Many neurobehavioral processes, including psychomotor, cognitive, and affection are negatively impacted by sleep deprivation (SD), which may be harmful to a person's physical and mental health. Heat shock proteins (Hsps) have been demonstrated to play a protective role in a number of neurodegenerative diseases and are essential for maintaining intracellular protein homeostasis, but their roles in SD remain elusive. A mouse SD model was constructed using a modified multi-platform water environment method. The cognitive function was tested by novel object recognition test and Y-maze test, and anxiety-like behaviors were assessed by open field test (OFT). Protein expression was determined by Western blotting assay and ELISA assay. We found that SD could profoundly enhance anxiety levels and impair cognitive function in mice. SD also reduced the expression levels of p-cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) and increased microglial activation and neuroinflammatory response in the hippocampus of mice. The intranasal injection of human recombinant Hsp70 protein could alleviate SD-induced anxiety and cognitive impairment, as well as restore pCREB and BDNF levels and reduce microglia-induced neuroinflammation in the hippocampus of SD mice. Hsp70 treatment might serve as a potential treatment for mitigating SD-related unfavorable symptoms.

Background: Sepsis is characterized by high morbidity and mortality rates, alongside limited therapeutic efficacy. Atrial fibrillation (AF), the most common arrhythmia, has been closely linked to sepsis in prior research. However, the specific mechanisms through which sepsis leads to new-onset AF remain poorly understood. This study focuses on identifying critical genes that are dysregulated in the development of new-onset AF within the context of sepsis, with the goal of uncovering new potential targets for its diagnosis and prevention.Material and methods: Our study began by applying Mendelian Randomization (MR) to assess the causal link between sepsis and AF. We then sourced sepsis and AF datasets from the Gene expression Omnibus (GEO) database. Using Weighted Gene Co-expression Network Analysis (WGCNA), we pinpointed key modules and genes associated with both sepsis and AF conditions. Protein-protein interaction (PPI) network was constructed. The Transcriptional Regulatory Relationships Unravelled by Sentence-based Text-mining (TRRUST) database helped build the transcription factor (TF) interaction network. Key genes were scrutinized through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to delve into their roles in new-onset AF's pathophysiology during sepsis. We employed the CIBERSORT algorithm to evaluate immune infiltration and the association between key genes and immune cells. The Connectivity Map (CMap) database facilitated the prediction of potential small molecule compounds targeting key genes. To culminate, an acute sepsis mouse model was developed to validate the implicated mechanisms of key genes involved in new-onset AF during sepsis, and to assess the prophylactic effectiveness of identified drug candidates.Results: MR revealed potential independent risk factors for new-onset AF in sepsis. S100A12 was identified as a core interaction gene with elevated levels in sepsis and AF, underscoring its diagnostic and predictive significance. S100A12, along with associated genes, was mainly linked to immune and inflammatory response signaling pathways, correlating with immune cell levels. Targeting S100A12 identifies five potential small molecule therapeutics: amlexanox, balsalazide, methandriol, olopatadine, and tiboloe. In animal studies, acute sepsis increased S100A12 expression in serum and atrial tissues, correlating positively with inflammatory markers (IL-1β, IL-6, TNF-α) and negatively with heart rate, indicating a predisposition to AF. Early amlexanox administration can reduced S100A12 expression, dampened inflammation, and lessened new-onset AF risk in sepsis.Conclusion: This study demonstrates that sepsis may independently increase the risk of new-onset AF. We identified S100A12 as a key gene influencing the new-onset AF in sepsis through immune regulation, presenting considerable diagnostic and predictive value. Notably, amlexanox, by targeting S100A12 emerges as the most clinical relevant intervention for managing new-onset AF in sepsis patients.

