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1.
ACS Appl Mater Interfaces ; 16(20): 26107-26120, 2024 May 22.
Article En | MEDLINE | ID: mdl-38725264

The slow anodic oxygen evolution reaction (OER) significantly limits electrocatalytic water splitting for hydrogen production. We proposed the electrocatalyst for glucose oxidation by Ta-doping NiFe LDH nanosheets to simultaneously obtain glucaric acid (GRA) and hydrogen gas as a useful byproduct. Superior glucose oxidation reaction (GOR) activity is demonstrated by the optimized Ta-NiFe LDH, which has a low overpotential of 192 mV, allowing for a small Tafel slope of 70 mV dec-1 and a current density of 50 mA cm-2. The Ta NiFe LDH-oxidized glucose to GRA with a 72.94% yield and 64.3% Faradaic efficiency at 1.45 VRHE. Herein, we report the Ta NiFe LDH/NF electrode for the GOR&hydrogen evolution reaction (HER), which exhibits a cell voltage of 1.62 V to reach a current density of 10 mA cm-2, which is 250 mV lower compared to OER&HER (1.87 V). This study reveals that GOR is an energy-efficient and cost-effective method for producing H2 and valorizing biomass.

2.
Invest Ophthalmol Vis Sci ; 65(5): 27, 2024 May 01.
Article En | MEDLINE | ID: mdl-38758638

Purpose: To demonstrate the first near-infrared adaptive optics fluorescence lifetime imaging ophthalmoscopy (NIR-AOFLIO) measurements in vivo of the human retinal pigment epithelial (RPE) cellular mosaic and to visualize lifetime changes at different retinal eccentricities. Methods: NIR reflectance and autofluorescence were captured using a custom adaptive optics scanning light ophthalmoscope in 10 healthy subjects (23-64 years old) at seven eccentricities and in two eyes with retinal abnormalities. Repeatability was assessed across two visits up to 8 weeks apart. Endogenous retinal fluorophores and hydrophobic whole retinal extracts of Abca4-/- pigmented and albino mice were imaged to probe the fluorescence origin of NIR-AOFLIO. Results: The RPE mosaic was resolved at all locations in five of seven younger subjects (<35 years old). The mean lifetime across near-peripheral regions (8° and 12°) was longer compared to near-foveal regions (0° and 2°). Repeatability across two visits showed moderate to excellent correlation (intraclass correlation: 0.88 [τm], 0.75 [τ1], 0.65 [τ2], 0.98 [a1]). The mean lifetime across drusen-containing eyes was longer than in age-matched healthy eyes. Fluorescence was observed in only the extracts from pigmented Abca4-/- mouse. Conclusions: NIR-AOFLIO was repeatable and allowed visualization of the RPE cellular mosaic. An observed signal in only the pigmented mouse extract infers the fluorescence signal originates predominantly from melanin. Variations observed across the retina with intermediate age-related macular degeneration suggest NIR-AOFLIO may act as a functional measure of a biomarker for in vivo monitoring of early alterations in retinal health.


Ophthalmoscopy , Optical Imaging , Retinal Pigment Epithelium , Humans , Retinal Pigment Epithelium/diagnostic imaging , Retinal Pigment Epithelium/metabolism , Ophthalmoscopy/methods , Adult , Middle Aged , Animals , Female , Mice , Male , Young Adult , Optical Imaging/methods , Reproducibility of Results , Infrared Rays , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Fluorescein Angiography/methods
3.
Biomed Pharmacother ; 176: 116765, 2024 May 23.
Article En | MEDLINE | ID: mdl-38788600

