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Background: There have been cases of colorectal cancer (CRC) metastasizing into the ovary. This study reports a case involving solitary ovarian metastasis (OM) from CRC, which is very rare in the absence of other pelvic and peritoneal metastases. This atypical clinical presentation added to the complexity of the diagnosis. Case Description: We report a case of solitary OM-CRC in a 48-year-old woman. The patient underwent CRC surgery and refused follow-up after three rounds of chemotherapy. Approximately 14 months later, the patient presented with vaginal bleeding for 2 months. The magnetic resonance imaging (MRI) showed a huge solid cystic mass in the right adnexa. Intraoperatively, the right ovary was found to be enlarged and smooth without adhesions. By careful examination of the abdominal cavity, no metastatic lesions were found in the left ovary and uterus, and no seedings were found in the rest of the pelvis and abdomen. After removal of the uterus and bilateral adnexa, the histologic examination revealed metastatic adenocarcinoma of the right ovary with a considered rectal carcinoma of origin. Positive staining for multiple tumor-associated markers, which further established the primary nature of CRC. These findings support a possible diagnosis of primary CRC and ovarian metastases. The patient recovered well after the operation and no recurrence or metastasis was seen 18 months after the operation. Conclusions: Solitary ovarian metastases from CRC can be better managed and treated by increasing clinicians' vigilance for this rare condition. This helps to improve the patient's prognosis and quality of life.
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SIRT6 is a key member of the mammalian sirtuin family of conserved nicotinamide adenine dinucleotide (NAD+ )-dependent deacetylases. Previous studies have shown that SIRT6 can regulate metabolism, DNA damage repair and aging. Ovarian aging process usually share similar mechanisms with general aging, which is characterized by decreases in both numbers of ovarian follicles and the quality of oocytes. It is reported that the expression level of SIRT6 was significantly decreased in the ovaries of aged mice, and the level of SIRT6 was positively correlated with ovarian reserve, indicating that SIRT6 may be potential markers of ovarian aging. However, its biological roles in follicular development are still unclear. Here, we explored the effect of SIRT6 on follicular development and found that ovarian development was interrupted in SIRT6 knockout (KO) mice, leading to disruptions of puberty and the estrus cycle, significant decreases in numbers of secondary and antral follicles, and decreased collagen in the ovarian stroma. Plod1, a lysyl hydroxylase that is vital for collagen crosslinking and deposition, was decreased at both the mRNA and protein levels in SIRT6-deficient ovaries and granulosa cells (GCs). Additionally, we found abnormal estrogen levels in both SIRT6 KO mice and SIRT6 KD GCs, accompanied by decreases in the levels of the estrogen biosynthesis genes Cyp11a1, Cyp19a1, Mgarp, and increases in the levels of TNF-α and NF-κB. These results confirmed the effect of SIRT6 on follicular development and revealed a possible molecular mechanism for SIRT6 involvement in follicular development via effects on estrogen biosynthesis and collagen formation.
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Ovario , Sirtuinas , Animales , Femenino , Ratones , Estrógenos/metabolismo , Mamíferos/metabolismo , Oocitos/metabolismo , Folículo Ovárico/metabolismo , Ovario/metabolismo , Sirtuinas/genética , Sirtuinas/metabolismo , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/metabolismoRESUMEN
CuX/TiO2 adsorbents with CuO as the active component were prepared via a simple impregnation method for efficient purification of phosphine (PH3) under the conditions of low temperatures (90 °C) and low oxygen concentration (1%). The PH3 breakthrough capacity of optimal adsorbent (Cu30/TiO2) is 136.2 mg(PH3)·gsorbent-1, and the excellent dephosphorization performance is mainly attributed to its abundant sur face-active oxygen and alkaline sites, large specific surface area, and strong interaction between CuO and the support TiO2. Surprisingly, CuO is converted to Cu3P after the dephosphorization by CuX/TiO2. Since Cu3P is a P-type semiconductor with high added value, the deactivated adsorbent (Cu3P/TiO2) is an efficient heterostructure photocatalyst for photocatalytic removal of Hg0 (gas) with the Hg0 removal performance of 92.64% under visible light. This study provides a feasible strategy for the efficient removal and resource conversion of PH3 under low-temperature conditions and the alleviation of the environmental risk of secondary pollution.
