[Analysis on preparation and characterization of asiaticoside-loaded flexible nanoliposomes].

Asiaticoside is a compound extracted from traditional Chinese medicine Centella asiatica, and mainly used in wound healing and scar repair in clinical, with notable efficacy. However, its poor transdermal absorption and short action time restrict its wide application. In this experiment, the reserve-phase-extrusion-lyophilization method was conducted to prepare the lyophilized asiaticoside-loaded flexible nanoliposomes (LAFL). Its characteristics including electron microscope structure, particle size, Zeta potential, entrapment rate, drug-loading rate, stability and drug release were determined with the intelligent transdermal absorption instrument. LAFL were white spheroids, with pH, particle size and zeta potential of 7. 03, 70. 14 nm and - 36. 5 mV, respectively. The average entrapment rate of the 3 batch samples were 31. 43% , and the average asiaticoside content in 1 mg lyophilized simple was 0. 134 mg. The results indicated that LAFL have good physicochemical properties and pharmaceutical characteristics, with an improved transdermal performance.

PSMA conjugated combinatorial liposomal formulation encapsulating genistein and plumbagin to induce apoptosis in prostate cancer cells.

Although the biomedical sciences have achieved tremendous success in developing novel approaches to managing prostate cancer, this disease remains one of the major health concerns among men worldwide. Liposomal formulations of single drugs have shown promising results in cancer treatment; however, the use of multi drugs has shown a better therapeutic index than individual drugs. The identification of cancer-specific receptors has added value to design targeted drug delivering nanocarriers. We have developed genistein and plumbagin co-encapsulating liposomes (∼120 nm) with PSMA specific antibodies to target prostate cancer cells selectively in this work. These liposomes showed >90 % decrease in PSMA expressing prostate cancer cell proliferation without any appreciable toxicity to healthy cells and human red blood cells. Release of plumbagin and genistein was found to decrease the expression of PI3/AKT3 signaling proteins and Glut-1 receptors (inhibited glucose uptake and metabolism), respectively. The decrease in migration potential of cells and induced apoptosis established the observed anti-proliferative effect in prostate cancer cell lines. The discussed strategy of developing novel, non-toxic, and PSMA specific antibody conjugated liposomes carrying genistein and plumbagin drugs may also be used for encapsulating other drugs and inhibit the growth of different types of cancers.

Mercaptobenzothiazole allergenicity-role of the thiol group.

The rubber accelerator, 2-mercaptobenzothiazole (MBT), is known to cause allergic contact dermatitis (ACD), but the mechanism is unknown. The role of the thiol group in MBT's allergenicity was investigated in the present study. Guinea pigs were sensitized to MBT using a modified guinea pig maximization test (GPMT) and reactivity was assessed toward 2-mercaptobenzothiazole disulfide (MBTS), 2-hydroxybenzothiazole (HBT; thiol-substituted), 2-(methylthio)benzothiazole (MTBT; thiol-blocked), and benzothiazole (BT; thiol-lacking). MBT and MBTS, but not BT, HBT, or MTBT, elicited ACD in MBT-sensitized animals, demonstrating that the thiol group is critical to MBT's allergenicity. In addition, both MBT and MBTS were shown to inhibit both glutathione reductase and thioredoxin reductase, and thus contribute to the stability of MBT-protein mixed disulfides. It is concluded that the probable haptenation mechanism of MBT is through initial oxidation to MBTS with subsequent reduction to form mixed disulfides with proteins.

Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition).

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treatments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. METHODS: National Health Commission of China assembled an expert committee for a revision of the guidelines. The committee included 33 members who are specialized in diagnosis and treatment of HFMD. RESULTS: Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia; (2) involvement of nervous system; (3) worsening respiratory rate and rhythm; (4) circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. CONCLUSION: The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

PPy@MIL-100 Nanoparticles as a pH- and Near-IR-Irradiation-Responsive Drug Carrier for Simultaneous Photothermal Therapy and Chemotherapy of Cancer Cells.

A medical nanoplatform with small size, low cost, biocompatibility, good biodegradability, and, in particular, multifunctionality has attracted much attention in the exploration of novel therapeutic methodologies. As an emerging material of self-assembled porous structure, metal-organic frameworks (MOFs) have high expectations because of their special properties compared to traditional porous materials. Therefore, integration of MOFs and functional materials is leading to the creation of new multifunctional composites/hybrids. Photothermal therapy (PTT), using near-IR (NIR) laser-absorbing nanomaterials as PTT agents, has shown encouraging therapeutic effects to photothermally ablate tumors. However, the most of widely used PTT agents are inorganic materials and nonbiodegradable. Herein, uniform polypyrrole (PPy) nanoparticles (NPs) with good biodegradability were synthesized by a microemulsion method. The PPy NPs were further coated with the mesoporous iron-based MOF structure MIL-100 by interaction between PPy NPs and MIL-100 precursors at room temperature. As a multifunctional nanoplatform, an anticancer drug could easily be loaded into the mesopores of the MIL-100 shell. The PPy core, as an organic photothermal agent, is able to photothermally ablate cancer cells and improve the efficacy of chemotherapy under NIR irradiation. The composites showed an outstanding in vivo synergistic anticancer capacity. Our work could encourage further study in the construction of a synergetic system using MOFs and organic PTT agents.

Computer simulation of biomolecule-biomaterial interactions at surfaces and interfaces.

