Yulu Zhou

Background: A functional deficiency in vitamin B12 is a prevalent condition among heart failure (HF) patients. Despite being a specific and sensitive marker for this deficiency, the study of methylmalonic acid (MMA) in the context of HF has been infrequent.Methods: Seven hundred and forty-seven individuals with HF were incorporated in this cross-sectional study who participated in the National Health and Nutrition Examination Survey (NHANES) from two periods, 1999 to 2004, and 2011 to 2014. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the risk of all-cause mortality were estimated using weighted multivariable Cox proportional hazard models. The non-linear association between MMA levels and all-cause mortality was investigated using restricted cubic spline (RCS) analyses.Results: Among 747 HF participants, 481 (57.3%) deaths were recorded during a follow-up period of 7.9 years. Elevated serum MMA levels were significantly associated with an increased risk of all-cause mortality (Tertile 3 compared with Tertile 1: adjusted HR: 1.52; 95% CI: 1.09, 2.13; p = 0.01), demonstrating a dose–response pattern (26% increased mortality risk per unit increase in lnMMA). B12 intake from diet was not significantly associated with mortality risk (p = 0.81). Although a minor statistically significant association was observed in serum B12 levels and mortality (p = 0.045), it disappeared after multivariate regression analysis. Moreover, the correlation between MMA and mortality risk was more prominent in HF populations with poorer health status, such as advanced age, current smokers, hypertension, diabetes, overweight, or low estimated glomerular filtration rate (eGFR).Conclusion: Our study indicated that a higher MMA level is associated with an increased all-cause mortality risk in HF populations, particularly in those aged 65 and above, current smokers, those with hypertension, diabetes, overweight, insufficient physical activity, or lower eGFR (2).

Systemic therapy is one of the most significant cancer treatments. However, drug resistance often appears and has become the primary cause of cancer therapy failure. Regulation of drug target, drug metabolism and drug efflux, cell death escape (apoptosis, autophagy, et al.), epigenetic changes, and many other variables are complicatedly involved in the mechanisms of drug resistance. In various types of cancers, long non-coding RNA H19 (lncRNA H19) has been shown to play critical roles in tumor development, proliferation, metastasis, and multiple drug resistance as well. The efficacy of chemotherapy, endocrine therapy, and targeted therapy are all influenced by the expression of H19, especially in breast cancer, liver cancer, lung cancer and colorectal cancer. Here, we summarize the relationship between lncRNA H19 and tumorigenesis, and illustrate the drug resistance mechanisms caused by lncRNA H19 as well. This review may provide more therapeutic potential targets for future cancer treatments.

Ferroptosis is a recently discovered distinct type of regulated cell death caused by the accumulation of lipid-based ROS. Metabolism and expression of specific genes affect the occurrence of ferroptosis, making it a promising therapeutic target to manage cancer. Here, we describe the current status of ferroptosis studies in breast cancer and trace the key regulators of ferroptosis back to previous studies. We also compare ferroptosis to common regulated cell death patterns and discuss the sensitivity to ferroptosis in different subtypes of breast cancer. We propose that viewing ferroptosis-related studies from a historical angle will accelerate the development of ferroptosis-based biomarkers and therapeutic strategies in breast cancer.