RESUMEN
Chemotherapy is a commonly effective treatment for most types of cancer. However, many patients experience a relapse due to minimal residual disease (MRD) after chemotherapy. Previous studies have analyzed the changes induced by chemotherapy for specific types of cancer, but our study is the first to comprehensively analyze MRD across various types of cancer. We included both bulk and single-cell RNA sequencing datasets. We compared the expression of the entire genome and calculated scores for canonical pathway signatures and immune infiltrates before and after chemotherapy across different types of cancer. Our findings revealed that DUSP1 was the most significantly and widely enriched gene in pan-cancer MRD. DUSP1 was found to be essential for MRD formation and played a role in T cell-fibroblast communications and the cytotoxic function of CD4 + T cells. Overall, our analysis provides a comprehensive understanding of the changes caused by chemotherapy and identifies potential targets for preventing and eliminating MRD, which could lead to long-term survival benefits for patients.
RESUMEN
Smart energy storage systems, such as electrochromic supercapacitor (ECSC) integrated technology, have drawn a lot of attention recently, and numerous developments have been made owing to their reliable performance. Developing novel electrode materials for ECSCs that embed two different technologies in a material is an exciting and emerging field of research. To date, the research into ECSC electrode materials has been ongoing with excellent efforts, which need to be systematically reviewed so that they can be used to develop more efficient ECSCs. This mini-review provides a general composition, main evaluation parameters and future perspectives for electrode materials of ECSCs as well as a brief overview of the published reports on ECSCs and performance statistics on the existing literature in this field.
RESUMEN
Neurofibromatosis type 1 (NF1) is a disorder in which RAS is constitutively activated due to the loss of the Ras-GTPase-activating activity of neurofibromin. RAS must be prenylated (i.e., farnesylated or geranylgeranylated) to traffic and function properly. Previous studies showed that the anti-growth properties of farnesyl monophosphate prodrug farnesyltransferase inhibitors (FTIs) on human NF1 malignant peripheral nerve sheath tumor (MPNST) cells are potentiated by co-treatment with lovastatin. Unfortunately, such prodrug FTIs have poor aqueous solubility. In this study, we synthesized a series of prodrug FTI polyamidoamine generation 4 (PAMAM G4) dendrimers that compete with farnesyl pyrophosphate for farnesyltransferase (Ftase) and assessed their effects on human NF1 MPNST S462TY cells. The prodrug 3-tert-butylfarnesyl monophosphate FTI-dendrimer (i.e., IG 2) exhibited improved aqueous solubility. Concentrations of IG 2 and lovastatin (as low as 0.1 µM) having little to no effect when used singularly synergistically suppressed cell proliferation, colony formation, and induced N-RAS, RAP1A, and RAB5A deprenylation when used in combination. Combinational treatment had no additive or synergistic effects on the proliferation/viability of immortalized normal rat Schwann cells, primary rat hepatocytes, or normal human mammary epithelial MCF10A cells. Combinational, but not singular, in vivo treatment markedly suppressed the growth of S462TY xenografts established in the sciatic nerves of immune-deficient mice. Hence, prodrug farnesyl monophosphate FTIs can be rendered water-soluble by conjugation to PAMAM G4 dendrimers and exhibit potent anti-tumor activity when combined with clinically achievable statin concentrations.
RESUMEN
Background: Mitral regurgitation (MR) is one of the common complications of heart failure (HF). The prevalence and characteristics of MR are rarely investigated, especially in the Chinese population. Objectives: The purpose of this study was to determine the prevalence and characteristics of non-organic MR in HF patients and subgroups defined by ejection fraction. Methods: A single-center, hospital-based, and retrospective chart review study included patients with heart failure admitted to the cardiovascular department from January 2017 to April 2020. Demographic characteristics, laboratory results, and echocardiogram results before discharge were analyzed in different groups defined by left ventricular ejection fraction (EF) using logistic regression and adjusted for confounders. Results: Finally, 2418 validated HF patients (age 67.2 ± 13.5 years; 68.03% men) were included. The prevalence of MR was 32.7% in HF, 16.7% in HF with preserve EF patients, 28.4% in HF with mid-range EF patients and 49.7% in HF with reduced EF (HFrEF) patients. In the HF with preserved EF group, multivariable logistic regression showed that 4 factors associated with MR including EF (odds ratio (OR) 0.954 (0.928-0.981), p = 0.001), left ventricular posterior wall thickness in diastolic phase (LVPWd) (OR 0.274 (0.081-0.932), p = 0.038), left atrium (LA) dimension (OR 2.049 (1.631-2.576), p < 0.001) and age (OR 1.024 (1.007-1.041), p = 0.007). In the HF with midrange EF group, multivariable logistic regression showed that 3 factors associated with MR including LA dimension (OR 2.009 (1.427-2.829), p < 0.001), triglycerides (TG) (OR 0.552 (0.359-0.849), p = 0.007) and digoxin (OR 2.836 (1.624-4.951), p < 0.001). In the HFrEF group, multivariable logistic regression showed that 7 factors associated with MR including EF (OR 0.969 (0.949-0.990), p = 0.004), (OR 0.161 (0.067-0.387), p < 0.001), LA dimension (OR 2.289 (1.821-2.878), p < 0.001), age (OR 1.016 (1.004-1.027)), p = 0.009), TG (OR 0.746 (0.595-0.936), p = 0.011), diuretics (OR 0.559 (0.334-0.934), p = 0.026) and ICD (OR 1.898 (1.074-3.354), p = 0.027). Conclusions: HF patients had a high burden of MR, particularly in the HFrEF group. Worsen cardiac structure (LA dimension and LVPWd) and function (EF), age, and medical treatment strategy played essential roles in MR.