Cancer-specific calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca

Layered dissolving microneedles as a need-based delivery system to simultaneously alleviate skin and joint lesions in psoriatic arthritis

Psoriatic arthritis (PsA) is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints, and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging. We developed a need-based layered dissolving microneedle (MN) system loading immunosuppressant tacrolimus (TAC) and anti-inflammatory diclofenac (DIC) in different layers of MNs,

Uptake and trafficking of different sized PLGA nanoparticles by dendritic cells in imiquimod-induced psoriasis-like mice model

Psoriasis is an autoimmune inflammatory disease, where dendritic cells (DCs) play an important role in its pathogenesis. In our previous work, we have demonstrated that topical delivery of curcumin-loaded poly (lactic-

Antibiofilm and anti-inflammatory potential of lignans with collegial effect: Secoisolariciresinol diglucoside and sesamin as antimicrobial sources

Linum usitatissimum (L.), the Flaxseed (FS) and Sesamum indicum (L.), the sesame seeds (SS) are rich sourcesof lignans, secoisolariciresinol diglucoside (SDG), and Sesamin (Sm), respectively. Synergistic effects of theSDG and Sm lignan samples were investigated in the present study, a first of its kind. The high performanceliquid chromatography fingerprint identified the presence of SDG and sesamin in FS and SS. Antimicrobialactivity of SDG+Sm combination by disc diffusion in opposition to Bacillus subtilis, Escherichia coli,Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus significantly arrests growthof the bacteria in comparison to independent use of SDG and Sm. Bacterial biofilm inhibition capacity ofSDG+Sm imaged by confocal laser scanning microscopy revealed the loss of microcolonies. SDG+Sm couldinhibit the 15-LOX and COX-2 enzyme at relatively lower concentrations. Furthermore, SDG+Sm quenchedfree radicals produced by Fenton’s reagent studied by DNA-protection assay indicating its robust antioxidantproperty in protecting the DNA. These results put together encourage the use of a combination of FS and SSseed lignans SDG+Sm in a wide range of applications as natural preservatives with pharmacological effects,such as anti-inflammatory agent and aid, in their promotion as nutraceuticals.

Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway

Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation (iTRAQ) 2D liquid chromatography with tandem mass spectrometric (LC-MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspase inhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation, and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species (ROS) generations. Further studies showed that PDT treatment with 0.08 µmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome , and activation of caspase-3, -9, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.

Transdermal characteristics and mechanism of asiaticoside nanoemulsions and asiaticoside nanoemulsions-based gels / 中国中药杂志

To prepare the asiaticoside nanoemulsions (ASI-NEs) and asiaticoside nanoemulsions-based gels (ASI-NBGs), compare them with the commercial cream of asiaticoside (ASI-C) in terms of transdermal characteristics, and investigate the transdermal mechanism of ASI-NEs and ASI-NBGs. Their transdermal characteristics were studied by using Franz diffusion cells. The effect of topical ASI-NEs and ASI-NBGs on ultrastructure of rabbit skin was evaluated by using HE staining method. The localization and the permeation pathway of asiaticoside were visually investigated by using laser scanning confocal microscope (CLSM). The transdermal studies in vitro showed that the cumulative amount of ASI permeated from ASI-NEs and ASI-NBGs at 12 h after application were (3 504.30±180.93), (1 187.40±128.88) μg·cm⁻² respectively, 6.57, 2.23 times of that in the control group of ASI-C; the drug deposition of ASI-NEs and ASI-NBGs in skin was (159.48±7.47), (120.53±5.71) μg·cm⁻² respectively, 5.93, 4.48 times of that of ASI-C. HE staining of the rabbit skin after application of ASI-NEs and ASI-NBGs showed that the epidermis structure was basically intact; stratum corneum was loosed and the keratin fragment was increased; at the same time, the gap of prickle cell was increased and the basal cells were arranged loosely. The study of CLSM showed that significant percutaneous enhancer effect was observed for ASI-NEs after the topical application of 6 h, as the fluorescent compound was penetrated in the dermis and diffused uniformly. The fluorescence area and the integral optical density (IOD) were 28.81, 32.51 times of that in the FITC aqueous solution group, respectively. The fluorescent preparations showed strong fluorescence in the epidermis, but weak in deeper layers; with the increase of treatment time, the fluorescence in deeper layer was increased and stronger in skin appendages. The prepared ASI-NEs and ASI-NBGs have good transdermal characteristics and the transdermal mechanism is related to breaking the ultrastructure of stratum corneum and penetrating by the path of skin adnexa.

