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2.
Risk Manag Healthc Policy ; 16: 2391-2404, 2023.
Article in English | MEDLINE | ID: mdl-38024489

ABSTRACT

To reveal the importance of the participation of the health insurance fund in the prevention and control of serious infectious diseases, this research retrospectively analyzed the case of the German statutory health insurance fund in response to the COVID-19 epidemic. Based on Germany's practical experience, this research offers a strategy idea for other countries with a social health insurance system, aiming to ensure that the health care system does not collapse rapidly due to medical resource shortage in the event of a pandemic. Firstly, this research conducted a documentary analysis to systematically collate the temporary and additional coverage measures provided by the health insurance fund from January to the end of July 2020, which sheds light on the pivotal role of these funds in epidemic prevention and control. Secondly, this research used comparative analysis to examine the time sequence of implementing these different types of coverage measures in the progression of the epidemic to illustrate how the health insurance fund adjusted its response measures. The health insurance fund was actively involved in the development of core strategies for combating the epidemic when it broke out, by taking part in joint multisectoral consultations. By using payment instruments flexibly, the fund led the implementation of epidemic prevention and control measures, as it could allocate health resources quickly and efficiently in emergencies. Furthermore, the health insurance fund played a critical role in transmitting information on the epidemic and guiding the insured to take appropriate protective measures. By fulfilling its role in health promotion, particularly in the area of health education, the fund provided important complementary and synergistic contributions to the prevention and control of the spread of infectious diseases. In summary, this research provides a new model for other countries for mobilizing a multi-sectoral response to infectious disease prevention and control, and emphasises the key role of the health insurance fund in responding to major public health crises.

3.
Risk Manag Healthc Policy ; 16: 1929-1939, 2023.
Article in English | MEDLINE | ID: mdl-37750073

ABSTRACT

After 75 years of reformed practice, general practitioners (GPs) in the UK have transformed from health gatekeepers who simply provide medical decision-making such as diagnostic and treatment services and referral services, to health agents who proactively provide more relevant health services such as immunizations, health monitoring and health management, etc. In order to discuss this transformation of the role of the general practitioner and the conditions for the evolution of the role, this study chose the documentary analysis method to provide a comprehensive overview of the legal and normative documents related to the general practitioner. Furthermore, this study uses a comparative analysis method to conclude the definition and role characteristics of GPs as health agents. This study summarises the general pattern of evolution of GPs into health agents. The transformation into a health agent relies on the interpersonal trust and rigorous institutional of society on the general practitioner system. The expansion of GPs' clientele and range of services, together with the motivation to proactively provide services, have combined to push for a "qualitative change" in the GP's role as health agent. The transformation of the role of the general practitioner to a health agent is a historical necessity. It responds to the evolution of society's understanding of health and the need for higher levels of health. Therefore, recognizing the role of GPs as health agents is important for optimizing the use of health care resources and improving the health of society by taking advantage of this role.

4.
Mar Pollut Bull ; 171: 112662, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34242955

ABSTRACT

On July 16, 2010, a pipeline explosion spilled 1500 tons of crude oil into the Port of Dalian, China. To identify taxa responses to the spill, we exploited seven years of monitoring data to examine the co-occurrence of taxon pairs and the variation of the macrobenthic community. Non-parametric correlation analysis was used to construct interaction networks of relationships between oil spill contaminants and macrobenthic taxa. We observed that the impacted macrobenthic community not restored before 2016. The tolerance/sensitivity of taxa was inconsistent with the studies of oil impacts in other locations. We suggest revision of the ecological group classification of Sabellidae, Lumbrineridae, Terebellidae, Sternaspidae, and Spionidae. The variation in the frequency of coexistence indicates the potential impact of oil spill pollution on resource occupation. The interaction network involving macrobenthic families and stressors associated with the oil spill highlights how different macrobenthic families respond to different combinations of stressors.


