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OBJECTIVE: To analyse the global burden, trends and cross-country inequalities of female breast and gynaecologic cancers (FeBGCs). DESIGN: Population-Based Study. SETTING: Data sourced from the Global Burden of Disease Study 2019. POPULATION: Individuals diagnosed with FeBGCs. METHODS: Age-standardised mortality rates (ASMRs), age-standardised Disability-Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age-standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index. MAIN OUTCOME MEASURES: The main outcome measures were the burden of FeBGCs and the trends in its inequalities over time. RESULTS: In 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30-510.51), cervical cancer: 210.64 (95% UI: 177.67-234.85), ovarian cancer: 124.68 (95% UI: 109.13-138.67) and uterine cancer: 210.64 (95% UI: 177.67-234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: -0.51 (95% CI: -0.57 to -0.45); Cervical cancer: -0.95 (95% CI: -0.99 to -0.89); Ovarian cancer: -0.08 (95% CI: -0.12 to -0.04); and Uterine cancer: -0.84 (95% CI: -0.93 to -0.75). In the Social Inequalities Analysis (1990-2019) the SII changed from 689.26 to 607.08 for Breast, from -226.66 to -239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4. CONCLUSIONS: The burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio-demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.
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SET domain containing 7(SETD7), a member of histone methyltransferases, is abnormally expressed in multiple tumor types. However, the biological function and underlying molecular mechanism of SETD7 in clear cell renal cell carcinoma (ccRCC) remain unclear. Here, we explored the biological effects of SETD7-TAF7-CCNA2 axis on proliferation and metastasis in ccRCC. We identified both SETD7 and TAF7 were up-regulated and significantly promoted the proliferation and migration of ccRCC cells. Concurrently, there was a significant positive correlation between the expression of SETD7 and TAF7, and the two were colocalized in the nucleus. Mechanistically, SETD7 methylates TAF7 at K5 and K300 sites, resulting in the deubiquitination and stabilization of TAF7. Furthermore, re-expression of TAF7 could partially restore SETD7 knockdown inhibited ccRCC cells proliferation and migration. In addition, TAF7 transcriptionally activated to drive the expression of cyclin A2 (CCNA2). And more importantly, the methylation of TAF7 at K5 and K300 sites exhibited higher transcriptional activity of CCNA2, which promotes formation and progression of ccRCC. Our findings reveal a unique mechanism that SETD7 mediated TAF7 methylation in regulating transcriptional activation of CCNA2 in ccRCC progression and provide a basis for developing effective therapeutic strategies by targeting members of SETD7-TAF7-CCNA2 axis.
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Carcinoma de Células Renales , Movimiento Celular , Proliferación Celular , N-Metiltransferasa de Histona-Lisina , Neoplasias Renales , Humanos , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Proliferación Celular/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Movimiento Celular/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/patología , Línea Celular Tumoral , Factores Asociados con la Proteína de Unión a TATA/metabolismo , Factores Asociados con la Proteína de Unión a TATA/genética , Metilación , Factor de Transcripción TFIID/metabolismo , Factor de Transcripción TFIID/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Male infertility has emerged as a global issue, partly attributed to psychological stress. However, the cellular and molecular mechanisms underlying the adverse effects of psychological stress on male reproductive function remain elusive. We created a psychologically stressed model using terrified-sound and profiled the testes from stressed and control rats using single-cell RNA sequencing. Comparative and comprehensive transcriptome analyses of 11,744 testicular cells depicted the cellular landscape of spermatogenesis and revealed significant molecular alterations of spermatogenesis suffering from psychological stress. At the cellular level, stressed rats exhibited delayed spermatogenesis at the spermatogonia and pachytene phases, resulting in reduced sperm production. Additionally, psychological stress rewired cellular interactions among germ cells, negatively impacting reproductive development. Molecularly, we observed the down-regulation of anti-oxidation-related genes and up-regulation of genes promoting reactive oxygen species (ROS) generation in the stress group. These alterations led to elevated ROS levels in testes, affecting the expression of key regulators such as ATF2 and STAR, which caused reproductive damage through apoptosis or inhibition of testosterone synthesis. Overall, our study aimed to uncover the cellular and molecular mechanisms by which psychological stress disrupts spermatogenesis, offering insights into the mechanisms of psychological stress-induced male infertility in other species and promises in potential therapeutic targets.
