Pi-inducedin-situaggregation of sevelamer nanoparticles for vascular embolization.

Decades have witnessed rapid progress of polymeric materials for vascular embolic or chemoembolic applications. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives,in situgelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackablein vivo. In this paper, we proposed a concept of 'responsive embolization'. Sevelamer, clinically proved as an inorganic phosphate binder, was ground into nanoparticles. Sevelamer nanoparticle is highly mobile and capable of swelling and aggregating in the presence of endogenous inorganic phosphate, thereby effectively occluding blood flow in the vessel as it was administered as an embolic agent for interventional therapy. Moreover, citrated sevelamer nanoparticles delayed the aggregation, preferable to penetrate deeply into the capillary system. On the rabbit VX2 liver cancer model, both sevelamer particles aggregates occlude the tumor feeding artery, but backflow was found for the pristine one, thereby citrate passivation of sevelamer nanoparticles endows it have potential from 'bench to bedside' as a new type of vascular embolic.

Eudragit S100-Coated Chitosan Nanoparticles Co-loading Tat for Enhanced Oral Colon Absorption of Insulin.

In order to improve oral absorption of insulin, especially the absorption at the colon, Eudragit S100® (ES)-coated chitosan nanoparticles loading insulin and a trans-activating transcriptional peptide (Tat) were employed as the vehicle. In vitro releases of insulin and Tat from ES-coated chitosan nanoparticles had a pH-dependant characteristic. A small amount of the contents was released from the coated nanoparticles at pH 1.2 simulated gastric fluid, while a fairly fast and complete release was observed in pH 7.4 medium. Caco-2 cell was used as the model of cellular transport and uptake studies. The results showed that the cellular transport and uptake of insulin for ES-coated chitosan nanoparticles co-loading insulin and Tat (ES-Tat-cNPs) were about 3-fold and 4-fold higher than those for the nanoparticles loading only insulin (ES-cNPs), respectively. The evaluations in vivo of ES-Tat-cNPs were conducted on diabetic rats and normal minipigs, respectively. The experimental results on rats revealed that the pharmacodynamical bioavailability of ES-Tat-cNPs had 2.16-fold increase compared with ES-cNPs. After oral administration of nanoparticle suspensions to the minipigs, insulin bioavailability of ES-Tat-cNPs was 1.73-fold higher than that of ES-cNPs, and the main absorption site of insulin was probably located in the colon for the two nanoparticles. In summary, this report provided an exploratory means for the improvement of oral absorption of insulin.

Metal-organic framework-based advanced therapeutic tools for antimicrobial applications.

The escalating concern over conventional antibiotic resistance has emphasized the urgency in developing innovative antimicrobial agents. In recent times, metal-organic frameworks (MOFs) have garnered significant attention within the realm of antimicrobial research due to their multifaceted antimicrobial attributes, including the sustained release of intrinsic or exogenous antimicrobial components, chemodynamically catalyzed generation of reactive oxygen species (ROS), and formation of photogenerated ROS. This comprehensive review provides a thorough overview of the synthetic approaches employed in the production of MOF-based materials, elucidating their underlying antimicrobial mechanisms in depth. The focal point lies in elucidating the research advancements across various antimicrobial modalities, encompassing intrinsic component release system, extraneous component release system, auto-catalytical system, and energy conversion system. Additionally, the progress of MOF-based antimicrobial materials in addressing wound infections, osteomyelitis, and periodontitis is meticulously elucidated, culminating in a summary of the challenges and potential opportunities inherent within the realm of antimicrobial applications for MOF-based materials. STATEMENT OF SIGNIFICANCE: Growing concerns about conventional antibiotic resistance emphasized the need for alternative antimicrobial solutions. Metal-organic frameworks (MOFs) have gained significant attention in antimicrobial research due to their diverse attributes like sustained antimicrobial components release, catalytic generation of reactive oxygen species (ROS), and photogenerated ROS. This review covers MOF synthesis and their antimicrobial mechanisms. It explores advancements in intrinsic and extraneous component release, auto-catalysis, and energy conversion systems. The paper also discusses MOF-based materials' progress in addressing wound infections, osteomyelitis, and periodontitis, along with existing challenges and opportunities. Given the lack of related reviews, our findings hold promise for future MOF applications in antibacterial research, making it relevant to your journal's readership.

Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives.

Intracellular cargo delivery, the introduction of small molecules, proteins, and nucleic acids into a specific targeted site in a biological system, is an important strategy for deciphering cell function, directing cell fate, and reprogramming cell behavior. With the advancement of nanotechnology, many researchers use nanoparticles (NPs) to break through biological barriers to achieving efficient targeted delivery in biological systems, bringing a new way to realize efficient targeted drug delivery in biological systems. With a similar size to many biomolecules, NPs possess excellent physical and chemical properties and a certain targeting ability after functional modification on the surface of NPs. Currently, intracellular cargo delivery based on NPs has emerged as an important strategy for genome editing regimens and cell therapy. Although researchers can successfully deliver NPs into biological systems, many of them are delivered very inefficiently and are not specifically targeted. Hence, the development of efficient, target-capable, and safe nanoscale drug delivery systems to deliver therapeutic substances to cells or organs is a major challenge today. In this review, on the basis of describing the research overview and classification of NPs, we focused on the current research status of intracellular cargo delivery based on NPs in biological systems, and discuss the current problems and challenges in the delivery process of NPs in biological systems.

Stable Co(II)-based coordination polymer as fluorescence sensor for the discriminative sensing of biomarker methylmalonic acid.

Three novel Co-based coordination polymers including {[Co(L)(µ3-O)1/3]2}n (1), {[Co(L)(bimb)]}n (2) and {[Co(L)(bimmb)1/2]}n (3) (H2L = 2,6-di(4-carboxylphenyl)-4-(4-(triazol-1-ylphenyl))pyridine), bimb = 1,4-bis(lmidazol) butane, bimmb = 1,4-bis(imidazole-1-ylmethyl)benzene) were successfully prepared under solvothermal conditions and characterized. Single-crystal X-ray diffraction analyses revealed that 1 possesses a 3D architecture composed of a trinuclear cluster [Co3N3(CO2)6(µ3-O)], 2 exhibits a 2D new topological framework with the point symbol (84·122)(8)2, whereas 3 shows a unique six-fold interpenetrated 3D framework with a (63·82·10)2(63)2(8) topology. Impressively, all of them can function as a highly selective and sensitive fluorescent sensor for the biomarker methylmalonic acid (MMA) via fluorescence quenching. The low detection limit, reusability and high anti-interference performance together make 1-3 become promising sensors for the practical detection of MMA. Furthermore, the successful application of MMA detection in urine sample was demonstrated, which may be a potential candidate for the further development of clinical diagnostic tools.

Integrated osteoimmunomodulatory strategies based on designing scaffold surface properties in bone regeneration.

Those who have used traditional biomaterials as bone substitutes have always regarded the immune response as an obstacle leading to implant failure. However, cumulative evidence revealed that blindly minimizing host immune reactions cannot induce successful bone regeneration. With the emergence of the new concept of osteoimmunology, the intimate mutual effects between the skeletal system and the immune system have been gradually recognized, promoting the innovation of biomaterials with osteoimmunomodulatory properties. By tuning the surface properties, biomaterials can precisely manipulate the osteoimmune environment favoring bone regeneration. In this review, we first reviewed the mutual effects between the skeletal system and the immune system to show the importance of immunomodulation on bone regeneration. Subsequently, we summarize the recent developments in surface modification strategies in terms of the surface physicochemical properties and surface coatings and explain how these modification strategies work.

Correlation and mechanism between cardiac magnetic resonance imaging and oral streptococcus count in patients with primary microvascular angina pectoris.

