Programming colloidal bonding using DNA strand-displacement circuitry.

As a strategy for regulating entropy, thermal annealing is a commonly adopted approach for controlling dynamic pathways in colloid assembly. By coupling DNA strand-displacement circuits with DNA-functionalized colloid assembly, we developed an enthalpy-mediated strategy for achieving the same goal while working at a constant temperature. Using this tractable approach allows colloidal bonding to be programmed for synchronization with colloid assembly, thereby realizing the optimal programmability of DNA-functionalized colloids. We applied this strategy to conditionally activate colloid assembly and dynamically switch colloid identities by reconfiguring DNA molecular architectures, thereby achieving orderly structural transformations; leveraging the advantage of room-temperature assembly, we used this method to prepare a lattice of temperature-sensitive proteins and gold nanoparticles. This approach bridges two subfields: dynamic DNA nanotechnology and DNA-functionalized colloid programming.

The effects of dimethyl fumarate on cytoplasmic LPS-induced noncanonical pyroptosis in periodontal ligament fibroblasts and dental pulp cells.

AIM: Pyroptosis is a type of inflammatory cell death and is related to pulpitis and apical periodontitis. In this study, the aim was to investigate how periodontal ligament fibroblasts (PDLFs) and dental pulp cells (DPCs) respond to pyroptotic stimuli and explore whether dimethyl fumarate (DMF) could block pyroptosis in PDLFs and DPCs. METHODOLOGY: Three methods (stimulation with lipopolysaccharide [LPS] plus nigericin, poly(dA:dT) transfection and LPS transfection) were used to induce pyroptosis in PDLFs and DPCs, two types of fibroblasts related to pulpitis and apical periodontitis. THP-1 cell was used as a positive control. Afterwards, PDLFs and DPCs were treated with or without DMF before inducing pyroptosis to examine the inhibitory effect of DMF. Pyroptotic cell death was measured by lactic dehydrogenase (LDH) release assays, cell viability assays, propidium iodide (PI) staining and flow cytometry. The expression levels of cleaved gasdermin D N-terminal (GSDMD NT), caspase-1 p20, caspase-4 p31 and cleaved PARP were examined by immunoblotting. Immunofluorescence analysis was used to detect the cellular distribution of GSDMD NT. RESULTS: Periodontal ligament fibroblasts and DPCs were more sensitive to cytoplasmic LPS-induced noncanonical pyroptosis than to canonical pyroptosis induced by stimulation with LPS priming plus nigericin or by poly(dA:dT) transfection. In addition, treatment with DMF attenuated cytoplasmic LPS-induced pyroptotic cell death in PDLFs and DPCs. Mechanistically, it was shown that the expression and plasma membrane translocation of GSDMD NT were inhibited in DMF-treated PDLFs and DPCs. CONCLUSIONS: This study indicates that PDLFs and DPCs are more sensitive to cytoplasmic LPS-induced noncanonical pyroptosis and that DMF treatment blocks pyroptosis in LPS-transfected PDLFs and DPCs by targeting GSDMD, suggesting DMF might be a promising drug for the management of pulpitis and apical periodontitis.

Construction of an Analysis Model of mRNA Markers in Menstrual Blood Based on Naïve Bayes and Multivariate Logistic Regression Methods.

OBJECTIVES: To establish the menstrual blood identification model based on Naïve Bayes and multivariate logistic regression methods by using specific mRNA markers in menstrual blood detection technology combined with statistical methods, and to quantitatively distinguish menstrual blood from other body fluids. METHODS: Body fluids including 86 menstrual blood, 48 peripheral blood, 48 vaginal secretions, 24 semen and 24 saliva samples were collected. RNA of the samples was extracted and cDNA was obtained by reverse transcription. Five menstrual blood-specific markers including members of the matrix metalloproteinase (MMP) family MMP3, MMP7, MMP11, progestogens associated endometrial protein (PAEP) and stanniocalcin-1 (STC1) were amplified and analyzed by electrophoresis. The results were analyzed by Naïve Bayes and multivariate logistic regression. RESULTS: The accuracy of the classification model constructed was 88.37% by Naïve Bayes and 91.86% by multivariate logistic regression. In non-menstrual blood samples, the distinguishing accuracy of peripheral blood, saliva and semen was generally higher than 90%, while the distinguishing accuracy of vaginal secretions was lower, which were 16.67% and 33.33%, respectively. CONCLUSIONS: The mRNA detection technology combined with statistical methods can be used to establish a classification and discrimination model for menstrual blood, which can distignuish the menstrual blood and other body fluids, and quantitative description of analysis results, which has a certain application value in body fluid stain identification.