Enhanced efficiency of stannous penetration and lipopolysaccharide neutralization by a novel stabilized stannous-containing sodium fluoride dentifrice / 实用口腔医学杂志

Objective:To evaluate the dental biofilm penetration efficiency of a novel stabilized stannous-containing sodium fluoride dentifric(EXP) and its lipopolysaccharide (LPS) neutralization efficiency.Methods:A controlled,randomized,examiner-blind in situ clinical trial was conducted with the treatment of PBS(control),EXP and a marketed stannous-containing sodium fluoride dentifrice (MKD).Fluorescent dye,fluorescent probe and fluorescence colocalization were used for sample examination and analysis.Results:EXP offered better stannous penetration into the biofilm than MKD and PBS(P ＜0.05),as well as greater LPS neutralization efficiency(P ＜0.05).There was a 96.52％ overlap of stannous ions and bounded LPS at the same sites treated by EXP.Conclusion:EXP is more effective than MKD in the delivery of stannous into the biofilm and in the neutralization of LPS.

A Confocal Laser Scanning Microscopic Study on the Distribution and Fluorescent Intensity of NPY-IR in the Cerebral Cortex of the Head Irradiated Rats / 체질인류학회지

The purpose of this study, the effects on the cerebral cortex of the rats after brain irradiation was to investigate the change of distribution and morphology of neuropeptide-Y (NPY) neurons. Radiation was produced by the linear accelerator 6MV X-ray. The animals were categorized into control and experimental groups and we use 45 Sprague-Dawley rats weighing about 200 ~250 gm. The head areas of the animals were positioned within the radiation field of 15 cmx20 cm and with the radiation depth of 2 cm. Sodium chloral hydrate-anesthetized rats were exposed to the radiation with the dose rate of 240 cGy/min. The total dose was 1,800 cGy(rad). Animals were sacrificed on 2 hours, 5 hours, 1 day, 2 days, 3 days, 1 week, weeks, 3 weeks after brain irradiation. Using ABC immunohistochemistry, morphology and distribution of neuropeptide-Y immunoreactive neurons (NPY-IR)were studied on the cerebral cortex of the control and brain-irradiated rats. We used light and confocal laser scanning microscopy (CLSM). The following results were obtained : 1. On control group, NPY-IR neurons were found in all layers of the primary motor and sensory cerebral cortex, and the NPY-IR neurons were concentrated within the layer II, III, IV, V and VI. The typical NPY-IR perikarya was bipolar and multipolar shape. 2. On 2 hours, 5 hours after X-irradiation, decreased number of NPY-IR neurons were detected in the primary motor and sensory cerebral cortex of the rats. Also shrunken and transformed NPY-IR neurons were detected in the primary motor and sensory cerebral cortex of the rats. 3. On 1 day, 2 days, 3 days after X-irradiation, morphology and distribution of NPY-IR neurons in the primary motor and sensory cerebral cortex was generally restored. 4. On 1 week, 2 weeks, 3 weeks after X-irradiation, morphology and distribution of NPY-IR neurons in the primary motor and sensory cerebral cortex was almost similar to control group. 5. In optical serial section analysis of NPY-IR neurons, high intensity of immunofluorescence were observed in a part of the 8 ~11 sections of the control and all irradiated groups. In optical single section analysis of NPY-IR neurons, red color (high fluorescence intensity) were observed in a part of 6, 7 sections of the control and all irradiated groups. From the above results, it was concluded that the release of neurotransmitters and transcapillary leakage of blood substance were occurred on 2 hours, 5 hours, 1 day after X-irradiation, but the condition was generally restored on 3 days and 7 days following X-irradiation.

Effect of Liposome Suspension on Distribution of Fluorescein Sodium in Rat Skin / 中国药房

OBJECTIVE:To study effect of liposome suspension on distribution of fluorescein sodium in the rat skin.METHODS:Using0.125%fluorescein sodium(NaFl)solution as control,the distribution of NaFl in epidermis and dermis at different time periods was observed under confocal laser scanning microscope in0.125%NaFl liposome suspension group(trial group).RESULTS:The fluorescent intensity peaks in epidermis and dermis of trial group were higher than those in skin layers of control group(P

Studies on the characterization of a molecule expressed on murine thymic stromalcells and activated thymocytes / 中国免疫学杂志

To identify the expression of the molecule recognized by Pf18-3 mAb (Pf18-3 molecule) on various cells. Meth-ods: The expression of pr18-3 molecule was assayed by flow cytometry and confocal laser scanning microscope . Result: The molecule recog-nized by Pf18-3 mAb expressed on TSC and other stromal cells. Whereas, fresh thymocytes were Pf18-3 negative. Interestingly, the expressionof Pf18-3 molecule was gradually up-regulated on thymocytes after activation by ConA. This molecule mainly expressed on CD4+ CD8+ andCD4+ CD8- cells. Under confocal laser scanning microscope, the staining of fluorescence showed as ring around the cell, it changed grsduallystronger and thicker with activation. Conclusion: This study indicated that the Pf18-3 molecule was co-expressive molecule of MTSC and acti-vated tlymocytes,it was concemed closely about the activation of CD4+ C D8+ and CD4+ CD8- cells.