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as Huzhang in traditional Chinese Medicine, can enhance blood circulation to eliminate wind pathogens and terminate coughing. Despite pharmacological evidence supporting the efficacy of R. japonica in suppressing edema-induced skin inflammation or connective tissue diseases, its pharmaceutical potential for treating AD-like skin inflammation remains unexplored. This study investigated the possible effects of R. japonica ethanol extract (RJE) on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation in NC/Nga mice. To elucidate the underlying mechanisms by which RJE inhibits skin inflammation, we examined the effect of RJE on IFN-γ/TNF-α-induced signal transducer and activator of transcription (STAT) signaling in human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Our findings revealed that RJE mitigates DfE-induced AD-like symptoms and skin barrier disruptions in mouse skin lesions. Moreover, RJE attenuated DfE-induced mast cell infiltration and serum levels of inflammatory cytokines (IL-1α, IL-1ß, IL-6, IL-23, IFN-γ, TNF-α, and GM-CSF). RJE also inhibited IFN-γ/TNF-α-induced chemokine levels and STAT3 phosphorylation in HEKs and HDFs. Virtual binding analysis of the RJE components suggested that emodin-8-ß-D-glucoside binds to Janus kinase (JAK) 1/2, thereby suppressing STAT signaling, which was confirmed by Western blot analysis. In conclusion, our results suggest that RJE may alleviate DfE-induced skin barrier dysfunction by inhibiting JAK/STAT signaling and the proinflammatory immune response through the suppression of inflammatory mediators in AD-like skin disease. These findings suggest that RJE has potential as an effective therapy for AD management.

4.
Antioxidants (Basel) ; 13(5)2024 May 04.
Article En | MEDLINE | ID: mdl-38790673

Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights.

5.
Food Sci Anim Resour ; 44(2): 443-463, 2024 Mar.
Article En | MEDLINE | ID: mdl-38764514

This study investigated the impact of activated carbon, palm activated carbon, and zeolite on horse oil (HO) extracted from horse neck fat using supercritical fluid extraction with deodorant-untreated HO (CON) as a comparison. The yield and lipid oxidation of deodorant untreated HO (CON) were not significantly affected by the three deodorants. However, deodorant-treated HOs exhibited significantly elevated levels of α-linolenic acid (C18:3n3) and eicosenoic acid (C20:1n9) compared to CON (p<0.05), while other fatty acids remained consistent. Zeolite-purified HO demonstrated significantly lower levels of volatile organic compounds (VOCs) than other treatments (p<0.05). Remarkably, zeolite decreased the concentration of pentane, 2,3-dimethyl (gasoline odor), by over 90%, from 177.17 A.U. ×106 in CON to 15.91 A.U. ×106. Zeolite also effectively eliminates sec-butylamine (ammonia and fishy odor) as compared to other deodorant-treated HOs (p<0.05). Additionally, zeolite reduced VOCs associated with the fruity citrus flavor, such as nonanal, octanal, and D-limonene in HO (p<0.05). This study suggests that integrating zeolite in supercritical fluid extraction enhances HO purification by effectively eliminating undesirable VOCs, presenting a valuable approach for producing high-quality HO production in the cosmetic and functional food industries.

6.
Nano Lett ; 2024 May 21.
Article En | MEDLINE | ID: mdl-38771649

Material advances in soft bioelectronics, particularly those based on stretchable nanocomposites─functional nanomaterials embedded in viscoelastic polymers with irreversible or reversible bonds─have driven significant progress in translational medical device research. The unique mechanical properties inherent in the stretchable nanocomposites enable stiffness matching between tissue and device, as well as its spontaneous mechanical adaptation to in vivo environments, minimizing undesired mechanical stress and inflammation responses. Furthermore, these properties allow percolative networks of conducting fillers in the nanocomposites to be sustained even under repetitive tensile/compressive stresses, leading to stable tissue-device interfacing. Here, we present an in-depth review of materials strategies, fabrication/integration techniques, device designs, applications, and translational opportunities of nanocomposite-based soft bioelectronics, which feature intrinsic stretchability, self-healability, tissue adhesion, and/or syringe injectability. Among many, applications to brain, heart, and peripheral nerves are predominantly discussed, and translational studies in certain domains such as neuromuscular and cardiovascular engineering are particularly highlighted.

7.
Biomed Pharmacother ; 175: 116770, 2024 May 20.
Article En | MEDLINE | ID: mdl-38772154

Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), often have concomitant mental disorders such as depression and anxiety. Therefore, a bidirectional approach involving the gut and brain axes is necessary for the prevention and treatment thereof. In this study, we explored the potential of Poncirus trifoliata extract (PT), traditionally known for its neuroprotective effects against gastrointestinal diseases, as a natural treatment agent for IBD in a dextran sulfate sodium (DSS)-induced colitis model. Oral administration of PT ameliorated weight loss and inflammatory responses in mice with DSS-induced colitis. Furthermore, PT treatment effectively restored the colon length and ameliorated enterocyte death by inhibiting DSS-induced reactive oxygen species (ROS)-mediated necroptosis. The main bioactive components of PT, poncirin and naringin, confirmed using ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-qTOF), can be utilized to regulate necroptosis. The antidepressant-like effects of PT were confirmed using open field test (OFT) and tail suspension test (TST). PT treatment also restored vascular endothelial cell integrity in the hippocampus. In the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) regions of the hippocampus, PT controlled the neuroinflammatory responses of proliferated microglia. In conclusion, PT, which contains high levels of poncirin and naringin, has potential as a bidirectional therapeutic agent that can simultaneously improve IBD-associated intestinal and mental disorders.

