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1.
Biomaterials ; 310: 122630, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38815456

ABSTRACT

Wearable diabetic healthcare devices have attracted great attention for real-time continuous glucose monitoring (CGM) using biofluids such as tears, sweat, saliva, and interstitial fluid via noninvasive ways. In response to the escalating global demand for CGM, these devices enable proactive management and intervention of diabetic patients with incorporated drug delivery systems (DDSs). In this context, multifunctional nanomaterials can trigger the development of innovative sensing and management platforms to facilitate real-time selective glucose monitoring with remarkable sensitivity, on-demand drug delivery, and wireless power and data transmission. The seamless integration into wearable devices ensures patient's compliance. This comprehensive review evaluates the multifaceted roles of these materials in wearable diabetic healthcare devices, comparing their glucose sensing capabilities with conventionally available glucometers and CGM devices, and finally outlines the merits, limitations, and prospects of these devices. This review would serve as a valuable resource, elucidating the intricate functions of nanomaterials for the successful development of advanced wearable devices in diabetes management.

2.
Int J Stem Cells ; 17(2): 120-129, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38773747

ABSTRACT

Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.

3.
Biofabrication ; 16(3)2024 May 28.
Article in English | MEDLINE | ID: mdl-38749417

ABSTRACT

Accurate simulation of different cell type interactions is crucial for physiological and precisein vitrodrug testing. Human tissue-resident macrophages are critical for modulating disease conditions and drug-induced injuries in various tissues; however, their limited availability has hindered their use inin vitromodeling. Therefore, this study aimed to create macrophage-containing organoid co-culture models by directly incorporating human-induced pluripotent stem cell (hiPSC)-derived pre-macrophages into organoid and scaffold cell models. The fully differentiated cells in these organoids exhibited functional characteristics of tissue-resident macrophages with enriched pan-macrophage markers and the potential for M1/M2 subtype specialization upon cytokine stimulation. In a hepatic organoid model, the integrated macrophages replicated typical intrinsic properties, including cytokine release, polarization, and phagocytosis, and the co-culture model was more responsive to drug-induced liver injury than a macrophage-free model. Furthermore, alveolar organoid models containing these hiPSC-derived macrophages also showed increased drug and chemical sensitivity to pulmonary toxicants. Moreover, 3D adipocyte scaffold models incorporating macrophages effectively simulated in vivo insulin resistance observed in adipose tissue and showed improved insulin sensitivity on exposure to anti-diabetic drugs. Overall, the findings demonstrated that incorporating hiPSC-derived macrophages into organoid culture models resulted in more physiological and sensitivein vitrodrug evaluation and screening systems.


Subject(s)
Coculture Techniques , Induced Pluripotent Stem Cells , Macrophages , Organoids , Organoids/cytology , Organoids/drug effects , Organoids/metabolism , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Humans , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Cell Differentiation/drug effects , Liver/cytology , Liver/drug effects , Models, Biological , Animals
4.
Ann Occup Environ Med ; 36: e11, 2024.
Article in English | MEDLINE | ID: mdl-38741681

