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Icariin has been shown the promising therapeutic potential to treat inflammatory airway diseases, yet its poor lung distribution and retention restrict the clinical applications. To this end, this work aimed to prepare an icariin-phospholipid complex (IPC) formulation for sustained nebulization delivery that enabled excellent inhalability, improved lung exposure and prolonged duration of action. Icariin was found to react with soybean phospholipid to form supramolecular IPC, which was able to self-assemble into nanoparticle suspension. The suspension was stable during steam sterilization and nebulization processes, and its aerosols generated by a commercial nebulizer exhibited excellent aerodynamic properties and delivery efficiency. In vitro studies showed that the formation of complex sustained drug release, enhanced lung affinity and slowed lung clearance. The drug distribution in lung epithelial lining fluid (ELF) also demonstrated in vivo sustained release after intratracheal administration to mice. In addition, compared to free icariin, IPC improved the drug exposure to lung tissues and immune cells in the ELF by 4.61-fold and 39.5-fold, respectively. This resulted in improved and prolonged local anti-inflammatory effects up to 24 h in mice with lipopolysaccharide (LPS)-induced acute lung injury. Moreover, IPC improved survival rate of mice with acute respiratory distress syndrome (ARDS). Overall, the present phospholipid complex represented a promising formulation of icariin for the treatment of acute lung injury/ARDS by nebulization delivery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microglia, resident immune cells in the central nervous system, constantly monitor the state of the surrounding brain activity. The animal model induced by sleep deprivation (SD) is widely used to study the pathophysiological mechanisms of insomnia and bipolar disorder. However, it remains unclear whether SD affects behaviors in young and aged male mice and microglia in various brain regions. In this study, we confirmed brain region-specific changes in microglial density and morphology in the accumbens nucleus (Acb), amygdala (AMY), cerebellum (Cb), corpus callosum (cc), caudate putamen, hippocampus (HIP), hypothalamus (HYP), medial prefrontal cortex (mPFC), and thalamus (TH) of young mice. In addition, the density of microglia in old mice was higher than that in young mice. Compared with young mice, old mice showed a markedly increased microglial size, decreased total length of microglial processes, and decreased maximum length. Importantly, we found that 48-h SD decreased microglial density and morphology in old mice, whereas SD increased microglial density and morphology in most observed brain regions in young mice. SD-induced hyperactivity was observed only in young mice but not in old mice. Moreover, microglial density (HIP, AMY, mPFC, CPu) was significantly positively correlated with behaviors in SD- and vehicle-treated young mice. Contrarily, negative correlations were shown between the microglial density (cc, Cb, TH, HYP, Acb, AMY) and behaviors in vehicle-treated young and old mice. These results suggest that SD dysregulates the homeostatic state of microglia in a region- and age-dependent manner. Microglia may be involved in regulating age-related behavioral responses to SD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hantavirus (HV) infection, which underlies hantavirus hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, remains to be a severe clinical challenge. Here, we synthesized small interfering RNAs (siRNAs) that target the encoding sequences of HV strain 76-118, and validated their inhibitory role in virus replication in HV-infected monkey kidney Vero E6 cells. A chimeric protein, 3G1-Cκ-tP, consisting of a single-chain antibody fragment (3G1) against the HV surface envelop glycoprotein, the constant region of human immunoglobulin κ chain (Cκ), and truncated protamine (amino acids 8-29, tP), was further generated. The fusion protein showed high affinity to HV antigen on the infected cell membrane, and internalized through clathrin-mediated endocytosis; it bound to siRNAs via the basic nucleic acid-rich protamine fragment, leading to their specific delivery into HV-infected cells and efficient inhibition of virus replication. An encephalitis mouse model was established via intracranial HV administration. Intraperitoneal injection of siRNAs complexed with 3G1-Cκ-tP achieved specific distribution of siRNAs in HV-infected brain cells, significantly reduced HV antigen levels, and effective protection from HV infection-derived animal death. These results provide a compelling rationale for novel therapeutic protocols designed for HV infection and related disorders., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Silica microspheres have been synthesized by phase separation and sol-gel transition coupled with emulsion method. The as-obtained material is characterized by scanning electron microscopy, nitrogen sorption, elemental analysis and particle size distribution measurements. The results demonstrated that the material featured with hierarchically porous structure, possessing both mesopores and penetrable macropores. The mesopores provide large surface area while the macropores traverse the silica particles, which may facilitate fast mass transfer as well as guarantee low backpressure when such materials are used for packed high-performance liquid chromatography (HPLC) column. Therefore, their preliminary applications as HPLC packings in fast separation and low-pressure separation have been attempted in the present study. Benzene, benzaldehyde and benzyl alcohol were separated within two minutes on the silica column at a flow rate of 7 mL min(-1). Vitamin E mixtures can also be baseline separated at a high flow rate of 8 mL min(-1). In addition, thirteen aromatic hydrocarbons were well separated on the octadecyl-bonded silica (ODS) column. In comparison with a commercial Kromasil ODS column, the pressure of the proposed column is much lower (<1/2) under the same chromatographic conditions, while comparable separation efficiency can be achieved.

