RESUMEN
Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.
Asunto(s)
Factores de Transcripción Forkhead , Ovario , Animales , Femenino , Humanos , Ratones , Factores de Transcripción Forkhead/genética , Perfilación de la Expresión Génica , Células de la Granulosa/metabolismo , Oocitos/metabolismo , Ovario/metabolismo , Proteínas Represoras/metabolismo , Factores de Transcripción/metabolismo , Insuficiencia Ovárica Primaria/genética , Insuficiencia Ovárica Primaria/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Envejecimiento/genéticaRESUMEN
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the immunofluorescence data shown in Fig. 2G, the mitochondria and lysosomestained images in Fig. 3C, the JC1 staining images in Fig. 4C and the immunofluorescence data in Fig. 5G were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time. In view of the fact that certain of the abovementioned data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 37223734, 2018; DOI: 10.3892/mmr.2018.8371].
RESUMEN
Background: Immune checkpoint inhibitors are a promising therapeutic strategy for breast cancer (BRCA) patients. The tumor microenvironment (TME) can downregulate the immune response to cancer therapy. Our study is aimed at finding a TME-related biomarker to identify patients who might respond to immunotherapy. Method: We downloaded raw data from several databases including TCGA and MDACC to identify TME hub genes associated with overall survival (OS) and the progression-free interval (PFI) by WGCNA. Correlations between hub genes and either tumor-infiltrating immune cells or immune checkpoints were conducted by ssGSEA. Result: TME-related green and black modules were selected by WGCNA to further screen hub genes. Random forest and univariate and multivariate Cox regressions were applied to screen hub genes (MYO1G, TBC1D10C, SELPLG, and LRRC15) and construct a nomogram to predict the survival of BRCA patients. The C-index for the nomogram was 0.713. A DCA of the predictive model revealed that the net benefit of the nomogram was significantly higher than others and the calibration curve demonstrated a good performance by the nomogram. Only TBC1D10C was correlated with both OS and the PFI (both p values < 0.05). TBC1D10C also had a high positive association with tumor-infiltrating immune cells and common immune checkpoints (PD-1, CTLA-4, and TIGIT). Conclusion: We constructed a TME-related gene signature model to predict the survival probability of BRCA patients. We also identified a hub gene, TBC1D10C, which was correlated with both OS and the PFI and had a high positive association with tumor-infiltrating immune cells and common immune checkpoints. TBC1D10C may be a new biomarker to select patients who may benefit from immunotherapy.
Asunto(s)
Neoplasias de la Mama , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Proteínas de la Membrana/genética , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
Long noncoding RNA (lncRNA) plays a critical role in the development of tumors. The aim of our study was construction of a lncRNA signature model to predict breast cancer (BRCA) patient survival. We downloaded RNA-seq data and relevant clinical information from the Cancer Genome Atlas (TCGA) database. Differentially expressed lncRNA were computed using the "edgeR" package and subjected to the univariate and multivariate Cox regression analysis. Corresponding protein-coding genes were used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. Finally, 521 differentially expression lncRNA were obtained. We constructed a ten-lncRNA signature model (LINC01208, RP5-1011O1.3, LINC01234, LINC00989, RP11-696F12.1, RP11-909N17.2, CTC-297N7.9, CTA-384D8.34, CTC-276P9.4, and MAPT-IT1) to predict BRCA patient survival using the multivariate Cox proportional hazard regression model. The C-index was 0.712, and AUC scores of training, test, and entire sets were 0.746, 0.717, and 0.732, respectively. Univariate Cox regression analysis indicated that age, tumor status, N status, M status, and risk score were significantly related to overall survival in patients with BRCA. Further, the multivariate analysis showed that risk score and M status had outstanding independent prognostic values, both with p < 0.001. The Gene Ontology (GO) function and KEEG pathway analysis was primarily enriched in immune response, receptor binding, external surface of plasma membrane, signal transduction, cytokine-cytokine receptor interaction, and cell adhesion molecules (CAMs). Finally, we constructed a ten-lncRNA signature model that can serve as an independent prognostic model to predict BRCA patient survival.
