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Introduction: Dyslipidemia commonly complicates type 2 diabetes mellitus, yet the relationship between glycosylated hemoglobin and blood lipid levels remains uncertain. Methods: This retrospective cross-sectional study included 27,158 participants from the People's Hospital of Yuxi. Statistical comparisons for continuous variables utilized analysis of variance (ANOVA), while chi-square analysis was employed for categorical variables. Boxplots assessed the concentration, dispersion, and deviation of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) distribution. A linear regression analysis examined the association between HbA1c and lipid profile, complemented by a fitting curve to visualize trends. Results: Participants who developed diabetes exhibited higher age and elevated Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, and FPG levels compared to those without diabetes (p < 0.001). Linear regression analysis demonstrated significant associations between HbA1c values and TC, TG, LDL-C, and HDL-C (p < 0.001). The plotted curve indicated that as TC, TG, and LDL levels increased, HbA1c levels rose, while HDL levels decreased. Conclusion: HbA1c was positively correlated with TC, TG, LDL-C, and negatively correlated with HDL-C in the population in the central Yunnan Plateau.
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BACKGROUND: Fine particular matter (PM2.5) has been associated with dementia, but limited information is available regarding the association between PM2.5 components and dementia. AIMS: We aimed to identify the major components of PM2.5 that affect cognitive function to further investigate its mechanism of action, and develop a prevention strategy for dementia. METHODS: In this study, we included 7804 participants aged ≥ 60 years recruited from seven counties in Zhejiang province, eastern China. The participants completed the baseline survey between 2014 and 2015, and were followed up until the end of 2020. We adopted single-component robust Poisson regression models for analyses, and estimated relative risks and 95% confidence intervals describing associations between the chemical constituents of PM2.5 exposure and incident cognitive impairment in those who were free from cognitive impairment at baseline. RESULTS: Significantly positive associations were observed between sulfate, nitrate, ammonium, and organic matter in PM2.5 and incident cognitive impairment across different exposure periods; the relative risks of 10-year exposure before enrollment ranged from 1.01 to 1.02. However, we did not find a significant association between black carbon and cognitive impairment. The point estimates of the relative risk values did not change substantially after performing the sensitivity analyses. CONCLUSIONS: Our findings strengthen the idea that long-term exposure to PM2.5 mass and its chemical components is associated with an elevated risk of incident cognitive impairment among older adults.
Subject(s)
Cognitive Dysfunction , Independent Living , Particulate Matter , Humans , Aged , Cognitive Dysfunction/epidemiology , Male , Particulate Matter/analysis , Particulate Matter/adverse effects , Female , China/epidemiology , Prospective Studies , Middle Aged , Environmental Exposure/adverse effects , Aged, 80 and over , Air Pollutants/analysis , Air Pollutants/adverse effects , Air Pollution/adverse effectsABSTRACT
Introduction: Depressive symptoms are often experienced by patients with arthritis and are correlated with poor health outcomes. However, the association between depressive symptoms and multidimensional factors (sociodemographic characteristics, health conditions, health behaviors, and social support) among older patients with arthritis in China remains poorly understood. This study aimed to explore the prevalence of depressive symptoms in older patients with arthritis in eastern China and identify the associated factors. Methods: We analyzed data of 1,081 older patients with arthritis using secondary data from 2014 to 2020 from a community-based ongoing study initiated in 2014 in eastern China. The prevalence of depressive symptoms was calculated, and univariate and multilevel logistic regression analyses were used to identify the associated factors. Results: The mean age of older patients with arthritis was 69.16 ± 7.13 years; 42.92% were men and 57.08% were women. The prevalence of depressive symptoms in older patients with arthritis was 14.99% (95% confidence interval: 12.91-17.26%), about 1.8 times higher than that in older adults without arthritis (8.49%, p < 0.001). Multilevel logistic regression identified perception of poor economic status (odds ratio [OR] = 5.52, p < 0.001), multimorbidity (OR = 1.96, p = 0.001), limitations in activities of daily living (OR = 2.36, p = 0.004), and living alone (OR = 3.13, p = 0.026) as factors positively associated with depressive symptoms. Patients diagnosed with arthritis at an older age had lower odds of experiencing depressive symptoms (OR = 0.67, p = 0.046). Conclusion: Screening for depressive symptoms is essential among older patients with arthritis, especially those who perceive themselves as having a poor economic status, are diagnosed at an earlier age, have multimorbidity, have limitations in activities of daily living, and live alone. The associations of age at arthritis diagnosis and dietary behaviors with depressive symptoms require further research.