ABSTRACT

Background: Occupational neck disability is a prevalent issue, especially among line workers, who are often exposed to elevated levels of cervical ergonomic stress. The aim of this study was to investigate the impact of neck posture and insulating stick use on neck disability in a specific occupational group in Korea. Methods: This cross-sectional study was conducted among 483 line workers in Gwangju and Jeonnam, Korea. Data were collected using the Neck Disability Index, Cervical Degenerative Index, and a structured questionnaire focusing on demographic and occupational factors. Logistic regression analysis was applied to determine the adjusted odds ratio (OR) and 95% confidence interval (CI) for neck posture and factors related to neck disability. Results: Neck disability prevalence was 17.2% among the participants. Multivariate logistic regression analysis showed that factors related to neck disability included age over 60 years (adjusted OR: 3.08; 95% CI: 1.63-5.83), depression (adjusted OR: 8.33; 95% CI: 3.85-18.00), a history of cervical trauma (adjusted OR: 2.13; 95% CI: 1.04-4.40), and radiological degenerative changes in the cervical spine (adjusted OR: 2.33; 95% CI: 1.26-4.33). In particular, the adjusted OR of neck disability among live-line workers was 2.10 (95% CI: 1.12-3.92) when compared with support workers (model 1). Other analysis models showed that use of insulating sticks for more than 10 hours per week (adjusted OR: 2.46; 95% CI: 1.32-4.61) and higher neck extension (adjusted OR: 2.98; 95% CI: 1.14-3.46) were significant work-related risk factors (model 2,3). Conclusions: Neck posture, age, depression, cervical trauma history, degenerative changes in the cervical spine, and use of insulating sticks are significant risk factors for neck disability among line workers in Korea. These findings highlight the need to improve the working environment and reduce the burden of cervical ergonomic stress among line workers.

5.
Mol Cancer ; 23(1): 87, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702773

ABSTRACT

BACKGROUND: Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging. METHODS: We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary PDAC samples with and without paired liver metastasis samples to understand the interplay between ITH and TME in the PDAC evolution and its clinical associations. RESULTS: scRNA-seq analysis revealed that even a small proportion (22%) of basal-like malignant ductal cells could lead to poor chemotherapy response and patient survival and that epithelial-mesenchymal transition programs were largely subtype-specific. The clonal homogeneity significantly increased with more prevalent and pronounced copy number gains of oncogenes, such as KRAS and ETV1, and losses of tumor suppressor genes, such as SMAD2 and MAP2K4, along PDAC progression and metastasis. Moreover, diverse immune cell populations, including naïve SELLhi regulatory T cells (Tregs) and activated TIGIThi Tregs, contributed to shaping immunosuppressive TMEs of PDAC through cellular interactions with malignant ductal cells in PDAC evolution. Importantly, the proportion of basal-like ductal cells negatively correlated with that of immunoreactive cell populations, such as cytotoxic T cells, but positively correlated with that of immunosuppressive cell populations, such as Tregs. CONCLUSION: We uncover that the proportion of basal-like subtype is a key determinant for chemotherapy response and patient outcome, and that PDAC clonally evolves with subtype-specific dosage changes of cancer-associated genes by forming immunosuppressive microenvironments in its progression and metastasis.


Subject(s)
Clonal Evolution , Liver Neoplasms , Pancreatic Neoplasms , Single-Cell Analysis , Tumor Microenvironment , Humans , Tumor Microenvironment/genetics , Liver Neoplasms/secondary , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Clonal Evolution/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Transcriptome , Epithelial-Mesenchymal Transition/genetics , Biomarkers, Tumor/genetics , Prognosis , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Male , Female , Single-Cell Gene Expression Analysis
6.
Curr Protoc ; 4(4): e1015, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38597874

ABSTRACT

Recent development of hepatic organoids (HOs) derived from human pluripotent stem cells (hPSCs) provides an alternative in vitro model that can mimic the human liver detoxification pathway for drug safety assessment. By recapitulating the high level of maturity and drug-metabolizing capacity of the liver in a three-dimensional organoid culture, HOs may allow researchers to assess drug toxicity and metabolism more accurately than animal models or hepatocellular carcinoma cells. Although this promising potential has contributed to the development of various protocols, only a few protocols are available to generate functional HOs with guaranteed CYP450 enzymatic activity, the key feature driving toxic responses during drug metabolism. Based on previously published protocols, we describe an optimized culture method that can substantially increase the expression and activity of CYP450s, in particular CYP3A4, CYP2C9, and CYP2C19, in HOs. To generate mass-produced and highly reproducible HOs required as models for toxicity evaluation, we first generated hepatic endodermal organoids (HEOs) from hPSCs capable of in vitro proliferation and cryopreservation. The stepwise protocol includes generating HEOs as well as efficient methods to enhance CYP450 expression and activity in terminally differentiated HOs. Furthermore, we present a simple protocol for the assessment of HO cytotoxicity, one of the hallmarks of drug-induced acute hepatotoxicity. The protocols are relatively straightforward and can be successfully used by laboratories with basic experience in culturing hPSCs. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Generation of hepatic endodermal organoids from human pluripotent stem cells Basic Protocol 2: Expansion and cryopreservation of hepatic endodermal organoids Basic Protocol 3: Differentiation of hepatic organoids from hepatic endodermal organoids Basic Protocol 4: Evaluation of hepatotoxicity using hepatic organoids Support Protocol: Human pluripotent stem cell culture.