Asunto(s)
Neoplasias de la Mama/genética , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante/genética , Calibración , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Sistemas de Lectura Abierta/genética , Pronóstico , Modelos de Riesgos Proporcionales , ARN Largo no Codificante/metabolismo , Reproducibilidad de los Resultados , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Acute appendicitis (AA) is one of the most common diseases faced by the surgeon in the emergency department. In clinical practice, how to diagnose patients with AA accurately is still challenging. METHODS: We conducted a prospective study of 84 patients who presented in the emergency department with suspected AA and measured fecal calprotectin (FC) value. The final diagnosis of AA was independently determined without reference to the test results of FC. Then, we retrospectively analyzed the FC value for identifying AA. RESULTS: FC value in patients with AA were significantly higher than that in patients without AA (240.5 vs. 68.5 ug/g, P < 0.001). Receiver-operating characteristic analyses demonstrated FC value to be highly sensitive and specific for the diagnosis of AA, as indicated by an overall area under the curve (AUC) of 0.928 (500 times of boot strap estimated 95% CI, 0.855-0.972), with an optimal cut off point of 106 ug/g. FC levels in 26 patients with simple AA were significantly lower than it in the 14 patients with suppurative AA (206 vs. 304ug/g, P = 0.001). CONCLUSIONS: FC test provides a sensitive, convenient and economical method to help facilitate the diagnosis of AA in emergency department. Especially for hospitals without computed tomography equipment or patients who are not suitable to exposed to radiation, FC test is of great significance for improving the diagnostic accuracy of AA.
Asunto(s)
Apendicitis/diagnóstico , Heces/química , Complejo de Antígeno L1 de Leucocito/análisis , Adulto , Anciano , Biomarcadores/análisis , Estudios de Casos y Controles , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Estudios RetrospectivosRESUMEN
Liraglutide is glucagonlike peptide1 receptor agonist used for treating patients with type 2 diabetes mellitus. The present study aimed to investigate the role and mechanism of liraglutide in repairing the infarcted heart following myocardial infarction. The results of the present study demonstrated that amplification of the dose of liraglutide for ~28 days was able to reduce cardiac fibrosis, inflammatory responses and myocardial death in the postinfarcted heart. In vitro, liraglutide protected cardiomyocyte mitochondria against the chronic hypoxic damage, inhibiting the mitochondrial apoptosis pathways. Mechanistically, liraglutide elevated the expression of NADdependent protein deacetylase sirtuin1 (SIRT1), which increased the expression of Parkin, leading to mitophagy activation. Protective mitophagy reversed cellular adenosine 5'triphosphate production, reduced cellular oxidative stress and balanced the redox response, sustaining mitochondrial homeostasis. Notably, following blockade of glucagonlike peptide 1 receptor or knockdown of Parkin, the beneficial effects of liraglutide on mitochondria disappeared. In conclusion, the results of the present study illustrated the protective role of liraglutide in repairing the infarcted heart via regulation of the SIRT1/Parkin/mitophagy pathway.
