Liver cancer is the fatal cause of cancer deaths worldwide due to its aggressiveness and lack of effective therapies. Tiliroside (C
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) is an active compound extracted from herb plant Tribulus ...terrestris L., which has been used as alternative therapy in clinic practice. However, its therapeutic use against liver cancer has not been previously reported. Here, we showed that Tiliroside exerted significantly higher anti-proliferation effect on liver cancer cell lines Hep3B and SNU-449 than on liver normal cell THLE-3 cells or NC group, respectively, by using MTS assay. Results from colony formation, immigration and invasion assays support the anticancer efficacy of Tiliroside and its low-toxic property while treating liver normal cell THLE-3. 3D spheroid formation and CD133 expression level also displays its anti-stemness effect. It has been showed that Tiliroside may function as Carbonic anhydrases XII (CAXII) inhibitor and affects apoptotic E2F1/E2F3/Caspase-3 axis by using CAXII esterase activity assay, Human carbonic anhydrase 12 (CA-12) ELISA Kit, quantitative reverse transcription PCR (RT-qPCR) as well as CaspACE Assay System, respectively. In summary, we demonstrate for the first time that Tiliroside suppresses liver cancer development possibly by acting as a novel CAXII inhibitor, which warrant further investigation on its therapeutic implications.
m6A-methyltransferase METTL3 and demethylase FTO regulate gene expression by dynamically modifying RNA methylation. However, their clinical relevance in renal Clear Cell Carcinoma (CCRCC) has not ...been well elucidated.
This study aims to investigate prognostic values of FTO and METTL3 mRNA and DNA methylation, their differential expression and associations with chemokines and inflammation-related genes in CCRCC.
Kaplan-Meier survival curves and multivariate cox regression were performed for survival analyses, and random-effects meta-analysis was conducted for differential expression of FTO and METTL3 in CCRCC.
A significantly negative correlation was observed between mRNA and DNA methylation for both FTO and METTL3. Survival analysis showed a superior survival in patients with either high FTO mRNA or low DNA methylation, or low METTL3 mRNA or high DNA methylation. The adjusted hazard ratios were 0.67 (95% CI: 0.49-0.91, p = 0.01) for high vs. low FTO mRNA, 2.17 (1.38-3.42, p = 0.0008) for high vs. low FTO DNA methylation, 1.97 (1.45-2.68, p < 0.0001) for high vs. low METTL3 mRNA, and 0.49 (0.31-0.79, p = 0.003) for high vs. low METTL3 DNA methylation, respectively. There was a significant interaction between FTO and METTL3 mRNA levels (p = 0.024). Upregulation of FTO and METTL3 with 1.64 folds (95% CI: 1.43-1.89) and 1.17 folds (1.02-1.35), respectively, was observed in CCRCC vs. normal kidney tissues. FTO and METTL3 mRNA showed opposite expressions of CD8+ T cell migration-related chemokines.
Dysregulated FTO and METTL3 may be involved in the disease development and progression, affecting immune response in CCRCC. FTO and METTL3 expression and DNA methylation are potential prognostic markers of CCRCC.
Hepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality but lacks effective treatments thus far. Although the emergence of immune checkpoint inhibitors in recent years has ...shed light on the treatment of HCC, a considerable number of patients are still unable to achieve durable and ideal clinical benefits. Therefore, refining the combination of immune checkpoint inhibitors (ICIs) to enhance the therapeutic effect has become a global research hotspot. Several histone deacetylase 2 inhibitors have shown advantages in ICIs in many solid cancers, except for HCC. Additionally, the latest evidence has shown that histone deacetylase 2 inhibition can regulate PD-L1 acetylation, thereby blocking the nuclear translocation of PD-L1 and consequently enhancing the efficacy of PD-1/PD-L1 inhibitors and improving anti-cancer immunity. Moreover, our team has recently discovered a novel HDAC2 inhibitor (HDAC2i), valetric acid (VA), that possesses great potential in HCC treatment as a monotherapy. Thus, a new combination strategy, combining HDAC2 inhibitors with ICIs, has emerged with significant development value. This perspective aims to ignite enthusiasm for exploring the application of ideal HDAC2 inhibitors with solid anti-tumor efficacy in combination with immunotherapy for HCC.
Purpose
HCC incidence has been continuously rising in the US for the past 30 years. To understand the increase in HCC risk, we conducted a case–control study in Connecticut, New Jersey and part of ...New York City.