Subject(s)
Chemical and Drug Induced Liver Injury , Animals , Humans , Chemical and Drug Induced Liver Injury/etiology , Cell Differentiation , Cell Line , Cryopreservation
7.
J World Fed Orthod ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38653656

ABSTRACT

Orthodontic uprighting or traction of an impacted mandibular second molar often necessitates invasive interventions. This report aims to illustrate the utilization of nickel-titanium wire segments inserted into small, simple tubes for uprighting mesially impacted mandibular second molars and also for scissor bite correction. The term "simple tube" refers to a tube without a bonding base attached to a tooth surface by covering it with flowable composite resin. Due to the absence of a bonding base, the simple tube is characterized by its diminutive size and minimal profile height, facilitating placement on partially exposed second molars and unconventional positioning to adjust the force geometry. In this case study, mesially-impacted mandibular second molars with scissor bite were uprighted in a 21-year-old male utilizing simple tubes. Simple tubes can be used for molar uprighting and scissor bite correction buccally and lingually.

8.
Transl Lung Cancer Res ; 13(2): 280-291, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38496698

ABSTRACT

Background: Limited disease (LD) small cell lung cancer (SCLC) treated with definitive concurrent chemoradiotherapy (CCRT) potentially experience disease recurrence. We investigated the feasibility of circulating-tumor DNA (ctDNA)-based genomic and fragmentome analyses to assess the risk of recurrence. Methods: Targeted sequencing was conducted using pre-treatment and on-treatment blood samples from definitive CCRT-treated patients with LD-SCLC (n=50). Based on 12-month recurrence-free survival (RFS), patients were categorized into persistent-response (PeR, n=29) and non-PeR (n=21) groups. Fragmentome analysis was conducted using ctDNA fragments of different lengths: P1 (100-155 bp) and P2 (160-180 bp). Results: Patients with TP53 (n=15) and RB1 (n=11) mutation in on-treatment samples demonstrated significantly shorter RFS than patients with wild-type (WT) (P=0.05, P=0.0014, respectively). Fragmentome analysis of all available on-treatment samples (n=26) revealed that the non-PeR group (n=10) had a significantly higher P1 range (P=0.003) and lower P2 range (P=0.002). The areas under the curves for P1, P2, and the fragmentation ratio (P1/P2) in distinguishing the PeR and non-PeR were 0.850, 0.725, and 0.900, respectively. Using optimal cut-off, longer RFSs were found with the low-fragmentation-ratio group than with the high-fragmentation-ratio group (not reached vs. 7.6 months, P=0.002). Patients with both WT RB1 and a low-fragmentation-ratio (n=10) showed better outcomes than patients with both mutated RB1 and a high-fragmentation-ratio (n=10; hazard ratio, 7.55; 95% confidence interval: 2.14-26.6; P=0.002). Conclusions: RB1 mutations and high fragmentation ratios correlated with early disease recurrence. Analyzing ctDNA could help in predicting early treatment failure and making clinical decisions for high-risk patients.

