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1.
Foods ; 13(10)2024 May 09.
Article in English | MEDLINE | ID: mdl-38790766

ABSTRACT

BACKGROUND: Metabolic changes in donkey meat during the early postmortem period have not been previously reported. METHODS: The LC-MS-based metabolomics technique was conducted to understand the metabolic profiles and identify the key metabolites of donkey meat in the first 48 h postmortem. RESULTS: The pH values showed a decreasing trend followed by an increasing trend. Shear force was the lowest at 4 h and the highest at 24 h (p < 0.05). For the metabolome, some candidate biomarker metabolites were identified, such as adenine, inosine, n-acetylhistidine, citric acid, isocitrate, and malic acid. Predominant metabolic pathways, such as citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism, and purine metabolism, were affected by aging time. Overabundant n-acetylhistidine was identified in LT, declined at 12 h postmortem aging, and then increased. This may explain the significantly lower pH at 12 h postmortem. Adenine was higher at 4 h postmortem, then declined. Decreased ADP may indicate a fast consumption of ATP and subsequent purine metabolism in donkey meat. CONCLUSIONS: The results of this study provided new insights into early postmortem aging of donkey meat quality.

2.
Life Sci ; 349: 122731, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38782354

ABSTRACT

AIMS: An increasing number of studies have highlighted the biological significance of neutrophil activation and polarization in tumor progression. However, the characterization of tumor-associated neutrophils (TANs) is inadequately investigated. MATERIALS AND METHODS: Patients' expression profiles were obtained from TCGA, GEO, and IMvigor210 databases. Six algorithms were used to assess immune cell infiltration. RNA sequencing was conducted to evaluate the differentially expressed genes between induced N1- and N2-like neutrophils. A TAN-associated risk score (TRS) model was established using a combination of weighted gene co-expression network analysis (WGCNA) and RNA-seq data and further assessed in pan-cancer. A clinical cohort of 117 GC patients was enrolled to assess the role of TANs in GC via immunohistochemistry (IHC). KEY FINDINGS: A TRS signature was built with 10 TAN-related genes (TRGs) and most TRGs were highly abundant in the TANs of the GC microenvironment. The TRS model could accurately predict patients' prognosis, as well as their responses to chemotherapy and immunotherapy. The TRS was positively correlated with pro-tumor immune cells and exhibited negative relationship with anti-tumor immune cells. Additional functional analyses revealed that the signature was positively related to pro-tumor and immunosuppression pathways, such as the hypoxia pathway, across pan-cancer. Furthermore, our clinical cohort demonstrated TANs as an independent prognostic factor for GC patients. SIGNIFICANCE: This study constructed and confirmed the value of a novel TRS model for prognostic prediction of GC and pan-cancer. Further evaluation of TRS and TANs will help strengthen the understanding of the tumor microenvironment and guide more effective therapeutic strategies.


Subject(s)
Neutrophils , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Neutrophils/metabolism , Tumor Microenvironment/genetics , Prognosis , Female , Male , Gene Expression Regulation, Neoplastic , Gene Expression Profiling/methods , Middle Aged , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Transcriptome , Data Analysis , Multiomics
3.
J Food Sci ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38685881

ABSTRACT

Lipids are crucial substances for the formation and retention of volatile compounds (VOCs). The lipid and VOC profiles of boiled donkey meat were investigated by lipidomics and volatilomics. In total, 4277 lipids belonging to 39 subclasses were identified, comprising 26.93% triglycerides (TGs), 15.74% phosphatidylcholins (PCs), and 9.40% phosphatidylethanolamines. The relative percentage of TG in the meat significantly decreases (p < 0.001) from 0 to 40 min, after which there is no significant change, whereas PCs, sphingomyelins, and methyl phosphatidylcholines (MePCs) show the opposite trend. TG(16:1_18:1_18:2) and TG(16:0_16:1_18:2) appear to be key lipids for retaining VOCs in boiled donkey meat. Furthermore, PC(18:3e_16:0) and MePC(31:0e) were found to be potential markers for discriminating donkey meat. A total of 83 VOCs were detected, including 25.30% aldehydes, 18.07% hydrocarbons, 14.46% ketones, and 13.25% alcohols. Eleven characteristic VOCs with relative odor activity values >1 were identified as the predominant flavor compounds in boiled donkey meat, mainly hexanal and 1-octen-3-ol. Of the 258 differential lipids, 72 of them, especially polyunsaturated-fatty acid-rich lipids, are the main contributors to the formation of VOCs. Together, the key lipids for retention and formation of VOCs in donkey meat were revealed, providing a theoretical basis for VOC regulation.

