Anesthetics, which include both local and general varieties, are a unique class of drugs widely utilized in clinical surgery to alleviate pain and promote relaxation in patients. Although numerous anesthetics and their traditional formulations are available in the market, only a select few exhibit excellent anesthetic properties that meet clinical requirements. The main challenges are the potential toxic and adverse effects of anesthetics, as well as the presence of the blood-brain barrier (BBB), which makes it difficult for most general anesthetics to effectively penetrate to the brain. Loading anesthetics onto nanocarriers as anesthetic nanomedicines might address these challenges and improve anesthesia effectiveness, reduce toxic and adverse effects, while significantly enhance the efficiency of general anesthetics passing through the BBB. Consequently, anesthetic nanomedicines play a crucial role in the field of anesthesia. Despite their significance, research on anesthetic nanomedicines is still in its infancy, especially when compared to other types of nanomedicines in terms of depth and breadth. Although local anesthetic nanomedicines have received considerable attention and essentially meet clinical needs, there are few reported instances of nanomedicines for general anesthetics. Given the extensive usage of anesthetics and the many of them need for improved performance, emerging anesthetic nanomedicines face both unparalleled opportunities and considerable challenges in terms of theory and technology. Thus, a comprehensive summary with systematic analyses of anesthetic nanomedicines is urgently required. This review provides a comprehensive summary of the classification, properties, and research status of anesthetic nanomedicines, along with an exploration of their opportunities and challenges. In addition, future research directions and development prospects are discussed. It is hoped that researchers from diverse disciplines will collaborate to study anesthetic nanomedicines and develop them as a valuable anesthetic dosage form for clinical surgery.

This study investigated the role of mitochondrial dynamics in postoperative cognitive dysfunction (POCD) and assessed the therapeutic potential of mitochondrial modulation, particularly through the inhibition of dynamin-related protein 1 (DRP1) with Mdivi-1. Our findings indicated that DRP1 inhibition substantially mitigated neuroinflammation mediated by microglial cells, contributing to improved cognitive function in POCD models. The administration of Mdivi-1 led to a notable decrease in mitochondrial fission, reduced reactive oxygen species (ROS) production, and stabilization of mitochondrial membrane potential, all of which correlate with diminished neuroinflammation, as evidenced by lower NOD-like receptor family pyrin domain containing 3 (NLRP3)/ interleukin-1β (IL-1β) expression in microglial cells. Importantly, Mdivi-1 treatment was also found to enhance synaptic plasticity, increasing synaptic spine density in the hippocampal region of POCD mice. This improvement in mitochondrial health and synaptic integrity was paralleled by enhanced cognitive performance, as demonstrated in Y-maze tests. These results underscored the critical role of mitochondrial dynamics in the pathophysiology of POCD and suggested that targeting mitochondrial dysfunction, specifically through DRP1 inhibition, could be an effective approach for POCD treatment.

The prevalence of diabetes-associated cognitive dysfunction (DACD) has increased to 13.5%. Dementia, as the most severe DACD, is the second leading cause of death in patients with diabetes mellitus. Hence, the potential mechanisms of DACD for slowing or halting its progression need to be urgently explored. Given that the sigma-1 receptor (Sig-1R), a chaperone protein located in the endoplasmic reticulum (ER)-mitochondrion contact membranes to regulate ER stress (ERS), is associated with cognitive outcomes in neurodegenerative diseases, this study aimed to investigate the role of astrocytic Sig-1R in DACD and its underlying mechanism. Here, we examined the levels of ERS and complement component 3/3a (C3/C3a) from primary astrocytes with different concentrations of glucose and treatment. Subsequently, HT22 neurons were cultured in different astrocyte-conditioned medium, and the expression of synaptic proteins was detected. We constructed type 1 diabetes mellitus (T1DM) model to evaluate the astrocytic Sig-1R mechanism on synapse and cognitive function changes. In vitro, high glucose concentration downregulated Sig-1R and aggravated ERS in astrocytes, resulting in synapse deficits. PRE-084, a high-affinity and selective Sig-1R agonist, inhibited astrocytic ERS and complement cascades and restored synaptic damage, while the Sig-1R antagonist displayed the opposite results. Moreover, C3a receptor antagonist (C3aRA) could mimic the effect of PRE-084 and exerted neuroprotective effects. In vivo, PRE-084 substantially reduced ER-mitochondrion contact, activation of ERS, and C3/C3a secretion in mice with T1DM. Additionally, the synaptic loss and neurobehavioral dysfunction of mice with T1DM were less pronounced in both the PRE-084 and C3aRA treatment groups. These findings demonstrated that Sig-1R activation reduced the astrocytic ER-mitochondrion contact, ERS activation, and complement-mediated synaptic damage in T1DM. This study suggested the mechanisms and potential therapeutic approaches for treating DACD.