Subject(s)
Petroleum Pollution , Petroleum , Polychaeta , Animals , Bays , Geologic Sediments , Humans , Petroleum Pollution/analysis
5.
Mar Pollut Bull ; 168: 112424, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33975157

ABSTRACT

It has been 14 years since the world's largest Ulva bloom appeared in the Yellow Sea, China in 2007. Although it is clear that the Ulva bloom originates from the culture system of Porphyra yezoensis (Nori) in the southern Yellow Sea, how to control it is still little understood. Since overwintering banks played a crucial role in the development of spring population of green algae on the cultivation ropes, here, a promising method was presented to prevent the development of Ulva bloom by the inactivation of the overwintering banks of green algae on the P. yezoensis cultivation ropes during February and early March. Chlorine dioxide, an environment-friendly disinfectant was used as algaecide with dosage of no lower than 40 mg/L at the contact time of 1 min. The overwintering green algae gradually disappeared within two weeks after the treatment. Furthermore, the growth of spring population of green algae on the cultivation ropes was effectively inhibited for at least eight weeks, which contribute to prevent the formation of floating populations during cultivation facilities collection. It was expected that the present method, if to be applied in the P. yezoensis cultivation areas in southern Yellow Sea, may mitigate the magnitude of the Ulva blooms in the Yellow Sea at a lower cost.


Subject(s)
Chlorophyta , Porphyra , Ulva , China , Eutrophication
6.
Methods Appl Fluoresc ; 9(2): 025003, 2021 Feb 13.
Article in English | MEDLINE | ID: mdl-33524966

ABSTRACT

A dual-functional nanosysterm is developed by means of Chlorin e6 (Ce6) as photosensitizer and 1,3-Diphenylisobenzofuran (DPBF) as fluorescent singlet oxygen (1O2) probe. Under 660 nm laser irradiation, Ce6 exhibites efficient 1O2 generation, and subsequently the production of 1O2 is assessed by the ratiometric fluorescence of PFO and DPBF under one-photon and two-photon excitation mode. The nanoparticles with excellent biocompatibility can be internalized into Hela cells and applied for tumor treatment. For intracellular PDT, the nanoparticles perform a high phototoxicity, while the PDT proccess can be evaluated in time by monitoring fluorescence signals of DPBF. This theranostic nanosysterm provides a facile strategy to fabricate 1O2-detection PDT, which can realize accurate and efficient photodynamic therapy based on singlet oxygen detection.


Subject(s)
Antineoplastic Agents/pharmacology , Fluorescent Dyes/chemistry , Nanoparticles/chemistry , Photosensitizing Agents/pharmacology , Singlet Oxygen/analysis , Singlet Oxygen/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/radiation effects , Benzofurans/chemistry , Cell Survival/drug effects , Chlorophyllides , HeLa Cells , Humans , Light , Nanoparticles/radiation effects , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/radiation effects , Polymers/chemistry , Porphyrins/chemistry , Porphyrins/pharmacology , Porphyrins/radiation effects , Singlet Oxygen/chemistry
7.
Phys Rev Lett ; 125(23): 237006, 2020 Dec 04.
Article in English | MEDLINE | ID: mdl-33337229

ABSTRACT

Recent experiments have tuned the monolayer 1T^{'}-WTe_{2} to be superconducting by electrostatic gating. Here, we theoretically study the phonon-mediated superconductivity in monolayer 1T^{'}-WTe_{2} via charge doping. We reveal that the emergence of soft-mode phonons with specific momentum is crucial to give rise to the superconductivity in the electron-doping regime, whereas no such soft-mode phonons and no superconductivity emerge in the hole-doping regime. We also find a superconducting dome, which can be attributed to the change of Fermi surface nesting conditions with electron doping. By taking into account the experimentally established strong anisotropy of temperature-dependent upper critical field H_{c2} between the in-plane and out-of-plane directions, we show that the superconducting state probably has the unconventional equal-spin-triplet pairing in the A_{u} channel of the C_{2h} point group. Our studies provide a promising understanding to the doping dependent superconductivity and strong anisotropy of H_{c2} in monolayer 1T^{'}-WTe_{2}, and can be extended to understand the superconductivity in other gated transition metal dichalcogenides.

8.
Adv Colloid Interface Sci ; 283: 102243, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32854016

ABSTRACT

Textile with deodorizing properties not only keeps the clothing smell fresh, but also is beneficial toward improving the level of indoor air quality, especially when the fibrous materials are used for buildings and furniture. This review summarizes and discusses the recent progress in developing smart textile with deodorizing property. In particular, the key deodorizing methods including enhanced adsorption, catalytic decomposition, source control and masking are brought to light. The theoretical concepts, mechanisms and the latest fabrication methods along with the deodorizing efficiency are discussed. Moreover, the current limitations of these methods are underlined and some recommendations for future research strategies in terms of deodorizing performance, textile engineering, fiber types and treatment impact on fiber mechanical properties are proposed. This review provides the latest state-of-the-art achievements in the field of deodorizing methods of textile, which will be a valuable platform for researchers and decision makers to design and develop novel functional textile products.