4.
Aging (Albany NY) ; 16(6): 5387-5411, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38484140

ABSTRACT

Prostate cancer (PCa) is a common malignancy in elderly men. We have applied Traditional Chinese Medicine CFF-1 in clinical treatments for PCa for several years. Here, we aimed to identify the underlying mechanism of CFF-1 on PCa using network pharmacology and experimental validation. Active ingredients, potential targets of CFF-1 were acquired from the public databases. Subsequently, protein-protein interaction (PPI) and the herbs-active ingredients-target network was constructed. A prognostic model for PCa was also constructed based on key targets. In vitro experiments using PCa cell lines CWR22Rv1 and PC-3 were carried out to validate the potential mechanism of CFF-1 on PCa. A total of 112 bioactive compounds and 359 key targets were screened from public databases. PPI and herbs-active ingredients-target network analysis determined 12 genes as the main targets of CFF-1 on PCa. Molecular docking studies indicated that the primary active ingredients of CFF-1 possess strong binding affinity to the top five hub targets. DNMT3B, RXRB and HPRT1 were found to be involved in immune regulation of PCa. In vitro, CFF-1 was found to inhibit PCa cell proliferation, migration, invasion and induce apoptosis via PI3K-Akt, HIF-1, TNF, EGFR-TKI resistance and PD-1 checkpoint signaling pathways. This study comprehensively elucidates the underlying molecular mechanism of CFF-1 against PCa, offering a strong rationale for clinical application of CFF-1 in PCa treatment.


Subject(s)
Network Pharmacology , Prostatic Neoplasms , Aged , Male , Humans , Medicine, Chinese Traditional , Molecular Docking Simulation , Phosphatidylinositol 3-Kinases , Prostatic Neoplasms/drug therapy , Proto-Oncogene Proteins c-akt
5.
BMC Public Health ; 24(1): 721, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38448863

ABSTRACT

BACKGROUND: Filial piety, as a major traditional norm in Chinese culture and in Chinese families, affects the attitudes and behaviors of adult children toward their parents and impacts their end-of-life decision-making and the quality of death of their parents. Death literacy is a novel concept aimed at promoting palliative care in the context of public health. AIMS: To understand attitudes and behaviors related to filial piety and to examine the role of death literacy in filial behaviors toward dying parents among residents in the Guangdong-Hong Kong-Macao Greater Bay Area of China. METHODS: A cross-sectional online survey that employed the convenient and snowball sampling methods was adopted. Filial Piety Representations at Parents' End of Life Scale and Death Literacy Index were used. RESULTS: This study identified a significant gap between the filial piety attitudes and behaviors of Chinese adult children. Gender, caregiving experience and death literacy were predictors of filial behaviors in an end-of-life context. CONCLUSION: Providing truth disclosure support, offering guidance to young adult children and caregivers of terminally ill fathers, and strengthening factual and community knowledge of death are necessary to enhance the reciprocal comfort of both adult children and dying parents in the context of Chinese filiality.