BACKGROUND: Although primary microvascular angina (PMVA) can be diagnosed clinically, the etiology and pathophysiology of PMVA remain unclear. The effects of conventional clinical medications (aspirin, statins, and nitrates) are unsatisfactory, and PMVA can lead to serious cardiovascular events. The present study was designed to analyze the correlation between the load perfusion cardiovascular magnetic resonance imaging (CMR) results and the Streptococcus sanguinis(S sanguinis) count and the correlations between the S sanguinis count in oral cavity subgingival plaque and changes in the plasma levels of platelet alpha-granule membrane glycoprotein 140 (GMP-140), fibrinopeptide A (FPA), von Willebrand factor (vWF), and homocysteine (Hcy) in patients with PMVA after increased anti-infective treatment of the oral cavity. This study also discusses the pathogenesis of PMVA from this perspective. The differences in the S sanguinis count in oral cavity subgingival plaque and oral health status between healthy people and PMVA patients will be compared, and the correlation between the oral cavity health status and disease in PMVA patients will be analyzed. METHODS: The present randomized controlled trial with a parallel control group will be conducted in 68 PMVA patients diagnosed by the in-patient cardiology department. The selected patients will be randomly divided into 2 groups, one receiving routine drug treatment and the other a combination of anti-infective treatments. The normal control group will comprise 30 healthy people with no infectious oral cavity disease matched by age and sex. We will conduct CMR, and the presence of S sanguinis in subgingival plaques will be used to determine the bacterial count in PMVA patients. Blood samples will also be collected to determine the levels of GMP-140, FPA, vWF, and Hcy. S sanguinis in the subgingival plaque of PMVA patients will be further analyzed after increasing the oral cavity anti-infective treatment; the resulting changes and their correlations with changes in GMP-140, FPA, vWF, and Hcy levels will be assessed. Additionally, the differences in the S sanguinis count and the oral cavity health status of oral cavity dental plaque between healthy people and PMVA patients will be determined, and the correlation between the oral cavity conditions and PMVA will be analyzed. The relationship between the perfusion CMR results and the oral cavity S sanguinis count of PMVA patients, and the potential pathogenesis, will be explored. We will use the SPSS19.0 statistical software package to analyze the data. The measurements will be expressed as means±standard deviation. Student t test will be used for intergroup comparisons, a relative number description will be used for the count data, and the chi-square test will be used for intergroup comparisons. Multivariate logistic regression will be performed to identify associations. A P value < .05 will be considered significant. DISCUSSION: In this study, the correlation between the perfusion CMR results and the S sanguinis count in oral cavity subgingival plaque of PMVA patients will be analyzed. Changes in the levels of GMP-140, FPA, vWF, and Hcy of PMVA patients after receiving increased oral cavity anti-infective treatment will be explored, and the difference in the S sanguinis count in oral cavity subgingival plaque and the oral cavity health status between healthy people and PMVA patients will be compared. ATRIAL REGISTRATION: Chinese Clinical Trial Registry, (http://www.chictr.org.cn/showprojen.aspx?proj=45091).

[Osteoimmunomodulatory effects of inorganic biomaterials in the process of bone repair].

Objective: To review the osteoimmunomodulatory effects and related mechanisms of inorganic biomaterials in the process of bone repair. Methods: A wide range of relevant domestic and foreign literature was reviewed, the characteristics of various inorganic biomaterials in the process of bone repair were summarized, and the osteoimmunomodulatory mechanism in the process of bone repair was discussed. Results: Immune cells play a very important role in the dynamic balance of bone tissue. Inorganic biomaterials can directly regulate the immune cells in the body by changing their surface roughness, surface wettability, and other physical and chemical properties, constructing a suitable immune microenvironment, and then realizing dynamic regulation of bone repair. Conclusion: Inorganic biomaterials are a class of biomaterials that are widely used in bone repair. Fully understanding the role of inorganic biomaterials in immunomodulation during bone repair will help to design novel bone immunomodulatory scaffolds for bone repair.

pH-sensitive chitosan nanoparticles loaded with dolutegravir as milk and food admixture for paediatric anti-HIV therapy.

The present study aims to develop Chitosan-based polymeric nanoparticles of anti-HIV drug Dolutegravir, to aid appropriate dose adjustment and ease of oral administration as milk and food admixture for children. The isolated Chitosan from the crab shell species Portunus Sanguinolentus has been characterized for their physicochemical properties. Nanoparticles were developed with varying ratio of drug: Chitosan and assessed for particle size (140-548 nm), zeta potential (+26.1 mV) with a maximum of 75 % drug content. Nanoparticles exhibited improved stability and drug release in the 0.1 N HCl medium compared to pure drug. The MTT assay and the Syncytia inhibition assay in C8166 (T-lymphatic cell line) infected with HIVIIIB viral strain, which showed better therapeutic efficiency and lesser cytotoxicity compared to the pure drug. In consonance with the data obtained, the use of chitosan from a novel source for drug delivery carrier has opened exceptional prospects for delivering drugs efficiently to paediatrics.