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Cobre , Mercurio , Catálisis , Mercurio/químicaRESUMEN
Sirtuin 6 (SIRT6) is a nuclear silencing information regulator that is widely expressed in brain. Inhibition of SIRT6 in the brain induced antidepressant effects in rodents. However, SIRT6 knockout in neurons induced developmental retardation and cognitive impairments. In this study, a mouse strain of astrocyte conditional knockout SIRT6 (AKO) was constructed. Unlike whole brain SIRT6 knockout mice, AKO mice did not show growth retardation. We showed that SIRT6 knockout in astrocytes did not impair the learning and memory ability of mice. Chronic unpredictable mild stress (CUMS) was used to evaluate the anti-depression and anti-anxiety effects in mice. In tail suspension test and forced swimming test, AKO mice did not show depression like phenotype induced by CUMS. In addition, knockout of SIRT6 in astrocytes alleviated the high anxiety level induced by CUMS in light and dark box test, open field test and elevated cross maze test. Three box social test showed that the deletion of SIRT6 in astrocytes changed the social preference of mice. Re-expression of SIRT6 in astrocytes mediated by adeno-associated virus reversed the social preference of AKO mice, but the re-expression also eliminated the anti-depression and anti-anxiety effects in AKO mice. Deletion of SIRT6 in astrocytes change the purine metabolic homeostasis of medial prefrontal cortex in mice. The results of transcriptomics and metabolomics analysis showed that the deletion of SIRT6 would change the purine metabolic pathway of cultured astrocytes and increase the contents of inosine and the second messenger cyclic adenosine monophosphate in astrocytes. In conclusion, knockout of SIRT6 in astrocytes induced anti-depression and anti-anxiety effects in mice without impairing the development and cognitive ability of mice.
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Ansiolíticos , Sirtuinas , Animales , Ratones , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico , Ansiedad/tratamiento farmacológico , Astrocitos/metabolismo , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Sirtuinas/antagonistas & inhibidores , Sirtuinas/genética , Sirtuinas/metabolismo , Estrés Psicológico/metabolismoRESUMEN
Although primary vesical calculi is an ancient disease, the mechanism of calculi formation remains unclear. In this study, we established a novel primary vesical calculi model with d,l-choline tartrate in mice. Compared with commonly used melamine and ethylene glycol models, our model was the only approach that induced vesical calculi without causing kidney injury. Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi, yet the effect of fat is overlooked. To assay the relationship of dietary fat with the formation of primary vesical calculi, d,l-choline tartrate-treated mice were fed a high-fat, low-fat, or normal-fat diet. Genetic changes in the mouse bladder were detected with transcriptome analysis. A high-fat diet remarkably reduced the morbidity of primary vesical calculi. Higher fatty acid levels in serum and urine were observed in the high-fat diet group, and more intact epithelia in bladder were observed in the same group compared with the normal- and low-fat diet groups, suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure. Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14 (Cxcl14) was upregulated in the bladders of high-fat diet-fed mice compared with those of normal- or low-fat diet-fed mice, which was consistent with histological observations. The expression of CXCL14 significantly increased in the bladder in the high-fat diet group. CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages, which led to phagocytosis of budding crystals and prevented accumulation of calculi. In human bladder epithelia (HCV-29) cells, high fatty acid supplementation significantly increased the expression of CXCL14. Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi, which provides new ideas for the reduction of morbidity of primary vesical calculi.
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Non-alcoholic fatty liver disease (NAFLD) was defined in 1980 and has the same histological characteristics as alcoholic liver disease except for alcohol consumption. After 40 years, the understanding of this disease is still imperfect. Without specific drugs available for treatment, the number of patients with NAFLD is increasing rapidly, and NAFLD currently affects more than one-quarter of the global population. NAFLD is mostly caused by a sedentary lifestyle and excessive energy intake of fat and sugar. To ameliorate or avoid NAFLD, people commonly replace high-fat foods with high-carbohydrate foods (especially starchy carbohydrates) as a way to reduce caloric intake and reach satiety. However, there are few studies that concentrate on the effect of carbohydrate intake on liver metabolism in patients with NAFLD, much fewer than the studies on fat intake. Besides, most of these studies are not systematic, which has made identification of the mechanism difficult. In this review, we collected and analysed data from studies on human and animal models and, surprisingly, found that carbohydrates and liver steatosis could be linked by inflammation. This review not only describes the effects of carbohydrates on NAFLD and body lipid metabolism but also analyses and predicts possible molecular pathways of carbohydrates in liver lipid synthesis that involve inflammation. Furthermore, the limitations of recent research and possible targets for regulating inflammation and lipogenesis are discussed. This review describes the effects of starchy carbohydrates, a nutrient signal, on NAFLD from the perspective of inflammation.
