Volume 4, Issue 3

As a key sensor of double-stranded DNA (dsDNA), cyclic GMP-AMP synthase (cGAS) detects cytosolic dsDNA and initiates the synthesis of 2′3′ cyclic GMP-AMP (cGAMP) that activates the stimulator of interferon genes (STING). This finally promotes the production of type I interferons (IFN-I) that is crucial for bridging innate and adaptive immunity. Recent evidence show that several antitumor therapies, including radiotherapy (RT), chemotherapy, targeted therapies and immunotherapies, activate the cGAS-STING pathway to provoke the antitumor immunity. In the last decade, the development of STING agonists has been a major focus in both basic research and the pharmaceutical industry. However, up to now, none of STING agonists have been approved for clinical use. Considering the broad expression of STING in whole body and the direct lethal effect of STING agonists on immune cells in the draining lymph node (dLN), research on the optimal way to activate STING in tumor microenvironment (TME) appears to be a promising direction. Moreover, besides enhancing IFN-I signaling, the cGAS-STING pathway also plays roles in senescence, autophagy, apoptosis, mitotic arrest, and DNA repair, contributing to tumor development and metastasis. In this review, we summarize the recent advances on cGAS-STING pathway’s response to antitumor therapies and the strategies involving this pathway for tumor treatment.

Mammalian lung development starts from a specific cluster of endodermal cells situated within the ventral foregut region. With the orchestrating of delicate choreography of transcription factors, signaling pathways, and cell–cell communications, the endodermal diverticulum extends into the surrounding mesenchyme, and builds the cellular and structural basis of the complex respiratory system. This review provides a comprehensive overview of the current molecular insights of mammalian lung development, with a particular focus on the early stage of lung cell fate differentiation and spatial patterning. Furthermore, we explore the implications of several congenital respiratory diseases and the relevance to early organogenesis. Finally, we summarize the unprecedented knowledge concerning lung cell compositions, regulatory networks as well as the promising prospect for gaining an unbiased understanding of lung development and lung malformations through state-of-the-art single-cell omics.

RNA-based therapeutics have emerged as a promising approach for the treatment of various diseases, including cancer, genetic disorders, and infectious diseases. However, the delivery of RNA molecules into target cells has been a major challenge due to their susceptibility to degradation and inefficient cellular uptake. To overcome these hurdles, DNA-based nano technology offers an unprecedented opportunity as a potential delivery platform for RNA therapeutics. Due to its excellent characteristics such as programmability and biocompatibility, these DNA-based nanostructures, composed of DNA molecules assembled into precise and programmable structures, have garnered significant attention as ideal building materials for protecting and delivering RNA payloads to the desired cellular destinations. In this review, we highlight the current progress in the design and application of three DNA-based nanostructures: DNA origami, lipid-nanoparticle (LNP) technology related to frame guided assembly (FGA), and DNA hydrogel for the delivery of RNA molecules. Their biomedical applications are briefly discussed and the challenges and future perspectives in this field are also highlighted.

A major worldwide health concern, chronic hepatitis B necessitates precise prognostic and diagnostic indicators for clinical guidance. This article highlights the clinical importance and current issues of the major markers used in both the detection and prognosis of chronic hepatitis B. An important indicator of an ongoing and persistent infection is the hepatitis B surface antigen. Hepatitis B virus DNA quantification monitoring aids in assessing viral load and hepatic cancer risk. While limited evidence of liver damage is provided by alanine aminotransferase levels, the hepatitis B core antibody verifies acute infection. Seroconversion to the hepatitis B e antibody is linked to a lower risk of disease development, and the hepatitis B e antigen status is a critical prognostic factor. Treatment choices are guided by a biopsy of the liver or minimally invasive liver fibrosis detection. Genotypes of the hepatitis B virus and host variables influence the prognosis by adding to the disease’s variability. Noninvasive techniques to evaluate the severity of the disease are provided by serum markers of fibrosis, such as the fibrosis score based on four criteria and the aspartate aminotransferase-to-platelet ratio index. The requirement for indicators that distinguish between distinct viral phases and increase specificity in evaluating liver damage is one of the challenges facing chronic hepatitis B research. Even though it is quite difficult to find reliable biomarkers for resistance especially when it comes to hepatocellular cancer risk estimation, there are advanced methods, which include imaging and omics that can help in improving the accuracy of the diagnostics and prognosis. Interventions early point that improve patient outcomes are made possible using diagnostics and prognostics as they are quite effective in managing the complicated landscape of chronic hepatitis B. Key in addressing these challenges today and improving the diagnostic and prognostic markers in the future, particularly those that would support the development of successful treatment plans for people living with chronic hepatitis B virus (HBV), are scientific research, technological advances and collaborations.

The protein, N-myc downstream-regulated gene 2 (NDRG2), a tumor suppressor, is significantly decreased or absent in many types of cancer. There is a significant negative correlation between the levels of NDRG2 and the development and progression of cancer tumor recurrence and tumor invasion, in different cancers. In contrast, the in vitro and in vivo overexpression of the NDRG2 protein decreases the proliferation, growth, adhesion and migration of many types of cancer cells. The in vitro overexpression of NDRG2 increases the efficacy of certain anticancer drugs in specific types of cancer cells. We hypothesize that the delivery of the mRNA of the NDRG2 protein, encapsulated by lipid nanoparticles, could represent a potential treatment of metastatic and drug-resistant cancers. This would be accomplished using a self-amplifying mRNA that encodes the NDRG2 protein and an RNA-dependent-RNA polymerase, obtained from an in vitro transcribed (IVT) mRNA. The IVT mRNA would be encapsulated in a lipid nanoformulation. The efficacy of the nanoformulation would be determined in cultured cancer cells and if the results are positive, nude mice transplanted with either drug-resistant or metastatic drug-resistant cancer cells, would be treated with the nano- formulation and monitored for efficacy and adverse effects. If the appropriate preclinical studies indicate this formulation is efficacious and safe, it is possible it could be evaluated in clinical trials.

Investigating the fine structure of mitochondria and their dynamic interactions with other organelles is crucial for unraveling the mechanisms underlying mitochondrial-related diseases. The development of super-resolution techniques has provided powerful visualization tools for mitochondrial research, which is significant for investigating mitochondrial cristae structure, the localization of mitochondrial-related protein complex, and the interactions between mitochondria and other organelles. In this perspective, we introduce several advanced super-resolution techniques and their applications in mitochondrial research, and discuss the potential roles these techniques may play in future studies of mitochondria.

Objectives The majority of esophageal squamous dysplasia (ESD) patients progress slowly, while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment. However, the molecular mechanisms underlying these clinical observations are still largely unknown. Methods By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma (ESCC) patients, we demonstrated lower somatic mutation and copy number alteration (CNA) burden in ESD compared with ESCC. Results Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD progression. Furthermore, we revealed that miR-4292 promoted ESD progression and could serve as a non-invasive diagnostic marker for ESD. Conclusions These findings largely expanded our understanding of ESD genetics and tumorigenesis, which possessed promising significance for improving early diagnosis, reducing overtreatment, and identifying high-risk ESD patients.