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1.
J Exp Clin Cancer Res ; 43(1): 170, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38886756

ABSTRACT

BACKGROUND: Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed. METHODS: An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3. Considering the challenges of limited pharmaco-accessibility to the bladder due to its pathophysiological structure and the partially undruggable nature of target molecules, we designed a dual siRNA system targeting both mRNAs. Subsequently, this dual siRNA system was encoded into the adenovirus 5/3 (Ad 5/3) to enhance in vivo delivery efficiency. RESULTS: Gene-targeting efficacy was assessed using cells isolated from xenografted tumors using a single-cell analysis system. Our strategy demonstrated a balanced downregulation of mTOR and STAT3 at the single-cell resolution, both in vitro and in vivo. This approach reduced tumor growth in bladder cancer xenograft and orthotopic animal experiments. In addition, increased infiltration of CD8+ T cells was observed in a humanized mouse model. We provided helpful and safe tissue distribution data for intravesical therapy of siRNAs coding adenoviruses. CONCLUSIONS: The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with "undruggability." Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses.


Subject(s)
STAT3 Transcription Factor , TOR Serine-Threonine Kinases , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/therapy , Humans , STAT3 Transcription Factor/metabolism , Animals , Mice , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , Administration, Intravesical , Female , Cell Line, Tumor , Xenograft Model Antitumor Assays
2.
Exp Mol Med ; 56(4): 904-921, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38556548

ABSTRACT

Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss. This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved muscle regeneration in animals with Duchenne muscular dystrophy (DMD) and facilitated muscle and fat recovery in animals with chemotherapy-induced sarcopenia. As an FDA-approved drug, dimenhydrinate could be applied for sarcopenia treatment after a relatively short development period, providing hope for individuals suffering from this debilitating condition.


Subject(s)
Autophagy , Transcriptome , Animals , Autophagy/drug effects , Mice , Humans , Protein Biosynthesis/drug effects , Disease Models, Animal , Muscle, Skeletal/metabolism , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Gene Expression Profiling , Sarcopenia/drug therapy , Sarcopenia/metabolism , Sarcopenia/pathology , Muscular Dystrophy, Duchenne/drug therapy , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/metabolism , Muscular Dystrophy, Duchenne/pathology
3.
Biomater Sci ; 12(2): 479-494, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38090986

ABSTRACT

Cartilage defects can be difficult to heal, potentially leading to complications such as osteoarthritis. Recently, a tissue engineering approach that uses scaffolds and growth factors has been proposed to regenerate new cartilage tissues. Herein, we investigated the application of hyaluronic acid (HA) gel loaded with transforming growth factor-beta 3 (TGF-ß3) for enhanced cartilage regeneration. We assessed the clinical conditions required to efficiently enhance the ability of the modified HA gel to repair defective cartilage. Based on our findings, the prepared HA gel exhibited good physicochemical and mechanical properties and was non-toxic and non-inflammatory. Moreover, HA gel-loaded TGF-ß3 (HAT) had improved biocompatibility and promoted the synthesis of cartilage-specific matrix and collagen, further improving its ability to repair defects. The application of HAT resulted in an initial burst release of HA, which degraded slowly in vivo. Finally, HAT combined with microfracture-inducing bone marrow stem cells could significantly improve the cartilage microenvironment and regeneration of cartilage defects. Our results indicate that HA is a suitable material for developing growth factor carriers, whereas HAT is a promising candidate for cartilage regeneration. Furthermore, this differentiated strategy provides a rapid and effective clinical approach for next-generation cartilage regeneration.


Subject(s)
Hyaluronic Acid , Mesenchymal Stem Cells , Hyaluronic Acid/chemistry , Transforming Growth Factor beta3/chemistry , Hydrogels/chemistry , Cartilage/metabolism , Transforming Growth Factors/metabolism , Transforming Growth Factors/pharmacology
4.
Korean J Neurotrauma ; 19(2): 218-226, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37431381

