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1.
Heliyon ; 10(17): e37134, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39286105

RESUMO

Radioactive Cs+ and I- ions are major components of nuclear wastewater, typically existing as counter ions. Due to their high water solubility and mobility, these ions can spread through contaminated water and soil into ecosystems, necessitating continuous removal and management. In this study, we synthesized a reusable bifunctional Ni@Pt/K2NiFe(CN)6 composite that can simultaneously remove radioactive Cs+ and I- ions and, for the first time, enable their separate recovery in aqueous solutions. In this material, K2NiFe(CN)6 acted as an electrochemically switched ion exchanger, controlling the adsorption/desorption of Cs+, while Pt enabled the spontaneous adsorption and electrochemical desorption of I-, and the magnetic Ni core allowed for efficient adsorbent recovery. The adsorption isotherms of both Cs+ and I- were best fitted using the Langmuir model, and the corresponding adsorption capacities were comparable to those of conventional adsorbents used for the separate removal of Cs+ and I-. Furthermore, the composite demonstrated stability over 100 sorption cycles, maintaining high recovery efficiencies of 97.9 % for Cs+ and 99.7 % for I-, thereby proving its reusability. Thus, the developed composite holds great promise for radioactive wastewater treatment and environmental restoration.

2.
J Korean Med Sci ; 39(36): e246, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39315441

RESUMO

BACKGROUND: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia. METHODS: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer's disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses. RESULTS: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18-7.18) and AD (HR, 3.22; 95% CI, 1.14-9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females. CONCLUSION: Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories.


Assuntos
Doença de Alzheimer , Encéfalo , Demência , Imageamento por Ressonância Magnética , Mastigação , Humanos , Masculino , Feminino , Idoso , Estudos Prospectivos , Fatores de Risco , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Pessoa de Meia-Idade , Estudos de Coortes , Modelos de Riscos Proporcionais , Fatores Sexuais , Cognição/fisiologia , Disfunção Cognitiva , Idoso de 80 Anos ou mais
3.
Vaccines (Basel) ; 12(8)2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39204012

RESUMO

This study presents a framework for determining the prioritization of vaccine introduction in the National Immunization Program (NIP) of the Republic of Korea, with a focus on case examples assessed in 2021 and 2023. We describe the predefined criteria for evaluating the prioritization of vaccines in the NIP and the established process in the Republic of Korea. These criteria included disease characteristics, vaccine characteristics, rationality and efficiency of resource allocation, and the acceptance of immunization. The process of prioritizing NIP introduction involved several sequential steps: a demand survey, evidence collection, preliminary evaluation, priority evaluation, and decision making. In 2021 and 2023, 14 and 25 committee members participated in evaluating the prioritization of vaccines in the NIP, respectively. Overall, 13 and 19 NIP vaccine candidates were included in the 2021 and 2023 evaluations, respectively. Through the Delphi survey and consensus processes, the priority order was determined: vaccination against Rotavirus infection was the top priority in 2021, while Influenza 4v (for chronic disease patients) took precedence in 2023. This study demonstrates an evidence-based decision-making process within the healthcare field. The outlined approach may provide valuable guidance for policymakers in other countries seeking to prioritize the inclusion of new vaccines in their NIP.

4.
NPJ Sci Food ; 8(1): 50, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112506

RESUMO

The burgeoning demand for plant-based meat analogs (PBMAs) stems from environmental, health, and ethical concerns, yet replicating the sensory attributes of animal meat remains challenging. This comprehensive review explores recent innovations in PBMA ingredients and methodologies, emphasizing advancements in texture, flavor, and nutritional profiles. It chronicles the transition from soy-based first-generation products to more diversified second- and third-generation PBMAs, showcasing the utilization of various plant proteins and advanced processing techniques to enrich sensory experiences. The review underscores the crucial role of proteins, polysaccharides, and fats in mimicking meat's texture and flavor and emphasizes research on new plant-based sources to improve product quality. Addressing challenges like production costs, taste, texture, and nutritional adequacy is vital for enhancing consumer acceptance and fostering a more sustainable food system.