Macrophage Polarization Modulated by NF-κB in Polylactide Membranes-Treated Peritendinous Adhesion.

Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF-κB signaling also plays a vital role in the process. It is hypothesized that NF-κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA-M) and adhesion. First, in vitro and in vivo experiments show that PLA-M induces NF-κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA-M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH-23 (a selective NF-κB inhibitor)-loaded PLA membrane (JSH-23/PLA-M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti-adhesion. JSH-23/PLA-M specifically inhibits NF-κB phosphorylation in macrophages and exhibits anti-inflammatory and anti-adhesion properties. The findings demonstrate that NF-κB phosphorylation has a critical role in PLA-induced M1 polarization and aggravating FBR to PLA-M. Additionally, JSH-23/PLA-M precisely targets modulation of NF-κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.

A survey on knowledge and attitudes towards molar-incisor hypomineralization among undergraduate and postgraduate students at the School of Stomatology, Wuhan University.

BACKGROUND: Molar incisor hypomineralization (MIH) is a developmental dental disease, and its clinical management challenges dentists. This study aimed to investigate the knowledge about MIH and the attitudes towards learning more about MIH among undergraduate and postgraduate students attending the School of Stomatology, Wuhan University. METHODS: This survey was based on a questionnaire modified based on previous studies. The questionnaire was sent to 540 undergraduate and postgraduate students from the School of Stomatology, Wuhan University. The questions covered their clinical experience, perceptions, clinical management, and preferences for further training. Data were analysed with the Chi-square test. RESULTS: We collected 368 questionnaires (response rate: 68%). Among them, 89% (328/368) were eligible for analysis. Most respondents (80%) had heard of MIH, primarily from classroom teaching. However, only 40% of the students had observed the disease clinically, and a relatively low proportion of students were familiar with the aetiology, prevalence, differential diagnosis, and treatment of MIH. Most respondents were highly enthusiastic and had great expectations about further systematic teaching about MIH. CONCLUSION: Most students in this study had heard of MIH, but few were familiar with the principles of its differential diagnosis. Systematic teaching about MIH is warranted.

Exploring the toxicity of the aged styrene-butadiene rubber microplastics to petroleum hydrocarbon-degrading bacteria under compound pollution system.

As a new pollutant, microplastics have increasingly drawn public attention to its toxic behavior in the environment. The aim was to investigate the effect of styrene-butadiene-rubber microplastics (mSBR) with different degrees of aging on petroleum hydrocarbon (PHC) degrading bacteria in an environment with simultaneously existing pollutants. A series of experiments were carried out to investigate the changes in the physical and chemical properties of mSBR with aging and to examine the influence of these changes on the inhibition of PHC-degrading bacteria by mSBR in the vicinity of coexisting pollutants. The results showed that in the early stage of ultraviolet aging (10d), the particle surface shows wrinkles, but the structure is intact. After reaching the late stage of aging (20d), nano-scale fragments were generated on the surface of mSBR, the average particle size decreased from 3.074 µm to 2.297 µm, and the zeta potential increased from - 25.1 mV to - 33.1 mV. The inhibitory effect of bacteria is greater. At the same time, these changes in the physicochemical properties increase the adsorption effect of Cd by 20%, and also improve the stability of mSBR in solution, whereby bacterial growth is inhibited by inhibiting the LPO activity and protein concentration of PHC degrading bacteria.

Liposomal formulation of HIF-1α inhibitor echinomycin eliminates established metastases of triple-negative breast cancer.