ABSTRACT

Objective: The patient with electrically injured myelopathy showed mild motor weakness without somatosensory pathway abnormalities. Few reports have been reported on the pathophysiological mechanisms of electrically injured myelopathy, and there is controversy about the exact pathological causes. This study aimed to investigate the ultrastructural changes in the electron microscopic findings of electrical spinal cord injury. Methods: Nine rats were used in this study. We performed 7 electrical shocks (frequency, 120 Hz; pulse width, 0.9 ms; duration, 3 seconds; current, 99 mA) using an electroconvulsive therapy (ECT) apparatus (57800 ECT unit; UGO BASILE). We used one ear and one contralateral hind limb as entry and exit sites, respectively. We only enrolled rats with hind limb weakness and performed electron microscopy evaluations of the spinal cord on the first day and 4 weeks after injury. Results: On the first day after injury, an electron microscopic examination showed a directly damaged area that appeared to be torn as physical damage, damaged myelin sheath, vacuolated axons in the myelin sheath, swollen Golgi apparatus, and injured mitochondria. Looking at changes in motor and sensory nerves, the sensory neurons showed recovered mitochondria and Golgi apparatus 4 weeks after injury; however, motor neurons still showed injured mitochondria, swollen Golgi apparatus, and endoplasmic reticulum. Conclusion: This study showed that recovery from ultrastructural injury was more rapid in sensory neurons than in motor neurons.

5.
Int J Biol Macromol ; 229: 486-495, 2023 Feb 28.
Article in English | MEDLINE | ID: mdl-36587641

ABSTRACT

Collagen, with low antigenicity and excellent cell adhesion, is a biomaterial mainly used for regenerating bone, cartilage, and skin, owing to its biocompatibility and biodegradability. Results from a previous study confirmed that a scaffold mixed with duck feet-derived collagen (DC) and Poly(lactic-co-glycolic acid) (PLGA) reduced inflammatory reaction and increased bone regeneration. To develop an optimal bone substitute we included hydroxyapatite (HAp), a key osteoconductive material, in a DC and PLGA mixture. We fabricated 0, 10, 20, 40, 60, and 80 wt% DC/PLGA/HAp scaffolds and studied their potential for bone tissue engineering. Characteristic analysis of the scaffold and seeding of rabbit bone marrow mesenchymal stem cells (rBMSCs) on the scaffold were conducted to investigate cell proliferation, osteogenic differentiation, and bone formation. We confirmed that increasing DC concentration not only improved the compressive strength of the DC/PLGA/HAp scaffold but also cell proliferation and osteogenic differentiation. It was found through comparison with previous studies that including HAp in the scaffold also promotes osteogenic differentiation. Our study thus shows through in vivo results that the 80 wt% DC/PLGA/HAp scaffold promotes bone mineralization and collagen deposition while reducing the inflammatory response. Hence, 80 wt% DC/PLGA/HAp has excellent potential as a biomaterial for bone regeneration applications.


Subject(s)
Durapatite , Osteogenesis , Animals , Rabbits , Durapatite/pharmacology , Polylactic Acid-Polyglycolic Acid Copolymer , Ducks , Tissue Scaffolds , Glycols , Bone Regeneration/physiology , Biocompatible Materials , Tissue Engineering/methods , Collagen
6.
Mol Neurobiol ; 60(1): 145-159, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36242734

ABSTRACT

Although a couple of studies have reported that mutant superoxide dismutase 1 (SOD1), one of the causative genes of familial amyotrophic lateral, interacts physically with lysyl-tRNA synthetase (KARS1) by a gain of function, there is limited evidence regarding the detailed mechanism about how the interaction leads to neuronal cell death. Our results indicated that the aminoacyl-tRNA synthetase-interacting multi-functional protein 2 (AIMP2) mediated cell death upon the interplay between mutant SOD1 and KARS1 in ALS. Binding of mutant SOD1 with KARS1 led to the release of AIMP2 from its original binding partner KARS1, and the free form of AIMP2 induced TRAF2 degradation followed by TNF-α-induced cell death. We also suggest a therapeutic application that overexpression of DX2, the exon 2-deleted antagonistic splicing variant of AIMP2 (AIMP2-DX2), reduced neuronal cell death in the ALS mouse model. Expression of DX2 suppressed TRAF2 degradation and TNF-α-induced cell death by competing mode of action against full-length AIMP2. Motor neuron differentiated form iPSC showed a resistance in neuronal cell death after DX2 administration. Further, intrathecal administration of DX2-coding adeno-associated virus (AAV) improved locomotive activity and survival in a mutant SOD1-induced ALS mouse model. Taken together, these results indicated that DX2 could prolong life span and delay the ALS symptoms through compensation in neuronal inflammation.