8.
Int J Food Microbiol ; 419: 110738, 2024 May 16.
Article En | MEDLINE | ID: mdl-38772219

This study investigates the possibility of utilizing drip as a non-destructive method for assessing the freshness and spoilage of chicken meat. The quality parameters [pH, volatile base nitrogen (VBN), and total aerobic bacterial counts (TAB)] of chicken meat were evaluated over a 13-day storage period in vacuum packaging at 4 °C. Simultaneously, the metabolites in the chicken meat and its drip were measured by nuclear magnetic resonance. Correlation (Pearson's and Spearman's rank) and pathway analyses were conducted to select the metabolites for model training. Binary logistic regression (model 1 and model 2) and multiple linear regression models (model 3-1 and model 3-2) were trained using selected metabolites, and their performance was evaluated using receiver operating characteristic (ROC) curves. As a result, the chicken meat was spoiled after 7 days of storage, exceeding 20 mg/100 g VBN and 5.7 log CFU/g TAB. The correlation analysis identified one organic acid, eight free amino acids, and five nucleic acids as highly correlated with chicken meat and its drip during storage. Pathway analysis revealed tyrosine and purine metabolism as metabolic pathways highly correlated with spoilage. Based on these findings, specific metabolites were selected for model training: ATP, glutamine, hypoxanthine, IMP, tyrosine, and tyramine. To predict the freshness and spoilage of chicken meat, model 1, trained using tyramine, ATP, tyrosine, and IMP from chicken meat, achieved a 99.9 % accuracy and had an ROC value of 0.884 when validated using drip metabolites. This model 1 was improved by training with tyramine and IMP from both chicken meat and its drip (model 2), which increased the ROC value for drip metabolites from 0.884 to 0.997. Finally, selected two metabolites (tyramine and IMP) can predict TAB and VBN quantitatively through models 3-1 and 3-2, respectively. Therefore, the model developed using metabolic changes in drip demonstrated the capability to non-destructively predict the freshness and spoilage of chicken meat at 4 °C. To make generic predictions, it is necessary to expand the model's applicability to various conditions, such as different temperatures, and validate its performance across multiple chicken batches.

9.
Obes Rev ; : e13762, 2024 May 07.
Article En | MEDLINE | ID: mdl-38715378

While a broad consensus exists that integrated nutrition and regular exercise are foundational for health maintenance and serve as a robust non-pharmacological strategy against cardiometabolic diseases, the nuanced interplay between these elements remains incompletely understood. Through multifaceted interactions, these factors profoundly influence primary metabolic organs, notably the skeletal muscle and adipose tissue. Despite the critical nature of this interactivity, a holistic understanding of the combined effects of physical activity and dietary practices is still emerging. This narrative review aims to elucidate the intertwined roles of nutrition and exercise. It provides a comprehensive overview of their synergistic dynamics and emphasizes the importance of a dual-focus approach in mitigating and managing cardiometabolic disorders, predominantly obesity and type 2 diabetes.