Subject(s)
Arthritis , Depression , Humans , Male , Female , Aged , China/epidemiology , Arthritis/epidemiology , Depression/epidemiology , Prevalence , Middle Aged , Risk Factors , Cross-Sectional Studies , Social Support , Aged, 80 and over , Logistic Models , Activities of Daily Living , Socioeconomic FactorsABSTRACT
When analyzing challenging samples, such as low-template DNA, analysts aim to maximize information while minimizing noise, often by adjusting the analytical threshold (AT) for optimal results. A potential approach involves calculating the AT based on the baseline signal distribution in electrophoresis results. This study investigates the impact of reagent kits, testing quarters, environmental conditions, and amplification cycles on baseline signals using historical records and experimental data on low-template DNA. Variations in these aspects contribute to differences in baseline signal patterns. Analysts should remain vigilant regarding routine instrument maintenance and reagent replacement, as these may affect baseline signals. Prompt analysis of baseline status and tailored adjustments to ATs under specific laboratory conditions are advised. A comparative analysis of published methods for calculating the optimal AT from a negative signal distribution highlighted the efficiency of utilizing baseline signals to enhance forensic genetic analysis, with the exception of extremely low-template samples and high-amplification cycles. Moreover, a user-friendly program for real-time analysis was developed, enabling prompt adjustments to ATs based on negative control profiles. In conclusion, this study provides insights into baseline signals, aiming to enhance genetic analysis accuracy across diverse laboratories. Practical recommendations are offered for optimizing ATs in forensic DNA analysis.
Subject(s)
DNA , Laboratories , DNA/geneticsABSTRACT
Next-generation sequencing (NGS) allows for better identification of insertion and deletion polymorphisms (InDels) and their combination with adjacent single nucleotide polymorphisms (SNPs) to form compound markers. These markers can improve the polymorphism of microhaplotypes (MHs) within the same length range, and thus, boost the efficiency of DNA mixture analysis. In this study, we screened InDels and SNPs across the whole genome and selected highly polymorphic markers composed of InDels and/or SNPs within 300 bp. Further, we successfully developed and evaluated an NGS-based panel comprising 55 loci, of which 24 were composed of both SNPs and InDels. Analysis of 124 unrelated Southern Han Chinese revealed an average effective number of alleles (Ae ) of 7.52 for this panel. The cumulative power of discrimination and cumulative probability of exclusion values of the 55 loci were 1-2.37 × 10-73 and 1-1.19 × 10-28 , respectively. Additionally, this panel exhibited high allele detection rates of over 97% in each of the 21 artificial mixtures involving from two to six contributors at different mixing ratios. We used EuroForMix to calculate the likelihood ratio (LR) and evaluate the evidence strength provided by this panel, and it could assess evidence strength with LR, distinguishing real and noncontributors. In conclusion, our panel holds great potential for detecting and analyzing DNA mixtures in forensic applications, with the capability to enhance routine mixture analysis.
Subject(s)
DNA Fingerprinting , Polymorphism, Single Nucleotide , Humans , Polymorphism, Single Nucleotide/genetics , Sequence Analysis, DNA , DNA/genetics , DNA/analysis , High-Throughput Nucleotide Sequencing , Gene FrequencyABSTRACT
With the ageing of society's population, neurodegenerative diseases have become an important factor affecting the quality of life and mortality in the elderly. Since its physiopathological processes are complex and the authorized medications have recently been shown to have several adverse effects, the development of safe and efficient medications is urgently needed. In this study, we looked at how ginsenoside Rg1 works to postpone neural stem cell ageing and brain ageing, giving it a solid scientific foundation for use as a therapeutic therapy for neurodegenerative diseases.
