Liposome and microemulsion loaded with ibuprofen: from preparation to mechanism of drug transport.

To compare the difference between liposome (LP) and microemulsion (ME) in delivering ibuprofen (IBU) transdermally and explore relative mechanism. IBU-LP and IBU-ME were prepared by ethanol injection and spontaneous emulsification, respectively. The percutaneous delivery was evaluated using Franz diffusion cells. Fourier transform infra-red spectroscopy (FTIR), differential scanning calorimetry (DSC), activation energy (Ea), and confocal laser scanning microscopy (CLSM) were used to investigate the transdermal mechanism. The particle size and encapsulation efficiency were 228.00 ± 8.60 nm, 86.68 ± 1.43%(w/w) for IBU-LP, and 56.74 ± 7.11 nm, 91.08 ± 3.27%(w/w) for IBU-ME. Percutaneous study showed that formulations enhanced permeation and drug retention in the skin. FTIR and DSC showed that the permeation occurred due to the interaction of the formulations with the lipid bilayer and the protein. The decrease in Ea (1.506 and 0.939 kcal/mol) revealed that the stratum corneum (SC) lipid bilayers were significantly disrupted and this destructive effect of IBU-LP was stronger. IBU-LP was superior to IBU-ME in the aspects of transdermal delivery of IBU.

An interdisciplinary approach to orthodontic treatment of a mutilated Class III malocclusion with mini-implants, dental implants, and an autotransplant.

This case report demonstrates the interdisciplinary treatment of a 24-year-old female. Her skeletal discrepancy, anterior crossbite, mutilated dentition, and midline deviation made it challenging to achieve satisfactory treatment results, especially without major orthognathic surgery. This article thoroughly discusses the decision-making process associated with various treatment alternatives, the biomechanical considerations with temporary skeletal anchorage devices, and the detailed operational process of dental implant restoration and autotransplantation. CLINICAL SIGNIFICANCE: Orthodontic treatment aims to obtain better facial and dental esthetics, achieve functional occlusion, and improve oral health. Treatment of patients with a mutilated dentition requires interdisciplinary teamwork from a group of professionals with various types of expertise. Orthodontists should be the navigator that generates the tooth movement and space redistribution, thus facilitating the subsequent functional rehabilitation under a well-organized occlusal architecture. Autotransplantation offers an economical and biologically-friendly opportunity to replace a missing tooth.

Mutual promotions between periodontitis and vascular calcification by rat animal model.

OBJECTIVE AND BACKGROUND: To study the relationship between periodontitis and vascular calcification by establishing rat model of chronic periodontitis and vascular calcification. METHODS: Forty male Wistar rats were divided into four groups randomly: control group, periodontitis group, vascular calcification group, and compound periodontitis and calcification group. Each group rats accepted the corresponding manages to establish the animal model. Clinical examinations and hematoxylin and eosin staining of periodontal tissue were taken to test the periodontal model; calcium assay, alkaline phosphatase activity, expression of mineral-related factors including osteopontin, alkaline phosphatase, core-binding factor-α1 and bone sialoprotein, hematoxylin and eosin staining and von Kossa staining of vascular tissue were taken to test the vascular calcification model; inflammatory factors including C-reactive protein, interleukin-1ß, tumor necrosis factor-α, interleukin-6, prostaglandin E2, and serum lipid in serum were also detected at the same time. RESULTS: The rat model was established. Inflammation of periodontal tissue and alveolar bone resorption in compound group and periodontitis group were more obvious than those in control group and vascular calcification group (P < .05). However, the calcium assay, alkaline phosphatase activity, and mineralized deposition in vascular calcification group and compound group were higher than those in control group and periodontitis group (P < .05), and compound group were the highest (P < .05); as for serum lipid, the level of total cholesterol and low-density lipoprotein-cholesterol in compound group and vascular calcification group were higher than that in control group and periodontitis group (P < .05), and compound group was the highest (P <.05); but the level of high-density lipoprotein cholesterol was higher in control group and periodontitis group. Inflammatory factors expression in serum were higher in compound group and periodontitis group, while mineral-related factors expression were higher in compoundgroup and vascular calcification group. CONCLUSION: There are some mutual promotions between periodontitis and vascular calcification, which might be related to the increasing inflammatory factors, lipids level, and mineral-related factors.