[Effects of oral implant prosthesis in patients with missing teeth and influence on gingival sulcus TNF-α, IL-6 and IL-8].

PURPOSE: To evaluate effects of oral implant prosthesis in patients with missing teeth and influence on gingival sulcus TNF-α, IL-6 and IL-8. METHODS: Ninety four cases with tooth missing from October 2014 to October 2016 were divided into 2 groups, with 47 in each group. Patients in the control group were treated with conventional restoration, experimental group were treated with oral implantation. The clinical effects, levels of TNF-α, IL-6 and IL-8, gingival state, dental functions, and complications between the two groups were compared. Statistical analysis was performed using SPSS8.0 software package. RESULTS: The total effective rate of the experimental group was significantly higher than the control group (95.74% vs 80.85%, P<0.05). TNF-α, IL-6 and IL-8 of the experimental group was significantly lower than the control group (3.55±0.42) µg/L, (25.90±3.24) µg/L, (69.34±8.65) µg/L vs (4.69±0.58) µg/L, (41.37±5.19) µg/L, (108.72±13.56) µg/L (P<0.05). The gingival state, dental functions of the experimental group were significantly better than the control group, and the complications was significantly less than the control group (P<0.05). CONCLUSIONS: The application of oral implant in dentition missing patients is satisfactory, which can inhibit the expression of TNF-α, IL-6 and IL-8, reduce local inflammatory response and improve dental function.

Near-infrared photothermal activation of microgels incorporating polypyrrole nanotransducers through droplet microfluidics.

Poly(N-isopropylacrylamide) (pNIPAM) composite microgels incorporating polypyrrole (PPy) nanoparticles were produced using droplet microfluidics. The composite microgels exhibited site-specific de-swelling-swelling properties that were activated by near-infrared light. Their applications for programmable drug release by pulsed-light control were also demonstrated.

Effects of oligo(3-hydroxyalkanoates) on the viability and insulin secretion of murine beta cells.

Biopolyesters of polyhydroxyalkanoates (PHAs), including poly-3-hydroxybutyrate (PHB), co-polyester of 3-hydroxybutyrate and 4-hydroxybutyrate (P3HB4HB), and co-polyester of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) have been well investigated for their biocompatibility. For in vivo application, it is very important that the degradation products of PHAs, especially the oligomers, are not harmful to the cells and surrounding tissues. In this study, in vitro effects of oligo(3-hydroxybutyrate) (OHB), oligo(3-hydroxybutyrate-co-4-hydroxybutyrate) (O3HB4HB) and oligo(3-hydroxybutyrate-co-3-hydroxyhexanoate) (OHBHHx) on growth and differentiation of the murine beta cell line NIT-1 were investigated. Among the three oligo-hydroxyalkanoates (Oligo-HAs), cells treated with OHBHHx displayed higher viability, as measured by CCK-8 assay. Flow cytometric analysis of NIT-1 cells indicated that Oligo-HAs had an inhibitory effect on cell apoptosis. The cytosolic Ca(2+) transient of NIT-1 cells increased when fed with 0.04 g/l Oligo-HAs. For gap junction intercellular communication of cells, the effect of OHBHHx was the best among all materials tested. More importantly, extracellular insulin secretion was up-regulated after growing in OHBHHx for 48 h. The results demonstrated that the degradation products of PHAs, especially OHBHHx from PHBHHx, were not harmful to the beta cells. Therefore, PHBHHx warrant further study for application as a pancreatic tissue engineering material.

Covalent immobilization of glucose oxidase onto poly(styrene-co-glycidyl methacrylate) monodisperse fluorescent microspheres synthesized by dispersion polymerization.