Hypoxia-inducible factor 1α (HIF-1α) is recognized as a prime molecular target for metastatic cancer. However, no specific HIF-1α inhibitor has been approved for clinical use. Here, we demonstrated that in vivo efficacy of echinomycin in solid tumors with HIF-1α overexpression is formulation-dependent. Compared to previously-used Cremophor-formulated echinomycin, which was toxic and ineffective in clinical trials, liposomal-echinomycin provides significantly more inhibition of primary tumor growth and only liposome-formulated echinomycin can eliminate established triple-negative breast cancer (TNBC) metastases, which are the leading cause of death from breast cancer, as available therapies remain minimally effective at this stage. Pharmacodynamic analyses reveal liposomal-echinomycin more potently inhibits HIF-1α transcriptional activity in primary and metastasized TNBC cells in vivo, the latter of which are HIF-1α enriched. The data suggest that nanoliposomal-echinomycin can provide safe and effective therapeutic HIF-1α inhibition and could represent the most potent HIF-1α inhibitor in prospective trials for metastatic cancer.

Mesenchymal TGF-ß signaling orchestrates dental epithelial stem cell homeostasis through Wnt signaling.

In mouse, continuous growth of the postnatal incisor is coordinated by two populations of multipotent progenitor cells, the dental papilla mesenchymal cells and dental epithelial stem cells, residing at the proximal end of the incisor, yet the molecular mechanism underlying the cooperation between mesenchymal and epithelial cells is largely unknown. Here, transforming growth factor-ß (TGF-ß) type II receptor (Tgfbr2) was specifically deleted within the postnatal dental papilla mesenchyme. The Tgfbr2-deficient mice displayed malformed incisors with wavy mineralized structures at the labial side as a result of increased differentiation of dental epithelial stem cells. We found that mesenchymal Tgfbr2 disruption led to upregulated expression of Wnt5a and downregulated expression of Fgf3/10 in the mesenchyme, both of which synergistically enhanced Lrp5/6-ß-catenin signaling in the cervical loop epithelium. In accord with these findings, mesenchyme-specific depletion of the Wnt transporter gene Wls abolished the aberrant mineralized structures caused by Tgfbr2 deletion. Thus, mesenchymal TGF-ß signaling provides a unifying mechanism for the homeostasis of dental epithelial stem cells via a Wnt signaling-mediated mesenchymal-epithelial cell interaction.

Mutation analysis in patients with nonsyndromic tooth agenesis using exome sequencing.

BACKGROUND: Tooth agenesis (TA) is a congenital abnormality that may present as syndromic or nonsyndromic. Considering its complex genetic aetiology, the aim of this study was to uncover the pathogenic mutants in patients with nonsyndromic TA and analyse the characteristics of these mutants. METHODS: Exome sequencing was performed to detect pathogenic variants in 72 patients from 43 unrelated families with nonsyndromic TA. All candidate variants were validated using Sanger sequencing. Bioinformatics and conformational analyses were performed to determine the pathogenic mechanisms of the mutants. RESULTS: The following eight mutations (six novel and two known) in six genes were identified in eight families: WNT10A [c.742C > T (p.R248*)], LRP6 [c.1518G > A (p.W506*), c.2791 + 1G > T], AXIN2 [c.133_134insGCCAGG (p.44_45insGQ)], PAX9 [c.439C > T (p.Q147*), c.453_454insCCAGC (p.L154QfsTer60)], MSX1 [c.603_604del (p.A203GfsTer10)] and PITX2 [c.522C > G (p.Y174*)]. Bioinformatics and conformational analyses showed that the protein structures were severely altered in these mutants, and indicated that these structural abnormalities may cause functional disabilities. CONCLUSIONS: Our study extends the mutation spectrum in patients with nonsyndromic TA and provides valuable data for genetic counselling. The pathogenic mechanisms of TA in patients/families with unknown causative variants need to be explored further.

Treatment Outcomes of Regenerative Endodontic Procedures in Traumatized Immature Permanent Necrotic Teeth: A Retrospective Study.