Asunto(s)
Liraglutida/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Sirtuina 1/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Apoptosis/efectos de los fármacos , Hipoxia de la Célula , Modelos Animales de Enfermedad , Liraglutida/farmacología , Masculino , Mitofagia/efectos de los fármacos , Infarto del Miocardio/patología , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Metformin (Met) is a widely used antidiabetic drug and has demonstrated interesting anticancer effects in various cancer models, alone or in combination with chemotherapeutic drugs. The aim of the present study is to investigate the synergistic effect of Met with cisplatin (Cis) on the tumor growth inhibition of gallbladder cancer cells (GBC-SD and SGC-996) and explore the underlying mechanism. Cells were treated with Met and/or Cis and subjected to cell viability, colony formation, apoptosis, cell cycle, western blotting, xenograft tumorigenicity assay and immunohistochemistry. The results demonstrated that Met and Cis inhibited the proliferation of gallbladder cancer cells, and combination treatment with Met and Cis resulted in a combination index < 1, indicating a synergistic effect. Co-treatment with Met and Cis caused G0/G1 phase arrest by upregulating P21, P27 and downregulating CyclinD1, and induced apoptosis through decreasing the expression of p-PI3K, p-AKT, and p-ERK. In addition, pretreatment with a specific AKT activator (IGF-1) significantly neutralized the pro-apoptotic activity of Met + Cis, suggesting the key role of AKT in this process. More importantly, in nude mice model, Met and Cis in combination displayed more efficient inhibition of tumor weight and volume in the SGC-996 xenograft mouse model than Met or Cis alone. Immunohistochemistry analysis suggests the combinations greatly suppressed tumor proliferation, which is consistent with our in vitro results. In conclusion, our findings indicate that the combination therapy with Met and Cis exerted synergistic antitumor effects in gallbladder cancer cells through PI3K/AKT/ERK pathway, and combination treatment with Met and Cis would be a promising therapeutic strategy for gallbladder cancer patients.
RESUMEN
Capacitive deionization (CDI) is an emerging technology that uniquely integrates energy storage and desalination. In this work, porous carbon nanosheets (PCNSs) with an ultrahigh specific surface area of 2853 m2/g were fabricated by the simple carbonization of starch followed by KOH activation for the electrode material of photovoltaic CDI. The CDI cell consisting of PCNSs electrodes exhibited a high salt adsorption capacity (SAC) of 15.6 mg/g at â¼1.1 V in 500 mg/L NaCl as well as high charge efficiency and low energy consumption. KOH activation played a key role in the excellent CDI performance as it not only created abundant pores on the surface of PCNSs but also made it fluffy and improved its graphitization degree, which are beneficial to the transport of ions and electrons. PCNSs are supposed to be a promising candidate for CDI electrode materials. The combination of solar cells and CDI may provide a new approach to reduce the energy cost of CDI and boost its commercial competitiveness.
Asunto(s)
Almidón , Purificación del Agua , Carbono , Electrodos , Porosidad , SalinidadRESUMEN
In this study, we sequenced and annotated the complete mitochondrial genome of Pampus argenteus (Perciformes: Stromateidae). The mitogenome is 17,098 bp in length, which contains 13 protein-coding genes, 2 rRNA genes, 23 tRNA genes and 2 non-coding regions: origin of light-strand replication (OL) and control region (D-loop). The overall nucleotide base composition of P. argenteus mtDNA is A 30.35%, C 25.55%, G 15.28% and T 28.82%, with an A + T content of 59.17%. Except for ND6 gene and eight tRNA genes, all other mitochondrial genes were encoded on the heavy strand. The mitochondrial genome of P. argenteus may be helpful to the studies on conservation genetics and stock evaluation of P. argenteus resource, as well as molecular phylogeny and species identification of Stromateidae.
Asunto(s)
Genoma Mitocondrial/genética , Perciformes/genética , Análisis de Secuencia de ADN , Animales , Genes de ARNr , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , ARN de Transferencia/genéticaRESUMEN
In this study, the complete mitochondrial genome of Pampus chinensis (Perciformes: Stromateidae) was determined. The mitogenome is 16,535 bp in length, which contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 2 non-coding regions: origin of light-strand replication (OL) and control region (D-loop). The overall mtDNA nucleotide base composition of P. chinensis is A 29.72%, C 28.10%, G 15.34%, and T 26.84%, with an A + T content of 56.56%. Except for ND6 gene and eight tRNA genes, all other mitochondrial genes were encoded on the heavy strand. The mitochondrial genome of P. chinensis may be helpful to the studies on stock evaluation and conservation genetics of P. chinensis resource, as well as molecular phylogeny of Stromateidae.