Subject(s)
Death , Literacy , Young Adult , Humans , Hong Kong , Macau , Cross-Sectional Studies , China
6.
Dementia (London) ; 23(4): 610-621, 2024 May.
Article in English | MEDLINE | ID: mdl-38374689

ABSTRACT

OBJECTIVE: Healthcare professionals as well as families play a vital role in ensuring the quality of care for people living with dementia. However, the relationships between healthcare professionals and families of people living with dementia are not extensively examined, particularly within the Chinese cultural context of dementia. The goal of this study was to explore the views of healthcare professionals on their relationships with families of people living with dementia. DESIGN: This qualitative study was grounded in the interpretative phenomenological analysis framework. METHODS: Data were collected using focus-group interviews. Qualitative data were transcribed verbatim and analysed using interpretative phenomenological analysis. RESULTS: The study recruited a total of 26 healthcare professionals from 3 long-term care facilities. The study found that conflicts were inherent in the relationships between professionals and families of people living with dementia, and conflicts were found to manifest in three core domains: 1) Families demonstrated a lack of understanding about dementia, 2) Professionals faced challenges in managing families' unrealistic expectations regarding the disease status and the prognosis of people living with dementia, 3) Families did not perceive themselves as being responsible for the care of people living with dementia. CONCLUSIONS: The present study found that the prevailing factor underpinning the relational conflicts between healthcare professionals and families of people living with dementia, as reported by healthcare professionals was the perceived lack of understanding about dementia amongst families of those affected.


Subject(s)
Attitude of Health Personnel , Dementia , Family , Focus Groups , Health Personnel , Professional-Family Relations , Qualitative Research , Humans , Dementia/psychology , Female , Male , Health Personnel/psychology , Family/psychology , Middle Aged , Adult , Caregivers/psychology
7.
Aging (Albany NY) ; 16(3): 2563-2590, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38315450

ABSTRACT

Targeting Protein for Xenopus Kinesin Like Protein 2 (TPX2) serves as a microtubule associated protein for the regulation of spindle assembly and tumorigenesis. We aim to investigate the prognostic and immunological role of TPX2 in pan-cancer. TCGA database, Tumor Immune Single-cell Hub (TISCH), and Human Protein Atlas (HPA) were retrieved to evaluate the expression pattern of TPX2 as well as its diagnostic and prognostic value in solid tumors. Genomic alterations of TPX2 were assessed with cBioPortal database. In vitro experiments in lung adenocarcinoma (LUAD) were performed to confirm the potential role of TPX2. Overexpression of TPX2 was found in 22 types of cancers, and was positively related with copy number variations (CNV) and negative with methylation. Up-regulated TPX2 could predict worse outcomes in the majority of cancers. Single-cell analysis revealed that TPX2 was mainly distributed in malignant cells (especially in glioma) and proliferating T cells. Genomic alteration of TPX2 was common in different types of tumors, while with prognostic value in two types of cancers. Additionally, significant correlations were found between TPX2 expression and tumor microenvironment (including stromal cells and immune cells) as well as immune related genes across cancer types. Drug sensitivity analysis revealed that TPX2 could predict response to chemotherapy and immunotherapy. Functional analyses demonstrated close relationship of TPX2 with immune function and malignant phenotypes. Finally, it was confirmed that knockdown of TPX2 could reduce proliferation and migration ability of LUAD cells. In summary, TPX2 could serve as a diagnostic and prognostic biomarker and a potential immunotherapy marker.


Subject(s)
DNA Copy Number Variations , Neoplasms , Humans , Tumor Microenvironment/genetics , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Neoplasms/genetics , Neoplasms/therapy , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Immunotherapy , Microtubule-Associated Proteins/genetics
8.
Food Sci Anim Resour ; 44(1): 165-177, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38229857