Subject(s)
Amyotrophic Lateral Sclerosis , Nuclear Proteins , Animals , Mice , Cell Death , Cell Line, Tumor , Mutation , Nuclear Proteins/metabolism , Superoxide Dismutase-1/metabolism , TNF Receptor-Associated Factor 2/genetics , TNF Receptor-Associated Factor 2/metabolism , Tumor Necrosis Factor-alpha/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Protein Isoforms
7.
Cancer Biomark ; 35(1): 99-109, 2022.
Article in English | MEDLINE | ID: mdl-35912727

ABSTRACT

BACKGROUND: Although lysyl-tRNA synthetase (KARS1) is predominantly located in the cytosol, it is also present in the plasma membrane where it stabilizes the 67-kDa laminin receptor (67LR). This physical interaction is strongly increased under metastatic conditions. However, the dynamic interaction of these two proteins and the turnover of KARS1 in the plasma membrane has not previously been investigated. OBJECTIVE: Our objective in this study was to identify the membranous location of KARS1 and 67LR and investigate if this changes with the developmental stage of epithelial ovarian cancer (EOC) and treatment with the inhibitor BC-K01. In addition, we evaluated the therapeutic efficacy of BC-K01 in combination with paclitaxel, as the latter is frequently used to treat patients with EOC. METHODS: Overall survival and prognostic significance were determined in EOC patients according to KARS1 and 67LR expression levels as determined by immunohistochemistry. Changes in the location and expression of KARS1 and 67LR were investigated in vitro after BC-K01 treatment. The effects of this compound on tumor growth and apoptosis were evaluated both in vitro and in vivo. RESULTS: EOC patients with high KARS1 and high 67LR expression had lower progression-free survival rates than those with low expression levels of these two markers. BC-K01 reduced cell viability and increased apoptosis in combination with paclitaxel in EOC cell xenograft mouse models. BC-K01 decreased membranous KARS1 expression, causing a reduction in 67LR membrane expression in EOC cell lines. BC-K01 significantly decreased in vivo tumor weight and number of nodules, especially when used in combination with paclitaxel. CONCLUSIONS: Co-localization of KARS1 and 67LR in the plasma membrane contributes to EOC progression. Inhibition of the KARS1-67LR interaction by BC-K01 suppresses metastasis in EOC.


Subject(s)
Lysine-tRNA Ligase , Ovarian Neoplasms , Animals , Carcinoma, Ovarian Epithelial/drug therapy , Cell Adhesion Molecules , Female , Humans , Lysine-tRNA Ligase/metabolism , Mice , Ovarian Neoplasms/drug therapy , Paclitaxel/pharmacology , Receptors, Laminin/genetics , Receptors, Laminin/metabolism , Ribosomal Proteins/genetics
8.
J Korean Assoc Oral Maxillofac Surg ; 48(4): 219-224, 2022 Aug 31.
Article in English | MEDLINE | ID: mdl-36043252

ABSTRACT

Objectives: There have been few studies to date on the residual effect of bisphosphonate. This study investigated the radiographic changes of mandibular cortical thickness upon bisphosphonate drug holiday. Materials and Methods: This retrospective study includes 36 patients diagnosed with MRONJ (medication-related osteonecrosis of the jaw) at Ajou University Dental Hospital in 2010-2021. All patients stopped taking bisphosphonate under consultation with the prescribing physicians. Panoramic radiographs were taken at the start of discontinuation (T0), 12 months after (T1), and 18 months after (T2) discontinuation of bisphosphonate, respectively. Mental index and panoramic mandibular index were calculated using Ledgerton's method. Paired t-tests were used to analyze differences over time. Results: The difference in indices (mental index and panoramic mandibular index) between T0 and T1 was not statistically significant (paired t-test, P>0.05). However, the difference in these indices between T1 and T2 was statistically significant (paired t-test, P<0.05). Conclusion: The cortical thickness of the mandible decreased in the late stage (after 18 months) as observed by panoramic radiograph.

