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1.
Gigascience ; 132024 Jan 02.
Article in English | MEDLINE | ID: mdl-38626723

ABSTRACT

BACKGROUND: Phenome-wide association studies (PheWASs) have been conducted on Asian populations, including Koreans, but many were based on chip or exome genotyping data. Such studies have limitations regarding whole genome-wide association analysis, making it crucial to have genome-to-phenome association information with the largest possible whole genome and matched phenome data to conduct further population-genome studies and develop health care services based on population genomics. RESULTS: Here, we present 4,157 whole genome sequences (Korea4K) coupled with 107 health check-up parameters as the largest genomic resource of the Korean Genome Project. It encompasses most of the variants with allele frequency >0.001 in Koreans, indicating that it sufficiently covered most of the common and rare genetic variants with commonly measured phenotypes for Koreans. Korea4K provides 45,537,252 variants, and half of them were not present in Korea1K (1,094 samples). We also identified 1,356 new genotype-phenotype associations that were not found by the Korea1K dataset. Phenomics analyses further revealed 24 significant genetic correlations, 14 pleiotropic associations, and 127 causal relationships based on Mendelian randomization among 37 traits. In addition, the Korea4K imputation reference panel, the largest Korean variants reference to date, showed a superior imputation performance to Korea1K across all allele frequency categories. CONCLUSIONS: Collectively, Korea4K provides not only the largest Korean genome data but also corresponding health check-up parameters and novel genome-phenome associations. The large-scale pathological whole genome-wide omics data will become a powerful set for genome-phenome level association studies to discover causal markers for the prediction and diagnosis of health conditions in future studies.


Subject(s)
Genome-Wide Association Study , Polymorphism, Single Nucleotide , Humans , Phenotype , Genetic Association Studies , Gene Frequency , Republic of Korea , Genotype
2.
Sensors (Basel) ; 24(7)2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38610573

ABSTRACT

A force plate is mainly used in biomechanics; it aims to measure the ground reaction force in a person's walking or standing position. In this study, a large-area force mat of the piezoresistance sensing type was developed, and a deep-learning-based weight measurement calibration method was applied to solve the problem in which measurements are not normalized because of physical limitations in hardware and signal processing. The test set was composed of the values measured at each point by weight and the value of the center of the pressure variable, and the measured value was predicted using a deep neural network (DNN) regression model. The calibration verification results show that the average weight errors range from a minimum of 0.06% to a maximum of 3.334%. This is simpler than the previous method, which directly measures the ratio of the resistance value to the measured weight of each sensor and derives an equation.

3.
J Acupunct Meridian Stud ; 17(2): 55-68, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38686429

ABSTRACT

Background: Parkinson's disease (PD) lacks disease-modifying drugs or sustainable interventions, creating an unmet treatment need. Investigating complementary and alternative medicines aims to improve PD patients' quality of life by alleviating symptoms and delaying the course of the disease. Objectives: In this single-center, prospective, observational, single-arm study, we aimed to assess the effectiveness and safety of acupuncture combined with exercise therapy and the Meridian Activation Remedy System (MARS). Methods: From March to October 2021, 13 PD patients with Hoehn and Yahr stages 1 to 3 were recruited. For 8 weeks, MARS intervention was carried out twice a week. T-statistics were used to evaluate functional near-infrared spectroscopy (fNIRS) and GAITRite outcomes. All of the remaining outcome variables were evaluated using the Wilcoxon signed-rank test. Results: The MARS intervention significantly reduced PD patients' Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDSUPDRS) Part III score (from 20.0 ± 11.8 to 8.8 ± 5.5, p = 0.003), 10-meter walk test speed (from 9.5 ± 1.8 to 8.7 ± 1.3 seconds, p = 0.040), and timed up and go time (from 9.8 ± 1.8 to 8.9 ± 1.4 seconds, p = 0.040). Moreover, the MDS-UPDRS Part II, fNIRS hemodynamics, 360-degree turn test, fall efficacy scale, and Parkinson's Disease Questionnaire 39 scores improved but not significantly. All participants completed the 8-week intervention without any adverse reactions. Conclusion: An 8-week MARS intervention improved motor symptoms in PD patients. In particular, improvements in UPDRS Part III scores exhibited large clinically important differences. The findings are encouraging, and a randomized controlled trial will be conducted to determine the efficacy and cost-effectiveness of MARS intervention.