Bioengineering of BRAF and COX2 inhibitor nanogels to boost the immunotherapy of melanoma via pyroptosis.

Glutathione-responsive nanogels (CDNPs) crosslinked via crosslinker DBHD with the BRAF inhibitor dabrafenib and the COX2 inhibitor celecoxib were fabricated. The CDNPs can effectively induce tumor cell pyroptosis to activate robust antitumor immunity. Additionally, CDNPs combined with αPD-1 antibody greatly inhibited tumor growth in a melanoma mouse model with a prolonged survival time.

Organic-inorganic calcium lignosulfonate compounds for soil acidity amelioration.

Soil acidification is a problem widely occurring worldwide, which severely threaten food security and agricultural sustainability. Calcium lignosulfonate (CaLS), a cheap and ecofriendly compound, is used for the first time to amend acid soil by utilizing its unique organic and inorganic functional moieties simultaneously. Both column leaching and incubation experiments were conducted to investigate the comparative effects of CaLS (four rates at 5, 10, 15, 20 g kg-1) and compared with conventional amendments, including gypsum (5 g kg-1), lignin (5 g kg-1), L + G (each at 5 g kg-1), and control. The soil pH, exchangeable acidity and base cations, organic carbon, and different Al fractions were determined to unravel the ameliorative performance and mechanism of the treatments. Regardless of application modes and dosages, the results demonstrated that CaLS incorporation significantly increased soil pH, exchangeable Ca2+, cation exchange capacity, and organic carbon and decreased the contents of exchangeable acidity, especially exchangeable Al3+. The ameliorative mechanism was that amendment material led to the displacement of H+ and Al3+ off soil colloids by Ca2+. These released H+ and Al3+ which complexed with lignosulfonate anions into soluble organo-Al were all quickly leached from the soil column. The CaLS addition enhanced the transformation of exchangeable Al3+ and low-to-medium organo-Al complexes into highly stable organically bound fractions and immobilized into the soil. The complexing of CaLS functional groups with Al3+ impeded Al3+ from undergoing hydrolysis to produce more H+. As an environmental-friendly material, CaLS can be a promising amendment for soil acidity and Al toxicity amelioration.

Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: Systematic review and meta-analysis of randomised and non-randomised studies.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD. OBJECTIVES: To assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects. STUDY DESIGN: Meta-analysis. SEARCH METHODS: Randomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger's test, and the trim and fill method were used to assess publication bias. RESULTS: In total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9-67.4) and 80.3% (95% CI 69.7-87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6-81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5-81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4-90.2%; skin, 52.5-80.6%; and liver, 41.8-71.8%. In cGVHD, the response rates were gastrointestinal, 30.1-70.4%; skin, 30.1-84.4%; lung, 27.0-83.0%; and mouth 3.5-98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications. CONCLUSIONS: Our systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.

Stepwise Size Shrinkage Cascade-Activated Supramolecular Prodrug Boosts Antitumor Immunity by Eliciting Pyroptosis.

Effective pyroptosis induction is a promising approach to potentiate cancer immunotherapy. However, the actual efficacy of the present pyroptosis inducers can be weakened by successive biological barriers. Here, a cascaded pH-activated supramolecular nanoprodrug (PDNP) with a stepwise size shrinkage property is developed as a pyroptosis inducer to boost antitumor immune response. PDNPs comprise multiple poly(ethylene glycol) (PEG) and doxorubicin (DOX) drug-polymer hybrid repeating blocks conjugated by ultra-pH-sensitive benzoic imine (bzi) and hydrazone (hyd) bonds. The PEG units endow its "stealth" property and ensure sufficient tumor accumulation. A sharp switch in particle size and detachment of PEG shielding can be triggered by the acidic extracellular pH to achieve deep intratumor penetration. Following endocytosis, second-stage size switching can be initiated by more acidic endolysosomes, and PDNPs disassociate into ultrasmall cargo to ensure accurate intracellular delivery. The cascaded pH activation of PDNPs can effectively elicit gasdermin E (GSDME)-mediated pyroptosis to enhance the immunological response. In combination with anti-PD-1 antibody, PDNPs can amplify tumor suppression and extend the survival of mice, which suggests a powerful immune adjuvant and pave the way for high-efficiency immune checkpoint blockade therapy.

