Role of Apoptosis in Cancer Resistance to Chemotherapy

Cancer is a leading cause of death in human beings. Surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy are common modalities for cancer treatment. However, cancer resistance is common in chemotherapy and often leads to therapeutic failure. This chapter addresses the role of apoptosis in tumor’s resistance to chemotherapy and the underlying mechanisms. Cancer cells are always resistant to apoptotic signals via a series of biochemical changes. Cancer cells are resistant to chemotherapeutic agents that are potent apoptosis inducers via multiple mechanisms, such as upregulated anti-apoptotic signals and downregulated pro-apoptotic signals, faulty apoptotic signaling, faulty apoptosis initiation and implementation, etc. We also discuss the possible approaches to overcoming cancer resistance to chemotherapy due to altered apoptosis

Maternal and fetal/neonatal outcomes of pregnancies complicated by pulmonary hypertension: a retrospective study of 154 patients

Objectives: To determine the main clinical and demographic outcomes related to Pulmonary Hypertension (PH) and adverse obstetric and fetal/neonatal outcomes. Methods: This study retrospectively analyzed the medical record data of 154 patients with PH who were admitted to the Third Affiliated Hospital of Guangzhou Medical University between January 2011 and December 2020. Results: According to the severity of elevated Pulmonary Artery Systolic Pressure (PASP), 82 women (53.2%) were included in the mild PH group, 34 (22.1%) were included in the moderate PH group, and 38 (24.7%) were included in the severe PH group. There were significant differences in the incidence of heart failure, premature delivery, Very-Low-Birth-Weight (VLBW) infants, and Small-for-Gestational-Age (SGA) infants among the three PH groups (p < 0.05). Five (3.2%) women died within 7-days after delivery, 7 (4.5%) fetuses died in utero, and 3 (1.9%) neonates died. The authors found that PASP was an independent risk factor for maternal mortality. After adjustment for age, gestational weeks, systolic blood pressure, Body Mass Index (BMI), mode of delivery, and anesthesia, the risk of maternal mortality in the severe PH group was 20.21 times higher than that in the mild-moderate PH group (OR = 21.21 [95% CI 1.7∼264.17]), p < 0.05. All 131 (85.1%) patients were followed up for 12 months postpartum. Conclusions: The authors found that the risk of maternal mortality in the severe PH group was significantly higher than that in the mild-moderate group, highlighting the importance of pulmonary artery pressure screening before pregnancy, early advice on contraception, and multidisciplinary care

HyperFormer: Learning Expressive Sparse Feature Representations via Hypergraph Transformer

Learning expressive representations for high-dimensional yet sparse features has been a longstanding problem in information retrieval. Though recent deep learning methods can partially solve the problem, they often fail to handle the numerous sparse features, particularly those tail feature values with infrequent occurrences in the training data. Worse still, existing methods cannot explicitly leverage the correlations among different instances to help further improve the representation learning on sparse features since such relational prior knowledge is not provided. To address these challenges, in this paper, we tackle the problem of representation learning on feature-sparse data from a graph learning perspective. Specifically, we propose to model the sparse features of different instances using hypergraphs where each node represents a data instance and each hyperedge denotes a distinct feature value. By passing messages on the constructed hypergraphs based on our Hypergraph Transformer (HyperFormer), the learned feature representations capture not only the correlations among different instances but also the correlations among features. Our experiments demonstrate that the proposed approach can effectively improve feature representation learning on sparse features.Comment: Accepted by SIGIR 202

Crucial Role of miR-433 in Regulating Cardiac Fibrosis

Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes. Conversely, inhibition of miR-433 exhibited opposite results. AZIN1 and JNK1 were identified as two target genes of miR-433. Decreased level of AZIN1 activated TGF-β1 while down-regulation of JNK1 resulted in activation of ERK and p38 kinase leading to Smad3 activation and ultimately cardiac fibrosis. Importantly, systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular dysfunction following myocardial infarction. Thus, our work suggests that miR-433 is a potential target for amelioration of cardiac fibrosis