ABSTRACT

Volatile compounds (VOCs) are an important factor affecting meat quality. However, the characteristic VOCs in different parts of donkey meat remain unknown. Accordingly, this study represents a preliminary investigation of VOCs to differentiate between different cuts of donkey meat by using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) combined with chemometrics analysis. The results showed that the 31 VOCs identified in donkey meat, ketones, alcohols, aldehydes, and esters were the predominant categories. A total of 10 VOCs with relative odor activity values ≥1 were found to be characteristic of donkey meat, including pentanone, hexanal, nonanal, octanal, and 3-methylbutanal. The VOC profiles in different parts of donkey meat were well differentiated using three- and two-dimensional fingerprint maps. Nine differential VOCs that represent potential markers to discriminate different parts of donkey meat were identified by chemometrics analysis. These include 2-butanone, 2-pentanone, and 2-heptanone. Thus, the VOC profiles in donkey meat and specific VOCs in different parts of donkey meat were revealed by HS-GC-IMS combined with chemometrics, whcih provided a basis and method of investigating the characteristic VOCs and quality control of donkey meat.

9.
Palliat Support Care ; : 1-9, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38031427

ABSTRACT

OBJECTIVES: This study aims at investigating the current status of death literacy and parent's death quality among adult children in China. A cross-sectional survey was conducted to explore the associations between death literacy and parent's death quality and to provide evidence for developing public policies for improving the quality of death and end-of-life care for the population in the Greater Bay Area (GBA) of China. METHODS: A cross-sectional design was adopted. Participants who experienced their father's and/or mother's death were recruited from 5 cities in the GBA of China in 2022. The Good Death Inventory (GDI) and the Death Literacy Index (DLI) were used to investigate the perceived quality of death of the parents of the participants and the death literacy of the participants. RESULTS: A total of 511 participants were recruited. Participants with higher GDI scores were positively associated with DLI scores (p < 0.001). Adult children who had close relationships before their parents' death also had higher levels of DLI. SIGNIFICANCE OF RESULTS: This study investigated death literacy among bereaved adult children in China, filling a gap in the investigation of death literacy among Chinese residents. It found that parents' death experience can have a significant impact on the death literacy of adult children, which may affect their understanding and preparation for their own eventual death. Promotion of family discussion on death, development of community palliative care, and improving public death literacy are urgently needed in China.

10.
Cell Res ; 33(11): 835-850, 2023 11.
Article in English | MEDLINE | ID: mdl-37726403

ABSTRACT

Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals, controlling metabolic states beyond energy metabolism. However, whether glycolytic metabolites also play a role in controlling cell fate remains unexplored. Here, we find that low levels of glycolytic metabolite 3-phosphoglycerate (3-PGA) can switch phosphoglycerate dehydrogenase (PHGDH) from cataplerosis serine synthesis to pro-apoptotic activation of p53. PHGDH is a p53-binding protein, and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2, both of which are also p53-binding proteins. This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis. Furthermore, we show that PHGDH mutants (R135W and V261M) that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions, while the mutants (T57A and T78A) unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma (HCC) cells, even in the presence of high glucose. In vivo, PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC, whereas PHGDH-R135W prevents apoptosis and promotes HCC growth, and knockout of Trp53 abolishes these effects above. Importantly, caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH. Together, these results unveil a mechanism by which glucose availability autonomously controls p53 activity, providing a new paradigm of cell fate control by metabolic substrate availability.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Mice , Phosphoglycerate Dehydrogenase/genetics , Phosphoglycerate Dehydrogenase/metabolism , Tumor Suppressor Protein p53/metabolism , Serine/metabolism , Cell Line, Tumor
11.
BMC Genomics ; 24(1): 481, 2023 Aug 24.
Article in English | MEDLINE | ID: mdl-37620752