Methods
Through rapid case ascertainment and random digit dialing, we recruited 673 incident HCC patients and 1,166 controls. Information on demographic and anthropometric characteristics, lifestyle factors, medical and family cancer histories, were ascertained through telephone interviews using a structured questionnaire. Saliva specimens were collected for testing hepatitis C virus (HCV) antibodies. Unconditional logistic regression models were utilized to calculate odds ratio (OR) and 95% confidence interval (CI) to determine HCC associations with risk factors.
Results
The study confirmed that HCV infection and obesity were important risk factors for HCC, ORs 110 (95% CI 59.2–204) and 2.13 (95% CI 1.52–3.00), respectively. High BMI and HCV infection had synergy in association with elevated HCC risk. Patients both obese and infected with HCV had HCC detected on average nearly 10 years earlier than those with neither factor. Diabetes, cigarette smoking and heavy alcohol intake were all associated with increased risk of HCC, whereas aspirin and other NSAID use were associated with reduced risk. HCC cases tended to attain less education, with lower household incomes, unmarried, and to have had more sexual partners than the controls.
Conclusions
Individuals at risk of HCC in the US comprise a unique population with low socioeconomic status and unhealthy lifestyle choices. Given the multifactorial nature, a comprehensive approach is needed in HCC prevention.
•PTS- doped PPy functionalized nanofibers mat (PTS-PPy NFsM) was prepared.•PTS-PPy NFsM proved to be effective sorbent for cationic dyes.•A high-throughput NFsM-based μ-SPE along with HPLC-DAD method ...was developed.•The method was successfully applied to real wastewater from the dyeing industry.•The proposed method proved simple, rapid, low-cost, reusable and eco-friendly.
This study used nanofibers mat (NFsM)-based micro-SPE (μ-SPE) in 96-well plate format as a novel high-throughput sample preparation technique prior to the determination of cationic dyes in wastewater using HPLC-DAD. P-Toluene sulfonate (PTS−) doped polypyrrole (PPy) functionalized NFsM (PTS-PPy NFsM) was optimized as SPE sorbent in aspects of PPy form (particles and NFsM) and its doped anions (Cl− and PTS−), which showed good extraction efficiency and adsorption capacity for cationic dyes (Auramine-O, Chrysoidine and Rhodamine-B). Under the optimal conditions, the limits of detection (LODs) were between 0.3 and 0.5μg/L, and the linearity was achieved in the concentration ranging from 1.0 to 150.0μg/L with correlation coefficients (R) between 0.992 and 0.999. Compared with the published SPE methods, this approach demonstrated its advantages such as shorter extraction time (0.3min per sample), lower requirement sorbent (2.0mg), lower volume of organic solvent (0.7mL), higher recovery (90.1–99.1%) and precision (RSDs<6.9%). With this developed method, we have successfully analyzed the dyeing industry wastewater, which meets the Discharge Standards of Water Pollutants for Dyeing and Finishing of Textile Industry in China. The concentrations of three analyzed cationic dyes were from 2.9 to 13.9μg/L. The NFsM-based μ-SPE technique is practically a high-throughput sample preparation procedure that can accurately assess the pollutants in the wastewater from dyeing industry.
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by poor prognosis, early recurrence, and the lack of durable chemotherapy responses and specific targeted ...treatments. In this preclinical study, we examines Tiliroside (TS, C
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), as one of the major compounds of Tribulus terrestris L. which has been used as an alternative therapy in clinic practice of breast cancer treatment, for its therapeutic use in TNBC. The association between CAXII expression level and survival probability of TNBC patients, and the difference of CAXII expression level between TNBC and normal samples were evaluated by using publicly accessible databases. To determine the anticancer efficacy of TS on TNBC cells, cell proliferation, wound healing, cell invasion, and 3D spheroid formation assays were performed and excellent anticancer activities of TS were displayed. Mouse models further demonstrated that TS significantly reduced the tumor burden and improved survival rate. The properties of TS as a novel CAXII inhibitor have also been evaluated by CAXII activity assay, pHi, pHe and lactate level assay. Further RT-PCR and Caspase-3 activity analyses also revealed the positive regulating effects of TS on E2F1,3/Caspase-3 axis in TNBC cells cultured in 2D or 3D systems. The findings indicate that TS suppresses TNBC progression as a potential novel CAXII inhibitor in preclinical experiments, which warrants further investigation on its therapeutic implications.
