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[[alternative]]PCK2 promotes invasion and epithelial-to-mesenchymal transition in triple-negative breast cancer by promoting TGF-β/SMAD3 signaling through inhibiting TRIM67-mediated SMAD3 ubiquitination
No full text[[abstract]]PCK2, which encodes mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M), is upregulated in various cancers. We demonstrated high expression of PEPCK-M in approximately half of triple-negative breast cancers (TNBCs) previously. TNBC is associated with an aggressive phenotype and a high metastasis rate. In this study, we investigated the role of PCK2 in TNBC. PCK2 knockdown suppressed proliferation and mTOR signaling in TNBC cells. In addition, cell invasion/migration ability and the expression of epithelial-to-mesenchymal transition (EMT) markers were positively correlated with PCK2 expression in TNBC cells via regulation of transforming growth factor-beta (TGF-beta)/SMAD3 signaling. SMAD3 was positively regulated by PCK2 in TNBC cells. Knockdown of SMAD3 in PCK2-overexpressing TNBC cells reduced the expression levels of EMT markers, Snail and Slug, and suppressed cell invasion/migration. In addition, PCK2 knockdown attenuated the stimulatory effect of TGF-beta on SMAD3 phosphorylation in TNBC cells. PEPCK-M promotes the protein and mRNA expression of SMAD3 via competitive binding to tripartite motif-containing 67 (TRIM67), an E3 ubiquitin ligase, to reduce SMAD3 ubiquitination, which leads to promoting nuclear translocation of SMAD3 and autoregulation of SMAD3 transcription. Moreover, high PCK2 mRNA expression was significantly associated with poor survival in TNBC patients. In conclusion, our study revealed for the first time that PCK2 activates TGF-beta/SMAD3 signaling by regulating the expression and phosphorylation of SMAD3 by inhibiting TRIM67-mediated SMAD3 ubiquitination and promoting the stimulatory effect of TGF-beta to promote TNBC invasion. The regulatory effect of PCK2 on mTOR and TGF-beta/SMAD3 signaling suggests that PCK2 is a potential therapeutic target for suppressing TNBC progression
Response to the comment of Wasti on "Association between severity of diabetic complications and risk of cancer in middle-aged patients with type 2 diabetes"
No full textNO pain! No cancer? The crosstalk between nociception, ROS, and cancer development
No full text[[abstract]]Transient receptor potential (TRP) channels, particularly those involved in nociception (nociceptive TRP channels), are implicated in both pain and cancer development. Activation of these channels by diverse stimuli triggers calcium influx, leading to mitochondrial oxidative stress and reactive oxygen species (ROS) accumulation. This ROS production contributes to both nociceptive signaling (causing pain) and aging processes, including genomic instability, a key driver of carcinogenesis. Although a direct causal link between pain and cancer onset remains elusive, the shared involvement of nociceptive TRP channels strongly suggests a correlation. This opinion article proposes targeting the crosstalk between nociceptive TRP channels and ROS as a promising therapeutic strategy to mitigate cancer and cancer-associated pain simultaneously. While further research is needed to definitively establish a causal relationship between pain and cancer risk, the available evidence suggests that inhibiting this pathway may offer significant benefits for both cancer prevention and treatment
Lifestyle, inflammageing, and poor physical performance in middle-aged and older adults: a prospective cohort study in Taiwan
No full text[[abstract]]Background and Aims Poor physical performance (PPP) in terms of weakness and slow walking speed is closely associated with frailty during ageing. We aimed to analyse the associations between modifiable lifestyle factors, inflammation markers (hs-CRP, D-dimer, and fibrinogen), and the odds of PPP and state transitions between normal and PPP in older adults.Methods A total of 3756 participants ( 55 years) in wave 1 (2009-2013) and wave 2 (2014-2019) of the Healthy Aging Longitudinal Study in Taiwan (HALST) were analysed. A logistic regression model was used to assess the associations between lifestyle factors (physical activity [PA], diet, and psychosocial health), inflammation markers, comorbidities, and PPP (two or more of the criteria: grip strength, 6-minute walking distance, or gait speed among the lowest 20%).Results In total, 229 and 149 of the 773 PPP participants at wave 1 reversed and persistent in PPP state at wave 2, respectively. Higher PA (OR 0.917, 95% CI 0.894-0.941), psychosocial health (OR 0.964, 95% CI 0.955-0.972), LDL-C, and education level had significant protective effects, whereas greater waist circumference, D-dimer, fibrinogen, longer sleeping time, and comorbidities were positively associated with PPP. Higher PA, psychosocial health, and diet scores were protective against conversion to PPP, and increased PA and higher psychosocial health score were significant for reversion.Conclusions Older adults are encouraged to engage in various forms of PA and participate in societal events to increase their physical performance. To avoid further deterioration in physical frailty, screening for PPP may be adopted as a standard clinical practice for older adults
Socioeconomic status in the association between use of personal care products and exposure to endocrine-disrupting chemicals in pregnant Taiwanese women