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Enfermedad del Hígado Graso no Alcohólico , Animales , Humanos , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Hígado , Lipogénesis , Inflamación/metabolismo , Carbohidratos/farmacología , Carbohidratos/uso terapéuticoRESUMEN
Although calorie restriction has been reported to extend lifespan in several organisms, animals subjected to calorie restriction consume not only fewer calories but also smaller quantities of food. Whether it is the overall restriction of calories or the coincidental reduction in the quantity of food consumed that mediates the anti-aging effects is unclear. Here, we subjected mice to five dietary interventions. We showed that both calorie and quantity restriction could improve early survival, but no maximum lifespan extension was observed in the mice fed isocaloric diet in which food quantity was reduced. Mice fed isoquant diet with fewer calories showed maximum lifespan extension and improved health among all the groups, suggesting that calorie intake rather than food quantity consumed is the key factor for the anti-aging effect of calorie restriction. Midlife liver gene expression correlations with lifespan revealed that calorie restriction raised fatty acid biosynthesis and metabolism and biosynthesis of amino acids but inhibited carbon metabolism, indicating different effects on fatty acid metabolism and carbohydrate metabolism. Our data illustrate the effects of calories and food quantity on the lifespan extension by calorie restriction and their potential mechanisms, which will provide guidance on the application of calorie restriction to humans.
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Envejecimiento/metabolismo , Restricción Calórica , Ingestión de Energía , Ácidos Grasos/metabolismo , Esperanza de Vida , Longevidad , Aminoácidos/metabolismo , Animales , Carbono/metabolismo , Dieta , Ácidos Grasos/biosíntesis , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BLRESUMEN
In mammals, DNA methylation is associated with aging. However, age-related DNA methylation changes during phase transitions largely remain unstudied in plants. Moso bamboo (Phyllostachys edulis) requires a very long time to transition from the vegetative to the floral phase. To comprehensively investigate the association of DNA methylation with aging, we present here single-base-resolution DNA methylation profiles using both high-throughput bisulfite sequencing and single-molecule nanopore-based DNA sequencing, covering the long period of vegetative growth and transition to flowering in moso bamboo. We discovered that CHH methylation gradually accumulates from vegetative to reproductive growth in a time-dependent fashion. Differentially methylated regions, correlating with chronological aging, occurred preferentially at both transcription start sites and transcription termination sites. Genes with CG methylation changes showed an enrichment of Gene Ontology (GO) categories in 'vegetative to reproductive phase transition of meristem'. Combining methylation data with mRNA sequencing revealed that DNA methylation in promoters, introns and exons may have different roles in regulating gene expression. Finally, circular RNA (circRNA) sequencing revealed that the flanking introns of circRNAs are hypermethylated and enriched in long terminal repeat (LTR) retrotransposons. Together, the observations in this study provide insights into the dynamic DNA methylation and circRNA landscapes, correlating with chronological age, which paves the way to study further the impact of epigenetic factors on flowering in moso bamboo.
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Envejecimiento/genética , Metilación de ADN , Flores/crecimiento & desarrollo , Poaceae/genética , ARN Circular/genética , ARN de Planta/genética , Envejecimiento/fisiología , Metilación de ADN/genética , Metilación de ADN/fisiología , Elementos Transponibles de ADN/genética , Elementos Transponibles de ADN/fisiología , Regulación de la Expresión Génica de las Plantas/genética , Estudio de Asociación del Genoma Completo , Poaceae/crecimiento & desarrollo , Poaceae/metabolismo , ARN Circular/metabolismo , ARN Circular/fisiología , ARN de Planta/metabolismo , ARN de Planta/fisiología , Análisis de Secuencia de ADN/métodosRESUMEN
A simple, low-cost, and universal gold nanoparticle (AuNP) aggregation-induced photothermal biosensing platform has been developed for the first time and applied for the visual quantitative genetic detection using a common thermometer. By exploiting the photothermal effect of target-induced gold nanoparticle aggregation, visual quantitative biochemical analysis can be achieved by simply recording temperature signals using a common thermometer. Compared to conventional genetic testing methods, it is label- and amplification-free and can be completed in 40 min without the aid of any advanced analytical instruments. Mycobacterium tuberculosis (MTB) DNA was used as a model target to demonstrate the application of this photothermal biosensing platform. Although no costly instrument was used, high sensitivity and specificity were achieved with the limit of detection (LOD) of 0.28 nM, which was nearly 10-fold lower than that of the colorimetric method using a spectrometer. This AuNP aggregation-induced photothermal biosensing strategy provides a simple, low-cost, and universal platform for broad application of visual quantitative detection of nucleic acids and many other biomolecules, particularly in point-of-care (POC) biosensing applications.