INTRODUCTION: This retrospective study aimed to evaluate the clinical and radiographic outcomes of regenerative endodontic procedures (REPs) for traumatic immature permanent teeth. Meanwhile, predictors influencing treatment outcomes were also analyzed to provide evidence for the management of immature teeth after different traumatic scenarios. METHODS: Traumatized immature permanent teeth diagnosed with pulp necrosis treated by REPs using blood clot or concentrated growth factor scaffolds with at least 6 months of follow-up were included from 2012 to 2021. Treatment outcomes were categorized as a success or failure and survival. Further root development was assessed in terms of the percentage changes in the apical diameter, root length, and radiographic root area. Among different injury types, the clinical and radiographic outcomes of REPs were evaluated by the Fisher exact test and the Kruskal-Wallis test, respectively. Survival analysis and Cox regression analysis were performed to identify significant predictors affecting outcomes. RESULTS: Sixty-two teeth with a mean of 22.3 months of follow-up satisfied the criteria, and 80.6% of the teeth had a successful outcome. A significant change was observed in a decrease of the apical diameter (69.3%) and an increase of the radiographic root area (22.6%) after REPs. Among different injury types, the success rates of REPs were as follows: fracture, 84.6%; luxation, 83.3%; combined injuries, 78.6%; and avulsion, 33.3% (P > .05). Fractured teeth had a significantly greater decrease of the apical diameter than combined injuries (P < .05). Avulsion was more prone to developing root resorption than fracture (P < .05). Scaffold was a significant predictor for success; a blood clot had a significantly reduced risk for failure than concentrated growth factor (hazard ratio = 16; 95% confidence interval, 2.1-125.2; P < .001). CONCLUSIONS: REPs provided satisfactory outcomes in traumatized immature permanent necrotic teeth. However, severe injuries, especially avulsion, should be determined carefully to perform REPs when resorption is expected. Scaffold selection may be an important consideration.

Mesenchymal Mycn participates in odontoblastic lineage commitment by regulating Krüppel-like Factor 4 (Klf4) in mice.

BACKGROUND: Commitment of mouse dental papilla cells (mDPCs) to the odontoblast lineage is critical for dentin formation, and this biological process is regulated by a complex transcription factor network. The transcription factor Mycn is a proto-oncogene that plays an important role in tumorigenesis and normal embryonic development. An early study revealed that Mycn is exclusively expressed in dental mesenchymal cells at E15.5, which implies a potential role of Mycn in dentinogenesis. However, the role of Mycn in dentin formation remains elusive. Thus, it is of considerable interest to elucidate the role of Mycn in dentin formation. METHODS: Mycnfl/fl; Osr2IresCre (MycnOsr2) and Mycnfl/fl; K14Cre (MycnK14) transgenic mice were generated, and micro-CT scans were performed to quantitatively analyse the volumetric differences in the molars and incisors of the mutants and their littermates. Mycn was also knocked down in vitro, and alkaline phosphatase (ALP) and alizarin red staining (ARS) were conducted. Cleavage under targets and tagmentation (CUT&Tag) analysis and dual luciferase assays were performed to identify direct downstream targets of Mycn. Immunofluorescence and immunochemistry staining and western blotting (WB) were performed to analyse the expression levels of potential targets. Quantitative PCR, WB, ALP and ARS were performed to test the rescue efficiency. RESULTS: Mesenchymal ablation of Mycn (MycnOsr2) led to defective dentin formation, while epithelial deletion (MycnK14) had no obvious effects on tooth development. ALP and ARS staining revealed that the commitment capacity of mDPCs to the odontoblast lineage was compromised in MycnOsr2 mice. CUT&Tag analysis identified Klf4 as a potential direct target of Mycn, and a dual luciferase reporter assay verified that Mycn could bind to the promotor region of Klf4 and directly activate its transcription. Reciprocally, forced expression of Klf4 partially recovered the odontoblastic differentiation capacity of mDPCs with Mycn knockdown. CONCLUSIONS: Our results elucidated that mesenchymal Mycn modulates the odontoblastic commitment of dental papilla cells by directly regulating Klf4. Our study illustrated the role of Mycn in dentin development and furthers our general comprehension of the transcription factor networks involved in the dentinogenesis process. Thus, these results may provide new insight into dentin hypoplasia and bioengineered dentin regeneration.