Biomaterial surfaces and interfaces are intrinsically complicated systems because they involve biomolecules, implanted biomaterials, and complex biological environments. It is difficult to understand the interaction mechanism between biomaterials and biomolecules through conventional experimental methods. Computer simulation is an effective way to study the interaction mechanism at the atomic and molecular levels. In this review, we summarized the recent studies on the interaction behaviors of biomolecules with three types of the most widely used biomaterials: hydroxyapatite (HA), titanium oxide (TiO2), and graphene(G)/graphene oxide(GO). The effects of crystal forms, crystallographic planes, surface defects, doping atoms, and water environments on biomolecules adsorption are discussed in detail. This review provides valuable theoretical guidance for biomaterial designing and surface modification.

[Effects of simulated body fluid flowing rate on bone-like apatite formation on porous calcium phosphate ceramics].

Objective. Bone-like apatite formation on the surface of calcium phosphate ceramics was believed to be the necessary step that new bone grows on the ceramics and to be relative to the osteoinductivity of the material. This study aimed at investigating the influence of the flow rate of simulated body fluid (SBF) (2 ml/min) in skeletal muscle upon the formation of bone-like apatite on porous calcium phosphate ceramics. Method. The dynamic condition was realized by controlling the SBF flowing in/out of the sample chamber of 100 ml. The flow rate of 2 ml/min is close to that in human muscle environment. The pH and inorganic ionic composition of SBF are close to those of human body fluid. Result. Bone-like apatite formation was relatively easier to occur in static SBF than in dynamic SBF. Experiment with flowing SBF (dynamic SBF) is better in mimicking the living body fluid than static SBF. Conclusion. The results from dynamic SBF may more truly show the relation between apatite layer formation and osteoinduction in biomaterials than that from in vitro experiments before.

Synthesis of hollow hydroxyapatite nanospheres by the control of nucleation and growth in a two phase system.

Hollow hydroxyapatite nanospheres were prepared by a two-phase approach by controlling nucleation and crystal growth processes. The cavities of hollow HA provide potential applications as new kinds of containers for carrying, filling in, or encapsulating other materials, thus constructing a multifunctional system with good biocompatibility.

Osteoinduction by Ca-P biomaterials implanted into the muscles of mice.

The osteoinduction of porous biphasic calcium phosphate ceramics (BCP) has been widely reported and documented, but little research has been performed on rodent animals, e.g., mice. In this study, we report osteoinduction in a mouse model. Thirty mice were divided into two groups. BCP materials (Sample A) and control ceramics (Sample B) were implanted into the leg muscle, respectively. Five mice in each group were killed at 15, 30, and 45 d after surgery. Sample A and Sample B were harvested and used for hematoxylin and eosin (HE) staining, immunohistochemistry (IHC) staining, and Alizarin Red S staining to check bone formation in the biomaterials. Histological analysis showed that no bone tissue was formed 15 d after implantation (0/5) in either of the two groups. Newly-formed bone tissues were observed in Sample A at 30 d (5/5) and 45 d (5/5) after implantation; the average amounts of newly-formed bone tissues were approximately 5.2% and 8.6%, respectively. However, we did not see any bone tissue in Sample B until 45 d after implantation. Bone-related molecular makers such as bone morphogenesis protein-2 (BMP-2), collagen type I, and osteopontin were detected by IHC staining in Sample A 30 d after implantation. In addition, the newly-formed bone was also confirmed by Alizarin Red S staining. Because this is the report of osteoinduction in the rodent animal on which all the biotechnologies were available, our results may contribute to further mechanism research.

[The study on three-dimension finite element analysis of the stress distribution in the mandible bone around dental implants].

OBJECTIVE: The aim of this study was to investigate how to model an accuracy 3-dimension Finite Element Analysis (3D-FEA) model. METHODS: Based on computed tomography (CT) scan data of a woman, a 3D finite element model of the first molar on the left was rebuilt by computer imagines process and computer aided design (CAD). Analysis of the stress distribution on a cylinder dental implant and in the bone around it was conducted. RESULTS: The stress distribution showed extremely asymmetry in bucco-lingual section: stress concentrated on the lingual side of the mandible; stress mainly was tensile in buccal side, and on the contrary compressive in lingual side. CONCLUSION: The results were more reliable because this model more really displayed the mandible.

Ionic effect on combing of single DNA molecules and observation of their force-induced melting by fluorescence microscopy.

Molecular combing is a powerful and simple method for aligning DNA molecules onto a surface. Using this technique combined with fluorescence microscopy, we observed that the length of lambda-DNA molecules was extended to about 1.6 times their contour length (unextended length, 16.2 microm) by the combing method on hydrophobic polymethylmetacrylate coated surfaces. The effects of sodium and magnesium ions and pH of the DNA solution were investigated. Interestingly, we observed force-induced melting of single DNA molecules.

[Staging and management of extracranial arteriovenous malformations].

OBJECTIVE: Congenital arteriovenous malformations(AVM) are considered to be the most difficult and challenging problems in the treatment of hemangiomas and vascular lesions. This study focused on the natural history, the clinical classification, the choice and effectiveness of various treatments. METHODS: This retrospective review included 83 patients with extracranial arteriovenous malformations, who were referred to our department over the past 6 years. The anatomic patterns, clinical staging, respective treatments, influential factors of endovascular treatment, causes of recurrence were analyzed. RESULTS: According to clinical manifestations, arteriovenous malformations were categorized as three clinical stages: the quiescence, the expansion and the decompensation stages. Most AVMS in the quiescence stage only require endovascular treatment while those in the decompensation stage require surgical resection. Angiography was performed not only for diagnosis of AVM but also as an initial therapeutic step in the form of embolization, which might be the only means to some AVM without surgical possibility or necessity. CONCLUSION: The new concept of staging and management is expected to be helpful for diagnosis and treatments of AVM.