9.
ACS Biomater Sci Eng ; 8(2): 588-597, 2022 02 14.
Article in English | MEDLINE | ID: mdl-34994537

ABSTRACT

To improve the mechanical properties of collagen hydrogels, which are widely utilized as biomaterials, post-cross-linking of collagen hydrogels was performed using polyrotaxane (PRX) as a cross-linker. Herein, carboxymethyl group-modified PRXs (CMPRs) composed of carboxymethylated α-cyclodextrins (α-CDs) threaded along poly(ethylene glycol) (PEG) capped with bulky stoppers were used to cross-link via reaction with the amino groups in the collagen. Four series of CMPRs with different α-CD threading ratios and axle PEG molecular weights were used for the post-cross-linking of the collagen hydrogels to verify the optimal CMPR chemical compositions. The post-cross-linking of the collagen hydrogels with CMPRs improved the swelling ratios and mechanical properties, such as viscoelasticity and tensile strength. Among the tested CMPRs, CMPRs with an axle PEG molecular weight of 35,000 (PEG35k) resulted in better mechanical properties than CMPRs with a PEG10k axis. Additionally, the cell adhesion and proliferation were greatly improved on the surface of the collagen hydrogels post-cross-linked with CMPRs with the PEG35k axle. These findings suggest that the molecular weight of an axle polymer in CMPRs is a more important parameter than the α-CD threading ratios. Accordingly, the post-cross-linking of hydrogels with PRXs is promising for improving the mechanical properties and biomaterial functions of collagen hydrogels.


Subject(s)
Rotaxanes , Cell Proliferation , Collagen/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Rotaxanes/chemistry , Rotaxanes/metabolism , Rotaxanes/pharmacology
10.
J Biomater Sci Polym Ed ; 33(6): 769-782, 2022 04.
Article in English | MEDLINE | ID: mdl-34913857

ABSTRACT

Collagen, a natural biomaterial derived from animal tissues, has attracted the attention of biomedical material researchers because of its excellent cell affinity and low rejection in vivo. In this study, collagen was extracted using livestock by-product flippers, and an experiment was performed to assess its application as a scaffold for bone tissue implantation. For this purpose, we fabricated 2%, and 3% duck's feet derived collagen (DC) sponges. We then compared them to hydroxyapatite (HAp)-coated DC sponges, and measured the porosity and pore size using scanning electron microscopy (SEM) to analyze the physical properties and morphology of DC and DC/HAp sponges. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were carried out to measure the proliferation of bone marrow stem cells (BMSCs) in DC and DC/HAp sponges. An alkaline phosphatase activity assay confirmed the osteogenic differentiation ability of BMSCs. Polymerase chain reaction (PCR) was performed to confirm the BMSC-specific genetic marker. The osteogenic potential was confirmed by the bone formation in an in vivo environment on the scaffold by histological and immunohistochemical analysis. Overall, this study shows that DC/HAp sponges have biocompatibility and good physical properties. Additionally, DC/HAp sponges show potential use as bone graft materials for tissue engineering applications.


Subject(s)
Ducks , Durapatite , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biomimetics , Bone Regeneration , Collagen/chemistry , Durapatite/chemistry , Osteogenesis , Tissue Engineering , Tissue Scaffolds/chemistry
11.
Polymers (Basel) ; 13(19)2021 Sep 26.
Article in English | MEDLINE | ID: mdl-34641097