9.
J Mater Chem B ; 8(5): 1033-1039, 2020 02 07.
Article in English | MEDLINE | ID: mdl-31939981

ABSTRACT

Photothermal therapy following microscopic temperature detection can avoid overheating effects or insufficient heating, and thus improve therapeutic efficacy. In this study, biocompatible dual-functional nanoparticles (NPs) are constructed from polypyrrole (PPy) and rhodamine B (RB) by a one-step modified polymerization method. The polypyrrole serves as a photothemal agent, and rhodamine B acts as a temperature-sensing probe. The polypyrrole-rhodamine B (PPy-RB) NPs possess a high photothermal effect on irradiation by 808 nm laser, and a competent temperature sensitivity for the real-time temperature monitoring based on the emission intensity response of rhodamine B. After acting on HepG2 cells, the PPy-RB NPs can effectively induce cancer cell death, and the microscopic temperature is monitored by fluorescence feedback from rhodamine B during PTT by laser confocal microscopy. Hence, the proposed approach can supply a facile and promising way for the fabrication of effective theranostic nanoplatforms assisted by self-monitoring of cancer therapeutic processes.


Subject(s)
Nanoparticles/chemistry , Photothermal Therapy , Polymers/pharmacology , Pyrroles/pharmacology , Rhodamines/pharmacology , Cell Survival/drug effects , Hep G2 Cells , Humans , Materials Testing , Particle Size , Polymers/chemistry , Pyrroles/chemistry , Rhodamines/chemistry , Surface Properties , Temperature , Tumor Cells, Cultured
10.
Mikrochim Acta ; 186(12): 842, 2019 11 25.
Article in English | MEDLINE | ID: mdl-31768653

ABSTRACT

Conjugated polymer hybrid nanoparticles (NPs) loaded with both indocyanine green (ICG) and 1,3-diphenylisobenzofuran (DPBF) are described. The NPs are dually functional in that ICG acts as the photosensitizer, and DPBF as a probe for singlet oxygen (1O2 probe). The nanoparticle core consists of the energy donating host poly(9,9-dioctylfluorenyl-2,7-diyl)-co-(2,5-p-xylene) (PFP). The polymer is doped with the energy acceptor DPBF. Ratiometric fluorometric detection of singlet oxygen is accomplished by measurement of fluorescence at wavelengths of 415 and 458 nm. In addition, the shell of the positively charged polymeric nanoparticles was modified, via electrostatic interaction, with negatively charged PDT drugs ICG. The integrated nanoparticles of type ICG-DPBF-PFP display effective photodynamic performance under 808-nm laser irradiation. The 1O2 sensing behaviors of samples are evaluated based on the ratiometric fluorescent responses produced by DPBF and PFP. 1O2 can be fluorimetically sensed with a detection limit of 28 µM. The multifunctional nanoprobes exhibit effortless cellular uptake, superior photodynamic activity and a rapid ratiometric response to 1O2. Graphical abstractSchematic of a dual-functional nanoplatform for photodynamic therapy (PDT) and singlet oxygen (1O2) feedback. It offers a new strategy for self-monitoring photodynamic ablation. FRET: fluorescence resonance energy transfer. Indocyanine green is attached in the shell of nanoparticles, and 1,3-diphenylisobenzofuran is doped into the energy donating host conjugated polymer.


Subject(s)
Benzofurans/chemistry , Indocyanine Green/chemistry , Nanoparticles/chemistry , Photosensitizing Agents/chemistry , Polylysine/chemistry , Singlet Oxygen/analysis , Benzofurans/toxicity , Fluorescence Resonance Energy Transfer , Hep G2 Cells , Humans , Indocyanine Green/radiation effects , Indocyanine Green/toxicity , Infrared Rays , Limit of Detection , Nanoparticles/toxicity , Photochemotherapy , Photosensitizing Agents/radiation effects , Photosensitizing Agents/toxicity , Polylysine/toxicity , Singlet Oxygen/chemistry
11.
J Chin Med Assoc ; 82(8): 655-658, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31169588

