Ischemic stroke (IS) ranks as a leading cause of death and disability globally. The blood-brain barrier (BBB) poses significant challenges for effective drug delivery to brain tissues. Recent decades have seen the development of targeted nanomedicine and biomimetic technologies, sparking substantial interest in biomimetic drug delivery systems for treating IS. These systems are devised by utilizing or replicating natural cells and their derivatives, offering promising new pathways for detection and transport across the BBB. Their multifunctionality and high biocompatibility make them effective treatment options for IS. In addition, the incorporation of engineering techniques has provided these biomimetic drug delivery systems with active targeting capabilities, enhancing the accumulation of therapeutic agents in ischemic tissues and specific cell types. This improvement boosts drug transport and therapeutic efficacy. However, it is crucial to thoroughly understand the advantages and limitations of various engineering strategies employed in constructing biomimetic delivery systems. Selecting appropriate construction methods based on the characteristics of the disease is vital to achieving optimal treatment outcomes. This review summarizes recent advancements in three types of engineered biomimetic drug delivery systems, developed from natural cells and their derivatives, for treating IS. It also discusses their effectiveness in application and potential challenges in future clinical translation.
Humans ; Drug Delivery Systems/methods* ; Ischemic Stroke/drug therapy* ; Animals ; Blood-Brain Barrier/metabolism* ; Stroke/drug therapy*

Ischemic stroke is the leading cause of disability and mortality worldwide. The blood‒brain barrier (BBB) is the first line of defense after ischemic stroke. Disruption of the BBB induced by brain microvascular endothelial cells (BMECs) dysfunction is a key event that triggers secondary damage to the central nervous system, where blood-borne fluids and immune cells penetrate the brain parenchyma, causing cerebral edema and inflammatory response and further aggravating brain damage. Here, we develop a novel artificial mesenchymal stem cell (MSC) extracellular vesicles by integrating MSC membrane proteins into liposomal bilayers, which encapsulated miR-132-3p with protective effects on BMECs. The artificial extracellular vesicles (MSCo/miR-132-3p) had low immunogenicity to reduce non-specific clearance by the mononuclear phagocytosis system (MPS) and could target ischemia-injured BMECs. After internalization into the damaged BMECs, MSCo/miR-132-3p escaped the lysosomes via the H_II phase transition of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and decreased cellular reactive oxygen species (ROS) and apoptosis levels by regulating the RASA1/RAS/PI3K/AKT signaling pathway. In the transient middle cerebral artery occlusion (tMCAO) models, MSCo/miR-132-3p targeted impaired brain regions (approximately 9 times the accumulation of plain liposomes at 12 h), reduced cerebral vascular disruption, protected BBB integrity, and decreased infarct volume (from 44.95% to 6.99%).

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

Objective : To investigate the antagonistic activity of Lactococcus garvieae SHAMU-LG6 against Staphy- lococcus . Methods : VITEK 2 GP identification card , Microflex LT MALDI-TOF mass spectrometer and 16S rDNA amplification sequencing were used to identify the strain species . The antagonistic activity of L. garvieae SHAMU- LG6 against different Staphylococcus was detected by Oxford cup method for bacterial inhibition ; the antimicrobial active components were preliminarily isolated and purified by adsorption on XAD16 nonionic macroporous resin , gradient ethanol elution and rotary evaporation drying. Results : L. garvieae SHAMU-LG6 exhibited potent antago- nistic effect against methicillin-resistant Staphylococcus aureus , methicillin-susceptible S. aureus , S. epidermidis , S. saprophyticus , S. lugdunensis , S. hominis , S. capitis and S. warneri , with inhibitory indices of 3 . 3 , 3 . 0 , 4. 3 , 2. 0 , 4. 0 , 3 . 5 , 3 . 8 , and 3 . 5 , respectively. The antimicrobial active components produced by L. garvieae SHAMU-LG6 were mainly present in 70% and 80% ethanol eluates . Conclusion L. garvieae SHAMU-LG6 ex- hibits a potent antagonistic effect on Staphylococcus , and the antimicrobial active components produced by it are ex- pected to be a lead compound for the development of novel antimicrobial agents .

OBJECTIVE To investigate the ameliorative effects and mechanism of Sanwei ganlu on hepatic fibrosis in rats. METHODS The rats were randomly divided into normal group， model group， silibinin group （positive control， 50 mg/kg）， and Sanwei ganlu low-dose， medium-dose， and high-dose groups （80， 250， 800 mg/kg）. Except for normal group， hepatic fibrosis rat models were established by intraperitoneal injection of CCl4 in the other groups of rats. Starting from the 6th week of modeling administration， they were given normal saline or corresponding drugs intragastrically at the same time. At the end of the ninth-week experiment， liver and spleen indexes of rats were calculated； the pathological structure and fibrosis changes of liver tissue were observed by HE， Masson and Sirus Red staining. The contents of alanine transaminase （ALT）， aspartate transaminase （AST）， procollagen type Ⅲ （PC Ⅲ）， collagen type Ⅳ （COL-Ⅳ）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and IL-1β in serum， and hyaluronic acid （HA） and laminin （LN） in liver tissue were all detected. RESULTS Compared with the model group， the liver injury and collagen fiber deposition of rats were improved to different extents in Sanwei ganlu groups and silibinin group； the contents of ALT， AST， PC Ⅲ， COL-Ⅳ， IL-6， TNF-α and IL-1β in serum as well as the contents of HA and LN in liver tissue significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Sanwei ganlu can alleviate the progression of hepatic fibrosis in rats， possibly by inhibiting the synthesis of collagen fiber， reducing transaminase content， down-regulating the levels of HA， LN， PC Ⅲ and COL-Ⅳ， and reducing the inflammatory response.

Objective:To investigate the distribution of potential suitable habitats for Ixodes persulcatus in Heilongjiang Province during different climatic periods. Methods:The geographical location data of Ixodes persulcatus in Heilongjiang Province from 1980 to 2023 were collected through literature search and field ecological investigation. The environmental factor variables were downloaded from the WorldClim website and the Resource and Environmental Science and Data Platform. A combination of SDMtune, ENMTools packages, and the maximum entropy (MaxEnt) model were used to predict the potential habitats of Ixodes persulcatus in Heilongjiang Province during different climatic periods and determine its dominant environmental factors. Among them, the time range of historical climatic period data was 1970 - 2000. The future climatic period data (2021 - 2040, 2041 - 2060) were selected as the low forcing scenario (SSP126 scenario) of the shared socioeconomic pathways (SSP) in the Beijing Climate Center - Climate System Model version 2-Medium Resolution, to simulate the impact of global warming on the distribution of potential habitats for Ixodes persulcatus in Heilongjiang Province. Results:A total of 83 geographical distribution sites of Ixodes persulcatus in Heilongjiang Province were obtained. After screening, 10 environmental factors were included in the MaxEnt model. Among them, the cumulative contribution percentage of annual precipitation, average annual temperature, and vegetation type was 67.3%. Compared with historical climatic period, the total potential habitats of Ixodes persulcatus in Heilongjiang Province increased from 29.81 × 10 4 km 2 to 32.24 × 10 4 km 2 in 2041 - 2060. The center of potential habitats moved to 47.75° N, and 128.66° E, with a northwest offset of 126.07° and a migration distance of 45.83 km. Conclusion:With global climate warming, the total potential habitats of Ixodes persulcatus in Heilongjiang Province has increased, showing an overall trend of migration to the northwest.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.