ABSTRACT

Wound recovery close to the function of the native skin is the goal of wound healing. In this study, we prepared foam dressings (FDs; 2-GHC-FD-1-9, 5-GHC-FD-1-9, and 10-GHC-FD-1-9) composed of various concentrations of gelatin, hyaluronic acid, and carboxymethyl chitosan, which are chemically interconnected through amide bond formation, for evaluating wound healing. Tensile and cell proliferation tests showed that 2-GHC-FD-1-9 are suitable for wound dressing. For further evaluation, three types of FDs, 2-GHC-FD-1, 2-GHC-FD-4, and 2-GHC-FD-8 were chosen. The results of animal intradermal reactivity, water vapor transmission rate, and absorption rate of the three FDs indicated that 2-GHC-FD-8 is the most appropriate scaffold for wound healing. For wound healing acceleration, various concentrations of fibroblast growth factor-7 (FGF-7) was soaked in 2-GHC-FD-8 (2-GHC-FD-8/F1-6) and evaluated by using scanning electron microscopy, cell proliferation, release behavior, and in vivo animal tests. The FDs showed interconnected porous structures, increased cell proliferation until 8.0 × 10-11 M, controlled release with initial burst within 1 h, and sustained release for 48 h. The results of the animal test showed an appropriate concentration of FGF-7 for wound healing. In addition, 2-GHC-FD-8 is a suitable scaffold for wound healing. Therefore, we suggest that 2-GHC-FD-8/F3 is a useful wound dressing for accelerating wound healing.

12.
RSC Adv ; 11(21): 12729-12738, 2021 Mar 29.
Article in English | MEDLINE | ID: mdl-35423796

ABSTRACT

Plasma-assisted nitrogen fixation is a promising sustainable and clean alternative to the classical Haber-Bosch process. However, the high energy consumption and low production rate of plasma-assisted nitrogen fixation limit its application. This study shows that the non-thermal (non-equilibrium) enhancement of the arc plasma significantly reduces the energy consumption of nitrogen fixation. The highest energy efficiency with high NO selectivity is observed with a low specific energy input (SEI). However, the highest production rate is reached at a high SEI. The studied process offers high NO selectivity (up to 95%) with low energy consumption (∼48 GJ per tN) at 0.1 kJ L-1 SEI, which is much lower than the previously reported value of plasma-assisted atmospheric nitrogen fixation and is close to that of the Haber-Bosch process.

13.
Polymers (Basel) ; 12(12)2020 Dec 09.
Article in English | MEDLINE | ID: mdl-33317040

ABSTRACT

A gellan gum (GG) hydrogel must demonstrate a number of critical qualities-low viscosity, degradability, desirable mechanical properties, anti-swelling properties, and biocompatibility-in order to be regarded as suitable for retinal pigment epithelium (RPE) regeneration. In this study, we investigated whether the application of an eggshell membrane (ESM) to a GG hydrogel improved these critical attributes. The crosslinking of the ESM/GG hydrogels was most effectively reduced, when a 4 w/v% ESM was used, leading to a 40% less viscosity and a 30% higher degradation efficiency than a pure GG hydrogel. The compressive moduli of the ESM/GG hydrogels were maintained, as the smaller pores formed by the addition of the ESM compensated for the slightly weakened mechanical properties of the ESM/GG hydrogels. Meanwhile, due to the relatively low hydrophilicity of ESM, a 4 w/v% ESM enabled an ESM/GG hydrogel to swell 30% less than a pure GG hydrogel. Finally, the similarity in components between the ESM and RPE cells facilitated the proliferation of the latter without any significant cytotoxicity.

14.
Oral Health Prev Dent ; 18(1): 799-806, 2020 Sep 04.
Article in English | MEDLINE | ID: mdl-32895664

ABSTRACT

PURPOSE: Periodontitis is characterised by inflammation of periodontium and alveolar bone loss. Gardenia jasminoides is reported to have anti-inflammatory effects. In this study, we investigated the effects of aqueous extract of G. jasminoides (GJ) on periodontitis. MATERIALS AND METHODS: Male Sprague-Dawley rats aged 7 weeks were randomly placed in three groups (n = 7); non-ligatured and non-treated (NL group), ligatured and distilled water-treated (L group) and ligatured and 100 mg/kg GJ-treated (GJ group). After oral administration of GJ for 14 days, the mandibles were removed for histology. In addition, RAW 264.7 cells were treated with 100 ng/ml receptor activator of nuclear factor-κΒ ligand (RANKL) and 1, 10 and 100 µg/ml GJ for 7 days to analyse the expression of periodontitis-related factors. RESULTS: In GJ-treated mice, the score of alveolar bone loss was statistically significantly attenuated compared with the L group. GJ treatment showed inhibition effect in the progress of cementum demineralisation. The expressions of proinflammatory cytokines in gingival tissue were statistically significantly regulated by GJ treatment. Additionally, GJ treatment showed the dose-dependent inhibition of RANKL-induced osteoclast formation. Furthermore, GJ treatment downregulated the RANKL-induced cytokine production in RAW 264.7 cells. CONCLUSION: In summary, GJ ameliorated periodontitis-induced alveolar bone loss via inhibiting transcription factors including nuclear factor-κB, c-fos and extracellular signal-regulated kinase signalling. Therefore, GJ might be a therapeutic option for treating periodontitis.