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Obesity may lead to cognitive impairment and psychiatric disorders, which are associated with alterations in the brain cortical structure. However, the exact causality remains inconclusive. We aimed to conduct two-sample Mendelian randomization (MR) analysis to identify the causal associations of obesity [body mass index (BMI), waist-hip ratio (WHR), and waist-hip ratio adjusted for BMI ((WHRadjBMI)) and brain cortical structure (cortical thickness and cortical surface area). Inverse-variance weighted (IVW) method was used as the main analysis, whereas a series of sensitivity analyses were employed to assess heterogeneity and pleiotropy. The main MR results showed that higher BMI significantly increased the cortical surface area of the transverse temporal (ß = 5.13 mm2, 95% confidence interval [CI]: 2.55-7.71, P = 9.9 × 10-5); higher WHR significantly decreased cortical surface area of the inferior temporal (ß = -38.60, 95% CI: -56.67- -20.54, P = 1.2 × 10-5), but significantly increased cortical surface area of the isthmus cingulate (ß = 14.25, 95% CI: 6.97-21.54, P = 1.2 × 10-4). No significant evidence of pleiotropy was found in the MR analyses. This study supports that obesity has a causal effect on the brain cortical structure. Further studies are warranted to understand the clinical outcomes caused by these effects.
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Disfunción Cognitiva , Análisis de la Aleatorización Mendeliana , Humanos , Encéfalo , Obesidad/genética , Índice de Masa Corporal , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido SimpleRESUMEN
Stress is an important environmental factor affecting mental health that cannot be ignored. Moreover, due to the great physiological differences between males and females, the effects of stress may vary by sex. Previous studies have shown that terrified-sound stress, meaning exposed mice to the recorded vocalizations in response to the electric shock by their kind to induce psychological stress, can cause cognitive impairment in male. In the study, we investigated the effects of the terrified-sound stress on adult female mice. METHODS: 32 adults female C57BL/6 mice were randomly divided into control (n = 16) and stress group (n = 16). Sucrose preference test (SPT)was carried out to evaluate the depressive-like behavior. Using Open field test (OFT) to evaluate locomotor and exploratory alterations in mice. Spatial learning and memory ability were measured in Morris Water maze test (MWM), Golgi staining and western blotting showed dendritic remodeling after stress. In addition, serum hormone quantifications were performed by ELISA. RESULTS: we found the sucrose preference of stress group was significantly decreased (p < 0.05) compared with control group; the escape latency of the stress group was significantly prolonged (p < 0.05), the total swimming distance and the number of target crossings(p < 0.05) were significantly increased (p < 0.05) in MWM; Endocrine hormone, Testosterone (T) (p < 0.05), GnRH (p < 0.05), FSH and LH levels was decreased; Golgi staining and western blotting showed a significant decrease in dendritic arborization, spine density and synaptic plasticity related proteins PSD95 and BDNF in the stress group. CONCLUSION: Terrified-sound stress induced depressive-like behaviors, locomotor and exploratory alterations. And impaired cognitive by altering dendritic remodeling and the expression of synaptic plasticity-related proteins. However, females are resilient to terrified-sound stress from a hormonal point of view.
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Disfunción Cognitiva , Plasticidad Neuronal , Animales , Femenino , Masculino , Ratones , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Depresión/etiología , Hipocampo/metabolismo , Hormonas/metabolismo , Ratones Endogámicos C57BL , Estrés Psicológico/metabolismo , Sacarosa/metabolismoRESUMEN
AIMS: Colon cancer (CC) is a prevalent malignancy worldwide and is one of the most easily altered cancers by dietary regulation. Petunidin 3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(ß-D-glucopyranoside) (Pt3R5G) isolated and purified from Lycium ruthenicum Murray, which exhibits highly efficient antioxidant activity and specific anticancer effects, is the flavonoids compound. We aimed to study the effect of Pt3R5G on CC cells and elucidate the potential underlying mechanisms. MAIN METHODS: Cell proliferation was measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and colony formation assays. Cell cycle, cell apoptosis and reactive oxygen species (ROS) analysis were performed by flow cytometry. RNA-sequencing was performed to elucidate the potential underlying mechanisms. The lipid peroxidation level of cells was detected by malondialdehyde (MDA) assay. The mitochondrial morphology of cells was inspected using a transmission electron microscope. Additionally, we overexpressed SLC7A11 to perform rescue experiments. In vivo, xenograft mice assay was performed to verify the effect of Pt3R5G on the growth of colon cancer. KEY FINDINGS: Pt3R5G reduced the cell activity by blocking the cell cycle in G0/G1 phase, inducing the apoptosis and ferroptosis in RKO cells. The overexpressed of SLC7A11, a significantly down-regulated expression gene caused by Pt3R5G, rescued the cell proliferation inhibition and ferroptosis process. Furthermore, Pt3R5G inhibited tumor growth in nude mice. Our study suggests that Pt3R5G inhibits RKO cell proliferation through mainly reducing ferroptosis by down-regulated SLC7A11. SIGNIFICANCE: As a potential therapeutic drug, Pt3R5G showed efficient anticancer activity through a variety of pathways.
