Preparation, optimisation, and in vitro-in vivo evaluation of febuxostat ternary solid dispersion.

The research aimed to prepare febuxostat (FEB) solid dispersion through solvent evaporation. Optimised solid dispersion composed of FEB, polyvinylpyrrolidone (PVP K30) and poloxamer at a ratio of 1:3:3 was characterised. Powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC) indicated FEB was transformed from crystalline into the amorphous state in solid dispersion and scanning electron microscopy (SEM) revealed the morphology. Fourier transform infrared spectroscopy (FT-IR) suggested the interactions formed between FEB and polymers. A remarkable increase was observed of the optimised formulation in saturation solubility, dissolution studies (96.17 ± 0.79% in pH 6.0), and bioavailability (Cmax 18.25 ± 2.44 vs. 7.72 ± 0.48 µg/mL and AUC0-∞ 53.62 ± 7.63 vs. 34.76 ± 2.45 µg·h/mL). Besides, the FEB solid dispersion showed great stability after 90 days storage. Thus, the present study supports the rationality of PVP K30 and poloxamer188 as co-carriers for the preparation of FEB solid dispersion.

Macrophage ADAM17 deficiency augments CD36-dependent apoptotic cell uptake and the linked anti-inflammatory phenotype.

RATIONALE: Apoptotic cell phagocytosis (efferocytosis) is mediated by specific receptors and is essential for resolution of inflammation. In chronic inflammation, apoptotic cell clearance is dysfunctional and soluble levels of several apoptotic cell receptors are elevated. Reports have identified proteolytic cleavage as a mechanism capable of releasing soluble apoptotic cell receptors, but the functional implications of their proteolysis are unclear. OBJECTIVE: To test the hypothesis that ADAM17-mediated cleavage of apoptotic cell receptors limits efferocytosis in vivo. METHODS AND RESULTS: In vivo comparison of macrophage efferocytosis in wild-type and Adam17-null hematopoietic chimeras demonstrates that ADAM17 deficiency leads to a 60% increase in efferocytosis and an enhanced anti-inflammatory phenotype in a model of peritonitis. In vitro uptake of phosphatidylserine liposomes identifies the dual-pass apoptotic cell receptor CD36 as a major contributor to enhanced efferocytosis, and CD36 surface levels are elevated on macrophages from Adam17-null mice. Further, temporal elevation of CD36 expression with inflammation may also contribute to its impact. Soluble CD36 from macrophage-conditioned media comprises 2 species based on Western blotting, and mass spectrometry identifies 3 N-terminal peptides that represent probable cleavage sites. Levels of soluble CD36 are decreased in Adam17-null conditioned media, providing evidence for involvement of ADAM17 in CD36 cleavage. Importantly, enhanced efferocytosis in vivo by macrophages lacking ADAM17 is CD36 dependent and accelerates macrophage clearance from the peritoneum, thus promoting resolution of inflammation and highlighting the impact of increased apoptotic cell uptake. CONCLUSIONS: Our studies demonstrate the importance of ADAM17-mediated proteolysis for in vivo efferocytosis regulation and suggest a possible mechanistic link between chronic inflammation and defective efferocytosis.

[Risk factors of hidden blood loss in percutaneous vertebral augmentation].

OBJECTIVE: To explore the risk factors of hidden blood loss in osteoporosis vertebral compression fractures during percutaneous vertebral augmentation. METHODS: From October 2018 to December 2019, 360 patients with osteoporosis vertebral compression fractures who received percutaneous vertebral augmentation were enrolled in this study. The factors analyzed included gender, age, surgical methods, disease course, height, weight, the operative segment, bone mineral density, amount of bone cement, operative time, percentage of height loss, percentage of vertebral height restoration, cement leakage, blood clotting function, preoperative and postoperative hemoglobin and hematocrit and other internal diseases. Total blood loss was calculated by Gross's formula, influential factors of the hidden blood loss were further analyzed by t-test, multivariate linear regression and one-way ANOVA analysis. RESULTS: Surgical methods, the operative segment, disease course, cement leakage, preoperative hemoglobin, cement leakage via the basivertebral and segmental vein were significantly correlated with hidden blood loss(P<0.05). CONCLUSION: Patients with percutaneous kyphoplasty, two-level and multi-level surgery, the course of the disease beyond 6 weeks, cement leakage via the basivertebral and segmental vein, and lower preoperative hemoglobin had more perioperative hidden blood loss.