In this study, micron-sized poly(styrene-co-glycidyl methacrylate) (PSt-GMA) fluorescent microspheres of 5.1microm in diameter were synthesized via dispersion polymerization of styrene and glycidyl methacrylate in the presence of 1,4-bis(5-phenyloxazol-2-yl) benzene (POPOP), which provided surface functional groups for covalent immobilization of enzymes. In an effort to study the biocompatibility of the microspheres' surface, glucose oxidase and beta-d-(+)-glucose were selected as a catalytic system for enzymatic assays. A colorimetric method was adopted in evaluating enzymatic activity by introducing horseradish peroxidase (HRP). Both the immobilization amount and the apparent activity of immobilized glucose oxidase from Aspergillus niger (GOD) were determined at different conditions. The results show that the immobilized enzymes retained approximately 28 to 34% activity, as compared with free enzymes, without pronounced alteration of the optimum pH and temperature. Kinetics studies show that the corresponding values of K(m) and V(max) are 23.2944 mM and 21.6450M/min.mg GOD for free enzymes and 35.1780 mM and 15.4799M/min.mg GOD for immobilized enzymes. The operational stability studies show that immobilized GOD could retain nearly 50% initial activity after being washed 20 times. The results suggest that the resultant PSt-GMA fluorescent microspheres provide a suitable surface for covalent immobilizing biomolecules; therefore, they have the potential of being used in fluorescence-based immunoassays in high-throughput screening or biosensors.

Production of polyhydroxyalkanoates with high 3-hydroxydodecanoate monomer content by fadB and fadA knockout mutant of Pseudomonas putida KT2442.

Pseudomonas putida KT2442 produces medium-chain-length (MCL) polyhydroxyalkanoates (PHA) consisting of 3-hydroxyhexanoate (HHx), 3-hydroxyoctanoate (HO), 3-hydroxydecanoate (HD), and 3-hydroxydodecanoate (HDD) from a wide-range of carbon sources. In this study, fadA and fadB genes encoding 3-ketoacyl-CoA thiolase and 3-hydroxyacyl-CoA dehydrogenase in P. putida KT2442 were knocked out to weaken the beta-oxidation pathway. Two-step culture was proven as the optimal method for PHA production in the mutant termed P. putida KTOY06. In a shake-flask culture, when dodecanoate was used as a carbon source, P. putida KTOY06 accumulated 84 wt % PHA, much higher than 50 wt % PHA in its wild type KT2442. The PHA monomer composition was completely different: the HDD fraction in PHA produced by KTOY06 was 41 mol %, much higher compared with 7.5 mol % only in KT2442. The fermentor-scale culture indicated the HDD fraction in PHA decreased during the culture time from 35 to 25 mol % in a one-step fermentation process or from 75 to 49 mol % in a two-step fermentation process. It is for the first time that PHA with a dominant HDD fraction was produced. Thermal and mechanical properties assays indicated that this new type PHA with a high HDD fraction had higher crystallinity and tensile strength than PHA with a low HDD fraction did, demonstrating an improved application property.

[Construction and identification of recombinant adenoviruses containing the gene fragments encoding Her2/neu extracellular and transmembrane domains].

OBJECTIVE: To construct eukaryotic expression vectors using recombinant adenovirus containing the gene fragments encoding Her2/neu extracellular first ligand-binding domain (Her2-ECD), full-length extracellular domain (Her2-ECD), and extracellular and transmembrane domain (Her2-TM). METHODS: The cDNAs were amplified by RT-PCR and inserted into shuttle pAdTrack-CMV plasmids. Viral plasmids were obtained from homologous recombination in E. coli BJ5183, and transfected into 293 cells via liposome. Formation of viral plaque and expression of green fluorescent protein were observed by fluorescence microscopy, and the target proteins were detected by Western blotting. RESULTS: The target cDNA fragments were amplified by PCR with expected lengths and the DNA sequences were confirmed against Genbank. Formation of viral plaque, expression of green fluorescent protein and the target proteins were detected in 293 cells transfected by the viral plasmids, which showed elevated expression of Her2/neu protein with the increase of multiplicity of infection (MOI). CONCLUSION: The eukaryotic expression vectors using recombinant adenovirus have been successfully constructed for expression of Her2/neu extracellular and transmembrane domains.