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Synthetic nanoparticles with surface bioconjugation are promising platforms for targeted therapy, but their simple biological functionalization is still a challenging task against the complex intercellular environment. Once synthetic nanoparticles enter the body, they are phagocytosed by immune cells by the immune system. Recently, the cell membrane camouflage strategy has emerged as a novel therapeutic tactic to overcome these issues by utilizing the fundamental properties of natural cells. Macrophage, a type of immune system cells, plays critical roles in various diseases, including cancer, atherosclerosis, rheumatoid arthritis, infection and inflammation, due to the recognition and engulfment function of removing substances and pathogens. Macrophage membranes inherit the surface protein profiles and biointerfacing properties of source cells. Therefore, the macrophage membrane cloaking can protect synthetic nanoparticles from phagocytosis by the immune cells. Meanwhile, the macrophage membrane can make use of the natural correspondence to accurately recognize antigens and target inflamed tissue or tumor sites. In this review, we have summarized the advances in the fabrication, characterization and homing capacity of macrophage membrane cloaking nanoparticles in various diseases, including cancers, immune diseases, cardiovascular diseases, central nervous system diseases, and microbial infections. Although macrophage membrane-camouflaged nanoparticles are currently in the fetal stage of development, there is huge potential and challenge to explore the conversion mode in the clinic. [ABSTRACT FROM AUTHOR]

Cancer is a major threat to the health of humans. Recently, various natural products including curcumin (CCM) have attracted enormous interest for efficacious cancer therapy. However, natural therapeutic agents still encounter certain challenges such as rapid clearance, low bioavailability, and poor tumor targeting. Recently, the platelet membrane (PM) camouflaged nanoparticle has provided a promising solution for cancer targeting therapy. Nevertheless, only limited efforts have been dedicated to systematically explore the mechanism of affinity between PM bioinspired nanoparticles and various tumor cells. Herein, a CCM-encapsulated platelet membrane biomimetic lipid vesicle (CCM@PL) with a size of 163.2 nm, zeta potential of −31.8 mV and encapsulation efficiency of 93.62% was developed. The values of the area under the concentration-time curve and mean residence time for CCM@PL were 3.08 times and 3.04 times those of CCM, respectively. Furthermore, this PM biomimetic carrier showed an excellent affinity against Huh-7, SK-OV-3 and MDA-MB-231 cell lines due to the biomolecular interaction between P-selectin on the PM and tumoral CD44 receptors. In addition, CCM@PL displayed enhanced cytotoxicity compared with free CCM and the synthetic formulation. Overall, our results suggest that this developed PM biomimetic lipid nanovector has great potential for targeted cancer treatment and natural components delivery. [ABSTRACT FROM AUTHOR]

Curcumin (CUR) is a promising natural product for hepatocellular carcinoma (HCC) therapy. However, its clinical application has been limited by some issues such as rapid clearance and inadequate tumor accumulation. To address these drawbacks, we developed platelet membrane-coated CUR-loaded PLGA nanoparticles (PCPNPs). In this work, due to the bioinspired strategy, the PCPNPs exhibited immune evasion, prolonged circulation, and improved accumulation at tumor sites compared to the traditional CUR formulation. The superior tumor targeting of PCPNPs was likely due to the interactions between platelet P-selectin and tumoral CD44. Furthermore, both in vitro and in vivo assays revealed that the PCPNPs showed outstanding anticancer efficacy without obvious toxicity. Therefore, PCPNPs represent a biosafe and promising anti-tumor strategy, overcoming the limitations associated with CUR. These findings not only contribute to the advancement of natural compound nano-formulation but also open new avenues for targeted cancer treatment. • For the first time the PCPNPs was developed. • The possible mechanisms (the cellular uptake, the pharmacokinetics, and tumor affinity) were preliminary explored. • Our work could provide a promising biomimetic nano-vector for cancer targeted therapy and phytochemicals delivery. [ABSTRACT FROM AUTHOR]