ABSTRACT

BACKGROUND: Thumb basal joint arthritis is a common, disabling condition of the hand. Ligament reconstruction and tendon interposition (LRTI) is one of the more common surgical solutions. We performed a retrospective study to evaluate long-term radiological and clinical outcomes of modified LRTI procedures in treating thumb basal joint arthritis. METHODS: A total of 91 hands (84 patients) with full chart records were enrolled in this study. The average age was 65.4 years, and the mean follow-up was 11.7 years (range, 1-21.6 years). We evaluated pain, joint stability, power-grip and key pinch strength, and thumb radial abduction angle as the functional outcomes, and measured the height of the trapezial space as the radiographic result. RESULTS: There were 66 and 23 hands with excellent and good results, respectively. The diminution of the trapezial space was 4.2 mm in the stage III group and 5.2 mm in the stage IV group. Power-grip and key pinch strength, and thumb radial abduction angle were better in those with stage III than in those with stage IV arthritis. Sixty-eight hands were followed up >5 years, and of them, 66 showed excellent or good results. CONCLUSION: With good and durable surgical outcomes, the modified LRTI procedure could be a good treatment for thumb basal joint arthritis.


Subject(s)
Carpometacarpal Joints/surgery , Ligaments, Articular/surgery , Osteoarthritis/surgery , Plastic Surgery Procedures/methods , Tendons/surgery , Thumb/surgery , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
12.
Methods Appl Fluoresc ; 6(3): 035008, 2018 Apr 27.
Article in English | MEDLINE | ID: mdl-29651992

ABSTRACT

Ratiometric fluorescent nanoparticles (NPs) under two-photon excitation are successfully developed for sensing dissolved oxygen. The NPs comprise the oxygen probe Pt(II)-porphyrins (PtTFPP) and fluorescent organic semiconducting polymer (PFO). PFO polymer acts as both a two-photon antenna and a reference dye, while PtTFPP absorbs the photonic energy transferred by the PFO under two-photon excitation at 740 nm to sense oxygen. The red fluorescence of PtTFPP is sensitive to oxygen with a quenching response of 88% from nitrogen saturation to oxygen saturation, and PFO gives oxygen-insensitive referenced blue fluorescence. The fluorescence quenching of the NPs against oxygen at two-photon excitation follows a linear Stern-Volmer behavior. The nanosensors exhibit low cytotoxic effects as well as effortless cellular uptake. When incorporated into cells, the ratio of the signals increases up to about 500% from oxygen-saturated to oxygen-free environment.


Subject(s)
Nanoparticles/chemistry , Platinum/chemistry , Polymers/chemistry , Porphyrins/chemistry , Humans
13.
J Chin Med Assoc ; 80(10): 669-672, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28606742

ABSTRACT

BACKGROUND: Carpal tunnel release (CTR) is considered effective in treating carpal tunnel syndrome (CTS), and diabetes is considered to complicate the outcome and recovery. However, the difference in recurrence rate between diabetic and non-diabetic patients after mini-open CTR in the long-term has not yet determined. METHODS: This study enrolled 1251 wrists (1091 patients), with 841 (67%) females and 480 (33%) males at a mean age of 58.5 years at operation. Patients were followed for a mean duration of 10.5 years. We retrospectively compared the recurrence rates of the Paine retinaculotome for mini-open CTR at wrist in diabetic and non-diabetic patients. RESULTS: In our study, a total of 161 wrists (13%) were in the diabetic patients and 1090 wrists (87%) were in the non-diabetic patients. Two wrists (1.24%) in the diabetic group and seven (0.6%) in the non-diabetic group exhibited recurrence (p = 0.325). CONCLUSION: The mini-open CTR with the Paine retinaculotome in diabetic patients didn't show significantly higher recurrence rate than that in non-diabetic patients in the long term.