5.
Microbiol Resour Announc ; 13(9): e0057324, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39162442

RESUMO

We report the complete genomes of Geobacillus stearothermophilus strains EF60045 and SJEF4-2 from Korean hot springs, with 3,769 and 3,625 thermophilic genes, respectively. G. stearothermophilus EF60045 shows four methylation patterns. G. stearothermophilus SJEF4-2 harbors three plasmids. These findings enhance understanding of Geobacillus strains, aiding in their development as microbial platform hosts.

6.
Biofabrication ; 16(4)2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39074508

RESUMO

This study proposed an optimized histogel construction method for histological analysis by applying lung cancer patient-derived organoids (PDOs) to the developed histo-pillar strip. Previously, there is the cultured PDOs damage problem during the histogel construction due to forced detachment of the Matrigel spots from the 96-well plate bottom. To address this issue, we cultured PDO on the proposed Histo-pillar strips and then immersed them in 4% paraformaldehyde fixation solution to self-isolate PDO without damage. The 4µl patient-derived cell (PDC)/Matrigel mixtures were dispensed on the surface of a U-shaped histo-pillar strip, and the PDCs were aggregated by gravity and cultured into PDOs. Cultured PDOs were self-detached by simply immersing them in a paraformaldehyde fixing solution without physical processing, showing about two times higher cell recovery rate than conventional method. In addition, we proposed a method for embedding PDOs under conditions where the histogel temperature was maintained such that the histogel did not harden, thereby improving the problem of damaging the histogel block in the conventional sandwich histogel construction method. We performed histological and genotyping analyses using tumor tissues and PDOs from two patients with lung adenocarcinoma. Therefore, the PDO culture and improved histogel block construction method using the histo-pillar strip proposed in this study can be employed as useful tools for the histological analysis of a limited number of PDCs.


Assuntos
Neoplasias Pulmonares , Organoides , Humanos , Organoides/metabolismo , Organoides/efeitos dos fármacos , Organoides/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Biomarcadores Tumorais/metabolismo , Laminina/química , Géis/química , Colágeno/química , Colágeno/metabolismo , Combinação de Medicamentos , Proteoglicanas/química
7.
J Bone Metab ; 31(2): 90-100, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38886967

RESUMO

BACKGROUND: Osteoporosis prevalence continues to escalate with the growth of the older adult population. In this study, we aimed to investigate the profile of osteoporosis treatment-related research articles published in the past 20 years using bibliometric analysis. METHODS: We analyzed all osteoporosis treatment-related articles published between 2001 and 2020 in the Web of Science (WoS) database using bibliometric methods. In the Title search section in WoS, we searched the documents using "osteoporosis treatment"-related keywords. We used the VOSviewer software to construct the bibliometric maps of keyword co-occurrences. RESULTS: Our search yielded 29,738 publications, 21,556 (72.5%) were original articles and 4,529 (15.2%) were review articles and review articles (4,529). We noticed a steady increase in the publication numbers from 2001 to 2020. The overall scientific publication number in WoS increased 3.5-fold, with the five most productive countries being the USA, China, Germany, the United Kingdom, and Japan. The largest contributor was the University of California system. The most productive journals were Osteoporosis International (1,679, 6.4%), Bone (832, 3.2%), and the Journal of Bone and Mineral Research (727, 2.8%). We observed increasing trends in the appearance of denosumab and teriparatide during the last two decades. In our keyword co-occurrence analysis, we constructed four keyword clusters using VOSviewer. CONCLUSIONS: In this study, we provided a gross overview of the visibility and productivity of research studies in osteoporosis treatment. Substantial changes have occurred in osteoporosis treatment over the last 20 years. The effector mechanism of anti-osteoporosis medications could be future hot spots in osteoporosis research. We believe that our study is a valuable guide for clinicians related to the global outputs of osteoporosis treatment.

8.
Anal Chem ; 96(25): 10246-10255, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38858132

RESUMO

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.