• Thermal isomerisation of pyrethrin I and II occurs in the injector and on-column. • Elevated injector T leads to greater production of isopyrethrin I and II isomers. • Above an oven T of about 200 °C, on-column isomerisation occurs. • GC×GC provides a valuable means for interpretation of the isomerisation process. • Natural pyrethrin retention index data on various column phases are investigated. This study aims to assess and qualitatively compare the visual presentation of chromatographic data from the isomerisation of natural pyrethrins – a group of pesticides derived from Chrysanthemum flowers – using one-dimensional gas chromatography (1DGC) and comprehensive two-dimensional gas chromatography (GC×GC). Molecular structural changes, such as thermal isomerisation in this case, occur during gas chromatography injection and separation, to provide characteristic patterns which may not be routinely recognised on the 1D chromatogram. To demonstrate the influence of analytical method parameters on isomerisation processes, variations in oven temperature (isothermal vs. temperature programmed analysis), inlet mode (split vs. splitless), inlet temperature, and carrier gas flow rate were investigated. Increasing oven temperature was the most significant factor affecting isomerisation. Splitless injection mode and increasing inlet temperature promoted isopyrethrin formation, while the effect of inlet temperature appeared minimal with a split injection technique, most likely due to the short residence time in the inlet. Increased carrier gas flow rates in a temperature programmed analysis reduced retention time and minimised isomerisation. The unique presentation of isopyrethrin peaks on a GC×GC contour plot allows for facile recognition of isomerisation especially at low concentrations, simplifies chromatogram interpretation, and aids in analyte identification. It also confirms that the isomerisation process is irreversible since the pyrethrin I and II compounds are absent throughout the bridge formation. These benefits support the use of GC×GC over 1DGC to study isomerisation. Additionally, due to limited data in the literature, Kováts retention indices and linear retention indices of the natural pyrethrins, including isopyrethrins, were experimentally determined on four columns: DB-5 ms UI, Rxi-17Sil MS, SLB-IL60i, and SLB-IL111i. [ABSTRACT FROM AUTHOR]

Cancer is a serious threat to human health, and chemotherapy for cancer is limited by severe side effects. Curcumin (CUR) is a commonly used natural product for antitumor treatment without safety concerns. However, low bioavailability and poor tumor accumulation are great obstacles for its clinical application. Our previous research has demonstrated that platelet membrane-camouflaged nanoparticles can efficiently ameliorate the in vivo kinetic characteristics and enhance the tumor affinity of payloads. Nevertheless, the antitumor efficiency of this formulation still needs to be thoroughly investigated, and its drug release behavior is limited. Herein, CUR-loaded platelet membrane bioinspired chitosan-modified liposome (PCLP-CUR) was constructed to improve CUR release. PCLP-CUR was shown to have long retention time, improved bioavailability, strong tumor targeting capacity and effective cellular uptake. The incorporation of chitosan enabled PCLP-CUR to release cargoes quickly under mild acidic tumor conditions, leading to more complete drug release and favoring subsequent treatment. Both in vitro and in vivo investigations showed that PCLP-CUR could significantly enhance the anticancer efficacy of CUR with minimal side effects through biomimetic membrane and chitosan modification. In summary, this developed delivery system can provide a promising strategy for tumor-targeting therapy and phytochemical delivery. [ABSTRACT FROM AUTHOR]

Hydrogen type ZSM-5 (HZ) and three supported NiMo catalysts (NiMoNaZ, NiMoHZ and NiMoMMHZ) prepared by incipient wetness impregnation method were systematically characterized and evaluated using 1,3,5-trimethylbenzene (1,3,5-TMB) as the model compound for heavy aromatic hydrodealkylation (HDAK). Among four catalysts, NiMoNaZ has the lowest HDAK activity; compared to HZ and NiMoHZ, NiMoMMHZ has superior 1,3,5-TMB HDAK performance. The characterization results demonstrate that suitable acidity and mesopores of MMHZ result in appropriate metal–support interaction and benefit formation and dispersion of Mo/Ni species in proximity to acid sites on NiMoMMHZ, thus facilitating both textural and chemical synergy between Mo/Ni and acidic sites. This not only improves hydrogenation and hydrogenolysis performance of Mo/Ni species, but facilitates cracking function of acid centers, conferring NiMoMMHZ with higher HDAK activity, selectivity and stability. The finding of this research opens a novel route of enhancing synergy effect between Mo/Ni and acid sites in zeolite supported MoNi catalysts for improving heavy aromatic HDAK performance. Synergism between Mo/Ni and acid sites on NiMo/ZSM-5 for heavy aromatic hydrodealkylation (HDAK) was revealed. [ABSTRACT FROM AUTHOR]