Subject(s)
Ginsenosides , Neural Stem Cells , Neurodegenerative Diseases , Humans , Aged , Galactose/metabolism , Galactose/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , NF-E2-Related Factor 2/metabolism , Sirtuin 1/metabolism , Quality of Life , Ginsenosides/metabolism , Ginsenosides/pharmacology , Ginsenosides/therapeutic use , Neural Stem Cells/metabolism , Neurodegenerative Diseases/metabolismABSTRACT
Longer-term deterioration in saliva secretion has been observed to occur in response to aging. The functional deterioration of the salivary gland damages swallowing and chewing abilities and consequently reduces life quality of the elderly. There are, however, only a few proven effective treatments for aging salivary secretion disorders. Ganoderma lucidum polysaccharide (GLP) has been applied to treat various diseases because of its safety, efficacy, and low cost. We investigated the protective effect of GLP on the submandibular gland (SMG) during aging. D-galactose (D-gal) was used to treat the aging mice, and the body weight, water consumption, saliva secretion, and flow rate were measured after 6 weeks of modeling. Micromorphological changes of the SMG were assessed by hematoxylin-eosin staining and transmission electron microscopy. RT-qPCR and Western blot were used to detect the expression of apoptotic proteins and inflammatory cytokines. Aquaporins (AQPs) and rhythmic protein expression were analyzed by immunohistochemistry and immunofluorescence. The results showed that GLP effectively promoted the expression of AQP5, AQP4, and AQP1, inhibited the release of TNF-α, IL-6, and Bax, and reduced inflammation and apoptosis. Further experiments showed that GLP promoted the up-regulation of core clock genes and proteins and restored the co-localized expression of CLOCK and AQP5 that were weakened during aging, helping to attenuate aging-induced weight loss, decreased salivation, and structural and functional damage. The findings of this work contribute to understanding the nature of age-related modifications in SMG by identifying changes in AQP5 expression and regulatory mechanisms linked to SMG dysfunction during aging. GLP is a potential drug for maintaining healthy salivary gland (SG) status and preventing SG deficiency in the elderly.
Subject(s)
Reishi , Salivation , Mice , Animals , Reishi/metabolism , Galactose , Aquaporin 5/metabolism , Aging , Polysaccharides/pharmacologyABSTRACT
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/ß-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.
Subject(s)
Cysts , Polycystic Kidney, Autosomal Dominant , Mice , Animals , Polycystic Kidney, Autosomal Dominant/drug therapy , Polycystic Kidney, Autosomal Dominant/metabolism , Polycystic Kidney, Autosomal Dominant/pathology , Cilia , Tubulin/metabolism , Hedgehog Proteins/metabolism , Kidney/pathology , Mice, Knockout , Cysts/metabolism , Cysts/pathology , TRPP Cation Channels/metabolism , Epithelial Cells/metabolismABSTRACT
Lactic acid bacteria (LAB) can produce a vast spectrum of antifungal metabolites to inhibit fungal growth. The purpose of this study was to elucidate the antifungal effect of isolated Weissella cibaria BYL4.2 on Penicillium chrysogenum, the antifungal activity of W. cibaria BYL4.2 against P. chrysogenum was evaluated by the superposition method, results showed that it had obviously antifungal activity against P. chrysogenum. Studying the probiotic properties of BYL4.2 and determining it as beneficial bacteria. Furtherly, different treatments were carried out to characterize the antifungal activity of cell-free supernatant (CFS) produced by W. cibaria BYL4.2, and it was shown that the CFS was pH-dependent, partly heat-sensitive, and was not influenced by proteinaceous treatment. The CFS of W. cibaria BYL4.2 was analyzed by high-performance liquid chromatography (HPLC) and found the highest content of lactic acid. Screening of metabolic markers by a non-targeted metabolomics approach based liquid chromatography-mass spectrometry (LC-MS). The results speculated that organic acid especially detected D-tartaric acid was the main antifungal substance of CFS, which could cause the down-regulation of metabolites in the ABC transporters pathway, thereby inhibiting the growth of P. chrysogenum. Therefore, this study may provide important information for the inhibitory mechanism of W. cibaria BYL4.2 on P. chrysogenum, and provide a basis for further research on the antifungal effect of Weissella.
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Background: To explore the association between soy product consumption and the risk of depression in the community. Methods: In 2014, a total of 10,901 older people were recruited from Zhejiang province, China, and completed food frequency interviews. Participants were followed up over the next 6 years, and depression was assessed at each visit. Finally, 6,253 participants were included in the present study. Mixed effects models were performed to analyze the association by multivariate adjustments for potential confounders. Results: Over four-fifths of the eligible participants took soy food at least one day per week. The mixed effects model has shown the adjusted odds ratios (95% CI) of high-frequency consumers (4-7 days per week) were 0.46 (0.39-0.54) for depression with a cut-off score of 5, compared with non-consumers. Conclusions: More frequent soy product consumption was associated with a lower risk of depression.