Subject(s)
Carpal Tunnel Syndrome/therapy , Diabetes Complications/therapy , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Recurrence , Retrospective Studies
14.
Stem Cell Res Ther ; 8(1): 39, 2017 02 21.
Article in English | MEDLINE | ID: mdl-28222767

ABSTRACT

BACKGROUND: Magnesium is essential for numerous physiological functions. Magnesium exists mostly in bone and the amount is dynamically regulated by skeletal remodeling. Accelerating bone mass loss occurs when magnesium intake is insufficient; whereas high magnesium could lead to mineralization defects. However, the underlying magnesium regulatory mechanisms remain elusive. In the present study, we investigated the effects of high extracellular magnesium concentration on osteogenic differentiation of mesenchymal stromal/stem cells (MSCs) and the role of magnesium transporter SLC41A1 in the mineralization process. METHODS: Murine MSCs derived from the bone marrow of BALB/c mouse or commercially purchased human MSCs were treated with osteogenic induction medium containing 5.8 mM magnesium chloride and the osteogenic differentiation efficiency was compared with that of MSCs in normal differentiation medium containing 0.8 mM magnesium chloride by cell morphology, gene expression profile of osteogenic markers, and Alizarin Red staining. Slc41a1 gene knockdown in MSCs was performed by siRNA transfection using Lipofectamine RNAiMAX, and the differentiation efficiency of siRNA-treated MSCs was also assessed. RESULTS: High concentration of extracellular magnesium ion inhibited mineralization during osteogenic differentiation of MSCs. Early osteogenic marker genes including osterix, alkaline phosphatase, and type I collagen were significantly downregulated in MSCs under high concentration of magnesium, whereas late marker genes such as osteopontin, osteocalcin, and bone morphogenetic protein 2 were upregulated with statistical significance compared with those in normal differentiation medium containing 0.8 mM magnesium. siRNA treatment targeting SLC41A1 magnesium transporter, a member of the solute carrier family with a predominant Mg2+ efflux system, accelerated the mineralization process and ameliorated the inhibition of mineralization caused by high concentration of magnesium. High concentration of magnesium significantly upregulated Dkk1 gene expression and the upregulation was attenuated after the Slc41a1 gene was knocked down. Immunofluorescent staining showed that Slc41a1 gene knockdown promoted the translocation of phosphorylated ß-catenin into nuclei. In addition, secreted MGP protein was elevated after Slc41a1 was knocked down. CONCLUSIONS: High concentration of extracellular magnesium modulates gene expression of MSCs during osteogenic differentiation and inhibits the mineralization process. Additionally, we identified magnesium transporter SLC41A1 that regulates the interaction of magnesium and MSCs during osteogenic differentiation. Wnt signaling is suggested to be involved in SLC41A1-mediated regulation. Tissue-specific SLC41A1 could be a potential treatment for bone mass loss; in addition, caution should be taken regarding the role of magnesium in osteoporosis and the design of magnesium alloys for implantation.


Subject(s)
Calcification, Physiologic/drug effects , Cation Transport Proteins/genetics , Magnesium/pharmacology , Mesenchymal Stem Cells/metabolism , Osteogenesis/drug effects , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/metabolism , Calcification, Physiologic/genetics , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Cation Transport Proteins/antagonists & inhibitors , Cation Transport Proteins/metabolism , Cell Differentiation , Collagen Type I/genetics , Collagen Type I/metabolism , Extracellular Matrix Proteins/genetics , Extracellular Matrix Proteins/metabolism , Gene Expression Regulation , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Ion Transport , Magnesium/metabolism , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mice , Mice, Inbred BALB C , Osteocalcin/genetics , Osteocalcin/metabolism , Osteogenesis/genetics , Osteopontin/genetics , Osteopontin/metabolism , Protein Isoforms/antagonists & inhibitors , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Sp7 Transcription Factor , Transcription Factors/genetics , Transcription Factors/metabolism , Wnt Signaling Pathway , Matrix Gla Protein
15.
Int J Mol Sci ; 18(1)2017 Jan 17.
Article in English | MEDLINE | ID: mdl-28106724

ABSTRACT

There is a growing interest in cell therapies using mesenchymal stromal cells (MSCs) for repairing bone defects. MSCs have the ability to differentiate into osteoprogenitors and osteoblasts as well as to form calcified bone matrix. However, the molecular mechanisms governing mineralization during osteogenic differentiation remain unclear. Non-collagenous proteins in the extracellular matrix are believed to control different aspects of the mineralization. Since osteocalcin is the most abundant non-collagenous bone matrix protein, the purpose of this study is to investigate the roles of osteocalcin in mineral species production during osteogenesis of MSCs. Using Raman spectroscopy, we found that the maturation of mineral species was affected by osteocalcin expression level. After osteocalcin was knocked down, the mineral species maturation was delayed and total hydroxyapatite was lower than the control group. In addition, the expression of osteogenic marker genes, including RUNX2, alkaline phosphatase, type I collagen, and osteonectin, was downregulated during osteogenic differentiation compared to the control group; whereas gene expression of osterix was upregulated after the knockdown. Together, osteocalcin plays an essential role for the maturation of mineral species and modulates osteogenic differentiation of MSCs. The results offer new insights into the enhancement of new bone formation, such as for the treatments of osteoporosis and fracture healing.