Comparison of Cement Leakage Rate and Severity After Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fractures Using Front-Opening Versus Side-Opening Cannulas.

The authors assessed the occurrence and severity of cement leakage (CL) following percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCFs) performed using front-opening cannulas (FOCs) vs side-opening cannulas (SOCs). This retrospective cohort study included 811 patients with single-level OVCFs who underwent PVP between March 2016 and September 2018. The 264 patients who met the inclusion criteria were divided into two groups according to whether the procedure was performed using a FOC (n=128) or a SOC (n=136). Visual analog scale score, Oswestry Disability Index, local kyphotic angle, vertebral height, amount of bone cement injected, and rate of CL were compared between the groups. Types of CL were classified according to postoperative computed tomography. The CL types were further classified according to severity (mild and severe). Visual analog scale score, Oswestry Disability Index, local kyphotic angle, and vertebral height were all significantly improved after surgery. The total incidence of CL was significantly higher for FOCs than for SOCs (P=.001). Similarly, the occurrence of the CL subtypes was significantly higher for FOCs than for SOCs (B type, P=.033; C type, P=.01; and S type, P=.015). Analysis of CL type severity revealed that the rates of severe D type (intradiskal leakage category of the C type) and severe S type were significantly lower for SOCs than for FOCs (P=.001), while the incidence of severe B type leaks was not significantly different between the groups (P=.443). Percutaneous vertebroplasty performed using SOCs decreases the incidence and severity of D type and S type CL compared with FOCs. Secondary classification of CL could help physicians better understand the severity of leakage and select a more appropriate surgical approach to reduce CL. [Orthopedics. 2021;44(3):134-140.].

Occurrence and Fate of Steroid Estrogens in a Chinese Typical Concentrated Dairy Farm and Slurry Irrigated Soil.

Animal husbandry is the second largest source of steroid estrogen (SE) pollutants in the environment, and it is significant to investigate the occurrence and fate of SEs discharged from concentrated animal feeding operations. In this research, with a Chinese typical concentrated dairy farm as the object, the concentrations of SEs (E1, 17α-E2, 17ß-E2, E3, and E1-S3) in slurry, lagoon water, and slurry-irrigated soil samples in summer, autumn, and winter were determined. The total concentrations of SEs (mainly E1, 17α-E2, and 17ß-E2) in slurry were very high in the range of 263.1-2475.08 ng·L-1. In the lagoon water, the removal efficiencies of the aerobic tank could reach up to 89.53%, with significant fluctuation in different seasons. In the slurry-irrigated soil, the maximum concentrations of SEs in the topsoil and subsoil were 21.54 ng·g-1 to 6.82 g·g-1, respectively. Most of the SEs tended to transport downward and accumulate in the soil accompanied with the complex mutual conversion. Correlations and hierarchical clustering analysis showed a variety of intertransformation among SEs, and the concentrations of SEs were correlated with various physicochemical indexes, such as TN and NO3--N of the slurry, chemical oxygen demand of the lagoon water, and the heavy metals of soil. In addition, 17ß-estradiol equivalency assessment and risk quotients indicated that the slurry irrigation and discharge of the lagoon water would cause potential estrogenic risks to the environment. Consequently, reasonable slurry irrigation and lagoon water discharge are essential to efficiently control SE pollution in the environment.

Tumor vasculature-targeting PEGylated peptide-drug conjugate prodrug nanoparticles improve chemotherapy and prevent tumor metastasis.

Metastasis is the main cause of death in cancer patients; therefore, new strategies or technologies that can inhibit the growth of primary tumors and their metastatic spread are extremely valuable. In this study, we selected an E-selectin-binding peptide as a targeting ligand and an inhibitor of metastasis, and conjugated this peptide with SN38 and PEG to produce an amphiphilic PEGylated peptide-drug conjugate (PDC). Novel self-assembled nanoparticles were then formed by the amphiphilic conjugate. The particles were actively targeted to the tumor vasculature by the peptide and passively to the tumor site by the enhanced permeability and retention (EPR) effect. As a nano-prodrug, this multifunctional conjugate (PEG-Pep-SN38) could reduce tumor growth, with an effect similar to that of irinotecan. Moreover, it could prolong the survival of mice bearing primary HCT116 tumors, which was not observed for its parent drug, SN38, nor the clinical prodrug of SN38 (irinotecan). Furthermore, this PDC prodrug prevented B16-F10 colonization in the lungs of mice. This study describes a new tumor vasculature-targeting PDC nano-prodrug with convenient preparation and high potential for cancer therapy, with the potential to be applied to other chemotherapeutic drugs.