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Buckwheat has beneficial effects on human intestinal health, which is often compounded with wheat to make food. Therefore, the effect of cereals mixture via in vitro fermentation on gut microbes and short-chain fatty acids (SCFAs) were investigated in this study. The mixture of wheat and tartary buckwheat (WT) produced more lactate and acetate, and the mixture of wheat and sweet buckwheat (WE) produced more propionate and butyrate. Compared with wheat (WA), the relative abundance of some beneficial bacteria significantly increased, such as Sutterella in WT and Faecalibacterium in WE. Cereals mixture also affected the expression of functional genes, involved in metabolic pathways and carbohydrate-active enzymes (CAZymes) that modulated SCFAs generation. This study provides new insights into the effects of sweet and tartary buckwheat on intestinal function, which is beneficial to applying both types of buckwheat in practical.
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Brusatol (BRU) is an important compound extracted from Brucea javanica oil, whose pharmacological effects are able to induce a series of biological effects, including inhibition of tumor cell growth, anti-inflammatory, antiviral, and antitumor. Currently, there are so few studies about the brusatol effects on colorectal cancer that its anticancer mechanism has not been clearly defined. In this study, we made an in-depth investigation into the brusatol effect towards the proliferation and metastasis of colon cancer and the possible mechanism. The inhibitory effect of BRU on the proliferation of colorectal cancer cells was unveiled via CCK-8 method and colony formation assay, while the inhibitory effect of BRU on migration and invasion of colorectal cancer cells was revealed by scratch assay and transwell assay. In addition, Western blot results also revealed that BRU inhibited not only the expressions of RhoA and ROCK1 but also the protein expressions of EMT-related markers e-cadherin, N-cadherin, Vimentin, MMP2, and MMP9 in colon cancer cells. Through the xenotransplantation model, our in vivo experiment further verified the antitumor effect of BRU on colon cancer cells in vitro, and the results were consistent with the protein expression trend. In conclusion, BRU may inhibit the proliferation and metastasis of colorectal cancer by influencing EMT through RhoA/ROCK1 pathway.
Subject(s)
Colonic Neoplasms , Quassins , Cadherins , Cell Movement , Cell Proliferation , Humans , Neoplastic Processes , Quassins/pharmacology , rho-Associated Kinases , rhoA GTP-Binding ProteinABSTRACT
Objective: To evaluate the longitudinal association of nut consumption with cognitive function in Chinese elderly. Methods: We analyzed the data from Zhejiang Ageing and Health Cohort Study including 9,028 participants. Nut consumption was evaluated in baseline questionnaire beginning at 2014. Cognitive function was assessed repeatedly through the Mini-Mental State Examination (MMSE) at baseline and three waves of follow-up (2015, 2016, and 2019-2020). Cognitive impairment was defined using education-specific cut-off points. Log-binomial regression models with the generalized estimating equations, controlled for an extensive range of potential confounders, were utilized to evaluate the association and estimate relative risk (RR). Results: After 6 years of follow-up, 3,266 (36.18%) participants were indicated as cognitive impairment by MMSE at least once. Compared with non-consumers or less-than-weekly consumers, participants consuming ≥70 g/week of nuts had 17% lower risks of cognitive impairment (RR = 0.83, 95% CI 0.75-0.91), whereas no association was found in those consuming <70 g/week of nuts. Moreover, relatively infrequent higher-amount consuming (≥70 g within one consuming day each week) was not associated with better cognitive performance. Furthermore, we did not observe significant effect modification caused by frequency of other food intake. Conclusion: Higher nut consumption was prospectively related to a lower risk of cognitive impairment in Chinese elderly.