ABSTRACT

BACKGROUND: Wulong geese (Anser cygnoides orientalis) are known for their excellent egg-laying performance. However, they show considerable population differences in egg-laying behavior. This study combined genome-wide selection signal analysis with transcriptome analysis (RNA-seq) to identify the genes related to high egg production in Wulong geese. RESULTS: A total of 132 selected genomic regions were screened using genome-wide selection signal analysis, and 130 genes related to high egg production were annotated in these regions. These selected genes were enriched in pathways related to egg production, including oocyte meiosis, the estrogen signaling pathway, the oxytocin signaling pathway, and progesterone-mediated oocyte maturation. Furthermore, a total of 890 differentially expressed genes (DEGs), including 340 up-regulated and 550 down-regulated genes, were identified by RNA-seq. Two genes - GCG and FAP - were common to the list of selected genes and DEGs. A non-synonymous single nucleotide polymorphism was identified in an exon of FAP. CONCLUSIONS: Based on genome-wide selection signal analysis and transcriptome data, GCG and FAP were identified as candidate genes associated with high egg production in Wulong geese. These findings could promote the breeding of Wulong geese with high egg production abilities and provide a theoretical basis for exploring the mechanisms of reproductive regulation in poultry.


Subject(s)
Geese , Transcriptome , Animals , Geese/genetics , Gene Expression Profiling , Genomics , Meiosis
12.
Hematology ; 28(1): 2251199, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37650932

ABSTRACT

Objective: Diffuse Large B-Cell Lymphoma (DLBCL) is a common and frequently occurring subtype of Non-Hodgkin Lymphoma (NHL). The effective treatment and prognosis of DLBCL are still urgently needed to be explored. This article aims to shed light on the connection between DLBCL survival and NR3C1 expression levels. Methods: First, we divided the 952 DLBCL patients into an NR3C1 high-expression group and an NR3C1 low-expression group and compared the baseline characteristics of the two groups. Second, we used multivariate analysis to predict the dependent variable for age, pathology, ECOG score, lactate dehydrogenase (LDH) ratio, and NR3C1 expression level. Finally, we analyzed the progression-free survival (PFS) and overall survival rate (OS) of DLBCL patients with high or low NR3C1 expression. Results: DLBCL patients with high NR3C1 expression had a better prognosis than those with low NR3C1 expression (OS, P < 0.0001). In DLBCL patients of CHOP therapy, high NR3C1 expression was associated with a good survival prognosis in OS (OS, P = 0.028). Conclusion: In multivariate analysis, NR3C1 high expression was an independent prognostic factor that predicted a longer OS of DLBCL (OS, P = 0.0003). NR3C1 is considered an independent predictor of DLBCL patients and can be used as a biomarker for the prognosis of DLBCL.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Humans , Prognosis , Lymphoma, Large B-Cell, Diffuse/genetics , L-Lactate Dehydrogenase , Gene Expression , Receptors, Glucocorticoid
13.
Front Public Health ; 11: 1140475, 2023.
Article in English | MEDLINE | ID: mdl-37250081

ABSTRACT

Objective: Applying public health approaches to address palliative care allows for a broader perspective. The Death Literacy Index (DLI) is a novel instrument designed to assess the knowledge and skills required to access, comprehend, and make informed decisions regarding end-of-life care. Translation of the DLI could strengthen the capacity to build desirable services and policies regarding dying and death. It could also help to identify the barriers to services and future advocacy efforts. Methods: The DLI was forward translated into Chinese and backward translated through two panels. Two rounds of cognitive interviews and a pilot test were conducted before the survey. A sample of 3,221 participants was recruited via an online survey in five cities in southern China (Guangzhou, Zhuhai, Jiangmen, Hong Kong and Macao) to evaluate the factor structure, validity and reliability of the translated DLI. Additionally, multi-group confirmatory factor analyses (MGCFA) were performed to examine measurement invariance across genders and the experiences of parental death. Results: Exploratory factor analysis showed a six-factor structure for the translated DLI, and confirmatory factor analysis confirmed the structure. The overall scale and subscales had high internal consistency and satisfactory validity. The results from MGCFA showed that death literacy was adequately invariant for different genders and experiences of parental death. Conclusion: The Chinese DLI is a reliable and valid instrument for measuring death literacy among people in southern China, and therefore can be used for both research and community practice.