Supernucleation, crystalline structure and thermal stability of bacterially synthesized poly(3-hydroxybutyrate) polyester tailored by thymine as a biocompatible nucleating agent.

Naturally occurring thymine (TM) was incorporated into bacterial poly(3-hydroxybutyrate) (PHB) polyester to fabricate a novel and green biocomposite. Both 0.5% and 1% TM exhibit supernucleation effect on PHB, and crystallization kinetics suggests TM significantly increased Tc and Xc, and substantially shortened t1/2 of PHB. Epitaxial nucleation caused by a perfect crystal lattice matching between PHB and TM, was proposed to elucidate nucleation mechanism of PHB. Hydrogen bond interaction exists between CO, C-O-C groups of PHB and -CH3 (or -CH)/-NH- group of TM. TM interacted with CO group of PHB crystalline phase rather than that of amorphous one. In addition, two new IR crystalline bands assigned to C-O-C group of PHB appeared in the presence of TM, which arises from shift of two amorphous ones, respectively. TM enhanced onset thermal degradation temperature of PHB, mainly attributed to increased degree of crystallinity of PHB and flame retardance effect of TM.

A comparison of the sealing abilities between Biodentine and MTA as root-end filling materials and their effects on bone healing in dogs after periradicular surgery.

OBJECTIVES: To compare the sealing ability and biocompatibility of Biodentine with mineral trioxide aggregate (MTA) when used as root-end filling materials. METHODOLOGY: The Cell Counting Kit-8 (CCK-8) assay was used to compare the cytotoxicity of MTA and Biodentine. Twenty-one extracted teeth with a single canal were immersed in an acidic silver nitrate solution after root-end filling. Then, the volume and depth of silver nitrate that infiltrated the apical portion of the teeth were analyzed using micro-computed tomography (micro-CT). Seventy-two roots from 3 female beagle dogs were randomly distributed into 3 groups and apical surgery was performed. After six months, the volume of the bone defect surrounding these roots was analyzed using micro-CT. RESULTS: Based on the results of the CCK-8 assay, MTA and Biodentine did not show statistically significant differences in cytotoxicity (P>0.05). The volume and the depth of the infiltrated nitrate solution were greater in the MTA group than in the Biodentine group (P<0.05). The volume of the bone defect was larger in the MTA group than in the Biodentine group. However, the difference was not significant (P>0.05). The volumes of the bone defects in the MTA and Biodentine groups were smaller than the group without any filling materials (P<0.05). CONCLUSIONS: MTA and Biodentine exhibited comparable cellular biocompatibility. Biodentine showed a superior sealing ability to MTA in root-end filling. Both Biodentine and MTA promoted periradicular bone healing in beagle dog periradicular surgery models.

A comparison of the sealing abilities between Biodentine and MTA as root-end filling materials and their effects on bone healing in dogs after periradicular surgery

ABSTRACT Objectives: To compare the sealing ability and biocompatibility of Biodentine with mineral trioxide aggregate (MTA) when used as root-end filling materials. Methodology: The Cell Counting Kit-8 (CCK-8) assay was used to compare the cytotoxicity of MTA and Biodentine. Twenty-one extracted teeth with a single canal were immersed in an acidic silver nitrate solution after root-end filling. Then, the volume and depth of silver nitrate that infiltrated the apical portion of the teeth were analyzed using micro-computed tomography (micro-CT). Seventy-two roots from 3 female beagle dogs were randomly distributed into 3 groups and apical surgery was performed. After six months, the volume of the bone defect surrounding these roots was analyzed using micro-CT. Results: Based on the results of the CCK-8 assay, MTA and Biodentine did not show statistically significant differences in cytotoxicity (P>0.05). The volume and the depth of the infiltrated nitrate solution were greater in the MTA group than in the Biodentine group (P<0.05). The volume of the bone defect was larger in the MTA group than in the Biodentine group. However, the difference was not significant (P>0.05). The volumes of the bone defects in the MTA and Biodentine groups were smaller than the group without any filling materials (P<0.05). Conclusions: MTA and Biodentine exhibited comparable cellular biocompatibility. Biodentine showed a superior sealing ability to MTA in root-end filling. Both Biodentine and MTA promoted periradicular bone healing in beagle dog periradicular surgery models.