Subject(s)
Calcification, Physiologic/genetics , Mesenchymal Stem Cells/metabolism , Osteocalcin/genetics , Osteogenesis/genetics , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Anthraquinones , Cell Differentiation/genetics , Cells, Cultured , Collagen Type I/genetics , Collagen Type I/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Durapatite/metabolism , Gene Expression , Mesenchymal Stem Cells/cytology , Osteocalcin/metabolism , Osteonectin/genetics , Osteonectin/metabolism , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Spectrum Analysis, Raman , Staining and Labeling/methods
16.
J Mater Chem B ; 5(9): 1856-1862, 2017 Mar 07.
Article in English | MEDLINE | ID: mdl-32263925

ABSTRACT

A type of polymeric nanoparticles loading indocyanine green and Pt(ii)-porphyrins (ICG-Pt-NPs) is constructed to achieve a synergistic effect of combined photothermal and two-photon activated photodynamic therapy. The nanoparticle core comprises the photosensitizer Pt(ii)-porphyrins (PtTFPP), and organic semiconducting polymer (PFO) that acts as a two-photon antenna. Negative ICG molecules, an NIR-absorbing photothermal dye, can be loaded into the positively charged poly-l-lysine (PLL) shell of the polymeric nanoparticles via electrostatic interaction. In these carefully designed ICG-PtTFPP integrated nanoparticles, PtTFPP absorbs the photonic energy transferred by the PFO polymer under two-photon laser excitation at 740 nm to induce photodynamic cancer cell death, while ICG offers nanoparticles a strong photothermal performance under 808 nm laser irradiation. Compared with photodynamic therapy or photothermal therapy alone, the combined therapy had a significantly synergistic effect and improved the therapeutic efficacy with near-infrared irradiation.

17.
Sci Rep ; 6: 37371, 2016 11 30.
Article in English | MEDLINE | ID: mdl-27901049

ABSTRACT

Lineage commitment and differentiation of mesenchymal stromal cells (MSCs) into osteoblasts in vitro is enhanced by a potent synthetic form of glucocorticoid (GC), dexamethasone (Dex). Paradoxically, when used chronically in patients, GCs exert negative effects on bone, a phenomenon known as glucocorticoid-induced osteoporosis in clinical practice. The mechanism on how GC differentially affects bone precursor cells to become mature osteoblasts during osteogenesis remains elusive. In this study, the dose and temporal regulation of Dex on MSC differentiation into osteoblasts were investigated. We found that continuous Dex treatment led to a net reduction of the maturation potential of differentiating osteoblasts. This phenomenon correlated with a decrease in glucocorticoid receptor (GR) expression, hastened degradation, and impaired sub cellular localization. Similarly, Histone Deacetylase 6 (HDAC6) expression was found to be regulated by Dex, co-localized with GR and this GR-HDAC6 complex occupied the promoter region of the osteoblast late marker osteocalcin (OCN). Combinatorial inhibition of HDAC6 and GR enhanced OCN expression. Together, the cross-talk between the Dex effector molecule GR and the inhibitory molecule HDAC6 provided mechanistic explanation of the bimodal effect of Dex during osteogenic differentiation of MSCs. These findings may provide new directions of research to combat glucocorticoid-induced osteoporosis.


Subject(s)
Dexamethasone/pharmacology , Histone Deacetylase 6/metabolism , Mesenchymal Stem Cells/drug effects , Osteogenesis/drug effects , Receptors, Glucocorticoid/metabolism , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Animals , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cell Line , Cell Line, Tumor , Cells, Cultured , Gene Expression/drug effects , Glucocorticoids/pharmacology , Histone Deacetylase 6/genetics , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice, Inbred BALB C , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteogenesis/genetics , Receptors, Glucocorticoid/genetics
18.
Sci Rep ; 6: 31547, 2016 08 16.
Article in English | MEDLINE | ID: mdl-27526936