Subject(s)
Acupuncture Therapy , Meridians , Parkinson Disease , Humans , Parkinson Disease/therapy , Parkinson Disease/physiopathology , Female , Male , Aged , Middle Aged , Prospective Studies , Acupuncture Therapy/methods , Treatment Outcome , Exercise Therapy/methods
4.
ACS Appl Mater Interfaces ; 16(9): 12095-12105, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38384197

ABSTRACT

Two-dimensional transition metal dichalcogenides (2D TMDCs) are considered promising alternatives to Si as channel materials because of the possibility of retaining their superior electronic transport properties even at atomic body thicknesses. However, the realization of high-performance 2D TMDC field-effect transistors remains a challenge owing to Fermi-level pinning (FLP) caused by gap states and the inherent high Schottky barrier height (SBH) within the metal contact and channel layer. This study demonstrates that high-quality van der Waals (vdW) heterojunction-based contacts can be formed by depositing semimetallic TiS2 onto monolayer (ML) MoS2. After confirming the successful formation of a TiS2/ML MoS2 heterojunction, the contact properties of vdW semimetal TiS2 were thoroughly investigated. With clean interfaces of the TiS2/ML MoS2 heterojunctions, atomic-layer-deposited TiS2 can induce gap-state saturation and suppress FLP. Consequently, compared with conventional evaporated metal electrodes, the TiS2/ML MoS2 heterojunctions exhibit a lower SBH of 8.54 meV and better contact properties. This, in turn, substantially improves the overall performance of the device, including its on-current, subthreshold swing, and threshold voltage. Furthermore, we believe that our proposed strategy for vdW-based contact formation will contribute to the development of 2D materials used in next-generation electronics.

5.
Biomed Pharmacother ; 171: 116153, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38232664

ABSTRACT

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease characterized by persistent inflammation and joint destruction. A lipid mediator (LM, namely, 17S-monohydroxy docosahexaenoic acid, resolvin D5, and protectin DX in a ratio of 3:47:50) produced by soybean lipoxygenase from DHA, exhibits anti-inflammatory activity. In this study, we determined the effect of LM on collagen antibody-induced arthritis (CAIA) in mice and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation in RAW264.7 cells. LM effectively downregulated the expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K, inhibited osteoclast formation, and suppressed the NF-κB signaling pathway in vitro. In vivo, LM at 10 µg/kg/day significantly decreased paw swelling and inhibited progression of arthritis in CAIA mice. Moreover, proinflammatory cytokine (tumor necrosis factor-α, interleukin (IL)-6, IL-1ß, IL-17, and interferon-γ) levels in serum were decreased, whereas IL-10 levels were increased following LM treatment. Furthermore, LM alleviated joint inflammation, cartilage erosion, and bone destruction in the ankles, which may be related to matrix metalloproteinase and Janus kinase (JAK)-signal transducer and activators of transcription (STAT) signaling pathway. Our findings suggest that LM attenuates arthritis severity, restores serum imbalances, and modifies joint damage. Thus, LM represents a promising therapy for relieving RA symptoms.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Mice , Animals , Osteoclasts , RANK Ligand/metabolism , Glycine max , Docosahexaenoic Acids/pharmacology , Arthritis, Rheumatoid/metabolism , Arthritis, Experimental/pathology , Inflammation/metabolism , Lipoxygenases/metabolism , Lipoxygenases/pharmacology
6.
Tissue Eng Regen Med ; 21(2): 209-221, 2024 02.
Article in English | MEDLINE | ID: mdl-37837499