One-pot fabrication of a polydopamine-based nanoplatform for GSH triggered trimodal ROS-amplification for cancer therapy.

Reactive oxygen species (ROS) based nanoplatforms have been considered as attractive and feasible candidates for cancer therapy. However, the activated endogenous antioxidant defense of cancer cells in response to the ROS attack greatly hinders their therapeutic efficacy. Although cancer-specific ROS amplification strategies have been widely explored, most of them suffer from tedious synthesis procedures and complex components, which will bring about undesired side effects and unsatisfactory results. Herein, we design a cancer-specific oxidative stress amplification nanomedicine (CA-Cu-PDA), which is simply fabricated through integrating the glutathione (GSH) responsive/depleting nanocarrier of copper-polydopamine (Cu-PDA) nanoparticles with a ROS-generating drug cinnamaldehyde (CA) via a facile one-pot polymerization route. It is verified that GSH could trigger the breakage of CA-Cu-PDA networks and the subsequent release of both copper ions and CA in cancer cells. The released copper ions efficiently oxidize GSH, thereby weakening the antioxidant system of cancer cells and increasing the ROS levels. On the other hand, extra ROS are generated by the reduced copper ions through a Fenton reaction, so that a synergistic ROS therapy with CA is achieved. Consequently, oxidative stress is specifically increased within cancer cells, leading to efficient cancer cell apoptosis, significant tumor suppression and minimized side effects. Such an ingenious structure realizes the interlocking cooperation and full utilization of each component's function, presenting promising perspectives for nanomedicine design.

Deep Learning-Based Three-Dimensional Oral Conical Beam Computed Tomography for Diagnosis.

In order to deeply study oral three-dimensional cone beam computed tomography (CBCT), the diagnosis of oral and facial surgical diseases based on deep learning was studied. The utility model related to a deep learning-based classification algorithm for oral neck and facial surgery diseases (deep diagnosis of oral and maxillofacial diseases, referred to as DDOM) is brought out; in this method, the DDOM algorithm proposed for patient classification, lesion segmentation, and tooth segmentation, respectively, can effectively process the three-dimensional oral CBCT data of patients and carry out patient-level classification. The segmentation results show that the proposed segmentation method can effectively segment the independent teeth in CBCT images, and the vertical magnification error of tooth CBCT images is clear. The average magnification rate was 7.4%. By correcting the equation of R value and CBCT image vertical magnification rate, the magnification error of tooth image length could be reduced from 7.4. According to the CBCT image length of teeth, the distance R from tooth center to FOV center, and the vertical magnification of CBCT image, the data closer to the real tooth size can be obtained, in which the magnification error is reduced to 1.0%. Therefore, it is proved that the 3D oral cone beam electronic computer based on deep learning can effectively assist doctors in three aspects: patient diagnosis, lesion localization, and surgical planning.

Liposomes encapsulated iridium(III) polypyridyl complexes enhance anticancer activity in vitro and in vivo.