Traumatic brain injury (TBI) is associated with intestinal barrier dysfunction. Although lycopene (Lyc) possesses anti-inflammatory properties, its specific protective effects against TBI-induced intestinal injury remain unclear. The purpose of this study was to explore the protective effects and mechanisms of Lyc on intestinal injury after TBI. Using a TBI mouse model, mice were divided into CON, TBI, Lyc-L (5 mg/kg/day), Lyc-M (10 mg/kg/day), and Lyc-H (20 mg/kg/day) groups with 14-day continuous treatment. Inflammatory cytokines, intestinal barrier function, and molecular pathways were assessed by enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and western blotting, respectively. A randomized controlled trial enrolled 74 TBI patients, with those in the TBI + Lyc group receiving 300 mL of daily tomato juice (Lyc 30 mg/day) for 14 days, and clinical data collected. In the TBI mouse model, Lyc dose-dependently reduced ileal pro-inflammatory factors (TNF-α, IL-18, IL-6) and enhanced intestinal barrier function—decreasing dysfunction biomarkers (I-FABP, D-LA, DAO, endotoxin) and alleviating pathological damage (lower Chiu score, higher villus height and crypt depth). Moreover, Lyc dose-dependently downregulated the protein expression of NLRP3, ASC, Caspase-1, and GSDMD-N in the ileum post-TBI. In clinical research, Lyc significantly reduced serum CRP and PCT levels, lowered the incidence of gastrointestinal complications, improved intestinal function scores, and increased Glasgow Coma Scale scores. Additionally, it shortened the length of intensive care unit and total hospital stays. Lyc protects against intestinal barrier dysfunction following TBI by suppressing NLRP3/Caspase-1/GSDMD-driven pyroptosis, a mechanism with potential clinical applications.

Local analgesia is a prevalent and cost-effective pain management strategy with minimal systemic side effects. At the same time, nanotechnology has been employed to achieve the sustained release of drugs to prolong the duration of local anesthetics (LAs). However, these traditional nanoformulations lack responsiveness and thus cannot achieve precise pain relief through on-demand administration. The emergence of “intelligent” nanosystems with stimulus-response capabilities has opened up new prospects in pain control. This review summarizes recent advancements in the design and application of triggerable LAs nanoformulations that can be activated by external stimuli such as light, ultrasound, or heat. These systems facilitate precise, patient-specific pain management, transforming the clinical approach from long-term suppression to controllable and on-demand relief. Finally, we discussed the current challenges and future prospects. A deeper understanding of this field will facilitate the development of superior analgesic solutions and ultimately improve the treatment outcomes for patients.

Acute inflammatory visceral pain (AIVP) is a prevalent yet challenging clinical condition associated with inflammatory diseases, characterized by diffuse pain that often escalates into nausea, vomiting, and systemic autonomic disturbances. The absence of effective and patient-centered therapies remains a significant clinical challenge. While dexmedetomidine (Dex) has demonstrated promising analgesic effects, its conventional intravenous administration involves slow infusion, heightening risks of infection and compromising patient comfort and compliance. Here, we present a breakthrough strategy using a hyaluronic acid (HA) hydrogel and microneedle-based transdermal system for Dex delivery to enhance clinical practicality. We successfully fabricated Dex-loaded HA hydrogel microneedles (MN/Dex), enabling efficient skin penetration and controlled drug release. Comprehensive biosafety evaluations, including skin irritation, cytotoxicity, and hemolysis assays, confirmed the excellent biocompatibility of the HA hydrogel microneedle system (HA-MN). In the acetic-acid-induced AIVP model, MN/Dex not only produced significant and sustained reduction in visceral and somatic hyperalgesia but also maintained normal physiological activity, avoiding sedation burden, preserving feeding behavior, and supporting natural mobility. MN/Dex offers a minimally invasive, easy-to-administer, and well-tolerated alternative to intravenous therapy, with the potential to transform outpatient management and improve quality of life for patients suffering from AIVP. This advanced delivery platform bridges a critical translational gap in pain management, combining efficacy with outstanding clinical adaptability.