No full text[[abstract]]Background Maternal exposure to endocrine-disrupting chemicals (EDCs), particularly those found in personal care products (PCPs), may affect child development. Socioeconomic inequalities in EDC exposure warrant further investigation. This study assessed the role of income and education in the association between PCP use and exposure to bisphenol A (BPA) and parabens in pregnant women.Methods Associations between PCP use and urinary concentrations of BPA and four parabens in pregnant women from the Taiwan Maternal and Infant Cohort Study were estimated using linear regression, with results expressed as the percentage change in concentrations for each additional PCP use per week. The analysis was stratified by income and education and predicted concentrations, and a 95% confidence interval (CI) was graphed according to the frequency of PCP use.Results Higher concentrations of methylparaben, ethylparaben, and propylparaben were associated with more frequent use of different PCPs, especially makeup. The above-lowest income group showed positive associations between frequency use of rinse-off PCPs and methylparaben (2.5%, 95%CI = 0.9%, 4.0%), propylparaben (2.8%, 95%CI = 0.3%, 5.3%), and between leave-on PCPs and methylparaben (3.1%, 95%CI = 1.8%, 4.4%), ethylparaben (2.2%, 95%CI = 0.1%, 4.2%), and propylparaben (2.8%, 95%CI = 0.8%, 4.9%). BPA was negatively associated with rinse-off PCPs (-1.2%, 95%CI = -2.3%, -0.2%). A positive association between leave-on PCPs and BPA was suggested in the lowest income group (1.7%, 95%CI = -0.4%, 3.7%). Predicted BPA concentrations were significantly higher in the lowest income group at higher frequencies of PCP use. Stratification by education showed the strongest associations in the postgraduate group for rinse-off PCPs with methylparaben (6.1%, 95%CI = 1.9%, 10.5%) and propylparaben (6.9%, 95%CI = 1.2%, 12.9%), as well as for leave-on PCPs with methylparaben (4.1%, 95%CI = 1.2%, 7.2%).Conclusion The associations observed between various PCPs and parabens suggest that reducing the use of certain PCPs in pregnant women could help lower paraben exposure. Higher levels of BPA in the lowest income group require further investigation of sources of BPA exposure, especially in disadvantaged populations
Deciphering lung adenocarcinoma evolution and the role of LINE-1 retrotransposition
No full text[[abstract]]Understanding lung cancer evolution can identify tools for intercepting its growth. In a landscape analysis of 1024 lung adenocarcinomas (LUAD) with deep whole-genome sequencing integrated with multiomic data, we identified 542 LUAD that displayed diverse clonal architecture. In this group, we observed an interplay between mobile elements, endogenous and exogenous mutational processes, distinct driver genes, and epidemiological features. Our results revealed divergent evolutionary trajectories based on tobacco smoking exposure, ancestry, and sex. LUAD from smokers showed an abundance of tobacco-related C:G>A:T driver mutations in KRAS plus short subclonal diversification. LUAD in never smokers showed early occurrence of copy number alterations and EGFR mutations associated with SBS5 and SBS40a mutational signatures. Tumors harboring EGFR mutations exhibited long latency, particularly in females of European-ancestry (EU_N). In EU_N, EGFR mutations preceded the occurrence of other driver genes, including TP53 and RBM10. Tumors from Asian never smokers showed a short clonal evolution and presented with heterogeneous repetitive patterns for the inferred mutational order. Importantly, we found that the mutational signature ID2 is a marker of a previously unrecognized mechanism for LUAD evolution. Tumors with ID2 showed short latency and high L1 retrotransposon activity linked to L1 promoter demethylation. These tumors exhibited an aggressive phenotype, characterized by increased genomic instability, elevated hypoxia scores, low burden of neoantigens, propensity to develop metastasis, and poor overall survival. Reactivated L1 retrotransposition-induced mutagenesis can contribute to the origin of the mutational signature ID2, including through the regulation of the transcriptional factor ZNF695, a member of the KZFP family. The complex nature of LUAD evolution creates both challenges and opportunities for screening and treatment plans
Luteinizing hormone induces murine hair loss through transient receptor potential canonical channel-mediated cell aging responses: Implications for female pattern hair loss pathogenesis
No full text[[abstract]]Menopause-related hormonal imbalances, particularly the decline in estrogen and the rise in luteinizing hormone (LH), are implicated in female pattern hair loss (FPHL). This study investigated LH's role in FPHL, as its precise function has remained unclear. Our results found that a significant association between elevated LH levels and FPHL. The binding of LH to LH receptor (LHR), activates downstream transient receptor potential canonical channels (TRPCs), which potentially mediate excess Ca(2+) signals to initiate cell aging responses. We revealed that LH causes reactive oxygen species (ROS) accumulation, Ca(2+) elevation and senescence in vibrissa follicles (VFs) and cell damage via DNA damage response (DDR), senescence, and senescence-associated secretory phenotype (SASP) activation in dermal papilla cells (DPCs). Hair loss in mice was due to LH-induced hair follicle (HF) damage and aging. The involvement of TRPCs in LH-induced pathogenesis was examined by treatment with TRPC inhibitors. Similarly, the balding area of FPHL showed higher levels of LHR compared to the non-balding area, while the expression of DDR-related genes, SASP-related genes and TRPCs were upregulated in scalp biopsies. Overall, we identified the impacts of LH/LHR signaling on the pathogenesis of FPHL, including TRPC-mediated cell aging responses in HFs