9.
Gastrointest Endosc ; 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38447660

ABSTRACT

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, more than 80% of PDACs are considered to be surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. This study aimed to establish a patient-derived organoid (PDO) platform from endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC. METHODS: Patients with suspected PDAC were prospectively enrolled at the Samsung Medical Center from 2015 to 2019. PDAC tissues were acquired by means of EUS-FNB to establish PDAC PDOs, which were comprehensively analyzed for histology, genomic sequencing, and high-throughput screening (HTS) drug sensitivity test. RESULTS: PDAC PDOs were established with a success rate of 83.2% (94/113). It took approximately 3 weeks from acquiring minimal EUS-FNB specimens to generating sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and genomic sequencing. The high concordance between PDAC tissues and matched PDOs was confirmed, and whole-exome sequencing revealed the increased detection of genetic alterations in PDOs compared with EUS-FNB tissues. The HTS drug sensitivity test showed clinical correlation between the ex vivo PDO response and the actual chemotherapeutic response of the study patients in the real world (13 out of 15 cases). In addition, whole-transcriptome sequencing identified candidate genes associated with nab-paclitaxel resistance, such as ITGB7, ANPEP, and ST3GAL1. CONCLUSIONS: This PDAC PDO platform allows several therapeutic drugs to be tested within a short time window and opens the possibility for timely personalized medicine as a "patient avatar model" in clinical practice.

10.
Exp Neurobiol ; 33(1): 18-24, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38471801

ABSTRACT

Panic disorder (PD), characterized by recurrent and intense panic attacks, presents a complex interplay between psychological and neurobiological factors. Although the amygdala and hippocampus have been studied extensively in the context of PD, the brainstem's involvement remains relatively underexplored. This study aims to address this gap by examining structural abnormalities within specific brainstem regions, including the medulla, pons, and midbrain. The study sample population comprised twenty-one adult patients diagnosed with PD and an age-gender-education-matched control group. Utilizing rigorous inclusion and exclusion criteria, confounding factors related to comorbid psychiatric conditions and brain structure abnormalities were minimized. Our findings revealed a significant reduction in medulla volume among PD patients, a finding that persisted even after correcting for individual differences in total intracranial volume. The medulla's role in cardiovascular regulation and autonomic function, coupled with its involvement in fear responses, underscores its potential significance in the pathophysiology of PD. This study elucidates the medulla's structural abnormalities as a potential biomarker for PD. Understanding the role of the brainstem in PD could pave the way for more targeted and effective interventions for this condition.

11.
Nutrients ; 16(5)2024 Feb 25.
Article in English | MEDLINE | ID: mdl-38474775

ABSTRACT

Protein tyrosine phosphatases (PTPs) are pivotal contributors to the development of type 2 diabetes (T2DM). Hence, directing interventions towards PTPs emerges as a valuable therapeutic approach for managing type 2 diabetes. In particular, PTPN6 and PTPN9 are targets for anti-diabetic effects. Through high-throughput drug screening, quercetagitrin (QG) was recognized as a dual-target inhibitor of PTPN6 and PTPN9. We observed that QG suppressed the catalytic activity of PTPN6 (IC50 = 1 µM) and PTPN9 (IC50 = 1.7 µM) in vitro and enhanced glucose uptake by mature C2C12 myoblasts. Additionally, QG increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-dependent phosphorylation of Akt in mature C2C12 myoblasts. It further promoted the phosphorylation of Akt in the presence of palmitic acid, suggesting the attenuation of insulin resistance. In summary, our results indicate QG's role as a potent inhibitor targeting both PTPN6 and PTPN9, showcasing its potential as a promising treatment avenue for T2DM.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Proto-Oncogene Proteins c-akt/metabolism , Insulin/metabolism , Phosphorylation , Protein Tyrosine Phosphatases/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism
12.
Chem Biol Interact ; 391: 110903, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38331335