10.
Food Funct ; 15(8): 4564-4574, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38584588

This study aimed to investigate the potential of beef peptides (BPs) in mitigating muscle atrophy induced by dexamethasone (DEX) with underlying three mechanisms in vitro (protein degradation, protein synthesis, and the oxidative stress pathway). Finally, the anti-atrophic effect of BPs was enhanced through purification and isolation. BPs were generated using beef loin hydrolyzed with alcalase/ProteAX/trypsin, each at a concentration of 0.67%, followed by ultrafiltration through a 3 kDa cut-off. BPs (10-100 µg mL-1) dose-dependently counteracted the DEX-induced reductions in myotube diameters, differentiation, fusion, and maturation indices (p < 0.05). Additionally, BPs significantly reduced FoxO1 protein dephosphorylation, thereby suppressing muscle-specific E3 ubiquitin ligases such as muscle RING-finger containing protein-1 and muscle atrophy F-box protein in C2C12 myotubes at concentrations exceeding 25 µg mL-1 (p < 0.05). BPs also enhanced the phosphorylation of protein synthesis markers, including mTOR, 4E-BP1, and p70S6K1, in a dose-dependent manner (p < 0.05) and increased the mRNA expression of antioxidant enzymes. Fractionated peptides derived from BPs, through size exclusion and polarity-based fractionation, also demonstrated enhanced anti-atrophic effects compared to BPs. These peptides downregulated the mRNA expression of primary muscle atrophy markers while upregulated that of antioxidant enzymes. Specifically, peptides GAGAAGAPAGGA (MW 924.5) and AFRSSTKK (MW 826.4) were identified from fractionated peptides of BPs. These findings suggest that BPs, specifically the peptide fractions GAGAAGAPAGGA and AFRSSTKK, could be a potential strategy to mitigate glucocorticoid-induced skeletal muscle atrophy by reducing the E3 ubiquitin ligase activity.


Muscle Fibers, Skeletal , Muscular Atrophy , Oxidative Stress , Peptides , Animals , Muscular Atrophy/drug therapy , Muscular Atrophy/metabolism , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/metabolism , Mice , Oxidative Stress/drug effects , Peptides/pharmacology , Cattle , Proteolysis/drug effects , Cell Line , Protein Biosynthesis/drug effects , Red Meat , Muscle Proteins/metabolism , Dexamethasone/pharmacology , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Phosphorylation , TOR Serine-Threonine Kinases/metabolism
11.
Am J Med Genet A ; : e63606, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38563110

The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined. Genotypic analyses included gene panels and whole-exome sequencing. All patients exhibited global developmental delay from early infancy, with motor development eventually reaching independent ambulation by 3 years of age. Language developmental delay varied significantly from nonverbal to simple sentences, which plateaued in all patients. Patients with the best language outcomes typically managed 2-3-word sentences, corresponding to a developmental age of 2-3 years. Epilepsy developed in 77% of patients, with onset consistently following developmental delays at a median age of 31 months. Longitudinal EEG data revealed a shift from occipital to frontal epileptiform discharges with age, suggesting a correlation with synaptic maturation. These findings suggest that the critical developmental plateau occurs between the ages of 2 and 5 years and is potentially influenced by epilepsy. By analyzing longitudinal data, our study contributes to a deeper understanding of SYNGAP1-related DEE, provides potential EEG biomarkers, and underlines the importance of early diagnosis and intervention to address this complex disorder.

12.
Biomater Sci ; 12(10): 2599-2613, 2024 May 14.
Article En | MEDLINE | ID: mdl-38546094

Decellularized extracellular matrix (dECM) has emerged as an exceptional biomaterial that effectively recapitulates the native tissue microenvironment for enhanced regenerative potential. Although various dECM bioinks derived from different tissues have shown promising results, challenges persist in achieving high-resolution printing of flexible tissue constructs because of the inherent limitations of dECM's weak mechanical properties and poor printability. Attempts to enhance mechanical rigidity through chemical modifications, photoinitiators, and nanomaterial reinforcement have often compromised the bioactivity of dECM and mismatched the desired mechanical properties of target tissues. In response, this study proposes a novel method involving a tissue-specific rheological modifier, gelatinized dECM. This modifier autonomously enhances bioink modulus pre-printing, ensuring immediate and precise shape formation upon extrusion. The hybrid bioink with GeldECM undergoes a triple crosslinking system-physical entanglement for pre-printing, visible light photocrosslinking during printing for increased efficiency, and thermal crosslinking post-printing during tissue culture. A meticulous gelatinization process preserves the dECM protein components, and optimal hybrid ratios modify the mechanical properties, tailoring them to specific tissues. The application of this sequential multiple crosslinking designs successfully yielded soft yet resilient tissue constructs capable of withstanding vigorous agitation with high shape fidelity. This innovative method, founded on mechanical modulation by GeldECM, holds promise for the fabrication of flexible tissues with high resilience.