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is characterized by chronic inflammation and joint damage. Methotrexate (MTX), a commonly used disease-modifying anti-rheumatic drug (DMARD) used in RA treatment. However, the continued use of DMARDs can cause adverse effects and result in limited therapeutic efficacy. Cartilage extracellular matrix (CECM) has anti-inflammatory and anti-vascular effects and promotes stem cell migration, adhesion, and differentiation into cartilage cells. METHODS: CECM was assessed the dsDNA, glycosaminoglycan, collagen contents and FT-IR spectrum of CECM. Furthermore, we determined the effects of CECM and MTX on cytocompatibility in the SW 982 cells and RAW 264.7 cells. The anti-inflammatory effects of CECM and MTX were assessed using macrophage cells. Finally, we examined the in vivo effects of CECM in combination with MTX on anti-inflammation control and cartilage degradation in collagen-induced arthritis model. Anti-inflammation control and cartilage degradation were assessed by measuring the serum levels of RA-related cytokines and histology. RESULTS: CECM in combination with MTX had no effect on SW 982, effectively suppressing only RAW 264.7 activity. Moreover, anti-inflammatory effects were enhanced when low-dose MTX was combined with CECM. In a collagen-induced arthritis model, low-dose MTX combined with CECM remarkably reduced RA-related and pro-inflammatory cytokine levels in the blood. Additionally, low-dose MTX combined with CECM exerted the best cartilage-preservation effects compared to those observed in the other therapy groups. CONCLUSION: Using CECM as an adjuvant in RA treatment can augment the therapeutic effects of MTX, reduce existing drug adverse effects, and promote joint tissue regeneration.


Subject(s)
Antirheumatic Agents , Arthritis, Experimental , Arthritis, Rheumatoid , Animals , Humans , Methotrexate/pharmacology , Methotrexate/therapeutic use , Arthritis, Experimental/drug therapy , Arthritis, Experimental/pathology , Spectroscopy, Fourier Transform Infrared , Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Cytokines/metabolism , Extracellular Matrix/metabolism , Anti-Inflammatory Agents , Cartilage/metabolism
7.
Angew Chem Int Ed Engl ; 62(48): e202312928, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-37842904

ABSTRACT

High-capacity Li-rich layered oxides using oxygen redox as well as transition metal redox suffer from its structural instability due to lattice oxygen escaped from its structure during oxygen redox and the following electrolyte decomposition by the reactive oxygen species. Herein, we rescued a Li-rich layered oxide based on 4d transition metal by employing an organic superoxide dismutase mimics as a homogeneous electrolyte additive. Guaiacol scavenged superoxide radicals via dismutation or disproportionation to convert two superoxide molecules to peroxide and dioxygen after absorbing lithium superoxide on its partially negative oxygen of methoxy and hydroxyl groups. Additionally, guaiacol was decomposed to form a thin and stable cathode-electrolyte interphase (CEI) layer, endowing the cathode with the interfacial stability.

8.
Int Immunopharmacol ; 124(Pt A): 110900, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37708704

ABSTRACT

Atopic dermatitis (AD) is a chronic inflammatory skin condition that primarily results from immune dysregulation. We determined the potential therapeutic benefits of lipid mediators (LM, 17S-monohydroxy DHA, resolvin D5, and protectin DX in a ratio of 3:47:50) produced by soybean lipoxygenase from DHA. The underlying molecular mechanisms involved in TNF-α/IFN-γ-stimulated HaCaT cells as well as its effect in an AD mouse model induced by DNCB in BALB/c mice were examined. The results indicated that LM effectively attenuates the production of inflammatory cytokines (IL-6 and IL-1ß) and chemokines (IL-8 and MCP-1) by inhibiting the NF-κB signaling pathway in TNF-α/IFN-γ-stimulated HaCaT cells. The oral administration of LM at 5 or 10 µg/kg/day significantly reduced skin lesions, epidermal thickness, and mast cell infiltration in AD mice. Furthermore, LM reduced the production of IgE and inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in the serum, modulated gut microbiota diversity, and restored the microbial composition. Overall, our findings suggest that LM represents a potential therapeutic agent for improving AD symptoms through its ability to suppress inflammatory cytokines and alter the composition of gut microbiota.