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OBJECTIVE: To investigate the injury of cyanate on the pulmonary function and morphology of C57/BL6N mice. METHODS: Forty male C57/BL6N mice were randomly divided into two groups: normal control group (20 mice) and cyanate group (20 mice). Mice were exposed to 100 mmol/L cyanate feeding for 4 weeks, and pulmonary Raw (Resistance in Air Way) was measured at the beginning and end of the experiment. The mice were sacrificed at the end of the fourth week of the experiment, and the lung tissues were collected for pathological observation and molecular detection of E-Cadherin and Fibronectin. Well-growing A549 cells in logarithmic growth phase were treated with cyanate at the concentrations of 0, 0.25, 0.5 and 1 mmol/L for 24 h, and the cell viability was detected by CCK8 method; reactive oxygen species ROS fluorescent probe (DCFH-DA) was used to detect the changes of ROS levels, and expressions of E-Cadherin and Fibronectin in cells and pulmonary tissues were detected by Western blot. RESULTS: At the beginning of the experiment, the pulmonary airway resistance values of the mice in the normal control group and the cyanate group were (1.82±0.76)cmH2O/(L·s) and (1.85±0.78)cmH2O/(L·s), respectively, with no significant difference. Four weeks later, the pulmonary airway resistance value of mice in the cyanate group was increased to (4.86±0.87)cmH2O/(L·s) (Pï¼0.01). The HE staining showed that, compared with the normal control group, the injured alveolar structure, the thickened tracheal wall and the significantly proliferated pulmonary interstitial tissue were observed in the cyanate group. The Masson staining showed that elastic fibers were deposited around the trachea of mice in the cyanate group. The results of CCK8 assay for the viability of A549 cells showed that 0.5 mmol/L cyanate exposure could reduce the viability (Pï¼0.01). The immunofluorescence staining showed that cyanate could increase ROS level in A549 cells by producing green fluorescence in a concentration-dependent manner. The results of Western blotting showed that 0.5 mmol/L of cyanate treatment on A549 cells could reduce the expression of E-Cadherin (Pï¼0.01) with increasing concentration of cyanate. The expression level of Fibronectin in A549 cells was increased with the increasing cyanate concentration, and there was a significant difference (Pï¼0.01) on 1 mmol/L cyanate. Western blot results of lung showed the decreasing expression of E-Cadherin (Pï¼0.01) and increasing expression of Fibronectin (Pï¼0.01) in cyanate mice. CONCLUSION: Pathological concentrations of cyanate can induce the proliferation of pulmonary interstitial tissue, fibrous deposition, and increased pulmonary airway resistance in mice, which may be related to damaged pulmonary epithelial cell viability, enhanced ROS production, and induced pathologic changes of extracellular matrix by cyanate.
Subject(s)
Fibronectins , Lung , Mice , Male , Animals , Humans , Reactive Oxygen Species/metabolism , Lung/metabolism , A549 CellsABSTRACT
BS Sufu is a fermented food that is made by mixed black soybeans and soybeans. Microbial communities and metabolites play an important role for the final product. We characterized microbial diversity of BS Sufu during fermentation by high-throughput DNA sequencing. Meanwhile, volatile compounds were investigated by solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS). The results showed that bacterial diversity was higher than that of fungi in BS Sufu. We found the existence of bacterial and fungal core communities, including Enterococcus, Enterobacter, Rhizopus, and Monascus. Network analysis indicated that bacterial and fungal communities maintain positive and negative interactions, which are important to shape the resident microbial communities in Sufu. In addition, 17 free amino acids (FAAs) were detected at the post-fermentation stage, and umami amino acid mainly contributed to taste of BS Sufu. Furtherly, a total of 79 volatile constituents in BS Sufu, including nine alcohols, 31 esters, and four aldehydes, form synergistically the unique odor of Sufu. Additionally, the correlations between microbiota and metabolites were analyzed. Our results suggested that these microbial taxa and metabolites contribute to the taste and flavor of BS Sufu. This study provided information for analysis of BS Sufu at different fermentation periods in terms of the microbial diversity and metabolites, and this information was important to understand the properties of mixed soybeans Sufu.