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Técnicas Biosensibles , ADN Bacteriano/análisis , Oro/química , Nanopartículas del Metal/química , Temperatura , Termómetros , Sondas de ADN/química , ADN Bacteriano/genética , Mycobacterium tuberculosis/genética , Tamaño de la Partícula , Procesos Fotoquímicos , Propiedades de SuperficieRESUMEN
Major depressive disorder (MDD) is a chronic mental disorder characterized by mixed symptoms and complex pathogenesis. With long history of practical application, traditional Chinese medicine (TCM) offers many herbs for the treatment and rehabilitation of chronic disease. In this study, we developed a modified Chinese herbal formula using Panax ginseng, Angelica Sinensis, Polygala tenuifolia Willd, and Ziziphi spinosae Semen (PAPZ), based on an ancient TCM prescription. The antidepressant effects of PAPZ were investigated with a corticosterone (CORT) model of depression in mice. Our results showed that administration of PAPZ ameliorated depression-like phenotypes in the CORT model. An anatomic study showed that chronic PAPZ administration upregulated the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampal tissue. The enzyme activity of superoxide dismutase was enhanced in hippocampal tissue, in line with a decreased malondialdehyde level. Taken together, these findings suggested that PAPZ has therapeutic effects in a mice depression model through increasing protein expression of BDNF and improving the anti-oxidation ability of the brain.
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Antioxidantes/uso terapéutico , Conducta Animal/efectos de los fármacos , Depresión/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Hipocampo/efectos de los fármacos , Magnoliopsida , Fitoterapia , Angelica sinensis , Animales , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antioxidantes/metabolismo , Antioxidantes/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Corticosterona , Depresión/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Hipocampo/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones Endogámicos C57BL , Panax , Polygala , Superóxido Dismutasa/metabolismo , ZiziphusRESUMEN
Circular RNAs, including circular exonic RNAs (circRNA), circular intronic RNAs (ciRNA) and exon-intron circRNAs (EIciRNAs), are a new type of noncoding RNAs. Growing shoots of moso bamboo (Phyllostachys edulis) represent an excellent model of fast growth and their circular RNAs have not been studied yet. To understand the potential regulation of circular RNAs, we systematically characterized circular RNAs from eight different developmental stages of rapidly growing shoots. Here, we identified 895 circular RNAs including a subset of mutually inclusive circRNA. These circular RNAs were generated from 759 corresponding parental coding genes involved in cellulose, hemicellulose and lignin biosynthetic process. Gene co-expression analysis revealed that hub genes, such as DEFECTIVE IN RNA-DIRECTED DNA METHYLATION 1 (DRD1), MAINTENANCE OF METHYLATION (MOM), dicer-like 3 (DCL3) and ARGONAUTE 1 (AGO1), were significantly enriched giving rise to circular RNAs. The expression level of these circular RNAs presented correlation with its linear counterpart according to transcriptome sequencing. Further protoplast transformation experiments indicated that overexpressing circ-bHLH93 generating from transcription factor decreased its linear transcript. Finally, the expression profiles suggested that circular RNAs may have interplay with miRNAs to regulate their cognate linear mRNAs, which was further supported by overexpressing miRNA156 decreasing the transcript of circ-TRF-1 and linear transcripts of TRF-1. Taken together, the overall profile of circular RNAs provided new insight into an unexplored category of long noncoding RNA regulation in moso bamboo.