Assuntos
Ensaios de Triagem em Larga Escala , Neoplasias Pulmonares , Organoides , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Organoides/metabolismo , Organoides/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia Celular , Técnicas de Cultura de Células em Três Dimensões , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
9.
Inorg Chem ; 63(19): 8832-8845, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38687621

RESUMO

To efficiently degrade organic pollutants, photocatalysts must be effective under both ultraviolet (UV) radiation and sunlight. We synthesized a series of new metal-organic frameworks by using mild hydrothermal conditions. These frameworks incorporate three distinct bipyridyl ligands: pyrazine (pyr), 4,4'-bipyridine (bpy), and 1,2-bis(4-pyridyl)ethane (bpe). The resulting compounds are denoted as [Cu(pyz)(H2O)2MF6], [Cu(bpy)2(H2O)2]·MF6, and [Cu(bpe)2(H2O)2]·MF6·H2O [M = Zr (1, 3, and 5) and Hf (2, 4, and 6)]. All six compounds exhibited a two-dimensional crystal structure comprising infinitely nonintersecting linear chains. Compound 3 achieved 100% degradation of methylene blue (MB) after 8 min under UV irradiation and 100 min under natural sunlight in the presence of H2O2 as the electron acceptor. For compound 5, 100% MB degradation was achieved after 120 min under sunlight and 10 min under UV light. Moreover, reactive radical tests revealed that the dominant species involved in photocatalytic degradation are hydroxyl (•OH), superoxide radicals (•O2-), and photogenerated holes (h+). The photodegradation process followed pseudo-first-order kinetics, with photodegradation rate constants of 0.362 min-1 (0.039 min-1) for 3 and 0.316 min-1 (0.033 min-1) for 5 under UV (sunlight) irradiation. The developed photocatalysts with excellent activity and good recyclability are promising green catalysts for degrading organic pollutants during environmental decontamination.

10.
Orthop J Sports Med ; 12(3): 23259671241226909, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38486807

RESUMO

Background: Researchers have attempted to understand the underlying mechanism of the Latarjet procedure; however, its effects on shoulder kinematics have not been well studied. Purpose/Hypothesis: The purpose was to analyze shoulder kinematics after the Latarjet procedure. It was hypothesized that the nonanatomic transfer of the coracoid process during the procedure would affect normal shoulder kinematics. Study Design: Controlled laboratory study. Methods: The study included 10 patients (age range, 20-52 years) who underwent the modified Latarjet procedure between June 2016 and November 2021. Computed tomography and fluoroscopy were conducted on both shoulder joints of all patients, and 3-dimensional models were reconstructed. The 3-dimensional coordinates were encoded on the reconstructed models, and shoulder kinematics were analyzed through a 3-dimensional-2-dimensional model-image registration technique. Scapular rotation parameters (scapular upward rotation, posterior tilt, external rotation, and scapulohumeral rhythm) were compared between the Latarjet and the nonsurgical contralateral sides during humeral abduction, as was anteroposterior (AP) translation relative to the glenoid center during active humeral external rotation. Results: The Latarjet side displayed significantly higher values of scapular upward rotation at higher degrees of humeral elevation (130°, 140°, and 150°) compared with the nonsurgical side (P = .027). Posterior tilt, external rotation, and scapulohumeral rhythm were not significantly different between sides. AP translation at maximal humeral rotation was not significantly different between sides (Latarjet, -0.06 ± 5.73 mm vs nonsurgical, 5.33 ± 1.60 mm; P = .28). Interestingly, on the Latarjet side, AP translation increased until 40° of humeral rotation (4.27 ± 4.64 mm) but began to decrease from 50° of humeral rotation. Conclusion: The Latarjet side demonstrated significant changes in scapular upward rotation during higher degrees of humeral elevation compared with the contralateral shoulder. Posterior movement of the humeral head at >50° of humeral rotation could be the desired effect of anterior stabilization; however, researchers should evaluate long-term complications such as osteoarthritis. Clinical Relevance: Analysis of shoulder kinematics after the Latarjet procedure could provide information regarding long-term outcomes and whether the procedure would affect the daily activities of patients.

11.
Am J Geriatr Psychiatry ; 32(8): 957-967, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38443296

RESUMO

BACKGROUND: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. METHODS: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. FINDINGS: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (ß = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (ß = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. INTERPRETATION: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults.