Background: Thrombocytopenia has long been considered an important complication of chemotherapy and radiotherapy, which severely limits the effectiveness of cancer treatment and the overall survival of patients. However, clinical treatment options are extremely limited so far. Ruxolitinib is a potential candidate. Methods: The impact of ruxolitinib on the differentiation and maturation of K562 and Meg-01 cells megakaryocytes (MKs) was examined by flow cytometry, Giemsa and Phalloidin staining. A mouse model of radiation-injured thrombocytopenia (RIT) was employed to evaluate the action of ruxolitinib on thrombocytopoiesis. Network pharmacology, molecular docking, drug affinity responsive target stability assay (DARTS), RNA sequencing, protein blotting and immunofluorescence analysis were applied to explore the targets and mechanisms of action of ruxolitinib. Results: Ruxolitinib can stimulate MK differentiation and maturation in a dose-dependent manner and accelerates recovery of MKs and thrombocytopoiesis in RIT mice. Biological targeting analysis showed that ruxolitinib binds directly to Toll Like Receptor 2 (TLR2) to activate Rac1/cdc42/JNK, and this action was shown to be blocked by C29, a specific inhibitor of TLR2. Conclusions: Ruxolitinib was first identified to facilitate MK differentiation and thrombocytopoiesis, which may alleviate RIT. The potential mechanism of ruxolitinib was to promote MK differentiation via activating the Rac1/cdc42/JNK pathway through binding to TLR2. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of Sanguisorba officinalis L., we studied its monomer, methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity accompanying with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving that MG could alleviate inflammation by regulating the TLR4/NF-κB pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate that MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-κB signaling pathway, and MG may be a promising therapeutic agent for UC treatment. [ABSTRACT FROM AUTHOR]

As a promising architecture reinforcement, the three-dimensional (3D) configuration of nanocarbon holds great prospects in achieving a strength-ductility combination for metal matrix composite (MMCs). However, due to the native deficiency of Al in catalyzing the growth of nanocarbon, constructing a nanocarbon network has been the long-term challenge for Al matrix composites (AMCs). Herein, we develop a new strategy for synthesizing AMCs reinforced by three-dimensional nanocarbon (3D-C) via plasma-enhanced chemical vapor deposition (PECVD) integrated with hot pressing (HP) as well as hot extrusion, demonstrating exceptional mechanical properties. The detailed characterization reveals that the in-situ generation of nanocarbon layers on the surface of Al powders is attributed to the initiation of isolated carbon islands, followed by merging and self-assembly, which is governed by the PECVD-assisted catalysis growth-regime. The subsequent welding of nanocarbon layers during the HP promotes the formation of interlocking 3D-C networks in Al matrix, enhancing the sintered densification of the composite. Such unique nanocarbon distribution configuration not only effectively constrains the coarsening and deformation of Al grains, but also notably accumulates dislocation under high stress conditions. Moreover, 3D-C with a strong interfacial bonding contributes to the toughness through the microcracks, bridging cracks as well deflecting cracks, which accounts for the high toughness of the composite. This work provides new insights into the 3D distribution configuration of reinforcements in AMCs to achieve the optimized mechanical performance of composites. • Three-dimensional nanocarbon network in Al matrix was successfully synthesized. • 3D-C network constrains grain deformation and facilitates dislocation accumulation. • High-coherent 'C-Al 2 O 3 -Al' interface contributes to strength-ductility combination. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is a common hematological disease caused by many factors. It usually complicates critical diseases and increases morbidity and mortality. The treatment of thrombocytopenia remains a great challenge in clinical practice, however, its treatment options are limited. In this study, the active monomer xanthotoxin (XAT) was screened out to explore its medicinal value and provide novel therapeutic strategies for the clinical treatment of thrombocytopenia. The effects of XAT on megakaryocyte differentiation and maturation were detected by flow cytometry, Giemsa and phalloidin staining. RNA-seq identified differentially expressed genes and enriched pathways. The signaling pathway and transcription factors were verified through WB and immunofluorescence staining. Tg (cd41: eGFP) transgenic zebrafish and mice with thrombocytopenia were used to evaluate the biological activity of XAT on platelet formation and the related hematopoietic organ index in vivo. XAT promoted the differentiation and maturation of Meg-01 cells in vitro. Meanwhile, XAT could stimulate platelet formation in transgenic zebrafish and recover platelet production and function in irradiation-induced thrombocytopenia mice. Further RNA-seq prediction and WB verification revealed that XAT activates the IL-1R1 target and MEK/ERK signaling pathway, and upregulates the expression of transcription factors related to the hematopoietic lineage to promote megakaryocyte differentiation and platelet formation. XAT accelerates megakaryocyte differentiation and maturation to promote platelet production and recovery through triggering IL-1R1 and activating the MEK/ERK signaling pathway, providing a new pharmacotherapy strategy for thrombocytopenia. [Display omitted] • The monomer of xanthotoxin is found to have potential for a novel pharmacotherapy of thrombocytopenia. • The signaling protein ERK may be key for xanthotoxin in promoting megakaryocyte differentiation and platelet production. • A new target for the pharmacological activity of xanthotoxin has been found in IL-1R1. • Quantitative xanthotoxin significantly improves platelet production and function without biological toxicity. [ABSTRACT FROM AUTHOR]

