Glutathione-depleting Liposome Adjuvant for Augmenting the Efficacy of a Glutathione Covalent Inhibitor Oridonin for Acute Myeloid Leukemia Therapy.

BACKGROUND: Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH. METHODS: We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug's water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes' surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug's impact on AML targets. RESULTS: We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells. CONCLUSION: The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.

Does the incorporation of strontium into calcium phosphate improve bone repair? A meta-analysis.

BACKGROUND: The application of calcium phosphate (CaP)-based bone substitutes plays an important role in periodontal regeneration, implant dentistry and alveolar bone reconstruction. The incorporation of strontium (Sr) into CaP-based bone substitutes appears to improve their biological properties, but the reported in vivo bone repair performance is inconsistent among studies. Herein, we conducted a systematic review and meta-analysis to investigate the in vivo performance of Sr-doped materials. METHODS: We searched PubMed, EMBASE (via OVIDSP), and reference lists to identify relevant animal studies. The search, study selection, and data extraction were performed independently by two investigators. Meta-analyses and sub-group analyses were conducted using Revman version 5.4.1. The heterogeneity between studies were assessed by I2. Publication bias was investigated through a funnel plot. RESULTS: Thirty-five studies were finally enrolled, of which 16 articles that reported on new bone formation (NBF) were included in the meta-analysis, covering 31 comparisons and 445 defects. The overall effect for NBF was 2.25 (95% CI 1.61-2.90, p < 0.00001, I2 = 80%). Eight comparisons from 6 studies reported the outcomes of bone volume/tissue volume (BV/TV), with an overall effect of 1.42 (95% CI 0.65-2.18, p = 0.0003, I2 = 75%). Fourteen comparisons reported on the material remaining (RM), with the overall effect being -2.26 (95% CI - 4.02 to - 0.50, p = 0.0009, I2 = 86%). CONCLUSIONS: Our study revealed that Sr-doped calcium phosphate bone substitutes improved in vivo performance of bone repair. However, more studies are also recommended to further verify this conclusion.

Synthesis of Poly(phenyltriazolylcarboxylate)s with Aggregation-Induced Emission Characteristics by Metal-Free 1,3-Dipolar Polycycloaddition of Phenylpropiolate and Azides.

Two soluble poly(phenyltriazolylcarboxylate)s (PPTCs) with high molecular weights (M w up to 26 800) are synthesized by the metal-free 1,3-dipolar polycycloadditions of 4,4'-isopropylidenediphenyl diphenylpropiolate (1) and tetraphenylethene-containing diazides (2) in dimethylformamide at 150 °C for 12 h in high yields (up to 93%). The resultant polymers are soluble in common organic solvents and are thermally stable with 5% weight loss temperatures higher than 375 °C. The PPTCs are nonemissive in solutions, but become highly luminescent upon aggregation, showing a phenomenon of aggregation-induced emission. Their aggregates can be used as fluorescent chemosensors for high-sensitivity detection of explosives.

A technique for immediate implant placement in mandibular multirooted teeth by the aid of a dynamic guidance system and preparing implant bed before tooth extraction.

Due to site-specific anatomical challenges, traditional immediate dental implant placement for mandibular multirooted molar sizes has many limitations. This technical report describes a modified approach for immediate dental implant placement in molar sites allowing for precise three-dimensional (3D) implant position and favourable clinical effect with the aid of a dynamic guidance system and flapless pre-extractive preparation of the implant bed.

Enhanced antibacterial properties and promoted cell proliferation in glass ionomer cement by modified with fluorinated graphene-doped.

In this study, we aimed to improve the properties of conventional glass ionomer cement (GIC), including mechanical properties, wear resistance, antibacterial properties and biological activity, by adding fluorinated graphene (FG). Composites of synthesised FG and GIC were examined after being combined at different mass proportions (0, 0.5, 1.0 and 2.0 wt%). The microstructure and morphology of FG prepared via the hydrothermal method was characterised using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The FG/GIC composite was obtained through the blending method and characterised using SEM. Then, the Vickers microhardness and the wear property of the FG/GIC composite-imitated brushing was measured. The plate count and dilution methods (10-fold) were adopted to investigate the antibacterial properties of FG/GIC by incubating Escherichia coli and Staphylococcus aureus. The biocompatibility of FG/GIC containing the adhesion and cytotoxicity of mouse fibroblast cells (L929) was estimated by the MTT and acridine orange (AO) fluorescent staining. Our results demonstrated that the hardness and abrasive wear resistance of the composites increased, and the microhardness parameter changes exhibited a gradual increase as the concentration continued to increase. A 2.0 wt% FG concentration could effectively improve the bacterial inhibition performance of GIC and was directly proportional to the concentration of FG. The composite materials showed no apparent cytotoxicity on normal L929 cells compared to the control group, and the materials exhibited no cytotoxic effect compared to traditional GIC. Thus, FG/GIC has potential therapeutic value in the field of dental treatment.