ABSTRACT

Cellular biophysical properties are novel biomarkers of cell phenotypes which may reflect the status of differentiating stem cells. Accurate characterizations of cellular biophysical properties, in conjunction with the corresponding biochemical properties could help to distinguish stem cells from primary cells, cancer cells, and differentiated cells. However, the correlated evolution of these properties in the course of directed stem cells differentiation has not been well characterized. In this study, we applied video particle tracking microrheology (VPTM) to measure intracellular viscoelasticity of differentiating human mesenchymal stromal/stem cells (hMSCs). Our results showed that osteogenesis not only increased both elastic and viscous moduli, but also converted the intracellular viscoelasticity of differentiating hMSCs from viscous-like to elastic-like. In contrast, adipogenesis decreased both elastic and viscous moduli while hMSCs remained viscous-like during the differentiation. In conjunction with bio- chemical and physical parameters, such as gene expression profiles, cell morphology, and cytoskeleton arrangement, we demonstrated that VPTM is a unique approach to quantify, with high data throughput, the maturation level of differentiating hMSCs and to anticipate their fate decisions. This approach is well suited for time-lapsed study of the mechanobiology of differentiating stem cells especially in three dimensional physico-chemical biomimetic environments including porous scaffolds.


Subject(s)
Cell Differentiation , Mesenchymal Stem Cells/cytology , Actins/metabolism , Adipogenesis , Focal Adhesions , Gene Expression Profiling , Humans , Mesenchymal Stem Cells/metabolism , Microscopy, Fluorescence , Osteogenesis , Rheology , Viscosity
19.
Sci Rep ; 6: 24495, 2016 Apr 19.
Article in English | MEDLINE | ID: mdl-27091541

ABSTRACT

The two-dimensional (2D) or three-dimensional (3D) multiway power dividers based on transformation optical theory are proposed in this paper. It comprises of several nonisotropic mediums and one isotropic medium without any lumped and distributed elements. By using finite embedded coordinate transformations, the incident beam can be split and bent arbitrarily in order to achieve effective power division and transmission. In addition, the location of the split point can be employed to obtain unequal power dividers. Finally, several typical examples of the generalized power divider without limitation in 3D space are performed, which shows that the proposed power divider can implement required functions with arbitrary power division and arbitrary transmission paths. The excellent simulated results verify the novel design method for power dividers.

20.
Sci Rep ; 5: 16522, 2015 Nov 12.
Article in English | MEDLINE | ID: mdl-26558702

ABSTRACT

Microenvironments that modulate fate commitments of mesenchymal stromal cells (MSCs) are composed of chemical and physical cues, but the latter ones are much less investigated. Here we demonstrate that intermittent fluid shear stress (IFSS), a potent and physiologically relevant mechanical stimulus, regulates osteogenic differentiation of MSCs through Transient receptor potential melastatin 7 (TRPM7)-Osterix axis. Immunostaining showed the localization of TRPM7 near or at cell membrane upon IFSS, and calcium imaging analysis demonstrated the transient increase of cytosolic free calcium. Expressions of osteogenic marker genes including Osterix, but not Runx2, were upregulated after three-hour IFSS. Phosphorylation of p38 and Smad1/5 was promoted by IFSS as well. TRPM7 gene knockdown abolished the promotion of bone-related gene expressions and phosphorylation. We illustrate that TRPM7 is mechanosensitive to shear force of 1.2 Pa, which is much lower than 98 Pa pressure loading reported recently, and mediates distinct mechanotransduction pathways. Additionally, our results suggest the differential roles of TRPM7 in endochondral and intramembranous ossification. Together, this study elucidates the mechanotransduction in MSCs fate commitments and displays an efficient mechano-modulation for MSCs osteogenic differentiation. Such findings should be taken into consideration when designing relevant scaffolds and microfluidic devices for osteogenic induction in the future.


Subject(s)
Mechanotransduction, Cellular , Mesenchymal Stem Cells/metabolism , Osteogenesis , Stress, Mechanical , TRPM Cation Channels/genetics , Animals , Biomarkers , Calcium/metabolism , Cell Differentiation , Cytoskeleton/metabolism , Gene Expression , Gene Expression Profiling , Gene Knockdown Techniques , Mechanotransduction, Cellular/genetics , Mice , Osteogenesis/genetics , Phosphorylation , Protein Transport , Smad1 Protein/metabolism , Smad5 Protein/metabolism , TRPM Cation Channels/antagonists & inhibitors , TRPM Cation Channels/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
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