Three iridium(III) complexes [Ir(ppy)2(CPIP)](PF6) (Ir-1, ppy = 2-phenylpyridine, CPIP = 2-(4-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline), [Ir(ppy)2(DCPIP)](PF6) (Ir-2, DCPIP = 2-(3,4-dichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) and [Ir(ppy)2(TCPIP)](PF6) (Ir-3, TCPIP = 2,3,5-trichlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) were synthesized and characterized. The complexes Ir-1, Ir-2 and Ir-3 were encapsulated in liposomes to form Ir-1-Lipo, Ir-2-Lipo and Ir-3-Lipo. Morphology, size distribution, and zeta potential of liposomes were examined by transmission electron microscopy (TEM) and Zetasizer. The cytotoxic activity in vitro of Ir-1, Ir-2 and Ir-3 against cancer A549, HTC-116, HepG2, BEL-7402, Eca-109, B16, HeLa SGC-7901 and normal NIH3T3 cells was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) method. Ir-2 and Ir-3 show no cytotoxic activity against the selected cancer cells, and Ir-1 displays moderate cytotoxic effect on the cell growth in A549 cells. However, Ir-1, Ir-2 and Ir-3 were encapsulated in liposomes, the cytotoxic activity was greatly enhanced. In particular, Ir-1-Lipo and Ir-2-Lipo can effectively inhibit the cell growth in A549 cells with a low IC50 value of 3.1 ± 0.3 and 1.2 ± 0.4 µM. The apoptosis was assayed by flow cytometry. Ir-1, Ir-2 and Ir-3 reveal weak apoptotic effect, whereas Ir-1-Lipo, Ir-2-Lipo and Ir-3-Lipo induce an apoptotic percentage of 55.6%, 69.3% and 16.7% in A549 cells, respectively. Specially, in the assay of antitumor activity in vivo, the inhibiting percentage of tumor growth induced by Ir-2 is 27.65%, while inhibiting percentage of tumor growth caused by Ir-2-Lipo is 57.45%. Obviously, the liposomes can enhance anticancer activity in vitro and in vivo compared with the complexes. The results show that the iridium(III) complexes encapsulated liposomes induce apoptosis in A549 cells through ROS-mediated lysosome-mitochondria dysfunction pathway and target the microtubules.

Biodegradable nanoparticles based on linoleic acid and poly(beta-malic acid) double grafted chitosan derivatives as carriers of anticancer drugs.

Novel chitosan derivatives carrying linoleic acid (LA) as hydrophobic moieties and poly(beta-malic acid) (PMLA) as hydrophilic moieties (LA/PMLA double grafted chitosan, LMC) were synthesized. It self-assembled into nanoparticles of 190-350 nm in water, which carried negative surface charges in physiological pH. The critical aggregation concentration of the LMC deceased with an increase in the LA content. Paclitaxel (PTX) was loaded into the LMC nanoparticles with a high loading efficiency and the maximum loading capacity of 9.9 +/- 0.4%. PTX-LMC nanoparticles exhibited a sustained release within 24 h in pH 7.4 phosphate-buffered saline (PBS), and the release rate was affected by the LA content and PMLA length. Hemolysis and acute toxicity assessment indicated that the LMC nanoparticles were safe drug carriers for i.v. administration. Additionally, PTX-LMC showed significantly potent tumor inhibition efficacy relative to that of TAXOL in S-180 bearing mice. Therefore, the LMC nanoparticles could be an effective and safe vehicle for systemic administration of hydrophobic drugs, especially PTX.

Fast on-fiber derivatization and GC/MS analysis of phytohormones in wheat based on pencil-type coated carbon fibers.

New coated carbon fibers (CCFs) have been synthesized, characterized and used as solid phase microextraction (SPME) matrix for the analysis of phytohormones (jasmonic acid, indole-3-acetic acid, and abscisic acid) in wheat samples. The SPME device, realized inserting CCFs in a pencil-type device, when coupled with gas chromatography-mass spectrometry, provides in few steps high recovery values (79-112%), fast on-fiber derivatization (30 s), good method reproducibility (RSD < 20%), low detection limits (0.5-2.1 ng g-1). The pencil-type CCFs-SPME device was successfully employed for the determination of phytohormone in wheat samples, allowing simple and quick extraction/derivatization/injection processes. The proposed device can be then considered as a promising and functional tool for fast and reliable extraction and preconcentration of analytes from real samples, allowing a simple derivatization procedure and direct injection in the chromatographic instrumentation.

Studies of anticancer activity in vitro and in vivo of iridium(III) polypyridyl complexes-loaded liposomes as drug delivery system.