Subject(s)
Alveolar Bone Loss , Gardenia , Periodontitis , Animals , Male , Mice , Osteoclasts , Rats , Rats, Sprague-Dawley
15.
Environ Int ; 145: 106113, 2020 12.
Article in English | MEDLINE | ID: mdl-32947162

ABSTRACT

Activated carbon has been extensively utilized to adsorb pollutants generated by industrial activities. There have been many attempts to efficiently produce activated carbon from spent coffee grounds in the field of environmental technology. In this study, the feasibility of the novel production of activated carbon from coffee ground waste using a plasma jet was evaluated. A rotating gliding arc generator was designed that used an N2 plasma jet for the carbonization process and a CO2 plasma jet for the activation process. It was confirmed that the coffee ground waste could be carbonized and activated by the two plasma jets in the same reactor. The characteristics of the surface morphologies of the activated carbon samples varied depending on the plasma treatment conditions, such as the electric power of the plasma jet and the treatment time. The results implied that the adsorption capacity of the activated carbon could be optimized by regulating the pore size and distribution based on the plasma treatment conditions with regard to the molecular size of the target adsorbate.


Subject(s)
Charcoal , Coffee , Adsorption , Plasma
16.
Polymers (Basel) ; 11(12)2019 Dec 14.
Article in English | MEDLINE | ID: mdl-31847323

ABSTRACT

The cytocompatibility of biological and synthetic materials is an important issue for biomaterials. Gelatin hydrogels are used as biomaterials because of their biodegradability. We have previously reported that the mechanical properties of gelatin hydrogels are improved by cross-linking with polyrotaxanes, a supramolecular compound composed of many cyclic molecules threaded with a linear polymer. In this study, the ability of gelatin hydrogels cross-linked by polyrotaxanes (polyrotaxane-gelatin hydrogels) for cell cultivation was investigated. Because the amount of polyrotaxanes used for gelatin fabrication is very small, the chemical composition was barely altered. The structure and wettability of these hydrogels are also the same as those of conventional hydrogels. Fibroblasts adhered on polyrotaxane-gelatin hydrogels and conventional hydrogels without any reduction or apoptosis of adherent cells. From these results, the polyrotaxane-gelatin hydrogels have the potential to improve the mechanical properties of gelatin without affecting cytocompatibility. Interestingly, when cells were cultured on polyrotaxane-gelatin hydrogels after repeated stress deformation, the cells were spontaneously oriented to the stretching direction. This cellular response was not observed on conventional hydrogels. These results suggest that the use of a polyrotaxane cross-linking agent can not only improve the strength of hydrogels but can also contribute to controlling reorientation of the gelatin.

17.
Polymers (Basel) ; 11(11)2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31683825

ABSTRACT

Tough mechanical properties are generally required for tissue substitutes used in regeneration of damaged tissue, as these substitutes must be able to withstand the external physical force caused by stretching. Gelatin, a biopolymer derived from collagen, is a biocompatible and cell adhesive material, and is thus widely utilized as a component of biomaterials. However, the application of gelatin hydrogels as a tissue substitute is limited owing to their insufficient mechanical properties. Chemical cross-linking is a promising method to improve the mechanical properties of hydrogels. We examined the potential of the chemical cross-linking of gelatin hydrogels with carboxy-group-modified polyrotaxanes (PRXs), a supramolecular polymer comprising a poly(ethylene glycol) chain threaded into the cavity of α-cyclodextrins (α-CDs), to improve mechanical properties such as stretchability and toughness. Cross-linking gelatin hydrogels with threading α-CDs in PRXs could allow for freely mobile cross-linking points to potentially improve the mechanical properties. Indeed, the stretchability and toughness of gelatin hydrogels cross-linked with PRXs were slightly higher than those of the hydrogels with the conventional chemical cross-linkers 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS). In addition, the hysteresis loss of gelatin hydrogels cross-linked with PRXs after repeated stretching and relaxation cycles in a hydrated state was remarkably improved in comparison with that of conventional cross-linked hydrogels. It is considered that the freely mobile cross-linking points of gelatin hydrogels cross-linked with PRXs attenuates the stress concentration. Accordingly, gelatin hydrogels cross-linked with PRXs would provide excellent mechanical properties as biocompatible tissue substitutes exposed to a continuous external physical force.