Subject(s)
Literacy , Humans , Male , Female , Reproducibility of Results , Psychometrics , China , Hong Kong
14.
Front Nutr ; 10: 1079799, 2023.
Article in English | MEDLINE | ID: mdl-37006938

ABSTRACT

The distinctive flavor compounds of donkey meat are unknown. Accordingly, in the present study, the volatile compounds (VOCs) in the meat from SanFen (SF) and WuTou (WT) donkeys were comprehensively analyzed by gas chromatography-ion mobility spectrometry (GC-IMS) combined with multivariate analysis. A total of 38 VOCs, of which 33.33% were ketones, 28.89% were alcohols, 20.00% were aldehydes, and 2.22% were heterocycles, were identified. Ketones and alcohols were significantly more abundant for SF than for WT, whereas aldehydes showed the opposite trend. The donkey meats from the two strains were well differentiated using topographic plots, VOC fingerprinting, and multivariate analysis. A total of 17 different VOCs were identified as potential markers for distinguishing the different strains, including hexanal-m, 3-octenal, oct-1-en-3-ol, and pentanal-d. These results indicate that GC-IMS combined with multivariate analysis is a convenient and powerful method for characterizing and discriminating donkey meat.

15.
Front Vet Sci ; 10: 1126138, 2023.
Article in English | MEDLINE | ID: mdl-37008357

ABSTRACT

Introduction: The number of the large-scale donkey breeding farms in China has increased dramatically. However, information regarding the situation of a Chinese donkey population under large-scale donkey breeding farms is limited. Methods: This survey report was conducted using questionnaires online to investigate the current situation of the donkey original breeding farms in China, in terms of donkey stock, local breeds, reproductive parameters, growth and lactation performance, and future perspectives. China has developed the donkey reserve system based on national, provincial and non-governmental (self-own) donkey original breeding farms. Results: In the present study, a total of 38 donkey original breeding farms concentrated in Northern of China were studied, and 52% of them keep their donkeys with a stocking density of 100-500 donkeys. China is rich in various local donkey breeds, and 16 local donkey breeds including large-sized, medium-sized and small-sized breeds were collected in our survey. Dezhou donkey are prevalent with a percentage of more than 57% of the total donkeys, while the Cullen donkeys belong to small-sized donkey breeds are scare. The reproductive efficiency and donkey productivity were different across donkey farms, indicating potential differences in management and breeding practices between different donkey original breeding farms. The artificial insemination has been performed in these donkey farms with an average proportion of 73%. Regarding the donkey productivity, the national and provincial donkey original breeding farms showed a higher birthweight and fat content in donkey milk than self-own farms. Furthermore, our results indicate that the donkey breeds with different body size also have important influence on the reproduction parameters and donkey productivity, with the large-sized donkeys had better performance compared to the small-sized donkeys. Discussion: In summary, our survey provided valuable baseline information on the situation of donkey population dynamics in the donkey original breeding farms. However, further study is required in the future to investigate the factors such as donkey health care, management and nutrition during breeding, fattening and lactation that influence donkey productivity under large-scale farm systems.