Two iridium(III) polypyridyl complexes [Ir(ppy)2(HPIP)](PF6) (Ir-1), [Ir(ppy)2(BHPIP)](PF6) (Ir-2) and their liposomes Ir-1-Lipo and Ir-2-Lipo were synthesized and characterized by elemental analysis, IR, 1H NMR and 13C NMR. The anticancer activity in vitro and in vivo was evaluated. The cytotoxic activity in vitro of the complexes and their liposomes Ir-1-Lipo and Ir-2-Lipo against cancer cells was investigated by MTT methods. Ir-1 and Ir-2 show no cytotoxic activity, while Ir-1-Lipo and Ir-2-Lipo exhibit high cytotoxic effect. The IC50 values range from 5.2 ±â€¯0.8 to 22.3 ±â€¯1.8 µM. The apoptosis, reactive oxygen species, the change of mitochondrial membrane potential, intracellular Ca2+ levels and a release of cytochrome c were investigated. The effect of Ir-1-Lipo and Ir-2-Lipo on microtubules was also explored. In the C57BL/6 mice model, Ir-1 only displays a tumor inhibitory rate of 23.21%, while lr-1-Lipo exhibits satisfactory in vivo antitumor efficacy with tumor inhibitory rate of 72.55%. This study demonstrates that complexes encapsulated in liposomes induce apoptosis in B16 through ROS-mediated lysosomal-mitochondria dysfunction, inhibition of polymerization of microtubules and induce cell cycle arrest at S phase.

Beneficial properties for insulin absorption using superporous hydrogel containing interpenetrating polymer network as oral delivery vehicles.

In this investigation, superporous hydrogels containing poly (acrylic acid-co-acrylamide)/O-carboxymethyl chitosan (O-CMC) full-interpenetrating polymer networks (SPH-IPNs) were evaluated for their potentials in effective insulin absorption via the oral route. Insulin release from the SPH-IPNs exhibited sensitivity towards pH and ionic strength. After drug loading and release, the circular dichroism (CD) spectra revealed that conformation of insulin had no significant alteration and bioactivity of insulin was well preserved according to hypoglycaemic effect in mice. Through their abilities to bind Ca(2+) and to entrap the enzymes, SPH-IPNs could partly inactivate trypsin and alpha-chymotrypsin, and SPH-IPN with higher O-CMC/monomer ratio appeared more potent. Swollen SPH-IPNs could attach mechanically and muco-adhere to the intestinal wall, thus achieving improved retentive properties compared to commonly used muco-adhesive excipient Carbopol 934. Transport of insulin across rat intestine and colon ex vivo was enhanced around two- to three-fold after application of the SPH-IPN. Insulin-loaded SPH-IPN showed significant hypoglycaemic effects following oral administration to healthy rats, achieving a 4.1% pharmacological availability compared to subcutaneous insulin injection. These pronounced properties demonstrated that the SPH-IPN would be a promising peroral carrier for insulin and other peptide drugs.

Function of self-forming dynamic membrane and biokinetic parameters' determination by microelectrode.

The self-forming dynamic membrane coupled bioreactor (SFDMBR), which uses coarse pore-sized material to separate solids and liquids in a bioreactor, has some advantages compared with membrane bioreactor (MBR) using micro-/ultra-filtration membranes such as low module cost and high flux. In this study, we investigate the microbial activity change of a self-forming dynamic membrane (DM) during its bio-fouling process by a microelectrode for O2. At a high flux of 40 L/m2h, the dissolved oxygen was determined to be depleted at the depth of 1.5-2.0 mm in the self-forming DM. Based on the dissolved oxygen concentration profiles in the self-forming DM, a reliable and simple model and computational procedure were developed to estimate the biokinetic parameters in the self-forming DM. Sensitivity analysis of the model revealed that the dissolved oxygen profiles are sufficiently sensitive to the maximum specific rates of oxygen uptake (q down curvemax,20), which were computed to be within the range of 3.8-11.1 mg O2/gSS h. q down curvemax,20 decreased sharply in the first 5 days with the development of the bio-fouling process in the surface cake layer of the self-forming DM and then reached a relatively steady state afterwards. The Monod half-saturation coefficient for oxygen (Ko) was computed to be in the range of 0.16-0.75 mgO2/L. In summary, the results gave new experimental evidence on the change of microbial activity in the self-forming DM during its bio-fouling process.