The combination of phototherapy and chemotherapy (chemo–photo combination therapy) is an excellent attempt for tumor treatment. The key requirement of this technology is the high drug-loading nanomedicines, which can load either chemotherapy drugs or phototherapy agents at the same nanomedicines and simultaneously deliver them to tumors, and play a multimode therapeutic role for tumor treatment. These nanomedicines have high drug-loading efficiency (>30%) and good tumor combination therapeutic effect with important clinical application potential. Although there are many reports of high drug-loading nanomedicines for tumor therapy at present, systematic analyses on those nanomedicines remain lacking and a comprehensive review is urgently needed. In this review, we systematically analyze the current status of developed high drug-loading nanomedicines for tumor chemo–photo combination therapy and summarize their types, methods, drug-loading properties, in vitro and in vivo applications. The shortcomings of the existing high drug-loading nanomedicines for tumor chemo–photo combination therapy and the possible prospective development direction are also discussed. We hope to attract more attention for researchers in different academic fields, provide new insights into the research of tumor therapy and drug delivery system and develop these nanomedicines as the useful tool for tumor chemo–photo combination therapy in the future.

Cognitive dysfunction has become the second leading cause of death among the diabetic patients. In pre-diabetic stage, blood-brain barrier (BBB) injury occurs and induced the microvascular complications of diabetes, especially, diabetes-associated cognitive dysfunction (DACD). Endothelial cells are the major component of BBB, on which the increased expression of CD40 could mediate BBB dysfunction in diabetics. Since platelets play an important role in regulating endothelial cell barrier function and over 95 % of the circulating soluble CD40 ligand (sCD40L) is derived from activated platelets, we speculated that the release of CD40L from activated platelets induced by diabetes was the key mechanism that aggravated BBB injury and leaded to DACD. We performed inhibition of platelet activation on diabetic and non-diabetic mice, with or without cilostazol treatment, and then compared cognitive function, platelet activation, BBB structure and permeability. In vitro, mouse brain microvascular endothelial cell line (b.End3) were exposed to CD40L for 24 h at 5.5 mM or 30 mM glucose media after silencing CD40 and HIF1α or not to investigate the effects of CD40 on BBB disruption and the underlying molecular pathways. Inhibition of platelet activation improved cognitive behaviors in diabetic mice, accompanied with reduced BBB permeability, increased tight junction proteins, balanced Aβ transporters, as well as attenuated Aβ deposition and hippocampal neurons damage. In vitro, CD40L increased HIF1α, diminished tight junction proteins and dysregulated Aβ transporters in b.End3 cells, which could be restored by CD40 siRNA and HIF1α siRNA. Hence, inhibition of platelet activation ameliorates DACD via alleviating BBB injury, which involving the regulation of CD40L-CD40-HIF1α signaling pathway. Our study may demonstrate a potential therapeutic target for the treatment of DACD.

Importance: Postoperative gastrointestinal dysfunction (POGD) may be caused by postoperative vagus nerve tension inhibition and systemic inflammation. Dexmedetomidine (Dex) increases vagus nerve tone and affords an anti-inflammatory property, which may play a role in pathogenesis.Objective: To investigate whether a higher dose of Dex enhances gastrointestinal function recovery.Design: In this retrospective study, patients receiving colorectal surgery at the First Affiliated Hospital of Xi’an Jiaotong University from 2017 to 2019 were included. We evaluated the postoperative flatus time between recipients who received loading plus maintenance dose of DEX (LMD group, 237 recipients) and those who recieved maintenance dose of DEX (MD group, 302 recipients). Data were analyzed by logical regression and stratified and interaction analyses. The simulated pharmacokinetics of two DEX regimens was compared using the Tivatrainer software. Thirty paired blood samples from patients whose propensity scores matched with POGD-related factors at 24 h postoperatively were randomly selected, and their tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), d-lactate (DLA), acetylcholine (Ach), interleukin (IL)-10, lipopolysaccharide (LPS), IL-6, and inducible nitric oxide synthase (iNOS) levels were measured.Setting: Operating rooms and general surgery wards.Participants: Among the 644 patients undergoing colorectal surgery, 12 who had a colostomy, 26 without Dex infusion, 20 whose Dex administration mode cannot be classified, and 47 with a history of intestinal surgery were excluded. A total of 539 patients were included.Result: Compared with the MD group, the LMD group had a shorter recovery time to flatus; lower incidences of nausea, vomiting, abdominal distension, and abdominal pain (p < 0.05); and a slightly decreased heart rate. The LMD group was the independent factor of POGD (OR = 0.59, 95% CI = 0.41–0.87, p = 0.007) without being reversed in stratified and interaction analyses and had higher Dex plasma concentration from skin incision to 8 h postoperatively. The LMD group had a 39% and 43% increase in Ach and IL-10 levels, respectively, and a 33%–77% decrease in TNF-α, IL-6, COX-2, iNOS, LPS, and DLA levels (p < 0.05).Conclusion: Adding an extra loading dose of Dex can increase parasympathetic tone and decrease inflammation; hence, it can enhance postoperative gastrointestinal function recovery following colorectal surgery.