9.
Bioengineering (Basel) ; 10(8)2023 Aug 08.
Article in English | MEDLINE | ID: mdl-37627828

ABSTRACT

BACKGROUND: The stability index estimation algorithm was derived and applied to develop and implement a balance ability diagnosis system that can be used in daily life. METHODS: The system integrated an approach based on sensory function interaction, called the clinical test of sensory interaction with balance. A capacitance and resistance sensing type force mat was fabricated, and a stability index prediction algorithm was developed and applied using the center of pressure variables. The stability index prediction algorithm derived a center of pressure variable for 103 elderly people by Nintendo Wii Balance Board to predict the stability index of the balance system (Biodex SD), and the accuracy of this approach was confirmed. RESULTS: As a result of testing with the test set, the linear regression model confirmed that the r-value ranged between 0.943 and 0.983. To confirm the similarity between the WBB and the flexible force mat, each measured center of pressure value was inputted and calculated in the developed regression model, and the result of the correlation coefficient validation confirmed an r-value of 0.96. CONCLUSION: The system developed in this study will be applicable to daily life in the home in the form of a floor mat.

10.
Sci Rep ; 13(1): 11600, 2023 Jul 18.
Article in English | MEDLINE | ID: mdl-37463993

ABSTRACT

A long-standing goal of CMOS-based logic devices is to meet the needs of key markets, including ultralow-power operation and high operation speed, along with the continuing miniaturization of the architecture. However, despite significant progress in their development, conventional CMOS-based devices still suffer from drawbacks such as introducing large unintended leakage currents and volatile behavior. Thus, reconfigurable logic gates based on magnetic domain (MD) have emerged as a highly promising option because they offer fast operation speeds, nonvolatility, and diverse logic functions in a single-device configuration. Here, we address multiple reconfigurable MD logic gates in a single two-channel Hall bar device by varying the voltage-driven read-current directions and selecting a non-inverting or inverting comparator in W/CoFeB/MgO/Ta stacks. The non-volatile MD switching behavior induced by spin-orbit torque significantly affects our logic gate functions, which are not necessarily synchronized to a single clock. By adapting MD switching by spin-orbit torque and anomalous Hall effect voltage outputs, we identified eight reconfigurable logic gates, including AND, NAND, NOR, OR, INH, Converse INH, Converse IMP, and IMP, in a single device. These experimental findings represent a significant step forward in a wide range of MD-based logic applications in the near future.

11.
Nano Lett ; 23(8): 3582-3591, 2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37027522

ABSTRACT

Over the past decade, lithium metal has been considered the most attractive anode material for high-energy-density batteries. However, its practical application has been hindered by its high reactivity with organic electrolytes and uncontrolled dendritic growth, resulting in poor Coulombic efficiency and cycle life. In this paper, we propose a design strategy for interface engineering using a conversion-type reaction of metal fluorides to evolve a LiF passivation layer and Li-M alloy. Particularly, we propose a LiF-modified Li-Mg-C electrode, which demonstrates stable long-term cycling for over 2000 h in common organic electrolytes with fluoroethylene carbonate (FEC) additives and over 700 h even without additives, suppressing unwanted side reactions and Li dendritic growth. With the help of phase diagrams, we found that solid-solution-based alloying not only facilitates the spontaneous evolution of a LiF layer and bulk alloy but also enables reversible Li plating/stripping inward to the bulk, compared with intermetallic compounds with finite Li solubility.