ABSTRACT

This study delves into the intricate mechanisms underlying drug-induced liver injury (DILI) with a specific focus on bromfenac, the withdrawn nonsteroidal anti-inflammatory drug. DILI is a pervasive concern in drug development, prompting market withdrawals and posing significant challenges to healthcare. Despite the withdrawal of bromfenac due to DILI, the exact role of its microsomal metabolism in inducing hepatotoxicity remains unclear. Herein, employing HepG2 cells with human liver microsomes and UDP-glucuronic acid (UDPGA), our investigation revealed a substantial increase in bromfenac-induced cytotoxicity in the presence of UDPGA, pointing to the significance of UDP-glucuronosyltransferase (UGT)-dependent metabolism in augmenting toxicity. Notably, among the recombinant UGTs examined, UGT2B7 emerged as a pivotal enzyme in the metabolic activation of bromfenac. Metabolite identification studies disclosed the formation of reactive intermediates, with bromfenac indolinone (lactam) identified as a potential mediator of hepatotoxic effects. Moreover, in cytotoxicity experiments, the toxicity of bromfenac lactam exhibited a 34-fold increase, relative to bromfenac. The toxicity of bromfenac lactam was mitigated by nicotinamide adenine dinucleotide phosphate-dependent metabolism. This finding underscores the role of UGT-dependent metabolism in generating reactive metabolites that contribute to the observed hepatotoxicity associated with bromfenac. Understanding these metabolic pathways and the involvement of specific enzymes, such as UGT2B7, provides crucial insights into the mechanisms of bromfenac-induced liver injury. In conclusion, this research sheds light on the metabolic intricacies leading to cytotoxicity induced by bromfenac, especially emphasizing the role of UGT-dependent metabolism and the formation of reactive intermediates like bromfenac lactam. These findings offer insight into the mechanistic basis of DILI and emphasize the importance of understanding metabolism-mediated toxicity.


Subject(s)
Benzophenones , Bromobenzenes , Chemical and Drug Induced Liver Injury , Uridine Diphosphate Glucuronic Acid , Humans , Uridine Diphosphate Glucuronic Acid/metabolism , Uridine Diphosphate Glucuronic Acid/pharmacology , Microsomes, Liver/metabolism , Glucuronosyltransferase/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Lactams/metabolism , Lactams/pharmacology , Glucuronides/metabolism
13.
Polymers (Basel) ; 16(2)2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38257053

ABSTRACT

The design of binders plays a pivotal role in achieving enduring high power in lithium-ion batteries (LIBs) and extending their overall lifespan. This review underscores the indispensable characteristics that a binder must possess when utilized in LIBs, considering factors such as electrochemical, thermal, and dispersion stability, compatibility with electrolytes, solubility in solvents, mechanical properties, and conductivity. In the case of anode materials, binders with robust mechanical properties and elasticity are imperative to uphold electrode integrity, particularly in materials subjected to substantial volume changes. For cathode materials, the selection of a binder hinges on the crystal structure of the cathode material. Other vital considerations in binder design encompass cost effectiveness, adhesion, processability, and environmental friendliness. Incorporating low-cost, eco-friendly, and biodegradable polymers can significantly contribute to sustainable battery development. This review serves as an invaluable resource for comprehending the prerequisites of binder design in high-performance LIBs and offers insights into binder selection for diverse electrode materials. The findings and principles articulated in this review can be extrapolated to other advanced battery systems, charting a course for developing next-generation batteries characterized by enhanced performance and sustainability.