Gelatin , Rheology , Tissue Engineering , Gelatin/chemistry , Animals , Extracellular Matrix/chemistry , Ink , Bioprinting , Biocompatible Materials/chemistry , Tissue Scaffolds/chemistry , Humans , Printing, Three-Dimensional
13.
Antioxidants (Basel) ; 13(3)2024 Mar 12.
Article En | MEDLINE | ID: mdl-38539873

Developing new plant varieties plays a crucial role in competitiveness in the agricultural and food industries and enhancing food security. Daehong (DH) is a new variety of Crataegus pinnatifida Bunge (CP); however, its physiological functions and potential as a nutraceutical ingredient remain unknown. Here, the efficacy of DH on inflammatory bowel disease (IBD) was investigated using dextran sulfate sodium (DSS)-induced colitis mice, and its relative pharmacological effects were analyzed against CP. DH improved colitis-induced weight loss, colon shortening, and inflammatory responses and reduced intestinal permeability. The reactive oxygen species (ROS)-mediated necroptotic signal that triggers enterocyte cell death in DSS-induced colitis was effectively controlled by DH, attributed to epicatechin. DSS-induced gut dysbiosis was recovered into a healthy gut microbiome environment by DH, increasing beneficial bacteria, like Akkermansia muciniphila, and changing harmful bacteria, including Bacteroides vulgatus and Peptostreptococcaceae. DH shows potential as a dietary or pharmaceutical ingredient to promote gut health and to prevent and treat IBD.

14.
Cancer Res Treat ; 56(2): 357-371, 2024 Apr.
Article En | MEDLINE | ID: mdl-38487832

PURPOSE: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2021. MATERIALS AND METHODS: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2021, with survival follow-up until December 31, 2022. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea. RESULTS: The number of new cancer diagnoses in 2021 increased by 27,002 cases (10.8%) compared to 2020. In 2021, newly diagnosed cancer cases and deaths from cancer were reported as 277,523 (age-standardized rate [ASR], 289.3 per 100,000) and 82,688 (ASR, 67.6 per 100,000), respectively. The overall cancer incidence rates increased by 3.3% annually from 1999 to 2012, and decreased by 5.3% from 2012 to 2015, thereafter, followed by non-significant changes. Cancer mortality rates have been decreasing since 2002, with more rapid decline in recent years (annual decrease of 2.8% from 2002 to 2013; 3.2% from 2013 to 2021). The 5-year relative survival between 2017 and 2021 was 72.1%, which contributed to prevalent cases reaching over 2.4 million in 2021. CONCLUSION: In 2021, the number of newly diagnosed cancer patients increased as healthcare utilization recovered from the coronavirus disease 2019-related declines of 2020. Revised cancer registration guidelines expanded the registration scope, particularly for stomach and colorectal cancer. Survival rates have improved over the years, leading to a growing population of cancer survivors, necessitating a comprehensive cancer control strategy. The long-term impact of the pandemic on cancer statistics requires future investigation.


Neoplasms , Humans , Incidence , Prevalence , Survival Rate , Republic of Korea/epidemiology
15.
J Control Release ; 368: 756-767, 2024 Apr.
Article En | MEDLINE | ID: mdl-38499090

Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be suboptimal. In this study, we generated liposomes using a combination of DSPE and DSPE-PEG-2 k lipids and loaded them with doxorubicin (DOX) and paclitaxel (PTX), to investigate the effects of light emitting diode (LED) irradiation on liposome structure and drug loading efficiency. Scanning and transmission electron microscopy revealed that the surface of liposomes irradiated with blue or near-infrared LEDs (LsLipo) was rougher and more irregular than that of non-LED-irradiated liposomes (NsLipo). Nuclear magnetic resonance analysis showed that the hydrogen peak originating from the lipid head groups was lower in LsLipo than in NsLipo preparations, indicating that LED irradiation changed the chemical and physical properties of the liposome. Structural changes, such as reduced rigidity, induced by LED irradiation, increased the loading efficiency of DOX and PTX. In vitro and in vivo experiments showed that LsLipo were more effective at inhibiting the growth of cancer cells than NsLipo. Our findings suggest that LED irradiation enhances the drug delivery efficacy of liposomes and offer new possibilities for improving drug delivery systems.