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Brotes de la Planta/crecimiento & desarrollo , Poaceae/genética , ARN de Planta/genética , ARN/genética , Regulación de la Expresión Génica de las Plantas , Estudio de Asociación del Genoma Completo , Brotes de la Planta/metabolismo , Poaceae/crecimiento & desarrollo , ARN Circular , TranscriptomaRESUMEN
Osteopenia, osteoporosis and bone salt metabolism disorder are common diseases in the aged and diabetics. From case reports of patients with T2DM, we have observed that metformin can decrease risk of bone fracture and promote bone formation. However, the underlying mechanism of metformin's effect on bone metabolism remains unknown. In our research, we show that metformin can promote proliferation of murine preosteoblast by regulating AMPK-mTORC2 and AKT-mTORC1 signaling axis. Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast. The interaction between SIRT6 and NF-κB is highly important in osteoblast differentiation just as the relationship between OPG and RANKL in the process of bone formation. During differentiation, we show that SIRT6 inhibits phosphorylation of NF-κB and that OPG increases while RANKL decrease in HG groups. In addition, ablation of sirt6 in mice causes phosphorylation of NF-κB at high-levels and RANKL increases slightly in femur bone cells. However, other bone formation marker proteins such as RUNX2, OSTERIX and OPG appear at low-levels in sirt6 KO mice. It has been confirmed that downregulation of OCT4 is critical incident in the differentiation of embryonic stem cells. Fortunately, we observe that SIRT6 can suppress OCT4 expression in murine preosteoblast and the expression of OCT4 is at high-level in sirt6 KO mice. Taken together, this study's results illuminate metformin's effect on bone metabolism under HG condition and help to elucidate why metformin can promote bone fracture healing of patients with T2DM.
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Hipoglucemiantes/farmacología , Metformina/farmacología , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Osteoblastos/efectos de los fármacos , Sirtuinas/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Ratones , Osteoblastos/metabolismoRESUMEN
Nacre is a widely used mineral medicine that has been reported to have beneficial effects in bone remodeling without an increase in inflammation. Water-soluble nacre matrix has been demonstrated to be responsible for the effect, yet core active ingredients are unknown. Pinctada fucata mantle gene 1 (PFMG1) was first discovered in the mantle tissue of Pinctada fucata. The protein has 2 EF-hands, a calcium-binding domain. PFMG1 protein can affect the growth of calcium carbonate crystals in vitro. Here, we demonstrate that PFMG1 affects cell-cycle distribution and promotes preosteoblast proliferation. PFMG1 accelerates preosteoblast differentiation and extracellular matrix mineralization. During the differentiation process, PFMG1 increases the expression level of osteoblastic marker genes and activates the Erk signaling pathway. PFMG1 also accelerates calcium crystal aggregation in culture medium and suppresses osteoclast formation. Moreover, PFMG1 prevents bone loss caused by ovariectomy. RNA sequencing analysis demonstrated that PFMG1 stimulates genes that are associated with tissue development and ossification, which indicated new genes that function in bone remodeling. Our findings demonstrate the therapeutic potential of PFMG1 from nacre as a novel medicine for osteoporosis.-Li, L., Wang, P., Hu, K., Wang, X., Cai, W., Ai, C., Liu, S., Wang, Z. PFMG1 promotes osteoblast differentiation and prevents osteoporotic bone loss.
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Diferenciación Celular/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Osteoblastos/metabolismo , Osteoporosis/prevención & control , Pinctada/genética , Proteínas de Plantas , Animales , Resorción Ósea , Calcificación Fisiológica/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular , Femenino , Ratones , Osteoblastos/patología , Osteoporosis/metabolismo , Osteoporosis/patología , Ovariectomía , Proteínas de Plantas/genética , Proteínas de Plantas/farmacologíaRESUMEN
We present a comprehensive software program, RAD-ADAPT, for the quantitative analysis of clonogenic assays in radiation biology. Two commonly used models for clonogenic assay analysis, the linear-quadratic model and single-hit multi-target model, are included in the software. RAD-ADAPT uses maximum likelihood estimation method to obtain parameter estimates with the assumption that cell colony count data follow a Poisson distribution. The program has an intuitive interface, generates model prediction plots, tabulates model parameter estimates, and allows automatic statistical comparison of parameters between different groups. The RAD-ADAPT interface is written using the statistical software R and the underlying computations are accomplished by the ADAPT software system for pharmacokinetic/pharmacodynamic systems analysis. The use of RAD-ADAPT is demonstrated using an example that examines the impact of pharmacologic ATM and ATR kinase inhibition on human lung cancer cell line A549 after ionizing radiation.