Assuntos
Depressão , Progressão da Doença , Multimorbidade , Humanos , Feminino , Masculino , Idoso , República da Coreia/epidemiologia , Depressão/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Vida Independente/estatística & dados numéricos , Estudos de Coortes
12.
Integr Med Res ; 13(1): 101020, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38298864

RESUMO

Background: Cancer cachexia-characterized by anorexia, body weight loss, skeletal muscle atrophy, and fat loss-affects nearly 80% of cancer patients and accounts for 20% of cancer deaths. Curcuma xanthorrhiza, known as Java turmeric, and its active compound xanthorrhizol (XAN) exhibit anticancer, anti-inflammatory, and antioxidant properties. However, the ameliorative effects of C. xanthorrhiza extract (CXE) and XAN on cancer-associated adipose atrophy remain unexplored. This study aimed to evaluate the therapeutic effects of CXE and XAN on cancer cachexia-induced adipose tissue wasting in CT26 tumor-bearing mice. Methods: CT26 cells were injected subcutaneously into the right flank of BALB/c mice to establish a cancer cachexia model. To evaluate the inhibitory effects of CXE and XAN on cancer cachexia, 50 and 100 mg/kg CXE and 15 mg/kg XAN were administered orally every day for 1 week. Results: CXE and XAN administration significantly attenuated the loss of body weight and epidydimal fat mass by cancer cachexia. In epididymal adipose tissues, administration of CXE or XAN inhibited white adipose tissue browning by repressing expression of the thermogenic genes. Simultaneously, CXE or XAN attenuated fat catabolism through the downregulation of lipolytic genes. The administration of CXE or XAN induced the expression of genes associated with adipogenesis and lipogenesis-related genes. Moreover, CXE or XAN treatment was associated with maintaining metabolic homeostasis; regulating the expression of adipokines and AMP-activated protein kinase (AMPK). Conclusions: CXE and XAN mitigate cancer-induced adipose tissue atrophy, primarily by modulating lipid metabolism and WAT browning, indicating their therapeutic potential for cachectic cancer patients.

13.
Telemed J E Health ; 30(5): 1297-1305, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38206789

RESUMO

Background: In response to the coronavirus disease-19 pandemic, audio-based telehealth services for consultation and medication prescription were temporarily introduced in Korea. This study investigated the impact of telehealth services on patterns of health care utilization and medication prescription in patients with hypertension or diabetes. Methods: The 2019 to 2021 Health Insurance Review and Assessment Service claims data were used. The difference-in-difference approach was used to investigate the effect of telehealth services between the case and control group before and after the intervention period. The pre-intervention period was from February 24, 2019, to February 23, 2020, and the post-intervention period from February 24, 2020, to February 23, 2021. The control group included individuals who used in-person outpatient services and the case group those who utilized both telehealth and in-person services. Results: A total of 250,640 patients with hypertension and 154,212 patients with diabetes were included. The use of telehealth services was associated with an increase in outpatient visits in those with hypertension (0.07, p = 0.0027) and diabetes (0.32, p < 0.0001). A decrease in hospitalizations (-0.2%, p = 0.0007) and emergency department visits (-0.11%, p = 0.0016) was found in individuals with hypertension. Policy implementation also resulted in an increase in medication possession ratio (MPR) and the proportion of appropriate prescription in patients with hypertension (MPR: 3.0%, p < 0.0001, prescription: 3.1%, p < 0.0001) and diabetes (MPR: 3.4%, p < 0.0001, prescription: 1.7%, p < 0.0001). Conclusions: The findings confirm a relationship between implementing telehealth services and improved patterns of health care utilization and medication prescription, suggesting the potential benefit of telehealth in managing chronic diseases.


Assuntos
COVID-19 , Diabetes Mellitus , Hipertensão , Aceitação pelo Paciente de Cuidados de Saúde , Telemedicina , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , COVID-19/epidemiologia , Telemedicina/estatística & dados numéricos , República da Coreia , Masculino , Feminino , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso , Adulto , Pandemias , SARS-CoV-2 , Prescrições de Medicamentos/estatística & dados numéricos
14.
R Soc Open Sci ; 11(1): 231129, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38204788

RESUMO

The gut mycobiome plays an important role in the health and disease of the human gut, but its exact function is still under investigation. While there is a wealth of information available on the bacterial community of the human gut microbiome, research on the fungal community is still relatively limited. In particular, technical methodologies for mycobiome analysis, especially the DNA extraction method for human faecal samples, varied in different studies. In the current study, two commercial kits commonly used in DNA extraction, the QIAamp® Fast DNA Stool Mini Kit and DNeasy PowerSoil Pro Kit, and one manual method, the International Human Microbiome Standards Protocol Q, were compared. Furthermore, the effectiveness of two different bead-beating machines, the Mini-Beadbeater-16 and FastPrep-24TM 5G, was compared in parallel. A mock fungal community with a known composition of fungal strains was also generated and included to compare different DNA extraction methods. Our results suggested that the method using the DNeasy PowerSoil Pro Kit and Mini-Beadbeater-16 provides the best results to extract DNA from human faecal samples. Based on our data, we propose a standard operating procedure for DNA extraction from human faecal samples for mycobiome analysis.

