The liver is a major metabolic organ that performs many essential biological functions such as detoxification and the synthesis of proteins and biochemicals necessary for digestion and growth. Any disruption in normal liver function can lead to the development of more severe liver disorders. Overall, about 3 million Americans have some type of liver disease and 5.5 million people have progressive liver disease or cirrhosis, in which scar tissue replaces the healthy liver tissue. An estimated 20% to 30% of adults have excess fat in their livers, a condition called steatosis. The most common etiologies for steatosis development are (1) high caloric intake that causes non-alcoholic fatty liver disease (NAFLD) and (2) excessive alcohol consumption, which results in alcohol-associated liver disease (ALD). NAFLD is now termed “metabolic-dysfunction-associated steatotic liver disease” (MASLD), which reflects its association with the metabolic syndrome and conditions including diabetes, high blood pressure, high cholesterol and obesity. ALD represents a spectrum of liver injury that ranges from hepatic steatosis to more advanced liver pathologies, including alcoholic hepatitis (AH), alcohol-associated cirrhosis (AC) and acute AH, presenting as acute-on-chronic liver failure. The predominant liver cells, hepatocytes, comprise more than 70% of the total liver mass in human adults and are the basic metabolic cells. Mitochondria are intracellular organelles that are the principal sources of energy in hepatocytes and play a major role in oxidative metabolism and sustaining liver cell energy needs. In addition to regulating cellular energy homeostasis, mitochondria perform other key physiologic and metabolic activities, including ion homeostasis, reactive oxygen species (ROS) generation, redox signaling and participation in cell injury/death. Here, we discuss the main mechanism of mitochondrial dysfunction in chronic liver disease and some treatment strategies available for targeting mitochondria.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, poor prognosis, and palliative treatments, due to the rapid upregulation of alternative compensatory pathways and desmoplastic reaction. miRNAs, small non-coding RNAs, have been recently identified as key players regulating cancer pathogenesis. Dysregulated miRNAs are associated with molecular pathways involved in tumor development, metastasis, and chemoresistance in PDAC, as well as other cancers. Targeted treatment strategies that alter miRNA levels in cancers have promising potential as therapeutic interventions. miRNA-345 (miR-345) plays a critical role in tumor suppression and is differentially expressed in various cancers, including pancreatic cancer (PC). The underlying mechanism(s) and delivery strategies of miR-345 have been investigated by us previously. Here, we summarize the potential therapeutic roles of miR-345 in different cancers, with emphasis on PDAC, for miRNA drug discovery, development, status, and implications. Further, we focus on miRNA nanodelivery system(s), based on different materials and nanoformulations, specifically for the delivery of miR-345.

Since its discovery in 2001, Human Metapneumovirus (hMPV) has been identified globally, exhibiting predictable seasonal outbreaks primarily affecting young children, the elderly, and individuals with preexisting health conditions. The virus is transmitted through airborne droplets and is responsible for a notable percentage of respiratory illnesses, particularly in children under five years of age, with hospitalization rates peaking in the first year of life. The complex immune response elicited by hMPV, characterized by a Th17-like profile and excessive mucus production, contributes to respiratory complications, emphasizing the need for effective management strategies. This review discusses various diagnostic methods, emphasizing the potential of combining serology with RT-PCR to enhance diagnostic accuracy during outbreaks. Furthermore, it addresses the therapeutic approaches, including the promise of recombinant interferons and ongoing research on the use of passive immunity through neutralizing antibodies. A comprehensive overview of hMPV, emphasizing the importance of continued research to improve diagnostic and therapeutic options for this significant respiratory pathogen, offers promising strategies for manipulating responses through targeted interventions.

CD45.1/CD45.2 congenic markers have been used to track hematopoietic lineage differentiation following hematopoietic stem and progenitor cell (HSPC) transplantation. However, several studies suggest that a bias exists in CD45.1 versus CD45.2 hematopoietic cell reconstitution from HSPCs. Meanwhile, no definitive comparison has been reported for mature immune cells as to whether the CD45.1/CD45.2 disparity can skew the immune cell response. In this study, using lymphocytopenia Rag1−/− CD45.2 mice as hosts, we assessed the reconstitution potential of CD45.1 versus CD45.2 lymphocytes following adoptive transfer of mature T and B cells. We have found a selective bias for CD8+ T cells in that CD45.1 cells showed significantly higher reconstitution compared with CD45.2 cells, whereas CD4+ T cells and CD19+ B cells showed equivalent reconstitution. These results suggest that CD45.1/CD45.2 markers may induce an alloreactive response or a survival bias specific to CD8+ T cells, and they therefore call for caution for using them as congenic markers in immunologic models.

All biological processes, from embryonic development to cancer, are tightly controlled by the interactions between genetics and epigenetics. An array of epigenetic modifications, such as DNA methylation, histone/chromatin modifications, and noncoding RNA-mediated targeting, are essential to regulate the heritable changes that occur during multiple cellular processes. A failure in proper regulation results in inappropriate gene expression that ultimately leads to pathological states. Groundbreaking advances in genomics and transcriptomics have revealed the potential involvement of epigenetics in various physiological and pathological states. The promising clinical and preclinical results shown by epigenetics drugs further underscore the central role of epigenetics in multiple human diseases, including cancer. AT rich interaction domain (ARID)-containing proteins are a family of evolutionarily conserved DNA binding proteins that regulate epigenetic modifications. Genome sequencing has revealed the existence of 15 ARID family proteins that are divided into 7 subfamilies based on their sequence and domain homology. Although the ARID family of proteins are implicated in cell growth, development, differentiation, and cancer, the diverse biological functions of many family members remain to be elucidated. Here, we focus on ARID4B to summarize its prominent role in embryonic stem cell differentiation and human malignancies.