15.
Korean J Intern Med ; 39(1): 172-183, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38031367

ABSTRACT

BACKGROUND/AIMS: This study aimed to identify the clinical characteristics of patients with concurrent rheumatoid arthritis (RA) and suspected non-tuberculous mycobacterial (NTM) infections as well as determine their prognostic factors. METHODS: We retrospectively reviewed the medical records of 91 patients with RA whose computed tomography (CT) findings suggested NTM infection. Subsequently, we compared the clinical characteristics between patients with and without clinical or radiological exacerbation of NTM-pulmonary disease (PD) and investigated the risk factors for the exacerbation and associated mortality. RESULTS: The mean age of patients with RA and suspected NTM-PD was 65.0 ± 10.2 years. The nodular/bronchiectatic (NB) form of NTM-PD was the predominant radiographic feature (78.0%). During follow-up, 36 patients (41.9%) experienced a radiological or clinical exacerbation of NTM-PD, whereas 12 patients (13.2%) died. Combined interstitial lung disease (ILD), microbiologically confirmed NTM-PD, and NB with the fibrocavitary (FC) form on chest CT were identified as risk factors for the clinical or radiological exacerbation of NTM-PD. Hydroxychloroquine use was identified as a good prognostic factor. Conversely, history of tuberculosis, ILD, smoking, microbiologically confirmed NTM-PD, and NB with the FC form on chest CT were identified as poor prognostic factors for mortality in suspected NTM-PD. CONCLUSION: ILD and NB with the FC form on chest CT were associated with NTM-PD exacerbation and mortality. Hydroxychloroquine use may lower the risk of NTM-PD exacerbation. Therefore, radiographic features and presence of ILD should be considered when predicting the prognosis of patients with RA and suspected NTM-PD.


Subject(s)
Arthritis, Rheumatoid , Lung Diseases, Interstitial , Lung Diseases , Mycobacterium Infections, Nontuberculous , Humans , Middle Aged , Aged , Nontuberculous Mycobacteria , Mycobacterium Infections, Nontuberculous/diagnostic imaging , Mycobacterium Infections, Nontuberculous/drug therapy , Prognosis , Retrospective Studies , Hydroxychloroquine , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy
16.
Sci Rep ; 13(1): 22482, 2023 12 18.
Article in English | MEDLINE | ID: mdl-38110532

ABSTRACT

Genomic hypomethylation has recently been identified as a determinant of therapeutic responses to immune checkpoint blockade (ICB). However, it remains unclear whether this approach can be applied to cell-free DNA (cfDNA) and whether it can address the issue of low tumor purity encountered in tissue-based methylation profiling. In this study, we developed an assay named iMethyl, designed to estimate the genomic hypomethylation status from cfDNA. This was achieved through deep targeted sequencing of young LINE-1 elements with > 400,000 reads per sample. iMethyl was applied to a total of 653 ICB samples encompassing lung cancer (cfDNA n = 167; tissue n = 137; cfDNA early during treatment n = 40), breast cancer (cfDNA n = 91; tissue n = 50; PBMC n = 50; cfDNA at progression n = 44), and ovarian cancer (tissue n = 74). iMethyl-liquid predicted ICB responses accurately regardless of the tumor purity of tissue samples. iMethyl-liquid was also able to monitor therapeutic responses early during treatment (3 or 6 weeks after initiation of ICB) and detect progressive hypomethylation accompanying tumor progression. iMethyl-tissue had better predictive power than tumor mutation burden and PD-L1 expression. In conclusion, our iMethyl-liquid method allows for reliable noninvasive prediction, early evaluation, and monitoring of clinical responses to ICB therapy.


Subject(s)
Breast Neoplasms , Cell-Free Nucleic Acids , Lung Neoplasms , Humans , Female , Cell-Free Nucleic Acids/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Leukocytes, Mononuclear/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Genomics/methods , Lung/pathology , Biomarkers, Tumor/genetics
17.
Immun Ageing ; 20(1): 67, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38001481

ABSTRACT

TLR4, a transmembrane receptor, plays a central role in the innate immune response. TLR4 not only engages with exogenous ligands at the cellular membrane's surface but also interacts with intracellular ligands, initiating intricate intracellular signaling cascades. Through MyD88, an adaptor protein, TLR4 activates transcription factors NF-κB and AP-1, thereby facilitating the upregulation of pro-inflammatory cytokines. Another adapter protein linked to TLR4, known as TRIF, autonomously propagates signaling pathways, resulting in heightened interferon expression. Recently, TLR4 has garnered attention as a significant factor in the regulation of symptoms in aging-related disorders. The persistent inflammatory response triggered by TLR4 contributes to the onset and exacerbation of these disorders. In addition, alterations in TLR4 expression levels play a pivotal role in modifying the manifestations of age-related diseases. In this review, we aim to consolidate the impact of TLR4 on cellular senescence and aging-related ailments, highlighting the potential of TLR4 as a novel therapeutic target that extends beyond immune responses.

