 1369317, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38813375

RESUMEN

Introduction: Embryo implantation requires synchronous communication between the embryo and maternal endometrium. Inadequate maternal endometrial receptivity is one of the principal causes for embryo implantation failure [especially repeated implantation failure (RIF)] when biopsied good-quality euploid embryos are transferred. An RNA-seq-based endometrial receptivity test (rsERT) was previously established to precisely guide successful embryo implantation. In this study, we aimed to evaluate the effect of personalized embryo transfer (pET) via rsERT on the clinical outcomes in patients with RIF. Methods: A total of 155 patients with RIF were included in the present retrospective study and were divided into two groups: 60 patients who underwent rsERT and pET (Group rsERT) and 95 patients who underwent standard frozen embryo transfer (FET) without rsERT (Group FET). Reproductive outcomes were compared for patients who underwent rsERT-guided pET and standard FET. Results: Forty percent (24/60) of the patients who underwent rsERT were receptive, and the remaining 60% (36/60) were non-receptive. The positive human chorionic gonadotropin (ß-hCG) rate (56.3% vs. 30.5%, P = 0.003) and clinical pregnancy rate (43.8% vs. 24.2%, P = 0.017) were significantly higher in Group rsERT patients than in FET group patients. Additionally, Group rsERT patients also showed a higher implantation rate (32.1% vs. 22.1%, P = 0.104) and live birth rate (35.4% vs. 21.1%, P = 0.064) when compared with FET patients, although without significance. For subpopulation analysis, the positive ß-hCG rate, clinical pregnancy rate, implantation rate, and live birth rate of receptive patients were not statistically significant different from those of non-receptive patients. Conclusions: The rsERT can significantly improve the pregnancy outcomes of RIF patients, indicating the clinical potential of rsERT-guided pET.

16.
Front Immunol ; 15: 1367253, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38646533

RESUMEN

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.


Asunto(s)
Herpesvirus Bovino 1 , Mycoplasma bovis , Vacunas Atenuadas , Vacunas Combinadas , Animales , Bovinos , Herpesvirus Bovino 1/inmunología , Vacunas Combinadas/inmunología , Vacunas Combinadas/administración & dosificación , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/administración & dosificación , Mycoplasma bovis/inmunología , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/efectos adversos , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/efectos adversos , Citocinas/metabolismo , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Infecciones por Mycoplasma/prevención & control , Infecciones por Mycoplasma/veterinaria , Infecciones por Mycoplasma/inmunología , Vacunas Marcadoras/inmunología , Vacunas Marcadoras/administración & dosificación , Vacunación/veterinaria , Eficacia de las Vacunas , Inmunidad Humoral , Complejo Respiratorio Bovino/prevención & control , Complejo Respiratorio Bovino/inmunología , Complejo Respiratorio Bovino/virología
17.
Toxics ; 12(4)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38668498

RESUMEN

Metal sulfides in waste rocks and tailings are susceptible to serious soil and water contamination due to the generation of acid mine drainage (AMD) during stockpiling. The hydrometallurgical process is one of the most essential heavy metal remediation technologies through harmless disposal and resource utilization of the waste sulfides. However, atmospheric hydrometallurgy of sulfides still faces great challenges due to low leaching efficiency and high cost. In this work, we proposed a cooperative leaching system (Fe2(SO4)3-O3) and investigated the oxidative dissolution process of sphalerite (ZnS). Under the optimal conditions, the extracted zinc reached 97.8%. Reactive oxygen species (ROS) (·OH, 1O2 and ·O2-) were identified in the radical quenching experiments. The dissolution of sphalerite did not show passivation due to the ozone's capability to oxidize the sulfur in sphalerite to sulfate. In addition, stirring rate, O3 inlet concentration, and Fe2(SO4)3 concentration had a significant effect on the dissolution of sphalerite. Meanwhile, the apparent activation energy was 24.11 kJ/mol based on kinetic fitting, which indicated that the controlling step of the reaction was mainly a diffusion process. This work demonstrated the cooperative effect of sphalerite leaching in the O3-Fe2(SO4)3 system and provided a theoretical reference for efficient and atmospheric dissolution of sphalerite.

18.
Molecules ; 18(9): 10944-52, 2013 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-24013408

RESUMEN

Chaetochromones A (1) and B (2), two novel polyketides, were isolated from the crude extract of fungus Chaetomium indicum (CBS.860.68) together with three known analogues PI-3(3), PI-4 (4) and SB236050 (5). The structures of these compounds were determined by HRESI-MS and NMR experiments. Chaetochromones A (1) and B (2) are a member of the polyketides family, which might originate from a similar biogenetic pathway as the known compounds PI-3 (3), PI-4 (4) and SB236050 (5). The biological activities of these secondary metabolites were evaluated against eight plant pathogens, including Alternaria alternata, Ilyonectria radicicola, Trichoderma viride pers, Aspergillus niger, Fusarium verticillioide, Irpex lacteus (Fr.), Poria placenta (Fr.) Cooke and Coriolus versicolor (L.) Quél. Compound 1 displayed moderate inhibitory rate (>60%) against the brown rot fungus Poria placenta (Fr.) Cooke, which causes significant wood decay. In addition, the cytotoxic activities against three cancer cell lines A549, MDA-MB-231, PANC-1 were also tested, without any inhibitory activities being detected.


Asunto(s)
Antifúngicos/química , Chaetomium/química , Cromonas/química , Policétidos/química , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Vías Biosintéticas , Línea Celular Tumoral , Chaetomium/metabolismo , Cromonas/aislamiento & purificación , Cromonas/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Hongos Mitospóricos/efectos de los fármacos , Conformación Molecular , Enfermedades de las Plantas/microbiología , Policétidos/aislamiento & purificación , Policétidos/farmacología
19.
Front Surg ; 10: 1182171, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37325415

RESUMEN

A 58-year-old male was admitted to the liver surgery ward of Peking Union Medical College Hospital as the result of recurrent cholangitis in the past six months. Preoperative abdominal CT and gastrointestinal radiography showed duodenal dilatation and reconstruction of gastrointestinal tract, which might be related to the laparotomy and hemostasis performed due to traffic accident 30 years ago. The operative method of that surgery might be the reason for the patient's choledocholithiasis and duodenal dilatation.

20.
Environ Sci Pollut Res Int ; 30(5): 12508-12520, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36109483

RESUMEN

Characterizing the anomalous diffusion behavior of sediment transport is a key factor in calculating sediment concentration. This study attempts to seek an equation that captures the nonlocal movement feature of the transport of an ensemble of sediment particles on ice-covered channels with a steady uniform flow field. Given that the fractional advection-dispersion equation with a noninteger order on the space term is nonlocal and able to describe the long-distance transport, a mathematical model with the Caputo fractional derivative is proposed to estimate the vertical diffusion of suspended sediment particles in the ice-covered channel. Results show that the fractional derivative model has a good predictive ability to the suspended sediment concentration as compared to the measurements. Especially in regions close to the undersurface of the ice cover, the proposed model matches better with experiments than the existing analytical model. Sensitivity analyses indicate that the strength of the turbulent diffusion effect dominates the uniformity of the sediment concentration profile. Besides, the sediment concentration is more sensitive to the variation of the boundary roughness than to the change of the sediment settling velocity. It should be noted that the sediment concentration reduces with the decrease of the order of the fractional derivative, which differs from the findings in previous studies.


Asunto(s)
Sedimentos Geológicos , Cubierta de Hielo , Modelos Teóricos , Difusión
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