18.
Phytomedicine ; 59: 152900, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30974310

ABSTRACT

BACKGROUND: Extracts derived from natural products have been used to produce health supplements or therapeutic agents in oriental medicine. Although these extracts contain various bioactive compounds, their applications are generally limited to a few previously known diseases. To effectively expand their use for the treatment of other conditions, systematic analysis should be conducted for repurposing. PURPOSE: The purpose of the present study was to investigate the new therapeutic efficacies of the Platycodon grandiflorum and ginseng extract using the CMAP-based gene expression analysis. METHODS: In the present study, we analyzed the expression patterns of differentially expressed genes (DEGs) from extracts as the basis for drug repurposing. Cells were treated with extracts or single compounds derived from nine natural products. DEG analysis indicated that the gene expression patterns of cells treated with P. grandiflorum and ginseng extracts were highly similar to those of cells treated with different types of Histone deacetylase (HDAC) inhibitors. To identify the new mechanism of these extracts, we carried out cell viability assay, TUNEL assay, HDAC enzyme activity assay and immunoblot analysis. RESULTS: In vitro experiments at the dose of 50 µg/ml of each extract did not affect cell death rate but significantly inhibited HDAC activity. Each extract was found to inhibit HDAC enzymatic activity and induce the expression of the p21. Furthermore, our results revealed that each extract stimulated cell death and inhibited cell proliferation. CONCLUSION: These findings demonstrate the HDAC-inhibiting activity of P. grandiflorum and ginseng extracts and further validate the effectiveness of DEG similarity-based repurposing of natural products.


Subject(s)
Biological Products/pharmacology , Drug Repositioning/methods , Histone Deacetylase Inhibitors/pharmacology , Plant Extracts/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Panax/chemistry , Platycodon/chemistry , Transcriptome/drug effects
19.
RSC Adv ; 9(56): 32403-32413, 2019 Oct 10.
Article in English | MEDLINE | ID: mdl-35529722

ABSTRACT

The proliferation of natural gas production had led to increased utilization of methane as a raw material for chemicals. The most significant bottleneck in this process is the high activation energy of methane. This paper reports the direct conversion of methane to acetylene in a novel rotating arc driven by AC electrical power. By feeding a sufficiently high concentration of CH4 (greater than 43%) diluted in H2 (the discharge gas) through the arc column, a low specific energy requirement (SER) of 10.2 kW h kg-1 C2H2 was achieved. The use of hydrogen as the discharge gas strongly suppressed soot formation during the methane conversion process under high methane concentration conditions, resulting in a carbon balance of greater than 95% and a C2H2 selectivity of greater than 90% while maintaining a methane conversion rate of greater than 70%, depending on the conditions. The novel rotating arc enabled the elongation of the arc column itself, which controlled heat loss and improved the energy use for reaction. The ability to control the arc length based on low-current type arc generation has additional benefits for reaction enhancement. These results demonstrate that arc control, optimization of the reaction conditions, and a full understanding of reaction pathway are viable means for the energy-efficient direct conversion of methane to acetylene.

20.
J Nanosci Nanotechnol ; 19(2): 932-935, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30360175

ABSTRACT

This paper describes utilization of dielectric barrier discharge (DBD) plasma interaction with impregnated surface nano-particles for plasma applications. The plasma generation characteristics on DBD plasma actuator and packed-bed reactor are investigated with unexpected objects as impregnated catalysts. The streamer generation of DBD plasma is influenced by different surface nano-particles of the impregnated catalyst between the discharge gaps. The practical use of DBD plasma-catalyst interaction is discussed.

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