16.
Exp Hematol Oncol ; 12(1): 28, 2023 Mar 07.
Article in English | MEDLINE | ID: mdl-36882855

ABSTRACT

BACKGROUND: Cell cycle dysregulation characterized by cyclin D1 overexpression is common in mantle cell lymphoma (MCL), while mitotic disorder was less studied. Cell division cycle 20 homologue (CDC20), an essential mitotic regulator, was highly expressed in various tumors. Another common abnormality in MCL is p53 inactivation. Little was known about the role of CDC20 in MCL tumorigenesis and the regulatory relationship between p53 and CDC20 in MCL. METHODS: CDC20 expression was detected in MCL patients and MCL cell lines harboring mutant p53 (Jeko and Mino cells) and wild-type p53 (Z138 and JVM2 cells). Z138 and JVM2 cells were treated with CDC20 inhibitor apcin, p53 agonist nutlin-3a, or in combination, and then cell proliferation, cell apoptosis, cell cycle, cell migration and invasion were determined by CCK-8, flow cytometry and Transwell assays. The regulatory mechanism between p53 and CDC20 was revealed by dual-luciferase reporter gene assay and CUT&Tag technology. The anti-tumor effect, safety and tolerability of nutlin-3a and apcin were investigated in vivo in the Z138-driven xenograft tumor model. RESULTS: CDC20 was overexpressed in MCL patients and cell lines compared with their respective controls. The typical immunohistochemical marker of MCL patients, cyclin D1, was positively correlated with CDC20 expression. CDC20 high expression indicated unfavorable clinicopathological features and poor prognosis in MCL patients. In Z138 and JVM2 cells, either apcin or nutlin-3a treatment could inhibit cell proliferation, migration and invasion, and induce cell apoptosis and cell cycle arrest. GEO analysis, RT-qPCR and WB results showed that p53 expression was negatively correlated with CDC20 expression in MCL patients, Z138 and JVM2 cells, while this relationship was not observed in p53-mutant cells. Dual-luciferase reporter gene assay and CUT&Tag assay revealed mechanistically that CDC20 was transcriptionally repressed by p53 through directly binding p53 to CDC20 promoter from - 492 to + 101 bp. Moreover, combined treatment of nutlin-3a and apcin showed better anti-tumor effect than single treatment in Z138 and JVM2 cells. Administration of nutlin-3a/apcin alone or in combination confirmed their efficacy and safety in tumor-bearing mice. CONCLUSIONS: Our study validates the essential role of p53 and CDC20 in MCL tumorigenesis, and provides a new insight for MCL therapeutics through dual-targeting p53 and CDC20.

17.
Pharmacogenomics J ; 23(4): 89-94, 2023 07.
Article in English | MEDLINE | ID: mdl-36918700

ABSTRACT

Acute myeloid leukemia (AML) is malignant clonal expansion of myeloid blasts with high heterogeneity and numerous molecular biomarkers have been found to judge the prognosis in some specific classifications of AML. Furthermore, as for patients with cytogenetically normal acute myeloid leukemia (CN-AML), we need to find more new biomarkers to predict the patients' outcomes. Recently, the expression level of Neuronal Calcium Sensor 1 (NCS1) has been associated with the prognosis of breast cancer and hepatocellular carcinoma, but nothing related has been reported about hematological malignancies. Therefore, we make this study to explore the relationship between the NCS1 expression level and CN-AML. We analyzed the relation between survival and NCS1 RNA expression through 75 CN-AML patients from Cancer Genome Atlas (TCGA) database and 433 CN-AML patients (3 independent datasets) from Gene Expression Omnibus (GEO) database. Additionally, we compared the NCS1 RNA expression between 138 leukemia stem cells positive (LSCs+) samples and 89 leukemia stem cells negative (LSCs-) samples from 78 AML patients from GSE76004 dataset. In our study, CN-AML patients with high expression level of NCS1 have longer EFS or OS. In addition, the NCS1 expression level in leukemia stem cells was low (p = 0.00039). According to these findings, we concluded that the high expression of NCS1 can predict favorable prognosis in CN-AML patients. Furthermore, our work put forward that NCS1 expresses lower in LSCs+, which might be an important mechanism to explain the aggressiveness of AML.


Subject(s)
Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/genetics , RNA
18.
Front Public Health ; 11: 1043144, 2023.
Article in English | MEDLINE | ID: mdl-36778560

ABSTRACT

Objectives: The study was the first to explore Chinese residents' preferred place of care at the end of life and preferred place of death in Macao. Methods: A cross-sectional questionnaire survey was conducted online and face-to-face. The questionnaire was designed in Chinese, and both online and face-to-face surveys were conducted in Chinese. The study was conducted in Macao. Macao residents aged 18 years and older were recruited. Results: A total of 737 responses were valid, 65% were female, aged between 19 and 101 years; 43.4% of respondents preferred to be cared for at home in the last 6 months; however, less than one-fifth preferred to die at home. One-third of respondents chose to die in the hospice, and over a quarter of them preferred to die in hospitals. Compared with people aged between 18 and 39 years, people aged between 40 and 64 years did not want to be cared for at home in the last 6 months, and they did not want to die at home either. Conclusion: The results of the study suggested that there is a need for palliative home care in Macao, and the government should consider developing such a service and review current laws and regulations in supporting the service. Education is equally important for healthcare professionals, enabling them to support palliative care development in the community.