MicroRNA-21 (miR-21) is considered an onco-microRNA given its abilities to suppress the actions of several tumor suppressor genes and to promote tumor cell growth, invasion and metastasis. Recently, ...transforming growth factor-beta (TGF-β) is found to up-regulate the expression of miR-21, and elevated miR-21 expression is seen frequently in breast cancer. To evaluate the effect of miR-21 on disease progression and its association with TGF-β, we analyzed miR-21 expression in breast cancer. Fresh tumor samples were collected during surgery from 344 patients diagnosed with primary breast cancer. The expression of miR-21 in tumor samples was measured with a TaqMan® microRNA assay using U6 as reference. Levels of miR-21 expression by disease stage, tumor grade, histology, hormone receptor status and lymph node involvement were compared. Cox proportional hazards regression analysis was performed to assess the association of miR-21 expression with disease-free and overall survival. The study results showed that the expression of miR-21 was detected in all tumor samples with substantial variation. High miR-21 expression was associated with features of aggressive disease, including high tumor grade, negative hormone receptor status, and ductal carcinoma. High miR-21 was also positively correlated with TGF-β1. No associations were found between patient survival and miR-21 expression among all patients, but high miR-21 was associated with poor disease-free survival in early stage patients (HR = 2.08, 95% CI: 1.08-4.00) despite no value for prognosis. The study supports the notion that miR-21 is an onco-microRNA for breast cancer. Elevated miR-21 expression may facilitate tumor progression, and TGF-β may up-regulate its expression.
Immunotherapy has been the fifth pillar of cancer treatment in the past decade. Chimeric antigen receptor (CAR) T-cell therapy is a newly designed adoptive immunotherapy that is able to target and ...further eliminate cancer cells by engaging with MHC-independent tumor-antigens. CAR T-cell therapy has exhibited conspicuous clinical efficacy in hematological malignancies, but more than half of patients will relapse. Of note, the efficacy of CAR T-cell therapy has been even more disappointing in solid tumors. These challenges mainly include (1) the failures of CAR T-cells to treat highly heterogeneous solid tumors due to the difficulty in identifying unique tumor antigen targets, (2) the expression of target antigens in non-cancer cells, (3) the inability of CAR T-cells to effectively infiltrate solid tumors, (4) the short lifespan and lack of persistence of CAR T-cells, and (5) cytokine release syndrome and neurotoxicity. In combination with these characteristics, the ideal CAR T-cell therapy for solid tumors should maintain adequate T-cell response over a long term while sparing healthy tissues. This article reviewed the status, clinical application, efficacy, safety, and challenges of CAR T-cell therapies, as well as the latest progress of CAR T-cell therapies for solid tumors. In addition, the potential strategies to improve the efficacy of CAR T-cells and prevent side effects in solid tumors were also explored.
Burnout is a health problem in nurses. Individuals with a certain personality are more susceptible to job-related burnout. General self-efficacy (GSE) is an important predictor of job-related ...burnout. The relationships between general self-efficacy, job-related burnout and different personality types are still not clear. This study aims to analyze the relationships of job-related burnout, stress, general self-efficacy and personality types, as well as their interactions in job-related burnout.
A cross-sectional survey of 860 nurses was conducted between June and July 2015 in China. We measured their job-related burnout using the scale of the Maslach Occupational Burnout Scale, and personality, stress, and GSE. Machine learning of generalized linear model were performed.
Maslach Burnout Inventory (MBI) professional efficacy was significantly associated with gender, marital status, age, job title and length of service. A machine learning algorithm showed that stress was the most important factor in job-related burnout, followed by GSE, personality type (introvert unstable), and job title. Individuals with low GSE and either introversion or unstable (high neuroticism) personality seemed to have stronger burnout when they faced stress (regardless of stress intensity) compared to others.
Stress, GSE and introvert unstable personality are the top three factors of job-related burnout. GSE moderates the effect of stress on burnout in nurses with extroversion or neuroticism personality. Reducing stress, increasing GSE, and more social support may alleviate job-related burnout in nurses. Nurses with introvert unstable personality should be given more social support in reducing stress and enhancing their GSE.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The steroidogenic acute regulatory protein (StAR) governs the rate-limiting step in steroidogenesis, and its expression varies depending on the needs of the specific tissue. Tight control of steroid ...production is essential for multiple processes involved in reproduction, including follicular development, ovulation, and endometrial synchronization. Recently, there has been a growing interest in the role of noncoding RNAs in the regulation of reproduction. Here we demonstrate that StAR is a novel target of the microRNA let-7, which itself is regulated by the long noncoding RNA (lncRNA) H19. Using human and murine cell lines, we show that overexpression of H19 stimulates StAR expression by antagonizing let-7, which inhibits StAR at the posttranscriptional level. Our results uncover a novel mechanism underlying the regulation of StAR expression and represent the first example of lncRNA-mediated control of the rate-limiting step of steroidogenesis. This work thus adds to the body of literature describing the multiple roles – in oncogenesis, cellular growth, glucose metabolism, and now, regulation of steroidogenesis – of this complex lncRNA.
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