Liposomes , Neoplasms , Humans , Liposomes/chemistry , Drug Delivery Systems , Paclitaxel/chemistry , Doxorubicin/chemistry , Neoplasms/drug therapy , Cell Line, Tumor
16.
Cancer Res Treat ; 56(2): 372-379, 2024 Apr.
Article En | MEDLINE | ID: mdl-38487833

PURPOSE: This study aimed to report the projected cancer incidence and mortality for the year 2024 to estimate Korea's current cancer burden. MATERIALS AND METHODS: Cancer incidence data from 1999 to 2021 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2022 were acquired from Statistics Korea. Cancer incidence and mortality were projected by fitting a linear regression model to observed age-specific cancer rates against their respective years and multiplying the projected age-specific rates by the anticipated age-specific population for 2024. A joinpoint regression model was used to determine the year in which the linear trend changed significantly; we only used the data of the latest trend for prediction. RESULTS: In total, 292,221 new cancer cases and 83,770 cancer deaths are expected to occur in Korea in 2024. The most common cancer site is expected to be the thyroid, followed by the colon and rectum, lung, breast, and stomach. These five cancers are expected to represent 55.7% of the overall burden of cancer in Korea. The most common type of cancer leading to death is expected to be lung cancer, followed by liver, colorectal, pancreatic, and stomach cancers. CONCLUSION: The age-standardized incidence rates for female breast and prostate cancers are estimated to continue to increase. These up-to-date estimates of the cancer burden in Korea could be an important resource for planning and evaluating cancer-control programs.


Lung Neoplasms , Neoplasms , Prostatic Neoplasms , Male , Humans , Incidence , Neoplasms/epidemiology , Korea/epidemiology , Republic of Korea/epidemiology
18.
J Control Release ; 367: 768-778, 2024 Mar.
Article En | MEDLINE | ID: mdl-38341178

Immunotherapy based on adoptive transfer of natural killer (NK) cells is a promising strategy for circumventing the limitations of cancer treatments. However, components of the immunosuppressive tumor microenvironment (TME), such as transforming growth factor-beta (TGF-ß), compromise the therapeutic efficacy of NK cells significantly. To address these limitations, we developed a novel method of engineering NK cells for adaptive transfer. The method is based on nanogels that serve two functions: (1) they overcome the TGF-ß-mediated stress environment of the TME, and (2) they enhance the direct anti-tumor activity of NK cells. Previously, we demonstrated that cationic compounds such as 25 K branched polyethylenimine (25 K bPEI) prime NK cells, putting them in a 'ready-to-fight' state. Based on these findings, we designed nanogels that have two primary characteristics: (1) they encapsulate galunisertib (Gal), which is used clinically to inhibit TGF-ß receptor activity, thereby blocking TGF-ß signaling; and (2) they provide cells with a surface coating of 25 K bPEI. When grown in culture medium containing TGF-ß, nanogel-treated NK cells demonstrated greater migration ability, degranulation activity, and cytotoxicity towards cancer cells than untreated NK cells. Additionally, the in vivo efficacy of nanogel-treated NK cells against PC-3 xenografts was significantly greater than that of Chem_NK cells primed by 25 K bPEI alone. These findings suggest that Gal-loaded 25 K bPEI-coated nanogels exert anti-tumor effects via chemical priming, as well suppressing the effects of TGF-ß on NK cells. We also expect 25 K bPEI-based nanogels to have great potential to overcome the suppressive effects of the TME through their NK cell-priming activity and delivery of the desired chemicals.


Cytotoxicity, Immunologic , Polyethylene Glycols , Polyethyleneimine , Transforming Growth Factor beta , Humans , Nanogels , Transforming Growth Factor beta/pharmacology , Cell Line, Tumor , Killer Cells, Natural , Tumor Microenvironment
20.
Medicine (Baltimore) ; 103(5): e37166, 2024 Feb 02.
Article En | MEDLINE | ID: mdl-38306513

RESULTS: After excluding 4 patients with an anesthesia duration of < 2 hours, data from 34 patients (1163 sets of tracheal and esophageal temperatures) were analyzed. Concordance correlation coefficient was 0.78. The overall mean bias (95% limits of agreement) between the tracheal and esophageal temperatures was -0.16°C (-0.65°C to 0.34°C). The percentage of temperature differences within ±â€…0.25°C was 73.5% ± 32.3, with a median of 89.4% [0,100]. The linear mixed-effects model revealed that the estimated intercept was 0.17°C with a 95% confidence interval (CI) of 0.13°C to 0.22°C. The duration of anesthesia and the number of temperature measurements were associated with higher concordance between the tracheal and esophageal temperatures in univariate analysis.


Body Temperature , Humidifiers , Humans , Temperature , Hot Temperature , Esophagus
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