Subject(s)
East Asian People , Terminal Care , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Cross-Sectional Studies , Hospitals , Macau , Surveys and Questionnaires
19.
Environ Sci Pollut Res Int ; 30(18): 52369-52379, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36840880

ABSTRACT

To explore the impact of embryonic exposure to phenanthrene (Phe), a typical tricyclic polycyclic aromatic hydrocarbon, on cardiac development in next generation, fertilized zebrafish embryos were exposed to 0.05, 0.5, 5 and 50 nM Phe for 96 h, and then transferred to clear water and raised to adulthood. The cardiac development in F1 larvae generated by adult females or males mated with unexposed zebrafish was assessed. Malformation and dysfunction of the heart, such as increased heart rate, arrhythmia, enlarged heart and abnormal contraction, were shown in both paternal and maternal F1 larvae. A greater impact on the distance between the sinus venosus and bulbus arteriosus was exhibited in maternal F1 larvae, while paternal F1 larvae displayed a more severe impact on heart rate and arrhythmia. The transcription of genes related to cardiac development was disturbed in F1 larvae. DNA methylation levels in the promoter of some genes were associated with their transcription. The expression of acetylated histone H3K9Ac and H3K14Ac in maternal F1 larvae was no significantly changed, but was significantly downregulated in paternal F1 larvae, which might be associated with the downregulated transcription of tbx5. These results indicate that exposure to Phe during embryogenesis adversely affects cardiac development in F1 generation, and the effects and toxic mechanisms showed sex-linked hereditary differences, highlighting the risk of Phe exposure in early life to heart health in next generation.


Subject(s)
Phenanthrenes , Water Pollutants, Chemical , Animals , Male , Female , Zebrafish , Larva/genetics , Heart , Arrhythmias, Cardiac , Phenanthrenes/toxicity , Water Pollutants, Chemical/toxicity
20.
Anim Biotechnol ; 34(5): 1786-1795, 2023 Nov.
Article in English | MEDLINE | ID: mdl-35302433

ABSTRACT

The main component of donkey meat is skeletal muscle, and different muscle fibers have been found to be associated with meat quality. However, RNA-seq technology has yet to be used to profile the transcriptomic changes of different muscles of the donkey. In this study, the characterizations of different muscles on the gene expression profiles of Dezhou donkey were obtained, the aim was to identify the important genes in donkey muscles, and aid in improving donkey meat quality via RNA-seq. In the donkey gluteus (DG) and donkey longissimus dorsi (DL) group, GO enrichment indicated that DEGs were mainly involved in the biological regulation and metabolic process, and KEGG analysis shows that a total of 427 DEGs were mapped to 216 KEGG pathways and 23 KEGG pathways were significantly enriched such as the ribosome, glycolysis/gluconeogenesis, glucagon signaling pathway and biosynthesis of amino acids pathways. Meanwhile, 504 DEGs were mapped to 223 KEGG pathways, in which 17 were significantly enriched including cardiac muscle contraction and oxytocin signaling pathway in donkey hamstring muscles (DH) and DL group. In addition, the tenderness in donkey meat might involve muscle fiber type and glucose metabolism, which might profit from the DEGs including MYH1, MYH7, TNNC1, TNNI3, TPM3, ALDOA, ENO3, and PGK1. The genes found in this study will provide some ideas for further understanding the molecular mechanism of donkey meat quality.


Subject(s)
Gene Expression Profiling , Transcriptome , Animals , RNA-Seq , Gene Expression Profiling/veterinary , Muscle, Skeletal/metabolism , Muscle Fibers, Skeletal
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