18.
J Chem Phys ; 159(18)2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37955325

ABSTRACT

Many modern anti-icing and anti-fouling coatings rely on soft, low surface energy elastomeric materials such as polydimethylsiloxane for their functionality. While the low surface energy is desirable for reducing adhesion, very little work considers the larger contribution to adhesive failure caused by the viscoelastic nature of elastomers. Here we examine several different siloxane elastomers using a JKR adhesion test, which was operated over a range of different speeds and temperatures. Additionally, we characterize the dynamic mechanical modulus over a large range of frequencies for each material. We note that surface energies of the materials are all similar, but variation in adhesion strength is clear in the data. The variation at low speeds is related to elastomer architecture but the speed dependence itself is independent of architecture. Qualitative correlations are noted between the JKR adhesion measurements and the dynamic moduli. Finally, an attempt is made to directly compare moduli and adhesion through the recent Persson-Brener model. Approximations of the model are shown to be inaccurate. The full model is found to be accurate at low speeds, although it fails to precisely capture higher speed behaviour.

19.
Acta Derm Venereol ; 103: adv11593, 2023 Nov 13.
Article in English | MEDLINE | ID: mdl-37955529

ABSTRACT

Atopic dermatitis is a chronic inflammatory skin  disease. Skin is the largest organ and plays a pivotal role in protecting the body. Not only does the skin act as a physical barrier against the external environment, but it also has its own immune system. Atopic dermatitis is caused by prolonged excessive inflammatory responses that worsen under imbalanced cutaneous immune system skin conditions. Although the prevalence and burden of atopic dermatitis is increasing, the standard therapeutic agents remain unclear due to  the complicated pathophysiology of the condition. The objective of this study is to examine the use of Magnoliae flos, the dried flower bud of Magnolia biondii or  related plants. The effects and underlying mechanism of  action of aqueous extract of the buds of Magnoliae flos (MF) were evaluated. Immortalized human keratinocytes (HaCaT) stimulated with tumour necrosis factor-α and interferon-γ mixture and NC/Nga mice stimulated with 2,4-dinitrochlorobenzene were used as atopic dermatitis models, in vitro and in vivo, respectively. The effects of MF were determined by measuring the suppression of pro-inflammatory signalling pathways, such as extracellular signal-regulated kinase or signal transducers and activators of transcription 1/3 and restoring skin barrier molecules. In conclusion, MF is a potential therapeutic alternative for the treatment of atopic dermatitis through repressing inflammatory pathways.


Subject(s)
Dermatitis, Atopic , Humans , Mice , Animals , Extracellular Signal-Regulated MAP Kinases/pharmacology , Immunoglobulin E , Cell Line , Skin/pathology , Inflammation , Tumor Necrosis Factor-alpha/metabolism , Flowers/metabolism , Cytokines
20.
RSC Adv ; 13(45): 31873-31880, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37915448

ABSTRACT

Olivine-type LiFePO4 (LFP) is considered a promising cathode material for lithium-ion batteries (LIBs) owing to its abundance, high specific capacity, and cycling performance. However, its poor electronic and ionic transportation properties degrade the high rate capability, which limits its use in high-energy-density LIBs for applications such as electric vehicles. Therefore, in this study, we propose a modification of the anion configuration through nitrogen substitution using ion implantation to improve electronic and ionic transport during lithiation/delithiation. We found that nitrogen substitution at the oxygen sites effectively improved the electrochemical properties through surface modification and charge-transfer kinetics. In particular, the increased amount of nitrogen substitution at the surface regions resulted in reduced ionic and electronic resistances. These modified characteristics led to a remarkable rate capability with a high capacity (128.2 mA h g-1 at 10C). We expect that these modified anion effects on the electrochemical properties can be effective in the design of cathode materials for LIBs.

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