Chromatin modifications play a crucial role in the regulation of gene expression. The repressor element-1 (RE1) silencing transcription factor (REST), also known as neuron-restrictive silencer factor (NRSF) and X2 box repressor (XBR), was found to regulate gene transcription by binding to chromatin and recruiting chromatin-modifying enzymes. Earlier studies revealed that REST plays an important role in the development and disease of the nervous system, mainly by repressing the transcription of neuron-specific genes. Subsequently, REST was found to be critical in other tissues, such as the heart, pancreas, skin, eye, and vascular. Dysregulation of REST was also found in nervous and non-nervous system cancers. In parallel, multiple strategies to target REST have been developed. In this paper, we provide a comprehensive summary of the research progress made over the past 28 years since the discovery of REST, encompassing both physiological and pathological aspects. These insights into the effects and mechanisms of REST contribute to an in-depth understanding of the transcriptional regulatory mechanisms of genes and their roles in the development and progression of disease, with a view to discovering potential therapeutic targets and intervention strategies for various related diseases.

Nonalcoholic fatty liver disease (NAFLD), a chronic condition associated with metabolic dysfunction and obesity, has reached epidemic proportions worldwide. Although early NAFLD can be treated with lifestyle changes, the treatment of advanced liver pathology, such as nonalcoholic steatohepatitis (NASH), remains a challenge. There are currently no FDA-approved drugs for NAFLD. Fibroblast growth factors (FGFs) play essential roles in lipid and carbohydrate metabolism and have recently emerged as promising therapeutic agents for metabolic diseases. Among them, endocrine members (FGF19 and FGF21) and classical members (FGF1 and FGF4) are key regulators of energy metabolism. FGF-based therapies have shown therapeutic benefits in patients with NAFLD, and substantial progress has recently been made in clinical trials. These FGF analogs are effective in alleviating steatosis, liver inflammation, and fibrosis. In this review, we describe the biology of four metabolism-related FGFs (FGF19, FGF21, FGF1, and FGF4) and their basic action mechanisms, and then summarize recent advances in the biopharmaceutical development of FGF-based therapies for patients with NAFLD.

Various lung diseases endanger people’s health. Side effects and pharmaceutical resistance complicate the treatment of acute lung injury, pulmonary fibrosis, and lung cancer, necessitating the development of novel treatments. Antimicrobial peptides (AMPs) are considered to serve as a viable alternative to conventional antibiotics. These peptides exhibit a broad antibacterial activity spectrum as well as immunomodulatory properties. Previous studies have shown that therapeutic peptides including AMPs had remarkable impacts on animal and cell models of acute lung injury, pulmonary fibrosis, and lung cancer. The purpose of this paper is to outline the potential curative effects and mechanisms of peptides in the three types of lung diseases mentioned above, which may be used as a therapeutic strategy in the future.

Peptide drug development has emerged as a prominent area in pharmaceutical research due to its high specificity and therapeutic potential. However, their biological activity, stability, and bioavailability are significantly influenced by interactions with counter-ions, which electrostatically bind to charged residues on peptide surfaces. This review systematically examines the multifaceted roles of counter-ions in modulating peptide structure and function. Counter-ions are classified into organic/inorganic and anionic/cationic categories, with their selection critically impacting peptide solubility, conformational stability, and activity. Inorganic counter-ions could enhance structural integrity, while organic counter-ions could mitigate toxicity risks. Notably, counter-ions can induce secondary structural transitions, directly affecting biological efficacy. Furthermore, counter-ions play pivotal roles in drug delivery systems, including nanoemulsions, self-emulsifying formulations, and lipid-based nanoparticles, where hydrophobic ion pairing improves encapsulation efficiency and oral bioavailability. In chromatography, ion-pairing reagents optimize peptide separation but may compromise mass spectrometry compatibility. Emerging analytical techniques, such as capillary electrophoresis and liquid chromatography–tandem mass spectrometry (LC-MS/MS), enhance counter-ion detection precision, addressing challenges in pharmaceutical quality control. Despite advancements, gaps remain in understanding ion-specific binding mechanisms and long-term safety profiles. This review underscores the necessity of tailoring counter-ion selection to balance efficacy, stability, and biocompatibility. Future research should prioritize elucidating molecular interaction dynamics and developing safer, high-affinity counter-ions to overcome current limitations in peptide drug development.

Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease, with a worldwide prevalence of more than 25%, and there is no approved drug for NAFLD specifically. In our previous study, the synthetic peptide AWRK6 was found to ameliorate NAFLD in mice. However, the mechanisms involved are still largely unknown. Here, AWRK6 treatment presented an alleviative effect on lipid accumulation induced by oleic acid in hepatocytes. Meanwhile, miR-5100 and miR-505 were found to be elevated by oleic acid induction and reversed by AWRK6 incubation. Further, the miR-5100 inhibitor inhibited oleic acid-induced lipid accumulation, and the alleviation effect of AWRK6 was partially counteracted by miR-5100 mimics. The screening of potential target genes revealed that a catalytic subunit of G6Pase G6PC was significantly inhibited by miR-5100 mimics transfection in both mRNA and protein levels. The direct targeting of miR-5100 on G6PC was verified by a Dual-Luciferase Reporter Assay. Moreover, the mRNA and protein levels of G6PC were found to be significantly increased by AWRK6 treatment. These results suggested that the peptide AWRK6 could alleviate lipid accumulation in hepatocytes, partly through reducing miR-5100 to restore one of its targets: G6PC. Thus, AWRK6 has the potential to treat NAFLD. Additionally, miR-5100 is a mediator of lipid accumulation in hepatocytes, which could be targeted by AWRK6.

Over the past few decades, the convergence of nanoelectronics and wearable technologies has driven paradigm-shifting advancements in cutaneous wound management. Skin-inspired engineering strategies utilizing functional nanomaterials with exceptional electromechanical properties have redefined the paradigm of therapeutic interventions in wearable biomedical systems. The flexible biosensors and nanomaterial-based electronics now enable multiplexed monitoring of dynamic wound biomarkers, including interstitial pH, temperature gradients, and moisture levels with real-time temporal precision. These closed-loop therapeutic platforms synergistically integrate continuous microenvironment surveillance with autonomous drug delivery, while enabling telemedicine through the Internet of Things-enabled remote diagnostics and Artificial Intelligence-driven clinical decision support. This review evaluated emerging innovations of wearable nanoelectronic devices, highlighting their utilization potential in the intervening of skin wound healing process. Future perspectives are proposed, focusing on self-adaptive systems powered by biomechanical energy harvesting, microbiome-responsive interfaces, and machine learning-optimized treatment protocols.