12.
Mar Drugs ; 21(2)2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36827121

ABSTRACT

Although the tumor bulk is initially reduced by 5-fluorouracil (5-FU), chemoresistance developed due to prolonged chemotherapy in colorectal cancer (CRC). The enrichment of cancer stem cells (CSCs) and the infiltration of tumor-associated macrophages (TAMs) contribute to chemoresistance and poor outcomes. A docosahexaenoic acid derivative developed by our group, 7S,15R-dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA), exerts antitumor effects against TAMs infiltration and CSCs enrichment in our previous study. The current study aimed to investigate whether diHEP-DPA was able to overcome chemoresistance to 5-FU in CRCs, together with the potential synergistic mechanisms in a CT26-BALB/c mouse model. Our results suggested that although 5-FU inhibited tumor growth, 5-FU enriched CSCs via the WNT/ß-catenin signaling pathway, resulting in chemoresistance in CRCs. However, we revealed that 5-FU promoted the infiltration of TAMs via the NF-kB signaling pathway and improved epithelial-mesenchymal transition (EMT) via the signal transducer and activator of the transcription 3 (STAT3) signaling pathway; these traits were believed to contribute to CSC activation. Furthermore, supplementation with diHEP-DPA could overcome drug resistance by decreasing the CSCs, suppressing the infiltration of TAMs, and inhibiting EMT progression. Additionally, the combinatorial treatment of diHEP-DPA and 5-FU effectively enhanced phagocytosis by blocking the CD47/signal regulatory protein alpha (SIRPα) axis. These findings present that diHEP-DPA is a potential therapeutic supplement to improve drug outcomes and suppress chemoresistance associated with the current 5-FU-based therapies for colorectal cancer.


Subject(s)
Colorectal Neoplasms , Fluorouracil , Mice , Animals , Humans , Fluorouracil/pharmacology , Drug Resistance, Neoplasm , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/pathology , Heterografts , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Wnt Signaling Pathway , Neoplastic Stem Cells
13.
Nutrients ; 15(2)2023 Jan 13.
Article in English | MEDLINE | ID: mdl-36678298

ABSTRACT

Although fish oil (FO) and lipid mediators (LM) derived from polyunsaturated fatty acids can prevent obesity, their combined effects and cellular metabolism remain unclear. Therefore, this study aimed to examine the potential protective and metabolic effects of FO in combination with LM (a mixture of 17S-monohydroxy docosahexaenoic acid, resolvin D5, and protectin DX [3:47:50], derived from docosahexaenoic acid (DHA)) on palmitic acid (PA)-induced HepG2 cells and high-fat- diet (HFD)-induced C57BL/6J mice after 9-week treatment. Lipid metabolism disorders and inflammation induced by HFD and PA were substantially reduced after FO and LM treatment. Further, FO and LM treatments reduced lipid accumulation by increasing fatty acid oxidation via peroxisome proliferator-activated receptor α and carnitine-palmitoyl transferase 1 as well as by decreasing fatty acid synthesis via sterol regulatory element-binding protein-1c and fatty acid synthase. Finally, FO and LM treatment reduced inflammation by blocking the NF-κB signaling pathway. Importantly, the combination of FO and LM exhibited more robust efficacy against nonalcoholic fatty liver disease, suggesting that FO supplemented with LM is a beneficial dietary strategy for treating this disease.


Subject(s)
Fish Oils , Lipid Metabolism , Animals , Humans , Mice , Diet, High-Fat , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/metabolism , Fish Oils/pharmacology , Fish Oils/metabolism , Hep G2 Cells , Inflammation/drug therapy , Inflammation/metabolism , Liver/metabolism , Mice, Inbred C57BL
14.
Arch Rehabil Res Clin Transl ; 5(4): 100274, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38163027

ABSTRACT

Objectives: To confirm the characteristics of gait events and muscle activity in the lower limbs of the affected and unaffected sides in patients with hemiplegia. Design: Cross-sectional study. Setting: Motion analysis laboratory of the Wonkwang University Gwangju Hospital. Participants: Outpatients, diagnosed with ischemic stroke more than 3 months and less than 9 months before participating in the study (N=29; 11 men, 18 women). Interventions: Not applicable. Main Outcome Measures: The gait event parameters and time- and frequency-domain electromyogram (EMG) parameters of the lower limbs of the affected and unaffected sides was determined using BTS motion capture with the Delsys Trigno Avanti EMG wireless system. Results: The swing time, stance phase, swing phase, single support phase, and median power frequency of the gastrocnemius muscle showed a significant difference between the affected and unaffected sides. Using a logistic regression model, the swing phase, single support phase, and median frequency of the gastrocnemius muscle were selected to classify the affected side. Conclusion: The single support phase of the affected side is shortened to reduce load bearing, which causes a reduction in the stance phase ratio. Unlike gait-event parameters, EMG data of hemiplegic stroke patients are difficult to generalize. Among them, the logistic regression model with some affected side parameters expected to be set as the severity and improvement baseline of the affected side. Additional data collection and generalization of muscle activity is required to improve the classification model.