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BACKGROUND: Abnormal tuftelin 1 (TUFT1) has been reported in multiple cancers and exhibits oncogenic roles in tumor progression. However, limited data are available on the relationship between TUFT1 and hepatocellular carcinoma (HCC), and the exact biological mechanism of TUFT1 is still poorly understood in HCC. AIM: To investigate TUFT1 expression in HCC and how interfering TUFT1 transcription affects HCC growth. METHODS: TUFT1 in HCC and non-HCC tissues based on databases of the Cancer Genome Atlas and Oncomine were analyzed, and TUFT1 in human HCC tissues on microarray were detected by immunohistochemistry for clinicopathological features, overall survival, and disease-free survival. HCC cells were transfected with constructed vectors of TUFT1 that interfere or over-express TUFT1 for analyzing the biological behaviors of HCC cells. Proliferation, invasion, migration, and apoptosis of cells were detected by cell counting kit-8, scratch assay, transwell tests, and flow cytometry and confirmed by Western blotting, respectively. RESULTS: Abnormal TUFT1 levels in databases expressed in HCC at messenger RNA (mRNA) level and HCC tissues were mainly located in cytoplasm and membrane. The level of TUFT1 expression in the HCC group was significantly higher (χ 2 = 18.563, P < 0.001) than that in the non-cancerous group, closely related to clinical staging, size, vascular invasion of tumor, hepatitis B e-antigen positive, and ascites (P < 0.01) of HCC patients, and negatively to HCC patients' overall survival and disease-free survival (P < 0.001). After interfering with TUFT1 transcription at mRNA level in the MHCC-97H cells by the specific TUFT1-short hairpin RNA, cell proliferation, invasion, and metastasis were significantly inhibited with increasing apoptosis rate. In contrast, proliferation, invasion, and migration were significantly enhanced after over-expression of TUFT1 mRNA in Hep3B cells in vitro. CONCLUSION: Oncogenic TUFT1 was associated with the progression of HCC and could be a potential molecular-target for inhibiting HCC growth.
Subject(s)
Carcinoma, Hepatocellular , Dental Enamel Proteins/genetics , Liver Neoplasms , Oncogene Proteins/genetics , Apoptosis , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Neoplasm InvasivenessABSTRACT
Lung adenocarcinoma (LUAD) is a tumor with high incidence. This study aimed to identify the central genes of LUAD. LUAD were analyzed by weighted gene co-expression network (WGCNA), and differentially expressed genes (DEGs) were identified. Samples were obtained from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases and included 515 LUAD samples and 347 normal samples. The WGCNA algorithm generated a total of 10 modules. The top 2 modules (MEturquoise and MEblue) with the highest correlation to LUAD were selected. Ten Hub genes (IL6, CDH1, PECAM1, SPP1, THBS1, HGF, SNCA, CDH5, CAV1, and DLC1) were screened in the intersecting genes of DEGs and WGCNA (MEturquoise and MEblue). Only SPP1 was correlated with LUAD poor survival, indicating that SPP1 may be a key Hub gene for LUAD. The competing endogenous RNA (ceRNA) network was constructed to analyze the regulatory relationship of Hub genes, and SPP1 may be directly regulated by 4 microRNAs (miRNAs) and indirectly regulated by 49 long noncoding RNAs (lncRNAs).
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The urea cycle (UC) removes the excess nitrogen and ammonia generated by nitrogen-containing compound composites or protein breakdown in the human body. Research has shown that changes in UC enzymes are not only related to tumorigenesis and tumor development but also associated with poor survival in hepatocellular, breast, and colorectal cancers (CRC), etc. Cytoplasmic ornithine, the intermediate product of the urea cycle, is a specific substrate for ornithine decarboxylase (ODC, also known as ODC1) for the production of putrescine and is required for tumor growth. Polyamines (spermidine, spermine, and their precursor putrescine) play central roles in more than half of the steps of colorectal tumorigenesis. Given the close connection between polyamines and cancer, the regulation of polyamine metabolic pathways has attracted attention regarding the mechanisms of action of chemical drugs used to prevent CRC, as the drug most widely used for treating type 2 diabetes (T2D), metformin (Met) exhibits antitumor activity against a variety of cancer cells, with a vaguely defined mechanism. In addition, the influence of metformin on the UC and putrescine generation in colorectal cancer has remained unclear. In our study, we investigated the effect of metformin on the UC and putrescine generation of CRC in vivo and in vitro and elucidated the underlying mechanisms. In nude mice bearing HCT116 tumor xenografts, the administration of metformin inhibited tumor growth without affecting body weight. In addition, metformin treatment increased the expression of monophosphate (AMP)-activated protein kinase (AMPK) and p53 in both HCT116 xenografts and colorectal cancer cell lines and decreased the expression of the urea cycle enzymes, including carbamoyl phosphate synthase 1 (CPS1), arginase 1 (ARG1), ornithine trans-carbamylase (OTC), and ODC. The putrescine levels in both HCT116 xenografts and HCT116 cells decreased after metformin treatment. These results demonstrate that metformin inhibited CRC cell proliferation via activating AMPK/p53 and that there was an association between metformin, urea cycle inhibition and a reduction in putrescine generation.