Microplastics negatively impact embryogenesis and modulate the immune response of the marine medaka Oryzias melastigma.

Microplastic (MP) pollution is an emerging contaminant in aquatic environments worldwide. Nonetheless, the developmental toxicity of MPs in the early life stages of fish and the mechanisms involved are not yet fully understood. The present study investigated the effects of different concentrations of polystyrene (PS) MPs on the early development of the marine model fish the medaka Oryzias melastigma. Our results showed that waterborne exposure to PS MPs significantly delayed the hatching time, altered the heartbeat and decreased the hatching rate of embryos. Furthermore, the genes involved in cardiac development, encoding for embryo-hatching enzymes, as well as inflammatory responses were significantly upregulated. The transcriptome results showed that mainly the pathways involved in metabolism, immune response, genetic information processing and diseases were significantly enriched. These results demonstrate that PS MPs negatively impact embryogenesis and the immune response of O. melastigma.

Modification of wheat bran insoluble dietary fiber with carboxymethylation, complex enzymatic hydrolysis and ultrafine comminution.

To improve the industrial application of wheat bran insoluble dietary fiber (W-IDF), three modification methods (carboxymethylation, complex enzymatic hydrolysis, and ultrafine comminution) were compared on the basis of structural, physicochemical, functional, and antioxidant properties of W-IDF. FT-IR, DSC and SEM analysis showed that modifications contributed to alteration in morphology and arrangement of chemical bonds in W-IDF. Carboxymethylation effectively improved the water retention (WRC), water swelling (WSC), and glucose adsorption capacities (GAC); complex enzymatic hydrolysis greatly improved the oil retention (ORC), GAC, and nitrite ion adsorption capacities (NIAC). Although ultrafine comminution reduced the WRC and ORC, while positively influenced the GAC and NIAC. Moreover, total phenol content, total antioxidant capacity, DPPH radical scavenging capacity, Fe2+ chelating capacity and total reducing power were improved in modified W-IDF. Our results confirmed that carboxymethylation can improve the nutritive quality and sensory properties of W-IDF (nutritive ingredient) in food products.

[Expression of OPG/RANK/RANKL in the rat dental pulp tissue of periodontitis combined with vascular calcification and its clinical significance].

PURPOSE: To study the expression and possible role of OPG/RANK/RANKLin the rat dental pulp of periodontitis combined with vascular calcification. METHODS: Thirty-six male Wister rats were randomly divided into 4 groups: control group(group C), periodontitis group(group CP), vascular calcification group(group VDN) and compound group(group CP+VDN). Each group underwent corresponding management to establish animal model. When the model was successful, the maxillae including molars were sectioned, pulp tissue was examined by H-E staining; Immunohistochemical staining method was used to evaluate the expression and ratio of OPG and RANKL in pulp tissues. Statistical analysis was carried out using SPSS 19.0 software package. RESULTS: The pulp tissue of group CP, VDN, CP+VDN showed varied degrees of damage, neutrophil infiltration, pulp vascular congestion, odontoblasts vacuolar changes, pulp necrosis by H-E staining, and the changes in CP+VDN group was the most significant, followed by CP group, VDN group. Immunohistochemistry showed OPG in pulp tissues in group CP, VDN, CP+VDN were significantly lower than that in normal group (P<0.05), and the expression in group CP+VDN was the least;Expression of RANKL in pulp tissues in group CP, VDN, CP+VDN were significantly higher than that in normal group(P<0.05)，and the expression in group CP+VDN was the highest. The ratio of OPG/RANKL in normal group was the highest, and the ratio in CP+VDN group was the lowest. CONCLUSIONS: Periodontitis and vascular calcification can damage the pulp tissue, periodontitis compound with vascular calcification may aggravate the injury; OPG/RANKL/RANK system may play an important role in pulp tissue injury.