15.
Nanotechnology ; 34(9)2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36541520

ABSTRACT

Tunnel field-effect transistors (TFETs) have garnered great interest as an option for the replacement of metal-oxide-semiconductor field-effect transistors owing to their extremely low off-current and fast switching suitable for low-power-consumption applications. However, conventional doped TFETs have the disadvantage of introducing undesirable random dopant fluctuation (RDF) events, which cause a large variance in the threshold voltage and ambipolar leakage current at negative gate voltages. In this study, a simple approach for charge plasma-based doping-less TFETs (DL-TFETs), including the Ge/Si bilayer frame, which affects the RDF and low on-current issues, was developed by the commercially available Silvaco Atlas device simulator. The use of the Ge/Si bilayer enhances the on-current and point subthreshold swing to 1.4 × 10-6A and 16.6 mV dec-1, respectively. In addition, the dependencies of the Ge/Si junction boundary position and Ge content were examined systematically to attain a firm understanding of the electrical features in DL-TFETs.

16.
Sensors (Basel) ; 22(22)2022 Nov 17.
Article in English | MEDLINE | ID: mdl-36433479

ABSTRACT

The Wii balance board (WBB) is a simplified force plate system used to evaluate the balancing ability of the elderly via a sensory interaction task to confirm a significant standing balance index. The accuracy of this system has been verified in previous studies. In this study, an instrumented and modified clinical test of sensory interaction on balance (i-mCTSIB) was performed on 84 elderly subjects, and the variables for center of pressure (CoP) were calculated using WBB for each task condition. The results indicate that the visual condition has a significant effect on the sway proprioceptive sensory variables with a foam condition as their complexity increases. In addition, the correlation between the variable and Berg Balance Scale was not confirmed since CTSIB is a sensory interaction on balance ability. Therefore, WBB can be used to evaluate balancing ability based on sensory interactions consisting of the surface condition.


Subject(s)
Video Games , Humans , Aged , Postural Balance , Proprioception
18.
Int J Biol Macromol ; 219: 109-120, 2022 Oct 31.
Article in English | MEDLINE | ID: mdl-35931291

ABSTRACT

In this work, novel biocompatible and reduction-responsive soft hydrogels were formulated from norbornene (Nb)-functionalized carboxymethyl cellulose (CMCNb). To cross-link the CMC-Nb via a highly bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction, we employed a water-soluble and reduction-responsive diselenide-based cross-linker possessing two terminal tetrazine (Tz) groups with varying molar concentrations (Nb/Tz molar ratios of 10/10, 10/05, and 10/2.5). The N2 microbubbles liberated as a by-product during the IEDDA reaction generated in-situ pores in hydrogel networks. The resulting hydrogels had highly porous structures and relatively soft mechanical properties (storage moduli in the range 74 ⁓160 Pa). The hydrogels showed high swelling ratios (>35 times), tunable gelation times (1-5 min), and excellent doxorubicin (DOX) loading efficiencies (>85 %). The hydrogels exhibited stimuli-responsive and fast release of DOX (99 %, after 12 h) in the presence of 10 mmol of glutathione as compared to the normal PBS solution (38 %). The cytotoxic effects of blank hydrogels were not observed against HEK-239 cells, while the DOX-encapsulated hydrogels exhibited anti-tumor activity in BT-20 cancer cells. The results indicate potential applications of the CMC-based soft hydrogels in injectable drug delivery systems.