Subject(s)
Colorectal Neoplasms/metabolism , Metabolic Networks and Pathways/drug effects , Metformin/pharmacology , Putrescine/biosynthesis , Urea/metabolism , Animals , Biomarkers , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Gene Expression , Gene Expression Profiling , Heterografts , Humans , MAP Kinase Signaling System/drug effects , Mice , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
This study aims to investigate healthcare workers' (HCWs) willingness to receive SARS-CoV-2 vaccine in Zhejiang and to discover the related influential factors. The survey was conducted in six regions of Zhejiang Province, China, and 13 hospitals and 12 Centers for Disease Control and Prevention (CDC) were incorporated into the survey research. Participants were healthcare workers and a total of 3726 questionnaires were collected online, of which 3634 (97.53%) were analyzed. The relationships between the factors and the willingness to get vaccinated against COVID-19 were computed as odds ratios (ORs) by means of multi-factor non-conditional logistic regression analysis. Of the 3634 participants, 2874 (79.09%) HCWs expressed their willingness to get vaccinated if the SARS-CoV-2 vaccine becomes available. Respondents who were younger than 50 years (OR = 1.502, 95% CI: 1.047-2.154), those who believed that they were somewhat likely (OR = 1.658, 95% CI: 1.297-2.120) or likely (OR = 1.893, 95% CI: 1.334-2.684) to get infected by SARS-COV-2 and those with a positive attitude toward the SARS-CoV-2 vaccine were more willing to get vaccinated. Furthermore, compared to doctors, nurses were more reluctant to get vaccinated. In addition, it was found that higher the education level, lower the willingness to get vaccinated. This study revealed that HCWs in Zhejiang Province had a high willingness to get vaccinated. Awareness about the vaccine's effectiveness and safety and the disease severity should be promoted among HCWs over 50 years of age and nurses to increase the willingness to get vaccinated.
Subject(s)
COVID-19 Vaccines , COVID-19 , China , Health Personnel , Humans , Middle Aged , SARS-CoV-2 , VaccinationABSTRACT
BACKGROUND: DNA primase subunit 1 (PRIM1) has been reported as a novel oncogene in several cancer types. However, its roles in hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate underlying mechanisms of PRIM1 and identify it as a potential molecular target for HCC. METHODS: Hub genes were screened between HCC tissues and normal liver tissues in 3 gene expression omnibus (GEO) datasets and the cancer genome atlas (TCGA). The expression features and prognostic value of one of the hub genes PRIM1 were analyzed by bioinformatic analyses and immunohistochemistry. Loss-of-function and gain-of-function studies were used to investigate the regulatory role of PRIM1 in HCC cells. Real-time (RT)-qPCR, western blotting, and ubiquitin immunoprecipitation assays were performed to explore the underlying mechanisms. The xenograft model was employed to detect the roles of PRIM1 in tumor growth in vivo. Finally, the 3D spheroid model was conducted to validate the role of PRIM1 in tumor growth and sorafenib resistance. RESULTS: The hub genes of HCC were screened in multiple bioinformatic datasets. PRIM1, as one of the hub genes, was significantly overexpressed in HCC tissues in mRNA and protein levels. In addition, high expression of PRIM1 indicated poor prognosis of HCC patients in TCGA, ICGC, and Nantong cohorts. Overexpression of PRIM1 promoted the proliferation, migration/invasion, and sorafenib resistance of HCC cells, with the decrease in apoptosis and cell cycle arrest. Mechanically, PRIM1 facilitated epithelial-mesenchymal transition (EMT) process and the activity of PI3K/AKT/mTOR signaling of HCC cells. Additionally, PRIM1 could cause the ubiquitination and degradation of P53 by upregulating Ubiquitin Conjugating Enzyme E2 C (UBE2C). Furthermore, knockdown of PRIM1 significantly inhibited the growth of xenograft tumors and HCC cells-derived spheroids with enhanced sorafenib resistance. CONCLUSION: This study implies that PRIM1 may play a key role in the progression of HCC and may serve as a potential target for HCC treatment.