Asunto(s)
Genoma Mitocondrial/genética , Perciformes/genética , Análisis de Secuencia de ADN , Animales , ADN Mitocondrial/genética , Genes de ARNr/genética , Anotación de Secuencia Molecular , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/genética , Filogenia , ARN de Transferencia/genéticaRESUMEN
In this study, we determined the complete mitogenome sequence of Schizopygopsis thermalis. The complete mitogenome of S. thermalis is 16,676 bp in length, which contains 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs and 2 non-coding regions: control region (D-loop) and origin of light-strand replication (OL). The complete mtDNA sequence of S. thermalis provides useful genetic markers for the studies on molecular systematic, population genetics and phylogeography.
Asunto(s)
Cyprinidae/genética , Genoma Mitocondrial/genética , Animales , Composición de Base/genética , Secuencia de Bases , China , Codón/genética , Orden Génico/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Especificidad de la EspecieRESUMEN
The complete mitochondrial DNA sequence of Gymnocypris namensis was determined and analyzed. The mitogenome of G. namensis is 16,674 bp long, containing 13 protein-coding genes, 22 tRNA genes, two rRNA genes and two non-coding regions: control region (D-loop) and origin of light-strand replication (OL). The gene order of G. namensis mitogenome is identical to that observed in most other vertebrates. The complete mitogenome sequence information of G. namensis can provide useful data for further studies on molecular systematics, taxonomic status, stock evaluation and conservation genetics.
Asunto(s)
Cyprinidae/genética , Genoma Mitocondrial/genética , Animales , Composición de Base/genética , Secuencia de Bases , Codón/genética , Orden Génico/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Especificidad de la Especie , TibetRESUMEN
Gymnocypris dobula is listed as Vulnerable (VU) status in the IUCN's Red List of Threatened Species. In this paper, complete mitochondrial DNA sequence of G. dobula was determined. The complete mitogenome is 16,720 bp in length, and consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding regions: control region (D-loop) and origin of light-strand replication (OL). The complete mitogenome sequence information of G. dobula is conducive to futher studies on molecular systematics, stock evaluation and conservation genetics.
Asunto(s)
Cyprinidae/genética , Genoma Mitocondrial/genética , Animales , Composición de Base/genética , Secuencia de Bases , China , Codón/genética , Orden Génico/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Especificidad de la EspecieRESUMEN
Pelteobagrus fulvidraco (yellow catfish) is a small-sized species in the family Bagridae, order Siluriformes. In this study, we determined the complete mitogenome sequence of P. fulvidraco and performed phylogenetic analysis with closely related species. The complete mitochondrial genome of P. fulvidraco was 16,527 bp in length, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding regions: control region (D-loop) and the origin of light-strand replication. We inferred that five markers in mitogenome, i.e. D-loop, ND5, 16SrRNA, COXI and ND1, may be suitable markers for studies on population genetics, phylogeny, conservation genetics and evolutionary adaptation mechanisms.
Asunto(s)
Bagres/genética , Genoma Mitocondrial/genética , Filogenia , Animales , Composición de Base/genética , Secuencia de Bases , China , Análisis por Conglomerados , Codón/genética , Evolución Molecular , Orden Génico/genética , Marcadores Genéticos/genética , Modelos Genéticos , Datos de Secuencia Molecular , Mutación/genética , Análisis de Secuencia de ADN , Especificidad de la EspecieRESUMEN
In this study, we sequenced and annotated the complete mitochondrial genome of Schizothorax waltoni (Cypriniformes:Cyprinidae). The mitogenome is 16,587 bp in length, which contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 2 non-coding regions: origin of light-strand replication (O(L)) and control region (D-loop). The overall nucleotide base composition of S. waltoni mtDNA is A 29.96%, C 27.07%, G 17.58%, and T 25.39%, with an A + T content of 55.35%. Except for ND6 gene and eight tRNA genes, all other mitochondrial genes were encoded on the heavy strand. The mitochondrial genome of S. waltoni can contribute to the studies on conservation genetics and stock evaluation of S. waltoni resource, as well as molecular phylogeny and species identification of Cyprinidae.