Background: The aim of this study was to investigate the effects of procalcitonin on the lipopolysaccharide (LPS)-induced changes in human leucocytes and porcine isolated coronary artery., Methods: Using flow cytometry, changes in forward scatter and intracellular calcium in human neutrophils and monocytes were determined after exposure to procalcitonin, calcitonin gene-related peptide (CGRP), LPS, and the known chemoattractants formylated methionine-leucine-phenylalanine (fMLP) and interleukin-8 (IL-8). In porcine isolated coronary artery, the effects of procalcitonin were evaluated using the contractile function change and the release of TNFalpha., Results: In human neutrophils and monocytes, procalcitonin (100 nM), but not CGRP, increased forward scatter and the expression of surface markers (CD16 and CD14, respectively) in a similar manner to 10 microg ml(-1) LPS. Procalcitonin, but not CGRP, also increased the proportion of cells exhibiting an increase in intracellular calcium ions similar to that produced by fMLP and IL-8. Acute exposure of the coronary artery to procalcitonin produced a small, endothelium-independent relaxation (approximately 15% of constrictor tone), but failed to modify subsequent relaxations to CGRP. After 16 h exposure, procalcitonin (100 nM) increased TNFalpha release from the coronary artery equivalent to 70% of that produced by LPS, but did not modify the inhibitory effect of LPS (100 microg ml(-1)) on contractile responses., Conclusions: Procalcitonin has a proinflammatory effect on human leucocytes and porcine coronary artery, but it is not capable of modulating LPS-induced changes in vascular responsiveness in vitro.

Background: Prolonged incubation of porcine isolated coronary artery (PCA) to lipopolysaccharide (LPS) causes a moderate reduction in vessel constrictive responsiveness. This has been attributed mainly to the induction of nitric oxide synthase (NOS). We aimed to investigate the role of induction of cyclo-oxygenase (COX) and expression of endothelin receptor 1-A (ET1(A)) in modulating the vascular responses of PCA in vitro., Methods: Segments of PCA were exposed to 100 microg ml(-1) LPS overnight. L-Arginine 0.4 mM was included in the medium in some preparations to examine the influence of intracellular nitric oxide, and the influence of extracellular donor sodium nitroprusside (SNP) was also examined in separate experiments. After overnight incubation, the contractile function of the artery was evaluated by the isometric tension recording test. The non-selective NOS inhibitor (L-NAME), non-selective COX inhibitor (indomethacin), COX-1 inhibitor (FR 122047), COX-2 inhibitor (NS 398), and ET1(A) receptor antagonist (FR 139317) were added into the organ bath 30 min before eliciting contractile responses to KCl or U46619 separately or in combinations. Vascular relaxations to 10 nM Substance P (SP) were also assessed., Results: L-Arginine did not potentiate the effects of LPS. SNP caused a quantitatively larger reduction in the responsiveness to KCl and U46619 compared with 100 microg ml(-1) LPS. Post exposure to a combination of indomethacin and FR 139317, indomethacin or NS 398 alone enhanced the inhibitory effects of LPS, but FR 122047 or FR 139317 alone failed to modify the responses to LPS. L-NAME fully reversed the changes induced by LPS combined with indomethacin and NS398. In terms of the relaxation by SP, LPS failed to change the magnitude; none of the agents used affected the response except L-NAME which abolished it., Conclusion: NOS and COX-2 are both activated by overnight exposure to LPS in vascular smooth muscle from PCA in vitro. The prostanoid produced by COX-2 functionally antagonizes the effects of induction of NOS.

Objective: The purpose of this study was to report our experience in the surgical treatment of 484 Chinese patients with follow-up in 255 cases., Methods: A retrospective analysis was conducted of all odontogenic keratocysts that were surgically treated and histopathologically diagnosed between 1962 and 1998. The odontogenic keratocysts were surgically treated with enucleation, marsupialization followed by secondary enucleation, and resection with or without continuity defects. The recurrence rate was evaluated for the patients followed more than 3 years., Results: Of a total of 489 odontogenic keratocysts, 327 (66.87%) were found in the mandible and 162 (33.13%) in the maxilla. Follow-up data were obtained in 255 patients. Recurrence was found in 31 cases (15.27%) in 203 patients treated with enucleation after an observation period of 3 to 29 years. Twenty-nine recurrences (17.79%) were found in 163 patients treated with enucleation alone, two recurrences (6.70%) were seen in 29 patients who received Carnoy's solution fixation of the cyst wall before enucleation, and no recurrence was found in 11 cases treated with marsupialization in combination with secondary enucleation. No recurrence was seen in 52 patients treated with resection., Conclusion: Odontogenic keratocysts treated with enucleation alone have a higher recurrence rate. Enucleation with adjunctive treatment can decrease recurrence rate. Radical excision has no recurrence but does have the highest morbidity rate and should be reserved for multiple recurrent cysts after conservative means.