Influence of inner circular sealing area impression method on the retention of complete dentures.

The aims of the present study were to describe an impression method of "inner circular sealing area" and to evaluate the effect of the method on retention, aesthetics and comfort of complete dentures, which lack labial base for patients with maxillary protrusions. Three patients were subjected to the experiment, and two sets of complete maxillary dentures were made for each patient; the first set was made without labial base via an inner circular sealing area method (experimental group) and the second had an intact base that was made with conventional methods (control group). Retention force tests were implemented with a tensile strength assessment device to assess the retention and a visual analogue scale (VAS) was used to evaluate the comfort between the two groups. Results showed larger retention force, better aesthetics and more comfort in the experimental group. The improved two-step impression method formed an inner circular sealing area that prevented damage to the peripheral border seal effect of the denture caused by incomplete bases and obtained better denture retention.

The genomic DNA immobilization on microcrystalline cellulose and its application to separate DNA-binding proteins from kumquat (Fortunella margarita Swingle).

A method of immobilizing genomic DNA on microcrystalline cellulose was described to isolate DNA-binding proteins. At first, DNA fragments were prepared by sonication and immobilized on cellulose phase. After the immobilization, DNA duplex formation was done. Using this microcrystalline cellulose affinity chromatography technique, DNA-binding proteins from kumquat (Fortunella margarita Swingle) leaf samples were isolated and then analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS). LC-MS/MS analysis showed that twenty-eight kinds of protein mainly including histones, protein-synthetic proteins and other DNA-binding proteins were identified. The identification list consists with the results in previous research on DNA-binding proteins isolation. It further suggests that the technique developed in this study can be applied to the effective isolation of DNA-binding proteins.

Graphene@poly(m-phenylenediamine) hydrogel fabricated by a facile post-synthesis assembly strategy.

The mixing of graphene oxide and protonated poly(m-phenylenediamine) (PmPD) nanoparticles generates floccus that can be readily transformed into graphene@PmPD hybrid hydrogel through redox reaction. This macroscopic material can be directly applied as a monolith column adsorbent for water purification.

Influence of Inner Circular Sealing Area Impression Method on the Retention of Complete Dentures

The aims of the present study were to describe an impression method of "inner circular sealing area" and to evaluate the effect of the method on retention, aesthetics and comfort of complete dentures, which lack labial base for patients with maxillary protrusions. Three patients were subjected to the experiment, and two sets of complete maxillary dentures were made for each patient; the first set was made without labial base via an inner circular sealing area method (experimental group) and the second had an intact base that was made with conventional methods (control group). Retention force tests were implemented with a tensile strength assessment device to assess the retention and a visual analogue scale (VAS) was used to evaluate the comfort between the two groups. Results showed larger retention force, better aesthetics and more comfort in the experimental group. The improved two-step impression method formed an inner circular sealing area that prevented damage to the peripheral border seal effect of the denture caused by incomplete bases and obtained better denture retention.

O objetivo deste caso foi descrever um método de impressão por "área de selamento circular interno" e avaliar o efeito deste método na retenção, estética e conforto de próteses totais sem base labial para pacientes com protrusão maxilar. Três pacientes foram objeto desta experiência e foram feitas duas próteses maxilares completas para cada um deles; a primeira foi elaborada sem base labial pelo método de área de selamento circular interno (grupo experimental) e a outra teve uma base feita pelo método convencional (grupo controle). Foram realizados testes de retenção com estudo de tensão para avaliar a retenção e para avaliação do conforto dos dois grupos, foi empregada a escala analógica visual (EAV). Os resultados demonstraram que o grupo experimental apresentou força de retenção maior, estética melhor e mais conforto. O método modificado de impressão em duas etapas formou uma área de selamento circular interno que evitou danos ao selamento periférico causados por bases incompletas e obteve melhor retenção da prótese.