Subject(s)
Hydrogels , Neoplasms , Carboxymethylcellulose Sodium/chemistry , Click Chemistry/methods , Doxorubicin/chemistry , Electrons , Glutathione , Hydrogels/chemistry , Neoplasms/drug therapy , Norbornanes/chemistry , Water
19.
Mol Med Rep ; 26(3)2022 Sep.
Article in English | MEDLINE | ID: mdl-35856414

ABSTRACT

Ulcerative colitis (UC) is difficult to eradicate as it leads to chronic inflammation in the digestive tract due to immune system malfunction. The present study demonstrated the protective effect of 7S,15R­dihydroxy­16S,17S­epoxy­docosapentaenoic acid (diHEP­DPA), which had been previously synthesized, on a dextran sulfate sodium (DSS)­induced BALB/c mouse model of UC. UC was induced with 4% DSS drinking water for 7 days. Initially, the anti­inflammatory effect of diHEP­DPA was confirmed by demonstrating that lipopolysaccharide­stimulated THP1 cells treated with diHEP­DPA decreased IL­6, TNF­α and nitrite levels by fluorescence­activated cell sorting (FACS) and Griess reagent kit. The results indicated that the administration of diHEP­DPA at 20 µg/kg significantly reduced the severity of colitis, as determined by hematoxylin and eosin staining. The levels of TNF­α, IL­6 and IL­1ß in the colon tissue and serum were significantly reduced in the diHEP­DPA + DSS­treated group compared with in the control group, as determined by FACS and ELISA kit. It was also observed that diHEP­DPA decreased myeloperoxidase (MPO) and nitrite levels in the colon tissues of diHEP­DPA + DSS­treated mice, as indicated using commercial MPO and nitric oxide kits. The diHEP­DPA+DSS­treated mice also exhibited decreased expression levels of phosporylated (p)­inhibitor κB protein, p­p65 and inducible nitric oxide synthase in the colon tissue by inhibiting inflammation, which were measured by reverse transcription­quantitative PCR and weatern blot analysis. Overall, the present study demonstrated the protective effect of diHEP­DPA against a severe colitis condition in vivo.


Subject(s)
Colitis, Ulcerative , Colitis , Animals , Colitis/metabolism , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Colon/metabolism , Dextran Sulfate/adverse effects , Disease Models, Animal , Fatty Acids, Unsaturated , Inflammation/metabolism , Interleukin-6/metabolism , Mice , Mice, Inbred BALB C , NF-kappa B/metabolism , Nitrites/metabolism , Tumor Necrosis Factor-alpha/metabolism
20.
Carbohydr Polym ; 288: 119389, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35450650

ABSTRACT

A novel physically and chemically double-crosslinked hydrogel derived from chitosan oligosaccharide/alginate (COS/Alg) was developed by using norbornene (Nb)-tetrazine (Tz) click reaction for ketoprofen delivery. The properties of the hydrogel were evaluated by rheological, FTIR, TGA, XRD, SEM, swelling and drug release studies. The Nb-Tz chemical cross-linking facilitated outstanding hydrophobic drug loading (44% wt/wt of ketoprofen) and sustained release through a hydrophobic interaction mechanism between the drug and the used polysaccharides. The COS/Alg electrostatics network (10/10 of NH2/COOH molar ratio) generated the pH responsiveness, suppressing the release in simulated gastric fluid (below 10% for 2 h) and enhancing the release in simulated intestinal fluids (up to 84% for 24 h). The prepared hydrogel was non-toxic to human HEK-293 cells (95% cell viability). This work opens up a potential approach for preparing hydrophilic hydrogels from natural polysaccharides that can be used in the delivery of hydrophobic drugs.


Subject(s)
Chitosan , Ketoprofen , Alginates/chemistry , Chitosan/chemistry , Drug Carriers/chemistry , Drug Delivery Systems , Drug Liberation , HEK293 Cells , Humans , Hydrogels/chemistry , Hydrogen-Ion Concentration , Niobium , Norbornanes
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