Asunto(s)
Cyprinidae/genética , ADN Mitocondrial/genética , Genoma Mitocondrial , Animales , Composición de Base , Cyprinidae/clasificación , Filogenia , Proteínas/genética , ARN Ribosómico/genética , ARN de Transferencia/genéticaRESUMEN
Ancherythroculter nigrocauda is a fish endemic to the upper reaches of the Yangtze River in China. In this study, we determined and analyzed the complete mitochondrial DNA (mtDNA) sequence of this species. The mitogenome is 16,623 bp in length. It consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 2 non-coding regions: origin of light-strand replication (O(L)) and control region (D-loop). This mitogenome sequence data can contribute to elucidate the evolutionary mechanisms, molecular systematics, and biogeography of Ancherythroculter and is useful to conservation genetics and stock evaluation for A. nigrocauda.
Asunto(s)
Cyprinidae/genética , ADN Mitocondrial/genética , Genoma Mitocondrial , Animales , Proteínas/genética , ARN Ribosómico/genética , ARN de Transferencia/genéticaRESUMEN
Schizothorax oconnori is mainly distributed in the Yarlung Zangbo River drainage in Tibet, China. S. oconnori is assessed as least concern species in International Union for Conservation of Nature Red List. In this paper, we determined the complete mitochondrial DNA (mtDNA) sequence of S. oconnori. The mitogenome is 16,590 bp in length. It consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 non-coding regions: origin of light-strand replication (O(L)) and control region (D-loop). The complete mitogenome sequence information of S. oconnori can be used in the studies on molecular systematics, stock evaluation and conservation genetics and will be helpful in the development of rational management strategies and sustainable utilization for S. oconnori resource.
Asunto(s)
Cyprinidae/genética , ADN Mitocondrial/genética , Genoma Mitocondrial , Animales , Proteínas/genética , ARN Ribosómico/genética , ARN de Transferencia/genéticaRESUMEN
In this paper, we determined complete mitochondrial DNA sequence of Schizopygopsis younghusbandi. The mitogenome is 16,674 bp in length, which includes 22 tRNA genes, 2 rRNA genes, 13 protein-coding genes, and 2 non-coding regions: control region (D-loop) and origin of light-strand replication (OL). The complete mitogenome sequence of S. younghusbandi is useful to the studies on taxonomic status, molecular systematics, stock evaluation, and conservation genetics.
Asunto(s)
Cyprinidae/genética , ADN Mitocondrial/genética , Genes Mitocondriales/genética , Genoma Mitocondrial/genética , Animales , Composición de Base/genética , Secuencia de Bases , Orden Génico/genética , Tamaño del Genoma/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADNRESUMEN
In this study, the complete mitochondrial DNA (mtDNA) sequence of Schizothorax wangchiachii has been determined. The mitogenome is 16,593 bp in length. It consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 2 non-coding regions: origin of light-strand replication (OL) and control region (D-loop). The complete mtDNA sequence of S. wangchiachii can contribute to elucidate the evolutionary mechanisms and biogeography of Schizothorax and is useful to stock evaluation and conservation genetics for S. wangchiachii.
Asunto(s)
Cyprinidae/genética , ADN Mitocondrial/genética , Genes Mitocondriales/genética , Genoma Mitocondrial/genética , Animales , Composición de Base , Secuencia de Bases , China , Cartilla de ADN/genética , Orden Génico/genética , Tamaño del Genoma/genética , Datos de Secuencia Molecular , Análisis de Secuencia de ADNRESUMEN
The complete mitochondrial DNA genome sequence of Ussuri catfish (Pseudobagrus ussuriensis) was determined. The mitochondrial genome sequence is a circular molecule with 16,536 bp in length. It contains 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 2 non-coding regions. The nucleotide acid composition of the entire mitogenome is 31.79% for A, 26.84% for T, 14.87% for G, and 26.50% for C, showing a high A+T content. The complete mitogenome sequence of P. ussuriensis can be used in the studies on molecular systematics, conservation genetics, and stock evaluation.