Radiation-induced thrombocytopenia (RIT) occurs widely and causes high mortality and morbidity in cancer patients who receive radiotherapy. However, specific drugs for treating RIT remain woefully inadequate. Here, we first developed a drug screening model using naive Bayes, a machine learning (ML) algorithm, to virtually screen the active compounds promoting megakaryopoiesis and thrombopoiesis. A natural product library was screened by the model, and methylophiopogonanone A (MO-A) was identified as the most active compound. The activity of MO-A was then validated in vitro and showed that MO-A could markedly induce megakaryocyte (MK) differentiation of K562 and Meg-01 cells in a concentration-dependent manner. Furthermore, the therapeutic action of MO-A on RIT was evaluated, and MO-A significantly accelerated platelet level recovery, platelet activation, megakaryopoiesis, MK differentiation in RIT mice. Moreover, RNA-sequencing (RNA-seq) indicated that the PI3K cascade was closely related to MK differentiation induced by MO-A. Finally, experimental verification demonstrated that MO-A obviously induced the expression of FGF1 and FGFR1, and increased the phosphorylation of PI3K, Akt and NF-κB. Blocking FGFR1 with its inhibitor dovitinib suppressed MO-A-induced MK differentiation, and PI3K, Akt and NF-κB phosphorylation. Similarly, inhibition of PI3K-Akt signal pathway by its inhibitor LY294002 suppressed MK differentiation, and PI3K, Akt and NF-κB phosphorylation induced by MO-A. Taken together, our study provides an efficient drug discovery strategy for hematological diseases, and demonstrates that MO-A is a novel countermeasure for treating RIT through activation of the FGF1/FGFR1/PI3K/Akt/NF-κB signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: For most patients with severely ankylosed hips, traditional surgical approaches do not provide sufficient exposure during THAs. We report our experience with a combined anterior and posterior approach using a lateral incision for total hip arthroplasty (THA) in patients with severe, spontaneous bony hip ankylosis.Methods: Between January 2004 and December 2008, patients with severe, spontaneous bony hip ankylosis underwent THA via a combined anterior and posterior approach using a lateral incision.Results: We included 47 patients (76 hips) with a mean age of 53 (range 22-72) years in our study. All surgeries were successful, and no significant postoperative complications occurred. The mean operative duration was 1.5 (range 1.3-1.7) hours, and mean blood loss was 490 (range 450-580) mL. The mean duration of follow-up was 5.5 (range 2-11) years. Harris hip score improved from 53 to 88 points postoperatively, and the outcome was good to excellent in 88.37% of cases. Heterotopic ossification occurred in 6 hips, and infection, which resolved with antibiotics, occurred in 1 patient.Conclusion: This combined anterior and posterior approach to THA using a lateral incision in patients with severe, spontaneous ankylosis provides very good exposure, protects the abduction unit and results in good to excellent postoperative recovery. [ABSTRACT FROM AUTHOR]