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Neoplasias del Colon , Ferroptosis , Sistema de Transporte de Aminoácidos y+/metabolismo , Animales , Apoptosis , Proliferación Celular , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Humanos , Ratones , Ratones DesnudosRESUMEN
Leucine rich repeat containing G protein-coupled receptor 6 (LGR6) belongs to the G protein-coupled receptor family, and it exhibits up-regulated expression in various types of human cancer. However, there are few reports of LGR6 contributing to gastric cancer (GC). Herein, we investigated the function of LGR6 and associated tumorigenic mechanisms in GC. LGR6 expression in GC was analyzed in the cancer genome atlas (TCGA) dataset and further confirmed in GC cell lines and fifteen paired tissue samples via quantitative real-time polymerase chain reaction (qRT-PCR). LGR6 expression was knocked down via small interfering RNA (siRNA), after which the impacts of silencing LGR6 on cell function were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), cell colony formation, wound-healing, and cell cycle assays. Western blot was performed to explore signaling pathways and regulatory mechanisms associated with LGR6 function. In this study, we showed that LGR6 was at higher levels in GC cell lines and gastric adenocarcinoma tissues. We found that silencing LGR6 in MKN-45 and BGC-823 cells inhibited cell proliferation and migration ability, which accompanied with an obvious regulation of MMP-9, ß-catenin, CCNA2, CDK-2, and ERK1/2. In conclusion, this study demonstrated that LGR6 could act as an oncogene and may be a therapeutic target in GC.
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Neoplasias Gástricas , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Oncogenes , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Receptores Acoplados a Proteínas G/genética , Neoplasias Gástricas/metabolismoRESUMEN
Stress is one of the leading causes of male infertility, but its exact function in testosterone synthesis has scarcely been reported. We found that adult male rats show a decrease in bodyweight, genital index and serum testosterone level after continual chronic stress for 21 days. Two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-MS analysis identified 10 differentially expressed proteins in stressed rats compared with controls. A strong protein interaction network was found to be centred on Atp5a1 among these proteins. Atp5a1 expression significantly decreased in Leydig cells after chronic stress. Transfection of Atp5a1 siRNAs decreased StAR, CYP11A1, and 17ß-HSD expression by damaging the structure of mitochondria in TM3 cells. This study confirmed that chronic stress plays an important role in testosterone synthesis by regulating Atp5a1 expression in Leydig cells.
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Células Intersticiales del Testículo , Testosterona , Animales , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Células Intersticiales del Testículo/metabolismo , Masculino , Mitocondrias/metabolismo , ATPasas de Translocación de Protón Mitocondriales , RatasRESUMEN
The innovation of biotechnologies has allowed the accumulation of omics data at an alarming rate, thus introducing the era of 'big data'. Extracting inherent valuable knowledge from various omics data remains a daunting problem in bioinformatics. Better solutions often need some kind of more innovative methods for efficient handlings and effective results. Recent advancements in integrated analysis and computational modeling of multi-omics data helped address such needs in an increasingly harmonious manner. The development and application of machine learning have largely advanced our insights into biology and biomedicine and greatly promoted the development of therapeutic strategies, especially for precision medicine. Here, we propose a comprehensive survey and discussion on what happened, is happening and will happen when machine learning meets omics. Specifically, we describe how artificial intelligence can be applied to omics studies and review recent advancements at the interface between machine learning and the ever-widest range of omics including genomics, transcriptomics, proteomics, metabolomics, radiomics, as well as those at the single-cell resolution. We also discuss and provide a synthesis of ideas, new insights, current challenges and perspectives of machine learning in omics.
