Macrophage-related therapeutic strategies: Regulation of phenotypic switching and construction of drug delivery systems.

Macrophages, as highly phenotypic plastic immune cells, play diverse roles in different pathological conditions. Changing and controlling the phenotypes of macrophages is considered a novel potential therapeutic intervention. Meanwhile, specific transmembrane proteins anchoring on the surface of the macrophage membrane are relatively conserved, supporting its functional properties, such as inflammatory chemotaxis and tumor targeting. Thus, a series of drug delivery systems related to specific macrophage membrane proteins are commonly used to treat chronic inflammatory diseases. This review summarizes macrophages-based strategies for chronic diseases, discusses the regulation of macrophage phenotypes and their polarization processes, and presents how to design and apply the site-specific targeted drug delivery systems in vivo based on the macrophages and their derived membrane receptors. It aims to provide a better understanding of macrophages in immunoregulation and proposes macrophages-based targeted therapeutic approaches for chronic diseases.

A modified Fangji Huangqi decoction ameliorates pulmonary artery hypertension via phosphatidylinositide 3-kinases/protein kinase B-mediated regulation of proliferation and apoptosis of smooth muscle cells in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary artery hypertension (PAH) is a progressive and fatal lung disease of multifactorial etiology, which arouses an enhanced interest in PAH disease therapy. Modified Fangji Huangqi decoction (MFJHQ), a traditional Chinese medicine (TCM) formula, has a crucial role in the treatment of PAH. However, the pharmacological roles and mechanisms of MFJHQ on PAH remain unknown. AIM OF THE STUDY: To investigate the effects and potential mechanism of MFJHQ on pulmonary vascular remodeling in PAH. MATERIAL AND METHODS: Ultra-performance liquid chromatography (UPLC) was employed to quantitate the principal components in MFJHQ. Rats were treated with MFJHQ by gavage for final 2 weeks in monocrotaline (MCT)-induced PAH rats. RNA-sequencing and network pharmacology analysis were performed to explore the potential mechanism. The primary rat pulmonary artery smooth muscle cells (PASMCs) were utilized to evaluate the regulatory effect of MFJHQ in vitro. RESULTS: Seven active components from MFJHQ were quantitated by UPLC. In rats with MCT-induced PAH, MFJHQ treatment significantly improved hemodynamic parameters, right ventricular hypertrophy index, lung function, and attenuated pulmonary vascular remodeling. Mechanistically, we further confirmed that MFJHQ inhibits MCT-induced phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt) pathway predicated by network pharmacology and RNA-sequencing analysis to reduce the proliferation of pulmonary arteries and promote pulmonary artery apoptosis in lung tissues. Additionally, MFJHQ hindered the proliferation and migration, and accelerated apoptosis in PDGF-BB-induced PASMCs in vitro, which can be enhanced by the presence of the PI3K inhibitor LY294002. CONCLUSIONS: Our results indicated that MFJHQ inhibited MCT-induced pulmonary vascular remodeling by decreasing proliferation and migration of PASMCs and promoting PASMC apoptosis through PI3K/Akt pathway, which provides a novel treatment option for PAH with multi-targeting mechanisms inspired by TCM theory.

Xuanfei Baidu Decoction regulates NETs formation via CXCL2/CXCR2 signaling pathway that is involved in acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening symptoms in Coronavirus Disease 2019 (COVID-19) patients. Xuanfei Baidu Decoction (XFBD) is a recommend first-line traditional Chinese medicine (TCM) formula therapeutic strategy for COVID-19 patients. Prior studies demonstrated the pharmacological roles and mechanisms of XFBD and its derived effective components against inflammation and infections through multiple model systems, which provided the biological explanations for its clinical use. Our previous work revealed that XFBD inhibited macrophages and neutrophils infiltration via PD-1/IL17A signaling pathway. However, the subsequent biological processes are not well elucidated. Here, we proposed a hypothesis that XFBD can regulate the neutrophils-mediated immune responses, including neutrophil extracellular traps (NETs) formation and the generation of platelet-neutrophil aggregates (PNAs) after XFBD administration in lipopolysaccharide (LPS)-induced ALI mice. The mechanism behind it was also firstly explained, that is XFBD regulated NETs formation via CXCL2/CXCR2 axis. Altogether, our findings demonstrated the sequential immune responses of XFBD after inhibiting neutrophils infiltration, as well as shedding light on exploiting the therapy of XFBD targeting neutrophils to ameliorate ALI during the clinical course.

Magnetic liposome as a dual-targeting delivery system for idiopathic pulmonary fibrosis treatment.

Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia, where M2 macrophages play an irreplaceable role in the anti-inflammatory progress. Targeting M2 macrophages and regulating their polarization may be a potential treatment strategy for IPF. Herein, we designed a magnetic liposome based dual-targeting delivery system for the IPF treatment, constructed by mannose-modified magnetic nanoparticles (MAN-MNPs) loaded on the surface of the liposome (MAN-MNPs@LP). The delivery system is capable of responding to a static magnetic field (SMF) and then recognizing in situ of M2 macrophages through the mannose receptor-dependent internalization. Firstly, a series of physical and chemical assays were used to characterize these nanoparticles. Subsequently, magnetic liposomes accumulation in the damaged lung with/without mannose modification and SMF were compared by in vivo imaging system. Finally, the reduction of M2 macrophages and inhibition of their polarization confirmed that the development of IPF was retarded due to the in situ release of encapsulated dexamethasone (Dex) in lungs under the SMF. Further investigation demonstrated that the expression of α-SMA and collagen deposition was reduced. Altogether, this dual-targeting delivery system can effectively deliver Dex into M2 macrophages in the lung, making it a novel and promising therapeutic system for the IPF treatment.

Multi-magnetic center ionic liquids for dispersive liquid-liquid microextraction coupled with in-situ decomposition based back-extraction for the enrichment of parabens in beverage samples.

In this paper, several new multi-magnetic center magnetic ionic liquids (MMILs) were prepared with paramagnetic component simultaneously contained in both the cation and anion and used as extractants to establish a dispersive liquid-liquid microextraction (DLLME) approach followed by in-situ MMIL decomposition based back-extraction for the enrichment and determination of four parabens in beverages. The appropriate MMIL was selected by investigating the extraction performances of the obtained MMILs combined with high performance liquid chromatography-ultraviolet detection (HPLC-UV), and some other experimental factors were explored. Under the optimized DLLME conditions, the four parabens exhibited coefficients of determination (R2) above 0.9987 in the linear range of 0.1-500 ng·mL-1 for ethylparaben, propylparaben and butylparaben and 0.2-500 ng·mL-1 for methylparaben. The limits of detection (LODs) and limits of quantification (LOQs) were respectively within 0.03-0.06 ng·mL-1 and 0.1-0.2 ng·mL-1, and the relative standard deviations (RSDs) for intra-day and inter-day precision were below 10.8%. Moreover, the application of the developed MMIL-based DLLME method in beverage samples exhibited recoveries within 81.3%-112.1% with RSDs of 0.3%-13.1% at three different spiked levels.

A new magnetic ionic liquid based salting-out assisted dispersive liquid-liquid microextraction for the determination of parabens in environmental water samples.

In this study, a new magnetic ionic liquid (MIL) was designed and prepared, containing a magnetic cation from the ligand N,N-dimethyl biguanide (DMBG) complexing with magnetic center Co2+ and a bis-trifluoromethanesulfonimide (NTf2-) anion. Using the MIL as the extraction solvent, a salting-out assisted dispersive liquid-liquid microextraction (SA-DLLME) combined with high performance liquid chromatography-ultraviolet detection (HPLC-UV) was established for the enrichment and detection of four parabens in environmental water samples. The one-factor-at-a-time experiment was employed to optimize the conditions affecting the extraction efficiency. Under the optimized extraction conditions, the limits of quantification (LOQs) of the four target analytes ranged from 2.0 ng mL-1 to 2.8 ng mL-1, and the coefficients of determination (R2) were above 0.9996 in the linear range of 2.8-400 ng mL-1. On the other hand, the method displayed good repeatability and accuracy with intra-day and inter-day relative standard deviations (RSDs) of 2.1-13.0% and recoveries of 82.0-114.6%. The established method was applied to real samples with recoveries within 81.6-125.4%, and the results demonstrated that the method was practical.

Three-dimensional flower-like SnS2 materials for dispersive solid-phase extraction of endocrine-disrupting phenols.

In this study, three-dimensional flower-like tin disulfide materials were prepared, and a highly efficient dispersive solid-phase extraction method was developed using the obtained three-dimensional tin disulfide adsorbents for the preconcentration and determination of six endocrine-disrupting phenols in combination with high-performance liquid chromatography-ultraviolet detection. Several important experimental parameters influencing extraction efficiency were investigated, including the amount of adsorbent, ultrasound time, sample solution pH, sample volume, type of elution solvent, desorption time, and the number of desorption times. Under the optimized experimental conditions, the developed method showed good linearity with the determination coefficients of 0.993-0.998 in the linear range of 0.5-400 ng/ml and low limits of detection in the range of 0.15-1.0 ng/ml, as well as satisfactory intra-day and inter-day precisions with relative standard deviations of 0.1-9.8%. Finally, the proposed method was successfully applied for the enrichment and determination of trace endocrine-disrupting phenols in milk, tea beverage, and plastic bottled water samples, and acceptable recoveries were obtained from 70.1% to 119.1% under four different spiked concentration levels. The results showed that the three-dimensional tin disulfide materials had great potential for the extraction of endocrine-disrupting phenols contaminants in environmental and food samples.

Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanfei Baidu Decoction (XFBD), one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, plays an important role in the treatment of mild and/or common patients with dampness-toxin obstructing lung syndrome. AIM OF THE STUDY: The present work aims to elucidate the protective effects and the possible mechanism of XFBD against the acute inflammation and pulmonary fibrosis. METHODS: We use TGF-ß1 induced fibroblast activation model and LPS/IL-4 induced macrophage inflammation model as in vitro cell models. The mice model of lung fibrosis was induced by BLM via endotracheal drip, and then XFBD (4.6 g/kg, 9.2 g/kg) were administered orally respectively. The efficacy and molecular mechanisms in the presence or absence of XFBD were investigated. RESULTS: The results proved that XFBD can effectively inhibit fibroblast collagen deposition, down-regulate the level of α-SMA and inhibit the migration of fibroblasts. IL-4 induced macrophage polarization was also inhibited and the secretions of the inflammatory factors including IL6, iNOS were down-regulated. In vivo experiments, the results proved that XFBD improved the weight loss and survival rate of the mice. The XFBD high-dose administration group had a significant effect in inhibiting collagen deposition and the expression of α-SMA in the lungs of mice. XFBD can reduce bleomycin-induced pulmonary fibrosis by inhibiting IL-6/STAT3 activation and related macrophage infiltration. CONCLUSIONS: Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.

Mitochondrial genome of Macrostemum floridum (Trichoptera).

Trichoptera are a group of the benthic organism, almost all of which live in water during their life cycle. Trichoptera usually develop through egg, larva, pupa, and moth stages. In its larval stage, Trichoptera usually live in water and are often called the caddisfly. In this study, the mitochondrial genome of Macrostemum floridum was analyzed. The total length of the mitochondrial genome is 15,424 bp and consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and one control region. The genome has a typical mitochondrial gene sequence of Trichoptera. Phylogenetic analysis of the mitochondrial genomes of 23 species of Trichoptera and Lepidoptera showed that M. floridum forms a monophyletic group with other species of Lepidoptera.

Characterization of the complete mitochondrial genome of Stenopsyche angustata (Trichoptera, Stenopsychidae).

Caddisflies of Stenopsyche angustata (Trichoptera, Stenopsychidae) are widely distributed in various freshwater bodies and a few species inhabit marine environments. The mitochondrial genome was sequenced by Illumina high-throughput sequencing, and then the complete mitochondrial genome sequence was obtained through splicing and assembly. The mitochondrial genome sequence size was 15,371 bp, comprising 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and a control region. Two of the protein-coding genes (COX 2 and nad 5) had an incomplete termination codon T. In addition, the start codon of all protein-coding genes was ATN, except for the start codon of the nad4l gene which was GTG. The base composition of the mitochondrial genome was 41.64% A, 35.03% T, 7.81% G, and 15.52% C.

Coupling mechanism between wear and oxidation processes of 304 stainless steel in hydrogen peroxide environments.

Stainless steel is widely used in strongly oxidizing hydrogen peroxide (H2O2) environments. It is crucial to study its wear behaviour and failure mode. The tribological properties and oxidation of 304 stainless steel were investigated using a MMW-1 tribo-tester with a three-electrode setup in H2O2 solutions with different concentrations. Corrosion current densities (CCDs), coefficients of frictions (COFs), wear mass losses, wear surface topographies, and metal oxide films were analysed and compared. The results show that the wear process and oxidation process interacted significantly with each other. Increasing the concentration of H2O2 or the oxidation time was useful to form a layer of integrated, homogeneous, compact and thick metal oxide film. The dense metal oxide films with higher mechanical strengths improved the wear process and also reduced the oxidation reaction. The wear process removed the metal oxide films to increase the oxidation reaction. Theoretical data is provided for the rational design and application of friction pairs in oxidation corrosion conditions.

[Effects of Siwu decoction on bone marrow protein expression of blood deficiency mice induced by cyclophosphamide].

OBJECTIVE: To study the effects of Siwu decoction on protein expression of blood deficiency mice induced by cyclophosphamide (CIX) and discuss the possible molecular mechanism on blood enriching function of Siwu decoction. METHOD: Blood deficiency mice were established by injecting ip with 250 mg x kg(-1) CTX. Proteomic technologies were applied to identify the different protein. RESULT: Siwu decoction could restore the changes of 12 up-regulated and 3 down-regulated proteins in bone marrow of blood deficiency mice induced by cyclosphosphamide. CONCLUSION: Siwu decoction could effect expression of proteins which functions including apoptosis, proliferation and differentiation of the haematopoietic stem/progenitor cell. The regulation in the molecular level might be the mechanism of stimulating hematopoiesis in bone marrow fo siwu decocetion.