Effectiveness of Platelet-Rich Fibrin as an Adjunctive Material to Bone Graft in Maxillary Sinus Augmentation: A Meta-Analysis of Randomized Controlled Trails.

PURPOSE: To date, it remains unknown whether the addition of platelet-rich fibrin (PRF) to bone grafts actually improves the effectiveness of maxillary sinus augmentation. This study aimed to perform a meta-analysis to evaluate the efficacy of PRF in sinus lift. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched. Randomized controlled studies were identified. The risk of bias was evaluated using the Cochrane Collaboration tool. RESULTS: Five RCTs were included in our meta-analysis. Clinical, radiographic, and histomorphometric outcomes were considered. No implant failure or graft failure was detected in all included studies within the follow-up period. The percentage of contact length between newly formed bone substitute and bone in the PRF group was lower but lacked statistical significance (3.90%, 95% CI, -2.91% to 10.71%). The percentages of new bone formation (-1.59%, 95% CI, -5.36% to 2.18%) and soft-tissue area (-3.73%, 95% CI, -10.11% to 2.66%) were higher in the PRF group but were not significantly different. The percentage of residual bone graft was not significant in either group (4.57%, 95% CI, 0% to 9.14%). CONCLUSIONS: Within the limitations of this review, it was concluded that there were no statistical differences in survival rate, new bone formation, contact between newly formed bone and bone substitute, percentage of residual bone graft (BSV/TV), and soft-tissue area between the non-PRF and PRF groups. Current evidence supporting the necessity of adding PRF to bone graft in sinus augmentation is limited.

Transalveolar sinus floor lift without bone grafting in atrophic maxilla: A meta-analysis.

We performed a meta-analysis aimed to assess the clinical results after transalveolar sinus floor lift without bone grafting in the atrophic maxilla. A systematic electronic literature search was conducted in PubMed, Embase and The Cochrane Library, followed by a manual search. Two reviewers independently extracted study data and conducted quality assessments. Ten non-controlled studies including 1484 implants and eight controlled studies (5 RCTs and 3 prospective studies) including 817 implants (451 implants in the non-graft group) were enrolled in this study. The survival rate of implants via the graft-free method was 98% (95%CI 96% to 100%). There was no significant difference in the survival rate between the non-graft group and the graft group (RR: 1.02; p = 0.18). No statistically significant difference in marginal bone loss was detected between the groups at 12 months (0.57, p = 0.07) or 36 months (0.05, p = 0.61). The endo-sinus bone gain in the non-graft group was significantly lower than in the graft group at 12 months (-1.10, p = 0.0001) and 36 months (-0.74, p = 0.02). Hence, the available evidence suggests that predictable results could be acquired through transalveolar sinus floor lift without bone grafting, while there may be a trend toward more endo-sinus bone gain with bone grafts.

Spatial distribution and pollution evaluation of heavy metals in Yangtze estuary sediment.

To analyze the spatial distribution patterns and ecological risks of heavy metals, 30 sediment samples were taken in the Yangtze River Estuary (YRE) in May 2011. The content of Al, As, Cr, Cu, Fe, Mn, Ni and Pb increased as follows: inner-region

Spatial variation, environmental risk and biological hazard assessment of heavy metals in surface sediments of the Yangtze River estuary.

30 samples of eight heavy metals were collected in February 2011 within Yangtze River estuary (YRE). The mean concentrations met the primary standard criteria based on Marine Sediments Quality of China. The spatial distribution showed that a gradient concentration decreased gradually from inner-estuary to river mouth. Anthropogenic inputs might be the main contributor, and fine grained sediments might also aggravate the heavy metal contamination. The assessment results indicated that the YRE was in low risk of contamination caused by every single heavy metal. However, it was in considerable degree of contamination considering combination of all the heavy metals. The toxicities of heavy metals might be elevated when heavy metals were in combination. Arsenic should be of primary concern due to its higher assessment values and the potential of adverse biological effects. And the concentration of As in the YRE had a trend to increase because of anthropogenic activities nearby.

Spatial variation, environmental assessment and source identification of heavy metals in sediments of the Yangtze River Estuary.

In order to analyze the spatial distribution patterns, pollution sources and ecological risks of heavy metals (As, Cd, Cr, Cu, Mn, Ni, Pb and Zn), 30 sediment samples were taken from in the Yangtze River Estuary (YRE). The results indicated that the contamination ranking of heavy metals was As>Cr>Cd>Ni>Mn>Pb>Zn>Cu. In the various areas, the pollution magnitude decreased as follows: adjacent sea>river mouth>inner-region. Compared to data published for other regions, the YRE data indicated that the sediment was not severely contaminated by heavy metals. In the YRE, natural and anthropogenic inputs dominated the distribution patterns of the heavy metals. Beyond that, the hydrodynamic conditions, such as the Taiwan warm current, coastal current and Yangtze diluted water, also caused distribution variations in the study areas.