17.
Int J Mol Sci ; 24(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38069026

RESUMO

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world. However, no effective treatment for the disease has yet been found. For this reason, several studies are being carried out on the treatment of CRC. Currently, there is limited understanding of the role of CPNE7 (copine-7) in CRC progression and metastasis. The results of this study show that CPNE7 exerts an oncogenic effect in CRC. First, CPNE7 was shown to be significantly up-regulated in CRC patient tissues and CRC cell lines compared to normal tissues according to IHC staining, qRT-PCR, and western blotting. Next, this study used both systems of siRNA and shRNA to suppress CPNE7 gene expression to check the CPNE7 mechanism in CRC. The suppressed CPNE7 significantly inhibited the growth of CRC cells in in vitro experiments, including migration, invasion, and semisolid agar colony-forming assay. Moreover, the modified expression of CPNE7 led to a decrease in the levels of genes associated with epithelial-mesenchymal transition (EMT). The epithelial genes E-cadherin (CDH1) and Collagen A1 were upregulated, and the levels of mesenchymal genes such as N-cadherin (CDH2), ZEB1, ZEB2, and SNAIL (SNAL1) were downregulated after CPNE7 inhibition. This study suggests that CPNE7 may serve as a potential diagnostic biomarker for CRC patients.


Assuntos
Neoplasias Colorretais , Transdução de Sinais , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , RNA Interferente Pequeno/genética
18.
SLAS Discov ; : 100131, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38101575

RESUMO

The Publisher regrets that this article is an accidental duplication of an article previously published at http://dx.doi.org/10.1016/j.slasd.2023.03.006. This duplication was due to an error in the publishing workflow and was not the responsibility of the authors or editors. As a result, the duplicate article has been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

19.
J Exp Clin Cancer Res ; 42(1): 309, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993887

RESUMO

BACKGROUND: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. METHODS: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. RESULTS: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. CONCLUSIONS: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Crizotinibe/uso terapêutico , Organoides
20.
BMC Med ; 21(1): 367, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37840129

RESUMO

BACKGROUND: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse. METHODS: Data was acquired from a community-based prospective cohort that included Koreans aged 60 years and over, randomly sampled from 13 districts nationwide. Data from the baseline assessment (conducted from November 2010 to October 2012) up to the 8-year follow-up assessment was analyzed from October 2021 to November 2022. At the last assessment, partners of the index participants were invited, and we included 814 couples in the analysis after excluding 51 with incomplete variables. Chronic illness burden of the participants was measured by the Cumulative Illness Rating Scale (CIRS). Multivariable linear regression and causal mediation analysis were used to examine the longitudinal effects of index chronic illness burden at baseline and its change during follow-up on future index and spouse CIRS scores. RESULTS: Index participants were divided based on baseline CIRS scores (CIRS < 6 points, n = 555, mean [SD] age 66.3 [4.79] years, 43% women; CIRS ≥ 6 points, n = 259, mean [SD] age 67.7 [4.76] years, 36% women). The baseline index CIRS scores and change in index CIRS scores during follow-up were associated with the spouse CIRS scores (ß = 0.154 [SE: 0.039], p < 0.001 for baseline index CIRS; ß = 0.126 [SE: 0.041], p = 0.002 for change in index CIRS) at the 8-year follow-up assessment. Subgroup analysis found similar results only in the high CIRS group. The baseline index CIRS scores and change in index CIRS scores during follow-up had both direct and indirect effects on the spouse CIRS scores at the 8-year follow-up assessment. CONCLUSIONS: The severity and course of one's chronic illnesses had a significant effect on their spouse's future chronic illness particularly when it was severe. Management strategies for chronic diseases that are centered on couples may be more effective.


Assuntos
Cônjuges , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Doença Crônica , Índice de Gravidade de Doença
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