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Inteligencia Artificial , Aprendizaje Automático , Biología Computacional/métodos , Genómica/métodos , Proteómica/métodosRESUMEN
This paper developed and evaluated a quantitative image analysis method to measure the concentration of the nanoparticles on which alkaline phosphatase (AP) was immobilized. These AP-labeled nanoparticles are widely used as signal markers for tagging biomolecules at nanometer and sub-nanometer scales. The AP-labeled nanoparticle concentration measurement can then be directly used to quantitatively analyze the biomolecular concentration. Micro-droplets are mono-dispersed micro-reactors that can be used to encapsulate and detect AP-labeled nanoparticles. Micro-droplets include both empty micro-droplets and fluorescent micro-droplets, while fluorescent micro-droplets are generated from the fluorescence reaction between the APs adhering to a single nanoparticle and corresponding fluorogenic substrates within droplets. By detecting micro-droplets and calculating the proportion of fluorescent micro-droplets to the overall micro-droplets, we can calculate the AP-labeled nanoparticle concentration. The proposed micro-droplet detection method includes the following steps: (1) Gaussian filtering to remove the noise of overall fluorescent targets, (2) a contrast-limited, adaptive histogram equalization processing to enhance the contrast of weakly luminescent micro-droplets, (3) an red maximizing inter-class variance thresholding method (OTSU) to segment the enhanced image for getting the binary map of the overall micro-droplets, (4) a circular Hough transform (CHT) method to detect overall micro-droplets and (5) an intensity-mean-based thresholding segmentation method to extract the fluorescent micro-droplets. The experimental results of fluorescent micro-droplet images show that the average accuracy of our micro-droplet detection method is 0.9586; the average true positive rate is 0.9502; and the average false positive rate is 0.0073. The detection method can be successfully applied to measure AP-labeled nanoparticle concentration in fluorescence microscopy.
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Nanopartículas , Fosfatasa Alcalina , Colorantes Fluorescentes , Humanos , Microscopía FluorescenteRESUMEN
Historical distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) and their carriers (i.e., organic matter and mineral particles) in the sediment cores of the Yangtze Estuary were investigated, with emphasis laid on the role of the Yangtze River. Grain size component of sediments (clay, silt, and sand) and organic carbon (black carbon and total organic carbon) in the sediment cores were markedly affected by water flux and sediment discharge of the Yangtze River. Qualitative and quantitative analysis results showed that sands and black carbon acted as the main carriers of PAHs. The sedimentation of two-ring to three-ring PAHs in the estuary had significant correlations with water flux and sediment discharge of the Yangtze River. The relative lower level of the four-ring and five-ring to six-ring PAHs concentrations appeared around the year 2003 and remained for the following several years. This time period accorded well with the water impoundment time of the Three Gorges Reservoir. The decreased level of two-ring to three-ring PAHs occurred in the year 1994, and the peak points around the year 2009 indicated that PAHs sedimentation in the estuary also had close relationship to severe drought and flood in the catchments. The findings presented in this paper could provide references for assessing the impacts of water flux and sediment discharge on the historical deposition of PAHs and their carriers in the Yangtze Estuary.
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Monitoreo del Ambiente , Estuarios , Sedimentos Geológicos/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Ríos , Agua/análisis , China , Movimientos del Agua , Contaminantes Químicos del Agua/análisisRESUMEN
As a systematic research at basin scale, this study explored the composition and concentration characteristics of 16 priority polycyclic aromatic hydrocarbons (PAHs) in sediments, water, and suspended particulate matter (SPM) in the water systems (rivers, lakes, and reservoirs) in the Hai River Basin through literature review. The sources and the ecosystem risks of PAHs in the sediments in the entire basin were specially discussed with diagnostic ration, PAHs composition, and an improved risk quotient method. Results showed that the total concentration of PAHs varied from 99.65 to 25,303 ng g(-1) dry weight in sediments, from 51.0 to 559.1 ng L(-1) in water, and from 4528 to 51,080 ng g(-1) dry weight in SPM, respectively. The dominant PAHs in the three examined phases were 2-3 rings in most waterbodies. PAHs in the rivers were from mixed sources (petrogenic and pyrolytic inputs), whereas those in lakes and reservoirs were mainly from biomass combustion and petroleum combustion. PAHs in the entire basin exhibited moderate to high ecological risk, and the rivers (especially Hai River, Jiyun River, Chaobai River, and Beiyun River) suffered higher ecological risk than reservoirs and lakes. Most of the rivers with higher PAHs risk flow through or around megacity Beijing and Tianjin.