Facile, noninvasive, and chemical-free hydrogen peroxide and glucose detection using a fluorescent cellulose hybrid film embedded with ptRu/carbon dots
No full text[[abstract]]Diabetes affects over 8.8% of the global population, driving demand for noninvasive glucose detection methods. Traditional enzymatic assays are sensitive but face challenges such as high cost, complex preparation, low stability, and enzyme denaturation. This study aimed to enhance glucose detection sensitivity with a noninvasive easy-to-use technique using a fluorescent cellulose film. Lignin-derived carbon dots (LCDs) were synthesized as cost-effective, stable nanozymes for fluorescence-based glucose sensing. It was found that doping noble metal Ru onto Pt/LCDs synthesized in water mimicked peroxidase enzyme and could enhance the reactivity and sensitivity to ultralow levels for glucose detection at room temperature. To fabricate a wearable sensor, a transparent cellulose film embedded with PtRu/LCDs and glucose oxidase (GOx) was fabricated for biocompatible glucose sensing. The film achieved sensitive detection in the range of 0.05-1.0 mM (R2 = 0.94) with a detection limit of 50 μM, suitable for noninvasive glucose detection in saliva, tears, and sweat. This study highlights the potential of the PtRu/LCD-based cellulose film for highly sensitive, wearable glucose sensors compatible with smartphone applications, offering a simple, real-time, noninvasive, fast, and chemical reagent-free glucose sensing for preventive healthcare
Development of pd-loaded hf-based metal-organic framework as a dual-modal contrast agent for photoacoustic imaging and computed tomography
No full text[[abstract]]Noninvasive cancer imaging significantly improves diagnostics by providing comprehensive structural and functional information about tumors. Herein, we explored palladium nanoparticles loaded hafnium-based metal-organic framework (MOF) (Hf-EDB), i.e., Pd@Hf-EDB as an efficient dual modal contrast agent for computed tomography (CT) and photoacoustic imaging (PAI). The synergistic collaborations between (i) high-Z element Hf-based MOF with superior X-rays absorbing capabilities, (ii) H2EDB linkers with special pi-donation and pi-acceptor characteristics capable of strongly anchoring noble metals, and (iii) Pd nanoparticles with broad absorption in the UV to near-infrared (NIR) regions due to strong interband transition are ideal for implementation in CT and PAI. The successful synthesis of Pd@Hf-EDB nanoparticles was confirmed through morphology, crystallinity, and compositional characterizations using X-ray diffraction, SEM, TEM, DLS, and EDS. Soft X-ray tomography verified cellular uptake via phagocytosis of Pd@Hf-EDB by BxPC-3 tumor cells. In-vitro experiments revealed superior CT imaging performance of Pd@Hf-EDB over traditional molecular contrast agents like Iohexol. Broad absorption range in the UV-vis/NIR regions and superior PAI capabilities of Pd@Hf-EDB relative to gold nanorods are reported. Furthermore, the in vivo xenograft model demonstrated significant contrast enhancements near the tumor, highlighting the excellent PAI and CT capabilities of the synthesized Pd@Hf-EDB
Effect of household dysfunction in childhood on general health and depression in adolescence in Taiwan: A longitudinal birth cohort study
No full text[[abstract]]Although the harmful health effects of childhood adversity have been a public health focus, the sensitive periods for its impact on different aspects of health outcomes in adolescence are unknown. We aimed to examine the effects of the timing of experiencing childhood household dysfunction on general health and depression in adolescence. Data were obtained from the Taiwan Birth Cohort Pilot Study (TBCS-P), and respondents with surveys completed from birth to 15 years were included as study participants. The primary independent variable was the timing of exposure to childhood household dysfunction with four categories- early (age 3-5), late (age 8-12), chronic, and never. The dependent variables were general health and depression at age 15. Approximately 40% of children experienced household dysfunction before age 12. Individuals exposed to childhood household dysfunction were more likely to have poor health and higher levels of depressive symptoms than those who had never experienced it. Across the timing of exposure to household dysfunction, children in the early (OR = 1.64, 95% CI = 1.09-2.49) group had the worst general health at age 15. Moreover, experiencing household dysfunction in late childhood was associated with the greatest depression scores (beta = 0.62, p = 0.063), despite not reaching significance. Household dysfunction in childhood has long-term adverse effects on health in adolescence, emphasizing with early and late childhood as particularly sensitive periods for the impacts of household dysfunction on health and depression, respectively. Preventing household dysfunction in childhood and mitigating its impact are needed to ensure healthy development throughout life